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Sample records for molecule icam-4 potential

  1. Novel secreted isoform of adhesion molecule ICAM-4: Potential regulator of membrane-associated ICAM-4 interactions

    SciTech Connect

    Lee, Gloria; Spring, Frances A.; Parons, Stephen F.; Mankelow, Tosti J.; Peters, Luanne L.; Koury, Mark J.; Mohandas, Narla; Anstee, David J.; Chasis, Joel Anne

    2003-02-18

    ICAM-4, a newly characterized adhesion molecule, is expressed early in human erythropoiesis and functions as a ligand for binding a4b1 and aV integrin-expressing cells. Within the bone marrow, erythroblasts surround central macrophages forming erythroblastic islands. Evidence suggests that these islands are highly specialized subcompartments where cell adhesion events, in concert with cytokines, play critical roles in regulating erythropoiesis and apoptosis. Since erythroblasts express a4b1 and ICAM-4 and macrophages exhibit aV, ICAM-4 is an attractive candidate for mediating cellular interactions within erythroblastic islands. To determine whether ICAM-4 binding properties are conserved across species, we first cloned and sequenced the murine homologue. The translated amino acid sequence showed 68 percent overall identity with human ICAM-4. Using recombinant murine ICAM-4 extracellular domains, we discovered that hematopoietic a4b1-expressing HEL cells and non-hematopoietic aV-expressing FLY cells adhered to mouse ICAM-4. Cell adhesion studies showed that FLY and HEL cells bound to mouse and human proteins with similar avidity. These data strongly suggest conservation of integrin-binding properties across species. Importantly, we characterized a novel second splice cDNA that would be predicted to encode an ICAM-4 isoform, lacking the membrane-spanning domain. Erythroblasts express both isoforms of ICAM-4. COS-7 cells transfected with GFP constructs of prototypic or novel ICAM-4 cDNA showed different cellular localization patterns. Moreover, analysis of tissue culture medium revealed that the novel ICAM-4 cDNA encodes a secreted protein. We postulate that secretion of this newly described isoform, ICAM-4S, may modulate binding of membrane-associated ICAM-4 and could thus play a critical regulatory role in erythroblast molecular attachments.

  2. Targeted Gene Deletion Demonstrates that Cell Adhesion MoleculeICAM-4 is Critical for Erythroblastic Island Formation

    SciTech Connect

    Lee, Gloria; Lo, Annie; Short, Sarah A.; Mankelow, Tosti J.; Spring, Frances; Parsons, Stephen F.; Mohandas, Narla; Anstee, David J.; Chasis, Joel Anne

    2006-02-15

    Erythroid progenitors differentiate in erythroblastic islands, bone marrow niches composed of erythroblasts surrounding a central macrophage. Evidence suggests that within islands adhesive interactions regulate erythropoiesis and apoptosis. We are exploring whether erythroid intercellular adhesion molecule-4 (ICAM-4), animmunoglobulin superfamily member, participates in island formation. Earlier, we identified alpha V integrins as ICAM-4 counter receptors. Since macrophages express alpha V, ICAM-4 potentially mediates island attachments. To test this, we generated ICAM-4 knockout mice and developed quantitative, live cell techniques for harvesting intact islands and for reforming islands in vitro. We observed a 47 percent decrease in islands reconstituted from ICAM-4 null marrow compared to wild type. We also found a striking decrease in islands formed in vivo in knockout mice. Further, peptides that block ICAM-4 alpha V adhesion produced a 53-57 percent decrease in reconstituted islands, strongly suggesting that ICAM-4 binding to macrophage alpha V functions in island integrity. Importantly, we documented that alpha V integrin is expressed in macrophages isolated from erythro blastic islands. Collectively, these data provide convincing evidence that ICAM-4 is critical in erythroblastic island formation via ICAM-4/alpha V adhesion and also demonstrate that the novel experimental strategies we developed will be valuable in exploring molecular mechanisms of erythroblastic island formation and their functional role in regulating erythropoiesis.

  3. Peptides based on alphaV-binding domains of erythrocyte ICAM-4 inhibit sickle red cell-endothelial interactions and vaso-occlusion in the microcirculation.

    PubMed

    Kaul, Dhananjay K; Liu, Xiao-du; Zhang, Xiaoqin; Mankelow, Tosti; Parsons, Stephen; Spring, Frances; An, Xiuli; Mohandas, Narla; Anstee, David; Chasis, Joel Anne

    2006-11-01

    Growing evidence shows that adhesion molecules on sickle erythrocytes interact with vascular endothelium leading to vaso-occlusion. Erythrocyte intercellular adhesion molecule-4 (ICAM-4) binds alphaV-integrins, including alphaVbeta3 on endothelial cells. To explore the contribution of ICAM-4 to vascular pathology of sickle cell disease, we tested the effects of synthetic peptides, V(16)PFWVRMS (FWV) and T(91)RWATSRI (ATSR), based on alphaV-binding domains of ICAM-4 and capable of inhibiting ICAM-4 and alphaV-binding in vitro. For these studies, we utilized an established ex vivo microvascular model system that enables intravital microscopy and quantitation of adhesion under shear flow. In this model, the use of platelet-activating factor, which causes endothelial oxidant generation and endothelial activation, mimicked physiological states known to occur in sickle cell disease. Infusion of sickle erythrocytes into platelet-activating factor-treated ex vivo rat mesocecum vasculature produced pronounced adhesion of erythrocytes; small-diameter venules were sites of maximal adhesion and frequent blockage. Both FWV and ATSR peptides markedly decreased adhesion, and no vessel blockage was observed with either of the peptides, resulting in improved hemodynamics. ATSR also inhibited adhesion in unactivated microvasculature. Although infused fluoresceinated ATSR colocalized with vascular endothelium, pretreatment with function-blocking antibody to alphaVbeta3-integrin markedly inhibited this interaction. Our data strengthen the thesis that ICAM-4 on sickle erythrocytes binds endothelium via alphaVbeta3 and that this interaction contributes to vaso-occlusion. Thus peptides or small molecule mimetics of ICAM-4 may have therapeutic potential.

  4. Regulation of Active ICAM-4 on Normal and Sickle Cell Disease RBCs via AKAPs Is Revealed by AFM.

    PubMed

    Zhang, Jing; Abiraman, Krithika; Jones, Sasia-Marie; Lykotrafitis, George; Andemariam, Biree

    2017-01-10

    Human healthy (wild-type (WT)) and homozygous sickle (SS) red blood cells (RBCs) express a large number of surface receptors that mediate cell adhesion between RBCs, and between RBCs and white blood cells, platelets, and the endothelium. In sickle cell disease (SCD), abnormal adhesion of RBCs to endothelial cells is mediated by the intercellular adhesion molecule-4 (ICAM-4), which appears on the RBC membrane and binds to the endothelial αvβ3 integrin. This is a key factor in the initiation of vaso-occlusive episodes, the hallmark of SCD. A better understanding of the mechanisms that control RBC adhesion to endothelium may lead to novel approaches to both prevention and treatment of vaso-occlusive episodes in SCD. One important mechanism of ICAM-4 activation occurs via the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA)-dependent signaling pathway. Here, we employed an in vitro technique called single-molecule force spectroscopy to study the effect of modulation of the cAMP-PKA-dependent pathway on ICAM-4 receptor activation. We quantified the frequency of active ICAM-4 receptors on WT-RBC and SS-RBC membranes, as well as the median unbinding force between ICAM-4 and αvβ3. We showed that the collective frequency of unbinding events in WT-RBCs is not significantly different from that of SS-RBCs. This result was confirmed by confocal microscopy experiments. In addition, we showed that incubation of normal RBCs and SS-RBCs with epinephrine, a catecholamine that binds to the β-adrenergic receptor and activates the cAMP-PKA-dependent pathway, caused a significant increase in the frequency of active ICAM-4 receptors in both normal RBCs and SS-RBCs. However, the unbinding force between ICAM-4 and the corresponding ligand αvβ3 remained the same. Furthermore, we demonstrated that forskolin, an adenylyl cyclase activator, significantly increased the frequency of ICAM-4 receptors in WT-RBCs and SS-RBCs, confirming that the activation of ICAM-4 is regulated

  5. Variation in the ICAM1–ICAM4–ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries

    PubMed Central

    Kim, Kwangwoo; Brown, Elizabeth E; Choi, Chan-Bum; Alarcón-Riquelme, Marta E; Kelly, Jennifer A; Glenn, Stuart B; Ojwang, Joshua O; Adler, Adam; Lee, Hye-Soon; Boackle, Susan A; Criswell, Lindsey A; Alarcón, Graciela S; Edberg, Jeffrey C; Stevens, Anne M; Jacob, Chaim O; Gilkeson, Gary S; Kamen, Diane L; Tsao, Betty P; Anaya, Juan-Manuel; Guthridge, Joel M; Nath, Swapan K; Richardson, Bruce; Sawalha, Amr H; Kang, Young Mo; Shim, Seung Cheol; Suh, Chang-Hee; Lee, Soo-Kon; Kim, Chang-sik; Merrill, Joan T; Petri, Michelle; Ramsey-Goldman, Rosalind; Vilá, Luis M; Niewold, Timothy B; Martin, Javier; Pons-Estel, Bernardo A; Vyse, Timothy J; Freedman, Barry I; Moser, Kathy L; Gaffney, Patrick M; Williams, Adrienne; Comeau, Mary; Reveille, John D; James, Judith A; Scofield, R Hal; Langefeld, Carl D; Kaufman, Kenneth M; Harley, John B; Kang, Changwon; Kimberly, Robert P; Bae, Sang-Cheol

    2012-01-01

    Objective Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin αΜ (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM. Methods The authors examined several markers in the ICAM1–ICAM4–ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case–control study of 17 481 unrelated participants from four ancestry populations. The single marker association and gene–gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed. Results The A-allele of ICAM1–ICAM4–ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (ORmeta=1.16, 95% CI 1.11 to 1.22; p=4.88×10−10 and ORmeta=1.67, 95% CI 1.55 to 1.79; p=3.32×10−46, respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10−5). Conclusion These findings are the first to suggest that an ICAM–integrin-mediated pathway contributes to susceptibility to SLE. PMID:22523428

  6. Fixman compensating potential for general branched molecules

    SciTech Connect

    Jain, Abhinandan; Kandel, Saugat; Wagner, Jeffrey; Larsen, Adrien; Vaidehi, Nagarajan

    2013-12-28

    The technique of constraining high frequency modes of molecular motion is an effective way to increase simulation time scale and improve conformational sampling in molecular dynamics simulations. However, it has been shown that constraints on higher frequency modes such as bond lengths and bond angles stiffen the molecular model, thereby introducing systematic biases in the statistical behavior of the simulations. Fixman proposed a compensating potential to remove such biases in the thermodynamic and kinetic properties calculated from dynamics simulations. Previous implementations of the Fixman potential have been limited to only short serial chain systems. In this paper, we present a spatial operator algebra based algorithm to calculate the Fixman potential and its gradient within constrained dynamics simulations for branched topology molecules of any size. Our numerical studies on molecules of increasing complexity validate our algorithm by demonstrating recovery of the dihedral angle probability distribution function for systems that range in complexity from serial chains to protein molecules. We observe that the Fixman compensating potential recovers the free energy surface of a serial chain polymer, thus annulling the biases caused by constraining the bond lengths and bond angles. The inclusion of Fixman potential entails only a modest increase in the computational cost in these simulations. We believe that this work represents the first instance where the Fixman potential has been used for general branched systems, and establishes the viability for its use in constrained dynamics simulations of proteins and other macromolecules.

  7. Potential energy landscapes of tetragonal pyramid molecules

    NASA Astrophysics Data System (ADS)

    Yoshida, Yuichiro; Sato, Hirofumi; Morgan, John W. R.; Wales, David J.

    2016-11-01

    Hiraoka et al. have developed a self-assembling system referred to as a nanocube (Hiraoka et al., 2008). In the present contribution a coarse-grained model for this system is analysed, focusing on how the potential energy landscape for self-assembly is related to the geometry of the building blocks. We find that six molecules assemble to form various clusters, with cubic and sheet structures the most stable. The relative stability is determined by the geometry of the building blocks.

  8. Neopterin as a potential cytoprotective brain molecule.

    PubMed

    Ghisoni, Karina; Martins, Roberta de Paula; Barbeito, Luis; Latini, Alexandra

    2015-12-01

    Neopterin, a byproduct of the tetrahydrobiopterin de novo pathway, is found in increased levels in cerebrospinal fluid and plasma and significantly increases upon damage, infection or during immune system activation. The production of this compound seems almost restricted to the monocyte/macrophage linage cells, in response to interferon-γ stimulation. However, it is unclear whether and which nervous cells are able to synthesize neopterin, respond to any stressor applied extracellularly, or even the role of the compound in the central nervous system. Here we propose a potential cytoprotective role of neopterin in the brain, and show evidence that cultured rat astrocytes are responsive to the molecule; the pterin elicited increased hemeoxygenase-1 cellular content and decreased oxidative stress induced by mitochondrial dysfunction. Further studies are needed to clarify neopterin's cytoprotective effects in the central nervous system, and its potential role in different neuroinflammatory diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Adsorbed molecules in external fields: Effect of confining potential.

    PubMed

    Tyagi, Ashish; Silotia, Poonam; Maan, Anjali; Prasad, Vinod

    2016-12-05

    We study the rotational excitation of a molecule adsorbed on a surface. As is well known the interaction potential between the surface and the molecule can be modeled in number of ways, depending on the molecular structure and the geometry under which the molecule is being adsorbed by the surface. We explore the effect of change of confining potential on the excitation, which is largely controlled by the static electric fields and continuous wave laser fields. We focus on dipolar molecules and hence we restrict ourselves to the first order interaction in field-molecule interaction potential either through permanent dipole moment or/and the molecular polarizability parameter. It is shown that confining potential shapes, strength of the confinement, strongly affect the excitation. We compare our results for different confining potentials.

  10. Adsorbed molecules in external fields: Effect of confining potential

    NASA Astrophysics Data System (ADS)

    Tyagi, Ashish; Silotia, Poonam; Maan, Anjali; Prasad, Vinod

    2016-12-01

    We study the rotational excitation of a molecule adsorbed on a surface. As is well known the interaction potential between the surface and the molecule can be modeled in number of ways, depending on the molecular structure and the geometry under which the molecule is being adsorbed by the surface. We explore the effect of change of confining potential on the excitation, which is largely controlled by the static electric fields and continuous wave laser fields. We focus on dipolar molecules and hence we restrict ourselves to the first order interaction in field-molecule interaction potential either through permanent dipole moment or/and the molecular polarizability parameter. It is shown that confining potential shapes, strength of the confinement, strongly affect the excitation. We compare our results for different confining potentials.

  11. Optical Stark decelerator for molecules with a traveling potential well

    NASA Astrophysics Data System (ADS)

    Deng, Lianzhong; Hou, Shunyong; Yin, Jianping

    2017-03-01

    We propose a versatile scheme to slow supersonically cooled molecules using a decelerating potential well, obtained by steering a focusing laser beam onto a pair of spinning reflective mirrors under a high-speed brake. The longitudinal motion of molecules in the moving red-detuned light field is analyzed and their corresponding phase-space stability is investigated. Trajectories of C H4 molecules under the influence of the potential well are simulated using the Monte Carlo method. For instance, with a laser beam of power 20 kW focused onto a spot of waist radius 40-100 μm, corresponding to a peak laser intensity on the order of ˜108W /c m2 , a C H4 molecule of ˜250 m /s can be decelerated to ˜10 m /s over a distance of a few centimeters on a time scale of hundreds of microseconds.

  12. General van der Waals potential for common organic molecules.

    PubMed

    Qi, Rui; Wang, Qiantao; Ren, Pengyu

    2016-10-15

    This work presents a systematic development of a new van der Waals potential (vdW2016) for common organic molecules based on symmetry-adapted perturbation theory (SAPT) energy decomposition. The Buf-14-7 function, as well as Cubic-mean and Waldman-Hagler mixing rules were chosen given their best performance among other popular potentials. A database containing 39 organic molecules and 108 dimers was utilized to derive a general set of vdW parameters, which were further validated on nucleobase stacking systems and testing organic dimers. The vdW2016 potential is anticipated to significantly improve the accuracy and transferability of new generations of force fields for organic molecules. Copyright © 2016. Published by Elsevier Ltd.

  13. NMR studies of electrostatic potential distribution around biologically important molecules.

    PubMed Central

    Likhtenshtein, G I; Adin, I; Novoselsky, A; Shames, A; Vaisbuch, I; Glaser, R

    1999-01-01

    A new experimental approach has been developed to study the distribution of local electrostatic potential around specific protons in biologically important molecules. The approach is the development of a method denoted as "spin label/spin probe," which was proposed by one of us (. Mol. Biol. 6:498-507). The proposed method is based upon the quantitative measurement of the contribution of differently charged nitroxide probes to the spin lattice relaxation rate (1/T1) of protons in the molecule of interest, followed by calculation of local electrostatic potential using the classical Debye equation. In parallel, the theoretical calculation of potential distribution with the use of the MacSpartan Plus 1.0 program has been performed. Application of the method to solutions of simple organic molecules (aliphatic and aromatic alcohols, aliphatic carboxylates (propionate anion), and protonated ethyl amine and imidazole) allowed us to estimate the effective potential around the molecules under investigation. These were found to be in good agreement with theoretically expected values. This technique was then applied to zwitterionic amino acids bearing neutral and charged side chains (glycine, lysine, histidine, and aspartic acid). The reliability of the general approach is proved by the data presented in this paper. Application of this new methodology can afford insight into the biochemical significance of electrostatic effects in biological systems. PMID:10388770

  14. Reduction potential prediction of some aromatic nitrogen containing molecules.

    SciTech Connect

    Assary, Rajeev S.; Brushett, Fikile R; Curtiss, Larry A.

    2014-10-20

    Accurate quantum chemical methods offer a reliable alternative to time-consuming experimental evaluations for obtaining a priori electrochemical knowledge of a large number of redox active molecules. In this contribution, quantum chemical calculations are performed to investigate the redox behavior of quinoxalines, a promising family of active materials for non-aqueous flow batteries, as a function of substituent group. The reduction potentials of 40 quinoxaline derivatives with a range of electron-donating and electron-withdrawing groups are computed. Calculations indicate the addition of electron-donating groups, particularly alkyl groups, can significantly lower the reduction potential albeit with a concomitant decrease in oxidative stability. A simple descriptor is derived for computing reduction potentials of quinoxaline derivatives from the LUMO energies of the neutral molecules without time-consuming free energy calculations. The relationship was validated for a broader set of aromatic nitrogen-containing molecules including pyrazine, phenazine, viologen, pyridine, pyrimidine, pyridazine, and quinoline, suggesting that it is a good starting point for large high-throughput computations to screen reduction windows of novel molecules.

  15. Exact path integral treatment of a diatomic molecule potential

    SciTech Connect

    Benamira, F.; Guechi, L.; Mameri, S.; Sadoun, M. A.

    2007-03-15

    A rigorous evaluation of the path integral for Green's function associated with a four-parameter potential for a diatomic molecule is presented. A closed form of Green's function is obtained for different shapes of this potential. When the deformation parameter {lambda} is {lambda}<0 or 0<{lambda}<1, it is found that the quantization conditions are transcendental equations that require a numerical solution. For {lambda}{>=}1 and r set-membership sign](1/{eta})ln {lambda},{infinity}[, the energy spectrum and the normalized wave functions of the bound states are derived. Particular cases of this potential which appear in the literature are also briefly discussed.

  16. Electronic structure of molecules using relativistic effective core potentials

    SciTech Connect

    Hay, P.J.

    1981-01-01

    Starting with one-component Cowan-Griffin relativistic Hartree-Fock orbitals, which successfully incorporate the mass-velocity and Darwin terms present in more complicated wavefunctions such as Dirac-Hartree-Fock, one can derive relativistic effective core potentials (RECP's) to carry out molecular calculations. These potentials implicitly include the dominant relativistic terms for molecules while allowing one to use the traditional quantum chemical techniques for studying the electronic structure of molecules. The effects of spin-orbit coupling can then be included using orbitals from such calculations using an effective 1-electron, 1-center spin-orbit operator. Applications to molecular systems involving heavy atoms, show good agreement with available spectroscopic data on molecular geometries and excitation energies.

  17. Angle-resolved effective potentials for disk-shaped molecules

    NASA Astrophysics Data System (ADS)

    Heinemann, Thomas; Palczynski, Karol; Dzubiella, Joachim; Klapp, Sabine H. L.

    2014-12-01

    We present an approach for calculating coarse-grained angle-resolved effective pair potentials for uniaxial molecules. For integrating out the intramolecular degrees of freedom we apply umbrella sampling and steered dynamics techniques in atomistically-resolved molecular dynamics (MD) computer simulations. Throughout this study we focus on disk-like molecules such as coronene. To develop the methods we focus on integrating out the van der Waals and intramolecular interactions, while electrostatic charge contributions are neglected. The resulting coarse-grained pair potential reveals a strong temperature and angle dependence. In the next step we fit the numerical data with various Gay-Berne-like potentials to be used in more efficient simulations on larger scales. The quality of the resulting coarse-grained results is evaluated by comparing their pair and many-body structure as well as some thermodynamic quantities self-consistently to the outcome of atomistic MD simulations of many-particle systems. We find that angle-resolved potentials are essential not only to accurately describe crystal structures but also for fluid systems where simple isotropic potentials start to fail already for low to moderate packing fractions. Further, in describing these states it is crucial to take into account the pronounced temperature dependence arising in selected pair configurations due to bending fluctuations.

  18. Angle-resolved effective potentials for disk-shaped molecules

    SciTech Connect

    Heinemann, Thomas Klapp, Sabine H. L.; Palczynski, Karol Dzubiella, Joachim

    2014-12-07

    We present an approach for calculating coarse-grained angle-resolved effective pair potentials for uniaxial molecules. For integrating out the intramolecular degrees of freedom we apply umbrella sampling and steered dynamics techniques in atomistically-resolved molecular dynamics (MD) computer simulations. Throughout this study we focus on disk-like molecules such as coronene. To develop the methods we focus on integrating out the van der Waals and intramolecular interactions, while electrostatic charge contributions are neglected. The resulting coarse-grained pair potential reveals a strong temperature and angle dependence. In the next step we fit the numerical data with various Gay-Berne-like potentials to be used in more efficient simulations on larger scales. The quality of the resulting coarse-grained results is evaluated by comparing their pair and many-body structure as well as some thermodynamic quantities self-consistently to the outcome of atomistic MD simulations of many-particle systems. We find that angle-resolved potentials are essential not only to accurately describe crystal structures but also for fluid systems where simple isotropic potentials start to fail already for low to moderate packing fractions. Further, in describing these states it is crucial to take into account the pronounced temperature dependence arising in selected pair configurations due to bending fluctuations.

  19. Angle-resolved effective potentials for disk-shaped molecules.

    PubMed

    Heinemann, Thomas; Palczynski, Karol; Dzubiella, Joachim; Klapp, Sabine H L

    2014-12-07

    We present an approach for calculating coarse-grained angle-resolved effective pair potentials for uniaxial molecules. For integrating out the intramolecular degrees of freedom we apply umbrella sampling and steered dynamics techniques in atomistically-resolved molecular dynamics (MD) computer simulations. Throughout this study we focus on disk-like molecules such as coronene. To develop the methods we focus on integrating out the van der Waals and intramolecular interactions, while electrostatic charge contributions are neglected. The resulting coarse-grained pair potential reveals a strong temperature and angle dependence. In the next step we fit the numerical data with various Gay-Berne-like potentials to be used in more efficient simulations on larger scales. The quality of the resulting coarse-grained results is evaluated by comparing their pair and many-body structure as well as some thermodynamic quantities self-consistently to the outcome of atomistic MD simulations of many-particle systems. We find that angle-resolved potentials are essential not only to accurately describe crystal structures but also for fluid systems where simple isotropic potentials start to fail already for low to moderate packing fractions. Further, in describing these states it is crucial to take into account the pronounced temperature dependence arising in selected pair configurations due to bending fluctuations.

  20. Effective intermolecular potential and critical point for C60 molecule

    NASA Astrophysics Data System (ADS)

    Ramos, J. Eloy

    2017-07-01

    The approximate nonconformal (ANC) theory is applied to the C60 molecule. A new binary potential function is developed for C60, which has three parameters only and is obtained by averaging the site-site carbon interactions on the surface of two C60 molecules. It is shown that the C60 molecule follows, to a good approximation, the corresponding states principle with n-C8H18, n-C4F10 and n-C5F12. The critical point of C60 is estimated in two ways: first by applying the corresponding states principle under the framework of the ANC theory, and then by using previous computer simulations. The critical parameters obtained by applying the corresponding states principle, although very different from those reported in the literature, are consistent with the previous results of the ANC theory. It is shown that the Girifalco potential does not correspond to an average of the site-site carbon-carbon interaction.

  1. A transferable classical potential for the water molecule.

    PubMed

    Baranyai, András; Kiss, Péter T

    2010-10-14

    We developed a new model for the water molecule which contains only three Gaussian charges. Using the gas-phase geometry the dipole moment of the molecule matches, the quadrupole moment closely approximates the experimental values. The negative charge is connected by a harmonic spring to its gas-phase position. The polarized state is identified by the equality of the intermolecular electrostatic force and the spring force acting on the negative charge. In each timestep the instantaneous position of the massless negative charge is determined by iteration. Using the technique of Ewald summation, we derived expressions for the potential energy, the forces, and the pressure for Gaussian charges. The only properties to be fitted are the half-width values of the Gaussian charge distributions and the parameters of the nonelectrostatic repulsion-attraction potential. We determined the properties of gas-phase clusters up to six molecules, the internal energy and density of ambient water and hexagonal ice. We calculated the equilibrium density of ice VII as a function of pressure. As an additional test, we calculated the pair-correlation function, the isotherm compressibility, the heat capacity, and the self-diffusion coefficients for ambient water. As far as we know, this is the first classical model of water which is able to estimate both ends of the phase diagram, the high pressure ice VII, and the gas clusters of water with excellent accuracy.

  2. Potential of Nonfullerene Small Molecules with High Photovoltaic Performance.

    PubMed

    Li, Wanning; Yao, Huifeng; Zhang, Hao; Li, Sunsun; Hou, Jianhui

    2017-09-05

    Over the past decades, fullerene derivatives have become the most successful electron acceptors in organic solar cells (OSCs) and have achieved great progress, with power conversion efficiencies (PCEs) of over 11 %. However, fullerenes have some drawbacks, such as weak absorption, limited energy-level tunability, and morphological instability. In addition, fullerene-based OSCs usually suffer from large energy losses of over 0.7 eV, which limits further improvements in the PCE. Recently, nonfullerene small molecules have emerged as promising electron acceptors in OSCs. Their highly tunable absorption spectra and molecular energy levels have enabled fine optimization of the resulting devices, and the highest PCE has surpassed 12 %. Furthermore, several studies have shown that OSCs based on small-molecule acceptors (SMA) have very efficient charge generation and transport efficiency at relatively low energy losses of below 0.6 eV, which suggests great potential for the further improvement of OSCs. In this focus review, we analyze the challenges and potential of SMA-based OSCs and discuss molecular design strategies for highly efficient SMAs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Chemical potential and dimensions of chain molecules in athermal environments

    NASA Astrophysics Data System (ADS)

    Escobedo, Fernando A.

    A recently developed method for the simulation of chemical potentials of chain molecules (EVALENCH) is applied here to obtain the chemical potential, the mean square end-to-end distance (R2n) and the mean square radius of gyration (R2g) of dilute chains in different athermal media. The environments considered in this work are a frozen network structure, a deformable network matrix and a monomeric solvent at various densities. The properties of all chain lengths smaller than a preset maximum are calculated in a single simulation. A novel method is also presented for locating and computing the fraction of sampling space available to append one segment of an existing chain. This method enhances the range of densities where simulations of chemical potential are feasible. Simulated chemical potentials are compared with the predictions of two theories; good agreement is found in both cases. We find that R2n and R2g are reduced as the density of the medium is increased (network or solvent), while they are increased when the network is frozen and as the monomeric solvent size is made larger than that of the chain sites. At the conditions studied here, no direct evidence of chain collapse is observed.

  4. First-in-class small molecule potentiators of cancer virotherapy

    PubMed Central

    Dornan, Mark H.; Krishnan, Ramya; Macklin, Andrew M.; Selman, Mohammed; El Sayes, Nader; Son, Hwan Hee; Davis, Colin; Chen, Andrew; Keillor, Kerkeslin; Le, Penny J.; Moi, Christina; Ou, Paula; Pardin, Christophe; Canez, Carlos R.; Le Boeuf, Fabrice; Bell, John C.; Smith, Jeffrey C.; Diallo, Jean-Simon; Boddy, Christopher N.

    2016-01-01

    The use of engineered viral strains such as gene therapy vectors and oncolytic viruses (OV) to selectively destroy cancer cells is poised to make a major impact in the clinic and revolutionize cancer therapy. In particular, several studies have shown that OV therapy is safe and well tolerated in humans and can infect a broad range of cancers. Yet in clinical studies OV therapy has highly variable response rates. The heterogeneous nature of tumors is widely accepted to be a major obstacle for OV therapeutics and highlights a need for strategies to improve viral replication efficacy. Here, we describe the development of a new class of small molecules for selectively enhancing OV replication in cancer tissue. Medicinal chemistry studies led to the identification of compounds that enhance multiple OVs and gene therapy vectors. Lead compounds increase OV growth up to 2000-fold in vitro and demonstrate remarkable selectivity for cancer cells over normal tissue ex vivo and in vivo. These small molecules also demonstrate enhanced stability with reduced electrophilicity and are highly tolerated in animals. This pharmacoviral approach expands the scope of OVs to include resistant tumors, further potentiating this transformative therapy. It is easily foreseeable that this approach can be applied to therapeutically enhance other attenuated viral vectors. PMID:27226390

  5. SOCS: potential immune checkpoint molecules for cancer immunotherapy.

    PubMed

    Chikuma, Shunsuke; Kanamori, Mitsuhiro; Mise-Omata, Setsuko; Yoshimura, Akihiko

    2017-02-11

    Inhibition of immune checkpoint molecules, PD-1 and CTLA4, has been shown to be a promising cancer treatment. PD-1 and CTLA4 inhibit TCR and co-stimulatory signals, respectively. The third T cell activation signal represents the signals from the cytokine receptors. The cytokine Interferon-γ (IFNγ) plays an important role in anti-tumor immunity by activating cytotoxic T cells (CTLs). Most cytokines use the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, and the suppressors of cytokine signaling (SOCS) family of proteins are major negative regulators of the JAK/STAT pathway. Among SOCS proteins, CIS, SOCS1, and SOCS3 proteins can be considered the third immunocheckpoint molecules since they regulate cytokine signals that control the polarization of CD4(+) T cells and the maturation of CD8(+) T cells. This review summarizes recent progress on CIS, SOCS1, and SOCS3 in terms of their anti-tumor immunity and potential applications. This article is protected by copyright. All rights reserved.

  6. Carbohydrate-containing molecules as potential biomarkers in colon cancer.

    PubMed

    Joo, Eun Ji; Weyers, Amanda; Li, Guoyun; Gasimli, Leyla; Li, Lingyun; Choi, Won Jun; Lee, Kyung Bok; Linhardt, Robert J

    2014-04-01

    Glycans play a critical role in physiological and pathological processes through interaction with a variety of ligands. Altered expression and dysregulation of these molecules can cause aberrant cellular function such as malignancy. Glycomics provide information of the structure and function of glycans, glycolipids, and glycoproteins such as proteoglycans, and may help to predict cancer development and progression as biomarkers. In this report, we compared the expression of proteoglycans, the content and structure of glycosaminoglycans and glycolipids between patient-matched normal and cancer tissues obtained from colon cancer patients. Tumor-related proteoglycans, glypican-3, and syndecan-1 showed downregulation in cancer tissues compared to normal tissues. In cancer tissue, the total amount of chondroitin sulfate (CS)/dermatan sulfate and heparan sulfate were lower and, interestingly, the level of disaccharide units of both 4S6S (CS-E) and 6S (CS-C) were higher compared to normal tissue. Also, overall lipids including glycolipids, a major glycomics target, were analyzed by hydrophilic interaction liquid chromatography mass spectrometry. Increase of lyso-phosphatidylcholine (phospholipid), sphingomyelin (sphigolipid), and four types of glycolipids (glucosylceramide, lactosylceramide, monosialic acid ganglioside, and globoside 4) in cancer tissue showed the possibility as potential biomarkers in colon cancer. While requiring the need for careful interpretation, this type of broad investigation gives us a better understanding of pathophysiological roles on glycosaminoglycans and glycolipids and might be a powerful tool for colon cancer diagnosis.

  7. Carbohydrate-Containing Molecules as Potential Biomarkers in Colon Cancer

    PubMed Central

    Joo, Eun Ji; Weyers, Amanda; Li, Guoyun; Gasimli, Leyla; Li, Lingyun; Choi, Won Jun

    2014-01-01

    Abstract Glycans play a critical role in physiological and pathological processes through interaction with a variety of ligands. Altered expression and dysregulation of these molecules can cause aberrant cellular function such as malignancy. Glycomics provide information of the structure and function of glycans, glycolipids, and glycoproteins such as proteoglycans, and may help to predict cancer development and progression as biomarkers. In this report, we compared the expression of proteoglycans, the content and structure of glycosaminoglycans and glycolipids between patient-matched normal and cancer tissues obtained from colon cancer patients. Tumor-related proteoglycans, glypican-3, and syndecan-1 showed downregulation in cancer tissues compared to normal tissues. In cancer tissue, the total amount of chondroitin sulfate (CS)/dermatan sulfate and heparan sulfate were lower and, interestingly, the level of disaccharide units of both 4S6S (CS-E) and 6S (CS-C) were higher compared to normal tissue. Also, overall lipids including glycolipids, a major glycomics target, were analyzed by hydrophilic interaction liquid chromatography mass spectrometry. Increase of lyso-phosphatidylcholine (phospholipid), sphingomyelin (sphigolipid), and four types of glycolipids (glucosylceramide, lactosylceramide, monosialic acid ganglioside, and globoside 4) in cancer tissue showed the possibility as potential biomarkers in colon cancer. While requiring the need for careful interpretation, this type of broad investigation gives us a better understanding of pathophysiological roles on glycosaminoglycans and glycolipids and might be a powerful tool for colon cancer diagnosis. PMID:24502776

  8. Potential of small-molecule fungal metabolites in antiviral chemotherapy.

    PubMed

    Roy, Biswajit G

    2017-08-01

    Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge. Decades of intense research yielded a handful of natural and synthetic therapeutic options. But emergence of new viruses and drug-resistant viral strains had made new drug development process a never-ending battle. Small-molecule fungal metabolites due to their vast diversity, stereochemical complexity, and preapproved biocompatibility always remain an attractive source for new drug discovery. Though, exploration of therapeutic importance of fungal metabolites has started early with discovery of penicillin, recent prediction asserted that only a small percentage (5-10%) of fungal species have been identified and much less have been scientifically investigated. Therefore, exploration of new fungal metabolites, their bioassay, and subsequent mechanistic study bears huge importance in new drug discovery endeavors. Though no fungal metabolites so far approved for antiviral treatment, many of these exhibited high potential against various viral diseases. This review comprehensively discussed about antiviral activities of fungal metabolites of diverse origin against some important viral diseases. This also highlighted the mechanistic details of inhibition of viral replication along with structure-activity relationship of some common and important classes of fungal metabolites.

  9. Up and away in the potential landscape of diatomic molecule potential energy curves

    NASA Astrophysics Data System (ADS)

    Stwalley, William C.

    2016-12-01

    The understanding of the potential curves of a given molecule has expanded in many ways during my last 52 years as an experimental and theoretical molecular chemist/physicist in graduate school in Chemistry at Harvard and in both the Chemistry and Physics Departments at University of Iowa and University of Connecticut. This expansion has been up in energy and vibrational and rotational quantum numbers and away from Re to long range as well. It is clear that Prof. Robert Le Roy, who I have known since the late 1960s, has made many important and greatly appreciated contributions to the landscape I describe below from my personal perspective, especially with regard to long range molecules and solution of the radial Schrödinger equations and related calculations.

  10. Spectra for Small Volatile Molecules for Potential Exoplanet Biosignature Gases

    NASA Astrophysics Data System (ADS)

    Zhan, Zhuchang; Seager, Sara; Bains, William; Eckman, Laura; Gandhi, Anshula; Lin, Zifan; Pajusalu, Mihkel; Petkowski, Janusz; Sha, Lizhou

    2015-12-01

    With thousands of exoplanets discovered orbiting nearby stars, the community anticipates that next-generation telescopes will have the capability to detect a few habitable planets and possibly find signs of life via biosignature gases in the atmosphere. We propose that life on another world could produce a large variety of gases. If a significant quantity of certain volatile molecule is produced, it could be considered as a biosignature gas. We have collected existing spectra for over 1000 volatile molecules from searching dozens of existing on-line databases. We present representative spectra for different classes of molecules, and discuss differences within each class. We highlight gases that, based on atmospheric lifetimes, might be observable if produced in abundance and offer an observational “triage” strategy.

  11. Electric potential invariants and ions-in-molecules effective potentials for molecular Rydberg states.

    PubMed

    Coy, Stephen L; Grimes, David D; Zhou, Yan; Field, Robert W; Wong, Bryan M

    2016-12-21

    The dependence of multipole moments and polarizabilities on external fields appears in many applications including biomolecular molecular mechanics, optical non-linearity, nanomaterial calculations, and the perturbation of spectroscopic signatures in atomic clocks. Over a wide range of distances, distributed multipole and polarizability potentials can be applied to obtain the variation of atom-centered atoms-in-molecules electric properties like bonding-quenched polarizability. For cylindrically symmetric charge distributions, we examine single-center and atom-centered effective polarization potentials in a non-relativistic approximation for Rydberg states. For ions, the multipole expansion is strongly origin-dependent, but we note that origin-independent invariants can be defined. The several families of invariants correspond to optimized representations differing by origin and number of terms. Among them, a representation at the center of dipole polarizability optimizes the accuracy of the potential with terms through 1/r(4). We formulate the single-center expansion in terms of polarization-modified effective multipole moments, defining a form related to the source-multipole expansion of Brink and Satchler. Atom-centered potentials are an origin independent alternative but are limited both by the properties allowed at each center and by the neglected effects like bond polarizability and charge flow. To enable comparisons between single-center effective potentials in Cartesian or spherical form and two-center effective potentials with differing levels of mutual induction between atomic centers, we give analytical expressions for the bond-length and origin-dependence of multipole and polarizability terms projected in the multipole and polarizability expansion of Buckingham. The atom-centered potentials can then be used with experimental data and ab initio calculations to estimate atoms-in-molecules properties. Some results are given for BaF(+) and HF showing the

  12. Electric potential invariants and ions-in-molecules effective potentials for molecular Rydberg states

    NASA Astrophysics Data System (ADS)

    Coy, Stephen L.; Grimes, David D.; Zhou, Yan; Field, Robert W.; Wong, Bryan M.

    2016-12-01

    The dependence of multipole moments and polarizabilities on external fields appears in many applications including biomolecular molecular mechanics, optical non-linearity, nanomaterial calculations, and the perturbation of spectroscopic signatures in atomic clocks. Over a wide range of distances, distributed multipole and polarizability potentials can be applied to obtain the variation of atom-centered atoms-in-molecules electric properties like bonding-quenched polarizability. For cylindrically symmetric charge distributions, we examine single-center and atom-centered effective polarization potentials in a non-relativistic approximation for Rydberg states. For ions, the multipole expansion is strongly origin-dependent, but we note that origin-independent invariants can be defined. The several families of invariants correspond to optimized representations differing by origin and number of terms. Among them, a representation at the center of dipole polarizability optimizes the accuracy of the potential with terms through 1/r4. We formulate the single-center expansion in terms of polarization-modified effective multipole moments, defining a form related to the source-multipole expansion of Brink and Satchler. Atom-centered potentials are an origin independent alternative but are limited both by the properties allowed at each center and by the neglected effects like bond polarizability and charge flow. To enable comparisons between single-center effective potentials in Cartesian or spherical form and two-center effective potentials with differing levels of mutual induction between atomic centers, we give analytical expressions for the bond-length and origin-dependence of multipole and polarizability terms projected in the multipole and polarizability expansion of Buckingham. The atom-centered potentials can then be used with experimental data and ab initio calculations to estimate atoms-in-molecules properties. Some results are given for BaF+ and HF showing the

  13. Integrated Computational Solution for Predicting Skin Sensitization Potential of Molecules

    PubMed Central

    Desai, Aarti; Singh, Vivek K.; Jere, Abhay

    2016-01-01

    Introduction Skin sensitization forms a major toxicological endpoint for dermatology and cosmetic products. Recent ban on animal testing for cosmetics demands for alternative methods. We developed an integrated computational solution (SkinSense) that offers a robust solution and addresses the limitations of existing computational tools i.e. high false positive rate and/or limited coverage. Results The key components of our solution include: QSAR models selected from a combinatorial set, similarity information and literature-derived sub-structure patterns of known skin protein reactive groups. Its prediction performance on a challenge set of molecules showed accuracy = 75.32%, CCR = 74.36%, sensitivity = 70.00% and specificity = 78.72%, which is better than several existing tools including VEGA (accuracy = 45.00% and CCR = 54.17% with ‘High’ reliability scoring), DEREK (accuracy = 72.73% and CCR = 71.44%) and TOPKAT (accuracy = 60.00% and CCR = 61.67%). Although, TIMES-SS showed higher predictive power (accuracy = 90.00% and CCR = 92.86%), the coverage was very low (only 10 out of 77 molecules were predicted reliably). Conclusions Owing to improved prediction performance and coverage, our solution can serve as a useful expert system towards Integrated Approaches to Testing and Assessment for skin sensitization. It would be invaluable to cosmetic/ dermatology industry for pre-screening their molecules, and reducing time, cost and animal testing. PMID:27271321

  14. Temperature independent spherical potential which reproduces exactly the second virial coefficient of nonpolar molecules

    SciTech Connect

    Shaw, M.S.; Johnson, J.D.

    1984-10-01

    An expression is derived for a temperature independent spherical potential which reproduces exactly the second virial coefficient for nonpolar molecules given the full anisotropic potential. Comparison is made with the median average over angles and the arithmetic average.

  15. New torsion potential expression for molecules without rotational symmetry

    NASA Astrophysics Data System (ADS)

    Ji, Xiaobo; Yan, Liuming; Lu, Wencong

    2008-06-01

    A new torsion potential function for bond rotations without rotational symmetry is proposed. This function is composed of a few Gaussian-type terms each corresponding to an eclipsed conformation of the 1,2 substituents of the C-C bonds. Different from the truncated Fourier series or the truncated cosine polynomial, it is easy to determine how many terms are needed to represent any type of torsion potential barrier at a glance using the Gaussian-type function. It could also intuitively deduce the physical meaning of the expansion parameters of the new torsion potential function, which corresponds to the barrier height, the dihedral defining the eclipsed conformations, and the size of the substituents, respectively. The new torsion potential function is also applied to the 1, 2-substituted haloethanes with satisfactory results, where three Gaussian-type terms corresponding to the fully eclipsed and the partially eclipsed conformations are needed.

  16. Potential energy surfaces and reaction dynamics of polyatomic molecules

    SciTech Connect

    Chang, Yan-Tyng

    1991-11-01

    A simple empirical valence bond (EVB) model approach is suggested for constructing global potential energy surfaces for reactions of polyatomic molecular systems. This approach produces smooth and continuous potential surfaces which can be directly utilized in a dynamical study. Two types of reactions are of special interest, the unimolecular dissociation and the unimolecular isomerization. For the first type, the molecular dissociation dynamics of formaldehyde on the ground electronic surface is investigated through classical trajectory calculations on EVB surfaces. The product state distributions and vector correlations obtained from this study suggest very similar behaviors seen in the experiments. The intramolecular hydrogen atom transfer in the formic acid dimer is an example of the isomerization reaction. High level ab initio quantum chemistry calculations are performed to obtain optimized equilibrium and transition state dimer geometries and also the harmonic frequencies.

  17. On the trends of Fukui potential and hardness potential derivatives in isolated atoms vs. atoms in molecules.

    PubMed

    Bhattacharjee, Rituparna; Roy, Ram Kinkar

    2014-10-28

    In the present study, trends of electronic contribution to molecular electrostatic potential [Vel(r¯)(r=0)], Fukui potential [v(+)f|(r=0) and v(-)f|(r=0)] and hardness potential derivatives [Δ(+)h(k) and Δ(-)h(k)] for isolated atoms as well as atoms in molecules are investigated. The generated numerical values of these three reactivity descriptors in these two electronically different situations are critically analyzed through the relevant formalism. Values of Vel(r¯) (when r → 0, i.e., on the nucleus) are higher for atoms in molecules than that of isolated atoms. In contrast, higher values of v(+)|(r=0) and v(-)|(r=0) are observed for isolated atoms compared to the values for atoms in a molecule. However, no such regular trend is observed for the Δ(+)h(k) and Δ(-)h(k) values, which is attributed to the uncertainty in the Fukui function values of atoms in molecules. The sum of Fukui potential and the sum of hardness potential derivatives in molecules are also critically analyzed, which shows the efficacy of orbital relaxation effects in quantifying the values of these parameters. The chemical consequence of the observed trends of these descriptors in interpreting electron delocalization, electronic relaxation and non-negativity of atomic Fukui function indices is also touched upon. Several commonly used molecules containing carbon as well as heteroatoms are chosen to make the investigation more insightful.

  18. Novel small molecules potentiate premature termination codon readthrough by aminoglycosides

    PubMed Central

    Baradaran-Heravi, Alireza; Balgi, Aruna D.; Zimmerman, Carla; Choi, Kunho; Shidmoossavee, Fahimeh S.; Tan, Jason S.; Bergeaud, Célia; Krause, Alexandra; Flibotte, Stéphane; Shimizu, Yoko; Anderson, Hilary J.; Mouly, Vincent; Jan, Eric; Pfeifer, Tom; Jaquith, James B.; Roberge, Michel

    2016-01-01

    Nonsense mutations introduce premature termination codons and underlie 11% of genetic disease cases. High concentrations of aminoglycosides can restore gene function by eliciting premature termination codon readthrough but with low efficiency. Using a high-throughput screen, we identified compounds that potentiate readthrough by aminoglycosides at multiple nonsense alleles in yeast. Chemical optimization generated phthalimide derivative CDX5-1 with activity in human cells. Alone, CDX5-1 did not induce readthrough or increase TP53 mRNA levels in HDQ-P1 cancer cells with a homozygous TP53 nonsense mutation. However, in combination with aminoglycoside G418, it enhanced readthrough up to 180-fold over G418 alone. The combination also increased readthrough at all three nonsense codons in cancer cells with other TP53 nonsense mutations, as well as in cells from rare genetic disease patients with nonsense mutations in the CLN2, SMARCAL1 and DMD genes. These findings open up the possibility of treating patients across a spectrum of genetic diseases caused by nonsense mutations. PMID:27407112

  19. A semi-empirical analytical potential for diatomic molecules at spherical fullerenes

    NASA Astrophysics Data System (ADS)

    Hernández-Rojas, J.; Bretón, J.; Gomez Llorente, J. M.

    1994-05-01

    A simple analytical semi-empirical potential for the interaction between a diatomic molecule and a spherical fullerene is proposed. The potential assumes a spherical continuum representation for the fullerene cage. Equilibrium positions and vibrational frequencies calculated with our expression are in good agreement with ab initio computations. The model is used in a systematic and comparative analysis of the statics of the fullerene endohedral complexes of small diatomic molecules.

  20. Effect of an improved molecular potential on strong-field tunneling ionization of molecules

    SciTech Connect

    Zhao Songfeng; Jin Cheng; Le, Anh-Thu; Lin, C. D.

    2010-09-15

    We study the effect of one-electron model potentials on the tunneling ionization rates of molecules in strong fields. By including electron correlation using the modified Leeuwen-Baerends (LB {alpha}) model, the binding energies of outer shells of molecules are significantly improved. However, we show that the tunneling ionization rates from the LB {alpha} do not differ much from the earlier calculations [Phys. Rev. A 81, 033423 (2010)], in which the local correlation potential was neglected.

  1. Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications.

    PubMed

    Laurencin, Cato T; Ashe, Keshia M; Henry, Nicole; Kan, Ho Man; Lo, Kevin W-H

    2014-06-01

    Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. However, common limitations with protein growth factors, such as high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host reduce potential clinical applications. New strategies for bone regeneration that involve inexpensive and stable small molecules can obviate these problems and have a significant impact on the treatment of skeletal injury and diseases. Over the past decade, a large number of small molecules with the potential of regenerating skeletal tissue have been reported in the literature. Here, we review this literature, paying specific attention to the prospects for small molecule-based bone-regenerative engineering. We also review the preclinical study of small molecules associated with bone regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Astrophysical molecules of A1H and CaH - RKR potential and dissociation energies

    NASA Astrophysics Data System (ADS)

    Narasimhamurthy, B.; Rajamanickam, N.

    1983-03-01

    The true potential energy curves for the electronic ground states of astrophysically important AlH and CaH molecules are constructed by the Rydberg-Klein-Rees method. Empirical potential functions, of three-parameters by Lippincott, of five-parameters by Hulburt and Hirschfelder and, of electronegativity by Szöke and Baitz, are examined for the adequacy to represent the true curve. From the best-fitting function, the dissociation energies D00 of AlH and CaH molecules are estimated to be 2.99±0.08 and 2.72±0.06 eV respectively.

  3. Bose polaronic soliton-molecule and vector solitons in PT -symmetric potential

    NASA Astrophysics Data System (ADS)

    Boudjemâa, Abdelâali

    2017-07-01

    We study analytically and numerically the properties of polaronic soliton molecules and vector solitons of a trapped Bose-Einstein condensate (BEC)-impurity mixture subjected to a PT -symmetric potential in a quasi one-dimensional geometry employing our time-dependent Hartree-Fock-Bogoliubov equations. Analytical results, based on a variational approach and checked with direct numerical simulations reveal that the width, chirp, the vibration frequency and the profile of impurity solitons are enhanced by varying the strengths of real and imaginary parts of PT -symmetric potential as well as the boson-boson and boson-impurity interaction. We address the impact of the imaginary part of the potential, which represents a gain-loss mechanism, on the dynamics and on the stability of the impurity soliton-molecule. We show that for sufficiently strong complex part of the potential, the single soliton exhibits a snake instability and the molecule destroys analogous to the dissociation of a diatomic molecule. We discuss, on the other hand, the formation of several unusual families of three-component vector solitons in the BEC-impurity mixture. An unconventional dark (D)-bright (B) soliton conversion is found.

  4. The complex susceptibility of a two-potential system of reorientating polar molecules

    NASA Astrophysics Data System (ADS)

    Gaiduk, Vladimir I.; Tseitlin, Boris M.; Gaiduk, Vladimir V.; McConnell, James

    1994-04-01

    The problem of accounting for the finiteness of collision times is elaborated from the viewpoint that the steady state law of motion of a dipolar particle is governed by two potentials. These describe the torque exerted on a given molecule by neighbouring particles. In liquids different classical laws of motion correspond to different potentials. We may consider that in a gaseous state one of the two potential functions U(ϑ) does not depend on the orientational angle of the rotor. In this case the usual quantum (equidistant) rotational spectrum of polar molecules results. Then the other potential, acting when gas particles are close one with another, may be introduced to describe classically the influence of collisions on the above discrete spectrum. The new approach employs fewer parameters of the molecular model than previously in the study of the two-potential state, since the number of particles in either state is expressed through lifetimes τ 1, τ 2 in the two states. Due to the mutual interference of the two potential states there occurs in a classical ensemble of molecules the sharpening of the frequency dependence of the absorption coefficient. The dielectric spectra at lower frequencies also change.

  5. Affibody molecules: potential for in vivo imaging of molecular targets for cancer therapy.

    PubMed

    Tolmachev, Vladimir; Orlova, Anna; Nilsson, Fredrik Y; Feldwisch, Joachim; Wennborg, Anders; Abrahmsén, Lars

    2007-04-01

    Targeting radionuclide imaging of tumor-associated antigens may help to select patients who will benefit from a particular biological therapy. Affibody molecules are a novel class of small (approximately 7 kDa) phage display-selected affinity proteins, based on the B-domain scaffold of staphylococcal protein A. A large library (3 x 10(9) variants) has enabled selection of high-affinity (up to 22 pM) binders for a variety of tumor-associated antigens. The small size of Affibody molecules provides rapid tumor localization and fast clearance from nonspecific compartments. Preclinical studies have demonstrated the potential of Affibody molecules for specific and high-contrast radionuclide imaging of HER2 in vivo, and pilot clinical data using indium-111 and gallium-68 labeled anti-HER2 Affibody tracer have confirmed its utility for radionuclide imaging in cancer patients.

  6. Dynamical Green's function and an exact optical potential for electron-molecule scattering including nuclear dynamics

    NASA Astrophysics Data System (ADS)

    Brand, Joachim; Cederbaum, Lorenz S.; Meyer, Hans-Dieter

    1999-10-01

    We derive a rigorous optical potential for electron-molecule scattering including the effects of nuclear dynamics by extending the common many-body Green's function approach to optical potentials beyond the fixed-nuclei limit for molecular targets. Our formalism treats the projectile electron and the nuclear motion of the target molecule on the same footing whereby the dynamical optical potential rigorously accounts for the complex many-body nature of the scattering target. One central result of the present work is that the common fixed-nuclei optical potential is a valid adiabatic approximation to the dynamical optical potential even when projectile and nuclear motion are (nonadiabatically) coupled as long as the scattering energy is well below the electronic excitation thresholds of the target. For extremely low projectile velocities, however, when the cross sections are most sensitive to the scattering potential, we expect the influences of the nuclear dynamics on the optical potential to become relevant. For these cases, a systematic way to improve the adiabatic approximation to the dynamical optical potential is presented that yields nonlocal operators with respect to the nuclear coordinates.

  7. Non-additivity of molecule-surface van der Waals potentials from force measurements.

    PubMed

    Wagner, Christian; Fournier, Norman; Ruiz, Victor G; Li, Chen; Müllen, Klaus; Rohlfing, Michael; Tkatchenko, Alexandre; Temirov, Ruslan; Tautz, F Stefan

    2014-11-26

    Van der Waals (vdW) forces act ubiquitously in condensed matter. Despite being weak on an atomic level, they substantially influence molecular and biological systems due to their long range and system-size scaling. The difficulty to isolate and measure vdW forces on a single-molecule level causes our present understanding to be strongly theory based. Here we show measurements of the attractive potential between differently sized organic molecules and a metal surface using an atomic force microscope. Our choice of molecules and the large molecule-surface separation cause this attraction to be purely of vdW type. The experiment allows testing the asymptotic vdW force law and its validity range. We find a superlinear growth of the vdW attraction with molecular size, originating from the increased deconfinement of electrons in the molecules. Because such non-additive vdW contributions are not accounted for in most first-principles or empirical calculations, we suggest further development in that direction.

  8. Nanoelectrode-Gated Detection of Individual Molecules with Potential for Rapid DNA Sequencing

    SciTech Connect

    Lee, James Weifu

    2007-01-01

    A systematic nanoelectrode-gated electron-tunneling molecular-detection concept with potential for rapid DNA sequencing has recently been invented at Oak Ridge National Laboratory (ORNL). A DNA molecule is a polymer that typically contains four different types of nucleotide bases: adenine (A), thymine (T), guanine (G), and cytosine (C) on its phosphate-deoxyribose chain. According to the nanoelectrode-gated molecular-detection concept, it should be possible to obtain genetic sequence information by probing through a DNA molecule base by base at a nanometer scale, as if looking at a strip of movie film. The nanoscale reading of DNA sequences is envisioned to take place at a nanogap (gate) defined by a pair of nanoelectrode tips as a DNA molecule moves through the gate base by base. The rationale is that sample molecules, such as the four different nucleotide bases, each with a distinct chemical composition and structure, should produce a specific perturbation effect on the tunneling electron beam across the two nanoelectrode tips. A sample molecule could thus be detected when it enters the gate. This nanoscience-based approach could lead to a new DNA sequencing technology that could be thousands of times faster than the current technology (Sanger's 'dideoxy' protocol-based capillary electrophoresis systems). Both computational and experimental studies are underway at ORNL towards demonstrating this nanotechnology concept.

  9. Non-additivity of molecule-surface van der Waals potentials from force measurements

    PubMed Central

    Wagner, Christian; Fournier, Norman; Ruiz, Victor G.; Li, Chen; Müllen, Klaus; Rohlfing, Michael; Tkatchenko, Alexandre; Temirov, Ruslan; Tautz, F. Stefan

    2014-01-01

    Van der Waals (vdW) forces act ubiquitously in condensed matter. Despite being weak on an atomic level, they substantially influence molecular and biological systems due to their long range and system-size scaling. The difficulty to isolate and measure vdW forces on a single-molecule level causes our present understanding to be strongly theory based. Here we show measurements of the attractive potential between differently sized organic molecules and a metal surface using an atomic force microscope. Our choice of molecules and the large molecule-surface separation cause this attraction to be purely of vdW type. The experiment allows testing the asymptotic vdW force law and its validity range. We find a superlinear growth of the vdW attraction with molecular size, originating from the increased deconfinement of electrons in the molecules. Because such non-additive vdW contributions are not accounted for in most first-principles or empirical calculations, we suggest further development in that direction. PMID:25424490

  10. Modeling of diatomic molecule using the Morse potential and the Verlet algorithm

    SciTech Connect

    Fidiani, Elok

    2016-03-11

    Performing molecular modeling usually uses special software for Molecular Dynamics (MD) such as: GROMACS, NAMD, JMOL etc. Molecular dynamics is a computational method to calculate the time dependent behavior of a molecular system. In this work, MATLAB was used as numerical method for a simple modeling of some diatomic molecules: HCl, H{sub 2} and O{sub 2}. MATLAB is a matrix based numerical software, in order to do numerical analysis, all the functions and equations describing properties of atoms and molecules must be developed manually in MATLAB. In this work, a Morse potential was generated to describe the bond interaction between the two atoms. In order to analyze the simultaneous motion of molecules, the Verlet Algorithm derived from Newton’s Equations of Motion (classical mechanics) was operated. Both the Morse potential and the Verlet algorithm were integrated using MATLAB to derive physical properties and the trajectory of the molecules. The data computed by MATLAB is always in the form of a matrix. To visualize it, Visualized Molecular Dynamics (VMD) was performed. Such method is useful for development and testing some types of interaction on a molecular scale. Besides, this can be very helpful for describing some basic principles of molecular interaction for educational purposes.

  11. Therapeutic potential of abalone and status of bioactive molecules: A comprehensive review.

    PubMed

    Suleria, H A R; Masci, P P; Gobe, G C; Osborne, S A

    2017-05-24

    Marine organisms are increasingly being investigated as sources of bioactive molecules with therapeutic applications as nutraceuticals and pharmaceuticals. In particular, nutraceuticals are gaining popularity worldwide owing to their therapeutic potential and incorporation in functional foods and dietary supplements. Abalone, a marine gastropod, contains a variety of bioactive compounds with anti-oxidant, anti-thrombotic, anti-inflammatory, anti-microbial, and anti-cancer activities. For thousands of years different cultures have used abalone as a traditional functional food believing consumption provides health benefits. Abalone meat is one of the most precious commodities in Asian markets where it is considered a culinary delicacy. Recent research has revealed that abalone is composed of many vital moieties like polysaccharides, proteins, and fatty acids that provide health benefits beyond basic nutrition. A review of past and present research is presented with relevance to the therapeutic potential of bioactive molecules from abalone.

  12. Ab initio potential energy surface for the highly nonlinear dynamics of the KCN molecule

    SciTech Connect

    Párraga, H.; Arranz, F. J. Benito, R. M.; Borondo, F.

    2013-11-21

    An accurate ab initio quantum chemistry study at level of quadratic configuration interaction method of the electronic ground state of the KCN molecule is presented. A fitting of the results to an analytical series expansion was performed to obtain a global potential energy surface suitable for the study of the associated vibrational dynamics. Additionally, classical Poincaré surfaces of section for different energies and quantum eigenstates were calculated, showing the highly nonlinear behavior of this system.

  13. Adhesion molecules expression in CLL: Potential impact on clinical and hematological parameters.

    PubMed

    Kamel, Azza M; El-Sharkawy, Nahla M; Osman, Randa A; Abd El-Fattah, Eman K; El-Noshokaty, Essam; Abd El-Hamid, Thoraya; Kandeel, Eman Z

    2016-03-01

    B-cell chronic lymphocytic leukemia (CLL) is marked by the accumulation of CD5+ B lymphocytes within the blood, bone marrow (BM), and secondary lymphoid tissues. Abnormalities in the expression and function of cell adhesion molecules may account for the patterns of intra-nodal growth and hematogenous spread of the malignant cells. Chemokines and integrin-mediated adhesion and trans-endothelial migration (TEM) are central aspects in trafficking and retention of hematopoietic cells in the BM and lymphoid organs. This work was conducted to study adhesion molecules status in CLL and its potential impact on both hematological and clinical parameters. The study included 78 newly diagnosed CLL patients. Immunophenotyping was performed on peripheral blood using the chronic lymphoid panel. Adhesion molecules (CD11a, CD11b, CD49d, CD49C, CD29 and CD38) were tested using monoclonal antibodies and analyzed by Flow Cytometry. Positive correlation was encountered between adhesion molecules: CD38 with CD49d (r=0.25, p=0.028), CD11a with CD11b, CD49d and CD29 (r=0.394, p=0.001; r=0.441, p=<0.01 and r=0.446, p<0.01 respectively) and CD29 with CD49c and CD49d (r=0.437, p<0.01; r=0.674, p<0.01 respectively). CD49c showed negative correlation with Rai staging (r=-0.269, p=0.033). CD11a and CD29 showed a significant relation with splenomegaly (p=0.04 and 0.03 respectively) and CD49d showed a significant relation with lymphadenopathy (p=0.02). The level of different adhesion molecules expression in CLL is apparently reflected on the potential migratory behavior of the leukemic cells to different organs. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  14. A Structure Based Model for the Prediction of Phospholipidosis Induction Potential of Small Molecules

    PubMed Central

    Sun, Hongmao; Shahane, Sampada; Xia, Menghang; Austin, Christopher P.; Huang, Ruili

    2012-01-01

    Drug-induced phospholipidosis (PLD), characterized by an intracellular accumulation of phospholipids and formation of concentric lamellar bodies, has raised concerns in the drug discovery community, due to its potential adverse effects. To evaluate the PLD induction potential, 4,161 non-redundant drug-like molecules from the National Institutes of Health Chemical Genomics Center (NCGC) Pharmaceutical Collection (NPC), the Library of Pharmacologically Active Compounds (LOPAC) and the Tocris Biosciences collection were screened in a quantitative high-throughput screening (qHTS) format. The potential of drug-lipid complex formation can be linked directly to the structures of drug molecules, and many PLD inducing drugs were found to share common structural features. Support vector machine (SVM) models were constructed by using customized atom types or Molecular Operating Environment (MOE) 2D descriptors as structural descriptors. Either the compounds from LOPAC or randomly selected from the entire dataset were used as the training set. The impact of training data with biased structural features and the impact of molecule descriptors emphasizing whole-molecule properties or detailed functional groups at the atom level on model performance were analyzed and discussed. Rebalancing strategies were applied to improve the predictive power of the SVM models. Using the under-sampling method, the consensus model using one third of the compounds randomly selected from the data set as the training set achieved high accuracy of 0.90 in predicting the remaining two thirds of the compounds constituting the test set, as measured by the area under the receiver operator characteristic curve (AUC-ROC). PMID:22725677

  15. Psmir: a database of potential associations between small molecules and miRNAs.

    PubMed

    Meng, Fanlin; Wang, Jing; Dai, Enyu; Yang, Feng; Chen, Xiaowen; Wang, Shuyuan; Yu, Xuexin; Liu, Dianming; Jiang, Wei

    2016-01-13

    miRNAs are key post-transcriptional regulators of many essential biological processes, and their dysregulation has been validated in almost all human cancers. Restoring aberrantly expressed miRNAs might be a novel therapeutics. Recently, many studies have demonstrated that small molecular compounds can affect miRNA expression. Thus, prediction of associations between small molecules and miRNAs is important for investigation of miRNA-targeted drugs. Here, we analyzed 39 miRNA-perturbed gene expression profiles, and then calculated the similarity of transcription responses between miRNA perturbation and drug treatment to predict drug-miRNA associations. At the significance level of 0.05, we obtained 6501 candidate associations between 1295 small molecules and 25 miRNAs, which included 624 FDA approved drugs. Finally, we constructed the Psmir database to store all potential associations and the related materials. In a word, Psmir served as a valuable resource for dissecting the biological significance in small molecules' effects on miRNA expression, which will facilitate developing novel potential therapeutic targets or treatments for human cancers. Psmir is supported by all major browsers, and is freely available at http://www.bio-bigdata.com/Psmir/.

  16. The dispersion interaction between quantum mechanics and effective fragment potential molecules

    SciTech Connect

    Smith, Quentin A.; Ruedenberg, Klaus; Gordon, Mark S.; Slipchenko, Lyudmila

    2012-06-26

    A method for calculating the dispersion energy between molecules modeled with the general effective fragment potential (EFP2) method and those modeled using a full quantum mechanics (QM) method, e.g., Hartree-Fock (HF) or second-order perturbation theory, is presented. C6 dispersion coefficients are calculated for pairs of orbitals using dynamic polarizabilities from the EFP2 portion, and dipole integrals and orbital energies from the QM portion of the system. Dividing by the sixth power of the distance between localized molecular orbital centroids yields the first term in the commonly employed London series expansion. A C8 term is estimated from the C6 term to achieve closer agreement with symmetry adapted perturbation theory values. Two damping functions for the dispersion energy are evaluated. By using terms that are already computed during an ordinary HF or EFP2 calculation, the new method enables accurate and extremely rapid evaluation of the dispersion interaction between EFP2 and QM molecules.

  17. Determination of adiabatic ionization potentials and electron affinities of energetic molecules with the Gaussian-4 method

    NASA Astrophysics Data System (ADS)

    Manaa, M. Riad

    2017-06-01

    Adiabatic ionization potentials (IPad) and electron affinities (EAad) are determined with the Gaussian-4 (G4) method for the energetic molecules PETN, RDX, β-δ-HMX, CL-17, TNB, TNT, CL-14, DADNE, TNA, and TATB. The IPad and EAad values are in the range of 8.43-11.73 and 0.74-2.86 eV, respectively. Variations are due to substitutional effects of electron withdrawing and donating functional groups. Enthalpies of formation are also determined for several of these molecules to augment the list of recently reported G4 values. The calculated IPad and EAad provide quantitative assessment of such molecular properties as chemical hardness, molecular electronegativity, and ;intrinsic; molecular physical hardness.

  18. Quantum phase transitions of atom-molecule Bose mixtures in a double-well potential.

    PubMed

    Relaño, A; Dukelsky, J; Pérez-Fernández, P; Arias, J M

    2014-10-01

    The ground state and spectral properties of Bose gases in double-well potentials are studied in two different scenarios: (i) an interacting atomic Bose gas, and (ii) a mixture of an atomic gas interacting with diatomic molecules. A ground state second-order quantum phase transition is observed in both scenarios. For large attractive values of the atom-atom interaction, the ground state is degenerate. For repulsive and small attractive interaction, the ground state is not degenerate and is well approximated by a boson coherent state. Both systems depict an excited state quantum phase transition. In both cases, a critical energy separates a region in which all the energy levels are degenerate in pairs, from another region in which there are no degeneracies. For the atomic system, the critical point displays a singularity in the density of states, whereas this behavior is largely smoothed for the mixed atom-molecule system.

  19. Early-Late Heterobimetallic Complexes Linked by Phosphinoamide Ligands. Tuning Redox Potentials and Small Molecule Activation

    SciTech Connect

    Thomas, Christine M.

    2015-08-01

    Recent attention in the chemical community has been focused on the energy efficient and environmentally benign conversion of abundant small molecules (CO2, H2O, etc.) to useful liquid fuels. This project addresses these goals by examining fundamental aspects of catalyst design to ultimately access small molecule activation processes under mild conditions. Specifically, Thomas and coworkers have targetted heterobimetallic complexes that feature metal centers with vastly different electronic properties, dictated both by their respective positions on the periodic table and their coordination environment. Unlike homobimetallic complexes featuring identical or similar metals, the bonds between metals in early/late heterobimetallics are more polarized, with the more electron-rich late metal center donating electron density to the more electron-deficient early metal center. While metal-metal bonds pose an interesting strategy for storing redox equivalents and stabilizing reactive metal fragments, the polar character of metal-metal bonds in heterobimetallic complexes renders these molecules ideally poised to react with small molecule substrates via cleavage of energy-rich single and double bonds. In addition, metal-metal interactions have been shown to dramatically affect redox potentials and promote multielectron redox activity, suggesting that metal-metal interactions may provide a mechanism to tune redox potentials and access substrate reduction/activation at mild overpotentials. This research project has provided a better fundamental understanding of how interactions between transition metals can be used as a strategy to promote and/or control chemical transformations related to the clean production of fuels. While this project focused on the study of homogeneous systems, it is anticipated that the broad conclusions drawn from these investigations will be applicable to heterogeneous catalysis as well, particularly on heterogeneous processes that occur at interfaces in

  20. Stabilizing potentials in bound state analytic continuation methods for electronic resonances in polyatomic molecules.

    PubMed

    White, Alec F; Head-Gordon, Martin; McCurdy, C William

    2017-01-28

    The computation of Siegert energies by analytic continuation of bound state energies has recently been applied to shape resonances in polyatomic molecules by several authors. We critically evaluate a recently proposed analytic continuation method based on low order (type III) Padé approximants as well as an analytic continuation method based on high order (type II) Padé approximants. We compare three classes of stabilizing potentials: Coulomb potentials, Gaussian potentials, and attenuated Coulomb potentials. These methods are applied to a model potential where the correct answer is known exactly and to the Πg2 shape resonance of N2(-) which has been studied extensively by other methods. Both the choice of stabilizing potential and method of analytic continuation prove to be important to the accuracy of the results. We conclude that an attenuated Coulomb potential is the most effective of the three for bound state analytic continuation methods. With the proper potential, such methods show promise for algorithmic determination of the positions and widths of molecular shape resonances.

  1. Stabilizing potentials in bound state analytic continuation methods for electronic resonances in polyatomic molecules

    DOE PAGES

    White, Alec F.; Head-Gordon, Martin; McCurdy, C. William

    2017-01-30

    The computation of Siegert energies by analytic continuation of bound state energies has recently been applied to shape resonances in polyatomic molecules by several authors. Here, we critically evaluate a recently proposed analytic continuation method based on low order (type III) Padé approximants as well as an analytic continuation method based on high order (type II) Padé approximants. We compare three classes of stabilizing potentials: Coulomb potentials, Gaussian potentials, and attenuated Coulomb potentials. These methods are applied to a model potential where the correct answer is known exactly and to the 2Πg shape resonance of N 2 - which hasmore » been studied extensively by other methods. Both the choice of stabilizing potential and method of analytic continuation prove to be important to the accuracy of the results. We then conclude that an attenuated Coulomb potential is the most effective of the three for bound state analytic continuation methods. With the proper potential, such methods show promise for algorithmic determination of the positions and widths of molecular shape resonances.« less

  2. Stabilizing potentials in bound state analytic continuation methods for electronic resonances in polyatomic molecules

    NASA Astrophysics Data System (ADS)

    White, Alec F.; Head-Gordon, Martin; McCurdy, C. William

    2017-01-01

    The computation of Siegert energies by analytic continuation of bound state energies has recently been applied to shape resonances in polyatomic molecules by several authors. We critically evaluate a recently proposed analytic continuation method based on low order (type III) Padé approximants as well as an analytic continuation method based on high order (type II) Padé approximants. We compare three classes of stabilizing potentials: Coulomb potentials, Gaussian potentials, and attenuated Coulomb potentials. These methods are applied to a model potential where the correct answer is known exactly and to the Π2g shape resonance of N2- which has been studied extensively by other methods. Both the choice of stabilizing potential and method of analytic continuation prove to be important to the accuracy of the results. We conclude that an attenuated Coulomb potential is the most effective of the three for bound state analytic continuation methods. With the proper potential, such methods show promise for algorithmic determination of the positions and widths of molecular shape resonances.

  3. Potential semiochemical molecules from birds: a practical and comprehensive compilation of the last 20 years studies.

    PubMed

    Campagna, Sylvie; Mardon, Jérôme; Celerier, Aurélie; Bonadonna, Francesco

    2012-01-01

    During the past 2 decades, considerable progress has been made in the study of bird semiochemistry, and our goal was to review and evaluate this literature with particular emphasis on the volatile organic constituents. Indeed, since the importance of social chemosignaling in birds is becoming more and more apparent, the search for molecules involved in chemical communication is of critical interest. These molecules can be found in different sources that include uropygial gland secretions, feather-surface compounds, and molecules from feces and skin. Although many studies have examined the chemical substances secreted by birds, research on bird chemical communication is still at the start, so new strategies for collecting samples and development of new methods of analysis are urgently required. As a first step, we built a database that brings together potential semiochemicals, using a unique chemical nomenclature for comparing different bird species and also for referencing the different classes of substances that can be found in order to adapt future parameters of analysis. The most important patterns of the wax fraction of preen secretions are highlighted and organized in an ordered table. We also draw up a list of various combinations of sampling and analytical techniques, so that each method can be compared at a glance. © The Author 2011. Published by Oxford University Press. All rights reserved.

  4. The role of endogenous molecules in modulating pain through transient receptor potential vanilloid 1 (TRPV1).

    PubMed

    Morales-Lázaro, Sara L; Simon, Sidney A; Rosenbaum, Tamara

    2013-07-01

    Pain is a physiological response to a noxious stimulus that decreases the quality of life of those sufferring from it. Research aimed at finding new therapeutic targets for the treatment of several maladies, including pain, has led to the discovery of numerous molecular regulators of ion channels in primary afferent nociceptive neurons. Among these receptors is TRPV1 (transient receptor potential vanilloid 1), a member of the TRP family of ion channels. TRPV1 is a calcium-permeable channel, which is activated or modulated by diverse exogenous noxious stimuli such as high temperatures, changes in pH, and irritant and pungent compounds, and by selected molecules released during tissue damage and inflammatory processes. During the last decade the number of endogenous regulators of TRPV1's activity has increased to include lipids that can negatively regulate TRPV1, as is the case for cholesterol and PIP2 (phosphatidylinositol 4,5-biphosphate) while, in contrast, other lipids produced in response to tissue injury and ischaemic processes are known to positively regulate TRPV1. Among the latter, lysophosphatidic acid activates TRPV1 while amines such as N-acyl-ethanolamines and N-acyl-dopamines can sensitize or directly activate TRPV1. It has also been found that nucleotides such as ATP act as mediators of chemically induced nociception and pain and gases, such as hydrogen sulphide and nitric oxide, lead to TRPV1 activation. Finally, the products of lipoxygenases and omega-3 fatty acids among other molecules, such as divalent cations, have also been shown to endogenously regulate TRPV1 activity. Here we provide a comprehensive review of endogenous small molecules that regulate the function of TRPV1. Acting through mechanisms that lead to sensitization and desensitization of TRPV1, these molecules regulate pathways involved in pain and nociception. Understanding how these compounds modify TRPV1 activity will allow us to comprehend how some pathologies are associated with

  5. The role of endogenous molecules in modulating pain through transient receptor potential vanilloid 1 (TRPV1)

    PubMed Central

    Morales-Lázaro, Sara L; Simon, Sidney A; Rosenbaum, Tamara

    2013-01-01

    Pain is a physiological response to a noxious stimulus that decreases the quality of life of those sufferring from it. Research aimed at finding new therapeutic targets for the treatment of several maladies, including pain, has led to the discovery of numerous molecular regulators of ion channels in primary afferent nociceptive neurons. Among these receptors is TRPV1 (transient receptor potential vanilloid 1), a member of the TRP family of ion channels. TRPV1 is a calcium-permeable channel, which is activated or modulated by diverse exogenous noxious stimuli such as high temperatures, changes in pH, and irritant and pungent compounds, and by selected molecules released during tissue damage and inflammatory processes. During the last decade the number of endogenous regulators of TRPV1's activity has increased to include lipids that can negatively regulate TRPV1, as is the case for cholesterol and PIP2 (phosphatidylinositol 4,5-biphosphate) while, in contrast, other lipids produced in response to tissue injury and ischaemic processes are known to positively regulate TRPV1. Among the latter, lysophosphatidic acid activates TRPV1 while amines such as N-acyl-ethanolamines and N-acyl-dopamines can sensitize or directly activate TRPV1. It has also been found that nucleotides such as ATP act as mediators of chemically induced nociception and pain and gases, such as hydrogen sulphide and nitric oxide, lead to TRPV1 activation. Finally, the products of lipoxygenases and omega-3 fatty acids among other molecules, such as divalent cations, have also been shown to endogenously regulate TRPV1 activity. Here we provide a comprehensive review of endogenous small molecules that regulate the function of TRPV1. Acting through mechanisms that lead to sensitization and desensitization of TRPV1, these molecules regulate pathways involved in pain and nociception. Understanding how these compounds modify TRPV1 activity will allow us to comprehend how some pathologies are associated with

  6. Methods for Using Ab Initio Potential Energy Surfaces in Studies of Gas-Phase Reactions of Energetic Molecules

    DTIC Science & Technology

    2014-08-20

    Ab Initio Potential Energy Surfaces in Studies of Gas-Phase Reactions of Energetic Molecules The focus of this research was to apply efficient...methods for using ab initio potential energy surfaces (PESs) computed with high levels of quantum chemistry theory to predict chemical reaction properties...in non peer-reviewed journals: Methods for Using Ab Initio Potential Energy Surfaces in Studies of Gas-Phase Reactions of Energetic Molecules Report

  7. Single-molecule fluorescence imaging of DNA at a potential-controlled interface.

    PubMed

    Peterson, Eric M; Harris, Joel M

    2013-07-02

    Many interfacial chemical phenomena are governed in part by electrostatic interactions between polyelectrolytes and charged surfaces; these phenomena can influence the performance of biosensors, adsorption of natural polyelectrolytes (humic substances) on soils, and production of polyelectrolyte multilayer films. In order to understand electrostatic interactions that govern these phenomena, we have investigated the behavior of a model polyelectrolyte, 15 kbp fluorescently labeled plasmid DNA, near a polarized indium tin oxide (ITO) electrode surface. The interfacial population of DNA was monitored in situ by imaging individual molecules through the transparent electrode using total-internal-reflection fluorescence microscopy. At applied potentials of +0.8 V versus Ag/AgCl, the DNA interfacial population near the ITO surface can be increased by 2 orders of magnitude relative to bulk solution. The DNA molecules attracted to the interface do not adsorb to ITO, but rather they remain mobile with a diffusion coefficient comparable to free solution. Ionic strength strongly influences the sensitivity of the interfacial population to applied potential, where the increase in the interfacial population over a +300 mV change in potential varies from 20% in 30 mM ionic strength to over 25-fold in 300 μM electrolyte. The DNA accumulation with applied potential was interpreted using a simple Boltzmann model to predict average ion concentrations in the electrical double layer and the fraction of interfacial detection volume that is influenced by applied potential. A Gouy-Chapman model was also applied to the data to account for the dependence of the ion population on distance from the electrode surface, which indicates that the net charge on DNA responsible for interactions with the polarized surface is low, on the order of one excess electron. The results are consistent with a small fraction of the DNA plasmid being resident in the double-layer and with counterions screening

  8. Calculation of chemical potentials of chain molecules by the incremental gauge cell method.

    PubMed

    Rasmussen, Christopher J; Vishnyakov, Aleksey; Neimark, Alexander V

    2011-12-07

    The gauge cell Monte Carlo method is extended to calculations of the incremental chemical potentials and free energies of linear chain molecules. The method was applied to chains of Lennard-Jones beads with stiff harmonic bonds up to 500 monomers in length. We show that the suggested method quantitatively reproduces the modified Widom particle insertion method of Kumar et al. [S. K. Kumar, I. Szleifer, and A. Z. Panagiotopoulos, Phys. Rev. Lett. 66(22), 2935 (1991)], and is by an order of magnitude more efficient for long chains in terms of the computational time required for the same accuracy of chemical potential calculations. The chain increment ansatz, which suggests that the incremental chemical potential is independent of the chain length, was tested at different temperatures. We confirmed that the ansatz holds only for coils above the θ temperature. Special attention is paid to the effects of the magnitude of adsorption potential and temperature on the behavior of single chains in confinements that are comparable in size with the free chain radius of gyration. At sufficiently low temperatures, the dependence of the incremental chemical potential on the chain length in wetting pores is superficially similar to a capillary condensation isotherm, reflecting monolayer formation following by pore volume filling, as the chain length increases. We find that the incremental gauge cell method is an accurate and efficient technique for calculations of the free energies of chain molecules in bulk systems and nanoconfinements alike. The suggested method may find practical applications, such as modeling polymer partitioning on porous substrates and dynamics of chain translocation into nanopores.

  9. Calculation of chemical potentials of chain molecules by the incremental gauge cell method

    NASA Astrophysics Data System (ADS)

    Rasmussen, Christopher J.; Vishnyakov, Aleksey; Neimark, Alexander V.

    2011-12-01

    The gauge cell Monte Carlo method is extended to calculations of the incremental chemical potentials and free energies of linear chain molecules. The method was applied to chains of Lennard-Jones beads with stiff harmonic bonds up to 500 monomers in length. We show that the suggested method quantitatively reproduces the modified Widom particle insertion method of Kumar et al. [S. K. Kumar, I. Szleifer, and A. Z. Panagiotopoulos, Phys. Rev. Lett. 66(22), 2935 (1991)], 10.1103/PhysRevLett.66.2935, and is by an order of magnitude more efficient for long chains in terms of the computational time required for the same accuracy of chemical potential calculations. The chain increment ansatz, which suggests that the incremental chemical potential is independent of the chain length, was tested at different temperatures. We confirmed that the ansatz holds only for coils above the θ temperature. Special attention is paid to the effects of the magnitude of adsorption potential and temperature on the behavior of single chains in confinements that are comparable in size with the free chain radius of gyration. At sufficiently low temperatures, the dependence of the incremental chemical potential on the chain length in wetting pores is superficially similar to a capillary condensation isotherm, reflecting monolayer formation following by pore volume filling, as the chain length increases. We find that the incremental gauge cell method is an accurate and efficient technique for calculations of the free energies of chain molecules in bulk systems and nanoconfinements alike. The suggested method may find practical applications, such as modeling polymer partitioning on porous substrates and dynamics of chain translocation into nanopores.

  10. Psmir: a database of potential associations between small molecules and miRNAs

    PubMed Central

    Meng, Fanlin; Wang, Jing; Dai, Enyu; Yang, Feng; Chen, Xiaowen; Wang, Shuyuan; Yu, Xuexin; Liu, Dianming; Jiang, Wei

    2016-01-01

    miRNAs are key post-transcriptional regulators of many essential biological processes, and their dysregulation has been validated in almost all human cancers. Restoring aberrantly expressed miRNAs might be a novel therapeutics. Recently, many studies have demonstrated that small molecular compounds can affect miRNA expression. Thus, prediction of associations between small molecules and miRNAs is important for investigation of miRNA-targeted drugs. Here, we analyzed 39 miRNA-perturbed gene expression profiles, and then calculated the similarity of transcription responses between miRNA perturbation and drug treatment to predict drug-miRNA associations. At the significance level of 0.05, we obtained 6501 candidate associations between 1295 small molecules and 25 miRNAs, which included 624 FDA approved drugs. Finally, we constructed the Psmir database to store all potential associations and the related materials. In a word, Psmir served as a valuable resource for dissecting the biological significance in small molecules’ effects on miRNA expression, which will facilitate developing novel potential therapeutic targets or treatments for human cancers. Psmir is supported by all major browsers, and is freely available at http://www.bio-bigdata.com/Psmir/. PMID:26759061

  11. Animal models of schizophrenia for molecular and pharmacological intervention and potential candidate molecules.

    PubMed

    Mouri, Akihiro; Nagai, Taku; Ibi, Daisuke; Yamada, Kiyofumi

    2013-05-01

    Schizophrenia is a severe and common psychiatric disease with a lifetime prevalence of 0.5% to 1% globally. Because of limitations of the experimental approach in humans, valid animal models are essential in the effort to identify novel therapeutics for schizophrenia. In most animal models of schizophrenia, second generation antipsychotic drugs are reported to be effective in ameliorating behavioral abnormalities, while clinical evidence indicates that some of the patients are resistant to the antipsychotic drug therapy. Accordingly, animal models of antipsychotic drug-resistant schizophrenia are needed for screening of novel agents that may be more effective than the existing antipsychotic drugs. Furthermore, utilization of appropriate behavioral tasks with reference to human testing is essential to facilitate the development of novel pharmacotherapeutic approaches for the treatment in schizophrenia. Experimental data suggest that there are different types of potential candidate molecules as novel antipsychotic drugs with some therapeutic effects on negative symptoms and cognitive deficits in schizophrenia. It is proposed that to develop novel antipsychotic drugs the efficacy of potential candidate molecules should be evaluated using animal models for treatment-resistant schizophrenia with appropriate behavioral tasks in reference to human testing. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Marine Microbial-Derived Molecules and Their Potential Use in Cosmeceutical and Cosmetic Products

    PubMed Central

    Corinaldesi, Cinzia; Barone, Giulio; Marcellini, Francesca; Dell’Anno, Antonio; Danovaro, Roberto

    2017-01-01

    The oceans encompass a wide range of habitats and environmental conditions, which host a huge microbial biodiversity. The unique characteristics of several marine systems have driven a variety of biological adaptations, leading to the production of a large spectrum of bioactive molecules. Fungi, fungi-like protists (such as thraustochytrids) and bacteria are among the marine organisms with the highest potential of producing bioactive compounds, which can be exploited for several commercial purposes, including cosmetic and cosmeceutical ones. Mycosporines and mycosporine-like amino acids, carotenoids, exopolysaccharides, fatty acids, chitosan and other compounds from these microorganisms might represent a sustainable, low-cost and fast-production alternative to other natural molecules used in photo-protective, anti-aging and skin-whitening products for face, body and hair care. Here, we review the existing knowledge of these compounds produced by marine microorganisms, highlighting the marine habitats where such compounds are preferentially produced and their potential application in cosmetic and cosmeceutical fields. PMID:28417932

  13. The Effective Group Potential, a New Method for the Study of Spectrum in Large Molecules: Tests and Perspectives

    SciTech Connect

    Heully, Jean-Louis; Poteau, Romuald; Berasaluce, Sandra; Alary, Fabienne

    2002-03-22

    The new method, called effective group potential, which generalizes the concept of effective core potential by including in a potential the effects of many atoms ligand, is used to calculate transition energies. Three molecules containing a metal atom (Cu, Cr, Ni) surrounded by NH3 ligands have been studied. It is shown that by replacing the NH3 group by an effective group potential, the characteristic transitions energies are very well reproduced at various ab initio levels. The transitions studied are transitions between open shells on the metallic center but also ligand to metal transitions where, though unexpected, quite reliable results were also obtained. This method is thus very well suited for the study of the spectrum of a large molecule under the condition that a separation between an active part plus some spectator groups can be made, a condition satisfied in most organometallic molecules as well as in biological molecules.

  14. Towards a List of Molecules as Potential Biosignature Gases for the Search for Life on Exoplanets

    NASA Astrophysics Data System (ADS)

    Seager, Sara; Bains, William; Petkowski, Janusz

    2015-12-01

    Thousands of exoplanets are known to orbit nearby stars. Plans for the next generation of space-based and ground-based telescopes are fueling the anticipation that a precious few habitable planets can be identified in the coming decade. Even more highly anticipated is the chance to find signs of life on these habitable planets by way of biosignature gases. But which gases should we search for? We expand on the search of possible biosignature gases and go beyond those studied so far, which include O2, O3, N2O, and CH4, as well as secondary metabolites: methanethiol (CH3SH), dimethyl sulfide ((CH3)2S), methyl chloride (CH3Cl), and carbonyl sulfide (CSO).We present the results of a project to map the chemical space of life’s metabolic products. We have constructed a systematic survey of all possible stable volatile molecules (up to N=6 non-H atoms), and identified those made by life on Earth. Some (such as methyl chloride) are made by Earth life in sufficiently substantial quantities to be candidate biosignatures in an Earth-like exoplanet’s atmosphere; some, such as stibine (SbH3), are produced only in trace amounts. Some entire categories of molecules are not made by Earth life (such as the silanes); these and other absences from the list of biogenic volatiles point to functional patterns in biochemical space. Such patterns may be different for different biochemistry, and so we cannot rule out any small, stable molecule as a candidate biosignature gas. Our goal is for the community to use the list to study the chemicals that might be potential biosignature gases on exoplanets with atmospheres and surface environments different from Earth’s.

  15. Documenting and harnessing the biological potential of molecules in Distributed Drug Discovery (D3) virtual catalogs.

    PubMed

    Abraham, Milata M; Denton, Ryan E; Harper, Richard W; Scott, William L; O'Donnell, Martin J; Durrant, Jacob D

    2017-04-28

    Virtual molecular catalogs have limited utility if member compounds are (i) difficult to synthesize or (ii) unlikely to have biological activity. The Distributed Drug Discovery (D3) program addresses the synthesis challenge by providing scientists with a free virtual D3 catalog of 73,024 easy-to-synthesize N-acyl unnatural α-amino acids, their methyl esters, and primary amides. The remaining challenge is to document and exploit the bioactivity potential of these compounds. In the current work, a search process is described that retrospectively identifies all virtual D3 compounds classified as bioactive hits in PubChem-cataloged experimental assays. The results provide insight into the broad range of drug-target classes amenable to inhibition and/or agonism by D3-accessible molecules. To encourage computer-aided drug discovery centered on these compounds, a publicly available virtual database of D3 molecules prepared for use with popular computer docking programs is also presented. © 2017 John Wiley & Sons A/S.

  16. Soluble adhesion molecules as markers for sepsis and the potential pathophysiological discrepancy in neonates, children and adults

    PubMed Central

    2014-01-01

    Sepsis is a severe and life-threatening systemic inflammatory response to infection that affects all populations and age groups. The pathophysiology of sepsis is associated with aberrant interaction between leukocytes and the vascular endothelium. As inflammation progresses, the adhesion molecules that mediate these interactions become shed from cell surfaces and accumulate in the blood as soluble isoforms that are being explored as potential prognostic disease biomarkers. We critically review the studies that have tested the predictive value of soluble adhesion molecules in sepsis pathophysiology with emphasis on age, as well as the underlying mechanisms and potential roles for inflammatory shedding. Five soluble adhesion molecules are associated with sepsis, specifically, E-selectin, L-selectin and P-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. While increased levels of these soluble adhesion molecules generally correlate well with the presence of sepsis, their degree of elevation is still poorly predictive of sepsis severity scores, outcome and mortality. Separate analyses of neonates, children and adults demonstrate significant age-dependent discrepancies in both basal and septic levels of circulating soluble adhesion molecules. Additionally, a range of both clinical and experimental studies suggests protective roles for adhesion molecule shedding that raise important questions about whether these should positively or negatively correlate with mortality. In conclusion, while predictive properties of soluble adhesion molecules have been researched intensively, their levels are still poorly predictive of sepsis outcome and mortality. We propose two novel directions for improving clinical utility of soluble adhesion molecules: the combined simultaneous analysis of levels of adhesion molecules and their sheddases; and taking age-related discrepancies into account. Further attention to these issues may provide better

  17. Soluble adhesion molecules as markers for sepsis and the potential pathophysiological discrepancy in neonates, children and adults.

    PubMed

    Zonneveld, Rens; Martinelli, Roberta; Shapiro, Nathan I; Kuijpers, Taco W; Plötz, Frans B; Carman, Christopher V

    2014-02-18

    Sepsis is a severe and life-threatening systemic inflammatory response to infection that affects all populations and age groups. The pathophysiology of sepsis is associated with aberrant interaction between leukocytes and the vascular endothelium. As inflammation progresses, the adhesion molecules that mediate these interactions become shed from cell surfaces and accumulate in the blood as soluble isoforms that are being explored as potential prognostic disease biomarkers. We critically review the studies that have tested the predictive value of soluble adhesion molecules in sepsis pathophysiology with emphasis on age, as well as the underlying mechanisms and potential roles for inflammatory shedding. Five soluble adhesion molecules are associated with sepsis, specifically, E-selectin, L-selectin and P-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. While increased levels of these soluble adhesion molecules generally correlate well with the presence of sepsis, their degree of elevation is still poorly predictive of sepsis severity scores, outcome and mortality. Separate analyses of neonates, children and adults demonstrate significant age-dependent discrepancies in both basal and septic levels of circulating soluble adhesion molecules. Additionally, a range of both clinical and experimental studies suggests protective roles for adhesion molecule shedding that raise important questions about whether these should positively or negatively correlate with mortality. In conclusion, while predictive properties of soluble adhesion molecules have been researched intensively, their levels are still poorly predictive of sepsis outcome and mortality. We propose two novel directions for improving clinical utility of soluble adhesion molecules: the combined simultaneous analysis of levels of adhesion molecules and their sheddases; and taking age-related discrepancies into account. Further attention to these issues may provide better

  18. Multi-Functional Diarylurea Small Molecule Inhibitors of TRPV1 with Therapeutic Potential for Neuroinflammation.

    PubMed

    Feng, Zhiwei; Pearce, Larry V; Zhang, Yu; Xing, Changrui; Herold, Brienna K A; Ma, Shifan; Hu, Ziheng; Turcios, Noe A; Yang, Peng; Tong, Qin; McCall, Anna K; Blumberg, Peter M; Xie, Xiang-Qun

    2016-07-01

    Transient receptor potential vanilloid type 1 (TRPV1), a heat-sensitive calcium channel protein, contributes to inflammation as well as to acute and persistent pain. Since TRPV1 occupies a central position in pathways of neuronal inflammatory signaling, it represents a highly attractive potential therapeutic target for neuroinflammation. In the present work, we have in silico identified a series of diarylurea analogues for hTRPV1, of which 11 compounds showed activity in the nanomolar to micromolar range as validated by in vitro biological assays. Then, we utilized molecular docking to explore the detailed interactions between TRPV1 and the compounds to understand the contributions of the different substituent groups. Tyr511, Leu518, Leu547, Thr550, Asn551, Arg557, and Leu670 were important for the recognition of the small molecules by TRPV1. A hydrophobic group in R2 or a polar/hydrophilic group in R1 contributed significantly to the activities of the antagonists at TRPV1. In addition, the subtle different binding pose of meta-chloro in place of para-fluoro in the R2 group converted antagonism into partial agonism, as was predicted by our short-term molecular dynamics (MD) simulation and validated by bioassay. Importantly, compound 15, one of our best TRPV1 inhibitors, also showed potential binding affinity (1.39 μM) at cannabinoid receptor 2 (CB2), which is another attractive target for immuno-inflammation diseases. Furthermore, compound 1 and its diarylurea analogues were predicted to target the C-X-C chemokine receptor 2 (CXCR2), although bioassay validation of CXCR2 with these compounds still needs to be performed. This prediction from the modeling is of interest, since CXCR2 is also a potential therapeutic target for chronic inflammatory diseases. Our findings provide novel strategies to develop a small molecule inhibitor to simultaneously target two or more inflammation-related proteins for the treatment of a wide range of inflammatory disorders including

  19. An insight into the potentially old-wonder molecule-quercetin: the perspectives in foresee.

    PubMed

    Rani, Nidhi; Velan, Lakshmi Palanisamy Thanga; Vijaykumar, Saravanan; Arunachalam, Annamalai

    2015-09-09

    Use of phyto-medicine and digitalization of phyto-compounds has been fallen enthralling field of science in recent years. Quercetin, a flavonoid with brilliant citron yellow pigment, is typically found in fruits and leafy vegetables in reasonable amount. Quercetin's potentials as an antioxidant, immune-modulator, antiinflammatory, anti-cancer, and others have been the subject of interest in this review. Although, profiling the insights in to the molecular characterization of quercetin with various targets provided the loop-holes in understanding the knowledge for the aforementioned mechanisms, still necessitates research globally to unearth it completely. Thus, the available science on the synthesis and significant role played by the old molecule - quercetin which does wonders even now have been vividly explained in the present review to benefit the scientific community.

  20. Clock-Enhancing Small Molecules and Potential Applications in Chronic Diseases and Aging

    PubMed Central

    Gloston, Gabrielle F.; Yoo, Seung-Hee; Chen, Zheng (Jake)

    2017-01-01

    Normal physiological functions require a robust biological timer called the circadian clock. When clocks are dysregulated, misaligned, or dampened, pathological consequences ensue, leading to chronic diseases and accelerated aging. An emerging research area is the development of clock-targeting compounds that may serve as drug candidates to correct dysregulated rhythms and hence mitigate disease symptoms and age-related decline. In this review, we first present a concise view of the circadian oscillator, physiological networks, and regulatory mechanisms of circadian amplitude. Given a close association of circadian amplitude dampening and disease progression, clock-enhancing small molecules (CEMs) are of particular interest as candidate chronotherapeutics. A recent proof-of-principle study illustrated that the natural polymethoxylated flavonoid nobiletin directly targets the circadian oscillator and elicits robust metabolic improvements in mice. We describe mood disorders and aging as potential therapeutic targets of CEMs. Future studies of CEMs will shed important insight into the regulation and disease relevance of circadian clocks. PMID:28360884

  1. Stress-induced molecules MICA as potential target for radioimmunotherapy of cancer

    NASA Astrophysics Data System (ADS)

    Abakushina, E. V.; Anokhin, Yu N.; Abakushin, D. N.; Kaprin, A. D.

    2017-01-01

    Improving the treatment of cancer, increasing their effectiveness and safety is the main objective in the medicine. Molecular nuclear medicine plays an important role in the therapy of cancer. Radioimmunotherapy (RIT) involves the use of antibodies conjugated with therapeutic radionuclides. More often for RIT use the radiolabeled monoclonal antibodies against tumor-associated antigens. Encouraging results have been achieved with this technology in the management of hematologic malignancies. On the contrary, solid tumors have been less responsive. Despite these encouraging results, new potential target for radioimmunodetection and RIT should be found. It was found to increase the level of tumor-associated molecules MICA in the serum of cancer patients. Use of anti-MICA monoclonal antibodies capable a specifically attach to cancer cell via NKG2D ligands and destroy it, is a very promising direction, both therapeutic and diagnostic standpoint.

  2. Three-body neutral dissociations of a multiply excited water molecule around the double ionization potential

    NASA Astrophysics Data System (ADS)

    Odagiri, Takeshi; Nakano, Motoyoshi; Tanabe, Takehiko; Kumagai, Yoshiaki; Suzuki, Isao H.; Kitajima, Masashi; Kouchi, Noriyuki

    2012-11-01

    The cross sections for emission of two fluorescence photons from a pair of excited fragments in photoexcitation of H2O have been measured as a function of the incident photon energy using the photon-photon coincidence technique. The cross section increased in the range 30-45 eV, i.e. in the vicinity of the double ionization potential of H2O. The increase of the cross section was attributed to three-body neutral dissociations of a water molecule via multiply excited states: H2O** → H(2p) + OH** → H(2p) + H(2p) + O(3P). Some multiply excited states of H2O were also found in the cross section curve around 65 eV.

  3. Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules

    PubMed Central

    Moseti, Dorothy; Regassa, Alemu; Kim, Woo-Kyun

    2016-01-01

    Adipogenesis is the process by which precursor stem cells differentiate into lipid laden adipocytes. Adipogenesis is regulated by a complex and highly orchestrated gene expression program. In mammalian cells, the peroxisome proliferator-activated receptor γ (PPARγ), and the CCAAT/enhancer binding proteins (C/EBPs) such as C/EBPα, β and δ are considered the key early regulators of adipogenesis, while fatty acid binding protein 4 (FABP4), adiponectin, and fatty acid synthase (FAS) are responsible for the formation of mature adipocytes. Excess accumulation of lipids in the adipose tissue leads to obesity, which is associated with cardiovascular diseases, type II diabetes and other pathologies. Thus, investigating adipose tissue development and the underlying molecular mechanisms is vital to develop therapeutic agents capable of curbing the increasing incidence of obesity and related pathologies. In this review, we address the process of adipogenic differentiation, key transcription factors and proteins involved, adipogenic regulators and potential anti-adipogenic bioactive molecules. PMID:26797605

  4. Virtual screening and statistical analysis in the design of new caffeine analogues molecules with potential epithelial anticancer activity.

    PubMed

    Costa, Josivan da Silva; Costa, Karina Da Silva Lopes; Cruz, Josiane Viana; Ramosb, Ryan da Silva; Silva, Luciane Barros; Barros Brasilc, Davi Do Socorro; Henrique Tomich de Paula da Silva, Carlos; Santos, Cleydson Breno Rodrigues Dos; Macêdoe, Williams Jorge da Cruz

    2017-07-11

    About 132 thousand cases of melanoma (more severe type of skin cancer) were registered in 2014 according to the world health organization. This type of cancer significantly affects the quality of life of individuals. Caffeine has shown potential inhibitory effect against epithelial cancer. In this study, it was proposed to obtain new caffeine-based molecules with potential epithelial anticancer activity. For this, a training set of 21 molecules was used for pharmacophore perception procedures. Multiple linear regression analyses were used to propose mono-, bi-, tri-, and tetra-parametric models applied in the prediction of the activity. The generated pharmacophore was used to select 350 molecules available at the ZINCpharmer server, followed by reduction to 24 molecules, after selection using the Tanimoto index, yielding 10 molecules after final selection by predicted activity values > 1.5229. These ten molecules had better pharmacokinetic properties than the other ones used as reference and within the clinically significant limits. Only two molecules show minor hits of toxicity and were submitted to molecular docking procedures, showing BFE (binding free energy) values lower than the reference values. Statistical analyses indicated strong negative correlations between BFE and pharmacophoric properties (high influence on BFE lowering) and practically null correlation between BFE and BBB. The two most promising molecules can be indicated as candidates for further in vitro and in vivo analyzes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Efficient computational methods for accurately predicting reduction potentials of organic molecules.

    PubMed

    Speelman, Amy L; Gillmore, Jason G

    2008-06-26

    A simple computational approach for predicting ground-state reduction potentials based upon gas phase geometry optimizations at a moderate level of density functional theory followed by single-point energy calculations at higher levels of theory in the gas phase or with polarizable continuum solvent models is described. Energies of the gas phase optimized geometries of the S0 and one-electron-reduced D0 states of 35 planar aromatic organic molecules spanning three distinct families of organic photooxidants are computed in the gas phase as well as well in implicit solvent with IPCM and CPCM solvent models. Correlation of the D0 - S0 energy difference (essentially an electron affinity) with experimental reduction potentials from the literature (in acetonitrile vs SCE) within a single family, or across families when solvent models are used, yield correlations with r(2) values in excess of 0.97 and residuals of about 100 mV or less, without resorting to computationally expensive vibrational calculations or thermodynamic cycles.

  6. Theoretical study of the CsNa molecule: adiabatic and diabatic potential energy and dipole moment.

    PubMed

    Mabrouk, N; Berriche, H

    2014-09-25

    The adiabatic and diabatic potential energy curves of the low-lying electronic states of the NaCs molecule dissociating into Na (3s, 3p) + Cs (6s, 6p, 5d, 7s, 7p, 6d, 8s, 4f) have been investigated. The molecular calculations are performed using an ab initio approach based on nonempirical pseudopotential, parametrized l-dependent polarization potentials and full configuration interaction calculations through the CIPCI quantum chemistry package. The derived spectroscopic constants (Re, De, Te, ωe, ωexe, and Be) of the ground state and lower excited states are compared with the available theoretical and experimental works. Moreover, accurate permanent and transition dipole moment have been determined as a function of the internuclear distance. The adiabatic permanent dipole moment for the first nine (1)Σ(+) electronic states have shown both ionic characters associated with electron transfer related to Cs(+)Na(-) and Cs(-)Na(+) arrangements. By a simple rotation, the diabatic permanent dipole moment is determined and has revealed a linear behavior, particularly at intermediate and large distances. Many peaks around the avoided crossing locations have been observed for the transition dipole moment between neighbor electronic states.

  7. Uncertainty of the potential curve minimum for diatomic molecules extrapolated from Dunham type coefficients

    NASA Astrophysics Data System (ADS)

    Ilieva, T.; Iliev, I.; Pashov, A.

    2016-12-01

    In the traditional description of electronic states of diatomic molecules by means of molecular constants or Dunham coefficients, one of the important fitting parameters is the value of the zero point energy - the minimum of the potential curve or the energy of the lowest vibrational-rotational level - E00 . Their values are almost always the result of an extrapolation and it may be difficult to estimate their uncertainties, because they are connected not only with the uncertainty of the experimental data, but also with the distribution of experimentally observed energy levels and the particular realization of set of Dunham coefficients. This paper presents a comprehensive analysis based on Monte Carlo simulations, which aims to demonstrate the influence of all these factors on the uncertainty of the extrapolated minimum of the potential energy curve U (Re) and the value of E00 . The very good extrapolation properties of the Dunham coefficients are quantitatively confirmed and it is shown that for a proper estimate of the uncertainties, the ambiguity in the composition of the Dunham coefficients should be taken into account.

  8. Ab Initio Characterization of Triatomic Bromine Molecules of Potential Interest in Stratospheric Chemistry

    NASA Technical Reports Server (NTRS)

    Lee. Timothy J.

    1995-01-01

    The equilibrium structures, harmonic vibrational frequencies, quadratic force fields, dipole moments, and IR intensities of several triatomic bromine compounds of known or potential importance in stratospheric ozone depletion chemistry have been determined using the CCSD(T) electron correlation method in conjunction with a basis set of triple zeta double polarized (TZ2P) quality. Specifically, the molecules included in the present study are HOBr, HBrO, FOBr, FBrO, BrNO, BrON, Br2O, BrBrO, BrCN, BrNC, ClOBr, ClBrO, and BrClO. Very accurate isomeric energy differences have also been determined at the CCSD(T) level with atomic natural orbital basis sets that include through g-type functions. In most cases, the isomer with a normal neutral Lewis dot structure is the lowest energy form, with the single exception that FBRO is predicted to be 11.1 kcal/mol (0 K) lower in energy than FOBr. In all cases, however, the hypervalent isomer is more stable relative to the isomer with a normal Lewis dot structure as compared to the chlorine analogs. Consistent with this observation, the energy of the last three molecules given above increases in the order ClOBr less than ClBrO less than BrClO. The CCSD(T)/TZ2P geometries and vibrational frequencies are in good agreement with the available experimental data. Heats of formation are determined for all species using a combination of theoretical isomeric, homodesmic, and isodesmic reaction energies. The accuracy of these quantities is ultimately dependent on the reliability of the experimental heat of formation of HOBr.

  9. Ab Initio Characterization of Triatomic Bromine Molecules of Potential Interest in Stratospheric Chemistry

    NASA Technical Reports Server (NTRS)

    Lee, Timothy J.

    1995-01-01

    The equilibrium structures, harmonic vibrational frequencies, quadratic force fields, dipole moments, and IR intensities of several triatomic bromine compounds of known or potential importance in stratospheric ozone depletion chemistry have been determined using the CCSD(T) electron correlation method in conjunction with a basis set of triple zeta double polarized (TZ2P) quality. Specifically, the molecules included in the present study are HOBr, HBrO, FOBr, FBrO, BrNO, BrON, Br2O, BrBrO, BrCN, BrNC, ClOBr, ClBrO, and BrClO. Very accurate isomeric energy differences have also been determined at the CCSD(T) level with atomic natural orbital basis sets that include through g-type functions. In most cases, the isomer with a normal neutral Lewis dot structure is the lowest energy form, with the single exception that FBrO is predicted to be 11.1 kcal/mol (0 K) lower in energy than FOBr. In all cases, however, the hypervalent isomer is more stable relative to the isomer with a normal Lewis dot structure as compared to the chlorine analogs. Consistent with this observation, the energy of the last three molecules given above increases in the order ClOBr less than ClBrO less than BrClO. The CCSD(T)/TZ2P geometries and vibrational frequencies are in good agreement with the available experimental data. Heats of formation are determined for all species using a combination of theoretical isomeric, homodesmic, and isodesmic reaction energies. The accuracy of these quantities is ultimately dependent on the reliability of the experimental heat of formation of HOBr.

  10. Stark-potential evaporative cooling of polar molecules in a novel optical-access opened electrostatic trap

    NASA Astrophysics Data System (ADS)

    Sun, Hui; Wang, Zhen-Xia; Wang, Qin; Li, Xing-Jia; Liu, Jian-Ping; Yin, Jian-Ping

    2015-11-01

    We propose a novel optical-access opened electrostatic trap to study the Stark-potential evaporative cooling of polar molecules by using two charged disk electrodes with a central hole of radius r0 =1.5 mm, and derive a set of new analytical equations to calculate the spatial distributions of the electrostatic field in the above charged-disk layout. Afterwards, we calculate the electric-field distributions of our electrostatic trap and the Stark potential for cold ND3 molecules, and analyze the dependences of both the electric field and the Stark potential on the geometric parameters of our charged-disk scheme, and find an optimal condition to form a desirable trap with the same trap depth in the x, y, and z directions. Also, we propose a desirable scheme to realize an efficient loading of cold polar molecules in the weak-field-seeking states, and investigate the dependences of the loading efficiency on both the initial forward velocity of the incident molecular beam and the loading time by Monte Carlo simulations. Our study shows that the maximal loading efficiency of our trap scheme can reach about 95%, and the corresponding temperature of the trapped cold molecules is about 28.8 mK. Finally, we study the Stark-potential evaporative cooling for cold polar molecules in our trap by the Monte Carlo method, and find that our simulated evaporative cooling results are consistent with our developed analytical model based on trapping-potential evaporative cooling.

  11. Quasi-one-dimensional cyano-phenylene aggregates: Uniform molecule alignment contrasts varying electrostatic surface potential

    NASA Astrophysics Data System (ADS)

    Balzer, Frank; Resel, Roland; Lützen, Arne; Schiek, Manuela

    2017-04-01

    The epitaxial growth of the mono-functionalized para-quaterphenylene molecule CNHP4 on muscovite mica is investigated. The vacuum deposited molecules aggregate into nanofibers of varying morphology. Due to muscovite's cm symmetry, almost mutually parallel fibers grow. Polarized light microscopy together with X-ray diffraction resolves the projected orientation of the molecules on the substrate surface and within the fibers. Several different contact planes with the substrate are detected. For all of them, the molecules orient with their long molecule axis approximately perpendicular to the grooved muscovite direction, so that the alignment of the molecules on the substrate is uniform. Kelvin probe force microscopy finds vastly different electrostatic properties of different fiber types and facets.

  12. A small molecule inhibitior of the NLRP3 inflammasome is a potential therapeutic for inflammatory diseases

    PubMed Central

    Coll, Rebecca C.; Robertson, Avril A. B.; Chae, Jae Jin; Higgins, Sarah C.; Muñoz-Planillo, Raúl; Inserra, Marco C.; Vetter, Irina; Dungan, Lara S.; Monks, Brian G.; Stutz, Andrea; Croker, Daniel E.; Butler, Mark S.; Haneklaus, Moritz; Sutton, Caroline E.; Núñez, Gabriel; Latz, Eicke; Kastner, Daniel L.; Mills, Kingston H. G.; Masters, Seth L.; Schroder, Kate; Cooper, Matthew A.; O’Neill, Luke A. J.

    2015-01-01

    The NLRP3 inflammasome is a component of the inflammatory process and its aberrant activation is pathogenic in inherited disorders such as the cryopyrin associated periodic syndromes (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes and atherosclerosis. We describe the development of MCC950, a potent, selective, small molecule inhibitor of NLRP3. MCC950 blocks canonical and non-canonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibits NLRP3 but not AIM2, NLRC4 or NLRP1 activation. MCC950 reduces Interleukin-1p (IL-1β) production in vivo and attenuates the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescues neonatal lethality in a mouse model of CAPS and is active in ex vivo samples from individuals with Muckle-Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for the further study of the NLRP3 inflammasome in human health and disease. PMID:25686105

  13. Soluble intercellular adhesion molecule-1: a potential biomarker for pain intensity in chronic pain patients.

    PubMed

    Luchting, Benjamin; Hinske, Ludwig Christian Giuseppe; Rachinger-Adam, Banafscheh; Celi, Leo Anthony; Kreth, Simone; Azad, Shahnaz Christina

    2017-03-01

    Pain therapy is strongly guided by patients' self-reporting. However, when self-reporting is not an option, pain assessment becomes a challenge and may lead to undertreatment of painful conditions. Pain is a complex and multifactorial phenomenon. Recent work has connected pain pathophysiology also with the inflammatory system. We therefore hypothesized that pain intensity could be predicted by cytokine-levels. In this observational, single-center study, we investigated 30 serum cytokines to predict pain intensity in a screening/follow-up set of 95 chronic pain patients and controls. We then prospectively validated soluble intercellular adhesion molecule-1 (sICAM-1)'s discriminatory capability (n = 21). sICAM-1 was significantly associated with patient-reported pain intensity and yielded differential serum levels in patients of varying degrees of pain intensity. Changes in pain ratings over time correlated with changes in sICAM-1 levels. Our findings suggest the possibility of a clinical use of sICAM-1 as a potential biomarker for pain intensity.

  14. A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs.

    PubMed

    Cao, Jianzhong; Forrest, J Craig; Zhang, Xuming

    2015-02-01

    With the recent emergence of Middle East Respiratory Syndrome coronavirus in humans and the outbreak of devastating porcine epidemic diarrhea coronavirus in swine, therapeutic intervention is urgently needed. However, anti-coronavirus drugs currently are not available. In an effort to assist rapid development of anti-coronavirus drugs, here we screened the NIH Clinical Collection in cell culture using a luciferase reporter-expressing recombinant murine coronavirus. Of the 727 compounds screened, 84 were found to have a significant anti-coronavirus effect. Further experiments revealed that 51 compounds blocked virus entry while 19 others inhibited viral replication. Additional validation studies with the top 3 inhibitors (hexachlorophene, nitazoxanide and homoharringtonine) demonstrated robust anti-coronavirus activities (a reduction of 6 to 8log10 in virus titer) with an IC50 ranging from 11nM to 1.2μM. Furthermore, homoharringtonine and hexachlorophene exhibited broad antiviral activity against diverse species of human and animal coronaviruses. Since the NIH Clinical Collection consists of compounds that have already been through clinical trials, these small molecule inhibitors have a great potential for rapid development as anti-coronavirus drugs.

  15. Small Molecule Modulators of Keap1-Nrf2-ARE Pathway as Potential Preventive and Therapeutic Agents$

    PubMed Central

    Magesh, Sadagopan; Chen, Yu; Hu, Longqin

    2012-01-01

    Keap1-Nrf2-ARE pathway represents one of the most important cellular defense mechanisms against oxidative stress and xenobiotic damage. Activation of Nrf2 signaling induces the transcriptional regulation of ARE-dependent expression of various detoxifying and antioxidant defense enzymes and proteins. Keap1-Nrf2-ARE signaling has become an attractive target for the prevention and treatment of oxidative stress-related diseases and conditions including cancer, neurodegenerative, cardiovascular, metabolic and inflammatory diseases. Over the last few decades, numerous Nrf2 inducers have been developed and some of them are currently undergoing clinical trials. Recently, over-activation of Nrf2 has been implicated in cancer progression as well as in drug resistance to cancer chemotherapy. Thus, Nrf2 inhibitors could potentially be used to improve the effectiveness of cancer therapy. Herein, we review the signaling mechanism of Keap1-Nrf2-ARE pathway, its disease relevance, and currently known classes of small molecule modulators. We also discuss several aspects of Keap1-Nrf2 interaction, Nrf2-based peptide inhibitor design, and the screening assays currently used for the discovery of direct inhibitors of Keap1-Nrf2 interaction. PMID:22549716

  16. Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis.

    PubMed

    Romani, Luigina; Oikonomou, Vasilis; Moretti, Silvia; Iannitti, Rossana G; D'Adamo, Maria Cristina; Villella, Valeria R; Pariano, Marilena; Sforna, Luigi; Borghi, Monica; Bellet, Marina M; Fallarino, Francesca; Pallotta, Maria Teresa; Servillo, Giuseppe; Ferrari, Eleonora; Puccetti, Paolo; Kroemer, Guido; Pessia, Mauro; Maiuri, Luigi; Goldstein, Allan L; Garaci, Enrico

    2017-05-01

    Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that compromise its chloride channel activity. The most common mutation, p.Phe508del, results in the production of a misfolded CFTR protein, which has residual channel activity but is prematurely degraded. Because of the inherent complexity of the pathogenetic mechanisms involved in CF, which include impaired chloride permeability and persistent lung inflammation, a multidrug approach is required for efficacious CF therapy. To date, no individual drug with pleiotropic beneficial effects is available for CF. Here we report on the ability of thymosin alpha 1 (Tα1)-a naturally occurring polypeptide with an excellent safety profile in the clinic when used as an adjuvant or an immunotherapeutic agent-to rectify the multiple tissue defects in mice with CF as well as in cells from subjects with the p.Phe508del mutation. Tα1 displayed two combined properties that favorably opposed CF symptomatology: it reduced inflammation and increased CFTR maturation, stability and activity. By virtue of this two-pronged action, Tα1 has strong potential to be an efficacious single-molecule-based therapeutic agent for CF.

  17. Cardioprotective Potentials of Plant-Derived Small Molecules against Doxorubicin Associated Cardiotoxicity

    PubMed Central

    Ojha, Shreesh; Al Taee, Hasan; Goyal, Sameer; Mahajan, Umesh B.; Patil, Chandrgouda R.; Arya, D. S.; Rajesh, Mohanraj

    2016-01-01

    Doxorubicin (DOX) is a potent and widely used anthracycline antibiotic for the treatment of several malignancies. Unfortunately, the clinical utility of DOX is often restricted due to the elicitation of organ toxicity. Particularly, the increased risk for the development of dilated cardiomyopathy by DOX among the cancer survivors warrants major attention from the physicians as well as researchers to develop adjuvant agents to neutralize the noxious effects of DOX on the healthy myocardium. Despite these pitfalls, the use of traditional cytotoxic drugs continues to be the mainstay treatment for several types of cancer. Recently, phytochemicals have gained attention for their anticancer, chemopreventive, and cardioprotective activities. The ideal cardioprotective agents should not compromise the clinical efficacy of DOX and should be devoid of cumulative or irreversible toxicity on the naïve tissues. Furthermore, adjuvants possessing synergistic anticancer activity and quelling of chemoresistance would significantly enhance the clinical utility in combating DOX-induced cardiotoxicity. The present review renders an overview of cardioprotective effects of plant-derived small molecules and their purported mechanisms against DOX-induced cardiotoxicity. Phytochemicals serve as the reservoirs of pharmacophore which can be utilized as templates for developing safe and potential novel cardioprotective agents in combating DOX-induced cardiotoxicity. PMID:27313831

  18. Small-molecule Hedgehog inhibitor attenuates the leukemia-initiation potential of acute myeloid leukemia cells.

    PubMed

    Fukushima, Nobuaki; Minami, Yosuke; Kakiuchi, Seiji; Kuwatsuka, Yachiyo; Hayakawa, Fumihiko; Jamieson, Catoriona; Kiyoi, Hitoshi; Naoe, Tomoki

    2016-10-01

    Aberrant activation of the Hedgehog signaling pathway has been implicated in the maintenance of leukemia stem cell populations in several model systems. PF-04449913 (PF-913) is a selective, small-molecule inhibitor of Smoothened, a membrane protein that regulates the Hedgehog pathway. However, details of the proof-of-concept and mechanism of action of PF-913 following administration to patients with acute myeloid leukemia (AML) are unclear. This study examined the role of the Hedgehog signaling pathway in AML cells, and evaluated the in vitro and in vivo effects of the Smoothened inhibitor PF-913. In primary AML cells, activation of the Hedgehog signaling pathway was more pronounced in CD34(+) cells than CD34(-) cells. In vitro treatment with PF-913 induced a decrease in the quiescent cell population accompanied by minimal cell death. In vivo treatment with PF-913 attenuated the leukemia-initiation potential of AML cells in a serial transplantation mouse model, while limiting reduction of tumor burden in a primary xenotransplant system. Comprehensive gene set enrichment analysis revealed that PF-913 modulated self-renewal signatures and cell cycle progression. Furthermore, PF-913 sensitized AML cells to cytosine arabinoside, and abrogated resistance to cytosine arabinoside in AML cells cocultured with HS-5 stromal cells. These findings imply that pharmacologic inhibition of Hedgehog signaling attenuates the leukemia-initiation potential, and also enhanced AML therapy by sensitizing dormant leukemia stem cells to chemotherapy and overcoming resistance in the bone marrow microenvironment. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  19. Ab initio potential energy surface for the carbon dioxide molecule pair and thermophysical properties of dilute carbon dioxide gas

    NASA Astrophysics Data System (ADS)

    Hellmann, Robert

    2014-10-01

    A four-dimensional intermolecular potential energy surface (PES) for two rigid carbon dioxide molecules was determined from quantum-chemical ab initio calculations. Interaction energies for 1229 CO2-CO2 configurations were computed at the CCSD(T) level of theory using basis sets up to aug-cc-pVQZ supplemented with bond functions. An analytical site-site potential function with seven sites per CO2 molecule was fitted to the interaction energies. The PES was validated by calculating the second virial coefficient as well as viscosity and thermal conductivity in the dilute-gas limit.

  20. Screening of Potential Lead Molecule as Novel MurE Inhibitor: Virtual Screening, Molecular Dynamics and In Vitro Studies.

    PubMed

    Zaveri, Kunal; Kiranmayi, Patnala

    2017-01-01

    The prevalence of multi-drug resistance S. aureus is one of the most challenging tasks for the treatment of nosocomial infections. Proteins and enzymes of peptidoglycan biosynthesis pathway are one among the well-studied targets, but many of the enzymes are unexplored as targets. MurE is one such enzyme featured to be a promising target. As MurE plays an important role in ligating the L-lys to stem peptide at third position that is crucial for peptidoglycan synthesis. To screen the potential MurE inhibitor by in silico approach and evaluate the best potential lead molecule by in vitro methods. In the current study, we have employed structure based virtual screening targeting the active site of MurE, followed by Molecular dynamics and in vitro studies. Virtual screening resulted in successful screening of potential lead molecule ((2R)-2-[[1-[(2R)- 2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan). The molecular dynamics of the MurE and Lead molecule complex emphasizes that lead molecule has shown stable interactions with active site residues Asp 406 and with Glu 460. In vitro studies demonstrate that the lead molecule shows antibacterial activity close to standard antibiotic Vancomycin and higher than that of Ampicillin, Streptomycin and Rifampicin. The MIC of lead molecule at 50μg/mL was observed to be 3.75 μg/mL, MBC being bactericidal with value of 6.25 μg/mL, cytotoxicity showing 34.44% and IC50 of 40.06μg/mL. These results suggest ((2R)-2-[[1-[(2R)-2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan) as a promising lead molecule for developing a MurE inhibitor against treatment of S. aureus infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. The potential of combi-molecules with DNA-damaging function as anticancer agents.

    PubMed

    Sun, Guohui; Fan, Tengjiao; Zhao, Lijiao; Zhou, Yue; Zhong, Rugang

    2017-03-01

    DNA-damaging agents, such as methylating agents, chloroethylating agents and platinum-based agents, have been extensively used as anticancer drugs. However, the side effects, high toxicity, lack of selectivity and resistance severely limit their clinical applications. In recent years, a strategy combining a DNA-damaging agent with a bioactive molecule (e.g., enzyme inhibitors) or carrier (e.g., steroid hormone and DNA intercalators) to produce a new 'combi-molecule' with improved efficacy or selectivity has been attempted to overcome these drawbacks. The combi-molecule simultaneously acts on two targets and is expected to possess better potency than the parent compounds. Many studies have shown DNA-damaging combi-molecules exhibiting excellent anticancer activity in vitro and in vivo. This review focuses on the development of combi-molecules, which possess increased DNA-damaging potency, anticancer efficacy and tumor selectivity and reduced side reactions than the parent compounds. The future opportunities and challenges in the discovery of combi-molecules were also discussed.

  2. Large pi-aromatic molecules as potential sensitizers for highly efficient dye-sensitized solar cells.

    PubMed

    Imahori, Hiroshi; Umeyama, Tomokazu; Ito, Seigo

    2009-11-17

    Recently, dye-sensitized solar cells have attracted much attention relevant to global environmental issues. Thus far, ruthenium(II) bipyridyl complexes have proven to be the most efficient TiO(2) sensitizers in dye-sensitized solar cells. However, a gradual increment in the highest power conversion efficiency has been recognized in the past decade. More importantly, considering that ruthenium is a rare metal, novel dyes without metal or using inexpensive metal are desirable for highly efficient dye-sensitized solar cells. Large pi-aromatic molecules, such as porphyrins, phthalocyanines, and perylenes, are important classes of potential sensitizers for highly efficient dye-sensitized solar cells, owing to their photostability and high light-harvesting capabilities that can allow applications in thinner, low-cost dye-sensitized solar cells. Porphyrins possess an intense Soret band at 400 nm and moderate Q bands at 600 nm. Nevertheless, the poor light-harvesting properties relative to the ruthenium complexes have limited the cell performance of porphyrin-sensitized TiO(2) cells. Elongation of the pi conjugation and loss of symmetry in porphyrins cause broadening and a red shift of the absorption bands together with an increasing intensity of the Q bands relative to that of the Soret band. On the basis of the strategy, the cell performance of porphyrin-sensitized solar cells has been improved intensively by the enhanced light absorption. Actually, some push-pull-type porphyrins have disclosed a remarkably high power conversion efficiency (6-7%) that was close to that of the ruthenium complexes. Phthalocyanines exhibit strong absorption around 300 and 700 nm and redox features that are similar to porphyrins. Moreover, phthalocyanines are transparent over a large region of the visible spectrum, thereby enabling the possibility of using them as "photovoltaic windows". However, the cell performance was poor, owing to strong aggregation and lack of directionality in the

  3. Theoretical study of the structure and analytic potential energy function for the ground state of the PO2 molecule

    NASA Astrophysics Data System (ADS)

    Zeng, Hui; Zhao, Jun

    2012-07-01

    In this paper, the energy, equilibrium geometry, and harmonic frequency of the ground electronic state of PO2 are computed using the B3LYP, B3P86, CCSD(T), and QCISD(T) methods in conjunction with the 6-311++G(3df, 3pd) and cc-pVTZ basis sets. A comparison between the computational results and the experimental values indicates that the B3P86/6-311++G(3df, 3pd) method can give better energy calculation results for the PO2 molecule. It is shown that the ground state of the PO2 molecule has C2ν symmetry and its ground electronic state is X2A1. The equilibrium parameters of the structure are RP-O = 0.1465 nm, ∠OPO = 134.96°, and the dissociation energy is Ed = 19.218 eV. The bent vibrational frequency ν1 = 386 cm-1, symmetric stretching frequency ν2 = 1095 cm-1, and asymmetric stretching frequency ν3 = 1333 cm-1 are obtained. On the basis of atomic and molecular reaction statics, a reasonable dissociation limit for the ground state of the PO2 molecule is determined. Then the analytic potential energy function of the PO2 molecule is derived using many-body expansion theory. The potential curves correctly reproduce the configurations and the dissociation energy for the PO2 molecule.

  4. Hybrid MP2/MP4 potential surfaces in VSCF calculations of IR spectra: applications for organic molecules.

    PubMed

    Knaanie, Roie; Šebek, Jiří; Kalinowski, Jaroslaw; Benny Gerber, R

    2014-02-05

    This study introduces an improved hybrid MP2/MP4 ab initio potential for vibrational spectroscopy calculations which is very accurate, yet without high computational demands. The method uses harmonic vibrational calculations with the MP4(SDQ) potential to construct an improved MP2 potential by coordinate scaling. This improved MP2 potential is used for the anharmonic VSCF calculation. The method was tested spectroscopically for four molecules: butane, acetone, ethylene and glycine. Very good agreement with experiment was found. For most of the systems, the more accurate harmonic treatment considerably improved the MP2 anharmonic results.

  5. Balanced Basis Sets in the Calculation of Potential Energy Curves for Diatomic Molecules.

    NASA Astrophysics Data System (ADS)

    Barclay, V. J.

    "Balanced" basis sets, which describe the internuclear region as well as the nuclear region, are examined in the context of an ab initio selection-extrapolation configuration -interaction method (MRD-CI). The sets are balanced by adding bond functions (BF's), which are s, p and d-type orbitals at the bond mid-point, to atomic-centred molecular basis sets, which have double and triple sets of valence -shell orbitals (DZ and TZ) and one or two sets of polarization functions (PF's). Potential energy curves and spectroscopic constants were calculated for the ground states of the hydrides H _2, OH, NaH, MgH, MH, SiH, PH, SH, HCl, and for the ionized species OH^+ and OH^{++}, and for the A^3Sigma_{u}, w^3Delta_{u} and B^3Pi_{g} excited states of N_2. The basis sets containing bond functions gave curves and constants superior to the DZP and (where calculated) TZPP results, and of quality similar to large basis set calculations in the literature. The single and double ionization potentials of OH, and the term energies of the N_2 excited states had error at the atomic asymptotes for all basis sets. The dissociation energies of the ground states of ten first-row diatomics (C_2, N_2, O_2, F_2, CN, CO, CF, NO, NF, and FO) were studied using balanced basis sets. A correlation was found to exist between the actual bond order of a species, and the number and kinds of orbitals which comprise the optimum BF. For MRD-CI diatomic calculations, the following BF's should be added to a DZP basis set (sp) (for a bond order of 1); 2(sp) (B. O. 1.5); (spd) (B. O. 2); 3(sp) (B. O. 2.5); 2(spd) (B. O. 3). The prescribed BF basis method was tested on the 26 second-row congeners Si _2, P_2, S _2, Cl_2, SiP, SiS, SiCl, PS, PCl, and ClS, and mixed-row congeners SiN, SiO, SiF, PO, PF, SF, SiC, PN, SO, ClF, CP, CS, CCl, NS, NCl, and ClO. An average error of 6% and a maximum error of 10% relative to known experimental D_{e }'s was found: compared to an average error of 18% for TZPP calculations

  6. The bionic retina: a small molecule with big potential for visual restoration.

    PubMed

    Drivas, Theodore G; Bennett, Jean

    2012-07-26

    In this issue of Neuron, Polosukhina et al. (2012) intravitreally deliver the light-activatable molecule acrylamide-azobenzene-quaternary ammonium (AAQ) to the eyes of mice with end-stage retinal degeneration. Results show that, with the appropriate illumination, AAQ restores light sensitivity and visual behavior.

  7. Theoretical demonstration of the potentiality of boron nitride nanotubes to encapsulate anticancer molecule.

    PubMed

    El Khalifi, Mohammed; Duverger, Eric; Gharbi, Tijani; Boulahdour, Hatem; Picaud, Fabien

    2015-11-28

    Anticancer drug transport is now becoming an important scientific challenge since it would allow localizing the drug release near the tumor cell, avoiding secondary medical effects. We present theoretical results, based on density functional theory and molecular dynamics simulations, which demonstrate the stability of functionalized single (10,10) boron nitride nanotubes (BNNTs) filled with anticancer molecule such as carboplatin (CPT). For this functionalized system we determine the dependence of the adsorption energy on the molecule displacement near the inner BNNTs surface, together with their local morphological and electrical changes and compare the values to the adsorption energy obtained on the outer surface. Quantum simulations show that the most stable physisorption state is located inside the nanotube, with no net charge transfer. This demonstrates that chemotherapeutic encapsulation is the most favorable way to transport drug molecules. The solvent effect and dispersion repulsion contributions are then taken into account using molecular dynamics simulations. Our results confirm that carboplatin therapeutic agents are not affected when they are adsorbed inside BNNTs by the surrounding water molecules.

  8. A novel caspase 8 selective small molecule potentiates TRAIL-induced cell death.

    PubMed

    Bucur, Octavian; Gaidos, Gabriel; Yatawara, Achani; Pennarun, Bodvael; Rupasinghe, Chamila; Roux, Jérémie; Andrei, Stefan; Guo, Bingqian; Panaitiu, Alexandra; Pellegrini, Maria; Mierke, Dale F; Khosravi-Far, Roya

    2015-05-11

    Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, but not alone. The molecule was identified through an in silico chemical screen for compounds with affinity for the caspase 8 homodimer's interface. The compound was experimentally validated to directly bind caspase 8, and to promote caspase 8 activation and cell death in single living cells or population of cells, upon TRAIL stimulation. Our approach is a proof-of-concept strategy leading to the discovery of a novel small molecule that not only stimulates TRAIL-induced apoptosis in cancer cells, but may also provide insights into the structure-function relationship of caspase 8 homodimers as putative targets in cancer.

  9. A novel caspase 8 selective small molecule potentiates TRAIL-induced cell death

    PubMed Central

    Bucur, Octavian; Gaidos, Gabriel; Yatawara, Achani; Pennarun, Bodvael; Rupasinghe, Chamila; Roux, Jérémie; Andrei, Stefan; Guo, Bingqian; Panaitiu, Alexandra; Pellegrini, Maria; Mierke, Dale F.; Khosravi-Far, Roya

    2015-01-01

    Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, but not alone. The molecule was identified through an in silico chemical screen for compounds with affinity for the caspase 8 homodimer’s interface. The compound was experimentally validated to directly bind caspase 8, and to promote caspase 8 activation and cell death in single living cells or population of cells, upon TRAIL stimulation. Our approach is a proof-of-concept strategy leading to the discovery of a novel small molecule that not only stimulates TRAIL-induced apoptosis in cancer cells, but may also provide insights into the structure-function relationship of caspase 8 homodimers as putative targets in cancer. PMID:25962125

  10. Genes and molecules that can potentiate or attenuate psychostimulant dependence: relevance of data from animal models to human addiction.

    PubMed

    Niwa, Minae; Yan, Yijin; Nabeshima, Toshitaka

    2008-10-01

    Recent evidence suggests that a variety of molecule products play critical roles in the transitions from recreational drug use to drug abuse, and then to drug dependence. Elucidation of the roles of specific molecules in the development of drug dependence can come from preclinical animal models and/or from clinical data. Among animal models, behavioral sensitization, conditioned place preference, drug discrimination, drug self-administration, and extensions of these basic procedures have been widely used to identify molecule products that might be involved in psychostimulant dependence. Repeated exposure to psychostimulants causes cellular adaptations in specific neuronal populations that are likely to contribute to dependence in some humans. In animal models, molecules that include shati, piccolo, tumor necrosis factor-alpha, and glial cell line-derived neurotrophic factor can act as antiaddictive factors. In some of these models, other molecules including matrix metalloproteinase and tissue plasminogen activator can act as proaddictive factors. We review evidence that the balance between levels of anti- and proaddictive factors induced by addictive drugs could play important roles in developing drug dependence. We focus on potential risk molecules in animal models for the development of methamphetamine dependence and their relevance to abusers. We propose that dynamic changes in the balance between levels of antiaddictive and proaddictive factors in the brain provide some of the determinants of susceptibility to drug dependence. Exploration of the roles that candidate molecules play in an appropriate repertoire of animal behavioral models, especially drug self-administration and extensions thereof, should thus help us to understand human stimulant dependence.

  11. Potential interstellar noble gas molecules: ArOH+ and NeOH+ rovibrational analysis from quantum chemical quartic force fields

    NASA Astrophysics Data System (ADS)

    Theis, Riley A.; Fortenberry, Ryan C.

    2016-03-01

    The discovery of ArH+ in the interstellar medium has shown that noble gas chemistry may be of more chemical significance than previously believed. The present work extends the known chemistry of small noble gas molecules to NeOH+ and ArOH+. Besides their respective neonium and argonium diatomic cation cousins, these hydroxyl cation molecules are the most stable small noble gas molecules analyzed of late. ArOH+ is once again more stable than the neon cation, but both are well-behaved enough for a complete quartic force field analysis of their rovibrational properties. The Ar-O bond in ArOH+ , for instance, is roughly three-quarters of the strength of the Ar-H bond in ArH+ highlighting the rigidity of this system. The rotational constants, geometries, and vibrational frequencies for both molecules and their various isotopologues are computed from ab initio quantum chemical theory at high-level, and it is shown that these cations may form in regions where peroxy or weakly-bound alcohols may be present. The resulting data should be of significant assistance for the laboratory or observational analysis of these potential interstellar molecules.

  12. Identification of small molecule Hes1 modulators as potential anticancer chemotherapeutics.

    PubMed

    Sail, Vibhavari; Hadden, M Kyle

    2013-03-01

    Hes1 is a key transcriptional regulator primarily controlled by the Notch signaling pathway, and recent studies have demonstrated both an oncogenic and tumor suppressor role for Hes1, depending on the cell type. Small molecules that activate and inhibit Hes1 activity hold promise as future anticancer chemotherapeutics. We have utilized a cell-based dual luciferase assay to identify modulators of Hes1 expression in a medium-throughput format. A modest screen was performed in HCT-116 colon cancer cell lines, and two small molecules were identified and characterized as Hes1 regulators. Compound 3 induced Hes1 expression and exhibited anticancer effects in pulmonary carcinoid tumor cells, a cell type in which the upregulated Notch/Hes1 signaling plays a tumor suppressive role. Treatment of HCT-116 cells with compound 12 resulted in Hes1 downregulation and antitumor effects.

  13. Antidiabetic potential of bioactive molecules coated chitosan nanoparticles in experimental rats.

    PubMed

    Perumal, Venkatachalam; Manickam, Thiyagarajan; Bang, Keuk-Soo; Velmurugan, Palanivel; Oh, Byung-Taek

    2016-11-01

    The present study was carried out to examine the antidiabetic effects of chitosan nanoparticles (CNPs) loaded with (Stevia rebaudiana leaf extract-SRLE) bioactive molecules in a rat model of streptozotocin (STZ) induced diabetes mellitus. Successful crosslinking of the bioactive molecules to the chitosan nanoparticles was confirmed by Fourier Transform Infrared Spectroscopy (FTIR). The colloidal characteristics of the synthesized nanoparticles were revealed by X-ray Diffraction (XRD) analysis. Morphological analysis by Transmission Electron Microscopy (TEM) revealed that thebioactive molecule-loaded CNPs were well-dispersed and spherical or polygonal in shape with an average size of<73.27nm than the z-average value (327nm) as measured by Dynamic Light Scattering (DLS). SRLE CNP-treated diabetic rats showed a significant reduction in their mean fasting blood glucose level compared with the diabetic control group. The serum levels of various enzymes viz., serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatases (ALP), lipid peroxidation, and antioxidant such as catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD) in the SRLE CNP-treated group were closer to normal levels than those in the diabetic control group. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Infrared Spectroscopic Studies of Matrix-Isolated Molecules with Potential Astrophysical Significance

    NASA Astrophysics Data System (ADS)

    Wehlburg, Christine Marie

    1997-08-01

    Many of the molecules purported to exist in interstellar space can only be generated in high temperature processes or are ions that are difficult to produce at high enough concentrations for spectroscopic analysis. The molecules investigated in this study, specifically, were polycyclic aromatic hydrocarbon (PAH) ions, carbon chain water complexes and carbon chain anions. PAHs are the proposed carriers of the unidentified interstellar (UIR) emission. The infrared investigation of pentacene and tetracene ions was pursued to provide data concerning the possibility that PAH cations were the source of the UIR emission. In this study, infrared features corresponding to both cation and anions for both molecules were observed for the first time. The most intense features for the neutral molecules were the CH out-of-plane wagging modes while the most intense cationic and anionic features were in the CC stretch and CH bending regions. The relative intensities from theoretical calculations were in reasonable agreement with experimental values with the exception of an overestimation for the intensities of the CH stretch in both neutral pentacene and tetracene. Carbon chain water complexes are very weakly bound species that are observed when graphite is vaporized at low power. The infrared features increase in intensity and new ones appear after annealing a matrix containing carbon chain molecules and H2O. The current study involved assignment of infrared features at 1959.4 and 2014.4 cm-1 to C6ċ H2O and C9ċ H2O, respectively. Assignments were based on the fact that both bands increased relative to the C9 and C6 bands when the concentration of H2O increased. The band assignments were further justified by a 12,13C study for C6/cdotH2O and the agreement of the theoretical shift, relative to the asymmetric stretch band of C9, for C9ċ H2O. In addition a new feature at 1550.4 cm-1 was tentatively assigned to C4ċ H2O. Finally, an isotopic study of a feature at 1721.8 cm-1

  15. Ab initio potential curves of the fragments and diatomics-in-molecules potential energy surfaces for the SH⋯Kr complex

    NASA Astrophysics Data System (ADS)

    Nemukhin, A. V.; Grigorenko, B. L.; Granovsky, A. A.

    1999-02-01

    Potential curves of the SH, KrH and KrS molecules needed for the diatomics-in-molecules (DIM) treatment of the ground and excited states of the SH(X,A)⋯Kr complex have been computed at the SOCI/CASSCF level. The ionic and ion-pair states of these diatomic fragments which play an essential role in the DIM model of intermolecular interactions have been considered as well. The new results for the ion-pair states of SH are compared to the corresponding data for OH. The curves for KrS and XeS [M. Yamanishi, K. Hirao, K. Yamashita, J. Chem. Phys. 108 (1998) 1514] are discussed. The main features of the empirical potential surfaces of the SH⋯Kr complex are reproduced by the DIM technique.

  16. Purely-long-range krypton molecules in singly and doubly excited binding potentials

    SciTech Connect

    Smith, Z. S.; Harmon, A.; Banister, J.; Norman, R.; Hoogeboom-Pot, K.; Walhout, M.

    2010-01-15

    Diatomic potentials for krypton are computed and also probed experimentally. For a probe-laser wavelength near 811 nm, several strong dipole-dipole interactions produce purely-long-range potential wells in the singly excited manifold of (s+p) potentials and in the doubly excited manifold of (p+p) and (s+d) potentials. Evidence of resonant photoassociation into bound states of these potential wells is observed in the emission of ions and ultraviolet photons from a magneto-optically trapped krypton cloud.

  17. Particle-localized ground state of atom-molecule Bose-Einstein condensates in a double-well potential

    SciTech Connect

    Motohashi, Atsushi; Nikuni, Tetsuro

    2010-09-15

    We study the effect of atom-molecule internal tunneling on the ground state of atom-molecule Bose-Einstein condensates in a double-well potential. In the absence of internal tunneling between atomic and molecular states, the ground state is symmetric, which has equal-particle populations in two wells. From the linear stability analysis, we show that the symmetric stationary state becomes dynamically unstable at a certain value of the atom-molecule internal tunneling strength. Above the critical value of the internal tunneling strength, the ground state bifurcates to the particle-localized ground states. The origin of this transition can be attributed to the effective attractive interatomic interaction induced by the atom-molecule internal tunneling. This effective interaction is similar to that familiar in the context of BCS-BEC crossover in a Fermi gas with Feshbach resonance. Furthermore, we point out the possibility of reentrant transition in the case of the large detuning between the atomic and molecular states.

  18. Scattering of a matter-wave single soliton and a two-soliton molecule by an attractive potential

    SciTech Connect

    Al-Marzoug, S. M.; Al-Amoudi, S. M.; Al Khawaja, U.; Bahlouli, H.; Baizakov, B. B.

    2011-02-15

    Scattering of a matter-wave single soliton and two-soliton molecule incident on the modified Poeschl-Teller potential well has been studied by means of a collective coordinate approach and numerical simulations of the Gross-Pitaevskii equation. Despite the attractive nature of the potential we observe total reflection of solitons in particular ranges of parameters, which is the signature of quantum behavior displayed by the matter-wave soliton. For other particular sets of parameters unscathed transmission of solitons and molecules through the potential well has been identified. A specific feature of this process is that the soliton passing through the potential well overtakes the freely propagating counterpart; i.e., its mean position appears to have been advanced in time. An array of such potentials makes the 'time advance' effect even more pronounced, so that scattered solitons move well ahead of nonscattered ones, fully preserving their initial shape and velocity. A possible application of the obtained results is pointed out.

  19. ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis

    PubMed Central

    Yamauchi, Yoshio; Yokoyama, Shinji; Chang, Ta-Yuan

    2016-01-01

    Mammalian cells synthesize various sterol molecules, including the C30 sterol, lanosterol, as cholesterol precursors in the endoplasmic reticulum. The build-up of precursor sterols, including lanosterol, displays cellular toxicity. Precursor sterols are found in plasma HDL. How these structurally different sterols are released from cells is poorly understood. Here, we show that newly synthesized precursor sterols arriving at the plasma membrane (PM) are removed by extracellular apoA-I in a manner dependent on ABCA1, a key macromolecule for HDL biogenesis. Analysis of sterol molecules by GC-MS and tracing the fate of radiolabeled acetate-derived sterols in normal and mutant Niemann-Pick type C cells reveal that ABCA1 prefers newly synthesized sterols, especially lanosterol, as the substrates before they are internalized from the PM. We also show that ABCA1 resides in a cholesterol-rich membrane domain resistant to the mild detergent, Brij 98. Blocking ACAT activity increases the cholesterol contents of this domain. Newly synthesized C29/C30 sterols are transiently enriched within this domain, but rapidly disappear from this domain with a half-life of less than 1 h. Our work shows that substantial amounts of precursor sterols are transported to a certain PM domain and are removed by the ABCA1-dependent pathway. PMID:26497474

  20. Investigation of Pyridine Carboxylic Acids in CM2 Carbonaceous Chondrites: Potential Precursor Molecules for Ancient Coenzymes

    NASA Technical Reports Server (NTRS)

    Smith, Karen E.; Callahan, Michael P.; Gerakines, Perry A.; Dworkin, Jason P.; House, Christopher H.

    2014-01-01

    The distribution and abundances of pyridine carboxylic acids (including nicotinic acid) in eight CM2 carbonaceous chondrites (ALH 85013, DOM 03183, DOM 08003, EET 96016, LAP 02333, LAP 02336, LEW 85311, and WIS 91600) were investigated by liquid chromatography coupled to UV detection and high resolution Orbitrap mass spectrometry. We find that pyridine monocarboxylic acids are prevalent in CM2-type chondrites and their abundance negatively correlates with the degree of pre-terrestrial aqueous alteration that the meteorite parent body experienced. We also report the first detection of pyridine dicarboxylic acids in carbonaceous chondrites. Additionally, we carried out laboratory studies of proton-irradiated pyridine in carbon dioxide-rich ices (a 1:1 mixture) to serve as a model of the interstellar ice chemistry that may have led to the synthesis of pyridine carboxylic acids. Analysis of the irradiated ice residue shows that a comparable suite of pyridine mono- and dicarboxylic acids was produced, although aqueous alteration may still play a role in the synthesis (and ultimate yield) of these compounds in carbonaceous meteorites. Nicotinic acid is a precursor to nicotinamide adenine dinucleotide, a likely ancient molecule used in cellular metabolism in all of life, and its common occurrence in CM2 chondrites may indicate that meteorites may have been a source of molecules for the emergence of more complex coenzymes on the early Earth.

  1. Investigation of Pyridine Carboxylic Acids in CM2 Carbonaceous Chondrites: Potential Precursor Molecules for Ancient Coenzymes

    NASA Technical Reports Server (NTRS)

    Smith, Karen E.; Callahan, Michael P.; Gerakines, Perry A.; Dworkin, Jason P.; House, Christopher H.

    2014-01-01

    The distribution and abundances of pyridine carboxylic acids (including nicotinic acid) in eight CM2 carbonaceous chondrites (ALH 85013, DOM 03183, DOM 08003, EET 96016, LAP 02333, LAP 02336, LEW 85311, and WIS 91600) were investigated by liquid chromatography coupled to UV detection and high resolution Orbitrap mass spectrometry. We find that pyridine monocarboxylic acids are prevalent in CM2-type chondrites and their abundance negatively correlates with the degree of pre-terrestrial aqueous alteration that the meteorite parent body experienced. We lso report the first detection of pyridine dicarboxylic acids in carbonaceous chondrites. Additionally, we carried out laboratory studies of proton-irradiated pyridine in carbon dioxide-rich ices (a 1:1 mixture) to serve as a model of the interstellar ice chemistry that may have led to the synthesis of pyridine carboxylic acids. Analysis of the irradiated ice residue shows that a comparable suite of pyridine mono- and dicarboxylic acids was produced, although aqueous alteration may still play a role in the synthesis (and ultimate yield) of these compounds in carbonaceous meteorites. Nicotinic acid is a precursor to nicotinamide adenine dinucleotide, a likely ancient molecule used in cellular metabolism in all of life, and its common occurrence in CM2 chondrites may indicate that meteorites may have been a source of molecules for the emergence of more complex coenzymes on the early Earth.

  2. Investigation of pyridine carboxylic acids in CM2 carbonaceous chondrites: Potential precursor molecules for ancient coenzymes

    NASA Astrophysics Data System (ADS)

    Smith, Karen E.; Callahan, Michael P.; Gerakines, Perry A.; Dworkin, Jason P.; House, Christopher H.

    2014-07-01

    The distribution and abundances of pyridine carboxylic acids (including nicotinic acid) in eight CM2 carbonaceous chondrites (ALH 85013, DOM 03183, DOM 08003, EET 96016, LAP 02333, LAP 02336, LEW 85311, and WIS 91600) were investigated by liquid chromatography coupled to UV detection and high resolution Orbitrap mass spectrometry. We find that pyridine monocarboxylic acids are prevalent in CM2-type chondrites and their abundance negatively correlates with the degree of pre-terrestrial aqueous alteration that the meteorite parent body experienced. We also report the first detection of pyridine dicarboxylic acids in carbonaceous chondrites. Additionally, we carried out laboratory studies of proton-irradiated pyridine in carbon dioxide-rich ices (a 1:1 mixture) to serve as a model of the interstellar ice chemistry that may have led to the synthesis of pyridine carboxylic acids. Analysis of the irradiated ice residue shows that a comparable suite of pyridine mono- and dicarboxylic acids was produced, although aqueous alteration may still play a role in the synthesis (and ultimate yield) of these compounds in carbonaceous meteorites. Nicotinic acid is a precursor to nicotinamide adenine dinucleotide, a likely ancient molecule used in cellular metabolism in all of life, and its common occurrence in CM2 chondrites may indicate that meteorites may have been a source of molecules for the emergence of more complex coenzymes on the early Earth.

  3. Scattering of slow electrons by polar molecules: Application of effective-range potential theory to HC1

    SciTech Connect

    Vanroose, Wim; McCurdy, C.W.; Rescigno, T.N.

    2003-06-19

    We present a non-empirical potential model for studying threshold vibrational excitation of polar molecules by electron impact. This work builds on the zero-range potential virtual state model of Gauyacq and Herzenberg (J.P. Gauyacq and A. Herzenberg, Phys. Rev. A 25, 2959 (1982)), using known analytic properties of the S-matrix for a dipole potential to predict the analytic continuation of the negative ion potential curve into the continuum. We derive an equation that determines the nuclear dynamics which can be solved without the need for an expansion in target vibrational states. The model is applied to e{sup -} - HCl and is found to capture the essential features of the observed excitation cross sections, including both the threshold peaks as well as oscillatory structures at energies above threshold.

  4. Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development

    PubMed Central

    Sharma, Charu; Sadek, Bassem; Goyal, Sameer N.; Sinha, Satyesh; Ojha, Shreesh

    2015-01-01

    The cannabinoid molecules are derived from Cannabis sativa plant which acts on the cannabinoid receptors types 1 and 2 (CB1 and CB2) which have been explored as potential therapeutic targets for drug discovery and development. Currently, there are numerous cannabinoid based synthetic drugs used in clinical practice like the popular ones such as nabilone, dronabinol, and Δ9-tetrahydrocannabinol mediates its action through CB1/CB2 receptors. However, these synthetic based Cannabis derived compounds are known to exert adverse psychiatric effect and have also been exploited for drug abuse. This encourages us to find out an alternative and safe drug with the least psychiatric adverse effects. In recent years, many phytocannabinoids have been isolated from plants other than Cannabis. Several studies have shown that these phytocannabinoids show affinity, potency, selectivity, and efficacy towards cannabinoid receptors and inhibit endocannabinoid metabolizing enzymes, thus reducing hyperactivity of endocannabinoid systems. Also, these naturally derived molecules possess the least adverse effects opposed to the synthetically derived cannabinoids. Therefore, the plant based cannabinoid molecules proved to be promising and emerging therapeutic alternative. The present review provides an overview of therapeutic potential of ligands and plants modulating cannabinoid receptors that may be of interest to pharmaceutical industry in search of new and safer drug discovery and development for future therapeutics. PMID:26664449

  5. Determination of interatomic potentials for diatomic molecules from low resolution spectra

    NASA Astrophysics Data System (ADS)

    Urbanczyk, T.; Koperski, J.; Pashov, A.

    2016-12-01

    Often, experimental spectra with only partially resolved rotational structure are observed. In such cases, determination of potential energy curves for the corresponding electronic states might be not as reliable as in the high resolution studies. In this paper, we estimate the uncertainties of the potential energy curve parameters, obtained from spectra with partially or not resolved rotational structure, where both frequencies and intensities are fitted. As an example, recently reported excitation spectrum of the B31(53P1) ← X10+(51S0) electronic transition in CdAr van der Waals complex is used. Two types of Morse functions are used to model the excited state potential, but method can be readily extended to more complex potential functions. It is shown, that for reliable estimation of the uncertainties of given potential function one should take into account the possible variation of the transition dipole moment function.

  6. Fusion Molecules of Heat Shock Protein HSPX with Other Antigens of Mycobacterium tuberculosis Show High Potential in Serodiagnosis of Tuberculosis.

    PubMed

    Khalid, Ruqyya; Afzal, Madeeha; Khurshid, Sana; Paracha, Rehan Zafar; Khan, Imran H; Akhtar, Muhammad Waheed

    Variable individual response against the antigens of Mycobacterium tuberculosis necessitates detection of multiple antibodies for enhancing reliability of serodiagnosis of tuberculosis. Fusion molecules consisting of two or more antigens showing high sensitivity would be helpful in achieving this objective. Antigens of M. tuberculosis HSPX and PE35 were expressed in a soluble form whereas tnPstS1 and FbpC1 were expressed as inclusion bodies at 37°C. Heat shock protein HSPX when attached to the N-termini of the antigens PE35, tnPstS1 and FbpC1, all the fusion molecules were expressed at high levels in E. coli in a soluble form. ELISA analysis of the plasma samples of TB patients against HSPX-tnPstS1 showed 57.7% sensitivity which is nearly the same as the expected combined value obtained after deducting the number of plasma samples (32) containing the antibodies against both the individual antigens. Likewise, the 54.4% sensitivity of HSPX-PE35 was nearly the same as that expected from the combined values of the contributing antigens. Structural analysis of all the fusion molecules by CD spectroscopy showed that α-helical and β-sheet contents were found close to those obtained through molecular modeling. Molecular modeling studies of HSPX-tnPstS1 and HSPX-PE35 support the analytical results as most of the epitopes of the contributing antigens were found to be available for binding to the corresponding antibodies. Using these fusion molecules in combination with other antigenic molecules should reduce the number of antigenic proteins required for a more reliable and economical serodiagnosis of tuberculosis. Also, HSPX seems to have potential application in soluble expression of heterologous proteins in E. coli.

  7. Fusion Molecules of Heat Shock Protein HSPX with Other Antigens of Mycobacterium tuberculosis Show High Potential in Serodiagnosis of Tuberculosis

    PubMed Central

    Khalid, Ruqyya; Afzal, Madeeha; Khurshid, Sana; Paracha, Rehan Zafar; Khan, Imran H.

    2016-01-01

    Variable individual response against the antigens of Mycobacterium tuberculosis necessitates detection of multiple antibodies for enhancing reliability of serodiagnosis of tuberculosis. Fusion molecules consisting of two or more antigens showing high sensitivity would be helpful in achieving this objective. Antigens of M. tuberculosis HSPX and PE35 were expressed in a soluble form whereas tnPstS1 and FbpC1 were expressed as inclusion bodies at 37°C. Heat shock protein HSPX when attached to the N-termini of the antigens PE35, tnPstS1 and FbpC1, all the fusion molecules were expressed at high levels in E. coli in a soluble form. ELISA analysis of the plasma samples of TB patients against HSPX-tnPstS1 showed 57.7% sensitivity which is nearly the same as the expected combined value obtained after deducting the number of plasma samples (32) containing the antibodies against both the individual antigens. Likewise, the 54.4% sensitivity of HSPX-PE35 was nearly the same as that expected from the combined values of the contributing antigens. Structural analysis of all the fusion molecules by CD spectroscopy showed that α-helical and β-sheet contents were found close to those obtained through molecular modeling. Molecular modeling studies of HSPX-tnPstS1 and HSPX-PE35 support the analytical results as most of the epitopes of the contributing antigens were found to be available for binding to the corresponding antibodies. Using these fusion molecules in combination with other antigenic molecules should reduce the number of antigenic proteins required for a more reliable and economical serodiagnosis of tuberculosis. Also, HSPX seems to have potential application in soluble expression of heterologous proteins in E. coli. PMID:27654048

  8. Fucoidan and Cancer: A Multifunctional Molecule with Anti-Tumor Potential

    PubMed Central

    Atashrazm, Farzaneh; Lowenthal, Ray M.; Woods, Gregory M.; Holloway, Adele F.; Dickinson, Joanne L.

    2015-01-01

    There is a wide variety of cancer types yet, all share some common cellular and molecular behaviors. Most of the chemotherapeutic agents used in cancer treatment are designed to target common deregulated mechanisms within cancer cells. Many healthy tissues are also affected by the cytotoxic effects of these chemical agents. Fucoidan, a natural component of brown seaweed, has anti-cancer activity against various cancer types by targeting key apoptotic molecules. It also has beneficial effects as it can protect against toxicity associated with chemotherapeutic agents and radiation. Thus the synergistic effect of fucoidan with current anti-cancer agents is of considerable interest. This review discusses the mechanisms by which fucoidan retards tumor development, eradicates tumor cells and synergizes with anti-cancer chemotherapeutic agents. Challenges to the development of fucoidan as an anti-cancer agent will also be discussed. PMID:25874926

  9. Junctional adhesion molecule-C promotes metastatic potential of HT1080 human fibrosarcoma.

    PubMed

    Fuse, Chiaki; Ishida, Yuuki; Hikita, Tomoya; Asai, Tomohiro; Oku, Naoto

    2007-03-16

    The junctional adhesion molecule (JAM) family is a key molecule in a process called transendothelial migration or diapedesis. Here, we report implications of JAM-C in cancer metastasis. We first determined the mRNA expression of JAMs in 19 kinds of cancer cell lines. JAM-C was expressed in most of tumors having potent metastatic properties. Especially in murine K-1735 melanoma cell lines, the highly metastatic sublines (M2 and X21) strongly expressed JAM-C when compared with the poorly metastatic ones (C-10 and C23). Next, we investigated the role of JAM-C in cancer metastasis by using human JAM-C (hJAM-C) gene-transfected HT1080 fibrosarcoma cells. In comparison with mock-transfected HT1080 cells, these cells showed a significant increase in the adhesion to various extracellular substrates and the invasion across a Matrigel-coated membrane. The knockdown of hJAM-C using small interfering RNA resulted in the suppression of both the adhesion and the invasion of HT1080 cells, suggesting that endogenous hJAM-C might be involved in tumor metastasis. Finally, we studied the role of hJAM-C in an in vivo experimental metastatic model. The results showed that the overexpression of hJAM-C in HT1080 cells significantly decreased the life spans of the tumorbearing mice. In contrast, the knockdown of hJAM-C in HT1080 cells suppressed the weight gain of the lungs with metastatic colonies. We conclude that the expression of JAM-C promotes metastasis by enhancing both the adhesion of cancer cells to extracellular matrices and the subsequent invasion.

  10. Mapping protein pockets through their potential small-molecule binding volumes: QSCD applied to biological protein structures

    NASA Astrophysics Data System (ADS)

    Mason, Keith; Patel, Nehal M.; Ledel, Aric; Moallemi, Ciamac C.; Wintner, Edward A.

    2004-01-01

    Previously we demonstrated a method, Quantized Surface Complementarity Diversity (QSCD), of defining molecular diversity by measuring shape and functional complementarity of molecules to a basis set of theoretical target surfaces [Wintner E.A. and Moallemi C.C., J. Med. Chem., 43 (2000) 1993]. In this paper we demonstrate a method of mapping actual protein pockets to the same basis set of theoretical target surfaces, thereby allowing categorization of protein pockets by their properties of shape and functionality. The key step in the mapping is a `dissection' algorithm that breaks any protein pocket into a set of potential small molecule binding volumes. It is these binding volumes that are mapped to the basis set of theoretical target surfaces, thus measuring a protein pocket not as a single surface but as a collection of molecular recognition environments.

  11. Assessment of the potential utility of different regions of Streptococcus uberis adhesion molecule (SUAM) for mastitis subunit vaccine development.

    PubMed

    Perrig, Melina Soledad; Veaute, Carolina; Renna, María Sol; Pujato, Nazarena; Calvinho, Luis; Marcipar, Iván; Barbagelata, María Sol

    2017-03-01

    Streptococcus uberis is one of the most prevalent pathogens causing clinical and subclinical mastitis worldwide. Among bacterial factors involved in intramammary infections caused by this organism, S. uberis adhesion molecule (SUAM) is one of the main virulence factors identified. This molecule is involved in S. uberis internalization to mammary epithelial cells through lactoferrin (Lf) binding. The objective of this study was to evaluate SUAM properties as a potential subunit vaccine component for prevention of S. uberis mastitis. B epitope prediction analysis of SUAM sequence was used to identify potentially immunogenic regions. Since these regions were detected all along the gene, this criterion did not allow selecting a specific region as a potential immunogen. Hence, four fractions of SUAM (-1fr, 2fr, 3fr and 4fr), comprising most of the protein, were cloned and expressed. Every fraction elicited a humoral immune response in mice as predicted by bioinformatics analysis. SUAM-1fr generated antibodies with the highest recognition ability towards SUAM native protein. Moreover, antibodies against SUAM-1fr produced the highest proportion of internalization inhibition of S. uberis to mammary epithelial cells. In conclusion, SUAM immunogenic and functionally relevant regions were identified and allowed to propose SUAM-1fr as a potential candidate for a subunit vaccine for S. uberis mastitis prevention.

  12. Effective Potential Energies and Transport Cross Sections for Atom-Molecule Interactions of Nitrogen and Nitrogen

    NASA Technical Reports Server (NTRS)

    Stallcop, James R.; Partridge, Harry; Levin, Eugene; Arnold, Jim (Technical Monitor)

    2001-01-01

    The potential energy surfaces for H2-N and N2-N interactions are calculated by accurate ab initio methods and applied to determine transport data. The results confirm that an effective potential energy for accurately determining transport properties can be calculated using a single orientation. A simple method is developed to determine the dispersion coefficients of effective potential energies Effective potential energies required for O2-O collisions are determ=ined. The H2-N, N2-N, O2-H, and O2-O collision integrals are calculated and tabulated for a large range of temperatures. The theoretical values of the N2-N and O2-O diffusion coefficients compare well with measured data available at room temperature.

  13. Effective Potential Energies and Transport Cross Sections for Atom-Molecule Interactions of Nitrogen and Nitrogen

    NASA Technical Reports Server (NTRS)

    Stallcop, James R.; Partridge, Harry; Levin, Eugene; Arnold, Jim (Technical Monitor)

    2001-01-01

    The potential energy surfaces for H2-N and N2-N interactions are calculated by accurate ab initio methods and applied to determine transport data. The results confirm that an effective potential energy for accurately determining transport properties can be calculated using a single orientation. A simple method is developed to determine the dispersion coefficients of effective potential energies Effective potential energies required for O2-O collisions are determ=ined. The H2-N, N2-N, O2-H, and O2-O collision integrals are calculated and tabulated for a large range of temperatures. The theoretical values of the N2-N and O2-O diffusion coefficients compare well with measured data available at room temperature.

  14. Positron-electron correlation-polarization potentials for the calculation of positron collisions with atoms and molecules*

    NASA Astrophysics Data System (ADS)

    Franz, Jan

    2017-02-01

    We present correlation-polarization potentials for the calculation of scattering cross sections of positrons with atoms and molecules. The potentials are constructed from a short-range correlation term and a long-range polarization term. For the short-range correlation term we present four different potentials that are derived from multi-component density functionals. For the long-range polarization term we employ a multi-term expansion. Quantum scattering calculations are presented for low energy collisions of positrons with two atomic targets (argon and krypton) and two molecular targets (nitrogen and methane). For collision energies below the threshold for Positronium formation our calculations of scattering cross sections are in good agreement with recent data sets from experiments and theory. Contribution to the Topical Issue "Low-Energy Interactions related to Atmospheric and Extreme Conditions", edited by S. Ptasinska, M. Smialek-Telega, A. Milosavljevic and B. Sivaraman.

  15. RKR1: A computer program implementing the first-order RKR method for determining diatomic molecule potential energy functions

    NASA Astrophysics Data System (ADS)

    Le Roy, Robert J.

    2017-01-01

    This paper describes computer program RKR1, which implements the first-order semiclassical Rydberg-Klein-Rees procedure for determining the potential energy function for a diatomic molecule from a knowledge of the dependence of the molecular vibrational energies Gv and inertial rotation constants Bv on the vibrational quantum number v. RKR1 allows the vibrational energies and rotational constants to be defined in terms of: (i) conventional Dunham polynomial expansions, (ii) near-dissociation expansions (NDE's), or (iii) the mixed Dunham/NDE "MXR" functions introduced by Tellinghuisen [J Chem Phys 2003; 118: 3532]. Internal convergence tests ascertain and report on the precision of the resulting turning points. For cases in which only vibrational data are available, RKR1 also allows an overall potential to be constructed by combining directly-calculated well widths with inner turning points generated from a Morse function. It can also automatically smooth over irregular or unphysical behavior of the steep inner wall of the potential.

  16. Interatomic potentials of the Hg-Kr Van der Waals molecule

    NASA Astrophysics Data System (ADS)

    Grycuk, T.; Czerwosz, E.

    1981-07-01

    The absorption spectrum of the Hg-Kr Van der Waals quasimolecule has been investigated in the spectral range from 250 to 1000 cm -1 about the center of the Hg 2537 Å line. The results of a careful analysis of this spectrum are presented, including the quasistatic line wings and satellites. Interatomic potentials for Hg-Kr in the ground electronic state 1o + as well as in the excited states 30 + and 31 have been deduced from the data. The ground state potential has been obtained by fitting the Maitland-Smith function to our experimental results and to some other data available in the literature. Its well depth is estimated to be 200 ± 20 cm -1. The potential curve of the 30 + excimer state for a wide range of separations has been obtained by means of the data inversion technique based on the quasistatic theory of line broadening. The well depth of this potential is found to be 430 ± 40 cm -1. A hypothesis concerning the origin of the blue satellites is proposed. The potential curve of the 31 state, determining the structure of the blue wing spectrum is also inferred.

  17. Photoisomerization dynamics of a rhodopsin-based molecule (potential molecular switch) with high quantum yields

    NASA Astrophysics Data System (ADS)

    Allen, Roland; Jiang, Chen-Wei; Zhang, Xiu-Xing; Fang, Ai-Ping; Li, Hong-Rong; Xie, Rui-Hua; Li, Fu-Li

    2015-03-01

    It is worthwhile to explore the detailed reaction dynamics of various candidates for molecular switches, in order to understand, e.g., the differences in quantum yields and switching times. Here we report density-functional-based simulations for the rhodopsin-based molecule 4-[4-Methylbenzylidene]-5-p-tolyl-3,4-dihydro-2H-pyrrole (MDP), synthesized by Sampedro et al. We find that the photoisomerization quantum yields are remarkably high: 82% for cis-to-trans, and 68% for trans-to-cis. The lifetimes of the S1 excited state in cis-MDP in our calculations are in the range of 900-1800 fs, with a mean value of 1270 fs, while the range of times required for full cis-to-trans isomerization are 1100-2000 fs, with a mean value of 1530 fs. In trans-MDP, the calculated S1 excited state lifetimes are 860-2140 fs, with a mean value of 1330 fs, and with the full trans-to-cis isomerization completed about 200 fs later. In both cases, the dominant reaction mechanism is rotation around the central C =C bond (connected to the pyrroline ring), and de-excitation occurs at an avoided crossing between the ground state and the lowest singlet state, near the midpoint of the rotational pathway. Research Fund for the Doctoral Program of Higher Education of China; Fundamental Research Funds for the Central Universities; Robert A. Welch Foundation; National Natural Science Foundation of China.

  18. Photoisomerization dynamics of a rhodopsin-based molecule (potential molecular switch) with high quantum yields

    NASA Astrophysics Data System (ADS)

    Jiang, Chen-Wei; Zhang, Xiu-Xing; Fang, Ai-Ping; Li, Hong-Rong; Xie, Rui-Hua; Li, Fu-Li; Allen, Roland E.

    2015-02-01

    It is worthwhile to explore the detailed reaction dynamics of various candidates for molecular switches, in order to understand, e.g., the differences in quantum yields and switching times. Here we report density-functional-based simulations for the rhodopsin-based molecule 4-[4-methylbenzylidene]-5-p-tolyl-3,4-dihydro-2H-pyrrole (MDP), synthesized by Sampedro et al We find that the photoisomerization quantum yields are remarkably high: 82% for cis-to-trans, and 68% for trans-to-cis. The lifetimes of the S1 excited state in cis-MDP in our calculations are in the range of 900-1800 fs, with a mean value of 1270 fs, while the range of times required for full cis-to-trans isomerization are 1100-2000 fs, with a mean value of 1530 fs. In trans-MDP, the calculated S1 excited state lifetimes are 860-2140 fs, with a mean value of 1330 fs, and with the full trans-to-cis isomerization completed about 200 fs later. In both cases, the dominant reaction mechanism is rotation around the central C=C bond (connected to the pyrroline ring), and de-excitation occurs at an avoided crossing between the ground state and the lowest singlet state, near the midpoint of the rotational pathway. Perhaps remarkably, but apparently because of electrostatic repulsion, the direction of rotation is the same for both reactions.

  19. Microbial inhibition of oral epithelial wound recovery: potential role for quorum sensing molecules?

    PubMed

    De Ryck, Tine; Vanlancker, Eline; Grootaert, Charlotte; Roman, Bart I; De Coen, Laurens M; Vandenberghe, Isabel; Stevens, Christian V; Bracke, Marc; Van de Wiele, Tom; Vanhoecke, Barbara

    2015-01-01

    Awareness of the impact of microbiota in both health and disease is growing. Using a new in vitro oral mucosa co-culture model, we recently showed a clear inhibition of epithelial wound healing in the presence of an oral microbial community. In this paper, we have used the same model in combination with specific oral microbial species to obtain a better insight into the role of the oral microbiota in wound healing. Monocultures of Klebsiella oxytoca and Lactobacillus salivarius significantly inhibited wound healing with ~20%, whereas Streptococcus mitis and S. oralis enhanced the healing process with ~15% in 24 h. Yet, neither S. oralis or S. mitis were able to counteract the inhibitory effects from K. oxytoca on wound healing. Other tested microbial species had no effect on wound healing. Apart from this species-dependency, the inhibitory effect on wound healing depended on a microbial threshold concentration. Further mechanistic experiments with K. oxytoca excluded different microbial factors and hypothesized that quorum sensing molecules might play a role in the inter-kingdom signalling during wound healing. These results are important for the development of new strategies for the management of (infected) wounds and ulcerations.

  20. Synchronization modulation of Na/K pump molecules can hyperpolarize the membrane resting potential in intact fibers.

    PubMed

    Chen, Wei; Dando, Robin

    2007-02-01

    Previously, we have theoretically studied the possibility of electrical rhythmic entrainment of carrier-mediated ion transporters, and experimentally realized synchronization and acceleration of the Na/K pumping rate in the cell membrane of skeletal muscle fibers by a specially designed synchronization modulation electric field. In these studies we either used cut fibers under a voltage clamp or intact fibers, but in the presence of ion channels blockers. A question remained as to whether the field-induced activation observed in the pump molecules could effectively increase the intracellular ionic concentration and the membrane potential at physiological conditions. In this paper, we studied the effects of the field on intact fibers without any channel blockers. We monitored the field-induced changes in the ionic concentration gradient across the cell membrane and the membrane potential non-invasively by using a fluorescent probe and confocal microscopic imaging techniques. The results clearly show that the entrainment of the pump molecules by the synchronization modulation electric field can effectively increase the ionic concentration gradient, and hence, hyperpolarize the membrane potential.

  1. Combined single channel and single molecule detection identifies subunit composition of STIM1-activated transient receptor potential canonical (TRPC) channels.

    PubMed

    Asanov, Alexander; Sampieri, Alicia; Moreno, Claudia; Pacheco, Jonathan; Salgado, Alfonso; Sherry, Ryan; Vaca, Luis

    2015-01-01

    Depletion of intracellular calcium ion stores initiates a rapid cascade of events culminating with the activation of the so-called Store-Operated Channels (SOC) at the plasma membrane. Calcium influx via SOC is essential in the initiation of calcium-dependent intracellular signaling and for the refilling of internal calcium stores, ensuring the regeneration of the signaling cascade. In spite of the significance of this evolutionary conserved mechanism, the molecular identity of SOC has been the center of a heated controversy spanning over the last 20 years. Initial studies positioned some members of the transient receptor potential canonical (TRPC) channel superfamily of channels (with the more robust evidence pointing to TRPC1) as a putative SOC. Recent evidence indicates that Stromal Interacting Molecule 1 (STIM1) activates some members from the TRPC family of channels. However, the exact subunit composition of TRPC channels remains undetermined to this date. To identify the subunit composition of STIM1-activated TRPC channels, we developed novel method, which combines single channel electrophysiological measurements based on the patch clamp technique with single molecule fluorescence imaging. We termed this method Single ion Channel Single Molecule Detection technique (SC-SMD). Using SC-SMD method, we have obtained direct evidence of the subunit composition of TRPC channels activated by STIM1. Furthermore, our electrophysiological-imaging SC-SMD method provides evidence at the molecular level of the mechanism by which STIM1 and calmodulin antagonize to modulate TRPC channel activity.

  2. A Small Molecule Inhibitor of Human RAD51 Potentiates Breast Cancer Cell Killing by Therapeutic Agents in Mouse Xenografts

    PubMed Central

    Huang, Fei; Mazin, Alexander V.

    2014-01-01

    The homologous recombination pathway is responsible for the repair of DNA double strand breaks. RAD51, a key homologous recombination protein, promotes the search for homology and DNA strand exchange between homologous DNA molecules. RAD51 is overexpressed in a variety of cancer cells. Downregulation of RAD51 by siRNA increases radio- or chemo-sensitivity of cancer cells. We recently developed a specific RAD51 small molecule inhibitor, B02, which inhibits DNA strand exchange activity of RAD51 in vitro. In this study, we used human breast cancer cells MDA-MB-231 to investigate the ability of B02 to inhibit RAD51 and to potentiate an anti-cancer effect of chemotherapeutic agents including doxorubicin, etoposide, topotecan, and cisplatin. We found that the combination of B02 with cisplatin has the strongest killing effect on the cancer cells. We then tested the effect of B02 and cisplatin on the MDA-MB-231 cell proliferation in mouse xenografts. Our results showed that B02 significantly enhances the therapeutic effect of cisplatin on tumor cells in vivo. Our current data demonstrate that use of RAD51-specific small molecule inhibitor represents a feasible strategy of a combination anti-cancer therapy. PMID:24971740

  3. Electron structure of molecules with very heavy atoms using effective core potentials

    SciTech Connect

    Pitzer, K.S.

    1982-01-01

    Topics covered include effective potential, Hamiltonian for valence-electron motion, molecular calculations, spin-spin coupling, L-S coupling, numerical results of molecular calculations, and results of configuration-interaction Slater-orbital calculations in L-S coupling. (GHT)

  4. The Calculation of Potential Energy Curves of Diatomic Molecules: The RKR Method.

    ERIC Educational Resources Information Center

    Castano, F.; And Others

    1983-01-01

    The RKR method for determining accurate potential energy curves is described. Advantages of using the method (compared to Morse procedure) and a TRS-80 computer program which calculates the classical turning points by an RKR method are also described. The computer program is available from the author upon request. (Author/JN)

  5. The Calculation of Potential Energy Curves of Diatomic Molecules: The RKR Method.

    ERIC Educational Resources Information Center

    Castano, F.; And Others

    1983-01-01

    The RKR method for determining accurate potential energy curves is described. Advantages of using the method (compared to Morse procedure) and a TRS-80 computer program which calculates the classical turning points by an RKR method are also described. The computer program is available from the author upon request. (Author/JN)

  6. Small molecules targeting glycogen synthase kinase 3 as potential drug candidates for the treatment of retinitis pigmentosa.

    PubMed

    Marchena, Miguel; Villarejo-Zori, Beatriz; Zaldivar-Diez, Josefa; Palomo, Valle; Gil, Carmen; Hernández-Sánchez, Catalina; Martínez, Ana; de la Rosa, Enrique J

    2017-12-01

    Retinitis pigmentosa (RP) is an inherited retinal dystrophy that courses with progressive degeneration of retinal tissue and loss of vision. Currently, RP is an unpreventable, incurable condition. We propose glycogen synthase kinase 3 (GSK-3) inhibitors as potential leads for retinal cell neuroprotection, since the retina is also a part of the central nervous system and GSK-3 inhibitors are potent neuroprotectant agents. Using a chemical genetic approach, diverse small molecules with different potency and binding mode to GSK-3 have been used to validate and confirm GSK-3 as a pharmacological target for RP. Moreover, this medicinal chemistry approach has provided new leads for the future disease-modifying treatment of RP.

  7. Identification of a potential conformationally disordered mesophase in a small molecule: experimental and computational approaches.

    PubMed

    Chakravarty, Paroma; Bates, Simon; Thomas, Leonard

    2013-08-05

    GNE068, a small organic molecule, was obtained as an amorphous form (GNE068-A) after isolation from ethanol and as a partially disordered form (GNE068-PC) from ethyl acetate. On subsequent characterization, GNE068-PC exhibited a number of properties that were anomalous for a two phase crystalline-amorphous system but consistent with the presence of a solid state phase having intermediate order (mesomorphous). Modulated DSC measurements of GNE068-PC revealed an overlapping endotherm and glass transition in the 135-145 °C range. ΔH of the endotherm showed strong heating rate dependence. Variable temperature XRPD (25-160 °C) revealed structure loss in GNE068-PC, suggesting the endotherm to be an "apparent melt". In addition, gentle grinding of GNE068-PC in a mortar led to a marked decrease in XRPD peak intensities, indicating a "soft" crystalline lattice. Computational analysis of XRPD data revealed the presence of two noncrystalline contributions, one of which was associated with GNE068-A. The second was a variable component that could be modeled as diffuse scattering from local disorder within the associated crystal structure, suggesting a mesomorphous system. Owing to the dominance of the noncrystalline diffuse scattering in GNE068-PC and the observed lattice deformation, the mesomorphous phase exhibited properties consistent with a conformationally disordered mesophase. Because of the intimate association of the residual solvent (ethyl acetate) with the lattice long-range order, loss of solvent on heating through the glass transition temperature of the local disorder caused irrecoverable loss of the long-range order. This precluded the observation of characteristic thermodynamic mesophase behavior above the glass transition temperature.

  8. Therapeutic Potential and Pharmaceutical Development of Thymoquinone: A Multitargeted Molecule of Natural Origin

    PubMed Central

    Goyal, Sameer N.; Prajapati, Chaitali P.; Gore, Prashant R.; Patil, Chandragouda R.; Mahajan, Umesh B.; Sharma, Charu; Talla, Sandhya P.; Ojha, Shreesh K.

    2017-01-01

    Thymoquinone, a monoterpene molecule is chemically known as 2-methyl-5-isopropyl-1, 4-benzoquinone. It is abundantly present in seeds of Nigella sativa L. that is popularly known as black cumin or black seed and belongs to the family Ranunculaceae. A large number of studies have revealed that thymoquinone is the major active constituent in N. sativa oil this constituent is responsible for the majority of the pharmacological properties. The beneficial organoprotective activities of thymoquinone in experimental animal models of different human diseases are attributed to the potent anti-oxidant and anti-inflammatory properties. Thymoquinone has also been shown to alter numerous molecular and signaling pathways in many inflammatory and degenerative diseases including cancer. Thymoquinone has been reported to possess potent lipophilicity and limited bioavailability and exhibits light and heat sensitivity. Altogether, these physiochemical properties encumber the successful formulation for the delivery of drug in oral dosages form and restrict the pharmaceutical development. In recent past, many efforts were undertaken to improve the bioavailability for clinical usage by manipulating the physiochemical parameters. The present review aimed to provide insights regarding the physicochemical characteristics, pharmacokinetics and the methods to promote pharmaceutical development and endorse the clinical usage of TQ in future by overcoming the associated physiochemical obstacles. It also enumerates briefly the pharmacological and molecular targets of thymoquinone as well as the pharmacological properties in various diseases and the underlying molecular mechanism. Though, a convincing number of experimental studies are available but human studies are not available with thymoquinone despite of the long history of use of black cumin in different diseases. Thus, the clinical studies including pharmacokinetic studies and regulatory toxicity studies are required to encourage the

  9. The (H2)2 potential surface and the interaction between hydrogen molecules at low temperatures

    NASA Astrophysics Data System (ADS)

    Burton, Peter G.; Senff, Ulrich E.

    1982-06-01

    The (H2)2 rigid rotor interaction potential has been calculated for the intermolecular distance range R = 3.0-11.0 a.u. for six relative orientations to estimate both the isotropic and anisotropic components of the full intermolecular potential. A partially optimized basis set limited in size to 78 independent Gaussian functions was used throughout the energy calculations, which required only very small corrections for basis set unsaturation effects. Correlation effects were computed both at the variational (single and) double excitation PNOCI level and using the CEPA2-PNO approximation to estimate higher order excitation effects. While the latter rigid-rotor surface may overestimate the strength of the H2-H2 interaction in the vicinity of the well by a few wave numbers in the rigid-rotor PNOCI surface from the present study, which we regard as an upper bound to the true rigid-rotor surface, is also slightly deeper than almost all previous theoretical and empirical ''fit'' potentials in the well region. Since low energy scattering experiments lack sensitivity to the precise well depth because of the long de Broglie wavelengths appropriate to scattering at energies comparable with the well depth, the significance of the current disagreement on the well depth between the rigid-rotor level of the theory (which puts it at least 27.5 cm-1) and experiment is uncertain. However, coupled with the present uncertainty stemming from the CI formalism of ˜±3 cm-1, is a further uncertainty due to the expected increase in intramolecular zero-point energies due to hindered H2 vibration within the dimer. A zero-point increase within each H2 at Re of 0.1% would effectively raise the rigid-rotor potentials by some 4 cm-1, bringing the well depth into line with experimental estimates. In the low energy part of the repulsive wall of the potential (where the relative importance of these small effects diminishes), which has been probed rather sensitively by recent rotationally

  10. Surface potential dependence of the distribution of charged dye molecules onto photosynthetic membranes.

    PubMed

    Masamoto, K; Matsuura, K; Itoh, S; Nishimura, M

    1981-02-01

    Partition of merocyanine dyes, which have a negative charge, onto photosynthetic membranes of chloroplasts and bacteria was analyzed by measuring the fluorescence intensity change, absorbance change, and amount of dye in the supernatant after centrifugation. The partition depended on the surface potential, which is a function of valence and concentration of ions in the medium. The distribution of dyes between the membrane and aqueous phase was determined after centrifugation. The logarithm of the ratio of distribution was linearly related to the logarithm of salt concentration as predicted from the Gouy-Chapman theory and the Boltzmann distribution. Plots of the logarithm of fluorescence intensity against the logarithm of KCl and MgSO4 concentrations gave two straight lines with a slope ratio of about two. The absorbance change upon salt addition was also explained by the Gouy-Chapman theory. The use of these dyes as probes of the surface potential of membranes is discussed.

  11. N-acetylation of three aromatic amine hair dye precursor molecules eliminates their genotoxic potential.

    PubMed

    Zeller, Andreas; Pfuhler, Stefan

    2014-01-01

    N-acetylation has been described as a detoxification reaction for aromatic amines; however, there is only limited data available showing that this metabolic conversion step changes their genotoxicity potential. To extend this database, three aromatic amines, all widely used as precursors in oxidative hair dye formulations, were chosen for this study: p-phenylenediamine (PPD), 2,5-diaminotoluene (DAT) and 4-amino-2-hydroxytoluene (AHT). Aiming at a deeper mechanistic understanding of the interplay between activation and detoxification for this chemical class, we compared the genotoxicity profiles of the parent compounds with those of their N-acetylated metabolites. While PPD, DAT and AHT all show genotoxic potential in vitro, their N-acetylated metabolites completely lack genotoxic potential as shown in the Salmonella typhimurium reversion assay, micronucleus test with cultured human lymphocytes (AHT), chromosome aberration assay with V79 cells (DAT) and Comet assay performed with V79 cells. For the bifunctional aromatic amines studied (PPD and DAT), monoacetylation was sufficient to completely abolish their genotoxic potential. Detoxification through N-acetylation was further confirmed by comparing PPD, DAT and AHT in the Comet assay using standard V79 cells (N-acetyltransferase (NAT) deficient) and two NAT-proficient cell lines,V79NAT1*4 and HaCaT (human keratinocytes). Here we observed a clear shift of dose-response curves towards decreased genotoxicity of the parent aromatic amines in the NAT-proficient cells. These findings suggest that genotoxic effects will only be found at concentrations where the N-acetylation (detoxifying) capacity of the cells is overwhelmed, indicating that a 'first-pass' effect in skin could be taken into account for risk assessment of these topically applied aromatic amines. The findings also indicate that the use of liver S-9 preparations, which generally underestimate Phase II reactions, contributes to the generation of irrelevant

  12. Cysteamine, the Molecule Used To Treat Cystinosis, Potentiates the Antimalarial Efficacy of Artemisinin▿

    PubMed Central

    Min-Oo, Gundula; Fortin, Anny; Poulin, Jean-François; Gros, Philippe

    2010-01-01

    Malaria continues to be a major threat to global health. Artemisinin combination therapy (ACT) is the recommended treatment for clinical malaria; however, recent reports of parasite resistance to artemisinin in certain areas where malaria is endemic have stressed the need for developing more efficacious ACT. We report that cysteamine (Cys), the aminothiol used to treat nephropathic cystinosis in humans, strongly potentiates the efficacy of artemisinin against the Plasmodium parasite in vivo. Using a mouse model of infection with Plasmodium chabaudi AS, we observe that Cys dosing used to treat cystinosis in humans can strongly potentiate (by 3- to 4-fold) the antimalarial properties of the artemisinin derivatives artesunate and dihydroartemisinin. Addition of Cys to suboptimal doses of artemisinin delays the appearance of blood parasitemia, strongly reduces the extent of parasite replication, and significantly improves survival in a model of lethal P. chabaudi infection. Cys, the natural product of the enzyme pantetheinase, has a history of safe use for the clinical management of cystinosis. Our findings suggest that Cys could be included in novel ACTs to improve efficacy against Plasmodium parasite replication, including artemisinin-resistant isolates. Future work will include clinical evaluation of novel Cys-containing ACTs and elucidation of the mechanism underlying the potentiation effect of Cys. PMID:20479197

  13. Inertial and bias effects in the rotational Brownian motion of rodlike molecules in a uniaxial potential

    NASA Astrophysics Data System (ADS)

    Kalmykov, Yuri P.; Titov, Sergey V.; Coffey, William T.

    2011-01-01

    Inertial effects in the rotational Brownian motion in space of a rigid dipolar rotator (needle) in a uniaxial potential biased by an external field giving rise to asymmetry are treated via the infinite hierarchy of differential-recurrence relations for the statistical moments (orientational correlation functions) obtained by averaging the Euler-Langevin equation over its realizations in phase space. The solutions of this infinite hierarchy for the dipole correlation function and its characteristic times are obtained using matrix continued fractions showing that the model simultaneously predicts both slow overbarrier (or interwell) relaxation at low frequencies accompanied by intermediate frequency Debye relaxation due to fast near-degenerate motion in the wells of the potential (intrawell relaxation) as well as the high frequency resonance (Poley) absorption due to librations of the dipole moments. It is further shown that the escape rate of a Brownian particle from a potential well as extended to the Kramers turnover problem via the depopulation factor yields a close approximation to the longest (overbarrier) relaxation time of the system. For zero and small values of the bias field parameter h, both the dipole moment correlation time and the longest relaxation time have Arrhenius behavior (exponential increase with increasing barrier height). While at values of h in excess of a critical value however far less than that required to achieve nucleation, the Arrhenius behavior of the correlation time disappears.

  14. Properties of a new hydrotrope hydrophobic molecule and its potential applications.

    PubMed

    Schnell, E; Touraud, D; Gick, R; Kunz, W

    2008-10-01

    In the present contribution, the properties of dipropylene glycol isobornyl ether (Pribelance) are discussed, especially in the context of microemulsion and emulsion formulations. Pribelance is a new low-toxic anti-foaming hydrotrope with excellent co-surfactant properties that has some similarities with long-chain alcohols, but in contrast to them, it is liquid at room temperature. In combination with another, more hydrophilic co-surfactant, it allows significant amounts of oil to be solubilized in water. Possible applications such as in cosmetics, as an anti-foaming agent or as additive to cooling lubricants are discussed. Further potential applications are plasticizers, fermentation systems, agrochemicals and waste-water treatments.

  15. Molecules that mimic apolipoprotein A-I: potential agents for treating atherosclerosis.

    PubMed

    Leman, Luke J; Maryanoff, Bruce E; Ghadiri, M Reza

    2014-03-27

    Certain amphipathic α-helical peptides can functionally mimic many of the properties of full-length apolipoproteins, thereby offering an approach to modulate high-density lipoprotein (HDL) for combating atherosclerosis. In this Perspective, we summarize the key findings and advances over the past 25 years in the development of peptides that mimic apolipoproteins, especially apolipoprotein A-I (apoA-I). This assemblage of information provides a reasonably clear picture of the state of the art in the apolipoprotein mimetic field, an appreciation of the potential for such agents in pharmacotherapy, and a sense of the opportunities for optimizing the functional properties of HDL.

  16. Molecules that Mimic Apolipoprotein A-I: Potential Agents for Treating Atherosclerosis

    PubMed Central

    Leman, Luke J.; Maryanoff, Bruce E.; Ghadiri, M. Reza

    2013-01-01

    Certain amphipathic α-helical peptides can functionally mimic many of the properties of full-length apolipoproteins, thereby offering an approach to modulate high-density lipoprotein (HDL) for combating atherosclerosis. In this Perspective, we summarize the key findings and advances over the past 25 years in the development of peptides that mimic apolipoproteins, especially apolipoprotein A-I (apoA-I). This assemblage of information provides a reasonably clear picture of the state of the art in the apolipoprotein mimetic field, an appreciation of the potential for such agents in pharmacotherapy, and a sense of the opportunities for optimizing the functional properties of HDL. PMID:24168751

  17. Angular distributions of electrons photoemitted from core levels of oriented diatomic molecules: Multiple scattering theory in non-spherical potentials

    SciTech Connect

    Diez Muino, R.; Rolles, D.; Garcia de Abajo, F.J.; Fadley, C.S.; Van Hove, M.A.

    2001-09-06

    We use multiple scattering in non-spherical potentials (MSNSP) to calculate the angular distributions of electrons photoemitted from the 1s-shells of CO and N2 gas-phase molecules with fixed-in-space orientations. For low photoelectron kinetic energies (E<50 eV), as appropriate to certain shape-resonances, the electron scattering must be represented by non-spherical scattering potentials, which are naturally included in our formalism. Our calculations accurately reproduce the experimental angular patterns recently measured by several groups, including those at the shape-resonance energies. The MSNSP theory thus enhances the sensitivity to spatial electronic distribution and dynamics, paving the way toward their determination from experiment.

  18. Full-dimensional, permutationally invariant and size-extensive potential energy surfaces for small molecules

    NASA Astrophysics Data System (ADS)

    Braams, B. J.; Bowman, Joel M.; Park, Seung; Stanton, John F.

    2005-03-01

    We have constructed full-dimensional potential energy surfaces for a variety of molecular systems, among them CH5+, H3O2-, H4O2, H5O2+, C2H2O, C3H3O, CH2O, and HOONO/HONO2. The property of invariance under permutations of like nuclei is built into the basis for the least-squares fitting procedure, and we relied on the MAGMA computational algebra system to find the invariants and to help generate the codes. The use of a cluster expansion (many-body expansion), going up to five-body or at most six-body terms, caters for dissociation and reaction processes and also for extension to larger systems. The fitted potential and its gradient are evaluated on a millisecond timescale, making it possible to do molecular dynamics or quantum Monte Carlo calculations at ab initio accuracy without anywhere near the cost that is normally associated with ab initio MD, or even with a Car-Parrinello treatment. We also use the fitted surface for MULTIMODE calculations of vibrational spectrum. The poster will present the computational approach and results for the mentioned systems.

  19. Parasite annexins--new molecules with potential for drug and vaccine development.

    PubMed

    Hofmann, Andreas; Osman, Asiah; Leow, Chiuan Yee; Driguez, Patrick; McManus, Donald P; Jones, Malcolm K

    2010-11-01

    In the last few years, annexins have been discovered in several nematodes and other parasites, and distinct differences between the parasite annexins and those of the hosts make them potentially attractive targets for anti-parasite therapeutics. Annexins are ubiquitous proteins found in almost all organisms across all kingdoms.Here, we present an overview of novel annexins from parasitic organisms, and summarize their phylogenetic and biochemical properties, with a view to using them as drug or vaccine targets. Building on structural and biological information that has been accumulated for mammalian and plant annexins, we describe a predicted additional secondary structure element found in many parasite annexins that may confer unique functional properties, and present a specific antigenic epitope for use as a vaccine.

  20. Investigations of the potential functions of weakly bound diatomic molecules and laser-assisted excitive Penning ionization

    SciTech Connect

    Goble, J.H. Jr.

    1982-05-01

    Three variations on the Dunham series expansion function of the potential of a diatomic molecule are compared. The differences among these expansions lie in the choice of the expansion variable, lambda. The functional form of these variables are lambda/sub s/ = l-r/sub e//r for the Simon-Parr-Finlan version, lambda/sub T/ - 1-(r/sub e//r)/sup p/ for that of Thakkar, and lambda/sub H/ = 1-exp(-rho(r/r/sub e/-1) for that of Huffaker. A wide selection of molecular systems are examined. It is found that, for potentials in excess of thirty kcal/mole, the Huffaker expansion provides the best description of the three, extrapolating at large internuclear separation to a value within 10% of the true dissociation energy. For potentials that result from the interaction of excited states, all series expansions show poor behavior away from the equilibrium internuclear separation of the molecule. The series representation of the potentials of weakly bound molecules are examined in more detail. The ground states of BeAr/sup +/, HeNe/sup +/, NaAr, and Ar/sub 2/ and the excited states of HeNe+, NaNe, and NaAr are best described by the Thakkar expansion. Finally, the observation of laser-assisted excitive Penning ionization in a flowing afterglow is reported. The reaction Ar(/sup 3/P/sub 2/) + Ca + h nu ..-->.. Ar + Ca/sup +/(5p /sup 2/P/sub J/) + e/sup -/ occurs when the photon energy, h nu, is approximately equal to the energy difference between the metastable argon and one of the fine structure levels of the ion's doublet. By monitoring the cascade fluorescence of the above reaction and comparing it to the flourescence from the field-free process Ar(/sup 3/P/sub 2/) + Ca ..-->.. Ar + Ca/sup +/(4p /sup 2/P/sub J/) + e/sup -/ a surprisingly large cross section of 6.7 x 10/sup 3/ A/sup 2/ is estimated.

  1. Invited review: Milk phospholipid vesicles, their colloidal properties, and potential as delivery vehicles for bioactive molecules.

    PubMed

    Arranz, E; Corredig, M

    2017-06-01

    The milk fat globule membrane (MFGM) is a unique colloidal assembly of phospholipids and proteins, with numerous potential applications as functional ingredient. The phospholipid components of the MFGM are gaining interest as they are a useful matrix for use as a constituent of delivery systems such as liposomes. Liposomes formulated with milk phospholipids are becoming an alternative to other sources of phospholipids such as soybean or egg yolk. However, incorporation of phospholipids fractionated from the milk fat globule membrane in dairy products requires an in-depth understanding of the functional properties of phospholipids. In particular, it is critical to understand which factors play a role in their stability and bioefficacy as delivery systems. Moreover, chemical and physical modifications of phospholipid liposomes occurring during digestion and the fate of the encapsulated compounds are very important to understand. This review discusses recent findings on the structure and functionality of MFGM, the bioactivity of the phospholipids fraction, their utilization as delivery systems, and their stability through gastrointestinal transit. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  2. Accurate Ionization Potentials and Electron Affinities of Acceptor Molecules: A Benchmark of GW Methods

    NASA Astrophysics Data System (ADS)

    Marom, Noa; Knight, Joseph; Wang, Xiaopeng; Gallandi, Lukas; Dolgounitcheva, Olga; Ren, Xinguo; Ortiz, Vincent; Rinke, Patrick; Korzdorfer, Thomas

    The performance of different GW methods is assessed for a set of 24 organic acceptors. Errors are evaluated with respect to coupled cluster singles, doubles, perturbative triples [CCSD(T)] reference data for the vertical ionization potentials (IPs) and electron affinities (EAs), extrapolated to the complete basis set limit. Additional comparisons are made to experimental data, where available. We consider fully self-consistent GW (scGW), partial self-consistency in the Green's function (scGW0) , non-self-consistent G0W0 based on several mean-field starting points, and a ``beyond GW'' second order screened exchange (SOSEX) correction to G0W0. The best performers overall are G0W0 + SOSEX and G0W0 based on an IP-tuned long range corrected hybrid functional with the former being more accurate for EAs and the latter for IPs. Both provide a balanced treatment of localized vs. delocalized states and valence spectra in good agreement with photoemission spectroscopy (PES) experiments.

  3. Staphylococcus epidermidis Biofilms: Functional Molecules, Relation to Virulence, and Vaccine Potential

    NASA Astrophysics Data System (ADS)

    Mack, Dietrich; Davies, Angharad P.; Harris, Llinos G.; Knobloch, Johannes K. M.; Rohde, Holger

    Medical device-associated infections, most frequently caused by Staphylococcus epidermidis and Staphylococcus aureus, are of increasing importance in modern medicine. The formation of adherent, multilayered bacterial biofilms is crucial in the pathogenesis of these infections. Polysaccharide intercellular adhesin (PIA), a homoglycan of β-1,6-linked 2-acetamido-2-deoxy-d-glucopyranosyl residues, of which about 15% are non-N-acetylated, is central to biofilm accumulation in staphylococci. It transpires that polysaccharides - structurally very similar to PIA - are also key to biofilm formation in a number of other organisms including the important human pathogens Escherichia coli, Aggregatibacter (Actinobacillus) actinomycetemcomitans, Yersinia pestis, and Bordetella spp. Apparently, synthesis of PIA and related polysaccharides is a general feature important for biofilm formation in diverse bacterial genera. Current knowledge about the structure and biosynthesis of PIA and related polysaccharides is reviewed. Additionally, information on their role in pathogenesis of biomaterial-related and other type of infections and the potential use of PIA and related compounds for prevention of infection is evaluated.

  4. A Small-Molecule Inhibitor of PIM Kinases as a Potential Treatment for Urothelial Carcinomas12

    PubMed Central

    Foulks, Jason M.; Carpenter, Kent J.; Luo, Bai; Xu, Yong; Senina, Anna; Nix, Rebecca; Chan, Ashley; Clifford, Adrianne; Wilkes, Marcus; Vollmer, David; Brenning, Benjamin; Merx, Shannon; Lai, Shuping; McCullar, Michael V.; Ho, Koc-Kan; Albertson, Daniel J.; Call, Lee T.; Bearss, Jared J.; Tripp, Sheryl; Liu, Ting; Stephens, Bret J.; Mollard, Alexis; Warner, Steven L.; Bearss, David J.; Kanner, Steven B.

    2014-01-01

    The proto-oncogene proviral integration site for moloney murine leukemia virus (PIM) kinases (PIM-1, PIM-2, and PIM-3) are serine/threonine kinases that are involved in a number of signaling pathways important to cancer cells. PIM kinases act in downstream effector functions as inhibitors of apoptosis and as positive regulators of G1-S phase progression through the cell cycle. PIM kinases are upregulated in multiple cancer indications, including lymphoma, leukemia, multiple myeloma, and prostate, gastric, and head and neck cancers. Overexpression of one or more PIM family members in patient tumors frequently correlates with poor prognosis. The aim of this investigation was to evaluate PIM expression in low- and high-grade urothelial carcinoma and to assess the role PIM function in disease progression and their potential to serve as molecular targets for therapy. One hundred thirty-seven cases of urothelial carcinoma were included in this study of surgical biopsy and resection specimens. High levels of expression of all three PIM family members were observed in both noninvasive and invasive urothelial carcinomas. The second-generation PIM inhibitor, TP-3654, displays submicromolar activity in pharmacodynamic biomarker modulation, cell proliferation studies, and colony formation assays using the UM-UC-3 bladder cancer cell line. TP-3654 displays favorable human ether-à-go-go-related gene and cytochrome P450 inhibition profiles compared with the first-generation PIM inhibitor, SGI-1776, and exhibits oral bioavailability. In vivo xenograft studies using a bladder cancer cell line show that PIM kinase inhibition can reduce tumor growth, suggesting that PIM kinase inhibitors may be active in human urothelial carcinomas. PMID:24953177

  5. The optimized effective potential and the self-interaction correction in density functional theory: Application to molecules

    SciTech Connect

    Garza, Jorge; Nichols, Jeffrey A.; Dixon, David A.

    2000-05-08

    The Krieger, Li, and Iafrate approximation to the optimized effective potential including the self-interaction correction for density functional theory has been implemented in a molecular code, NWChem, that uses Gaussian functions to represent the Kohn and Sham spin-orbitals. The differences between the implementation of the self-interaction correction in codes where planewaves are used with an optimized effective potential are discussed. The importance of the localization of the spin-orbitals to maximize the exchange-correlation of the self-interaction correction is discussed. We carried out exchange-only calculations to compare the results obtained with these approximations, and those obtained with the local spin density approximation, the generalized gradient approximation and Hartree-Fock theory. Interesting results for the energy difference (GAP) between the highest occupied molecular orbital, HOMO, and the lowest unoccupied molecular orbital, LUMO, (spin-orbital energies of closed shell atoms and molecules) using the optimized effective potential and the self-interaction correction have been obtained. The effect of the diffuse character of the basis set on the HOMO and LUMO eigenvalues at the various levels is discussed. Total energies obtained with the optimized effective potential and the self-interaction correction show that the exchange energy with these approximations is overestimated and this will be an important topic for future work. (c) 2000 American Institute of Physics.

  6. Time-dependent density functional study of the electronic potential energy curves and excitation spectrum of the oxygen molecule.

    PubMed

    Guan, Jingang; Wang, Fan; Ziegler, Tom; Cox, Hazel

    2006-07-28

    Orbital energies, ionization potentials, molecular constants, potential energy curves, and the excitation spectrum of O(2) are calculated using time-dependent density functional theory (TDDFT) with Tamm-Dancoff approximation (TDA). The calculated negative highest occupied molecular orbital energy (-epsilon(HOMO)) is compared with the energy difference ionization potential for five exchange correlation functionals consisting of the local density approximation (LDAxc), gradient corrected Becke exchange plus Perdew correlation (B(88X)+P(86C)), gradient regulated asymptotic correction (GRAC), statistical average of orbital potentials (SAOP), and van Leeuwen and Baerends asymptotically correct potential (LB94). The potential energy curves calculated using TDDFT with the TDA at internuclear distances from 1.0 to 1.8 A are divided into three groups according to the electron configurations. The 1pi(u) (4)1pi(g) (2) electron configuration gives rise to the X (3)Sigma(g) (-), a (1)Delta(g), and b (1)Sigma(g) (+) states; the 1pi(u) (3)1pi(g) (3) electron configuration gives rise to the c (1)Sigma(u) (-), C (3)Delta(u), and A (3)Sigma(u) (+) states; and the B (3)Sigma(u) (-), A (1)Delta(u), and f (1)Sigma(u) (+) states are determined by the mixing of two or more electron configurations. The excitation spectrum of the oxygen molecule, calculated with the aforementioned exchange correlation functionals, shows that the results are quite sensitive to the choice of functional. The LDAxc and the B(88X)+P(86C) functionals produce similar spectroscopic patterns with a single strongly absorbing band positioned at 19.82 and 19.72 eV, respectively, while the asymptotically corrected exchange correlation functionals of the SAOP and the LB94 varieties yield similar excitation spectra where the computed strongly absorbing band is located at 16.09 and 16.42 eV, respectively. However, all of the exchange correlation functionals yield only one strongly absorbing band (oscillator strength

  7. Novel macrocyclic molecules based on 12a-N substituted 16-membered azalides and azalactams as potential antifungal agents.

    PubMed

    Wang, Xiaolei; Zhang, Shun; Pang, Yanlong; Yuan, Huihui; Liang, Xiaomei; Zhang, Jianjun; Wang, Daoquan; Wang, Mingan; Dong, Yanhong

    2014-02-12

    Novel macrocyclic molecules comprising sulfonyl and acyl moiety at the position N-12a of 16-membered azalides (6a-n) and azalactams (10a-r) scaffold were synthesized from cyclododecanone 1 as starting material via 5 steps and 4 steps, respectively. The antifungal activity of these compounds against Sclerotinia sclerotiorum, Pyricularia oryzae, Botrytis cinerea, Rhizoctonia solani and Phytophthora capsici were evaluated and found that compounds possessing α-exomethylene (6c, 6d, 6e and 6g) showed antifungal activity comparable to commercial fungicide Chlorothalonil against P. oryzae and compounds possessing p-chlorobenzoyl exhibited enhanced antifungal activity than those with other substituents against S. sclerotiorum, P. oryzae, and B. cinerea. These findings suggested that the α-exomethylene and p-chlorobenzoyl may be two potential pharmacological active groups with antifungal activities.

  8. Orthogonal coordinates for the dynamics of four bodies and for the representation of potentials of tetra-atomic molecules

    NASA Astrophysics Data System (ADS)

    Ragni, Mirco; Bitencourt, Ana Carla P.; Aquilanti, Vincenzo

    We discuss systems of orthogonal coordinates for the dynamical treatment of four particles, generated by making extensive use of the concept of kinematic rotations, which act on coordinates of the particles and are represented by matrices only dependent on their masses. The explicit representations of the kinetic rotation matrices are given: this allows us to define alternative particle schemes, such as those based on the Jacobi and Radau-Smith vectors, as well as on mixed types of vectors, of possible interest for specific molecules or aggregates. A list is given of relevant formulas connecting these coordinate sets to the geometrical parameters (internuclear distances, bond and dihedral angles) of use for the representation of the potential energy surface of four atomic systems. Applications are indicated for molecular and cluster physics.0

  9. Effects of Tilt Angle, DNA Concentration, and Surface Potential on Directed Alignment of DNA Molecule for the Application to Nanodevices

    NASA Astrophysics Data System (ADS)

    Kim, Hyung Jin; Hong, Byungyou

    2013-03-01

    This paper reports an efficient approach to control both the density and direction of highly aligned DNA molecules and thus DNA-templated gold nanowires (AuNWs) on Si chips. We utilized tilting method to prepare stretched DNA structures on SiO2/Si substrate and found important parameters in the alignment process that tilt angle, DNA concentration, and surface potential are controlled the density and structure of DNA aligned on the surface. In additional, we also can be directly connected DNA-templated AuNWs between two terminal electrodes on Si chips. This method also describes a simple way to form singled, bundled and networked DNA arrays on Si substrates.

  10. Analytic functions for potential energy curves, dipole moments, and transition dipole moments of LiRb molecule.

    PubMed

    You, Yang; Yang, Chuan-Lu; Wang, Mei-Shan; Ma, Xiao-Guang; Liu, Wen-Wang; Wang, Li-Zhi

    2016-01-15

    The analytic potential energy functions (APEFs) of the X(1)Σ(+), 2(1)Σ(+), a(3)Σ(+), and 2(3)Σ(+) states of the LiRb molecule are obtained using Morse long-range potential energy function with damping function and nonlinear least-squares method. These calculations were based on the potential energy curves (PECs) calculated using the multi-reference configuration interaction (MRCI) method. The reliability of the APEFs is confirmed using the curves of their first and second derivatives. By using the obtained APEFs, the rotational and vibrational energy levels of the states are determined by solving the Schrödinger equation of nuclear movement. The spectroscopic parameters, which are deduced using Dunham expansion, and the obtained rotational and vibrational levels are compared with the reported theoretical and experimental values. The correlation effect of the electrons of the inner shell remarkably improves the results compared with the experimental spectroscopic parameters. For the first time, the APEFs for the dipole moments and transition dipole moments of the states have been determined based on the curves obtained from the MRCI calculations. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Identification of small molecule inhibitors of ERCC1-XPF that inhibit DNA repair and potentiate cisplatin efficacy in cancer cells

    PubMed Central

    Arora, Sanjeevani; Heyza, Joshua; Zhang, Hao; Kalman-Maltese, Vivian; Tillison, Kristin; Floyd, Ashley M.; Chalfin, Elaine M.; Bepler, Gerold; Patrick, Steve M.

    2016-01-01

    ERCC1-XPF heterodimer is a 5′-3′ structure-specific endonuclease which is essential in multiple DNA repair pathways in mammalian cells. ERCC1-XPF (ERCC1-ERCC4) repairs cisplatin-DNA intrastrand adducts and interstrand crosslinks and its specific inhibition has been shown to enhance cisplatin cytotoxicity in cancer cells. In this study, we describe a high throughput screen (HTS) used to identify small molecules that inhibit the endonuclease activity of ERCC1-XPF. Primary screens identified two compounds that inhibit ERCC1-XPF activity in the nanomolar range. These compounds were validated in secondary screens against two other non-related endonucleases to ensure specificity. Results from these screens were validated using an in vitro gel-based nuclease assay. Electrophoretic mobility shift assays (EMSAs) further show that these compounds do not inhibit the binding of purified ERCC1-XPF to DNA. Next, in lung cancer cells these compounds potentiated cisplatin cytotoxicity and inhibited DNA repair. Structure activity relationship (SAR) studies identified related compounds for one of the original Hits, which also potentiated cisplatin cytotoxicity in cancer cells. Excitingly, dosing with NSC16168 compound potentiated cisplatin antitumor activity in a lung cancer xenograft model. Further development of ERCC1-XPF DNA repair inhibitors is expected to sensitize cancer cells to DNA damage-based chemotherapy. PMID:27650543

  12. Identification of small molecule inhibitors of ERCC1-XPF that inhibit DNA repair and potentiate cisplatin efficacy in cancer cells.

    PubMed

    Arora, Sanjeevani; Heyza, Joshua; Zhang, Hao; Kalman-Maltese, Vivian; Tillison, Kristin; Floyd, Ashley M; Chalfin, Elaine M; Bepler, Gerold; Patrick, Steve M

    2016-11-15

    ERCC1-XPF heterodimer is a 5'-3' structure-specific endonuclease which is essential in multiple DNA repair pathways in mammalian cells. ERCC1-XPF (ERCC1-ERCC4) repairs cisplatin-DNA intrastrand adducts and interstrand crosslinks and its specific inhibition has been shown to enhance cisplatin cytotoxicity in cancer cells. In this study, we describe a high throughput screen (HTS) used to identify small molecules that inhibit the endonuclease activity of ERCC1-XPF. Primary screens identified two compounds that inhibit ERCC1-XPF activity in the nanomolar range. These compounds were validated in secondary screens against two other non-related endonucleases to ensure specificity. Results from these screens were validated using an in vitro gel-based nuclease assay. Electrophoretic mobility shift assays (EMSAs) further show that these compounds do not inhibit the binding of purified ERCC1-XPF to DNA. Next, in lung cancer cells these compounds potentiated cisplatin cytotoxicity and inhibited DNA repair. Structure activity relationship (SAR) studies identified related compounds for one of the original Hits, which also potentiated cisplatin cytotoxicity in cancer cells. Excitingly, dosing with NSC16168 compound potentiated cisplatin antitumor activity in a lung cancer xenograft model. Further development of ERCC1-XPF DNA repair inhibitors is expected to sensitize cancer cells to DNA damage-based chemotherapy.

  13. Analytic functions for potential energy curves, dipole moments, and transition dipole moments of LiRb molecule

    NASA Astrophysics Data System (ADS)

    You, Yang; Yang, Chuan-Lu; Wang, Mei-Shan; Ma, Xiao-Guang; Liu, Wen-Wang; Wang, Li-Zhi

    2016-01-01

    The analytic potential energy functions (APEFs) of the X1Σ+, 21Σ+, a3Σ+, and 23Σ+ states of the LiRb molecule are obtained using Morse long-range potential energy function with damping function and nonlinear least-squares method. These calculations were based on the potential energy curves (PECs) calculated using the multi-reference configuration interaction (MRCI) method. The reliability of the APEFs is confirmed using the curves of their first and second derivatives. By using the obtained APEFs, the rotational and vibrational energy levels of the states are determined by solving the Schrödinger equation of nuclear movement. The spectroscopic parameters, which are deduced using Dunham expansion, and the obtained rotational and vibrational levels are compared with the reported theoretical and experimental values. The correlation effect of the electrons of the inner shell remarkably improves the results compared with the experimental spectroscopic parameters. For the first time, the APEFs for the dipole moments and transition dipole moments of the states have been determined based on the curves obtained from the MRCI calculations.

  14. Nrf2 and HSF-1 Pathway Activation via Hydroquinone-Based Proelectrophilic Small Molecules is Regulated by Electrochemical Oxidation Potential.

    PubMed

    Satoh, Takumi; Stalder, Romain; McKercher, Scott R; Williamson, Robert E; Roth, Gregory P; Lipton, Stuart A

    2015-01-01

    Activation of the Kelch-like ECH-associated protein 1/nuclear factor (erythroid-derived 2)-like 2 and heat-shock protein 90/heat-shock factor-1 signal-transduction pathways plays a central role in combatting cellular oxidative damage and related endoplasmic reticulum stress. Electrophilic compounds have been shown to be activators of these transcription-mediated responses through S-alkylation of specific regulatory proteins. Previously, we reported that a prototype compound (D1, a small molecule representing a proelectrophilic, para-hydroquinone species) exhibited neuroprotective action by activating both of these pathways. We hypothesized that the para-hydroquinone moiety was critical for this activation because it enhanced transcription of these neuroprotective pathways to a greater degree than that of the corresponding ortho-hydroquinone isomer. This notion was based on the differential oxidation potentials of the isomers for the transformation of the hydroquinone to the active, electrophilic quinone species. Here, to further test this hypothesis, we synthesized a pair of para- and ortho-hydroquinone-based proelectrophilic compounds and measured their redox potentials using analytical cyclic voltammetry. The redox potential was then compared with functional biological activity, and the para-hydroquinones demonstrated a superior neuroprotective profile.

  15. Brain-penetrant, orally bioavailable microtubule-stabilizing small molecules are potential candidate therapeutics for Alzheimer's disease and related tauopathies.

    PubMed

    Lou, Kevin; Yao, Yuemang; Hoye, Adam T; James, Michael J; Cornec, Anne-Sophie; Hyde, Edward; Gay, Bryant; Lee, Virginia M-Y; Trojanowski, John Q; Smith, Amos B; Brunden, Kurt R; Ballatore, Carlo

    2014-07-24

    Microtubule (MT) stabilizing drugs hold promise as potential treatments for Alzheimer's disease (AD) and related tauopathies. However, thus far epothilone D has been the only brain-penetrant MT-stabilizer to be evaluated in tau transgenic mice and in AD patients. Furthermore, this natural product exhibits potential deficiencies as a drug candidate, including an intravenous route of administration and the inhibition of the P-glycoprotein (Pgp) transporter. Thus, the identification of alternative CNS-active MT-stabilizing agents that lack these potential limitations is of interest. Toward this objective, we have evaluated representative compounds from known classes of non-naturally occurring MT-stabilizing small molecules. This led to the identification of selected triazolopyrimidines and phenylpyrimidines that are orally bioavailable and brain-penetrant without disruption of Pgp function. Pharmacodynamic studies confirmed that representative compounds from these series enhance MT-stabilization in the brains of wild-type mice. Thus, these classes of MT-stabilizers hold promise for the development of orally active, CNS-directed MT-stabilizing therapies.

  16. dPotFit: A computer program to fit diatomic molecule spectral data to potential energy functions

    NASA Astrophysics Data System (ADS)

    Le Roy, Robert J.

    2017-01-01

    This paper describes program dPotFit, which performs least-squares fits of diatomic molecule spectroscopic data consisting of any combination of microwave, infrared or electronic vibrational bands, fluorescence series, and tunneling predissociation level widths, involving one or more electronic states and one or more isotopologs, and for appropriate systems, second virial coefficient data, to determine analytic potential energy functions defining the observed levels and other properties of each state. Four families of analytical potential functions are available for fitting in the current version of dPotFit: the Expanded Morse Oscillator (EMO) function, the Morse/Long-Range (MLR) function, the Double-Exponential/Long-Range (DELR) function, and the 'Generalized Potential Energy Function' (GPEF) of Šurkus, which incorporates a variety of polynomial functional forms. In addition, dPotFit allows sets of experimental data to be tested against predictions generated from three other families of analytic functions, namely, the 'Hannover Polynomial' (or "X-expansion") function, and the 'Tang-Toennies' and Scoles-Aziz 'HFD', exponential-plus-van der Waals functions, and from interpolation-smoothed pointwise potential energies, such as those obtained from ab initio or RKR calculations. dPotFit also allows the fits to determine atomic-mass-dependent Born-Oppenheimer breakdown functions, and singlet-state Λ-doubling, or 2Σ splitting radial strength functions for one or more electronic states. dPotFit always reports both the 95% confidence limit uncertainty and the "sensitivity" of each fitted parameter; the latter indicates the number of significant digits that must be retained when rounding fitted parameters, in order to ensure that predictions remain in full agreement with experiment. It will also, if requested, apply a "sequential rounding and refitting" procedure to yield a final parameter set defined by a minimum number of significant digits, while ensuring no

  17. Antitumor potential of a synthetic interferon-alpha/PLGF-2 positive charge peptide hybrid molecule in pancreatic cancer cells

    PubMed Central

    Yin, Hongmei; Chen, Naifei; Guo, Rui; Wang, Hong; Li, Wei; Wang, Guanjun; Cui, Jiuwei; Jin, Haofan; Hu, Ji-Fan

    2015-01-01

    Pancreatic cancer is the most aggressive malignant disease, ranking as the fourth leading cause of cancer-related death among men and women in the United States. Interferon alpha (IFNα) has been used to treat pancreatic cancer, but its clinical application has been significantly hindered due to the low antitumor activity. We used a “cDNA in-frame fragment library” screening approach to identify short peptides that potentiate the antitumor activity of interferons. A short positively charged peptide derived from the C-terminus of placental growth factor-2 (PLGF-2) was selected to enhance the activity of IFNα. For this, we constructed a synthetic interferon hybrid molecule (SIFα) by fusing the positively charged PLGF-2 peptide to the C-terminus of the human IFNα. Using human pancreatic cell lines (ASPC and CFPAC1) as a model system, we found that SIFα exhibited a significantly higher activity than did the wild-type IFNα in inhibiting the tumor cell growth. The enhanced activity of the synthetic SIFα was associated with the activation of interferon pathway target genes and the increased binding of cell membrane receptor. This study demonstrates the potential of a synthetic SIFα as a novel antitumor agent. PMID:26584517

  18. Metronomic Small Molecule Inhibitor of Bcl-2 (TW-37) Is Antiangiogenic and Potentiates the Antitumor Effect of Ionizing Radiation

    SciTech Connect

    Zeitlin, Benjamin D.; Spalding, Aaron C.; Campos, Marcia S.; Ashimori, Naoki; Dong Zhihong; Wang Shaomeng; Lawrence, Theodore S.; Noer, Jacques E.

    2010-11-01

    Purpose: To investigate the effect of a metronomic (low-dose, high-frequency) small-molecule inhibitor of Bcl-2 (TW-37) in combination with radiotherapy on microvascular endothelial cells in vitro and in tumor angiogenesis in vivo. Methods and Materials: Primary human dermal microvascular endothelial cells were exposed to ionizing radiation and/or TW-37 and colony formation, as well as capillary sprouting in three-dimensional collagen matrices, was evaluated. Xenografts vascularized with human blood vessels were engineered by cotransplantation of human squamous cell carcinoma cells (OSCC3) and human dermal microvascular endothelial cells seeded in highly porous biodegradable scaffolds into the subcutaneous space of immunodeficient mice. Mice were treated with metronomic TW-37 and/or radiation, and tumor growth was evaluated. Results: Low-dose TW-37 sensitized primary endothelial cells to radiation-induced inhibition of colony formation. Low-dose TW-37 or radiation partially inhibited endothelial cell sprout formation, and in combination, these therapies abrogated new sprouting. Combination of metronomic TW-37 and low-dose radiation inhibited tumor growth and resulted in significant increase in time to failure compared with controls, whereas single agents did not. Notably, histopathologic analysis revealed that tumors treated with TW-37 (with or without radiation) are more differentiated and showed more cohesive invasive fronts, which is consistent with less aggressive phenotype. Conclusions: These results demonstrate that metronomic TW-37 potentiates the antitumor effects of radiotherapy and suggest that patients with head and neck cancer might benefit from the combination of small molecule inhibitor of Bcl-2 and radiation therapy.

  19. Potential Function of Granulysin, Other Related Effector Molecules and Lymphocyte Subsets in Patients with TB and HIV/TB Coinfection

    PubMed Central

    Pitabut, Nada; Sakurada, Shinsaku; Tanaka, Takahiro; Ridruechai, Chutharut; Tanuma, Junko; Aoki, Takahiro; Kantipong, Pacharee; Piyaworawong, Surachai; Kobayashi, Nobuyuki; Dhepakson, Panadda; Yanai, Hideki; Yamada, Norio; Oka, Shinichi; Okada, Masaji; Khusmith, Srisin; Keicho, Naoto

    2013-01-01

    Background: Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy. Objective: To investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9+Vδ2+ T cells, CD4+ T cells and CD8+ T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection. Methods: Circulating granulysin, perforin, granzyme-B and IFN-γ levels were determined by ELISA. The isoforms of granulysin were analyzed by Western blot analysis. The effector cells were analyzed by flow cytometry. Results: Circulating granulysin and perforin levels in TB patients were lower than healthy controls, whereas the granulysin levels in HIV/TB coinfection were much higher than in any other groups, TB and HIV with or without receiving HAART, which corresponded to the number of CD8+ T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17kDa, 15kDa and 9kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed. Conclusion: The results suggested that the alteration of circulating granulysin has potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection. PMID:23801887

  20. Caffeine prevents sleep loss-induced deficits in long-term potentiation and related signaling molecules in the dentate gyrus.

    PubMed

    Alhaider, Ibrahim A; Aleisa, Abdulaziz M; Tran, Trinh T; Alkadhi, Karim A

    2010-04-01

    We have previously reported that caffeine prevented sleep deprivation-induced impairment of long-term potentiation (LTP) of area CA1 as well as hippocampus-dependent learning and memory performance in the radial arm water maze. In this report we examined the impact of long-term (4-week) caffeine consumption (0.3 g/L in drinking water) on synaptic plasticity (Alhaider et al., 2010) deficit in the dentate gyrus (DG) area of acutely sleep-deprived rats. The sleep deprivation and caffeine/sleep deprivation groups were sleep-deprived for 24 h by using the columns-in-water technique. We tested the effect of caffeine and/or sleep deprivation on LTP and measured the basal levels as well as stimulated levels of LTP-related molecules in the DG. The results showed that chronic caffeine administration prevented the impairment of early-phase LTP (E-LTP) in the DG of sleep-deprived rats. Additionally, chronic caffeine treatment prevented the sleep deprivation-associated decreases in the basal levels of the phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) and brain derived neurotrophic factor (BDNF) as well as in the stimulated levels of P-CaMKII in the DG area. The results suggest that chronic use of caffeine prevented anomalous changes in the basal levels of P-CaMKII and BDNF associated with sleep deprivation and as a result contributes to the revival of LTP in the DG region.

  1. Potential roles of myeloperoxidase and hypochlorous acid in metabolism and toxicity of alkene hydrocarbons and drug molecules containing olefinic moieties.

    PubMed

    Zhang, Xin-Yu; Elfarra, Adnan A

    2017-05-01

    Adverse drug reactions (ADRs) pose a significant health problem and are generally attributed to reactive metabolites. Olefinic moieties in drugs can undergo cytochrome P450-mediated bioactivation to produce reactive metabolites but myeloperoxidase (MPO)-mediated bioactivation of these moieties has not been reported. Thus, small molecules of alkene hydrocarbons are used as model compounds to characterize the MPO-mediated metabolism. Areas covered: The authors focus on MPO-mediated metabolism of alkene hydrocarbons to form chlorohydrins and the potential role of chlorohydrins in alkene toxicity and carcinogenicity. A case study is presented, in which a carcinogenic alkene, 1,3-butadiene, is demonstrated to form 1-chloro-2-hydroxy-3-butene (CHB) through the MPO-mediated pathway. Further bioactivation of CHB yields a cross-linking metabolite, 1-chloro-3-buten-2-one (CBO), which is highly reactive toward glutathione, proteins, nucleosides, and DNA. Toxicity and mutagenicity of CHB and CBO are also presented. Expert opinion: Alkene hydrocarbons readily undergo MPO-mediated bioactivation to form chlorohydrins, which can further be biotransformed into proteins/DNA-modifying reactive metabolites. Therefore, chlorohydrin formation may play an important role in alkene toxicity and carcinogenicity. Olefinic moieties in drugs are expected to undergo similar bioactivation, which may contribute to ADRs. Studies to investigate the roles of MPO and chlorohydrin formation in ADRs are thus warranted.

  2. Calculation of rotation-vibration energy levels of the ammonia molecule based on an ab initio potential energy surface

    NASA Astrophysics Data System (ADS)

    Polyansky, Oleg L.; Ovsyannikov, Roman I.; Kyuberis, Aleksandra A.; Lodi, Lorenzo; Tennyson, Jonathan; Yachmenev, Andrey; Yurchenko, Sergei N.; Zobov, Nikolai F.

    2016-09-01

    An ab initio potential energy surface (PES) for gas-phase ammonia NH3 has been computed using the methodology pioneered for water (Polyansky et al., 2013). Multireference configuration interaction calculations are performed at about 50 000 points using the aug-cc-pCVQZ and aug-cc-pCV5Z basis sets and basis set extrapolation. Relativistic and adiabatic surfaces are also computed. The points are fitted to a suitable analytical form, producing the most accurate ab initio PES for this molecule available. The rotation-vibration energy levels are computed using nuclear motion program TROVE in both linearised and curvilinear coordinates. Better convergence is obtained using curvilinear coordinates. Our results are used to assign the visible spectrum of 14NH3 recorded by Coy and Lehmann (1986). Rotation-vibration energy levels for the isotopologues NH2D, NHD2, ND3 and 15NH3 are also given. An ab initio value for the dissociation energy D0 of 14NH3 is also presented.

  3. Systems Based Study of the Therapeutic Potential of Small Charged Molecules for the Inhibition of IL-1 Mediated Cartilage Degradation

    PubMed Central

    Kar, Saptarshi; Smith, David W.; Gardiner, Bruce S.; Grodzinsky, Alan J.

    2016-01-01

    Inflammatory cytokines are key drivers of cartilage degradation in post-traumatic osteoarthritis. Cartilage degradation mediated by these inflammatory cytokines has been extensively investigated using in vitro experimental systems. Based on one such study, we have developed a computational model to quantitatively assess the impact of charged small molecules intended to inhibit IL-1 mediated cartilage degradation. We primarily focus on the simplest possible computational model of small molecular interaction with the IL-1 system—direct binding of the small molecule to the active site on the IL-1 molecule itself. We first use the model to explore the uptake and release kinetics of the small molecule inhibitor by cartilage tissue. Our results show that negatively charged small molecules are excluded from the negatively charged cartilage tissue and have uptake kinetics in the order of hours. In contrast, the positively charged small molecules are drawn into the cartilage with uptake and release timescales ranging from hours to days. Using our calibrated computational model, we subsequently explore the effect of small molecule charge and binding constant on the rate of cartilage degradation. The results from this analysis indicate that the small molecules are most effective in inhibiting cartilage degradation if they are either positively charged and/or bind strongly to IL-1α, or both. Furthermore, our results showed that the cartilage structural homeostasis can be restored by the small molecule if administered within six days following initial tissue exposure to IL-1α. We finally extended the scope of the computational model by simulating the competitive inhibition of cartilage degradation by the small molecule. Results from this model show that small molecules are more efficient in inhibiting cartilage degradation by binding directly to IL-1α rather than binding to IL-1α receptors. The results from this study can be used as a template for the design and

  4. Systems Based Study of the Therapeutic Potential of Small Charged Molecules for the Inhibition of IL-1 Mediated Cartilage Degradation.

    PubMed

    Kar, Saptarshi; Smith, David W; Gardiner, Bruce S; Grodzinsky, Alan J

    2016-01-01

    Inflammatory cytokines are key drivers of cartilage degradation in post-traumatic osteoarthritis. Cartilage degradation mediated by these inflammatory cytokines has been extensively investigated using in vitro experimental systems. Based on one such study, we have developed a computational model to quantitatively assess the impact of charged small molecules intended to inhibit IL-1 mediated cartilage degradation. We primarily focus on the simplest possible computational model of small molecular interaction with the IL-1 system-direct binding of the small molecule to the active site on the IL-1 molecule itself. We first use the model to explore the uptake and release kinetics of the small molecule inhibitor by cartilage tissue. Our results show that negatively charged small molecules are excluded from the negatively charged cartilage tissue and have uptake kinetics in the order of hours. In contrast, the positively charged small molecules are drawn into the cartilage with uptake and release timescales ranging from hours to days. Using our calibrated computational model, we subsequently explore the effect of small molecule charge and binding constant on the rate of cartilage degradation. The results from this analysis indicate that the small molecules are most effective in inhibiting cartilage degradation if they are either positively charged and/or bind strongly to IL-1α, or both. Furthermore, our results showed that the cartilage structural homeostasis can be restored by the small molecule if administered within six days following initial tissue exposure to IL-1α. We finally extended the scope of the computational model by simulating the competitive inhibition of cartilage degradation by the small molecule. Results from this model show that small molecules are more efficient in inhibiting cartilage degradation by binding directly to IL-1α rather than binding to IL-1α receptors. The results from this study can be used as a template for the design and development

  5. Theoretical investigation of electronic states and spectroscopic properties of tellurium selenide molecule employing relativistic effective core potentials.

    PubMed

    Chattopadhyaya, Surya; Nath, Abhijit; Das, Kalyan Kumar

    2014-04-24

    Ab initio based relativistic configuration interaction calculations have been performed to study the electronic states and spectroscopic properties of tellurium selenide (TeSe) - the heaviest heteronuclear diatomic group 16-16 molecule. Potential energy curves of several spin-excluded (Λ-S) electronic states of TeSe have been constructed and spectroscopic constants of low-lying bound Λ-S states within 3.85 eV are reported in the first stage of calculations. The X(3)Σ(-), a(1)Δ and b(1)Σ(+) are found as the ground, first excited and second excited state, respectively, at the Λ-S level and all these three states are mainly dominated by …π(4)π(*2) configuration. The computed ground state dissociation energy is in very good agreement with the experimental results. In the next stage of calculations, effects of spin-orbit coupling on the potential energy curves and spectroscopic properties of the species are investigated in details and compared with the existing experimental results. After inclusion of spin-orbit coupling the X(3)(1)Σ(-)(0(+)) is found as the ground-state spin component of TeSe. The computed spin-orbit splitting between two components of X(3)Σ(-) state is 1285 cm(-1). Also, significant amount of spin-orbit splitting are found between spin-orbit components (Ω-components) of several other excited states. Transition moments of some important spin-allowed and spin-forbidden transitions are calculated from configuration interaction wave functions. The spin-allowed transition B(3)Σ(-)-X(3)Σ(-) and spin-forbidden transition b(1)Σ(+)(0(+))-X(3)(1)Σ(-)(0(+)) are found to be the strongest in their respective categories. Electric dipole moments of all the bound Λ-S states along with those of the two Ω-components of X(3)Σ(-) are also calculated in the present study.

  6. Formal redox potentials of organic molecules in ionic liquids on the basis of quaternary nitrogen cations as adiabatic electron affinities.

    PubMed

    Seto, Kunimasa; Nakayama, Tatsushi; Uno, Bunji

    2013-09-19

    Formal redox potentials E°' involving neutral species R and radical anions R(•-) in ionic liquids (ILs) composed of ammonium, pyridinium, and imidazolium cations are discussed from the point of view of the adiabatic electron affinity as a molecular property. The dependence of the 1,4-benzoquinone (BQ)/BQ(•-) redox process in CH2Cl2 and CH3CN is primarily investigated over a wide concentration range of ILs as the supporting electrolyte. A logarithmic relationship involving a positive shift of E°' with increasing concentration is obtained when the concentration is changed from 0.01 to 1.0 M. The relationship of E°' at IL concentrations greater than 1.0 M gradually reaches a plateau and remains there even for the neat ILs. It is found that the E°' values in the neat ILs are not influenced by the measurement conditions, and that they remain considerably dependent on the nature and concentration of the electrolyte when measured using the traditional method involving molecular solvents combined with a supporting electrolyte (0.1-0.5 M). The difference in the E°' values observed in the ammonium and pyridinium ILs is only several millivolts. In addition, ESR and self-consistent isodensity polarized continuum model calculation results reveal that the potential shift toward positive values upon the transition from molecular solvents containing ILs to neat ILs is adequately accounted for by changes in the electrostatic interaction of R(•-) taken into the cavity composed of the solvent and IL. On the other hand, the first reduction waves of quinones, electron-accepting molecules, and polynuclear aromatic hydrocarbons are reversibly or quasi-reversibly observed in the ILs. The electrochemical stability of the ILs is exploited in the facile measurement of these quasi-reversible waves at quite negative potentials, such as for the naphthalene (NP)/NP(•-) couple. Notably, the E°' values obtained in the ammonium ILs correlate well with the calculated standard redox

  7. Global Calculations Using Potential Functions and Effective Hamiltonian Models for Vibration-Rotation Spectroscopy and Dynamics of Small Polyatomic Molecules

    NASA Astrophysics Data System (ADS)

    Tuyterev, Vladimir

    2010-06-01

    It has become increasingly common to use accurate potential energy surfaces and dipole moment surfaces for predictions and assignment of high-resolution vibration-rotation molecular spectra. These surfaces are obtained either from high-level ab initio electronic structure calculations or from a direct fit to experimental spectroscopic data. The talk will continue a discussion of some recent advances in the domain of the "potentiology". The role of basis extrapolations, of the Born-Oppenheimer breakdown corrections , in particular for very highly excited vibration states will be considered. As effective polyad Hamiltonians and band transition moment operators are still widely used for data reductions in high-resolutions molecular spectroscopy, experimental spectra analyses invoke a need for accurate methods of building physically meaningful effective models from ab initio surfaces. This involves predictions for various spectroscopic constants, including vibration dependence of rotational and centrifugal distortion and resonance coupling parameters. Topics planned for discussion include: high-order Contact Transformations of rovibrational Hamiltonians and of the dipole moment for small polyatomic molecules; convergence issues; the role of the anharmonicity in a potential energy function and of resonance couplings on the normal mode mixing and on vib-rot assignments with application to high energy vibration levels of SO_2 and to ozone near the dissociation limit; intensity anomalies in H_2S / HDS / D_2S spectra, relation of the shape of ab initio dipole moment surfaces with a "mystery" of nearly vanishing symmetry allowed bands. A full account for symmetry properties requires efficient theoretical tools for transformations of molecular Hamiltonians such as irreducible tensor formalism, applications using phosphine and methane potentials will be discussed. Both potential functions and effective polyad Hamiltonians allow studying changes in quasi-classical vibration

  8. Utilization of photoinduced charge-separated state of donor-acceptor-linked molecules for regulation of cell membrane potential and ion transport.

    PubMed

    Numata, Tomohiro; Murakami, Tatsuya; Kawashima, Fumiaki; Morone, Nobuhiro; Heuser, John E; Takano, Yuta; Ohkubo, Kei; Fukuzumi, Shunichi; Mori, Yasuo; Imahori, Hiroshi

    2012-04-11

    The control of ion transport across cell membranes by light is an attractive strategy that allows targeted, fast control of precisely defined events in the biological membrane. Here we report a novel general strategy for the control of membrane potential and ion transport by using charge-separation molecules and light. Delivery of charge-separation molecules to the plasma membrane of PC12 cells by a membranous nanocarrier and subsequent light irradiation led to depolarization of the membrane potential as well as inhibition of the potassium ion flow across the membrane. Photoregulation of the cell membrane potential and ion transport by using charge-separation molecules is highly promising for control of cell functions. © 2012 American Chemical Society

  9. Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in the Transmissible Tasmanian Devil Facial Tumor Disease

    PubMed Central

    Flies, Andrew S.; Blackburn, Nicholas B.; Lyons, Alan Bruce; Hayball, John D.; Woods, Gregory M.

    2017-01-01

    Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population. We have recently demonstrated that the inhibitory checkpoint molecule PD-L1 is upregulated on Tasmanian devil (Sarcophilus harrisii) facial tumor cells in response to the interferon-gamma cytokine. As this could play a role in immune evasion by tumor cells, we performed a thorough comparative analysis of checkpoint molecule protein sequences among Tasmanian devils and eight other species. We report that many of the key signaling motifs and ligand-binding sites in the checkpoint molecules are highly conserved across the estimated 162 million years of evolution since the last common ancestor of placental and non-placental mammals. Specifically, we discovered that the CTLA-4 (MYPPPY) ligand-binding motif and the CTLA-4 (GVYVKM) inhibitory domain are completely conserved across all nine species used in our comparative analysis, suggesting that the function of CTLA-4 is likely conserved in these species. We also found that cysteine residues for intra- and intermolecular disulfide bonds were also highly conserved. For instance, all 20 cysteine residues involved in disulfide bonds in the human 4-1BB molecule were also present in devil 4-1BB. Although many key sequences were conserved, we have also identified immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and immunoreceptor tyrosine-based switch motifs (ITSMs

  10. Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in the Transmissible Tasmanian Devil Facial Tumor Disease.

    PubMed

    Flies, Andrew S; Blackburn, Nicholas B; Lyons, Alan Bruce; Hayball, John D; Woods, Gregory M

    2017-01-01

    Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population. We have recently demonstrated that the inhibitory checkpoint molecule PD-L1 is upregulated on Tasmanian devil (Sarcophilus harrisii) facial tumor cells in response to the interferon-gamma cytokine. As this could play a role in immune evasion by tumor cells, we performed a thorough comparative analysis of checkpoint molecule protein sequences among Tasmanian devils and eight other species. We report that many of the key signaling motifs and ligand-binding sites in the checkpoint molecules are highly conserved across the estimated 162 million years of evolution since the last common ancestor of placental and non-placental mammals. Specifically, we discovered that the CTLA-4 (MYPPPY) ligand-binding motif and the CTLA-4 (GVYVKM) inhibitory domain are completely conserved across all nine species used in our comparative analysis, suggesting that the function of CTLA-4 is likely conserved in these species. We also found that cysteine residues for intra- and intermolecular disulfide bonds were also highly conserved. For instance, all 20 cysteine residues involved in disulfide bonds in the human 4-1BB molecule were also present in devil 4-1BB. Although many key sequences were conserved, we have also identified immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and immunoreceptor tyrosine-based switch motifs (ITSMs

  11. Double-well potential energy curve of cadmium-krypton molecule in the B1(5(3)P1) excited state.

    PubMed

    Lukomski, M; Koperski, J; Czajkowski, M

    2002-06-01

    The real shape of a double-well B1(5(3)P1)-state potential in CdKr van der Waals molecule was reconstructed applying both the experimental data, using a Birge-Sponer method-based analysis of the B1 <-- X0+(5(1)S0) transition in excitation spectrum, and theoretical result of recent ab initio calculation. An inverse perturbation approach method was used for defining an accurate B1-state potential energy curve.

  12. Slags in a Large Variation Range of Oxygen Potential Based on the Ion and Molecule Coexistence Theory

    NASA Astrophysics Data System (ADS)

    Yang, Xue-Min; Li, Jin-Yan; Zhang, Meng; Chai, Guo-Min; Zhang, Jian

    2014-12-01

    A thermodynamic model for predicting sulfide capacity of CaO-FeO-Fe2O3-Al2O3-P2O5 slags in a large variation range of oxygen potential corresponding to mass percentage of FetO from 1.88 to 55.50 pct, i.e., IMCT- model, has been developed by coupling with the deduced desulfurization mechanism of the slags based on the ion and molecule coexistence theory (IMCT). The developed IMCT- model has been verified through comparing the determined sulfide capacity after Ban-ya et al.[20] with the calculated by the developed IMCT- model and the calculated by the reported sulfide capacity models such as the KTH model. Mass percentage of FetO as 6.75 pct corresponding to the mass action concentration of FetO as 0.0637 or oxygen partial as 2.27 × 10-6 Pa is the criterion for distinguishing reducing and oxidizing zones for the slags. Sulfide capacity of the slags in reducing zone is controlled by reaction ability of CaO regardless of slag oxidization ability. However, sulfide capacity of the slags in oxidizing zone shows an obvious increase tendency with the increasing of slag oxidization ability. Sulfide capacity of the slags in reducing zone keeps almost constant with variation of the simplified complex basicity (pct CaO)/((pct Al2O3) + (pct P2O5)), or optical basicity, or the mass action concentration ratios of N FeO/ N CaO, , , and . Sulfide capacity of the slags in oxidizing zone shows an obvious increase with the increasing of the simplified complex basicity (pct CaO)/((pct Al2O3) + (pct P2O5)) or optical basicity, or the aforementioned mass action concentration ratios. Thus, the aforementioned mass action concentration ratios and the corresponding mass percentage ratios of various iron oxides to basic oxide CaO are recommended to represent the comprehensive effect of various iron oxides and basic oxide CaO on sulfide capacity of the slags.

  13. Design, Synthesis, and Biological Evaluation of Coumarin-Triazole Hybrid Molecules as Potential Antitumor and Pancreatic Lipase Agents.

    PubMed

    Kahveci, Bahittin; Yılmaz, Fatih; Menteşe, Emre; Ülker, Serdar

    2017-08-01

    The design, synthesis, and investigation of antitumor and anti-lipase activities of some coumarin-triazole hybrid molecules are reported. The synthesis of these hybrid molecules was performed under microwave irradiation and conventional heating procedures. The newly synthesized hybrid molecules were investigated as inhibitors against four tumor cell lines (BT20 human breast carcinoma, SK-Mel 128 melanoma, DU-145 prostate carcinoma, and A549 lung carcinoma) and porcine pancreatic lipase (PPL). Most of these compounds showed notable antitumor activities against the tested tumor cell lines, and compounds 8i and 8l showed the best anti-lipase activity of 99.30 ± 0.56% and 99.85 ± 1.21%, respectively, at a concentration of 10 μM. © 2017 Deutsche Pharmazeutische Gesellschaft.

  14. Potential immunosuppressive and antiinflammatory activities of Malaysian medicinal plants characterized by reduced cell surface expression of cell adhesion molecules.

    PubMed

    Tanaka, S; Yoichi, S; Ao, L; Matumoto, M; Morimoto, K; Akimoto, N; Honda, G; Tabata, M; Oshima, T; Masuda, T; bin Asmawi, M Z; Ismail, Z; Yusof, S M; Din, L B; Said, I M

    2001-12-01

    In the search for agents effective against immune-mediated disorders and inflammation, we have screened Malaysian medicinal plants for the ability to inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of murine endothelial cells (F-2), and mouse myeloid leukaemia cells (M1), respectively. Of 41 kinds (29 species, 24 genera, 16 families) of Malaysian plants tested, 10 and 19 plant samples significantly downregulated the expression of ICAM-1 and VCAM-1, respectively. Bioassay-directed fractionation of an extract prepared from the bark of Goniothalamus andersonii showed that its ingredients, goniothalamin (1) and goniodiol (2) inhibited the cell surface expression of both ICAM-1 and VCAM-1. The present results suggest that Malaysian medicinal plants may be abundant natural resources for immunosuppressive and antiinflammatory substances. Copyright 2001 John Wiley & Sons, Ltd.

  15. Kojic acid--a new leading molecule for a preparation of compounds with an anti-neoplastic potential.

    PubMed

    Novotný, L; Rauko, P; Abdel-Hamid, M; Váchalková, A

    1999-01-01

    Kojic acid as a molecule of natural origin may serve as template for the synthesis of new biologically active compounds. The synthetic KA (pyranone) derivatives possess various kinds of biological activities which are related by their similarity to flavonoids. The most important property is the antifungal and antineoplastic activity and capability of chelating metals. It is shown that the antineoplastic activity of kojic acid derivatives is based on various mechanisms of action on different levels of cellular metabolism and functions what makes this compound interesting for future investigation as cytotoxic agent.

  16. The Role of Histone Deacetylases in Neurodegenerative Diseases and Small-Molecule Inhibitors as a Potential Therapeutic Approach

    NASA Astrophysics Data System (ADS)

    Bürli, Roland W.; Thomas, Elizabeth; Beaumont, Vahri

    Neurodegenerative disorders are devastating for patients and their social environment. Their etiology is poorly understood and complex. As a result, there is clearly an urgent need for therapeutic agents that slow down disease progress and alleviate symptoms. In this respect, interference with expression and function of multiple gene products at the epigenetic level has offered much promise, and histone deacetylases play a crucial role in these processes. This review presents an overview of the biological pathways in which these enzymes are involved and illustrates the complex network of proteins that governs their activity. An overview of small molecules that interfere with histone deacetylase function is provided.

  17. Can Femtosecond Transient Absorption Spectroscopy Predict the Potential of Small Molecules as Perspective Donors for Organic Photovoltaics?

    NASA Astrophysics Data System (ADS)

    DiScipio, Regina; Sauve, Genevieve; Crespo-Hernández, Carlos E.

    2015-06-01

    The utility of a perspective donor or acceptor molecule for photoelectric applications is difficult to predict a priori. This hinders productive synthetic exploration and necessitates lengthy device optimization procedures for reasonable estimation of said molecule's applicability. Using femtosecond broadband transient absorption spectroscopy, supported by time-dependent density functional theory computations and steady-state-absorption and emission spectroscopies, we have characterized a family of perspective optoelectronic compounds, in an effort to predict their relative performance in organic photovoltaic devices from information accrued from excited-state dynamics and photophysical properties. A series of tetraphenylazadipyrromethene (ADP) complexes chelated with three different metal centers was investigated. We have determined that the chelating metal has little effect on the ground state properties of this family. However their excited state dynamics are strongly modulated by the metal. Specifically, the zinc-chelated ADP complex remains in the excited state tenfold longer than the cobalt or nickel complexes. We assert that this is key photophysical property that should make the zinc complex outperform the other two complexes in photovoltaic applications. This hypothesis is supported by preliminary power conversion efficiency results in devices.

  18. Laboratory Anion Chemistry: Implications for the DIBs, and a Potential Formation Mechanism for a Known Interstellar Molecule

    NASA Technical Reports Server (NTRS)

    Eichelberger, B.; Barckholtz, C.; Stepanovic, M.; Bierbaum, V.; Snow, T.

    2002-01-01

    Due to recent interest in molecular anions as possible interstellar species, we have carried out several laboratory studies of anion chemistry. The reactions of the series C(sub n)(sup -); and C(sub n)H(sup -) with H and H2 were studied to address the viability of such species in the diffuse interstellar medium and to address their ability to be carriers of the diffuse interstellar bands (DIBs). These same molecules were also reacted with N and O to show possible heteroatomic products. C(sub m)N(sup - was a particularly stable product from the reaction of C(sub n)(sup -) + N. C3N(sup -) was further reacted with H to study chemistry that could produce HC3N, a known interstellar species. The reactions were done in a flowing afterglow selected ion flow tube apparatus (FA-SIFT). The anions were generated in an electron impact or cold cathode discharge source and the anion of interest was then selected by a quadrupole mass filter. The selected ion was then reacted with the atomic or molecular species in the flow tube and products were detected by another quadrupole. While the C(sub n)(sup -) species do not appear to be viable DIB carriers, their possible presence could provide a mechanism for the formation of known heteroatomic neutral molecules detected in the interstellar medium (ISM).

  19. Potential pharmacokinetic interactions of therapeutic cytokines or cytokine modulators on small-molecule drugs: mechanistic understanding via studies using in vitro systems.

    PubMed

    Zhou, Jin; Li, Feng

    2014-01-01

    The potential pharmacokinetic interactions between macromolecules and small-molecule drugs have received more and more attention with the increasing development of macromolecule therapeutics. Studies have shown that cytokines can differentially modulate drug-metabolizing enzymes and transporters, which raises concerns on the potential interactions of therapeutic cytokines and cytokine modulators on the disposition of small-molecule drugs. Although many in vitro studies have been conducted to characterize the effects of cytokines on drug-metabolizing enzymes and transporters, these studies were limited to only a handful of cytokines, such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-α, and interferon. It is also challenging to translate these in vitro results to in vivo. In addition, information on the impact of cytokine modulators on drug-metabolizing enzymes and transporters is rather limited. More research is needed in this area. The present review is to provide a summary of the in vitro findings on the pharmacokinetic interactions of therapeutic cytokines and cytokine modulators on small-molecule drugs. Discussion on current challenges in assessing these interactions is also included.

  20. The pharmacology and therapeutic potential of small molecule inhibitors of acid-sensing ion channels in stroke intervention.

    PubMed

    Leng, Tian-dong; Xiong, Zhi-gang

    2013-01-01

    In the nervous system, a decrease in extracellular pH is a common feature of various physiological and pathological processes, including synaptic transmission, cerebral ischemia, epilepsy, brain trauma, and tissue inflammation. Acid-sensing ion channels (ASICs) are proton-gated cation channels that are distributed throughout the central and peripheral nervous systems. Following the recent identification of ASICs as critical acid-sensing extracellular proton receptors, growing evidence has suggested that the activation of ASICs plays important roles in physiological processes such as nociception, mechanosensation, synaptic plasticity, learning and memory. However, the over-activation of ASICs is also linked to adverse outcomes for certain pathological processes, such as brain ischemia and multiple sclerosis. Based on the well-demonstrated role of ASIC1a activation in acidosis-mediated brain injury, small molecule inhibitors of ASIC1a may represent novel therapeutic agents for the treatment of neurological disorders, such as stroke.

  1. Cell-based small-molecule compound screen identifies fenretinide as potential therapeutic for translocation-positive rhabdomyosarcoma.

    PubMed

    Herrero Martín, David; Boro, Aleksandar; Schäfer, Beat W

    2013-01-01

    A subset of paediatric sarcomas are characterized by chromosomal translocations encoding specific oncogenic transcription factors. Such fusion proteins represent tumor specific therapeutic targets although so far it has not been possible to directly inhibit their activity by small-molecule compounds. In this study, we hypothesized that screening a small-molecule library might identify already existing drugs that are able to modulate the transcriptional activity of PAX3/FOXO1, the fusion protein specifically found in the pediatric tumor alveolar rhabdomyosarcoma (aRMS). Towards this end, we established a reporter cell line based on the well characterized PAX3/FOXO1 target gene AP2ß. A library enriched in mostly FDA approved drugs was screened using specific luciferase activity as read-out and normalized for cell viability. The most effective inhibitor identified from this screen was Fenretinide. Treatment with this compound resulted in down-regulation of PAX3/FOXO1 mRNA and protein levels as well as in reduced expression of several of its direct target genes, but not of wild-type FOXO1, in a dose- and time-dependent manner. Moreover, fenretinide induced reactive oxygen species and apoptosis as shown by caspase 9 and PARP cleavage and upregulated miR-9. Importantly, it demonstrated a significant anti-tumor effect in vivo. These results are similar to earlier reports for two other pediatric tumors, namely neuroblastoma and Ewing sarcoma, where fenretinide is under clinical development. Our results suggest that fenretinide might represent a novel treatment option also for translocation-positive rhabdomyosarcoma.

  2. Cell-Based Small-Molecule Compound Screen Identifies Fenretinide as Potential Therapeutic for Translocation-Positive Rhabdomyosarcoma

    PubMed Central

    Herrero Martín, David; Boro, Aleksandar; Schäfer, Beat W.

    2013-01-01

    A subset of paediatric sarcomas are characterized by chromosomal translocations encoding specific oncogenic transcription factors. Such fusion proteins represent tumor specific therapeutic targets although so far it has not been possible to directly inhibit their activity by small-molecule compounds. In this study, we hypothesized that screening a small-molecule library might identify already existing drugs that are able to modulate the transcriptional activity of PAX3/FOXO1, the fusion protein specifically found in the pediatric tumor alveolar rhabdomyosarcoma (aRMS). Towards this end, we established a reporter cell line based on the well characterized PAX3/FOXO1 target gene AP2ß. A library enriched in mostly FDA approved drugs was screened using specific luciferase activity as read-out and normalized for cell viability. The most effective inhibitor identified from this screen was Fenretinide. Treatment with this compound resulted in down-regulation of PAX3/FOXO1 mRNA and protein levels as well as in reduced expression of several of its direct target genes, but not of wild-type FOXO1, in a dose- and time-dependent manner. Moreover, fenretinide induced reactive oxygen species and apoptosis as shown by caspase 9 and PARP cleavage and upregulated miR-9. Importantly, it demonstrated a significant anti-tumor effect in vivo. These results are similar to earlier reports for two other pediatric tumors, namely neuroblastoma and Ewing sarcoma, where fenretinide is under clinical development. Our results suggest that fenretinide might represent a novel treatment option also for translocation-positive rhabdomyosarcoma. PMID:23372815

  3. Dissociation of multiple hydrogen molecules on the non-planar aluminium cluster: stationary points on the Al6 + nH2 potential energy surface

    NASA Astrophysics Data System (ADS)

    Moc, Jerzy

    2013-02-01

    Compared to clusters of transition metal atoms, H-H bond activation by main Group metal clusters is much less known. Here, we have examined a potential new way of obtaining a novel alane Al6H8 through addition of multiple H2 molecules to the aluminium hexamer, i.e., Al6 + nH2 (n=1-4) reactions. To this end, systematic high level quantum chemical modeling calculations using density functional theory (DFT) and coupled-cluster singles-doubles-perturbative triples (CCSD(T)) method in conjunction with the aug-cc-pVTZ basis set were performed to identify the lowest energy barrier paths for the consecutive dissociation of several hydrogen molecules on Al6, the smallest aluminium cluster with a three-dimensional ground-state structure. These computational results are relevant to the issues of hydrogen storage and novel stable alanes.

  4. Toward a List of Molecules as Potential Biosignature Gases for the Search for Life on Exoplanets and Applications to Terrestrial Biochemistry.

    PubMed

    Seager, S; Bains, W; Petkowski, J J

    2016-06-01

    Thousands of exoplanets are known to orbit nearby stars. Plans for the next generation of space-based and ground-based telescopes are fueling the anticipation that a precious few habitable planets can be identified in the coming decade. Even more highly anticipated is the chance to find signs of life on these habitable planets by way of biosignature gases. But which gases should we search for? Although a few biosignature gases are prominent in Earth's atmospheric spectrum (O2, CH4, N2O), others have been considered as being produced at or able to accumulate to higher levels on exo-Earths (e.g., dimethyl sulfide and CH3Cl). Life on Earth produces thousands of different gases (although most in very small quantities). Some might be produced and/or accumulate in an exo-Earth atmosphere to high levels, depending on the exo-Earth ecology and surface and atmospheric chemistry. To maximize our chances of recognizing biosignature gases, we promote the concept that all stable and potentially volatile molecules should initially be considered as viable biosignature gases. We present a new approach to the subject of biosignature gases by systematically constructing lists of volatile molecules in different categories. An exhaustive list up to six non-H atoms is presented, totaling about 14,000 molecules. About 2500 of these are CNOPSH compounds. An approach for extending the list to larger molecules is described. We further show that about one-fourth of CNOPSH molecules (again, up to N = 6 non-H atoms) are known to be produced by life on Earth. The list can be used to study classes of chemicals that might be potential biosignature gases, considering their accumulation and possible false positives on exoplanets with atmospheres and surface environments different from Earth's. The list can also be used for terrestrial biochemistry applications, some examples of which are provided. We provide an online community usage database to serve as a registry for volatile molecules

  5. Toward a List of Molecules as Potential Biosignature Gases for the Search for Life on Exoplanets and Applications to Terrestrial Biochemistry

    NASA Astrophysics Data System (ADS)

    Seager, S.; Bains, W.; Petkowski, J. J.

    2016-06-01

    Thousands of exoplanets are known to orbit nearby stars. Plans for the next generation of space-based and ground-based telescopes are fueling the anticipation that a precious few habitable planets can be identified in the coming decade. Even more highly anticipated is the chance to find signs of life on these habitable planets by way of biosignature gases. But which gases should we search for? Although a few biosignature gases are prominent in Earth's atmospheric spectrum (O2, CH4, N2O), others have been considered as being produced at or able to accumulate to higher levels on exo-Earths (e.g., dimethyl sulfide and CH3Cl). Life on Earth produces thousands of different gases (although most in very small quantities). Some might be produced and/or accumulate in an exo-Earth atmosphere to high levels, depending on the exo-Earth ecology and surface and atmospheric chemistry. To maximize our chances of recognizing biosignature gases, we promote the concept that all stable and potentially volatile molecules should initially be considered as viable biosignature gases. We present a new approach to the subject of biosignature gases by systematically constructing lists of volatile molecules in different categories. An exhaustive list up to six non-H atoms is presented, totaling about 14,000 molecules. About 2500 of these are CNOPSH compounds. An approach for extending the list to larger molecules is described. We further show that about one-fourth of CNOPSH molecules (again, up to N = 6 non-H atoms) are known to be produced by life on Earth. The list can be used to study classes of chemicals that might be potential biosignature gases, considering their accumulation and possible false positives on exoplanets with atmospheres and surface environments different from Earth's. The list can also be used for terrestrial biochemistry applications, some examples of which are provided. We provide an online community usage database to serve as a registry for volatile molecules including

  6. Pseudo hard-sphere potential for use in continuous molecular-dynamics simulation of spherical and chain molecules.

    PubMed

    Jover, J; Haslam, A J; Galindo, A; Jackson, G; Müller, E A

    2012-10-14

    We present a continuous pseudo-hard-sphere potential based on a cut-and-shifted Mie (generalized Lennard-Jones) potential with exponents (50, 49). Using this potential one can mimic the volumetric, structural, and dynamic properties of the discontinuous hard-sphere potential over the whole fluid range. The continuous pseudo potential has the advantage that it may be incorporated directly into off-the-shelf molecular-dynamics code, allowing the user to capitalise on existing hardware and software advances. Simulation results for the compressibility factor of the fluid and solid phases of our pseudo hard spheres are presented and compared both to the Carnahan-Starling equation of state of the fluid and published data, the differences being indistinguishable within simulation uncertainty. The specific form of the potential is employed to simulate flexible chains formed from these pseudo hard spheres at contact (pearl-necklace model) for m(c) = 4, 5, 7, 8, 16, 20, 100, 201, and 500 monomer segments. The compressibility factor of the chains per unit of monomer, m(c), approaches a limiting value at reasonably small values, m(c) < 50, as predicted by Wertheim's first order thermodynamic perturbation theory. Simulation results are also presented for highly asymmetric mixtures of pseudo hard spheres, with diameter ratios of 3:1, 5:1, 20:1 over the whole composition range.

  7. Gram-Negative Pneumonia Alters Large-Vein Cell-Adhesion Molecule Profile and Potentiates Experimental Stasis Venous Thrombosis.

    PubMed

    Obi, Andrea T; Andraska, Elizabeth; Kanthi, Yogendra; Luke, Catherine E; Elfline, Megan; Madathilparambil, Suresh; Siahaan, Teruna J; Jaffer, Farouc A; Wakefield, Thomas W; Raghavendran, Krishnan; Henke, Peter K

    2016-01-01

    Pneumonia is a significant risk factor for the development of venous thrombosis (VT). Cell-adhesion molecules (CAMs) are linked to the pathogenesis of both pneumonia and VT. We hypothesized that remote infection would confer a prothrombogenic milieu via systemic elevation of CAMs. Lung injury was induced in wild-type (C57BL/6) mice by lung contusion or intratracheal inoculation with Klebsiella pneumoniae or saline controls. K. pneumoniae-treated mice and controls additionally underwent inferior vena cava (IVC) ligation to generate VT. Lung-contusion mice demonstrated no increase in E-selectin or P-selectin whereas mice infected with K. pneumoniae demonstrated increased circulating P-selectin, ICAM-1, VCAM-1 and thrombin-antithrombin (TAT) complexes. Mice with pneumonia formed VT 3 times larger than controls, demonstrated significantly more upregulation of vein-wall and systemic CAMs, and formed erythrocyte-rich thrombi. Elevated CAM expression was identified in mice with pneumonia, but not lung contusion, indicating that the type of inflammatory stimulus and the presence of infection drive the vein-wall response. Elevation of CAMs was associated with amplified VT and may represent an alternate mechanism by which to target the prevention of VT. © 2016 S. Karger AG, Basel.

  8. Folate deficiency and aberrant expression of cell adhesion molecule 1 are potential indicators of prognosis in laryngeal squamous cell carcinoma

    PubMed Central

    Chang, Hao; Ma, Min; Ma, Rui; Zhang, Chao; Zeng, Wei; Xing, Lu Qi

    2016-01-01

    The etiology of laryngeal squamous cell carcinoma (LSCC) has not yet been adequately examined. Therefore, the present study aimed to investigate the association between serum folate deficiency and abnormal expression of the cell adhesion molecule 1 (CADM1) protein in the progression of LSCC. Samples were collected from 60 patients with LSCC and 30 healthy people. Radioimmunoassays and immunohistochemical staining were performed to measure serum folate levels and CADM1 protein expression, respectively. The results demonstrated that CADM1 expression in LSCC specimens was significantly lower than in adjacent normal tissues (χ2=28.229, P<0.001), which was associated with histological differentiation and clinical stage (P=0.010 and 0.020, respectively). Levels of serum folate in patients with LSCC were significantly lower than those observed in healthy individuals (P=0.002). Furthermore, TSLCl expression and serum folate levels were positively correlated in LSCC (r=0.642, P=0.001). Thus, the present study determined that decreased CADM1 protein expression and low levels of serum folate were correlated with an increased severity of LSCC. PMID:28105160

  9. Klein-Gordon equation particles in exponential-type molecule potentials and their thermodynamic properties in D dimensions

    NASA Astrophysics Data System (ADS)

    Ikot, A. N.; Lutfuoglu, B. C.; Ngwueke, M. I.; Udoh, M. E.; Zare, S.; Hassanabadi, H.

    2016-12-01

    In this paper we use the Nikiforov-Uvarov method to obtain the approximate solutions for the Klein-Gordon equation with the deformed five-parameter exponential-type potential (DFPEP) model. We also obtain solutions for the Schrödinger equation in the presence of DFPEP in non-relativistic limits. In addition, we calculate in the non-relativistic limits thermodynamics properties, such as vibrational mean energy U, free energy F and the specific heat capacity C. Special cases of the potential are also discussed.

  10. The Chirped-Pulse Fourier Transform Microwave Cp-Ftmw Spectrum and Potential Energy Calculations for AN Aromatic Claisen Rearrangement Molecule, Allyl Phenyl Ether

    NASA Astrophysics Data System (ADS)

    Grubbs, G. S. Grubbs, Ii; Cooke, S. A.; Novick, Stewart E.

    2012-06-01

    Claisen rearrangement ethers are a fundamental organic, pericyclic rearrangement reaction reagent. In the mechanism of a Claisen rearrangement, a vinyl allyl ether is needed to provide the necessary Lewis acid/base sites on the molecule for the rearrangement and are simply heated. This rearrangement was first discovered by heating up the title molecule, allyl phenyl ether. However, much like the Diels-Alder, Cope, and other pericyclic reactions, conformation and coordination of chemical groups is key to the Claisen mechanism. In this study, the authors present some structural characteristics of allyl phenyl ether from an analysis of the microwave spectra in the 8-14 GHz region using a CP-FTMW spectrometer. This is, to the authors knowledge, the first known microwave region study of the title molecule. Three conformers have been observed and assigned to date and will be discussed. Along with the rotational spectra, geometry calculations and potential energy surfaces performed at the MP2/6-311G++(3d,2p) level will be discussed and compared to the experimental results. Modeling the Claisen aromatic rearrangement mechanism using CP-FTMW spectroscopy will also be discussed. L. Claisen Chemische Berichte 45, 3157, October 1912.

  11. Two-electron R-matrix approach to calculations of potential-energy curves of long-range Rydberg molecules

    NASA Astrophysics Data System (ADS)

    Tarana, Michal; Čurík, Roman

    2016-05-01

    We introduce a computational method developed for study of long-range molecular Rydberg states of such systems that can be approximated by two electrons in a model potential of the atomic cores. The method is based on a two-electron R-matrix approach inside a sphere centered on one of the atoms. The wave function is then connected to a Coulomb region outside the sphere via a multichannel version of the Coulomb Green's function. This approach is applied to a study of Rydberg states of Rb2 for internuclear separations R from 40 to 320 bohrs and energies corresponding to n from 7 to 30. We report bound states associated with the low-lying 3Po resonance and with the virtual state of the rubidium atom that turn into ion-pair-like bound states in the Coulomb potential of the atomic Rydberg core. The results are compared with previous calculations based on single-electron models employing a zero-range contact-potential and short-range modele potential. Czech Science Foundation (Project No. P208/14-15989P).

  12. Electrostatic Potential Determined Magnetic Dynamics Observed in Two Mononuclear β-Diketone Dysprosium(III) Single-Molecule Magnets.

    PubMed

    Cen, Pei-Pei; Zhang, Sheng; Liu, Xiang-Yu; Song, Wei-Ming; Zhang, Yi-Quan; Xie, Gang; Chen, San-Ping

    2017-03-20

    Two β-diketone mononuclear Dy(III) compounds, formulated as Dy(BTFA)3(H2O)2 (1) and Dy(BTFA)3(bpy) (2) (BTFA = 3-benzoyl-1,1,1-trifluoroacetone, bpy = 2,2'-bipyridine), were prepared. Compound 1 can be identified to transform to 2 in the attendance of bpy coligand, when the local geometry symmetry of eight-coordinated Dy(III) ion changes from a dodecahedron (D2d) in 1 to a square antiprism (D4d) in 2. Fine-tuning structure aroused by auxiliary ligand has dramatical impact on magnetic properties of compounds 1 and 2. Magnetic investigations demonstrate that both 1 and 2 display dynamic magnetic relaxation of single-molecule magnets (SMMs) behavior with different effective barriers (ΔE/kB) of 93.09 K for 1 under zero direct-current (DC) field as well as 296.50 K for 1 and 151.01 K for 2 under 1200 Oe DC field, respectively. As noticed, compound 1 possesses higher effective barrier than 2, despite 1 exhibiting a lower geometrical symmetry of the Dy(III) ion. Ab initio studies reveal that the Kramers doublet ground state is predominantly axial with the gz tensors of two compounds matching the Ising-limit factor of 20 anticipated for the pure MJ = ±15/2 state. Electrostatic analysis confirms the uniaxial anisotropy directions, highlighting that the proper electrostatic distribution of the coordination sphere around Ln(III) center is the critical factor to improve the magnetic anisotropy and determine the dynamic behaviors of SMMs.

  13. Mitogenic signals and transforming potential of Nyk, a newly identified neural cell adhesion molecule-related receptor tyrosine kinase.

    PubMed Central

    Ling, L; Kung, H J

    1995-01-01

    Nyk/Mer is a recently identified receptor tyrosine kinase with neural cell adhesion molecule-like structure (two immunoglobulin G-like domains and two fibronectin III-like domains) in its extracellular region and belongs to the Ufo/Axl family of receptors. The ligand for Nyk/Mer is presently unknown, as are the signal transduction pathways mediated by this receptor. We constructed and expressed a chimeric receptor (Fms-Nyk) composed of the extracellular domain of the human colony-stimulating factor 1 receptor (Fms) and the transmembrane and cytoplasmic domains of human Nyk/Mer in NIH 3T3 fibroblasts in order to investigate the mitogenic signaling and biochemical properties of Nyk/Mer. Colony-stimulating factor 1 stimulation of the Fms-Nyk chimeric receptor in transfected NIH 3T3 fibroblasts leads to a transformed phenotype and generates a proliferative response in the absence of other growth factors. We show that phospholipase C gamma, phosphatidylinositol 3-kinase/p70 S6 kinase, Shc, Grb2, Raf-1, and mitogen-activated protein kinase are downstream components of the Nyk/Mer signal transduction pathways. In addition, Nyk/Mer weakly activates p90rsk, while stress-activated protein kinase, Ras GTPase-activating protein (GAP), and GAP-associated p62 and p190 proteins are not activated or tyrosine phosphorylated by Nyk/Mer. An analysis comparing the Nyk/Mer signal cascade with that of the epidermal growth factor receptor indicates substrate preferences by these two receptors. Our results provide a detailed description of the Nyk/Mer signaling pathways. Given the structural similarity between the Ufo/Axl family receptors, some of the information may also be applied to other members of this receptor tyrosine kinase family. PMID:8524223

  14. A molecular dynamics-based algorithm for evaluating the glycosaminoglycan mimicking potential of synthetic, homogenous, sulfated small molecules

    PubMed Central

    Nagarajan, Balaji; Sankaranarayanan, Nehru Viji; Patel, Bhaumik B.

    2017-01-01

    Glycosaminoglycans (GAGs) are key natural biopolymers that exhibit a range of biological functions including growth and differentiation. Despite this multiplicity of function, natural GAG sequences have not yielded drugs because of problems of heterogeneity and synthesis. Recently, several homogenous non-saccharide glycosaminoglycan mimetics (NSGMs) have been reported as agents displaying major therapeutic promise. Yet, it remains unclear whether sulfated NSGMs structurally mimic sulfated GAGs. To address this, we developed a three-step molecular dynamics (MD)-based algorithm to compare sulfated NSGMs with GAGs. In the first step of this algorithm, parameters related to the range of conformations sampled by the two highly sulfated molecules as free entities in water were compared. The second step compared identity of binding site geometries and the final step evaluated comparable dynamics and interactions in the protein-bound state. Using a test case of interactions with fibroblast growth factor-related proteins, we show that this three-step algorithm effectively predicts the GAG structure mimicking property of NSGMs. Specifically, we show that two unique dimeric NSGMs mimic hexameric GAG sequences in the protein-bound state. In contrast, closely related monomeric and trimeric NSGMs do not mimic GAG in either the free or bound states. These results correspond well with the functional properties of NSGMs. The results show for the first time that appropriately designed sulfated NSGMs can be good structural mimetics of GAGs and the incorporation of a MD-based strategy at the NSGM library screening stage can identify promising mimetics of targeted GAG sequences. PMID:28182755

  15. Constructing an Interpolated Potential Energy Surface of a Large Molecule: A Case Study with Bacteriochlorophyll a Model in the Fenna-Matthews-Olson Complex.

    PubMed

    Kim, Chang Woo; Rhee, Young Min

    2016-11-08

    Constructing a reliable potential energy surface (PES) is a key step toward computationally studying the chemical dynamics of any molecular system. The interpolation scheme is a useful tool that can closely follow the accuracy of quantum chemical means at a dramatically reduced computational cost. However, applying interpolation to building a PES of a large molecule is not a straightforward black-box approach, as it frequently encounters practical difficulties associated with its large dimensionality. Here, we present detailed courses of applying interpolation toward building a PES of a large chromophore molecule. We take the example of S0 and S1 electronic states of bacteriochlorophyll a (BChla) molecules in the Fenna-Matthews-Olson light harvesting complex. With a reduced model molecule that bears BChla's main π-conjugated ring, various practical approaches are designed for improving the PES quality in a stable manner and for fine-tuning the final surface such that the surface can be adopted for long time molecular dynamics simulations. Combined with parallel implementation, we show that interpolated mechanics/molecular mechanics (IM/MM) simulations of the entire complex in the nanosecond time scale can be conducted readily without any practical issues. With 1500 interpolation data points for each chromophore unit, the PES error relative to the reference quantum chemical calculation is found to be ∼0.15 eV in the thermally accessible region of the conformational space, together with ∼0.01 eV error in S0 - S1 transition energies. The performance issue related to the use of a large interpolation database within the framework of our parallel routines is also discussed.

  16. Small and efficient basis sets for the evaluation of accurate interaction energies: aromatic molecule-argon ground-state intermolecular potentials and rovibrational states.

    PubMed

    Cybulski, Hubert; Baranowska-Łączkowska, Angelika; Henriksen, Christian; Fernández, Berta

    2014-11-06

    By evaluating a representative set of CCSD(T) ground state interaction energies for van der Waals dimers formed by aromatic molecules and the argon atom, we test the performance of the polarized basis sets of Sadlej et al. (J. Comput. Chem. 2005, 26, 145; Collect. Czech. Chem. Commun. 1988, 53, 1995) and the augmented polarization-consistent bases of Jensen (J. Chem. Phys. 2002, 117, 9234) in providing accurate intermolecular potentials for the benzene-, naphthalene-, and anthracene-argon complexes. The basis sets are extended by addition of midbond functions. As reference we consider CCSD(T) results obtained with Dunning's bases. For the benzene complex a systematic basis set study resulted in the selection of the (Z)Pol-33211 and the aug-pc-1-33321 bases to obtain the intermolecular potential energy surface. The interaction energy values and the shape of the CCSD(T)/(Z)Pol-33211 calculated potential are very close to the best available CCSD(T)/aug-cc-pVTZ-33211 potential with the former basis set being considerably smaller. The corresponding differences for the CCSD(T)/aug-pc-1-33321 potential are larger. In the case of the naphthalene-argon complex, following a similar study, we selected the (Z)Pol-3322 and aug-pc-1-333221 bases. The potentials show four symmetric absolute minima with energies of -483.2 cm(-1) for the (Z)Pol-3322 and -486.7 cm(-1) for the aug-pc-1-333221 basis set. To further check the performance of the selected basis sets, we evaluate intermolecular bound states of the complexes. The differences between calculated vibrational levels using the CCSD(T)/(Z)Pol-33211 and CCSD(T)/aug-cc-pVTZ-33211 benzene-argon potentials are small and for the lowest energy levels do not exceed 0.70 cm(-1). Such differences are substantially larger for the CCSD(T)/aug-pc-1-33321 calculated potential. For naphthalene-argon, bound state calculations demonstrate that the (Z)Pol-3322 and aug-pc-1-333221 potentials are of similar quality. The results show that these

  17. The significance of interaction potentials of water with other molecules in the EOS of high explosives products

    SciTech Connect

    van Thiel, M.; Ree, F.H.; Haselman, L.C. Jr.

    1993-07-01

    The chemical equilibrium and thermodynamic properties of detonated explosive mixtures at high temperature (T) and pressure (P) depend critically on all interactions between the major products. Improvements in the homomolecular interaction of nitrogen, carbon-dioxide, and condensed carbon have had significant effects on detonation properties of LX-14 (an HMX formulation). Extensive work on O, N, and C products also showed the importance of including high temperature unstable species in determining the potential-constant of the major products of detonation. That work also showed the need to improve the unlike pair interaction constants in our statistical mechanical chemical equilibrium theory (CHEQ). Thirdly, a recent comparison of experimental and theoretical detonation velocities (D) indicated that the original set of interaction potentials used contains canceling errors that limit the overall effectiveness of the code as a predictor of high P and T properties of reactive mixtures. This study proceeds from explosives with simple product mixtures, RX-23-AB, HNB, and PETN, to HMX-like mixtures. The present set of potential constants is compared to the experimental EOS used for a number of experimental systems that use LX-14.

  18. An Improved Empirical Potential for the Highly Multi-Reference Sextuply Bonded Transition Metal Benchamrk Molecule Cr_2

    NASA Astrophysics Data System (ADS)

    Dattani, Nikesh S.; Tomza, Michal; Li Manni, Giovanni

    2016-06-01

    The ground electronic state of the chromium dimer dissociates into Cr (^7S) + Cr (^7S) and therefore the fragments are highly open shell systems with a total of 12 singly occupied orbitals among its constituent atoms. It is considered one of the most difficult homonuclear diatomics for ab initio methods because of its highly multi-reference character. Therefore, every new multi-reference method must be tested against this benchmark system. However, the best empirical potential to compare with, has its own weaknesses. The photoelectron measurements of v=0-9 were fitted to a Morse potential (an old function which has only one parameter controlling the shape from r_e to D_e), and also inverted using a semi-classical theory into a potential after combining these data with measurements from what were hypothesized to be v=24-43. This bridging of a ˜2000 cm-1 gap in data back in 1993 was a valiant spectroscopic analysis. However since 1993, there have been enormous improvements in the field of potentiology. In 2011 a Morse/long-range (MLR) function successfully bridged a gap of more than 5000 cm-1 in experimental data^a, and in 2013 an experiment with ±0.000 02 cm-1 resolution confirmed that the 2011 MLR predicted the energy levels in the very center of this gap correctly within ˜ 1 cm-1,^b. While ab initio methods have very recently been able to predict differences in energy levels correctly to within 1 cm-1 for Li_2 ^c and to a lesser extent for BeH^d, ab initio methods have still not had this level of success for predicting binding energies. The MLR function not only has more flexibility than the original Morse function, but it also converges mathematically to the correct long-range limit expected by the state-of-the-art theory. Fitting the data to an MLR potential function in the Schrödinger equation allows for a fully quantum mechanical treatment over the entire range of data. By avoiding a semi-classical treatment, and using this more flexible, more

  19. The extracellular matrix molecule tenascin-R and its HNK-1 carbohydrate modulate perisomatic inhibition and long-term potentiation in the CA1 region of the hippocampus.

    PubMed

    Saghatelyan, A K; Gorissen, S; Albert, M; Hertlein, B; Schachner, M; Dityatev, A

    2000-09-01

    Perisomatic inhibition of pyramidal cells regulates efferent signalling from the hippocampus. The striking presence of HNK-1, a carbohydrate expressed by neural adhesion molecules, on perisomatic interneurons and around somata of CA1 pyramidal neurons led us to apply monoclonal HNK-1 antibodies to acute murine hippocampal slices. Injection of these antibodies decreased GABAA receptor-mediated perisomatic inhibitory postsynaptic currents (pIPSCs) but did not affect dendritic IPSCs or excitatory postsynaptic currents. The decrease in the mean amplitude of evoked pIPSCs by HNK-1 antibodies was accompanied by an increase in the coefficient of variation of pIPSC amplitude, number of failures and changes in frequency but not amplitude of miniature IPSCs, suggesting that HNK-1 antibodies reduced efficacy of evoked GABA release. HNK-1 antibodies did not affect pIPSCs in knock-out mice deficient in the extracellular matrix molecule tenascin-R which carries the HNK-1 carbohydrate as analysed by immunoblotting in synaptosomal fractions prepared from the CA1 region of the hippocampus. For control, HNK-1 antibody was applied to acute sections of mice deficient in the neural cell adhesion molecule NCAM, another potential carrier of HNK-1, and resulted in decrease of pIPSCs as observed in wild-type mice. Reduction in perisomatic inhibition is expected to promote induction of long-term potentiation (LTP) by increasing the level of depolarization during theta-burst stimulation. Indeed, LTP was increased by HNK-1 antibody applied before stimulation. Moreover, LTP was reduced by an HNK-1 peptide mimic, but not control peptide. These results provide first evidence that tenascin-R and its associated HNK-1 carbohydrate modulate perisomatic inhibition and synaptic plasticity in the hippocampus.

  20. Second-harmonic generation of biological interfaces: probing the membrane protein bacteriorhodopsin and imaging membrane potential around GFP molecules at specific sites in neuronal cells of C. elegans

    NASA Astrophysics Data System (ADS)

    Lewis, Aaron; Khatchatouriants, Artium; Treinin, Millet; Chen, Zhongping; Peleg, Gadi; Friedman, Noga; Bouevitch, Oleg; Rothman, Zvi; Loew, Leslie; Sheres, Mordechai

    1999-07-01

    Second-harmonic generation (SHG) is applied to problems of probing membrane proteins and functionally imaging around selective sites and at single molecules in biological membranes. The membrane protein bacteriorhodopsin (bR) has been shown to have large second-harmonic (SH) intensities that are modulated by protein/retinylidene chromophore interactions. The nonlinear optical properties of model compounds, which simulate these protein chromophore interactions in retinal proteins, are studied in this work by surface SHG and by hyper-Rayleigh scattering. Our results indicate that non-conjugated charges and hydrogen bonding effects have a large effect on the molecular hyperpolarizability of the retinal chromophore. However, mbR, the model system studies suggest that polarizable amino acids strongly affect the vertically excited state of the retinylidene chromophore and appear to play the major role in the observed protein enhancement (>50%) of the retinylidene chromophore molecular hyperpolarizability and associated induced dipole. Furthermore, the data provide insights on emulating these interactions for the design of organic nonlinear optical materials. Our studies have also led to the development of dyes with large SH intensities that can be embedded in cell membranes and can functionally image membrane potential. Single molecules of such dyes in selected single molecular regions of a cell membrane have been detected. SHG from green fluorescent protein (GFP) selectively expressed in concert with a specific protein in neuronal cells in a transgenic form of the worm C. elegans is also reported. The membrane potential around the GFP molecules expressed in these cells has been imaged with SHG in live animals.

  1. Angle-Dependent Ionization of Small Molecules by Time-Dependent Configuration Interaction and an Absorbing Potential.

    PubMed

    Krause, Pascal; Schlegel, H Bernhard

    2015-06-04

    The angle-dependence of strong field ionization of O2, N2, CO2, and CH2O has been studied theoretically using a time-dependent configuration interaction approach with a complex absorbing potential (TDCIS-CAP). Calculation of the ionization yields as a function of the direction of polarization of the laser pulse produces three-dimensional surfaces of the angle-dependent ionization probability. These three-dimensional shapes and their variation with laser intensity can be interpreted in terms of ionization from the highest occupied molecular orbital (HOMO) and lower lying orbitals, and the Dyson orbitals for the ground and excited states of the cations.

  2. Small-molecule inhibitors of proteins involved in base excision repair potentiate the anti-tumorigenic effect of existing chemotherapeutics and irradiation

    PubMed Central

    Reed, April M; Fishel, Melissa L; Kelley, Mark R

    2009-01-01

    There has been a recent upsurge in the development of small-molecule inhibitors specific to DNA repair proteins or proteins peripherally involved in base excision repair and the DNA damage response. These specific, nominally toxic inhibitors are able to potentiate the effect of existing cancer cell treatments in a wide array of cancers. One of the largest obstacles to overcome in the treatment of cancer is incomplete killing with initial cancer treatments, leading to resistant cancer. The progression of our understanding of cancer and normal cell responses to DNA damage has allowed us to develop biomarkers that we can use to help us predict responses of cancers, more specifically target cancer cells and overcome resistance. Initial successes using these small-molecule DNA repair inhibitors in target-validation experiments and in the early stages of clinical trials indicate an important role for these inhibitors, and allow for the possibility of a future in which cancers are potentially treated in a highly specific, individual manner. PMID:19519210

  3. Rotation and vibration of diatomic molecule in the spatially-dependent mass Schrödinger equation with generalized q-deformed Morse potential

    NASA Astrophysics Data System (ADS)

    Ikhdair, Sameer M.

    2009-06-01

    The analytic solutions of the spatially-dependent mass Schrödinger equation of diatomic molecules with the centrifugal term l(l+1)/r2 for the generalized q-deformed Morse potential are obtained approximately by means of a parametric generalization of the Nikiforov-Uvarov (NU) method combined with the Pekeris approximation scheme. The energy eigenvalues and the corresponding normalized radial wave functions are calculated in closed form with a physically motivated choice of a reciprocal Morse-like mass function, m(r)=m0/(1-δe)2,0⩽δ<1, where a and re are the range of the potential and the equilibrium position of the nuclei. The constant mass case when δ→0 is also studied. The energy states for H 2, LiH, HCl and CO diatomic molecules are calculated and compared favourably well with those obtained by using other approximation methods for arbitrary vibrational n and rotational l quantum numbers.

  4. Fragrances and other materials in deodorants: search for potentially sensitizing molecules using combined GC-MS and structure activity relationship (SAR) analysis.

    PubMed

    Rastogi, S C; Lepoittevin, J P; Johansen, J D; Frosch, P J; Menné, T; Bruze, M; Dreier, B; Andersen, K E; White, I R

    1998-12-01

    Deodorants are one of the most frequently-used types of cosmetics and are a source of allergic contact dermatitis. Therefore, a gas chromatography - mass spectrometric analysis of 71 deodorants was performed for identification of fragrance and non-fragrance materials present in marketed deodorants. Futhermore, the sensitizing potential of these molecules was evaluated using structure activity relationships (SARs) analysis. This was based on the presence of 1 or more chemically reactive site(s), in the chemical structure, associated with sensitizing potential. Among the many different substances used to formulate cosmetic products (over 3500), 226 chemicals were identified in a sample of 71 deodorants. 84 molecules were found to contain at least 1 structural alert, and 70 to belong to, or be susceptible to being metabolized into, the chemical group of aldehydes, ketones and alpha,beta-unsaturated aldehydes, ketone or esters. The combination of GC-MS and SARs analysis could be helpful in the selection of substances for supplementary investigations regarding sensitizing properties. Thus, it may be a valuable tool in the management of contact allergy to deodorants and for producing new deodorants with decreased propensity to cause contact allergy.

  5. Vasorelaxant activity of extracts obtained from Apium graveolens: Possible source for vasorelaxant molecules isolation with potential antihypertensive effect

    PubMed Central

    Jorge, Vergara-Galicia; Ángel, Jimenez-Ramirez Luis; Adrián, Tun-Suarez; Francisco, Aguirre-Crespo; Anuar, Salazar-Gómez; Samuel, Estrada-Soto; Ángel, Sierra-Ovando; Emmanuel, Hernandez-Nuñez

    2013-01-01

    Objective To investigate vasorelaxant effect of organic extracts from Apium graveolens (A. graveolens) which is a part of a group of plants subjected to pharmacological and phytochemical study with the purpose of offering it as an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects. Methods An ex vivo method was employed to assess the vasorelaxant activity. This consisted of using rat aortic rings with and without endothelium precontracted with norepinephrine. Results All extracts caused concentration-dependent relaxation in precontracted aortic rings with and without endothelium; the most active extracts were Dichloromethane and Ethyl Acetate extracts from A. graveolens. These results suggested that secondary metabolites responsible for the vasorelaxant activity belong to a group of compounds of medium polarity. Also, our evidence showed that effect induced by dichloromethane and ethyl acetate extracts from A. graveolens is mediated probably by calcium antagonism. Conclusions A. graveolens represents an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects. PMID:24075341

  6. Potential drug - nanosensor conjugates: Raman, infrared absorption, surface - enhanced Raman, and density functional theory investigations of indolic molecules

    NASA Astrophysics Data System (ADS)

    Pięta, Ewa; Paluszkiewicz, Czesława; Oćwieja, Magdalena; Kwiatek, Wojciech M.

    2017-05-01

    An extremely important aspect of planning cancer treatment is not only the drug efficiency but also a number of challenges associated with the side effects and control of this process. That is why it is worth paying attention to the promising potential of the gold nanoparticles combined with a compound treated as a potential drug. This work presents Raman (RS), infrared absorption (IR) and surface-enhanced Raman scattering (SERS) spectroscopic investigations of N-acetyl-5-methoxytryptamine (melatonin) and α-methyl-DL-tryptophan, regarding as anti breast cancer agents. The experimental spectroscopic analysis was supported by the quantum-chemical calculations based on the B3LYP hybrid density functional theory (DFT) at the B3LYP 6-311G(d,p) level of theory. The studied compounds were adsorbed onto two colloidal gold nanosensors synthesized by a chemical reduction method using sodium borohydride (SB) and trisodium citrate (TC), respectively. Its morphology characteristics were obtained using transmission electron microscopy (TEM). It has been suggested that the NH moiety from the aromatic ring, a well-known proton donor, causes the formation of hydrogen bonds with the negatively charged gold surface.

  7. Expression of Osteogenic Molecules in the Caudate Nucleus and Gray Matter and Their Potential Relevance for Basal Ganglia Calcification in Hypoparathyroidism

    PubMed Central

    Millo, Tabin; Mishra, Shruti; Das, Madhuchhanda; Kapoor, Mansi; Tomar, Neeraj; Saha, Soma; Roy, Tara Shankar; Sreenivas, Vishnubhatla

    2014-01-01

    Background: Basal ganglia calcification (BGC) is an interesting example of ectopic calcification in patients with hypoparathyroidism. Its pathogenesis and reasons for predilection of calcification at basal ganglia are not clear. Objective: To assess the expression of osteogenesis-related molecules in the caudate nucleus and surface gray matter (an area spared from calcification) and discuss potential relevance of the results in context of BGC in idiopathic hypoparathyroidism. Methods: Caudate nucleus and gray matter were obtained from 14 autopsies performed in accidental deaths. The mRNA expression of bone transcription factors (RUNX2/osterix), bone morphogenetic proteins (BMPs) 2 and 4, osteonectin, osteopontin, osteocalcin, vitamin D receptor, calcium sensing-receptor, Na phosphate transporters (PiTs) 1 and 2, N-methyl-D-aspartate receptor 2B (NMDAR2B), carbonic anhydrase II (CA-II), PTH1 receptor (PTH1R), PTH2R, and PTHrP were assessed by RT-PCR. Western blot, spot densitometry, and immunohistochemistry were performed to assess protein expression of molecules showing differences in mRNA expression between caudate and gray tissues. Results: The mean mRNA expression of PiT1 (11.0 ± 10.39 vs 32.9 ± 20.98, P = .003) and PTH2R (1.6 ± 1.47 vs 13.7 ± 6.11, P = .001) were significantly lower in the caudate nucleus than the gray matter. The expression of osteonectin, osteopontin, and CA-II were significantly higher in the caudate nucleus than the gray matter (P = .01, .001, and .04, respectively). The mRNA expression of other molecules was comparable in the 2 tissues. The protein expression of both CA-II and osteonectin was 24% higher and PiT1 17% lower in caudate than the gray matter. The differences in the PTH2R and osteopontin protein expression were not appreciable. Conclusions: The presence of several osteogenic molecules in caudate nucleus indicates that BGC would probably be the outcome of an active process. The differences in expression of these molecules in

  8. Classical and Mexican hat-type potential energy curve for the hydrogen molecule from a confined Kratzer oscillator

    NASA Astrophysics Data System (ADS)

    van Hooydonk, G.

    2016-03-01

    We review harmonic oscillator theory for closed, stable quantum systems. The H2 potential energy curve (PEC) of Mexican hat-type, calculated with a confined Kratzer oscillator, is better than the Rydberg-Klein-Rees (RKR) H2 PEC. Compared with QM, the theory of chemical bonding is simplified, since a confined Kratzer oscillator can also lead to the long sought for universal function, once called the Holy Grail of Molecular Spectroscopy. This is validated by reducing PECs for different bonds H2, HF, I2, N2 and O2 to a single one. The equal probability for H2, originating either from HA + HB or HB + HA, is quantified with a Gauss probability density function. At the Bohr scale, a confined harmonic oscillator behaves properly at the extremes of bound two-nucleon quantum systems.

  9. Modeling of Human Prokineticin Receptors: Interactions with Novel Small-Molecule Binders and Potential Off-Target Drugs

    PubMed Central

    Levit, Anat; Yarnitzky, Talia; Wiener, Ayana; Meidan, Rina; Niv, Masha Y.

    2011-01-01

    Background and Motivation The Prokineticin receptor (PKR) 1 and 2 subtypes are novel members of family A GPCRs, which exhibit an unusually high degree of sequence similarity. Prokineticins (PKs), their cognate ligands, are small secreted proteins of ∼80 amino acids; however, non-peptidic low-molecular weight antagonists have also been identified. PKs and their receptors play important roles under various physiological conditions such as maintaining circadian rhythm and pain perception, as well as regulating angiogenesis and modulating immunity. Identifying binding sites for known antagonists and for additional potential binders will facilitate studying and regulating these novel receptors. Blocking PKRs may serve as a therapeutic tool for various diseases, including acute pain, inflammation and cancer. Methods and Results Ligand-based pharmacophore models were derived from known antagonists, and virtual screening performed on the DrugBank dataset identified potential human PKR (hPKR) ligands with novel scaffolds. Interestingly, these included several HIV protease inhibitors for which endothelial cell dysfunction is a documented side effect. Our results suggest that the side effects might be due to inhibition of the PKR signaling pathway. Docking of known binders to a 3D homology model of hPKR1 is in agreement with the well-established canonical TM-bundle binding site of family A GPCRs. Furthermore, the docking results highlight residues that may form specific contacts with the ligands. These contacts provide structural explanation for the importance of several chemical features that were obtained from the structure-activity analysis of known binders. With the exception of a single loop residue that might be perused in the future for obtaining subtype-specific regulation, the results suggest an identical TM-bundle binding site for hPKR1 and hPKR2. In addition, analysis of the intracellular regions highlights variable regions that may provide subtype specificity

  10. Identification of a melampomagnolide B analog as a potential lead molecule for treatment of acute myelogenous leukemia.

    PubMed

    Albayati, Zaineb A F; Janganati, Venumadhav; Chen, Zheng; Ponder, Jessica; Breen, Philip J; Jordan, Craig T; Crooks, Peter A

    2017-02-01

    A series of carbamate derivatives of the antileukemic sesquiterpene melampomagnolide B (MMB) has been synthesized utilizing a 1,2,4-triazole carbamate conjugate of MMB as an intermediate synthon. Five imidazole- and benzimidazole-carbamate analogs of MMB (8a-8e) were prepared and evaluated for anti-leukemic activity against cultured M9 ENL1 AML cells. All the analogs exhibited improved anti-leukemic activity (EC50=0.90-3.93μM) when compared to parthenolide and the parent sesquiterpene, MMB (EC50=7.0μM and 15.5μM, respectively). The imidazole carbamate analog, 8a (EC50=0.9μM), was 16 times more potent than MMB. The comparative bioavailabilities of 8a and MMB were determined in BALB/c mice following oral dosing of these compounds. It has been demonstrated that the absolute plasma bioavailabilities of MMB and 8a were 6.7±0.8%, and 45.5±2%, respectively. These results indicate that, compared to MMB, the PK parameters for 8a display significantly improved bioavailability and exposure after oral administration. Analog 8a is considered to be a potential clinical candidate for treatment of acute myelogenous leukemia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Molecular dynamics in the isothermal-isobaric ensemble: the requirement of a "shell" molecule. III. Discontinuous potentials.

    PubMed

    Uline, Mark J; Corti, David S

    2008-07-07

    Based on the approach of Gruhn and Monson [Phys. Rev. E 63, 061106 (2001)], we present a new method for deriving the collisions dynamics for particles that interact via discontinuous potentials. By invoking the conservation of the extended Hamiltonian, we generate molecular dynamics (MD) algorithms for simulating the hard-sphere and square-well fluids within the isothermal-isobaric (NpT) ensemble. Consistent with the recent rigorous reformulation of the NpT ensemble partition function, the equations of motion impose a constant external pressure via the introduction of a shell particle of known mass [M. J. Uline and D. S. Corti, J. Chem. Phys. 123, 164101 (2005); 123, 164102 (2005)], which serves to define uniquely the volume of the system. The particles are also connected to a temperature reservoir through the use of a chain of Nose-Hoover thermostats, the properties of which are not affected by a hard-sphere or square-well collision. By using the Liouville operator formalism and the Trotter expansion theorem to integrate the equations of motion, the update of the thermostat variables can be decoupled from the update of the positions of the particles and the momentum changes upon a collision. Hence, once the appropriate collision dynamics for the isobaric-isenthalpic (NpH) equations of motion is known, the adaptation of the algorithm to the NpT ensemble is straightforward. Results of MD simulations for the pure component square-well fluid are presented and serve to validate our algorithm. Finally, since the mass of the shell particle is known, the system itself, and not a piston of arbitrary mass, controls the time scales for internal pressure and volume fluctuations. We therefore consider the influence of the shell particle algorithm on the dynamics of the square-well fluid.

  12. Molecule nanoweaver

    DOEpatents

    Gerald, II; Rex, E [Brookfield, IL; Klingler, Robert J [Glenview, IL; Rathke, Jerome W [Homer Glen, IL; Diaz, Rocio [Chicago, IL; Vukovic, Lela [Westchester, IL

    2009-03-10

    A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

  13. Use of a High-Throughput Phenotypic Screening Strategy to Identify Amplifiers, a Novel Pharmacological Class of Small Molecules That Exhibit Functional Synergy with Potentiators and Correctors.

    PubMed

    Giuliano, Kenneth A; Wachi, Shinichiro; Drew, Lawrence; Dukovski, Danijela; Green, Olivia; Bastos, Cecilia; Cullen, Matthew D; Hauck, Sheila; Tait, Bradley D; Munoz, Benito; Lee, Po-Shun; Miller, John Preston

    2017-09-01

    Cystic fibrosis (CF) is a lethal genetic disorder caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite recent groundbreaking approval of genotype-specific small-molecule drugs, a significant portion of CF patients still lack effective therapeutic options that address the underlying cause of the disease. Through a phenotypic high-throughput screen of approximately 54,000 small molecules, we identified a novel class of CFTR modulators called amplifiers. The identified compound, the characteristics of which are represented here by PTI-CH, selectively increases the expression of immature CFTR protein across different CFTR mutations, including F508del-CFTR, by targeting the inefficiencies of early CFTR biosynthesis. PTI-CH also augments the activity of other CFTR modulators and was found to possess novel characteristics that distinguish it from CFTR potentiator and corrector moieties. The PTI-CH-mediated increase in F508del-CFTR did not elicit cytosolic or endoplasmic reticulum-associated cellular stress responses. Based on these data, amplifiers represent a promising new class of CFTR modulators for the treatment of CF that can be used synergistically with other CFTR modulators.

  14. Theoretical study on the ground state of the polar alkali-metal-barium molecules: Potential energy curve and permanent dipole moment

    SciTech Connect

    Gou, Dezhi; Kuang, Xiaoyu Gao, Yufeng; Huo, Dongming

    2015-01-21

    In this paper, we systematically investigate the electronic structure for the {sup 2}Σ{sup +} ground state of the polar alkali-metal-alkaline-earth-metal molecules BaAlk (Alk = Li, Na, K, Rb, and Cs). Potential energy curves and permanent dipole moments (PDMs) are determined using power quantum chemistry complete active space self-consistent field and multi-reference configuration interaction methods. Basic spectroscopic constants are derived from ro-vibrational bound state calculation. From the calculations, it is shown that BaK, BaRb, and BaCs molecules have moderate values of PDM at the equilibrium bond distance (BaK:1.62 D, BaRb:3.32 D, and BaCs:4.02 D). Besides, the equilibrium bond length (4.93 Å and 5.19 Å) and dissociation energy (0.1825 eV and 0.1817 eV) for the BaRb and BaCs are also obtained.

  15. Theoretical study on the ground state of the polar alkali-metal-barium molecules: Potential energy curve and permanent dipole moment

    NASA Astrophysics Data System (ADS)

    Gou, Dezhi; Kuang, Xiaoyu; Gao, Yufeng; Huo, Dongming

    2015-01-01

    In this paper, we systematically investigate the electronic structure for the 2Σ+ ground state of the polar alkali-metal-alkaline-earth-metal molecules BaAlk (Alk = Li, Na, K, Rb, and Cs). Potential energy curves and permanent dipole moments (PDMs) are determined using power quantum chemistry complete active space self-consistent field and multi-reference configuration interaction methods. Basic spectroscopic constants are derived from ro-vibrational bound state calculation. From the calculations, it is shown that BaK, BaRb, and BaCs molecules have moderate values of PDM at the equilibrium bond distance (BaK:1.62 D, BaRb:3.32 D, and BaCs:4.02 D). Besides, the equilibrium bond length (4.93 Å and 5.19 Å) and dissociation energy (0.1825 eV and 0.1817 eV) for the BaRb and BaCs are also obtained.

  16. Virus-like particles presenting interleukin-33 molecules: immunization characteristics and potentials of blockingIL-33/ST2 pathway in allergic airway inflammation.

    PubMed

    Long, Qiong; Huang, Weiwei; Yao, Yufeng; Yang, Xu; Sun, Wenjia; Jin, Xiaomei; Li, Yang; Chu, Xiaojie; Liu, Cunbao; Peng, Zhikang; Ma, Yanbing

    2014-01-01

    We sought to develop an IL-33 vaccine and evaluate its efficacy in a mouse model of asthma. The full-length molecules of putative mature IL-33 were inserted into the immunodominant epitope region of hepatitis B core antigen using gene recombination techniques. The expressed chimeric protein presented as virus-like particles (VLPs) under observation using an electron microscopy. To investigate immunization characteristics of the VLPs, mice were immunized by using different doses, adjuvants, and routes. The VLPs induced sustained and high titers of IL-33-specific IgG and IgA even without the use of a conventional adjuvant, and the lowered ratio of IgG1/IgG2a in vaccinated mice indicated a shift from Th2 to Th1-like responses. To assess the vaccine effects on blocking the signaling of IL-33/ST2 pathway, mice receiving 3 vaccinations subjected to intraperitoneal sensitization and intranasal challenge with ovalbumin (OVA). Control animals received carrier or PBS in place of the vaccine. Immunization with the VLPs significantly suppressed inflammatory cell number and IL-33 level in BALF. OVA -induced goblet cell hyperplasia and lung tissue inflammatory cell infiltration were significantly suppressed in vaccinated mice. Our data indicate that IL-33 molecule-based vaccine, which may block IL-33/ST2 signaling pathway on a persistent basis, holds potential for treatment of asthma and, by extension, other diseases where overexpressed IL-33 plays a pivotal role in pathogenesis.

  17. Thermodynamics properties study of diatomic molecules with q-deformed modified Poschl-Teller plus Manning Rosen non-central potential in D dimensions using SUSYQM approach

    NASA Astrophysics Data System (ADS)

    Suparmi, A.; Cari, C.; Pratiwi, B. N.

    2016-04-01

    D-dimensional Dirac equation of q-deformed modified Poschl-Teller plus Manning Rosen non-central potential was solved using supersymmetric quantum mechanics (SUSY QM). The relativistic energy spectra were analyzed by using SUSY QM and shape invariant properties from radial part of D dimensional Dirac equation and the angular quantum numbers were obtained from angular part of D dimensional Dirac equation. The SUSY operators was used to generate the D dimensional relativistic wave functions both for radial and angular parts. In the non-relativistic limit, the relativistic energy equation was reduced to the non-relativistic energy. In the classical limit, the partition function of vibrational, the specific heat of vibrational, and the mean energy of vibrational of some diatomic molecules were calculated from the equation of non-relativistic energy with the help of error function and Mat-lab 2011.

  18. Ab initio ro-vibrational Hamiltonian in irreducible tensor formalism: a method for computing energy levels from potential energy surfaces for symmetric-top molecules

    NASA Astrophysics Data System (ADS)

    Rey, M.; Nikitin, A. V.; Tyuterev, Vl. G.

    2010-08-01

    A theoretical approach to study ro-vibrational molecular states from a full nuclear Hamiltonian expressed in terms of normal-mode irreducible tensor operators is presented for the first time. Each term of the Hamiltonian expansion can thus be cast in the tensor form in a systematic way using the formalism of ladder operators. Pyramidal XY3 molecules appear to be good candidates to validate this approach which allows taking advantage of the symmetry properties when doubly degenerate vibrational modes are considered. Examples of applications will be given for PH3 where variational calculations have been carried out from our recent potential energy surface [Nikitin et al., J. Chem. Phys. 130, 244312 (2009)].

  19. Selective inhibition of MBNL1–CCUG interaction by small molecules toward potential therapeutic agents for myotonic dystrophy type 2 (DM2)†

    PubMed Central

    Wong, Chun-Ho; Fu, Yuan; Ramisetty, Sreenivasa Rao; Baranger, Anne M.; Zimmerman, Steven C.

    2011-01-01

    Myotonic dystrophy type 2 (DM2) is an incurable neuromuscular disease caused by expanded CCUG repeats that may exhibit toxicity by sequestering the splicing regulator MBNL1. A series of triaminotriazine- and triaminopyrimidine-based small molecules (ligands 1–3) were designed, synthesized and tested as inhibitors of the MBNL1–CCUG interaction. Despite the structural similarities of the triaminotriazine and triaminopyrimidine units, the triaminopyrimidine-based ligands bind with low micromolar affinity to CCUG repeats (Kd ∼ 0.1–3.6 µM) whereas the triaminotriazine ligands do not bind CCUG repeats. Importantly, these simple and small triaminopyrimidine ligands exhibit both strong inhibition (Ki ∼ 2 µM) of the MBNL1–CCUG interaction and high selectivity for CCUG repeats over other RNA targets. These experiments suggest these compounds are potential lead agents for the treatment of DM2. PMID:21768123

  20. Virtual screening of natural inhibitors to the predicted HBx protein structure of Hepatitis B Virus using molecular docking for identification of potential lead molecules for liver cancer

    PubMed Central

    Pathak, Rajesh Kumar; Baunthiyal, Mamta; Taj, Gohar; Kumar, Anil

    2014-01-01

    The HBx protein in Hepatitis B Virus (HBV) is a potential target for anti-liver cancer molecules. Therefore, it is of interest to screen known natural compounds against the HBx protein using molecular docking. However, the structure of HBx is not yet known. Therefore, the predicted structure of HBx using threading in LOMET was used for docking against plant derived natural compounds (curcumin, oleanolic acid, resveratrol, bilobetin, luteoline, ellagic acid, betulinic acid and rutin) by Molegro Virtual Docker. The screening identified rutin with binding energy of -161.65 Kcal/mol. Thus, twenty derivatives of rutin were further designed and screened against HBx. These in silico experiments identified compounds rutin01 (-163.16 Kcal/mol) and rutin08 (- 165.76 Kcal/mol) for further consideration and downstream validation. PMID:25187683

  1. Evaluating the potential of thermal read-out techniques combined with molecularly imprinted polymers for the sensing of low-weight organic molecules.

    PubMed

    van Grinsven, B; Betlem, K; Cleij, T J; Banks, C E; Peeters, M

    2017-01-01

    In recent years, there has been a tremendous increase in the papers published on synthetic recognition elements. Molecularly imprinted polymers (MIPs), also referred to as "man-made mimics" of antibodies, are able to rebind their template molecules with high affinity. Advantages compared with those of natural receptors include their excellent thermal and chemical stability, low cost, and ease of the production process. However, their use in commercial biosensors is limited owing to the difficulty to incorporate MIPs into suitable sensing platforms and traditional detection techniques, such as chromatography, that require bulky and sophisticated equipment. In this review, we evaluate the potential to use MIPs combined with thermal read-out for the detection of low-weight organic molecules. We discuss thermal methods to study MIP-template complexation and to determine neurotransmitters concentrations. In particular, we highlight the heat-transfer method, a recent technique that is straightforward and low cost and requires minimal instrumentation. Until now, sample preparation involves a 2-step process, making it time-consuming, and measuring biological samples is difficult owing to the noise in the signal. Different sample preparation methods are discussed, and it will be demonstrated how this affects the thermal response. An outlook is given in novel methods that can simplify and speed up sample preparation. Finally, we show a novel thermal technique, which is based on the analysis of transport of thermal waves rather than evaluating the fixed heat-transfer resistance. Through applying the concept of thermal waves, signal-noise ratio is significantly increased, which results in lower detection limits and has potential for the study of biological samples. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Estimating the intrinsic limit of the Feller-Peterson-Dixon composite approach when applied to adiabatic ionization potentials in atoms and small molecules

    NASA Astrophysics Data System (ADS)

    Feller, David

    2017-07-01

    Benchmark adiabatic ionization potentials were obtained with the Feller-Peterson-Dixon (FPD) theoretical method for a collection of 48 atoms and small molecules. In previous studies, the FPD method demonstrated an ability to predict atomization energies (heats of formation) and electron affinities well within a 95% confidence level of ±1 kcal/mol. Large 1-particle expansions involving correlation consistent basis sets (up to aug-cc-pV8Z in many cases and aug-cc-pV9Z for some atoms) were chosen for the valence CCSD(T) starting point calculations. Despite their cost, these large basis sets were chosen in order to help minimize the residual basis set truncation error and reduce dependence on approximate basis set limit extrapolation formulas. The complementary n-particle expansion included higher order CCSDT, CCSDTQ, or CCSDTQ5 (coupled cluster theory with iterative triple, quadruple, and quintuple excitations) corrections. For all of the chemical systems examined here, it was also possible to either perform explicit full configuration interaction (CI) calculations or to otherwise estimate the full CI limit. Additionally, corrections associated with core/valence correlation, scalar relativity, anharmonic zero point vibrational energies, non-adiabatic effects, and other minor factors were considered. The root mean square deviation with respect to experiment for the ionization potentials was 0.21 kcal/mol (0.009 eV). The corresponding level of agreement for molecular enthalpies of formation was 0.37 kcal/mol and for electron affinities 0.20 kcal/mol. Similar good agreement with experiment was found in the case of molecular structures and harmonic frequencies. Overall, the combination of energetic, structural, and vibrational data (655 comparisons) reflects the consistent ability of the FPD method to achieve close agreement with experiment for small molecules using the level of theory applied in this study.

  3. Brain-Penetrant, Orally Bioavailable Microtubule-Stabilizing Small Molecules Are Potential Candidate Therapeutics for Alzheimer’s Disease and Related Tauopathies

    PubMed Central

    2015-01-01

    Microtubule (MT) stabilizing drugs hold promise as potential treatments for Alzheimer’s disease (AD) and related tauopathies. However, thus far epothilone D has been the only brain-penetrant MT-stabilizer to be evaluated in tau transgenic mice and in AD patients. Furthermore, this natural product exhibits potential deficiencies as a drug candidate, including an intravenous route of administration and the inhibition of the P-glycoprotein (Pgp) transporter. Thus, the identification of alternative CNS-active MT-stabilizing agents that lack these potential limitations is of interest. Toward this objective, we have evaluated representative compounds from known classes of non-naturally occurring MT-stabilizing small molecules. This led to the identification of selected triazolopyrimidines and phenylpyrimidines that are orally bioavailable and brain-penetrant without disruption of Pgp function. Pharmacodynamic studies confirmed that representative compounds from these series enhance MT-stabilization in the brains of wild-type mice. Thus, these classes of MT-stabilizers hold promise for the development of orally active, CNS-directed MT-stabilizing therapies. PMID:24992153

  4. Redox potentials of primary electron acceptor quinone molecule (QA)- and conserved energetics of photosystem II in cyanobacteria with chlorophyll a and chlorophyll d.

    PubMed

    Allakhverdiev, Suleyman I; Tsuchiya, Tohru; Watabe, Kazuyuki; Kojima, Akane; Los, Dmitry A; Tomo, Tatsuya; Klimov, Vyacheslav V; Mimuro, Mamoru

    2011-05-10

    In a previous study, we measured the redox potential of the primary electron acceptor pheophytin (Phe) a of photosystem (PS) II in the chlorophyll d-dominated cyanobacterium Acaryochloris marina and a chlorophyll a-containing cyanobacterium, Synechocystis. We obtained the midpoint redox potential (E(m)) values of -478 mV for A. marina and -536 mV for Synechocystis. In this study, we measured the redox potentials of the primary electron acceptor quinone molecule (Q(A)), i.e., E(m)(Q(A)/Q(A)(-)), of PS II and the energy difference between [P680·Phe a(-)·Q(A)] and [P680·Phe a·Q(A)(-)], i.e., ΔG(PhQ). The E(m)(Q(A)/Q(A)(-)) of A. marina was determined to be +64 mV without the Mn cluster and was estimated to be -66 to -86 mV with a Mn-depletion shift (130-150 mV), as observed with other organisms. The E(m)(Phe a/Phe a(-)) in Synechocystis was measured to be -525 mV with the Mn cluster, which is consistent with our previous report. The Mn-depleted downshift of the potential was measured to be approximately -77 mV in Synechocystis, and this value was applied to A. marina (-478 mV); the E(m)(Phe a/Phe a(-)) was estimated to be approximately -401 mV. These values gave rise to a ΔG(PhQ) of -325 mV for A. marina and -383 mV for Synechocystis. In the two cyanobacteria, the energetics in PS II were conserved, even though the potentials of Q(A)(-) and Phe a(-) were relatively shifted depending on the special pair, indicating a common strategy for electron transfer in oxygenic photosynthetic organisms.

  5. Interstellar molecules

    NASA Technical Reports Server (NTRS)

    Townes, C. H.

    1976-01-01

    Progress in the discovery and study of interstellar molecules is summarized. The 36 molecular species thus far identified in interstellar space are listed in several groups which include simple hydrides, oxides, and sulfides, various derivatives of ammonia, molecules involving linear carbon chains, cyanides, and molecules related in structure to formaldehyde, alcohols, or ethers. Several free radicals are described, the discovery of molecules in external galaxies is discussed, and possible mechanisms for molecular formation are noted. Methods for examining relative isotopic abundances by measuring molecules in interstellar clouds are outlined, mechanisms for the excitation of interstellar molecules are reviewed, and values are presented for the C-12/C-13 abundance ratio in a number of interstellar clouds. The detection of interstellar masers is discussed along with pumping mechanisms and masing transitions in H2CO, CH, OH, and SiO. The nature of dense interstellar clouds is examined in terms of several simple and complex cloud models, with emphasis on multiple condensation models.

  6. Full dimensional potential energy surface for the ground state of H{sub 4}{sup +} system based on triatomic-in-molecules formalism

    SciTech Connect

    Sanz-Sanz, Cristina E-mail: cristina.sanz@gmail.com; Roncero, Octavio; Paniagua, Miguel; Aguado, Alfredo

    2013-11-14

    In this work, we present a global potential energy surface for the ground electronic state of the H{sub 4}{sup +} based on ab initio calculations. The final fit is based on triatomics-in-molecules (TRIM) approximation and it includes extra four-body terms for the better description of some discrepancies found on the TRIM model. The TRIM method itself allows a very accurate description of the asymptotic regions. The global fit uses more than 19 000 multireference configuration interaction ab initio points. The global potential energy surface has an overall root mean square error of 0.013 eV for energies up to 2 eV above the global minimum. This work presents an analysis of the stationary points, reactant and product channels, and crossing between the two lowest TRIM adiabatic states. It is as well included a brief description of the two first excited states of the TRIM matrix, concluding that TRIM method is a very good approximation not only for the ground state but also for at least two of the excited states of H{sub 4}{sup +} system.

  7. Fixed-node diffusion Monte Carlo potential energy curve of the fluorine molecule F{sub 2} using selected configuration interaction trial wavefunctions

    SciTech Connect

    Giner, Emmanuel; Scemama, Anthony; Caffarel, Michel

    2015-01-28

    The potential energy curve of the F{sub 2} molecule is calculated with Fixed-Node Diffusion Monte Carlo (FN-DMC) using Configuration Interaction (CI)-type trial wavefunctions. To keep the number of determinants reasonable and thus make FN-DMC calculations feasible in practice, the CI expansion is restricted to those determinants that contribute the most to the total energy. The selection of the determinants is made using the CIPSI approach (Configuration Interaction using a Perturbative Selection made Iteratively). The trial wavefunction used in FN-DMC is directly issued from the deterministic CI program; no Jastrow factor is used and no preliminary multi-parameter stochastic optimization of the trial wavefunction is performed. The nodes of CIPSI wavefunctions are found to reduce significantly the fixed-node error and to be systematically improved upon increasing the number of selected determinants. To reduce the non-parallelism error of the potential energy curve, a scheme based on the use of a R-dependent number of determinants is introduced. Using Dunning’s cc-pVDZ basis set, the FN-DMC energy curve of F{sub 2} is found to be of a quality similar to that obtained with full configuration interaction/cc-pVQZ.

  8. Cellular toxicity induced by the photorelease of a caged bioactive molecule: design of a potential dual-action Ru(II) complex.

    PubMed

    Sgambellone, Mark A; David, Amanda; Garner, Robert N; Dunbar, Kim R; Turro, Claudia

    2013-07-31

    The series [Ru(tpy)(CH3CN)3](2+) (1), cis-[Ru(tpy)(CH3CN)2Cl](+) (2), and [Ru(tpy)(5CNU)3](2+) (3), where tpy = 2,2':6',2″-terpyridine and 5CNU = 5-cyanouracil, was synthesized, and their photochemical properties were investigated for use as potential photodynamic therapy (PDT) agents. When irradiated with visible light, 1-3 exhibit efficient exchange of the axial CH3CN or 5CNU ligand with H2O solvent molecules. Complexes 1-3 also exhibit photoinitiated binding to DNA when irradiated with λirr ≥ 395 nm light, and DNA binding can be accessed for 2 with λirr > 645 nm, well within the PDT window. Since 3 binds DNA and simultaneously releases biologically active 5CNU, it has the potential to be a dual-action therapeutic agent. Indeed, 3 is cytotoxic upon irradiation with visible light, whereas 1 is not under similar experimental conditions. The lack of toxicity imparted by 1 is explained by the exchange of only one CH3CN ligand in the complex under the irradiation conditions used for the cellular studies. Strategies are being sought to increase the quantum yields of ligand exchange and the cellular penetration of these compounds.

  9. C-type lectin-like molecule-1 (CLL1)-targeted TRAIL augments the tumoricidal activity of granulocytes and potentiates therapeutic antibody-dependent cell-mediated cytotoxicity.

    PubMed

    Wiersma, Valerie R; de Bruyn, Marco; Shi, Ce; Gooden, Marloes J M; Wouters, Maartje C A; Samplonius, Douwe F; Hendriks, Djoke; Nijman, Hans W; Wei, Yunwei; Zhou, Jin; Helfrich, Wijnand; Bremer, Edwin

    2015-01-01

    The therapeutic effect of anti-cancer monoclonal antibodies stems from their capacity to opsonize targeted cancer cells with subsequent phagocytic removal, induction of antibody-dependent cell-mediated cytotoxicity (ADCC) or induction of complement-mediated cytotoxicity (CDC). The major immune effector cells involved in these processes are natural killer (NK) cells and granulocytes. The latter and most prevalent blood cell population contributes to phagocytosis, but is not effective in inducing ADCC. Here, we report that targeted delivery of the tumoricidal protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to granulocyte marker C-type lectin-like molecule-1 (CLL1), using fusion protein CLL1:TRAIL, equips granulocytes with high levels of TRAIL. Upon CLL1-selective binding of this fusion protein, granulocytes acquire additional TRAIL-mediated cytotoxic activity that, importantly, potentiates antibody-mediated cytotoxicity of clinically used therapeutic antibodies (e.g., rituximab, cetuximab). Thus, CLL1:TRAIL could be used as an adjuvant to optimize the clinical potential of anticancer antibody therapy by augmenting tumoricidal activity of granulocytes.

  10. Discovery of small-molecule inhibitors of HCV NS3-4A protease as potential therapeutic agents against HCV infection.

    PubMed

    Chen, Shu-Hui; Tan, Seng-Lai

    2005-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with liver cirrhosis that often leads to hepatic failure and hepatocellular carcinoma (HCC). HCV infection has become a global health threat and the main cause of adult liver transplants in developed nations. Current approved anti-HCV therapies (interferon and pegylated interferon alone or in combination with ribavirin) are not effective in eliminating the viral infection in a significant population of patients (e.g., those infected with HCV genotype 1). Furthermore, these therapies are plagued with many undesirable side effects. Therefore, the HCV epidemic represents a huge unmet medical need that has triggered intensive research efforts towards the development of more effective drugs. Given its essential role in the process of HCV replication, the viral NS3/4A serine protease is arguably the most thoroughly characterized HCV enzyme and the most intensively pursued anti-HCV target for drug development. This is further fueled by the successful use of small-molecule inhibitors of the human immunodeficiency virus (HIV) viral protease, which have had an impressive effect on HIV-related morbidity and mortality, offering hope that analogous drugs might also have a similar impact against HCV. Here, we review the recent progress and development of small-molecule inhibitors of the HCV NS3/4A protease. In particular, we focus on the discovery of VX-950, the latest HCV NS3-4A protease inhibitor to be advanced to clinical studies. While the challenges of designing potent inhibitors of the viral protease have been solved, as highlighted by BILN 2061 and VX-950, it is still too early to determine whether these efforts will eventually yield promising drug candidates. For the emerging small-molecule HCV inhibitors, viral resistance will likely be a big problem. Thus, combination therapy of different drugs with different targets/mechanisms will be necessary to effectively inhibit HCV replication. It is also hoped that a

  11. Characterization of Brain-Penetrant Pyrimidine-Containing Molecules with Differential Microtubule-Stabilizing Activities Developed as Potential Therapeutic Agents for Alzheimer’s Disease and Related Tauopathies

    PubMed Central

    Kovalevich, Jane; Cornec, Anne-Sophie; Yao, Yuemang; James, Michael; Crowe, Alexander; Lee, Virginia M.-Y.; Trojanowski, John Q.; Smith, Amos B.

    2016-01-01

    The microtubule (MT)–stabilizing protein tau disengages from MTs and forms intracellular inclusions known as neurofibrillary tangles in Alzheimer’s disease and related tauopathies. Reduced tau binding to MTs in tauopathies may contribute to neuronal dysfunction through decreased MT stabilization and disrupted axonal transport. Thus, the introduction of brain-penetrant MT-stabilizing compounds might normalize MT dynamics and axonal deficits in these disorders. We previously described a number of phenylpyrimidines and triazolopyrimidines (TPDs) that induce tubulin post-translational modifications indicative of MT stabilization. We now further characterize the biologic properties of these small molecules, and our results reveal that these compounds can be divided into two general classes based on the cellular response they evoke. One group composed of the phenylpyrimidines and several TPD examples showed a bell-shaped concentration-response effect on markers of MT stabilization in cellular assays. Moreover, these compounds induced proteasome-dependent degradation of α- and β-tubulin and caused altered MT morphology in both dividing cells and neuron cultures. In contrast, a second group comprising a subset of TPD molecules (TPD+) increased markers of stable MTs in a concentration-dependent manner in dividing cells and in neurons without affecting total tubulin levels or disrupting MT architecture. Moreover, an example TPD+ compound was shown to increase MTs in a neuron culture model with induced tau hyperphosphorylation and associated MT deficits. Several TPD+ compounds were shown to be both brain penetrant and orally bioavailable, and a TPD+ example increased MT stabilization in the mouse brain, making these compounds potential candidate therapeutics for neurodegenerative tauopathies such as Alzheimer’s disease. PMID:26980057

  12. A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee.

    PubMed

    Deshmukh, V; Hu, H; Barroga, C; Bossard, C; Kc, S; Dellamary, L; Stewart, J; Chiu, K; Ibanez, M; Pedraza, M; Seo, T; Do, L; Cho, S; Cahiwat, J; Tam, B; Tambiah, J R S; Hood, J; Lane, N E; Yazici, Y

    2017-09-06

    Osteoarthritis (OA) is a degenerative disease characterized by loss of cartilage and increased subchondral bone within synovial joints. Wnt signaling affects the pathogenesis of OA as this pathway modulates both the differentiation of osteoblasts and chondrocytes, and production of catabolic proteases. A novel small-molecule Wnt pathway inhibitor, SM04690, was evaluated in a series of in vitro and in vivo animal studies to determine its effects on chondrogenesis, cartilage protection and synovial-lined joint pathology. A high-throughput screen was performed using a cell-based reporter assay for Wnt pathway activity to develop a small molecule designated SM04690. Its properties were evaluated in bone-marrow-derived human mesenchymal stem cells (hMSCs) to assess chondrocyte differentiation and effects on cartilage catabolism by immunocytochemistry and gene expression, and glycosaminoglycan breakdown. In vivo effects of SM04690 on Wnt signaling, cartilage regeneration and protection were measured using biochemical and histopathological techniques in a rodent acute cruciate ligament tear and partial medial meniscectomy (ACLT + pMMx) OA model. SM04690 induced hMSC differentiation into mature, functional chondrocytes and decreased cartilage catabolic marker levels compared to vehicle. A single SM04690 intra-articular (IA) injection was efficacious in a rodent OA model, with increased cartilage thickness, evidence for cartilage regeneration, and protection from cartilage catabolism observed, resulting in significantly improved Osteoarthritis Research Society International (OARSI) histology scores and biomarkers, compared to vehicle. SM04690 induced chondrogenesis and appeared to inhibit joint destruction in a rat OA model, and is a candidate for a potential disease modifying therapy for OA. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Mind Molecules

    PubMed Central

    Snyder, Solomon H.

    2011-01-01

    Scientific styles vary tremendously. For me, research is largely about the unfettered pursuit of novel ideas and experiments that can test multiple ideas in a day, not a year, an approach that I learned from my mentor Julius “Julie” Axelrod. This focus on creative conceptualizations has been my métier since working in the summers during medical school at the National Institutes of Health, during my two years in the Axelrod laboratory, and throughout my forty-five years at Johns Hopkins University School of Medicine. Equally important has been the “high” that emerges from brainstorming with my students. Nothing can compare with the eureka moments when, together, we sense new insights and, better yet, when high-risk, high-payoff experiments succeed. Although I have studied many different questions over the years, a common theme emerges: simple biochemical approaches to understanding molecular messengers, usually small molecules. Equally important has been identifying, purifying, and cloning the messengers' relevant biosynthetic, degradative, or target proteins, at all times seeking potential therapeutic relevance in the form of drugs. In the interests of brevity, this Reflections article is highly selective, and, with a few exceptions, literature citations are only of findings of our laboratory that illustrate notable themes. PMID:21543333

  14. Therapeutic potential of a distinct population of human amniotic fluid mesenchymal stem cells and their secreted molecules in mice with acute hepatic failure.

    PubMed

    Zagoura, Dimitra S; Roubelakis, Maria G; Bitsika, Vasiliki; Trohatou, Ourania; Pappa, Kalliopi I; Kapelouzou, Alkistis; Antsaklis, Aristidis; Anagnou, Nicholas P

    2012-06-01

    There is increasing interest in the therapeutic potential of human mesenchymal stem cells (hMSCs), especially in diseases such as acute hepatic failure (AHF) that are predominantly caused by a variety of drugs and viruses. In previous studies, a distinct population termed human spindle-shaped MSCs were isolated and expanded from second trimester amniotic fluid (AF-MSCs) and characterised based on their phenotype, pluripotency and differentiation potential. AF-MSCs, hepatic progenitor-like (HPL) cells and hepatocyte-like (HL) cells derived from AF-MSCs were transplanted into CCl₄-injured NOD/SCID mice with the AHF phenotype in order to evaluate their therapeutic potential. Conditioned medium (CM) derived from AF-MSCs or HPL cells was then delivered intrahepatically in order to determine whether the engraftment of the cells or their secreted molecules are the most important agents for liver repair. Both HPL cells and AF-MSCs were incorporated into CCl(4)-injured livers; HPL cell transplantation had a greater therapeutic effect. In contrast, HL cells failed to engraft and contribute to recovery. In addition, HPL-CM was found to be more efficient than CM derived from AF-MSCs in treatment of the liver. Proteome profile analysis of HPL-CM indicated the presence of anti-inflammatory factors such as interleukins IL-10, IL-1ra, IL-13 and IL-27 which may induce liver recovery. Blocking studies of IL-10 secretion from HPL cells confirmed the therapeutic significance of this cytokine in the AHF mouse model. Human spindle-shaped AF-MSCs or HPL cells might be valuable tools to induce liver repair and support liver function by cell transplantation. More importantly, the factors they release may also play an important role in cell treatment in diseases of the liver.

  15. Full-Dimensional Potential Energy and Dipole Moment Surfaces of GeH4 Molecule and Accurate First-Principle Rotationally Resolved Intensity Predictions in the Infrared.

    PubMed

    Nikitin, A V; Rey, M; Rodina, A; Krishna, B M; Tyuterev, Vl G

    2016-11-17

    Nine-dimensional potential energy surface (PES) and dipole moment surface (DMS) of the germane molecule are constructed using extended ab initio CCSD(T) calculations at 19 882 points. PES analytical representation is determined as an expansion in nonlinear symmetry adapted products of orthogonal and internal coordinates involving 340 parameters up to eighth order. Minor empirical refinement of the equilibrium geometry and of four quadratic parameters of the PES computed at the CCSD(T)/aug-cc-pVQZ-DK level of the theory yielded the accuracy below 1 cm(-1) for all experimentally known vibrational band centers of five stable isotopologues of (70)GeH4, (72)GeH4, (73)GeH4, (74)GeH4, and (76)GeH4 up to 8300 cm(-1). The optimized equilibrium bond re = 1.517 594 Å is very close to best ab initio values. Rotational energies up to J = 15 are calculated using potential expansion in normal coordinate tensors with maximum errors of 0.004 and 0.0006 cm(-1) for (74)GeH4 and (76)GeH4. The DMS analytical representation is determined through an expansion in symmetry-adapted products of internal nonlinear coordinates involving 967 parameters up to the sixth order. Vibration-rotation line intensities of five stable germane isotopologues were calculated from purely ab initio DMS using nuclear motion variational calculations with a full account of the tetrahedral symmetry of the molecules. For the first time a good overall agreement of main absorption features with experimental rotationally resolved Pacific Northwest National Laboratory spectra was achieved in the entire range of 700-5300 cm(-1). It was found that very accurate description of state-dependent isotopic shifts is mandatory to correctly describe complex patterns of observed spectra at natural isotopic abundance resulting from the superposition of five stable isotopologues. The data obtained in this work will be made available through the TheoReTS information system.

  16. Erythroid Adhesion Molecules in Sickle Cell Anaemia Infants: Insights Into Early Pathophysiology.

    PubMed

    Brousse, Valentine; Colin, Yves; Pereira, Catia; Arnaud, Cecile; Odièvre, Marie Helene; Boutemy, Anne; Guitton, Corinne; de Montalembert, Mariane; Lapouméroulie, Claudine; Picot, Julien; Le Van Kim, Caroline; El Nemer, Wassim

    2015-01-01

    Sickle cell anaemia (SCA) results from a single mutation in the β globin gene. It is seldom symptomatic in the first semester of life. We analysed the expression pattern of 9 adhesion molecules on red blood cells, in a cohort of 54 SCA and 17 non-SCA very young infants of comparable age (median 144 days, 81-196). Haemoglobin F (HbF) level was unsurprisingly elevated in SCA infants (41.2% ± 11.2) and 2-4 fold higher than in non-SCA infants, yet SCA infants presented significantly decreased Hb level and increased reticulocytosis. Cytometry analysis evidenced a specific expression profile on reticulocytes of SCA infants, with notably an increased expression of the adhesion molecules Lu/BCAM, ICAM-4 and LFA-3, both in percentage of positive cells and in surface density. No significant difference was found on mature red cells. Our findings demonstrate the very early onset of reticulocyte membrane modifications in SCA asymptomatic infants and allow an insight into the first pathological changes with the release of stress reticulocytes expressing a distinctive profile of adhesion molecules.

  17. ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model.

    PubMed

    Heravi, Mitra; Kumala, Slawomir; Rachid, Zakaria; Jean-Claude, Bertrand J; Radzioch, Danuta; Muanza, Thierry M

    2015-06-01

    ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Western blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Strategies for potential age dating of fingerprints through the diffusion of sebum molecules on a nonporous surface analyzed using time-of-flight secondary ion mass spectrometry.

    PubMed

    Muramoto, Shin; Sisco, Edward

    2015-08-18

    Age dating of fingerprints could have a significant impact in forensic science, as it has the potential to facilitate the judicial process by assessing the relevance of a fingerprint found at a crime scene. However, no method currently exists that can reliably predict the age of a latent fingerprint. In this manuscript, time-of-flight secondary ion imaging mass spectrometry (TOF-SIMS) was used to measure the diffusivity of saturated fatty acid molecules from a fingerprint on a silicon wafer. It was found that their diffusion from relatively fresh fingerprints (t ≤ 96 h) could be modeled using an error function, with diffusivities (mm(2)/h) that followed a power function when plotted against molecular weight. The equation x = 0.02t(0.5) was obtained for palmitic acid that could be used to find its position in millimeters (where the concentration is 50% of its initial value or c0/2) as a function of time in hours. The results show that on a clean silicon substrate, the age of a fingerprint (t ≤ 96 h) could reliably be obtained through the extent of diffusion of palmitic acid.

  19. Dynamics of H{sub 2} Eley-Rideal abstraction from W(110): Sensitivity to the representation of the molecule-surface potential

    SciTech Connect

    Pétuya, R. Larrégaray, P.; Crespos, C.; Busnengo, H. F.; Martínez, A. E.

    2014-07-14

    Dynamics of the Eley-Rideal (ER) abstraction of H{sub 2} from W(110) is analyzed by means of quasi-classical trajectory calculations. Simulations are based on two different molecule-surface potential energy surfaces (PES) constructed from Density Functional Theory results. One PES is obtained by fitting, using a Flexible Periodic London-Eyring-Polanyi-Sato (FPLEPS) functional form, and the other by interpolation through the corrugation reducing procedure (CRP). Then, the present study allows us to elucidate the ER dynamics sensitivity on the PES representation. Despite some sizable discrepancies between both H+H/W(110) PESs, the obtained projectile-energy dependence of the total ER cross sections are qualitatively very similar ensuring that the main physical ingredients are captured in both PES models. The obtained distributions of the final energy among the different molecular degrees of freedom barely depend on the PES model, being most likely determined by the reaction exothermicity. Therefore, a reasonably good agreement with the measured final vibrational state distribution is observed in spite of the pressure and material gaps between theoretical and experimental conditions.

  20. Conformational analysis of bis(methylthio)methane and diethyl sulfide molecules in the liquid phase: reverse Monte Carlo studies using classical interatomic potential functions

    NASA Astrophysics Data System (ADS)

    Gereben, Orsolya; Pusztai, László

    2013-11-01

    Series of flexible molecule reverse Monte Carlo calculations, using bonding and non-bonding interatomic potential functions (FMP-RMC), were performed starting from previous molecular dynamics results that had applied the OPLS-AA and EncadS force fields. During RMC modeling, the experimental x-ray total scattering structure factor was approached. The discrepancy between experimental and calculated structure factors, in comparison with the molecular dynamics results, decreased substantially in each case. The room temperature liquid structure of bis(methylthio)methane is excellently described by the FMP-RMC simulation that applied the EncadS force field parameters. The main conformer was found to be AG with 55.2%, followed by 37.2% of G+G+ (G-G-) and 7.6% of AA; the stability of the G+G+ (G-G-) conformer is most probably caused by the anomer effect. The liquid structure of diethyl sulfide can be best described by applying the OPLS-AA force field parameters during FMP-RMC simulation, although in this case the force field parameters were found to be not fully compatible with experimental data. Here, the two main conformers are AG (50.6%) and the AA (40%). In addition to findings on the actual real systems, a fairly detailed comparison between traditional and FMP-RMC methodology is provided.

  1. Dynamics of H2 Eley-Rideal abstraction from W(110): Sensitivity to the representation of the molecule-surface potential

    NASA Astrophysics Data System (ADS)

    Pétuya, R.; Larrégaray, P.; Crespos, C.; Busnengo, H. F.; Martínez, A. E.

    2014-07-01

    Dynamics of the Eley-Rideal (ER) abstraction of H2 from W(110) is analyzed by means of quasi-classical trajectory calculations. Simulations are based on two different molecule-surface potential energy surfaces (PES) constructed from Density Functional Theory results. One PES is obtained by fitting, using a Flexible Periodic London-Eyring-Polanyi-Sato (FPLEPS) functional form, and the other by interpolation through the corrugation reducing procedure (CRP). Then, the present study allows us to elucidate the ER dynamics sensitivity on the PES representation. Despite some sizable discrepancies between both H+H/W(110) PESs, the obtained projectile-energy dependence of the total ER cross sections are qualitatively very similar ensuring that the main physical ingredients are captured in both PES models. The obtained distributions of the final energy among the different molecular degrees of freedom barely depend on the PES model, being most likely determined by the reaction exothermicity. Therefore, a reasonably good agreement with the measured final vibrational state distribution is observed in spite of the pressure and material gaps between theoretical and experimental conditions.

  2. Expectation-maximization of the potential of mean force and diffusion coefficient in Langevin dynamics from single molecule FRET data photon by photon.

    PubMed

    Haas, Kevin R; Yang, Haw; Chu, Jhih-Wei

    2013-12-12

    The dynamics of a protein along a well-defined coordinate can be formally projected onto the form of an overdamped Lagevin equation. Here, we present a comprehensive statistical-learning framework for simultaneously quantifying the deterministic force (the potential of mean force, PMF) and the stochastic force (characterized by the diffusion coefficient, D) from single-molecule Förster-type resonance energy transfer (smFRET) experiments. The likelihood functional of the Langevin parameters, PMF and D, is expressed by a path integral of the latent smFRET distance that follows Langevin dynamics and realized by the donor and the acceptor photon emissions. The solution is made possible by an eigen decomposition of the time-symmetrized form of the corresponding Fokker-Planck equation coupled with photon statistics. To extract the Langevin parameters from photon arrival time data, we advance the expectation-maximization algorithm in statistical learning, originally developed for and mostly used in discrete-state systems, to a general form in the continuous space that allows for a variational calculus on the continuous PMF function. We also introduce the regularization of the solution space in this Bayesian inference based on a maximum trajectory-entropy principle. We use a highly nontrivial example with realistically simulated smFRET data to illustrate the application of this new method.

  3. Collisions of excited Na atoms with H2 molecules. I. Ab initio potential energy surfaces and qualitative discussion of the quenching process

    NASA Astrophysics Data System (ADS)

    Botschwina, Peter; Meyer, Wilfried; Hertel, Ingolf V.; Reiland, W.

    1981-12-01

    Potential energy surfaces have been calculated for the four lowest electronic states of Na (3 2S, 3 2P)+H2(1Σ+g) by means of the RHF-SCF and PNO-CEPA methods. For the so-called quenching process of Na (3 2P) by H2 at low initial translational energies (E-VRT energy transfer) the energetically most favorable path occurs in C2v symmetry, since—at intermediate Na-H2 separation—the ? 2B2 potential energy surface is attractive. From the CEPA calculations, the crossing point of minimal energy between the ? 2A1 and ? 2B2 surfaces is obtained at Rc = 3.57 a.u. and rc = 2.17 a.u. with an energy difference to the asymptotic limit (R = ∞, r = re) of -0.06 eV. It is thus classically accessible without any initial translational energy, but at low initial translational energies (˜0.1 eV) quenching will be efficient only for arrangements of collision partners close to C2v symmetry. There is little indication of an avoiding crossing with an ionic intermediate correlating asymptotically with Na+ and H2- as was assumed in previous discussions of the quenching process. The dependence of the total quenching cross sections on the initial translational energy is discussed by means of the ''absorbing sphere'' model, taking the initial zero-point vibrational energy of the hydrogen molecule into account. New experimental data of the product channel distribution in H2 for center-of-mass forward scattering are presented. The final vibrational states v' = 3, 2, 1, and 0 of H2 are populated to about 26%, 61%, 13%, and 0%, respectively. The observed distributions in H2 (and D2) may be rationalized by simple dynamic considerations on the basis of the calculated surfaces.

  4. Porous organic molecules

    NASA Astrophysics Data System (ADS)

    Holst, James R.; Trewin, Abbie; Cooper, Andrew I.

    2010-11-01

    Most synthetic materials that show molecular-scale porosity consist of one-, two- or three-dimensional networks. Porous metal-organic frameworks in particular have attracted a lot of recent attention. By contrast, discrete molecules tend to pack efficiently in the solid state, leaving as little empty space as possible, which leads to non-porous materials. This Perspective discusses recent developments with discrete organic molecules that are porous in the solid state. Such molecules, which may be either crystalline or amorphous, can be categorized as either intrinsically porous (containing permanent covalent cavities) or extrinsically porous (inefficiently packed). We focus on the possible advantages of organic molecules over inorganic or hybrid systems in terms of molecular solubility, choice of components and functionalities, and structural mobility and responsiveness in non-covalent extended solids. We also highlight the potential for 'undiscovered' porous systems among the large number of cage-like organic molecules that are already known.

  5. Single molecule electronic devices.

    PubMed

    Song, Hyunwook; Reed, Mark A; Lee, Takhee

    2011-04-12

    Single molecule electronic devices in which individual molecules are utilized as active electronic components constitute a promising approach for the ultimate miniaturization and integration of electronic devices in nanotechnology through the bottom-up strategy. Thus, the ability to understand, control, and exploit charge transport at the level of single molecules has become a long-standing desire of scientists and engineers from different disciplines for various potential device applications. Indeed, a study on charge transport through single molecules attached to metallic electrodes is a very challenging task, but rapid advances have been made in recent years. This review article focuses on experimental aspects of electronic devices made with single molecules, with a primary focus on the characterization and manipulation of charge transport in this regime. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Mobius Molecules

    ERIC Educational Resources Information Center

    Eckert, J. M.

    1973-01-01

    Discusses formation of chemical molecules via Mobius strip intermediates, and concludes that many special physics-chemical properties of the fully closed circular form (1) of polyoma DNA are explainable by this topological feature. (CC)

  7. Interstellar Molecules

    ERIC Educational Resources Information Center

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  8. Modeling Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

  9. Interstellar Molecules

    ERIC Educational Resources Information Center

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  10. Mobius Molecules

    ERIC Educational Resources Information Center

    Eckert, J. M.

    1973-01-01

    Discusses formation of chemical molecules via Mobius strip intermediates, and concludes that many special physics-chemical properties of the fully closed circular form (1) of polyoma DNA are explainable by this topological feature. (CC)

  11. Enumerating molecules.

    SciTech Connect

    Visco, Donald Patrick, Jr.; Faulon, Jean-Loup Michel; Roe, Diana C.

    2004-04-01

    This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

  12. Spectroscopic (FT-IR, FT-Raman, UV, 1H and 13C NMR) profiling and computational studies on methyl 5-methoxy-1H-indole-2-carboxylate: A potential precursor to biologically active molecules

    NASA Astrophysics Data System (ADS)

    Almutairi, Maha S.; Xavier, S.; Sathish, M.; Ghabbour, Hazem A.; Sebastian, S.; Periandy, S.; Al-Wabli, Reem I.; Attia, Mohamed I.

    2017-04-01

    Methyl 5-methoxy-1H-indole-2-carboxylate (MMIC) was prepared via esterification of commercially available 5-methoxyindole-2-carboxylic acid. The title molecule MMIC was characterised using FT-IR and FT-Raman in the ranges of 4000-500 and 4000-50 cm-1, respectively. The fundamental modes of the vibrations were assigned and the UV-visible spectrum of the MMIC molecule was recorded in the range of 200-400 nm to explore its electronic nature. The HOMO-LUMO energy distribution was calculated and the bonding and anti-bonding structures of the title molecule were studied and analysed using the natural bond orbital (NBO) approach. The reactivity of the MMIC molecule was also investigated and both the positive and negative centres of the molecule were identified using chemical descriptors and molecular electrostatic potential (MEP) analysis. The chemical shifts of the 1H and 13C NMR spectra were noted and the magnetic field environment of the MMIC molecule are discussed. The non-linear optical (NLO) properties of the title molecule were studied based on its calculated values of polarisability and hyperpolarisability. All computations were obtained by DFT methods using the 6-311++G (d,p) basis set.

  13. The Jak2 Small Molecule Inhibitor, G6, Reduces the Tumorigenic Potential of T98G Glioblastoma Cells In Vitro and In Vivo

    PubMed Central

    Keserű, György M.; Bisht, Kirpal S.; Wamsley, Heather L.; Sayeski, Peter P.

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common and the most aggressive form of primary brain tumor. Jak2 is a non-receptor tyrosine kinase that is involved in proliferative signaling through its association with various cell surface receptors. Hyperactive Jak2 signaling has been implicated in numerous hematological disorders as well as in various solid tumors including GBM. Our lab has developed a Jak2 small molecule inhibitor known as G6. It exhibits potent efficacy in vitro and in several in vivo models of Jak2-mediated hematological disease. Here, we hypothesized that G6 would inhibit the pathogenic growth of GBM cells expressing hyperactive Jak2. To test this, we screened several GBM cell lines and found that T98G cells express readily detectable levels of active Jak2. We found that G6 treatment of these cells reduced the phosphorylation of Jak2 and STAT3, in a dose-dependent manner. In addition, G6 treatment reduced the migratory potential, invasive potential, clonogenic growth potential, and overall viability of these cells. The effect of G6 was due to its direct suppression of Jak2 function and not via off-target kinases, as these effects were recapitulated in T98G cells that received Jak2 specific shRNA. G6 also significantly increased the levels of caspase-dependent apoptosis in T98G cells, when compared to cells that were treated with vehicle control. Lastly, when T98G cells were injected into nude mice, G6 treatment significantly reduced tumor volume and this was concomitant with significantly decreased levels of phospho-Jak2 and phospho-STAT3 within the tumors themselves. Furthermore, tumors harvested from mice that received G6 had significantly less vimentin protein levels when compared to tumors from mice that received vehicle control solution. Overall, these combined in vitro and in vivo results indicate that G6 may be a viable therapeutic option against GBM exhibiting hyperactivation of Jak2. PMID:25162558

  14. ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

    SciTech Connect

    Heravi, Mitra; Kumala, Slawomir; Rachid, Zakaria; Jean-Claude, Bertrand J.; Radzioch, Danuta; Muanza, Thierry M.

    2015-06-01

    Purpose: ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. Methods and Materials: The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Western blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Results: Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Conclusions: Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings.

  15. Therapeutic Potential of Secreted Molecules Derived from Human Amniotic Fluid Mesenchymal Stem/Stroma Cells in a Mice Model of Colitis.

    PubMed

    Legaki, E; Roubelakis, M G; Theodoropoulos, G E; Lazaris, A; Kollia, A; Karamanolis, G; Marinos, E; Gazouli, M

    2016-10-01

    Inflammatory bowel diseases (IBDs) are the result of pathological immune responses due to environmental factors or microbial antigens into a genetically predisposed individual. Mainly due to their trophic properties, a mounting interest is focused on the use of human mesenchymal stem/stromal cells (hMSCs) to treat IBD disease in animal models. The aim of the study is to test whether the secreted molecules, derived from a specific population of second trimester amniotic fluid mesenchymal stem/stromal cells, the spindle-shaped MSCs (SS-AF-MSCs), could be utilized as a novel therapeutic, cell free approach for IBD therapy. Induction of colitis was achieved by oral administration of dextran sulphate sodium (DSS) (3 % w/v in tap water), for 5 days, to 8-week-old NOD/SCID mice. The progression of colitis was assessed on a daily basis through recording the body weight, stool consistency and bleeding. Conditioned media (CM) derived from SS-AF-MSCs were collected, concentrated and then delivered intraperitoneally into DSS treated mice. To evaluate and determine the inflammatory cytokine levels, histopathological approach was applied. Administration of CM derived from SS-AF-MSCs cells reduced the severity of colitis in mice. More importantly, TGFb1 protein levels were increased in the mice received CM, while TNFa and MMP2 protein levels were decreased, respectively. Accordingly, IL-10 was significantly increased in mice received CM, whereas TNFa and IL-1b were decreased at mRNA level. Our results demonstrated that CM derived from SS-AF-MSCs cells is able to ameliorate DSS-induced colitis in immunodeficient colitis mouse model, and thus, it has a potential for use in IBD therapy.

  16. Imaging-Based High-Throughput Screening Assay To Identify New Molecules with Transmission-Blocking Potential against Plasmodium falciparum Female Gamete Formation

    PubMed Central

    Miguel-Blanco, Celia; Lelièvre, Joël; Delves, Michael J.; Bardera, Ana I.; Presa, Jesús L.; López-Barragán, María José; Ruecker, Andrea; Marques, Sara; Sinden, Robert E.

    2015-01-01

    In response to a call for the global eradication of malaria, drug discovery has recently been extended to identify compounds that prevent the onward transmission of the parasite, which is mediated by Plasmodium falciparum stage V gametocytes. Lately, metabolic activity has been used in vitro as a surrogate for gametocyte viability; however, as gametocytes remain relatively quiescent at this stage, their ability to undergo onward development (gamete formation) may be a better measure of their functional viability. During gamete formation, female gametocytes undergo profound morphological changes and express translationally repressed mRNA. By assessing female gamete cell surface expression of one such repressed protein, Pfs25, as the readout for female gametocyte functional viability, we developed an imaging-based high-throughput screening (HTS) assay to identify transmission-blocking compounds. This assay, designated the P. falciparum female gametocyte activation assay (FGAA), was scaled up to a high-throughput format (Z′ factor, 0.7 ± 0.1) and subsequently validated using a selection of 50 known antimalarials from diverse chemical families. Only a few of these agents showed submicromolar 50% inhibitory concentrations in the assay: thiostrepton, methylene blue, and some endoperoxides. To determine the best conditions for HTS, a robustness test was performed with a selection of the GlaxoSmithKline Tres Cantos Antimalarial Set (TCAMS) and the final screening conditions for this library were determined to be a 2 μM concentration and 48 h of incubation with gametocytes. The P. falciparum FGAA has been proven to be a robust HTS assay faithful to Plasmodium transmission-stage cell biology, and it is an innovative useful tool for antimalarial drug discovery which aims to identify new molecules with transmission-blocking potential. PMID:25801574

  17. Effect of the electrostatic surface potential on the oligomerization of full-length human recombinant prion protein at single-molecule level

    NASA Astrophysics Data System (ADS)

    Wang, Bin; Lou, Zhichao; Zhang, Haiqian; Xu, Bingqian

    2016-03-01

    The electrostatic surface potential (ESP) of prion oligomers has critical influences on the aggregating processes of the prion molecules. The atomic force microscopy (AFM) and structural simulation were combined to investigate the molecular basis of the full-length human recombinant prion oligomerization on mica surfaces. The high resolution non-intrusive AFM images showed that the prion oligomers formed different patterns on mica surfaces at different buffer pH values. The basic binding units for the large oligomers were determined to be prion momoners (Ms), dimers (Ds), and trimers (Ts). The forming of the D and T units happened through the binding of hydrophobic β-sheets of the M units. In contrast, the α-helices of these M, D, and T units were the binding areas for the formation of large oligomers. At pH 4.5, the binding units M, D, and T showed clear polarized ESP distributions on the surface domains, while at pH 7.0, they showed more evenly distributed ESPs. Based on the conformations of oligomers observed from AFM images, the D and T units were more abundantly on mica surface at pH 4.5 because the ESP re-distribution of M units helped to stabilize these larger oligomers. The amino acid side chains involved in the binding interfaces were stabilized by hydrogen bonds and electrostatic interactions. The detailed analysis of the charged side chains at pH 4.5 indicated that the polarized ESPs induced the aggregations among M, D, and T to form larger oligomers. Therefore, the hydrogen bonds and electrostatic interactions worked together to form the stabilized prion oligomers.

  18. Collisions of excited Na atoms with H/sub 2/ molecules. I. Ab initio potential energy surfaces and qualitative discussion of the quenching process

    SciTech Connect

    Botschwina, P.; Meyer, W.; Hertel, I.V.; Reiland, W.

    1981-12-01

    Potential energy surfaces have been calculated for the four lowest electronic states of Na (3 /sup 2/S, 3 /sup 2/P)+H/sub 2/(/sup 1/..sigma../sup +//sub g/) by means of the RHF--SCF and PNO--CEPA methods. For the so-called quenching process of Na (3 /sup 2/P) by H/sub 2/ at low initial translational energies (E--VRT energy transfer) the energetically most favorable path occurs in C/sub 2v/ symmetry, since: at intermediate Na--H/sub 2/ separation: the A /sup 2/B/sub 2/ potential energy surface is attractive. From the CEPA calculations, the crossing point of minimal energy between the X /sup 2/A/sub 1/ and A /sup 2/B/sub 2/ surfaces is obtained at R/sub c/ = 3.57 a.u. and r/sub c/ = 2.17 a.u. with an energy difference to the asymptotic limit (R = infinity, r = r/sub e/) of -0.06 eV. It is thus classically accessible without any initial translational energy, but at low initial translational energies (approx.0.1 eV) quenching will be efficient only for arrangements of collision partners close to C/sub 2v/ symmetry. There is little indication of an avoiding crossing with an ionic intermediate correlating asymptotically with Na/sup +/ and H/sub 2//sup -/ as was assumed in previous discussions of the quenching process. The dependence of the total quenching cross sections on the initial translational energy is discussed by means of the ''absorbing sphere'' model, taking the initial zero-point vibrational energy of the hydrogen molecule into account. New experimental data of the product channel distribution in H/sub 2/ for center-of-mass forward scattering are presented. The final vibrational states v' = 3, 2, 1, and 0 of H/sub 2/ are populated to about 26%, 61%, 13%, and 0%, respectively. The observed distributions in H/sub 2/ (and D/sub 2/) may be rationalized by simple dynamic considerations on the basis of the calculated surfaces.

  19. Renoprotective effects of berberine and its potential effect on the expression of β-arrestins and intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in streptozocin-diabetic nephropathy rats.

    PubMed

    Tang, Li-Qin; Ni, Wei-Jian; Cai, Ming; Ding, Hai-Hua; Liu, Sheng; Zhang, Shan-Tang

    2016-09-01

    Berberine has been shown to exert protective effects against diabetic nephropathy (DN), but the mechanisms involved have not been fully characterized. The aim of the present study was to explore the effects of berberine on the expression of β-arrestins, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in DN rat kidneys and investigate the underlying molecular mechanisms. To create the DN model, rats fed a high-fat and high-glucose diet were injected with a single dose of streptozotocin (35 mg/kg, i.p.). Then, DN rats were either treated or not with berberine (50, 100, 200 mg/kg per day, i.g., 8 weeks). Periodic acid-Schiff staining was used to evaluate renal histopathological changes. Renal tissue levels of β-arrestin 1 and β-arrestin 2 were determined by Western blot analysis, whereas immunohistochemistry was used to determine renal ICAM-1 and VCAM-1 levels. Berberine (100, 200 mg/kg) ameliorated the histopathological changes in the diabetic kidney. Western blot analysis revealed significant increases in ICAM-1 and VCAM-1 levels in the kidneys of DN rats, which were reversed by treatment with 100 and 200 mg/kg berberine. In addition, berberine treatment (50, 100, 200 mg/kg) increased diabetic-induced decreases in β-arrestin 1 and β-arrestin 2. Berberine exhibited renoprotective effects in DN rats. The underlying molecular mechanisms may be associated with changes in the levels and regulation of β-arrestin expression, as well as ICAM-1 and VCAM-1 levels in the rat kidney. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  20. Polyatomic molecule vibrations

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Polyatomic molecule vibrations are analyzed as harmonic vibrations along normal coordinates. The energy eigenvalues are found for linear and nonlinear symmetric triatomic molecules for valence bond models of the potential function with arbitrary coupling coefficients; such models can usually be fitted to observed energy levels with reasonably good accuracy. Approximate normal coordinates for the H2O molecule are discussed. Degenerate vibrational modes such as occur in CO2 are analyzed and expressions for Fermi resonance between close-lying states of the same symmetry are developed. The bending modes of linear triatomic molecules are expressed in terms of Laguerre polynomials in cylindrical coordinates as well as in terms of Hermite polynomials in Cartesian coordinates. The effects of large-amplitude bending such as occur in the C3 molecule are analyzed, along with anharmonic effects, which split the usually degenerate bending mode energy levels. Finally, the vibrational frequencies, degeneracies, and symmetry properties of XY3, X2Y2, and XY4 type molecules are discussed.

  1. Understanding ultracold polar molecules

    NASA Astrophysics Data System (ADS)

    Julienne, Paul

    2009-05-01

    The successful production of a dense sample of ultracold ground state KRb polar molecules [1] opens the door to a new era of research with dipolar gases and lattices of such species. This feat was achieved by first associating a K and a Rb atom to make a weakly bound Feshbach molecule and then coherently transferring the population to the ground vibrational level of the molecule. This talk focuses on theoretical issues associated with making and using ultracold polar molecules, using KRb as an example [2]. Full understanding of this species and the processes by which it is made requires taking advantage of accurate molecular potentials [3], ab initio calculations [4], and the properties of the long-range potential. A highly accurate model is available for KRb for all bound states below the ground state separated atom limit and could be constructed for other species. The next step is to develop an understanding of the interactions between polar molecules, and their control in the ultracold domain. Understanding long-range interactions and threshold resonances will be crucial for future work. [1] K.-K. Ni, et al, Science 322, 231(2008). [2] P. S. Julienne, arXiv:0812:1233. [3] Pashov et al., Phys. Rev. A76, 022511 (2007). [4] S. Kotochigova, et al., arXiv:0901.1486.

  2. Towards temperature-dependent coarse-grained potentials of side-chain interactions for protein folding simulations. I: molecular dynamics study of a pair of methane molecules in water at various temperatures.

    PubMed

    Sobolewski, Emil; Makowski, Mariusz; Oldziej, Stanislaw; Czaplewski, Cezary; Liwo, Adam; Scheraga, Harold A

    2009-09-01

    By means of molecular dynamics simulations of a pair of methane molecules in a TIP3P periodic water box with the NVT scheme at six temperatures and, additionally, the NPT scheme at three temperatures ranging from T = 283 to 373 K, we determined the potential of mean force (PMF) of pairs of interacting methane molecules in water as functions of distance between the methane molecules. The PMFs converge to a single baseline only for r> 11 A at all temperatures. The curves of the dimensionless PMF obtained at different temperatures with the NVT scheme overlap almost perfectly in the region of the contact minimum and still very well in the regions of the desolvation maximum and the solvent-separated minimum, which suggests that the temperature-dependent hydrophobic interaction potentials at constant volume in united-residue force fields can be obtained by scaling the respective dimensionless potentials by RT, R being the universal gas constant. For the dimensionless potentials of mean force obtained with the NPT scheme, the depth of the contact minimum increases, whereas the height of the desolvation maximum and the depth of the solvent-separated minimum decrease with temperature, in agreement with results reported in the literature.

  3. An accurate density functional theory for the vapor-liquid interface of associating chain molecules based on the statistical associating fluid theory for potentials of variable range

    NASA Astrophysics Data System (ADS)

    Gloor, Guy J.; Jackson, George; Blas, Felipe J.; del Río, Elvira Martín; de Miguel, Enrique

    2004-12-01

    A Helmholtz free energy density functional is developed to describe the vapor-liquid interface of associating chain molecules. The functional is based on the statistical associating fluid theory with attractive potentials of variable range (SAFT-VR) for the homogenous fluid [A. Gil-Villegas, A. Galindo, P. J. Whitehead, S. J. Mills, G. Jackson, and A. N. Burgess, J. Chem. Phys. 106, 4168 (1997)]. A standard perturbative density functional theory (DFT) is constructed by partitioning the free energy density into a reference term (which incorporates all of the short-range interactions, and is treated locally) and an attractive perturbation (which incorporates the long-range dispersion interactions). In our previous work [F. J. Blas, E. Martı´n del Rı´o, E. de Miguel, and G. Jackson, Mol. Phys. 99, 1851 (2001); G. J. Gloor, F. J. Blas, E. Martı´n del Rı´o, E. de Miguel, and G. Jackson, Fluid Phase Equil. 194, 521 (2002)] we used a mean-field version of the theory (SAFT-HS) in which the pair correlations were neglected in the attractive term. This provides only a qualitative description of the vapor-liquid interface, due to the inadequate mean-field treatment of the vapor-liquid equilibria. Two different approaches are used to include the correlations in the attractive term: in the first, the free energy of the homogeneous fluid is partitioned such that the effect of correlations are incorporated in the local reference term; in the second, a density averaged correlation function is incorporated into the perturbative term in a similar way to that proposed by Toxvaerd [S. Toxvaerd, J. Chem. Phys. 64, 2863 (1976)]. The latter is found to provide the most accurate description of the vapor-liquid surface tension on comparison with new simulation data for a square-well fluid of variable range. The SAFT-VR DFT is used to examine the effect of molecular chain length and association on the surface tension. Different association schemes (dimerization, straight and

  4. Dependences of Q-branch integrated intensity of linear-molecule pendular spectra on electric-field strength and rotational temperature and its potential applications

    PubMed Central

    Deng, Min; Wang, Hailing; Wang, Qin; Yin, Jianping

    2016-01-01

    We calculate the pendular-state spectra of cold linear molecules, and investigated the dependences of “Q-branch” integrated intensity of pendular spectra on both electric-field strength and molecular rotation-temperature. A new multi-peak structure in the “Q-branch” spectrum is appearing when the Stark interaction strength ω = μE/B equal to or larger than the critical value. Our study shows that the above results can be used not only to measure the electric-field vector and its spatial distribution in some electrostatic devices, such as the Stark decelerator, Stark velocity filter and electrostatic trap and so on, but also to survey the orientation degree of cold linear molecules in a strong electrostatic field. PMID:27231057

  5. Resveratrol-loaded nanoparticles conjugated with kidney injury molecule-1 as a drug delivery system for potential use in chronic kidney disease.

    PubMed

    Lin, Yuh-Feng; Lee, Yu-Hsuan; Hsu, Yung-Ho; Chen, Yi-Jie; Lin, Yuan-Feng; Cheng, Fong-Yu; Chiu, Hui-Wen

    2017-09-08

    We used resveratrol (Res)-loaded nanoparticles (Res NPs) as a novel method for improving the pharmacokinetic properties of Res and analyzed the effect of Res NPs in chronic kidney disease (CKD). We coupled anti-kidney injury molecule-1 antibodies to Res NPs and analyzed safety and efficacy. Res NPs had low toxicity and induced autophagy. Res NPs inhibited the NLRP3 inflammasome and IL-1β secretion. Higher NLRP3 expression levels were observed in peripheral blood monocytic cells of CKD patients than healthy individuals. Treatment with kidney injury molecule-1-Res NPs significantly reduced creatinine and protected against tubulointerstitial injury in a murine model of CKD. Res NPs through NLRP3 inflammasome attenuation and autophagy induction may be as a strategy to prevent CKD.

  6. Dependences of Q-branch integrated intensity of linear-molecule pendular spectra on electric-field strength and rotational temperature and its potential applications

    NASA Astrophysics Data System (ADS)

    Deng, Min; Wang, Hailing; Wang, Qin; Yin, Jianping

    2016-05-01

    We calculate the pendular-state spectra of cold linear molecules, and investigated the dependences of “Q-branch” integrated intensity of pendular spectra on both electric-field strength and molecular rotation-temperature. A new multi-peak structure in the “Q-branch” spectrum is appearing when the Stark interaction strength ω = μE/B equal to or larger than the critical value. Our study shows that the above results can be used not only to measure the electric-field vector and its spatial distribution in some electrostatic devices, such as the Stark decelerator, Stark velocity filter and electrostatic trap and so on, but also to survey the orientation degree of cold linear molecules in a strong electrostatic field.

  7. The potential utility of predicted one bond carbon-proton coupling constants in the structure elucidation of small organic molecules by NMR spectroscopy.

    PubMed

    Venkata, Chandrasekhar; Forster, Mark J; Howe, Peter W A; Steinbeck, Christoph

    2014-01-01

    NMR spectroscopy is the most popular technique used for structure elucidation of small organic molecules in solution, but incorrect structures are regularly reported. One-bond proton-carbon J-couplings provide additional information about chemical structure because they are determined by different features of molecular structure than are proton and carbon chemical shifts. However, these couplings are not routinely used to validate proposed structures because few software tools exist to predict them. This study assesses the accuracy of Density Functional Theory for predicting them using 396 published experimental observations from a diverse range of small organic molecules. With the B3LYP functional and the TZVP basis set, Density Functional Theory calculations using the open-source software package NWChem can predict one-bond CH J-couplings with good accuracy for most classes of small organic molecule. The root-mean-square deviation after correction is 1.5 Hz for most sp3 CH pairs and 1.9 Hz for sp2 pairs; larger errors are observed for sp3 pairs with multiple electronegative substituents and for sp pairs. These results suggest that prediction of one-bond CH J-couplings by Density Functional Theory is sufficiently accurate for structure validation. This will be of particular use in strained ring systems and heterocycles which have characteristic couplings and which pose challenges for structure elucidation.

  8. The Potential Utility of Predicted One Bond Carbon-Proton Coupling Constants in the Structure Elucidation of Small Organic Molecules by NMR Spectroscopy

    PubMed Central

    Venkata, Chandrasekhar; Forster, Mark J.; Howe, Peter W. A.; Steinbeck, Christoph

    2014-01-01

    NMR spectroscopy is the most popular technique used for structure elucidation of small organic molecules in solution, but incorrect structures are regularly reported. One-bond proton-carbon J-couplings provide additional information about chemical structure because they are determined by different features of molecular structure than are proton and carbon chemical shifts. However, these couplings are not routinely used to validate proposed structures because few software tools exist to predict them. This study assesses the accuracy of Density Functional Theory for predicting them using 396 published experimental observations from a diverse range of small organic molecules. With the B3LYP functional and the TZVP basis set, Density Functional Theory calculations using the open-source software package NWChem can predict one-bond CH J-couplings with good accuracy for most classes of small organic molecule. The root-mean-square deviation after correction is 1.5 Hz for most sp3 CH pairs and 1.9 Hz for sp2 pairs; larger errors are observed for sp3 pairs with multiple electronegative substituents and for sp pairs. These results suggest that prediction of one-bond CH J-couplings by Density Functional Theory is sufficiently accurate for structure validation. This will be of particular use in strained ring systems and heterocycles which have characteristic couplings and which pose challenges for structure elucidation. PMID:25365289

  9. The Crystal Structure of OprG from Pseudomonas aeruginosa a Potential Channel for Transport of Hydrophobic Molecules across the Outer Membrane

    SciTech Connect

    D Touw; D Patel; b van den Berg

    2011-12-31

    The outer membrane (OM) of Gram-negative bacteria provides a barrier to the passage of hydrophobic and hydrophilic compounds into the cell. The OM has embedded proteins that serve important functions in signal transduction and in the transport of molecules into the periplasm. The OmpW family of OM proteins, of which P. aeruginosa OprG is a member, is widespread in Gram-negative bacteria. The biological functions of OprG and other OmpW family members are still unclear. The outer membrane (OM) of Gram-negative bacteria provides a barrier to the passage of hydrophobic and hydrophilic compounds into the cell. The OM has embedded proteins that serve important functions in signal transduction and in the transport of molecules into the periplasm. The OmpW family of OM proteins, of which P. aeruginosa OprG is a member, is widespread in Gram-negative bacteria. The biological functions of OprG and other OmpW family members are still unclear. The crystal structure, together with recent biochemical data, suggests that OprG and other OmpW family members form channels that mediate the diffusion of small hydrophobic molecules across the OM by a lateral diffusion mechanism similar to that of E. coli FadL.

  10. HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer’s disease

    PubMed Central

    Fujita, Kyota; Motoki, Kazumi; Tagawa, Kazuhiko; Chen, Xigui; Hama, Hiroshi; Nakajima, Kazuyuki; Homma, Hidenori; Tamura, Takuya; Watanabe, Hirohisa; Katsuno, Masahisa; Matsumi, Chiemi; Kajikawa, Masunori; Saito, Takashi; Saido, Takaomi; Sobue, Gen; Miyawaki, Atsushi; Okazawa, Hitoshi

    2016-01-01

    Alzheimer’s disease (AD) is the most common neurodegenerative disease, but it remains an intractable condition. Its pathogenesis is predominantly attributed to the aggregation and transmission of two molecules, Aβ and tau; however, other pathological mechanisms are possible. Here, we reveal that phosphorylation of MARCKS, a submembrane protein that regulates the stability of the actin network, occurs at Ser46 prior to aggregation of Aβ and is sustained throughout the course of AD in human and mouse brains. Furthermore, HMGB1 released from necrotic or hyperexcitatory neurons binds to TLR4, triggers the specific phosphorylation of MARCKS via MAP kinases, and induces neurite degeneration, the classical hallmark of AD pathology. Subcutaneous injection of a newly developed monoclonal antibody against HMGB1 strongly inhibits neurite degeneration even in the presence of Aβ plaques and completely recovers cognitive impairment in a mouse model. HMGB1 and Aβ mutually affect polymerization of the other molecule, and the therapeutic effects of the anti-HMGB1 monoclonal antibody are mediated by Aβ-dependent and Aβ-independent mechanisms. We propose that HMGB1 is a critical pathogenic molecule promoting AD pathology in parallel with Aβ and tau and a new key molecular target of preclinical antibody therapy to delay the onset of AD. PMID:27557632

  11. The coupled cluster approach with a hybrid treatment of connected triple excitations: Spectroscopic constants in open-shell diatomic molecules, and bond-breaking or twisting potential energy surfaces

    NASA Astrophysics Data System (ADS)

    Kou, Zhuangfei; Shen, Jun; Xu, Enhua; Li, Shuhua

    2012-06-01

    A coupled cluster singles, doubles, and a hybrid treatment of triples [denoted as CCSD(T)-h] has been applied to investigate the equilibrium geometries and harmonic frequencies of five diatomic open-shell molecules, bond breaking potential energy surfaces in C2 and F2+, and the twisting potential energy surface of ethylene. In the present work, CCSD(T)-h calculations are based on the restricted or restricted open-shell Hartree-Fock (RHF or ROHF) reference. A general procedure for constructing the active RHF or ROHF orbitals is proposed. A comparison of CCSD(T)-h with other CC methods show that for all systems CCSD(T)-h is an excellent approximation to CCSDT, being much better than CCSD(T) especially when a molecule exhibits strong multireference character.

  12. Spin-orbit configuration interaction study of potential energy curves and transition probabilities of the mercury hydride molecule and tests of relativistic effective core potentials for Hg, Hg + , and Hg2 +

    NASA Astrophysics Data System (ADS)

    Alekseyev, Aleksey B.; Liebermann, Heinz-Peter; Buenker, Robert J.; Hirsch, Gerhard

    1996-03-01

    Ab initio CI calculations have been carried out for the low-energy states of the mercury hydride molecule HgH and its isotopomers. A relativistic effective core potential (RECP) given by Ross et al. [J. Chem. Phys. 93, 6654 (1990)] is employed to describe all but the Hg 5d and 6s valence electrons. Tests for a series of low-lying states of Hg, Hg+, and Hg2+ demonstrate that 0.1 eV accuracy is obtained at the SCF level with a high-quality basis set for this RECP in comparison with all-electron Dirac-Fock results up to 32 eV excitation energy. The DF values are themselves in error by 1-3 eV on the average compared to experiment, but the present CI calculations based on this RECP lead to considerably higher accuracy because of the importance of correlation effects in such determinations. Energy differences (12 cases) between states with the same number of electrons are computed to an accuracy of 0.1-0.2 eV in all cases after the spin-orbit interaction is included. These results compare favorably with those obtained by Häussermann et al. [Mol. Phys. 78, 1211 (1993)] with a ... 5s2 5p6 5d10 6s2 RECP and a corresponding larger AO basis to describe the more tightly bound electrons. Good agreement is found for the spectroscopic constants of the HgH molecule in its lowest four electronic states: X 2Σ+1/2, A1 2Π1/2, A2 2Π3/2, and B 2Σ+1/2 (maximal errors of 1000 cm-1 for Te, 0.03 Å for re and 150 cm-1 for ωe). An RKR curve reported for the A1 state is shown to be in error beyond r=4.0 a0 because of its failure to describe a key avoided crossing with the B state. Radiative lifetimes computed for the A 2Π multiplets are both found to agree with values deduced from experiment to within 40%. The calculations find no difference in the HgH and HgD radiative lifetimes for either the A1 or the A2 states, whereas a large distinction in the measured A1 lifetimes of the two isotopomers is observed, thereby supporting the previous experimental conclusion that strong

  13. Single-Molecule Bioelectronics

    PubMed Central

    Rosenstein, Jacob K.; Lemay, Serge G.; Shepard, Kenneth L.

    2014-01-01

    Experimental techniques which interface single biomolecules directly with microelectronic systems are increasingly being used in a wide range of powerful applications, from fundamental studies of biomolecules to ultra-sensitive assays. Here we review several technologies which can perform electronic measurements of single molecules in solution: ion channels, nanopore sensors, carbon nanotube field-effect transistors, electron tunneling gaps, and redox cycling. We discuss the shared features among these techniques that enable them to resolve individual molecules, and discuss their limitations. Recordings from each of these methods all rely on similar electronic instrumentation, and we discuss the relevant circuit implementations and potential for scaling these single-molecule bioelectronic interfaces to high-throughput arrayed sensing platforms. PMID:25529538

  14. Dimethylamine Addition to Formaldehyde Catalyzed by a Single Water Molecule: A Facile Route for Atmospheric Carbinolamine Formation and Potential Promoter of Aerosol Growth.

    PubMed

    Louie, Matthew K; Francisco, Joseph S; Verdicchio, Marco; Klippenstein, Stephen J; Sinha, Amitabha

    2016-03-10

    We use ab initio calculations to investigate the energetics and kinetics associated with carbinolamine formation resulting from the addition of dimethylamine to formaldehyde catalyzed by a single water molecule. Further, we compare the energetics for this reaction with that for the analogous reactions involving methylamine and ammonia separately. We find that the reaction barrier for the addition of these nitrogen-containing molecules onto formaldehyde decreases along the series ammonia, methylamine, and dimethylamine. Hence, starting with ammonia, the reaction barrier can be "tuned" by the substitution of an alkyl group in place of a hydrogen atom. The reaction involving dimethylamine has the lowest barrier with the transition state being 5.4 kcal/mol below the (CH3)2NH + H2CO + H2O separated reactants. This activation energy is significantly lower than that for the bare reaction occurring without water, H2CO + (CH3)2NH, which has a barrier of 20.1 kcal/mol. The negative barrier associated with the single-water molecule catalyzed reaction of dimethylamine with H2CO to form the carbinolamine (CH3)2NCH2OH suggests that this reaction should be energetically feasible under atmospheric conditions. This is confirmed by rate calculations which suggest that the reaction will be facile even in the gas phase. As amines and oxidized organics containing carbonyl functional groups are common components of secondary organic aerosols, the present finding has important implications for understanding how larger, less volatile organic compounds can be generated in the atmosphere by combining readily available smaller components as required for promoting aerosol growth.

  15. Scanning the potential energy surface for synthesis of dendrimer-wrapped gold clusters: design rules for true single-molecule nanostructures.

    PubMed

    Thompson, Damien; Hermes, Jens P; Quinn, Aidan J; Mayor, Marcel

    2012-04-24

    The formation of true single-molecule complexes between organic ligands and nanoparticles is challenging and requires careful design of molecules with size, shape, and chemical properties tailored for the specific nanoparticle. Here we use computer simulations to describe the atomic-scale structure, dynamics, and energetics of ligand-mediated synthesis and interlinking of 1 nm gold clusters. The models help explain recent experimental results and provide insight into how multidentate thioether dendrimers can be employed for synthesis of true single-ligand-nanoparticle complexes and also nanoparticle-molecule-nanoparticle "dumbbell" nanostructures. Electronic structure calculations reveal the individually weak thioether-gold bonds (325 ± 36 meV), which act collectively through the multivalent (multisite) anchoring to stabilize the ligand-nanoparticle complex (∼7 eV total binding energy) and offset the conformational and solvation penalties involved in this "wrapping" process. Molecular dynamics simulations show that the dendrimer is sufficiently flexible to tolerate the strained conformations and desolvation penalties involved in fully wrapping the particle, quantifying the subtle balance between covalent anchoring and noncovalent wrapping in the assembly of ligand-nanoparticle complexes. The computed preference for binding of a single dendrimer to the cluster reveals the prohibitively high dendrimer desolvation barrier (1.5 ± 0.5 eV) to form the alternative double-dendrimer structure. Finally, the models show formation of an additional electron transfer channel between nitrogen and gold for ligands with a central pyridine unit, which gives a stiff binding orientation and explains the recently measured larger interparticle distances for particles synthesized and interlinked using linear ligands with a central pyridine rather than a benzene moiety. The findings stress the importance of organic-inorganic interactions, the control of which is central to the

  16. Effects of molecular potential and geometry on atomic core-level photoemission over an extended energy range - the case study of CO molecule

    NASA Astrophysics Data System (ADS)

    Kukk, E.; Ayuso, D.; Thomas, T. D.; Decleva, P.; Patanen, M.; Argenti, L.; Plésiat, E.; Palacios, A.; Kooser, K.; Travnikova, O.; Mondal, S.; Kimura, M.; Sakai, K.; Miron, C.; Martín, F.; Ueda, K.

    2014-04-01

    We report an experimental and theoretical study of single-molecule inner-shell photoemission over an extended range of photon energies. The vibrational ratios v=1/v=0 from the C 1s photoelectron spectra, although mostly determined by the bond length change, are shown to be affected also by photoelectron recoil and scattering on the neighboring oxygen atom. Density functional theory is used to encompass all these effect in unified treatment. It is also demonstrated that the DFT calculations can be used as a means to extract dynamic and static molecular geometry values.

  17. Potential energy surfaces for atomic oxygen reactions: Formation of singlet and triplet biradicals as primary reaction products with unsaturated organic molecules

    NASA Technical Reports Server (NTRS)

    Jaffe, Richard L.

    1987-01-01

    The experimental study of the interaction of atomic oxygen with organic polymer films under LEO conditions has been hampered by the inability to conduct detailed experiments in situ. As a result, studies of the mechanism of oxygen atom reactions have relied on laboratory O-atom sources that do not fully reproduce the orbital environment. For example, it is well established that only ground electronic state O atoms are present at LEO, yet most ground-based sources are known to produce singlet O atoms and molecules and ions in addition to O(3P). Engineers should not rely on such facilities unless it can be demonstrated either that these different O species are inert or that they react in the same fashion as ground state atoms. Ab initio quantum chemical calculations have been aimed at elucidating the biradical intermediates formed during the electrophilic addition of ground and excited-state O atoms to carbon-carbon double bonds in small olefins and aromatic molecules. These biradicals are critical intermediates in any possible insertion, addition and elimination reaction mechanisms. Through these calculations, we will be able to comment on the relative importance of these pathways for O(3P) and O(1D) reactions. The reactions of O atoms with ethylene and benzene are used to illustrate the important features of the mechanisms of atomic oxygen reaction with unsaturated organic compounds and polymeric materials.

  18. The genetically modified polysialylated form of neural cell adhesion molecule-positive cells for potential treatment of X-linked adrenoleukodystrophy.

    PubMed

    Jang, Jiho; Kim, Han-Soo; Kang, Joon Won; Kang, Hoon-Chul

    2013-01-01

    Cell transplantation of myelin-producing exogenous cells is being extensively explored as a means of remyelinating axons in X-linked adrenoleukodystrophy. We determined whether 3,3',5-Triiodo-L-thyronine (T3) overexpresses the ABCD2 gene in the polysialylated (PSA) form of neural cell adhesion molecule (NCAM)-positive cells and promotes cell proliferation and favors oligodendrocyte lineage differentiation. PSA-NCAM+ cells from newborn Sprague-Dawley rats were grown for five days on uncoated dishes in defined medium with or without supplementation of basic fibroblast growth factor (bFGF) and/or T3. Then, PSA-NCAM+ spheres were prepared in single cells and transferred to polyornithine/fibronectin-coated glass coverslips for five days to determine the fate of the cells according to the supplementation of these molecules. T3 responsiveness of ABCD2 was analyzed using real-time quantitative polymerase chain reaction, the growth and fate of cells were determined using 5-bromo-2-deoxyuridine incorporation and immunocytochemistry, respectively. Results demonstrated that T3 induces overexpression of the ABCD2 gene in PSA-NCAM+ cells, and can enhance PSA-NCAM+ cell growth in the presence of bFGF, favoring an oligodendrocyte fate. These results may provide new insights into investigation of PSA-NCAM+ cells for therapeutic application to X-linked adrenoleukodystrophy.

  19. Targeting the intrinsically disordered structural ensemble of α-synuclein by small molecules as a potential therapeutic strategy for Parkinson's disease.

    PubMed

    Tóth, Gergely; Gardai, Shyra J; Zago, Wagner; Bertoncini, Carlos W; Cremades, Nunilo; Roy, Susan L; Tambe, Mitali A; Rochet, Jean-Christophe; Galvagnion, Celine; Skibinski, Gaia; Finkbeiner, Steven; Bova, Michael; Regnstrom, Karin; Chiou, San-San; Johnston, Jennifer; Callaway, Kari; Anderson, John P; Jobling, Michael F; Buell, Alexander K; Yednock, Ted A; Knowles, Tuomas P J; Vendruscolo, Michele; Christodoulou, John; Dobson, Christopher M; Schenk, Dale; McConlogue, Lisa

    2014-01-01

    The misfolding of intrinsically disordered proteins such as α-synuclein, tau and the Aβ peptide has been associated with many highly debilitating neurodegenerative syndromes including Parkinson's and Alzheimer's diseases. Therapeutic targeting of the monomeric state of such intrinsically disordered proteins by small molecules has, however, been a major challenge because of their heterogeneous conformational properties. We show here that a combination of computational and experimental techniques has led to the identification of a drug-like phenyl-sulfonamide compound (ELN484228), that targets α-synuclein, a key protein in Parkinson's disease. We found that this compound has substantial biological activity in cellular models of α-synuclein-mediated dysfunction, including rescue of α-synuclein-induced disruption of vesicle trafficking and dopaminergic neuronal loss and neurite retraction most likely by reducing the amount of α-synuclein targeted to sites of vesicle mobilization such as the synapse in neurons or the site of bead engulfment in microglial cells. These results indicate that targeting α-synuclein by small molecules represents a promising approach to the development of therapeutic treatments of Parkinson's disease and related conditions.

  20. Targeting the Intrinsically Disordered Structural Ensemble of α-Synuclein by Small Molecules as a Potential Therapeutic Strategy for Parkinson’s Disease

    PubMed Central

    Tóth, Gergely; Gardai, Shyra J.; Zago, Wagner; Bertoncini, Carlos W.; Cremades, Nunilo; Roy, Susan L.; Tambe, Mitali A.; Rochet, Jean-Christophe; Galvagnion, Celine; Skibinski, Gaia; Finkbeiner, Steven; Bova, Michael; Regnstrom, Karin; Chiou, San-San; Johnston, Jennifer; Callaway, Kari; Anderson, John P.; Jobling, Michael F.; Buell, Alexander K.; Yednock, Ted A.; Knowles, Tuomas P. J.; Vendruscolo, Michele; Christodoulou, John; Dobson, Christopher M.; Schenk, Dale; McConlogue, Lisa

    2014-01-01

    The misfolding of intrinsically disordered proteins such as α-synuclein, tau and the Aβ peptide has been associated with many highly debilitating neurodegenerative syndromes including Parkinson’s and Alzheimer’s diseases. Therapeutic targeting of the monomeric state of such intrinsically disordered proteins by small molecules has, however, been a major challenge because of their heterogeneous conformational properties. We show here that a combination of computational and experimental techniques has led to the identification of a drug-like phenyl-sulfonamide compound (ELN484228), that targets α-synuclein, a key protein in Parkinson’s disease. We found that this compound has substantial biological activity in cellular models of α-synuclein-mediated dysfunction, including rescue of α-synuclein-induced disruption of vesicle trafficking and dopaminergic neuronal loss and neurite retraction most likely by reducing the amount of α-synuclein targeted to sites of vesicle mobilization such as the synapse in neurons or the site of bead engulfment in microglial cells. These results indicate that targeting α-synuclein by small molecules represents a promising approach to the development of therapeutic treatments of Parkinson’s disease and related conditions. PMID:24551051

  1. Towards single molecule DNA sequencing

    NASA Astrophysics Data System (ADS)

    Liu, Hao

    Single molecule DNA Sequencing technology has been a hot research topic in the recent decades because it holds the promise to sequence a human genome in a fast and affordable way, which will eventually make personalized medicine possible. Single molecule differentiation and DNA translocation control are the two main challenges in all single molecule DNA sequencing methods. In this thesis, I will first introduce DNA sequencing technology development and its application, and then explain the performance and limitation of prior art in detail. Following that, I will show a single molecule DNA base differentiation result obtained in recognition tunneling experiments. Furthermore, I will explain the assembly of a nanofluidic platform for single strand DNA translocation, which holds the promised to be integrated into a single molecule DNA sequencing instrument for DNA translocation control. Taken together, my dissertation research demonstrated the potential of using recognition tunneling techniques to serve as a general readout system for single molecule DNA sequencing application.

  2. Effects of molecular potential and geometry on atomic core-level photoemission over an extended energy range: The case study of the CO molecule

    NASA Astrophysics Data System (ADS)

    Kukk, E.; Ayuso, D.; Thomas, T. D.; Decleva, P.; Patanen, M.; Argenti, L.; Plésiat, E.; Palacios, A.; Kooser, K.; Travnikova, O.; Mondal, S.; Kimura, M.; Sakai, K.; Miron, C.; Martín, F.; Ueda, K.

    2013-09-01

    We report an experimental and theoretical study of single-molecule inner-shell photoemission measured over an extended range of photon energies. The vibrational intensity ratios I(ν=1)/I(ν=0) from the C 1s photoelectron spectra of carbon monoxide, although mostly determined by the bond length change upon ionization, are shown to be affected also by photoelectron recoil and by scattering from the neighboring oxygen atom. Static-exchange density functional theory (DFT) is used to encompass all these effects in a unified theoretical treatment. The ab initio calculations show that the vibrational ratio as a function of the photoelectron momentum is sensitive to both the ground-state internuclear distance and its contraction upon photoionization. We present a proof-of-principle application of DFT calculations as a quantitative structural analysis tool for extracting the dynamic and static molecular geometry parameters simultaneously.

  3. Spectroscopic and magnetic studies of erbium(III)-TEMPO complex as a potential single-molecule magnet: Interplay of the crystal-field and exchange coupling effects

    NASA Astrophysics Data System (ADS)

    Karbowiak, Mirosław; Rudowicz, Czesław; Nakamura, Takeshi; Murakami, Rina; Ishida, Takayuki

    2016-10-01

    Crystallographic, spectroscopic, and magnetic studies of three-center systems: lanthanoid-Ln3+ ions doubly-coordinated by TEMPO (2,2,6,6-tetramethylpiperidin-1-oxyl) radicals [Ln-TEMPO2] are reported. The temperature dependence of alternating-current magnetic susceptibility indicates the single-molecule-magnet behavior of Er-TEMPO2, exhibiting relatively slow magnetization relaxation. Well-resolved absorption spectra were obtained only for Er-TEMPO2. Other samples yielded spectra not amenable for meaningful interpretation. The crystal-field parameters (CFPs) determined from the measured Er3+-energy levels served as starting CFPs for fitting the direct-current magnetic susceptibility result. Compatibility of the so-determined and fine-tuned CFPs, and interplay between crystal-field-related effects and exchange-coupling effects are considered. Exchange couplings in Ln-TEMPO2 appear antiferromagnetic and unexpectedly large.

  4. The gonadotropin releasing hormone (GnRH)-like molecule in prosobranch Patella caerulea: potential biomarker of endocrine-disrupting compounds in marine environments.

    PubMed

    De Lisa, Emilia; Carella, Francesca; De Vico, Gionata; Di Cosmo, Anna

    2013-02-01

    It has been reported that endocrine disrupter compounds (EDCs) interfere with the endocrine system, mimicking the action of sex steroid hormones in different species of mollusks. Prosobranchs are frequently used as a reliable bioindicator to evaluate EDC exposure. In this article, we evaluate the effects of the xenoestrogen 4-n-nonylphenol (NP) in the prosobranch gastropod Patella caerulea, which exhibits protandrous hermaphroditism as its reproductive strategy. We isolated a partial sequence of a GnRH-like molecule from the gonads of Patella caerulea. The deduced amino acid sequence is highly homologous to that reported for the Lottia gigantea GnRH. Patella caerulea GnRH (pGnRH) mRNA expression is widespread in both male and female germ lines during gametogenesis. We suggest pGnRH as a novel biomarker for the early assessment of presence of EDCs and monitoring short and long-term impacts on Patella caerulea community structure.

  5. Experimental and theoretical investigation of the molecular structure, conformational stability, hyperpolarizability, electrostatic potential, thermodynamic properties and NMR spectra of pharmaceutical important molecule: 4‧-Methylpropiophenone

    NASA Astrophysics Data System (ADS)

    Karunakaran, V.; Balachandran, V.

    2014-07-01

    Combined experimental and theoretical studies have been performed on the structure and vibrational spectra (IR and Raman spectra) of 4‧-methylpropiophenone (MPP). The FT-IR and FT-Raman spectra of 4‧-methylpropiophenone (MPP) have been recorded in the region 4000-400 cm-1 and 3500-100 cm-1, respectively. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FT-IR and FT-Raman spectra. A detailed interpretation of the infrared and Raman spectra of MPP are also reported based on total energy distribution (TED). The observed and the calculated frequencies are found to be in good agreement. The 1H and 13C NMR chemical shifts have been calculated by Gauge-Independent Atomic Orbital (GIAO) method with B3LYP/6-311++G(d,p). The natural bond orbital (NBO), natural hybrid orbital (NHO) analysis and electronic properties, such as HOMO and LUMO energies, were performed by DFT approach. The calculated HOMO and LUMO energies show that charge transfer occurs within molecule. The first order hyperpolarizability (β0) of the novel molecular system and related properties (βtot, α0 and Δα) of MPP are calculated using DFT/6-311++G(d,p) method on the finite-field approach. The Mulliken charges, the values of electric dipole moment (μ) of the molecule were computed using DFT calculations. The thermodynamic functions of the title compound were also performed at the above method and basis set.

  6. A four-dimensional potential energy surface and predicted infrared spectra for the Ne-D2O van der Waals complex in the ν2 bending region of D2O molecule

    NASA Astrophysics Data System (ADS)

    He, Shanshan; Chen, Dong; Li, Ya; Feng, Eryin; Huang, Wuying

    2016-11-01

    In this paper, a four-dimensional potential energy surface (PES) for the Ne-D2O complex is constructed theoretically. The calculations are carried out at CCSD(T) level with large basis sets augmented with mid-bond functions. The PES includes explicit dependence on the ν2 symmetric bending coordinate Q2 of the D2O molecule. Two vibrationally averaged potentials in the ground and first excited bending states are obtained respectively. Using these two potentials we calculate the bound states of the complexes. The theoretical rovibrational transition frequencies for three bands: П(111,ν2 = 1)←Σ000, Σ(111,ν2 = 1)←Σ000 and n = 1, Σ(000,ν2 = 1)←Σ000 are predicted and generally in good agreement with the experimental observed values.

  7. A Novel Small Molecule Inhibitor of Candida albicans Biofilm Formation, Filamentation and Virulence with Low Potential for the Development of Resistance

    PubMed Central

    Pierce, Christopher G.; Chaturvedi, Ashok K.; Lazzell, Anna L.; Powell, Alexander T.; Saville, Stephen. P.; McHardy, Stanton F.; Lopez-Ribot, Jose L.

    2015-01-01

    Background/Objectives Candida albicans is the principal causative agent of candidiasis, the most common fungal infection in humans. Candidiasis represents the third-to-fourth most frequent nosocomial infection worldwide, as this normal commensal of humans causes opportunistic infections in an expanding population of immune- and medically-compromised patients. These infections are frequently associated with biofilm formation, which complicates treatment and contributes to unacceptably high mortality rates. Methods To address the pressing need for new antifungals we have performed a high content screen of 20,000 small molecules in a chemical library (NOVACore™) to identify compounds that inhibit C. albicans biofilm formation, and conducted a series of follow-up studies to examine the in vitro and in vivo activity of the identified compounds. Results The screen identified a novel series of diazaspiro-decane structural analogs which were largely represented among the bioactive compounds. Characterization of the leading compound from this series indicated that it inhibits processes associated with C. albicans virulence, most notably biofilm formation and filamentation, without having an effect on overall growth or eliciting resistance. This compound demonstrated in vivo activity in clinically-relevant murine models of both invasive and oral candidiasis and as such represents a promising lead for antifungal drug development. Furthermore, these results provide proof of concept for the implementation of anti-virulence approaches against C. albicans and other fungal infections that would be less likely to foster the emergence of resistance. PMID:26691764

  8. Structural and Energetic Impact of Non-Natural 7-Deaza-8-Azaadenine and Its 7-Substituted Derivatives on H-Bonding Potential with Uracil in RNA Molecules.

    PubMed

    Chawla, Mohit; Credendino, Raffaele; Oliva, Romina; Cavallo, Luigi

    2015-10-15

    Non-natural (synthetic) nucleobases, including 7-ethynyl- and 7-triazolyl-8-aza-7-deazaadenine, have been introduced in RNA molecules for targeted applications, and have been characterized experimentally. However, no theoretical characterization of the impact of these modifications on the structure and energetics of the corresponding H-bonded base pair is available. To fill this gap, we performed quantum mechanics calculations, starting with the analysis of the impact of the 8-aza-7-deaza modification of the adenine skeleton, and we moved then to analyze the impact of the specific substituents on the modified 8-aza-7-deazaadenine. Our analysis indicates that, despite of these severe structural modifications, the H-bonding properties of the modified base pair gratifyingly replicate those of the unmodified base pair. Similar behavior is predicted when the same skeleton modifications are applied to guanine when paired to cytosine. To stress further the H-bonding pairing in the modified adenine-uracil base pair, we explored the impact of strong electron donor and electron withdrawing substituents on the C7 position. Also in this case we found minimal impact on the base pair geometry and energy, confirming the validity of this modification strategy to functionalize RNAs without perturbing its stability and biological functionality.

  9. Rotational excitation of symmetric top molecules by collisions with atoms: Close coupling, coupled states, and effective potential calculations for NH3-He

    NASA Technical Reports Server (NTRS)

    Green, S.

    1976-01-01

    The formalism for describing rotational excitation in collisions between symmetric top rigid rotors and spherical atoms is presented both within the accurate quantum close coupling framework and also the coupled states approximation of McGuire and Kouri and the effective potential approximation of Rabitz. Calculations are reported for thermal energy NH3-He collisions, treating NH3 as a rigid rotor and employing a uniform electron gas (Gordon-Kim) approximation for the intermolecular potential. Coupled states are found to be in nearly quantitative agreement with close coupling results while the effective potential method is found to be at least qualitatively correct. Modifications necessary to treat the inversion motion in NH3 are discussed.

  10. Investigation of Nonadiabatic Effects for the Vibrational Spectrum of a Triatomic Molecule: The Use of a Single Potential Energy Surface with Distance-Dependent Masses for H3().

    PubMed

    Jaquet, Ralph; Khoma, Mykhaylo V

    2017-09-21

    On the basis of first-principles, the influence of nonadiabatic effects on the vibrational bound states of H3(+) has been investigated using distance-dependent reduced masses and only one single potential energy surface. For these new vibrational calculations, potentials based on explicitly correlated wave functions are used where, in addition, adiabatic corrections and relativistic contributions are taken into account. For the first time, several different fully distance-dependent reduced mass surfaces in three dimensions have been incorporated in the vibrational calculations.

  11. Accurate determination of pair potentials for a C{sub w}H{sub x}N{sub y}O{sub z} system of molecules: A semiempirical method

    SciTech Connect

    Thiel, M. van; Ree, F.H.; Haselman, L.C.

    1995-03-01

    Statistical mechanical chemical equilibrium calculations of the properties of high-pressure high-temperature reactive C,H,N,O mixtures are made to derive an accurate self-consistent set of inter-molecular potentials for the product molecules. Previous theoretical efforts to predict such properties relied in part on Corresponding States theory and shock wave data of argon. More recent high-pressure Hugoniot measurements on a number of elements and molecules allow more accurate determination of the potentials of these materials, and explicit inclusion of additional dissociation products. The present discussion briefly reviews the previous analysis and the method used to produce a self-consistent set of potentials from shock data on N{sub 2}, O{sub 2}, H{sub 2}, NO, an N{sub 2} + O{sub 2} mixture, carbon, CO{sub 2}, and CO, as well as some simple explosive product mixtures from detonation of hexanitrobenzene, PETN, and a mixture of hydrazine nitrate, hydrazine and water. The results are tested using the data from an HMX explosive formulations. The effect of the non-equilibrium nature of carbon clusters is estimated using data for TNT as a standard to determine a nonequilibrium equation of state for carbon. The resulting parameter set is used in a survey of 27 explosives. For the subset that contains no fluorine or two-phase carbon effects the rms deviation from experimental detonation velocity is 1.2%.

  12. On the potential involvement of CD11d in co-stimulating the production of interferon-γ by natural killer cells upon interaction with neutrophils via intercellular adhesion molecule-3

    PubMed Central

    Costantini, Claudio; Micheletti, Alessandra; Calzetti, Federica; Perbellini, Omar; Tamassia, Nicola; Albanesi, Cristina; Vermi, William; Cassatella, Marco A.

    2011-01-01

    Interaction between neutrophils and other leukocytes plays a variety of important roles in regulating innate and adaptive immune responses. Recently, we have shown that neu-trophils amplify NK cell/6-sulfo LacNAc+ dendritic cells (slanDC)-mediated cytokine production, by potentiating IL-12p70 release by slanDC via CD18/ICAM-1 and directly co-stimulating IFNγ production by NK cells via ICAM-3. Herein, we have identified additional molecules involved in the interactions among neutrophils, NK cells and slanDC. More specifically, we provide evidence that: i) the cross-talk between neutrophils and NK cells is mediated by ICAM-3 and CD11d/CD18, respectively; ii) slanDC potentiate the production of IFNγ by NK cells via CD11a/CD18. Altogether, our studies shed more light on the role that adhesion molecules play within the neutrophil/NK cell/slanDC network. Our data also have potential implications in the pathogenesis of diseases driven by hyperactivated leukocytes, such as Sweet’s syndrome, in which a neutrophil/NK cell co-localization is frequently observed. PMID:21712539

  13. Excited-state potential-energy surfaces of metal-adsorbed organic molecules from linear expansion Δ-self-consistent field density-functional theory (ΔSCF-DFT)

    NASA Astrophysics Data System (ADS)

    Maurer, Reinhard J.; Reuter, Karsten

    2013-07-01

    Accurate and efficient simulation of excited state properties is an important and much aspired cornerstone in the study of adsorbate dynamics on metal surfaces. To this end, the recently proposed linear expansion Δ-self-consistent field method by Gavnholt et al. [Phys. Rev. B 78, 075441 (2008)], 10.1103/PhysRevB.78.075441 presents an efficient alternative to time consuming quasi-particle calculations. In this method, the standard Kohn-Sham equations of density-functional theory are solved with the constraint of a non-equilibrium occupation in a region of Hilbert-space resembling gas-phase orbitals of the adsorbate. In this work, we discuss the applicability of this method for the excited-state dynamics of metal-surface mounted organic adsorbates, specifically in the context of molecular switching. We present necessary advancements to allow for a consistent quality description of excited-state potential-energy surfaces (PESs), and illustrate the concept with the application to Azobenzene adsorbed on Ag(111) and Au(111) surfaces. We find that the explicit inclusion of substrate electronic states modifies the topologies of intra-molecular excited-state PESs of the molecule due to image charge and hybridization effects. While the molecule in gas phase shows a clear energetic separation of resonances that induce isomerization and backreaction, the surface-adsorbed molecule does not. The concomitant possibly simultaneous induction of both processes would lead to a significantly reduced switching efficiency of such a mechanism.

  14. A first-principle protocol for calculating ionization energies and redox potentials of solvated molecules and ions: Theory and application to aqueous phenol and phenolate

    PubMed Central

    Ghosh, Debashree; Roy, Anirban; Seidel, Robert; Winter, Bernd; Bradforth, Stephen; Krylov, Anna I.

    2012-01-01

    The effect of hydration on the lowest vertical ionization energy (VIE) of phenol and phenolate solvated in bulk water was characterized using the equation-of-motion ionization potential coupled-cluster (EOM-IP-CCSD) and effective fragment potential (EFP) methods (referred to as EOM/EFP), and determined experimentally by valence photo-emission measurements using microjets and synchrotron radiation. The computed solvent-induced shifts in VIEs (ΔVIE) are −0.66 eV and +5.72 eV for phenol and phenolate, respectively. Our best estimates of the absolute values of VIEs (7.9 and 7.7 eV for phenol and phenolate) agree reasonably well with the respective experimental values (7.8±0.1 eV and 7.1±0.1 eV). The EOM/EFP scheme was benchmarked against full EOM-IP-CCSD using micro-solvated phenol and phenolate clusters. A protocol for calculating redox potentials with EOM/EFP was developed based on linear response approximation (LRA) of free energy determination. The oxidation potentials of phenol and phenolate calculated using LRA and EOM/EFP are 1.32 V and 0.89 V, respectively; they agree well with experimental values. PMID:22497288

  15. Generation of a pair of photons through the three-body dissociation of a multiply excited water molecule around the double ionization potential

    NASA Astrophysics Data System (ADS)

    Odagiri, Takeshi; Nakano, Motoyoshi; Tanabe, Takehiko; Kumagai, Yoshiaki; Suzuki, Isao H.; Kouchi, Noriyuki

    2009-11-01

    The cross sections for the generation of a photon-pair from excited fragments in photoexcitation of H2O have been measured as a function of incident photon energy. The multiply excited states of H2O have been observed even above the adiabatic double ionization potential.

  16. Streptococcus pneumoniae Cell-Wall-Localized Phosphoenolpyruvate Protein Phosphotransferase Can Function as an Adhesin: Identification of Its Host Target Molecules and Evaluation of Its Potential as a Vaccine

    PubMed Central

    Mizrachi Nebenzahl, Yaffa; Blau, Karin; Kushnir, Tatyana; Shagan, Marilou; Portnoi, Maxim; Cohen, Aviad; Azriel, Shalhevet; Malka, Itai; Adawi, Asad; Kafka, Daniel; Dotan, Shahar; Guterman, Gali; Troib, Shany; Fishilevich, Tali; Gershoni, Jonathan M; Braiman, Alex; Mitchell, Andrea M; Mitchell, Timothy J; Porat, Nurith; Goliand, Inna; Chalifa Caspi, Vered; Swiatlo, Edwin; Tal, Michael; Ellis, Ronald; Elia, Natalie; Dagan, Ron

    2016-01-01

    In Streptococcus pneumonia, phosphoenolpyruvate protein phosphotransferase (PtsA) is an intracellular protein of the monosaccharide phosphotransferase systems. Biochemical and immunostaining methods were applied to show that PtsA also localizes to the bacterial cell-wall. Thus, it was suspected that PtsA has functions other than its main cytoplasmic enzymatic role. Indeed, recombinant PtsA and anti-rPtsA antiserum were shown to inhibit adhesion of S. pneumoniae to cultured human lung adenocarcinoma A549 cells. Screening of a combinatorial peptide library expressed in a filamentous phage with rPtsA identified epitopes that were capable of inhibiting S. pneumoniae adhesion to A549 cells. The insert peptides in the phages were sequenced, and homologous sequences were found in human BMPER, multimerin1, protocadherin19, integrinβ4, epsin1 and collagen type VIIα1 proteins, all of which can be found in A549 cells except the latter. Six peptides, synthesized according to the homologous sequences in the human proteins, specifically bound rPtsA in the micromolar range and significantly inhibited pneumococcal adhesion in vitro to lung- and tracheal-derived cell lines. In addition, the tested peptides inhibited lung colonization after intranasal inoculation of mice with S. pneumoniae. Immunization with rPtsA protected the mice against a sublethal intranasal and a lethal intravenous pneumococcal challenge. In addition, mouse anti rPtsA antiserum reduced bacterial virulence in the intravenous inoculation mouse model. These findings showed that the surface-localized PtsA functions as an adhesin, PtsA binding peptides derived from its putative target molecules can be considered for future development of therapeutics, and rPtsA should be regarded as a candidate for vaccine development. PMID:26990554

  17. MiRNA-548ah, a potential molecule associated with transition from immune tolerance to immune activation of chronic hepatitis B.

    PubMed

    Xing, Tong-Jing; Xu, Hong-Tao; Yu, Wen-Qing; Wang, Bian; Zhang, Jing

    2014-08-19

    The present study aims to identify the differently expressed microRNA (miRNA) molecules and target genes of miRNA in the immune tolerance (IT) and immune activation (IA) stages of chronic hepatitis B (CHB). miRNA expression profiles of peripheral blood mononuclear cells (PBMCs) at the IT and IA stages of CHB were screened using miRNA microarrays and authenticated using a quantitative real-time polymerase chain reaction (RT-PCR). Gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the significant functions and pathways of possible target genes of miRNAs. Assays of the gain and loss of function of the miRNAs were performed to verify the target genes in THP-1 cell lines. The luciferase reporter test was used on 293T cells as direct targets. Significantly upregulated miR-548 and miR-4804 were observed in the miRNA microarrays and confirmed by RT-PCR in PBMCs at the IT and IA stages of CHB. GO and KEGG analysis revealed that MiR-548 and miR-4804 could be involved in numerous signaling pathways and protein binding activity. IFNγR1 was predicted as a target gene and validated as the direct gene of MiR-548. Significant negative correlation was found between the miR-548ah and mRNA levels of IFN-γR1 in CHB patients. The abnormal expression profiles of miRNA in PBMCs could be closely associated with immune activation of chronic HBV infection. miR-548, by targeting IFN-γR1, may represent a mechanism that can facilitate viral pathogenesis and help determine new therapeutic molecular targets.

  18. Consistent force field modeling of matrix isolated molecules. V. Minimum energy path potential to the conformer conversion of 1,2-difluoroethane: Ar 364, ab initio calculation of electric multipole moments and electric polarization contribution to the conversion barrier

    NASA Astrophysics Data System (ADS)

    Gunde, R.; Ha, T.-K.; Günthard, H. H.

    1990-08-01

    In this paper results of consistent force field modeling (CFF) of the potential function to conversion of the gauche (g) to the trans (t) conformer of 1,2-difluoroethane (DFE) isolated in an argon matrix will be reported. Starting point are locally stable configurations gDFE:Ar 364 (defect GH1) and tDFE:Ar 364 (TH1) obtained in previous work from CFF modeling of a cube shaped Ar 364 fragment containing one DFE molecule in its center. Using the dihedral angle of DFE as an independent parameter the minimum energy path of the conversion process gDFE:Ar 364→tDFE:Ar 364 will be determined by CFF energy minimization. Determination of the minimum energy path is found to require large numbers of energy minimization steps and to lead to a rather complicated motion of the molecule with respect to the crystal fragment. Surprisingly the molecule-matrix interactions lead to a reduction of the g-t barrier by ≈500 cal/mol and to a stabilization of the trans species by ≈500 cal/mol. This finding is a consequence of a delicate interplay of matrix-molecule and matrix-matrix interactions. Calculation of the electric polarization energy (induced dipole-first-order polarization approximation) is based on extended ab initio calculations of dipole and quadrupole moments and a bond polarizability estimate of the first-order polarizability of DFE as a function of the internal rotation angle, on Fourier expansion of multipole components and use of symmetry for reduction of the order of the linear system defining the (self-consistent) induced dipole moments of all Ar atoms. Electric polarization is found to alter the potential function of the conversion process in a profound way: the g-t barrier and the t-g energy difference are increased to ≈3000 cal/mol and to ≈1500 cal/mol respectively (≈2500 and ≈530 cal/mol respectively for free DFE). Further applications of the technique developed in this work to related problems of matrix isolated molecules, e.g., vibrational matrix

  19. MRD-CI potential surfaces using balanced basis sets. IV. The H/sub 2/ molecule and the H/sub 3/ surface

    SciTech Connect

    Wright, J.S.; Kruus, E.

    1986-12-15

    The utility of midbond functions in molecular calculations was tested in two cases where the correct results are known: the H/sub 2/ potential curve and the collinear H/sub 3/ potential surface. For H/sub 2/, a variety of basis sets both with and without bond functions was compared to the exact nonrelativistic potential curve of Kolos and Wolniewicz (J. Chem. Phys. 43, 2429 (1965)). It was found that optimally balanced basis sets at two levels of quality were the double zeta single polarization plus sp bond function basis (BF1) and the triple zeta double polarization plus two sets of sp bond function basis (BF2). These gave bond dissociation energies D/sub e/ = 4.7341 and 4.7368 eV, respectively (expt. 4.7477 eV). Four basis sets were tested for basis set superposition errors, which were found to be small relative to basis set incompleteness and therefore did not affect any conclusions regarding basis set balance. Basis sets BF1 and BF2 were used to construct potential surfaces for collinear H/sub 3/, along with the corresponding basis sets DZ*P and TZ*PP which contain no bond functions. Barrier heights of 12.52, 10.37, 10.06, and 9.96 kcal/mol were obtained for basis sets DZ*P, TZ*PP, BF1, and BF2, respectively, compared to an estimated limiting value of 9.60 kcal/mol. Difference maps, force constants, and relative rms deviations show that the bond functions improve the surface shape as well as the barrier height.

  20. First-principle interaction potentials for metastable He(3S) and Ne(3P) with closed-shell molecules: application to Penning-ionizing systems.

    PubMed

    Hapka, Michał; Chałasiński, Grzegorz; Kłos, Jacek; Zuchowski, Piotr S

    2013-07-07

    We present new interaction potential curves, calculated from first-principles, for the He((3)S, 1s(1)2s(1))···H2 and He((3)S)···Ar systems, relevant in recent Penning ionization experiments of Henson et al. [Science 338, 234 (2012)]. Two different approaches were applied: supermolecular using coupled cluster (CC) theory and perturbational within symmetry-adapted perturbation theory (SAPT). Both methods gave consistent results, and the potentials were used to study the elastic scattering and determine the positions of shape resonances for low kinetic energy (up to 1 meV). We found a good agreement with the experiment. In addition, we investigated two other dimers composed of metastable Ne ((3)P, 2p(5)3s(1)) and ground state He and Ar atoms. For the Ne((3)P)···He system, a good agreement between CC and SAPT approaches was obtained. The Ne((3)P)···Ar dimer was described only with SAPT, as CC gave divergent results. Ne* systems exhibit extremely small electronic orbital angular momentum anisotropy of the potentials. We attribute this effect to screening of an open 2p shell by a singly occupied 3s shell.

  1. Dissociative electron attachment to the H2O molecule. II. Nuclear dynamics on coupled electronic surfaces within the local complex potential model

    NASA Astrophysics Data System (ADS)

    Haxton, Daniel J.; Rescigno, T. N.; McCurdy, C. W.

    2007-01-01

    We report the results of a first-principles study of dissociative electron attachment to H2O . The cross sections were obtained from nuclear dynamics calculations carried out in full dimensionality within the local complex potential model by using the multiconfiguration time-dependent Hartree method. The calculations employ our previously obtained global, complex-valued, potential-energy surfaces for the three ( B12 , A12 , and B22 ) electronic Feshbach resonances involved in this process. These three metastable states of H2O- undergo several degeneracies, and we incorporate both the Renner-Teller coupling between the B12 and A12 states as well as the conical intersection between the A12 and B22 states into our treatment. The nuclear dynamics are inherently multidimensional and involve branching between different final product arrangements as well as extensive excitation of the diatomic fragment. Our results successfully mirror the qualitative features of the major fragment channels observed, but are less successful in reproducing the available results for some of the minor channels. We comment on the applicability of the local complex potential model to such a complicated resonant system.

  2. An optical conveyor for molecules.

    PubMed

    Weinert, Franz M; Braun, Dieter

    2009-12-01

    Trapping single ions under vacuum allows for precise spectroscopy in atomic physics. The confinement of biological molecules in bulk water is hindered by the lack of comparably strong forces. Molecules have been immobilized to surfaces, however often with detrimental effects on their function. Here, we optically trap molecules by creating the microscale analogue of a conveyor belt: a bidirectional flow is combined with a perpendicular thermophoretic molecule drift. Arranged in a toroidal geometry, the conveyor accumulates a hundredfold excess of 5-base DNA within seconds. The concentrations of the trapped DNA scale exponentially with length, reaching trapping potential depths of 14 kT for 50 bases. The mechanism does not require microfluidics, electrodes, or surface modifications. As a result, the trap can be dynamically relocated. The optical conveyor can be used to enhance diffusion-limited surface reactions, redirect cellular signaling, observe individual biomolecules over a prolonged time, or approach single-molecule chemistry in bulk water.

  3. Oncogenic microRNA 17-92 cluster is regulated by epithelial cell adhesion molecule and could be a potential therapeutic target in retinoblastoma.

    PubMed

    Kandalam, Moutushy Mitra; Beta, Madhu; Maheswari, Uma K; Swaminathan, S; Krishnakumar, Subramanian

    2012-01-01

    Several miRNAs have been reported as candidate oncogenes and tumor suppressors, which are involved in the pathways specifically altered during tumorigenesis or metastasis. The miR 17-92 cluster located in 13q31 locus might contribute to retinoblastoma (RB) oncogenesis as 13q31 is amplified often in RB. We attempted to identify the factors involved in the regulation of miR 17-92 cluster in RB. Real-time quantitative reverse transcriptase PCR was performed to study the expression of the miR 17-92 cluster in primary RB tumors and in Y79 cells after epithelial cell adhesion molecule (EpCAM) silencing. EpCAM was silenced using siRNA and confirmed by western blotting. The Y79 cells were transfected with individual and mixed antagomirs and studied the cell viability by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, invasion by matrigel analysis and caspase-3 expression by flow cytometry. The relative expression of miR 17-92 cluster, compared to that of a normal retina, ranged from 25 to 220 fold (p<0.0001), miR-18 being highly expressed in RB. Post EpCAM silencing resulted in a significant decrease (p<0.01) in the expression of the miR 17-92 cluster by 4 to eightfold in Y79 cells. Y79 cells transfected with an antagomirs mix (all 5 miRNAs) showed decreased cell viability (p<0.001) and cell invasion (p<0.001). Similarly, Y79 cells treated with antagomirs mix showed increased expression of caspase-3 (p<0.001), which confirms the anti-proliferative effect of antagomirs. This study has showed varied expression of the miR17-92 cluster in primary RB tumors. EpCAM influences miR 17-92 cluster expression in retinoblastoma. In addition, we showed that the miR 17-92 cluster plays a role in RB cell proliferation and invasion. Therefore, targeting the miRNA 17-92 cluster may be beneficial for controlling Y79/RB cell proliferation and invasion.

  4. Highlight on the indigenous organic molecules detected on Mars by SAM and potential sources of artifacts and backgrounds generated by the sample preparation

    NASA Astrophysics Data System (ADS)

    Buch, A.; Belmahdi, I.; Szopa, C.; Freissinet, C.; Glavin, D. P.; Coll, P. J.; Cabane, M.; Millan, M.; Eigenbrode, J. L.; Navarro-Gonzalez, R.; Stern, J. C.; Pinnick, V. T.; Coscia, D.; Teinturier, S.; Stambouli, M.; Dequaire, T.; Mahaffy, P. R.

    2015-12-01

    and molecules that may constitute organic material precursors sources. References: [1] Mahaffy, P. et al. (2012) Space Sci Rev, 170, 401-478. [2] Glavin, D. et al. (2013), JGR. [3] Leshin L. et al. (2013), Science, [4] Williams, A.J., Eigenbrode, J.L.,m Floyd, M.M., Wilhelm, M.B., and Mahaffy, P.R., (2015), GSA. [5] Eigenbrode, J.L. et al. (2010), LPSC, abst.1460.

  5. Improving In Vivo Efficacy of Bioactive Molecules: An Overview of Potentially Antitumor Phytochemicals and Currently Available Lipid-Based Delivery Systems

    PubMed Central

    Torres, Carlos; Vázquez, Luis; Reglero, Guillermo; Fornari, Tiziana

    2017-01-01

    Cancer is among the leading causes of morbidity and mortality worldwide. Many of the chemotherapeutic agents used in cancer treatment exhibit cell toxicity and display teratogenic effect on nontumor cells. Therefore, the search for alternative compounds which are effective against tumor cells but reduce toxicity against nontumor ones is of great importance in the progress or development of cancer treatments. In this sense, scientific knowledge about relevant aspects of nutrition intimately involved in the development and progression of cancer progresses rapidly. Phytochemicals, considered as bioactive ingredients present in plant products, have shown promising effects as potential therapeutic/preventive agents on cancer in several in vitro and in vivo assays. However, despite their bioactive properties, phytochemicals are still not commonly used in clinical practice due to several reasons, mainly attributed to their poor bioavailability. In this sense, new formulation strategies are proposed as carriers to improve their bioefficacy, highlighting the use of lipid-based delivery systems. Here, we review the potential antitumoral activity of the bioactive compounds derived from plants and the current studies carried out in animal and human models. Furthermore, their association with lipids as a formulation strategy to enhance their efficacy in vivo is also reported. The development of high effective bioactive supplements for cancer treatment based on the improvement of their bioavailability goes through this association. PMID:28555156

  6. Cell adhesion molecules and sleep.

    PubMed

    O'Callaghan, Emma Kate; Ballester Roig, Maria Neus; Mongrain, Valérie

    2017-03-01

    Cell adhesion molecules (CAMs) play essential roles in the central nervous system, where some families are involved in synaptic development and function. These synaptic adhesion molecules (SAMs) are involved in the regulation of synaptic plasticity, and the formation of neuronal networks. Recent findings from studies examining the consequences of sleep loss suggest that these molecules are candidates to act in sleep regulation. This review highlights the experimental data that lead to the identification of SAMs as potential sleep regulators, and discusses results supporting that specific SAMs are involved in different aspects of sleep regulation. Further, some potential mechanisms by which SAMs may act to regulate sleep are outlined, and the proposition that these molecules may serve as molecular machinery in the two sleep regulatory processes, the circadian and homeostatic components, is presented. Together, the data argue that SAMs regulate the neuronal plasticity that underlies sleep and wakefulness. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  7. Water molecules orientation in surface layer

    NASA Astrophysics Data System (ADS)

    Klingo, V. V.

    2000-08-01

    The water molecules orientation has been investigated theoretically in the water surface layer. The surface molecule orientation is determined by the direction of a molecule dipole moment in relation to outward normal to the water surface. Entropy expressions of the superficial molecules in statistical meaning and from thermodynamical approach to a liquid surface tension have been found. The molecules share directed opposite to the outward normal that is hydrogen protons inside is equal 51.6%. 48.4% water molecules are directed along to surface outward normal that is by oxygen inside. A potential jump at the water surface layer amounts about 0.2 volts.

  8. TargetHunter: an in silico target identification tool for predicting therapeutic potential of small organic molecules based on chemogenomic database.

    PubMed

    Wang, Lirong; Ma, Chao; Wipf, Peter; Liu, Haibin; Su, Weiwei; Xie, Xiang-Qun

    2013-04-01

    Target identification of the known bioactive compounds and novel synthetic analogs is a very important research field in medicinal chemistry, biochemistry, and pharmacology. It is also a challenging and costly step towards chemical biology and phenotypic screening. In silico identification of potential biological targets for chemical compounds offers an alternative avenue for the exploration of ligand-target interactions and biochemical mechanisms, as well as for investigation of drug repurposing. Computational target fishing mines biologically annotated chemical databases and then maps compound structures into chemogenomical space in order to predict the biological targets. We summarize the recent advances and applications in computational target fishing, such as chemical similarity searching, data mining/machine learning, panel docking, and the bioactivity spectral analysis for target identification. We then described in detail a new web-based target prediction tool, TargetHunter (http://www.cbligand.org/TargetHunter). This web portal implements a novel in silico target prediction algorithm, the Targets Associated with its MOst SImilar Counterparts, by exploring the largest chemogenomical databases, ChEMBL. Prediction accuracy reached 91.1% from the top 3 guesses on a subset of high-potency compounds from the ChEMBL database, which outperformed a published algorithm, multiple-category models. TargetHunter also features an embedded geography tool, BioassayGeoMap, developed to allow the user easily to search for potential collaborators that can experimentally validate the predicted biological target(s) or off target(s). TargetHunter therefore provides a promising alternative to bridge the knowledge gap between biology and chemistry, and significantly boost the productivity of chemogenomics researchers for in silico drug design and discovery.

  9. Explicit solvent simulations of the aqueous oxidation potential and reorganization energy for neutral molecules: gas phase, linear solvent response, and non-linear response contributions.

    PubMed

    Guerard, Jennifer J; Tentscher, Peter R; Seijo, Marianne; Samuel Arey, J

    2015-06-14

    First principles simulations were used to predict aqueous one-electron oxidation potentials (Eox) and associated half-cell reorganization energies (λaq) for aniline, phenol, methoxybenzene, imidazole, and dimethylsulfide. We employed quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations of the oxidized and reduced species in an explicit aqueous solvent, followed by EOM-IP-CCSD computations with effective fragment potentials for diabatic energy gaps of solvated clusters, and finally thermodynamic integration of the non-linear solvent response contribution using classical MD. A priori predicted Eox and λaq values exhibit mean absolute errors of 0.17 V and 0.06 eV, respectively, compared to experiment. We also disaggregate Eox into several well-defined free energy properties, including the gas phase adiabatic free energy of ionization (7.73 to 8.82 eV), the solvent-induced shift in the free energy of ionization due to linear solvent response (-2.01 to -2.73 eV), and the contribution from non-linear solvent response (-0.07 to -0.14 eV). The linear solvent response component is further apportioned into contributions from the solvent-induced shift in vertical ionization energy of the reduced species (ΔVIEaq) and the solvent-induced shift in negative vertical electron affinity of the ionized species (ΔNVEAaq). The simulated ΔVIEaq and ΔNVEAaq are found to contribute the principal sources of uncertainty in computational estimates of Eox and λaq. Trends in the magnitudes of disaggregated solvation properties are found to correlate with trends in structural and electronic features of the solute. Finally, conflicting approaches for evaluating the aqueous reorganization energy are contrasted and discussed, and concluding recommendations are given.

  10. Structure-Based Development of Small Molecule PFKFB3 Inhibitors: A Framework for Potential Cancer Therapeutic Agents Targeting the Warburg Effect

    SciTech Connect

    Seo, Minsuh; Kim, Jeong-Do; Neau, David; Sehgal, Inder; Lee, Yong-Hwan

    2012-02-10

    Cancer cells adopt glycolysis as the major source of metabolic energy production for fast cell growth. The HIF-1-induced PFKFB3 plays a key role in this adaptation by elevating the concentration of Fru-2,6-BP, the most potent glycolysis stimulator. As this metabolic conversion has been suggested to be a hallmark of cancer, PFKFB3 has emerged as a novel target for cancer chemotherapy. Here, we report that a small molecular inhibitor, N4A, was identified as an initial lead compound for PFKFB3 inhibitor with therapeutic potential. In an attempt to improve its potency, we determined the crystal structure of the PFKFB3 {sm_bullet} N4A complex to 2.4 {angstrom} resolution and, exploiting the resulting molecular information, attained the more potent YN1. When tested on cultured cancer cells, both N4A and YN1 inhibited PFKFB3, suppressing the Fru-2,6-BP level, which in turn suppressed glycolysis and, ultimately, led to cell death. This study validates PFKFB3 as a target for new cancer therapies and provides a framework for future development efforts.

  11. N2 non-thermal atmospheric pressure plasma promotes wound healing in vitro and in vivo: Potential modulation of adhesion molecules and matrix metalloproteinase-9.

    PubMed

    Kang, Sung Un; Choi, Jae Won; Chang, Jae Won; Kim, Kang Il; Kim, Yeon Soo; Park, Ju Kyeong; Kim, Yang Eun; Lee, Yun Sang; Yang, Sang Sik; Kim, Chul-Ho

    2017-02-01

    Advances in physics and biology have made it possible to apply non-thermal atmospheric pressure plasma (NTP) in the biomedical field. Although accumulating evidence suggests that NTP has various medicinal effects, such as facilitating skin wound healing on exposed tissue while minimizing undesirable tissue damage, the underlying molecular mechanisms are not fully understood. In this study, NTP generated from N2 optimized wound healing in the scratch wound healing assay. In addition, matrix metalloproteinase (MMP)-9 expression and enzyme activity increased and the urokinase-type plasminogen activator (uPA) system was activated after NTP treatment. We also showed that NTP treatment increased Slug and TCF8/ZEB1 expression and decreased that of E-cadherin, suggesting induction of the epithelial-to-mesenchymal transition (EMT). The effect of N2 NTP was verified on rat wound model. Taken together, these results suggest that N2 NTP promotes wound healing by inducing the EMT and activating the MMP-9/uPA system. These findings show the therapeutic potential of NTP for skin wound healing.

  12. Vibrational, structural and electronic properties investigation by DFT calculations and molecular docking studies with DNA topoisomerase II of strychnobrasiline type alkaloids: A theoretical approach for potentially bioactive molecules

    NASA Astrophysics Data System (ADS)

    Costa, Renyer A.; Oliveira, Kelson M. T.; Costa, Emmanoel Vilaça; Pinheiro, Maria L. B.

    2017-10-01

    A combined experimental and theoretical DFT study of the structural, vibrational and electronic properties of strychnobrasiline and 12-hydroxy-10,11-dimethoxystrychnobrasiline is presented using the Becke three-parameter Lee-Yang-Parr function (B3LYP) and 6-311G(2d,p) basis set. The theoretical geometry optimization data were compared with the X-ray data for a similar structure in the associated literature, showing close values. The calculated HOMO-LUMO gap values showed that the presence of substituents in the benzene ring influences the quantum properties which are directly related to the reactive properties. Theoretical UV spectra agreed well with the measured experimental data, with bands assigned. In addition, Natural Bond Orbitals (NBOs), Mapped molecular electrostatic potential surface (MEPS) and NLO calculations were also performed at the same theory level. The theoretical vibrational analysis revealed several characteristic vibrations that may be used as a diagnostic tool for other strychnobrasiline type alkaloids, simplifying their identification and structural characterization. Molecular docking calculations with DNA Topoisomerase II-DNA complex showed binding free energies values of -8.0 and -9.5 kcal/mol for strychnobrasiline and 12-hydroxy-10,11-dimethoxystrychnobrasiline respectively, while for amsacrine, used for the treatment of leukemia, the binding free energy ΔG presented a value of -10.0 kcal/mol, suggesting that strychnobrasiline derivative alkaloids might exhibit an antineoplastic activity.

  13. A selected ion flow tube study of the reactions of NO + and O + 2 ions with some organic molecules: The potential for trace gas analysis of air

    NASA Astrophysics Data System (ADS)

    Španěl, Patrik; Smith, David

    1996-02-01

    A study has been carried out using our selected ion flow tube apparatus of the reactions of NO+ and O+2 ions in their vibronic ground states with ten organic species: the hydrocarbons, benzene, toluene, isoprene, cyclopropane, and n-pentane; the oxygen-containing organics, methanol, ethanol, acetaldehyde, acetone, and diethyl ether. The major objectives of this work are, on the one hand, to fully understand the processes involved in these reactions and, on the other hand, to explore the potential of NO+ and O+2 as chemical ionization agents for the analysis of trace gases in air and on human breath. Amongst the NO+ reactions, charge transfer, hydride-ion transfer, and termolecular association occur, and the measured rate coefficients, k, for the reactions vary from immeasurably small to the maximum value, collisional rate coefficient, kc. The O+2 reactions are all fast, in each case the k being equal to or an appreciable fraction of kc, and charge transfer producing the parent organic ion or dissociative charge transfer resulting in two or three fragments of the parent ion are the reaction processes that occur. We conclude from these studies, and from previous studies, that NO+ ions and O+2 ions can be used to great effect as chemical ionization agents for trace gas analysis, especially in combination with H3O+ ions which we now routinely use for this purpose.

  14. Electronic structure of donor-spacer-acceptor molecules of potential interest for molecular electronics. IV. Geometry and device properties of P3CNQ and Q3CNQ

    NASA Astrophysics Data System (ADS)

    Broo, Anders; Zerner, Michael C.

    1995-07-01

    Z-β-(1-hexadecyl-4-quinolinium)-α-cyano-4-styryldicyanomethanide (C 16H 33-Q3CNQ) and the pyridinium analogue Z-β-(1-hexadecyl-4-pyridinium)-α-cyano-4-styryldicyanomethanide (C 16H 33-P3NCQ) are two very promising candidates for molecular device design. We obtain the geometry of the ground and excited state of these systems using the PM3 quantum mechanical model. The absorption spectra in vacuum and in solution are calculated using the INDO/Cl model, and compared to experimental spectra. The solvatochromic shift of the absorption spectra was calculated using a self-consistent reaction field approach. The observed bleaching of Langmuir-Blodgett films and solutions of C 16H 33-Q3CNQ and C 16H 33-P3CNQ is explained as resulting from a twisted configuration formed without barrier upon absorption into a twisted intramolecular charge transfer state. The observed rectification is explained from a ground state potential energy surface with two minima, one of which is characterized by a very large dipole moment. The relative energy of these minima is easily shifted by an electric field. The overall electron transport rate is found to be very small due to the small electronic coupling between the mono-layers of the L-B film. Thus, the electron transport through the sample is likely through defects of the L-B film. A way to increase the electronic coupling between the mono-layers is also discussed.

  15. Potential energy surfaces for ground and excited electronic states of the CF3I molecule and their relevance to its A-band photodissociation.

    PubMed

    Alekseyev, Aleksey B; Liebermann, Heinz-Peter; Buenker, Robert J

    2013-05-14

    The multireference spin-orbit (SO) configuration interaction (CI) method in its Λ-S contracted SO-CI version is employed to calculate two-dimensional potential energy surfaces for the ground and low-lying excited states of CF3I relevant to its photodissociation in the lowest absorption band (A band). The computed equilibrium geometry for the X̃A1 ground state and vibrational frequency ν3 for the C-I stretch mode agree well with available experimental data. The (3)Q0(+) state dissociating to the excited I((2)P1/2) limit is found to have a minimum of 1570 cm(-1) significantly shifted to larger internuclear distances (RC-I = 5.3 a0) relative to the ground state. Similar to the CH3I case, this makes a single-exponent approximation commonly employed for analysis of the CF3I recoil dynamics unsuitable. The 4E((3)A1) state possessing an allowed transition from the ground state and converging to the same atomic limit as (3)Q0(+) is calculated to lie too high in the Franck-Condon region to have any significant impact on the A-band absorption. The computed vertical excitation energies for the (3)Q1, (3)Q0(+), and (1)Q states indicate that the A-band spectrum must lie approximately between 31,300 and 45,200 cm(-1), i.e., between 220 and 320 nm. This result is in very good agreement with the measured absorption spectrum.

  16. Amino Acid-Derived 1,2-Benzisothiazolinone Derivatives as Novel Small-Molecule Antifungal Inhibitors: Identification of Potential Genetic Targets

    PubMed Central

    Alex, Deepu; Gay-Andrieu, Francoise; May, Jared; Thampi, Linta; Dou, Dengfeng; Mooney, Aileen; Groutas, William

    2012-01-01

    We have identified four synthetic compounds (DFD-VI-15, BD-I-186, DFD-V-49, and DFD-V-66) from an amino acid-derived 1,2-benzisothiazolinone (BZT) scaffold that have reasonable MIC50 values against a panel of fungal pathogens. These compounds have no structural similarity to existing antifungal drugs. Three of the four compounds have fungicidal activity against Candida spp., Cryptococcus neoformans, and several dermatophytes, while one is fungicidal to Aspergillus fumigatus. The kill rates of our compounds are equal to those in clinical usage. The BZT compounds remain active against azole-, polyene-, and micafungin-resistant strains of Candida spp. A genetics-based approach, along with phenotype analysis, was used to begin mode of action (MOA) studies of one of these compounds, DFD-VI-15. The genetics-based screen utilized a homozygous deletion collection of approximately 4,700 Saccharomyces cerevisiae mutants. We identified mutants that are both hypersensitive and resistant. Using FunSpec, the hypersensitive mutants and a resistant ace2 mutant clustered within a category of genes related directly or indirectly to mitochondrial functions. In Candida albicans, the functions of the Ace2p transcription factor include the regulation of glycolysis. Our model is that DFD-VI-15 targets a respiratory pathway that limits energy production. Supporting this hypothesis are phenotypic data indicating that DFD-VI-15 causes increased cell-reactive oxidants (ROS) and a decrease in mitochondrial membrane potential. Also, the same compound has activity when cells are grown in a medium containing glycerol (mitochondrial substrate) but is much less active when cells are grown anaerobically. PMID:22687516

  17. Amino acid-derived 1,2-benzisothiazolinone derivatives as novel small-molecule antifungal inhibitors: identification of potential genetic targets.

    PubMed

    Alex, Deepu; Gay-Andrieu, Francoise; May, Jared; Thampi, Linta; Dou, Dengfeng; Mooney, Aileen; Groutas, William; Calderone, Richard

    2012-09-01

    We have identified four synthetic compounds (DFD-VI-15, BD-I-186, DFD-V-49, and DFD-V-66) from an amino acid-derived 1,2-benzisothiazolinone (BZT) scaffold that have reasonable MIC(50) values against a panel of fungal pathogens. These compounds have no structural similarity to existing antifungal drugs. Three of the four compounds have fungicidal activity against Candida spp., Cryptococcus neoformans, and several dermatophytes, while one is fungicidal to Aspergillus fumigatus. The kill rates of our compounds are equal to those in clinical usage. The BZT compounds remain active against azole-, polyene-, and micafungin-resistant strains of Candida spp. A genetics-based approach, along with phenotype analysis, was used to begin mode of action (MOA) studies of one of these compounds, DFD-VI-15. The genetics-based screen utilized a homozygous deletion collection of approximately 4,700 Saccharomyces cerevisiae mutants. We identified mutants that are both hypersensitive and resistant. Using FunSpec, the hypersensitive mutants and a resistant ace2 mutant clustered within a category of genes related directly or indirectly to mitochondrial functions. In Candida albicans, the functions of the Ace2p transcription factor include the regulation of glycolysis. Our model is that DFD-VI-15 targets a respiratory pathway that limits energy production. Supporting this hypothesis are phenotypic data indicating that DFD-VI-15 causes increased cell-reactive oxidants (ROS) and a decrease in mitochondrial membrane potential. Also, the same compound has activity when cells are grown in a medium containing glycerol (mitochondrial substrate) but is much less active when cells are grown anaerobically.

  18. The roles of BTG3 expression in gastric cancer: a potential marker for carcinogenesis and a target molecule for gene therapy.

    PubMed

    Gou, Wen-feng; Yang, Xue-feng; Shen, Dao-fu; Zhao, Shuang; Liu, Yun-peng; Sun, Hong-zhi; Takano, Yasuo; Su, Rong-jian; Luo, Jun-sheng; Zheng, Hua-chuan

    2015-08-14

    BTG (B-cell translocation gene) can inhibit cell proliferation, metastasis and angiogenesis, cell cycle progression, and induce differentiation in various cells. Here, we found that BTG3 overexpression inhibited proliferation, induced S/G2 arrest, differentiation, autophagy, apoptosis, suppressed migration and invasion in MKN28 and MGC803 cells (p < 0.05). BTG3 transfectants showed a higher mRNA expression of p27, Bax, 14-3-3, Caspase-3, Caspase-9, Beclin 1, NF-κB, IL-1, -2, -4, -10 and -17, but a lower mRNA expression of p21, MMP-9 and VEGF than the control and mock (p < 0.05). At protein level, BTG3 overexpression increased the expression of CDK4, AIF, LC-3B, Beclin 1 and p38 (p < 0.05), but decreased the expression of p21 and β-catenin in both transfectants (p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG3 transfectants showed lower viability and higher apoptosis than the control in both time- and dose-dependent manners (p < 0.05). BTG3 expression was restored after 5-aza-2'-deoxycytidine or MG132 treatment in gastric cancer cells. BTG3 expression was decreased in gastric cancer in comparison to the adjacent mucosa (p < 0.05), and positively correlated with venous invasion and dedifferentiation of cancer (p < 0.05). It was suggested that BTG3 expression might contribute to gastric carcinogenesis. BTG3 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer.

  19. Spectroscopic constants of diatomic molecules computed correcting Hartree-Fock or general-valence-bond potential-energy curves with correlation-energy functionals

    NASA Astrophysics Data System (ADS)

    Pérez-Jordá, José M.; San-Fabián, Emilio; Moscardó, Federico

    1992-04-01

    The Kohn-Sham energy with exact exchange [using the exact Hartree-Fock (HF) exchange but an approximate correlation-energy functional] may be computed very accurately by adding the correlation obtained from the HF density to the total HF energy. Three density functionals are used: local spin density (LSD), LSD with self-interaction correction, and LSD with generalized gradient correction. This scheme has been extended (Lie-Clementi, Colle-Salvetti, and Moscardo-San-Fabian) to be used with general-valence-bond (GVB) energies and wave functions, so that the extra correlation included in the GVB energy is not counted again. The effect of all these approximate correlations on HF or GVB spectroscopic constants (Re,ωe, and De) is studied. Approximate relations showing how correlation affects them are derived, and may be summarized as follows: (1) the effect on Re and ωe depends only on the correlation derivative at Re, and (2) the effect on De depends mainly on the correlation difference between quasidissociated and equilibrium geometries. A consequence is that all the correlation corrections tested here give larger ωe and De and shorter Re than the uncorrected HF or GVB values. This trend is correct for De for both HF and GVB. For Re and ωe, it is correct in most cases for GVB, but it often fails for the HF cases. A comparison is made with Kohn-Sham calculations with both exchange and correlation approximated. As a final conclusion, it is found that, within the present scheme, a qualitatively correct HF or GVB potential-energy curve, together with a correlation-energy approximation with correct dissociation behavior, is crucial for obtaining good estimates of spectroscopic constants.

  20. Cytosolic phospholipase A2 (cPLA2) IVA as a potential signature molecule in cigarette smoke condensate induced pathologies in alveolar epithelial lineages.

    PubMed

    Yadav, Subodh K; Sharma, Sanjeev K; Farooque, Abdullah; Kaushik, Gaurav; Kaur, Balwinder; Pathak, Chander M; Dwarakanath, Bilikere S; Khanduja, Krishan L

    2016-08-15

    Smoking is one of the leading causes of millions of deaths worldwide. During cigarette smoking, most affected and highly exposed cells are the alveolar epithelium and generated oxidative stress in these cells leads to death and damage. Several studies suggested that oxidative stress causes membrane remodeling via Phospholipase A2s but in the case of cigarette smokers, mechanistically study is not yet fully defined. In view of present perspective, we evaluated the involvement of cytosolic phospholipase A2 (cPLA2) IVA as therapeutic target in cigarette smoke induced pathologies in transformed type I and type II alveolar epithelial cells. Transformed type I (WI26) and type II (A549) alveolar epithelial cells were used for the present study. Cigarette smoke condensate (CSC) was prepared from most commonly used cigarette (Gold Flake with filter) by the Indian population. CSC-induced molecular changes were evaluated through cell viability using MTT assay, reactive oxygen species (ROS) measurement using 2,7 dichlorodihydrofluorescin diacetate (DCFH-DA), cell membrane integrity using fluorescein diacetate (FDA) and ethidium bromide (EtBr) staining, super oxide dismutase (SOD) levels, cPLA2 activity and molecular involvement of specific cPLA2s at selected 24 h time period. CSC-induced response on both type of epithelial cells shown significantly reduction in cell viability, declined membrane integrity, with differential escalation of ROS levels in the range of 1.5-15 folds and pointedly increased cPLA2 activity (p < 0.05). Likewise, we observed distinction antioxidant potential in these two types of lineages as type I cells had considerably higher SOD levels when compared to type II cells (p < 0.05). Further molecular expression of all cPLA2s increased significantly in a dose dependent manner, specifically cytosolic phospholipase A2 IVA with maximum manifestation of 3.8 folds. Interestingly, CSC-induced ROS levels and cPLA2s expression were relatively higher in A

  1. The determination of potential energy curve and dipole moment of the (5)0{sup +} electronic state of {sup 85}Rb{sup 133}Cs molecule by high resolution photoassociation spectroscopy

    SciTech Connect

    Yuan, Jinpeng; Zhao, Yanting Ji, Zhonghua; Li, Zhonghao; Xiao, Liantuan; Jia, Suotang; Kim, Jin-Tae

    2015-12-14

    We present the formation of ultracold {sup 85}Rb{sup 133}Cs molecules in the (5)0{sup +} electronic state by photoassociation and their detection via resonance-enhanced two-photon ionization. Up to v = 47 vibrational levels including the lowest v = 0 vibrational and lowest J = 0 levels are identified with rotationally resolved high resolution photoassociation spectra. Precise Dunham coefficients are determined for the (5)0{sup +} state with high accuracy, then the Rydberg-Klein-Rees potential energy curve is derived. The electric dipole moments with respect to the vibrational numbers of the (5)0{sup +} electronic state of {sup 85}Rb{sup 133}Cs molecule are also measured in the range between 1.9 and 4.8 D. These comprehensive studies on previously unobserved rovibrational levels of the (5)0{sup +} state are helpful to understand the molecular structure and discover suitable transition pathways for transferring ultracold atoms to deeply bound rovibrational levels of the electronic ground state.

  2. AW00179 potentiates TRAIL-mediated death of human lung cancer H1299 cells through ROS-JNK-c-Jun-mediated up-regulation of DR5 and down-regulation of anti-apoptotic molecules.

    PubMed

    Hwang, Mi-Kyung; Ryu, Byung Jun; Kim, Seong Hwan

    2012-10-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in tumor cells, but when used alone, it is not effective at treating TRAIL-resistant tumors. This resistance is challenging for TRAIL-based anti-cancer therapies. In this study, we found that 1-(4-trifluoromethoxy-phenyl)-3-[4-(5-trifluoromethyl-2,5-dihydro-pyrazol-1-yl)-phenyl]-urea (AW00179) sensitized human lung cancer H1299 cells to TRAIL-mediated apoptosis. Even in the absence of TRAIL, AW00179 strongly induced DR5 expression and decreased the expression of anti-apoptotic proteins, suggesting that the sensitizing effect of AW00179 on TRAIL-mediated apoptosis is due to increased levels of DR5 protein and decreased anti-apoptotic molecules. AW00179 also induced the activation of c-Jun and ERK; however, a pharmacologic inhibition study revealed that JNK-c-Jun signaling is involved in the induction of DR5 expression. In addition, reactive oxygen species (ROS) appear to be involved in AW00179 activity. In conclusion, AW00179 has the potential to sensitize H1299 cells to TRAIL-mediated apoptosis through two distinct mechanisms: ROS-JNK-c-Jun-mediated up-regulation of DR5, and down-regulation of anti-apoptotic molecules.

  3. Physics of Molecules

    NASA Astrophysics Data System (ADS)

    Williams, D.; Murdin, P.

    2000-11-01

    Many varieties of molecule have been detected in the Milky Way and in other galaxies. The processes by which these molecules are formed and destroyed are now broadly understood (see INTERSTELLAR CHEMISTRY). These molecules are important components of galaxies in two ways. Firstly, radiation emitted by molecules enables us to trace the presence of diffuse gas, to infer its physical properties and ...

  4. Dihydrino molecule identification

    SciTech Connect

    Mills, R.L.; Good, W.R. ); Shaubach, R.M. )

    1994-01-01

    Three sets of heat production and [open quotes]ash[close quotes] identification data are presented. An exothermic reaction is reported wherein the electrons of hydrogen and deuterium atoms are stimulated to relax to quantized potential energy levels below that of the [open quotes]ground state[close quotes] via electrochemical reactants K[sup +] and K[sup +]; Pd[sup 2+] and Li[sup +]; or Pd and O[sub 2] of redox energy resonant with the energy hole that stimulates this transition. Calorimetry of pulsed current and continuous electrolysis of aqueous potassium carbonate (K[sup +]/K[sup +] electrocatalytic couple) at a nickel cathode were performed. The excess output power of 41 W exceeded by a factor >8 the total input power given by the product of the electrolysis voltage and current. The product of the exothermic reaction is atoms having electrons of energy below the ground state, which are predicted to form molecules. The predicted molecules were identified by their lack of reactivity with oxygen, by separation from molecular deuterium by cryofiltration, and by mass spectroscopic analysis. 15 refs., 12 figs., 9 tabs.

  5. Second virial coefficients for chain molecules

    SciTech Connect

    Bokis, C.P.; Donohue, M.D. . Dept. of Chemical Engineering); Hall, C.K. . Dept. of Chemical Engineering)

    1994-01-01

    The importance of having accurate second virial coefficients in phase equilibrium calculations, especially for the calculation of dew points, is discussed. The square-well potentials results in a simple but inaccurate equation for the second virial coefficient for small, spherical molecules such as argon. Here, the authors present a new equation for the second virial coefficient of both spherical molecules and chain molecules which is written in a form similar to that for the square-well potential. This new equation is accurate in comparison to Monte Carlo simulation data on second virial coefficients for square-well chain molecules and with second virial coefficients obtained from experiments on n-alkanes.

  6. [Adhesion molecules and diabetes mellitus].

    PubMed

    Urso, C; Hopps, E; Caimi, G

    2010-01-01

    Adhesion molecules play a significant role in leukocyte migration across the endothelium and are also involved in regulating immune system. It is shown that diabetic patients have an increase of soluble adhesion molecules (sICAM-1, sICAM-2, sVCAM-1, sE-selectin, sL-selectin, sP-selectin) considered an integral part of inflammatory state. This inflammation is responsible for the increased cardiovascular risk of these patients. There is a close link between hyperglycemia, oxidative stress, coagulopathy and inflammation and between these factors and the vascular damage. Various studies have showed the potential role of adhesion molecules in the pathogenesis of diabetic vasculopathy. They promote leukocyte recruitment, which is one of the initial steps in the genesis of atherosclerotic plaque. Adhesion molecules are also involved in the pathogenesis of diabetes mellitus type 1; sICAM-1 would have a particular immunomodulatory role in the process of destroying beta-cells and could be used as a subclinical marker of insulitis. Plasma levels of soluble adhesion molecules correlate with hyperglycemia, insulin resistance, dyslipidemia and obesity; they are associated with the development of nephropathy, retinopathy, myocardial infarction, stroke and obliterant peripheral arterial disease in diabetic type 1 and 2. Given the role of these molecules in endothelial dysfunction genesis and tissue damage associated with diabetes, they could constitute a therapeutic target for the prevention of genesis and progression of chronic complications of diabetic disease.

  7. Electrochromic Graphene Molecules

    DOE PAGES

    Ji, Zhiqiang; Doorn, Stephen K.; Sykora, Milan

    2015-03-13

    Polyclic aromatic hydrocarbons, also called Graphene Molecules (GMs), with chemical composition C132H36(COOH)2 were synthesized in-situ on the surface of transparent nanocrystaline indium tin oxide (nc-ITO) electrodes. Their electronic structure was studied electrochemically and spectro-electrochemically. Variations in the potential applied onto the nc-ITO/GM electrodes induce only small changes in the observed current but they produce dramatic changes in the absorption of the GMs, which are associated with their oxidation and reduction. Analysis of the absorption changes using modified Nernst equation is used to determine standard potentials associated with the individual charge transfer processes. For the GMs prepared here these were foundmore » to be E1,ox 0 = 0.77± 0.01 V and E2,ox 0 = 1.24 ± 0.02 V vs. NHE for the first and second oxidation and E1,red 0 = -1.50 ± 0.04 V for the first reduction. The charge transfer processes are found to be non-ideal. The non-ideality factors associated with the oxidation and reduction processes suggest presence of strong interactions between the GM redox centers. Under the conditions of potential cycling GMs show rapid (seconds) color change with high contrast and stability. An electrochromic application is demonstrated wherein the GMs are used as the optically active component.« less

  8. Phase structure of soliton molecules

    SciTech Connect

    Hause, A.; Hartwig, H.; Seifert, B.; Stolz, H.; Boehm, M.; Mitschke, F.

    2007-06-15

    Temporal optical soliton molecules were recently demonstrated; they potentially allow further increase of data rates in optical telecommunication. Their binding mechanism relies on the internal phases, but these have not been experimentally accessible so far. Conventional frequency-resolved optical gating techniques are not suited for measurement of their phase profile: Their algorithms fail to converge due to zeros both in their temporal and their spectral profile. We show that the VAMPIRE (very advanced method of phase and intensity retrieval of E-fields) method performs reliably. With VAMPIRE the phase profile of soliton molecules has been measured, and further insight into the mechanism is obtained.

  9. Phase structure of soliton molecules

    NASA Astrophysics Data System (ADS)

    Hause, A.; Hartwig, H.; Seifert, B.; Stolz, H.; Böhm, M.; Mitschke, F.

    2007-06-01

    Temporal optical soliton molecules were recently demonstrated; they potentially allow further increase of data rates in optical telecommunication. Their binding mechanism relies on the internal phases, but these have not been experimentally accessible so far. Conventional frequency-resolved optical gating techniques are not suited for measurement of their phase profile: Their algorithms fail to converge due to zeros both in their temporal and their spectral profile. We show that the VAMPIRE (very advanced method of phase and intensity retrieval of E -fields) method performs reliably. With VAMPIRE the phase profile of soliton molecules has been measured, and further insight into the mechanism is obtained.

  10. Redox-gated electron transport in electrically wired ferrocene molecules

    NASA Astrophysics Data System (ADS)

    Xiao, Xiaoyin; Brune, Daniel; He, Jin; Lindsay, Stuart; Gorman, Christopher B.; Tao, Nongjian

    2006-07-01

    We have synthesized cysteamine-terminated ferrocene molecules and determined the dependence of the electron transport properties of the molecules on their redox states by measuring the current through the molecules as a function of the electrode potential. The current fluctuates over a large range, but its average value increases with the potential. We attribute the current fluctuation and its increase with the potential to the switching of the molecules from low-conductance reduced state to high-conductance oxidized state.

  11. Electronic control inside a molecule : towards single molecule devices

    NASA Astrophysics Data System (ADS)

    Lastapis, Mathieu; Fukuma, Yurie; Boland, John

    2006-03-01

    The chimerical single molecule engineering has been proven to be accessible through the use of scanning tunnelling microscopy (STM) [1]. In this field, one particularly attractive area is the study of single molecules adsorbed on semiconductor surfaces. It has been recently demonstrated that a spatial fine control of the molecular dynamics is possible through the use of tunnelling current [2]. In order to improve the electronic control of a single molecule, we are currently investigating a promising system: CaF2 on Si(111). This system has been extensively studied as a model system to deposit insulator on silicon. Here we are using this system to electronically decouple the molecule from the substrate. I will present LT STM experiments on atomically thick CaF islands on Si(111). The measured electronic properties of these islands demonstrate their potential as ideal templates to study single molecules. Finally I will present some preliminary results on N-HBC [3] adsorbed on a CaF island. [1] G. Binnig and H. Rohrer, ``In touch with atoms'', Rev. Mod. Phys. 71, S324-S330 (1999) [2] M. Lastapis et al, Science, 308, 1000 (2005) [3] S.Draper et al, JACS, 126, 8694 (2004)

  12. Positron scattering from simple molecules

    NASA Astrophysics Data System (ADS)

    Singh, Suvam; Dutta, Sangita; Naghma, Rahla; Antony, Bobby

    2017-07-01

    A modified version of spherical complex optical potential formalism is employed to calculate the positron scattering cross sections over a wide energy range from near positronium formation threshold to 5000 eV. In the present study, the interaction potential of the positron-target scattering system is developed under an optical potential framework for the calculation of positron scattering total cross sections for CH4, CO, CO2, H2, N2O and NO molecules. The results obtained are in good agreement with most of the available experimental and theoretical values in terms of its shape and magnitude. A characteristic increase in cross section is observed for all the molecules near the positronium formation threshold, which signifies the emergence of positronium formation along with other inelastic channels.

  13. Electrical conduction through DNA molecule.

    PubMed

    Abdalla, S

    2011-09-01

    Several disorder parameters, inside the DNA molecule, lead to localization of charge carriers inside potential wells in the lowest unoccupied and highest occupied molecular orbits (LUMO and HOMO) which affects drastically the electrical conduction through the molecule, and demonstrates that the band carriers play an essential role in the conduction mechanism. So, a model is presented to shed light on the role of electrons of the LUMO in the electrical conduction through the DNA molecule. DC-, AC-conductivity and dielectric permittivity experimental data are well fitted with the presented model giving evidence that the free carriers in the LUMO and HOMO are responsible to make the DNA molecule conductor, insulator or semiconductor. The obtained results show that the localized charge carriers in the DNA molecule are characterized by four different types of relaxation phenomena which are thermally activated by corresponding four activation energies at 0.56 eV, 0.33 eV, 0.24 eV, and 0.05 eV respectively. Moreover, the calculations after the model, at room temperature, show that the time of the relaxation times of the current carriers are in the order of 5 × 10(-2)s, 1.74 × 10(-4)s, 5 × 10(-7)s, and 1.6 × 10(-10)s, respectively.

  14. Oldenlandia diffusa suppresses metastatic potential through inhibiting matrix metalloproteinase-9 and intercellular adhesion molecule-1 expression via p38 and ERK1/2 MAPK pathways and induces apoptosis in human breast cancer MCF-7 cells.

    PubMed

    Chung, Tae-Wook; Choi, Hyunju; Lee, Ji-Min; Ha, Sun-Hyung; Kwak, Choong-Hwan; Abekura, Fukushi; Park, Jun-Young; Chang, Young-Chae; Ha, Ki-Tae; Cho, Seung-Hak; Chang, Hyeun Wook; Lee, Young-Choon; Kim, Cheorl-Ho

    2017-01-04

    Oldenlandia diffusa (OD) has long been known as an apoptotic inducer in breast tumors in ethnomedicine. To scientifically confirm the anti-breast cancer effects of water, methanol (MeOH) and butanol (BuOH) extracts of O. diffusa on cell apoptosis, matrix metalloproteinases (MMPs), intercellular adhesion molecule (ICAM)-1 and intracellular signaling in MCF-7 breast cancer cells. MeOH extracts (MOD) and BuOH extracts (BOD) were prepared and examined for their ability to inhibit phorbol myristate acetate (PMA)-induced matrix metalloproteinase (MMP)-9 and intercellular adhesion molecule (ICAM)-1 expressions in MCF-7 human breast cancer cells. Additionally, transwell migration, invasion and transcriptional activity were assessed. Results of immunofluorescence confocal microscopy for translocation of NF-κB and p-ERK and p-p38 were also checked. Finally, apoptotic signals including processed caspase-8, caspase-7, poly ADP-ribose polymerase, Bax and Bcl-2 were examined. MOD and BOD specifically inhibited PMA-induced MMP-9 expression as well as invasive and migration potential via ICAM-1. The inhibitory activity was also based on the suppressed transcriptional activity in MCF-7 breast cancer cells. Results of immunofluorescence confocal microscopy showed that translocation of NF-κB decreased upon BOD and MOD treatments, with a decreased level of p-ERK and p-p38 phosphorylation. In addition, treatment of MCF-7 cells with MOD and BOD activated apoptosis-linked proteins including enzymatically active forms of processed caspase-8, caspase-7 and poly ADP-ribose polymerase, together with increased expression of mitochondrial apoptotic protein, Bax and decreased expression of Bcl-2. The results indicate that OD as an anti-metastatic agent suppresses the metastatic response by targeting p-ERK, p-38 and NF-κB, thus reducing the invasion capacity of MCF-7 breast cancer cells through inhibition of MMP-9 and ICAM-1 expression and plays an important role in the regulation of breast

  15. Formation of Ultracold Molecules

    SciTech Connect

    Cote, Robin

    2016-01-28

    Advances in our ability to slow down and cool atoms and molecules to ultracold temperatures have paved the way to a revolution in basic research on molecules. Ultracold molecules are sensitive of very weak interactions, even when separated by large distances, which allow studies of the effect of those interactions on the behavior of molecules. In this program, we have explored ways to form ultracold molecules starting from pairs of atoms that have already reached the ultracold regime. We devised methods that enhance the efficiency of ultracold molecule production, for example by tuning external magnetic fields and using appropriate laser excitations. We also investigates the properties of those ultracold molecules, especially their de-excitation into stable molecules. We studied the possibility of creating new classes of ultra-long range molecules, named macrodimers, thousand times more extended than regular molecules. Again, such objects are possible because ultra low temperatures prevent their breakup by collision. Finally, we carried out calculations on how chemical reactions are affected and modified at ultracold temperatures. Normally, reactions become less effective as the temperature decreases, but at ultracold temperatures, they can become very effective. We studied this counter-intuitive behavior for benchmark chemical reactions involving molecular hydrogen.

  16. Circularly Polarized Luminescence from Simple Organic Molecules.

    PubMed

    Sánchez-Carnerero, Esther M; Agarrabeitia, Antonia R; Moreno, Florencio; Maroto, Beatriz L; Muller, Gilles; Ortiz, María J; de la Moya, Santiago

    2015-09-21

    This article aims to show the identity of "circularly polarized luminescent active simple organic molecules" as a new concept in organic chemistry due to the potential interest of these molecules, as availed by the exponentially growing number of research articles related to them. In particular, it describes and highlights the interest and difficulty in developing chiral simple (small and non-aggregated) organic molecules able to emit left- or right-circularly polarized light efficiently, the efforts realized up to now to reach this challenging objective, and the most significant milestones achieved to date. General guidelines for the preparation of these interesting molecules are also presented.

  17. Electrochromic Graphene Molecules

    SciTech Connect

    Ji, Zhiqiang; Doorn, Stephen K.; Sykora, Milan

    2015-03-13

    Polyclic aromatic hydrocarbons, also called Graphene Molecules (GMs), with chemical composition C132H36(COOH)2 were synthesized in-situ on the surface of transparent nanocrystaline indium tin oxide (nc-ITO) electrodes. Their electronic structure was studied electrochemically and spectro-electrochemically. Variations in the potential applied onto the nc-ITO/GM electrodes induce only small changes in the observed current but they produce dramatic changes in the absorption of the GMs, which are associated with their oxidation and reduction. Analysis of the absorption changes using modified Nernst equation is used to determine standard potentials associated with the individual charge transfer processes. For the GMs prepared here these were found to be E1,ox 0 = 0.77± 0.01 V and E2,ox 0 = 1.24 ± 0.02 V vs. NHE for the first and second oxidation and E1,red 0 = -1.50 ± 0.04 V for the first reduction. The charge transfer processes are found to be non-ideal. The non-ideality factors associated with the oxidation and reduction processes suggest presence of strong interactions between the GM redox centers. Under the conditions of potential cycling GMs show rapid (seconds) color change with high contrast and stability. An electrochromic application is demonstrated wherein the GMs are used as the optically active component.

  18. The status of molecules

    SciTech Connect

    Barnes, T. :

    1994-10-01

    This report summarizes the experimental and theoretical status of hadronic molecules, which are weakly-bound states of two or more hadrons. We begin with a brief history of the subject and discuss a few good candidates, and then abstract some signatures for molecules which may be of interest in the classification of possible molecule states. Next we argue that a more general understanding of 2 {yields} 2 hadron-hadron scattering amplitudes will be crucial for molecule searches, and discuss some of our recent work in this area. We conclude with a discussion of a few more recent molecule candidates (notably the f{sub o}(1710)) which are not well established as molecules but satisfy some of the expected signatures.

  19. [Endothelial cell adhesion molecules].

    PubMed

    Ivanov, A N; Norkin, I A; Puchin'ian, D M; Shirokov, V Iu; Zhdanova, O Iu

    2014-01-01

    The review presents current data concerning the functional role of endothelial cell adhesion molecules belonging to different structural families: integrins, selectins, cadherins, and the immunoglobulin super-family. In this manuscript the regulatory mechanisms and factors of adhesion molecules expression and distribution on the surface of endothelial cells are discussed. The data presented reveal the importance of adhesion molecules in the regulation of structural and functional state of endothelial cells in normal conditions and in pathology. Particular attention is paid to the importance of these molecules in the processes of physiological and pathological angiogenesis, regulation of permeability of the endothelial barrier and cell transmigration.

  20. Intensity calculations of HCN molecules

    NASA Astrophysics Data System (ADS)

    Yasmin, Kausar

    2006-10-01

    Accurate spectroscopic data of HCN are required for many astronomical calculations and modeling. HCN molecules are present in the atmosphere of carbon stars and in galactic centers. Ro-vibrational energy levels and intensity calculations were carried out using the full coupled cluster model and radau coordinates. Accurate ab initio calculated potential energy surface^1 and dipole moment surface^2 were used for computation. The computed values were compared with Hitran^99.^

  1. Metagenomic small molecule discovery methods

    PubMed Central

    Charlop-Powers, Zachary; Milshteyn, Aleksandr; Brady, Sean F.

    2014-01-01

    Metagenomic approaches to natural product discovery provide the means of harvesting bioactive small molecules synthesized by environmental bacteria without the requirement of first culturing these organisms. Advances in sequencing technologies and general metagenomic methods are beginning to provide the tools necessary to unlock the unexplored biosynthetic potential encoded by the genomes of uncultured environmental bacteria. Here, we highlight recent advances in sequence- and functional- based metagenomic approaches that promise to facilitate antibiotic discovery from diverse environmental microbiomes. PMID:25000402

  2. Gibbs Free Energy of Hydrolytic Water Molecule in Acyl-Enzyme Intermediates of a Serine Protease: A Potential Application for Computer-Aided Discovery of Mechanism-Based Reversible Covalent Inhibitors.

    PubMed

    Masuda, Yosuke; Yamaotsu, Noriyuki; Hirono, Shuichi

    2017-01-01

    In order to predict the potencies of mechanism-based reversible covalent inhibitors, the relationships between calculated Gibbs free energy of hydrolytic water molecule in acyl-trypsin intermediates and experimentally measured catalytic rate constants (kcat) were investigated. After obtaining representative solution structures by molecular dynamics (MD) simulations, hydration thermodynamics analyses using WaterMap™ were conducted. Consequently, we found for the first time that when Gibbs free energy of the hydrolytic water molecule was lower, logarithms of kcat were also lower. The hydrolytic water molecule with favorable Gibbs free energy may hydrolyze acylated serine slowly. Gibbs free energy of hydrolytic water molecule might be a useful descriptor for computer-aided discovery of mechanism-based reversible covalent inhibitors of hydrolytic enzymes.

  3. Enzymatic DNA molecules

    NASA Technical Reports Server (NTRS)

    Joyce, Gerald F. (Inventor); Breaker, Ronald R. (Inventor)

    1998-01-01

    The present invention discloses deoxyribonucleic acid enzymes--catalytic or enzymatic DNA molecules--capable of cleaving nucleic acid sequences or molecules, particularly RNA, in a site-specific manner, as well as compositions including same. Methods of making and using the disclosed enzymes and compositions are also disclosed.

  4. Molecules between the Stars.

    ERIC Educational Resources Information Center

    Verschuur, Gerrit L.

    1987-01-01

    Provides a listing of molecules discovered to date in the vast interstellar clouds of dust and gas. Emphasizes the recent discoveries of organic molecules. Discusses molecular spectral lines, MASERs (microwave amplification by stimulated emission of radiation), molecular clouds, and star birth. (TW)

  5. Molecules between the Stars.

    ERIC Educational Resources Information Center

    Verschuur, Gerrit L.

    1987-01-01

    Provides a listing of molecules discovered to date in the vast interstellar clouds of dust and gas. Emphasizes the recent discoveries of organic molecules. Discusses molecular spectral lines, MASERs (microwave amplification by stimulated emission of radiation), molecular clouds, and star birth. (TW)

  6. Nonadiabatic reaction of energetic molecules.

    PubMed

    Bhattacharya, Atanu; Guo, Yuanqing; Bernstein, Elliot R

    2010-12-21

    Energetic materials store a large amount of chemical energy that can be readily converted into mechanical energy via decomposition. A number of different ignition processes such as sparks, shocks, heat, or arcs can initiate the excited electronic state decomposition of energetic materials. Experiments have demonstrated the essential role of excited electronic state decomposition in the energy conversion process. A full understanding of the mechanisms for the decomposition of energetic materials from excited electronic states will require the investigation and analysis of the specific topography of the excited electronic potential energy surfaces (PESs) of these molecules. The crossing of multidimensional electronic PESs creates a funnel-like topography, known as conical intersections (CIs). CIs are well established as a controlling factor in the excited electronic state decomposition of polyatomic molecules. This Account summarizes our current understanding of the nonadiabatic unimolecular chemistry of energetic materials through CIs and presents the essential role of CIs in the determination of decomposition pathways of these energetic systems. Because of the involvement of more than one PES, a decomposition process involving CIs is an electronically nonadiabatic mechanism. Based on our experimental observations and theoretical calculations, we find that a nonadiabatic reaction through CIs dominates the initial decomposition process of energetic materials from excited electronic states. Although the nonadiabatic behavior of some polyatomic molecules has been well studied, the role of nonadiabatic reactions in the excited electronic state decomposition of energetic molecules has not been well investigated. We use both nanosecond energy-resolved and femtosecond time-resolved spectroscopic techniques to determine the decomposition mechanism and dynamics of energetic species experimentally. Subsequently, we employ multiconfigurational methodologies (such as, CASSCF

  7. Dynamics of Activated Molecules

    SciTech Connect

    Mullin, Amy S.

    2016-11-16

    Experimental studies have been performed to investigate the collisional energy transfer processes of gas-phase molecules that contain large amounts of internal energy. Such molecules are prototypes for molecules under high temperature conditions relevant in combustion and information about their energy transfer mechanisms is needed for a detailed understanding and modeling of the chemistry. We use high resolution transient IR absorption spectroscopy to measure the full, nascent product distributions for collisions of small bath molecules that relax highly vibrationally excited pyrazine molecules with E=38000 cm-1 of vibrational energy. To perform these studies, we developed new instrumentation based on modern IR light sources to expand our experimental capabilities to investigate new molecules as collision partners. This final report describes our research in four areas: the characterization of a new transient absorption spectrometer and the results of state-resolved collision studies of pyrazine(E) with HCl, methane and ammonia. Through this research we have gained fundamental new insights into the microscopic details of relatively large complex molecules at high energy as they undergo quenching collisions and redistribute their energy.

  8. Classical density functional theory for the prediction of the surface tension and interfacial properties of fluids mixtures of chain molecules based on the statistical associating fluid theory for potentials of variable range.

    PubMed

    Llovell, Fèlix; Galindo, Amparo; Blas, Felipe J; Jackson, George

    2010-07-14

    The statistical associating fluid theory for attractive potentials of variable range (SAFT-VR) density functional theory (DFT) developed by [G. J. Gloor et al., J. Chem. Phys. 121, 12740 (2004)] is revisited and generalized to treat mixtures. The Helmholtz free-energy functional, which is based on the SAFT-VR approach for homogeneous fluids, is constructed by partitioning the free-energy density into a reference term (which incorporates all of the short-range interactions and is treated locally) and an attractive perturbation (which incorporates the long-range dispersion interactions). In this work, two different functionals are compared. In the first, one uses a mean-field version of the theory to treat the long-range dispersive interaction, incorporating an approximate treatment of the effect of the correlations on the attractive energy between the segments by introducing a short-range attractive contribution in the reference term. In the second, one approximates the correlation function of the molecular segments in the inhomogeneous system with that of a homogeneous system for an average density of the two positions, following the ideas proposed by Toxvaerd [S. Toxvaerd, J. Chem. Phys. 64, 2863 (1976)]. The SAFT-VR DFT formalism is then used to study interfacial properties and adsorption phenomena at the interface. A detailed analysis of the influence of the molecular parameters on the surface tension and density/composition profiles of the mixtures is undertaken for binary mixtures of molecules of different chain length, segment diameter, dispersive energy, and attractive range. The effect of the asymmetry of the molecular species on the adsorption phenomena is examined in some depth. The adequacy of the approach is demonstrated by comparing the theoretical predictions with the interfacial properties of some real mixtures. The relative merits of the two approximate free-energy functionals are assessed by examining the vapor-liquid interfacial tension of

  9. Heavy exotic molecules

    NASA Astrophysics Data System (ADS)

    Liu, Yizhuang; Zahed, Ismail

    We briefly review the formation of pion-mediated heavy-light exotic molecules with both charm and bottom, under the general structures of chiral and heavy quark symmetries. The charm isosinglet exotic molecules with JPC = 1++ binds, which we identify as the reported neutral X(3872). The bottom isotriplet exotic with JPC = 1+- binds, and is identified as a mixed state of the reported charged exotics Zb+(10610) and Zb+(10650). The bound bottom isosinglet molecule with JPC = 1++ is a possible neutral Xb(10532) to be observed.

  10. Heavy exotic molecules

    NASA Astrophysics Data System (ADS)

    Liu, Yizhuang; Zahed, Ismail

    We briefly review the formation of pion-mediated heavy-light exotic molecules with both charm and bottom, under the general structures of chiral and heavy quark symmetries. The charm isosinglet exotic molecules with JPC = 1++ binds, which we identify as the reported neutral X(3872). The bottom isotriplet exotic with JPC = 1+1 binds, and is identified as a mixed state of the reported charged exotics Zb+(10610) and Zb-(10650). The bound bottom isosinglet molecule with JPC = 1++ is a possible neutral Xb(10532) to be observed.

  11. Of Molecules and Models.

    ERIC Educational Resources Information Center

    Brinner, Bonnie

    1992-01-01

    Presents an activity in which models help students visualize both the DNA process and transcription. After constructing DNA, RNA messenger, and RNA transfer molecules; students model cells, protein synthesis, codons, and RNA movement. (MDH)

  12. Single-Molecule Enzymology

    SciTech Connect

    Xie, Xiaoliang; Lu, H PETER.

    1999-06-04

    Viewing a movie of an enzyme molecule made from molecular dynamics (MD) simulation, we see incredible details of molecular motions, be it a change of the conformation or the action of a chemical reaction.

  13. Of Molecules and Models.

    ERIC Educational Resources Information Center

    Brinner, Bonnie

    1992-01-01

    Presents an activity in which models help students visualize both the DNA process and transcription. After constructing DNA, RNA messenger, and RNA transfer molecules; students model cells, protein synthesis, codons, and RNA movement. (MDH)

  14. Laser cooling of a diatomic molecule.

    PubMed

    Shuman, E S; Barry, J F; Demille, D

    2010-10-14

    It has been roughly three decades since laser cooling techniques produced ultracold atoms, leading to rapid advances in a wide array of fields. Laser cooling has not yet been extended to molecules because of their complex internal structure. However, this complexity makes molecules potentially useful for a wide range of applications. For example, heteronuclear molecules possess permanent electric dipole moments that lead to long-range, tunable, anisotropic dipole-dipole interactions. The combination of the dipole-dipole interaction and the precise control over molecular degrees of freedom possible at ultracold temperatures makes ultracold molecules attractive candidates for use in quantum simulations of condensed-matter systems and in quantum computation. Also, ultracold molecules could provide unique opportunities for studying chemical dynamics and for tests of fundamental symmetries. Here we experimentally demonstrate laser cooling of the polar molecule strontium monofluoride (SrF). Using an optical cycling scheme requiring only three lasers, we have observed both Sisyphus and Doppler cooling forces that reduce the transverse temperature of a SrF molecular beam substantially, to a few millikelvin or less. At present, the only technique for producing ultracold molecules is to bind together ultracold alkali atoms through Feshbach resonance or photoassociation. However, proposed applications for ultracold molecules require a variety of molecular energy-level structures (for example unpaired electronic spin, Omega doublets and so on). Our method provides an alternative route to ultracold molecules. In particular, it bridges the gap between ultracold (submillikelvin) temperatures and the ∼1-K temperatures attainable with directly cooled molecules (for example with cryogenic buffer-gas cooling or decelerated supersonic beams). Ultimately, our technique should allow the production of large samples of molecules at ultracold temperatures for species that are chemically

  15. Affibody molecules as engineered protein drugs

    PubMed Central

    Frejd, Fredrik Y; Kim, Kyu-Tae

    2017-01-01

    Affibody molecules can be used as tools for molecular recognition in diagnostic and therapeutic applications. There are several preclinical studies reported on diagnostic and therapeutic use of this molecular class of alternative scaffolds, and early clinical evidence is now beginning to accumulate that suggests the Affibody molecules to be efficacious and safe in man. The small size and ease of engineering make Affibody molecules suitable for use in multispecific constructs where AffiMabs is one such that offers the option to potentiate antibodies for use in complex disease. PMID:28336959

  16. Circularly Polarized Luminescence from Simple Organic Molecules

    PubMed Central

    Sánchez-Carnerero, Esther M.; Agarrabeitia, Antonia R.; Moreno, Florencio; Maroto, Beatriz L.; Muller, Gilles; Ortiz, María J.

    2015-01-01

    This article aims to show the identity of “CPL-active simple organic molecules” as a new concept in Organic Chemistry due to the potential interest of these molecules, as availed by the exponentially growing number of research articles related to them. In particular, it describes and highlights the interest and difficulty in developing chiral simple (small and nonaggregated) organic molecules able to emit left- or right-circularly polarized light efficiently, the efforts realized up to now to reach this challenging objective, and the most significant milestones achieved to date. General guidelines for the preparation of these interesting molecules are also presented. PMID:26136234

  17. Enhancement of the cytotoxic potential of the mixed EGFR and DNA-targeting 'combi-molecule' ZRBA1 against human solid tumour cells by a bis-quinazoline-based drug design approach.

    PubMed

    Al-Safadi, Sherin; Domarkas, Juozas; Han, YingShan; Brahimi, Fouad; Jean-Claude, Bertrand J

    2012-06-01

    ZRBA1 is a quinazoline-based molecule termed 'combi-molecule' designed to block the epidermal growth factor receptor (EGFR) and further degrade to FD105, an EGFR inhibitor plus a DNA-alkylating agent. To augment the potency of ZRBA1, we designed JDE52, a bistriazene that, following degradation, was 'programmed' to yield higher concentrations of the free inhibitor FD105 and a more cytotoxic bifunctional DNA-damaging species. The results indicated that JDE52 was capable of inducing significant blockade of EGFR phosphorylation, DNA strand breaks and interstrand cross-links in human cells. The fluorescent property of FD105, the secondary inhibitor that both JDE52 and ZRBA1 are capable of releasing, has permitted the analysis of its levels in tumour cells by ultraviolet flow cytometry. It was found that JDE52 was indeed capable of significantly releasing higher levels of fluorescence (P<0.05) in human tumour cells when compared with ZRBA1. Apoptosis was triggered by JDE52 at a faster rate than ZRBA1 and led to higher levels of cell killing. The results in toto suggest that the superior potency of JDE52, when compared with ZRBA1, may be imputed to mechanisms associated with the generation of higher intracellular concentrations of FD105 and to the induction of DNA cross-links. These combined mechanisms (blockade of EGFR-tyrosine kinase and induction of cross-links) contributed to an accelerated rate of apoptosis by JDE52. This study conclusively demonstrated that designing molecules as prodrugs of high levels of quinazoline inhibitors of EGFR and bifunctional DNA cross-linking species is a valid strategy to enhance the potency of mixed EGFR-DNA-targeting combi-molecules.

  18. Positronium ions and molecules

    NASA Technical Reports Server (NTRS)

    Ho, Y. K.

    1990-01-01

    Recent theoretical studies on positronium ions and molecules are discussed. A positronium ion is a three particle system consisting of two electrons in singlet spin state, and a positron. Recent studies include calculations of its binding energy, positron annihilation rate, and investigations of its doubly excited resonant states. A positronium molecule is a four body system consisting of two positrons and two electrons in an overall singlet spin state. The recent calculations of its binding energy against the dissociation into two positronium atoms, and studies of auto-detaching states in positronium molecules are discussed. These auto-dissociating states, which are believed to be part of the Rydberg series as a result of a positron attaching to a negatively charged positronium ion, Ps-, would appear as resonances in Ps-Ps scattering.

  19. MOLECULES IN {eta} CARINAE

    SciTech Connect

    Loinard, Laurent; Menten, Karl M.; Guesten, Rolf; Zapata, Luis A.; Rodriguez, Luis F.

    2012-04-10

    We report the detection toward {eta} Carinae of six new molecules, CO, CN, HCO{sup +}, HCN, HNC, and N{sub 2}H{sup +}, and of two of their less abundant isotopic counterparts, {sup 13}CO and H{sup 13}CN. The line profiles are moderately broad ({approx}100 km s{sup -1}), indicating that the emission originates in the dense, possibly clumpy, central arcsecond of the Homunculus Nebula. Contrary to previous claims, CO and HCO{sup +} do not appear to be underabundant in {eta} Carinae. On the other hand, molecules containing nitrogen or the {sup 13}C isotope of carbon are overabundant by about one order of magnitude. This demonstrates that, together with the dust responsible for the dimming of {eta} Carinae following the Great Eruption, the molecules detected here must have formed in situ out of CNO-processed stellar material.

  20. Molecules as Automata

    NASA Astrophysics Data System (ADS)

    Cardelli, Luca

    Molecular biology investigates the structure and function of biochemical systems starting from their basic building blocks: macromolecules. A macromolecule is a large, complex molecule (a protein or a nucleic acid) that usually has inner mutable state and external activity. Informal explanations of biochemical events trace individual macromolecules through their state changes and their interaction histories: a macromolecule is endowed with an identity that is retained through its transformations, even through changes in molecular energy and mass. A macromolecule, therefore, is qualitatively different from the small molecules of inorganic chemistry. Such molecules are stateless: in the standard notation for chemical reactions they are seemingly created and destroyed, and their atomic structure is used mainly for the bookkeeping required by the conservation of mass.

  1. Photochemistry of interstellar molecules

    NASA Technical Reports Server (NTRS)

    Stief, L. J.

    1971-01-01

    The photochemistry of two diatomic and eight polyatomic molecules is discussed quantitatively. For an interstellar molecule, the lifetime against photodecomposition depends upon the absorption cross section, the quantum yield or probability of dissociation following photon absorption, and the interstellar radiation field. The constant energy density of Habing is used for the unobserved regions of interstellar radiation field, and the field in obscuring clouds is estimated by combining the constant flux with the observed interstellar extinction curve covering the visible and ultraviolet regions. Lifetimes against photodecomposition in the unobscured regions and as a function of increasing optical thickness in obscuring clouds are calculated for the ten species. The results show that, except for CO, all the molecules have comparable lifetimes of less than one hundred years. Thus they can exist only in dense clouds and can never have been exposed to the unobscured radiation. The calculations further show that the lifetimes in clouds of moderate opacity are of the order of one million years.

  2. Single molecule diffraction.

    PubMed

    Spence, J C H; Doak, R B

    2004-05-14

    For solving the atomic structure of organic molecules such as small proteins which are difficult to crystallize, the use of a jet of doped liquid helium droplets traversing a continuous high energy electron beam is proposed as a means of obtaining electron diffraction patterns (serial crystallography). Organic molecules (such as small proteins) within the droplet (and within a vitreous ice jacket) may be aligned by use of a polarized laser beam. Iterative methods for solving the phase problem are indicated. Comparisons with a related plan for pulsed x-ray diffraction from single proteins in a molecular beam are provided.

  3. DNA: An Extensible Molecule

    NASA Astrophysics Data System (ADS)

    Cluzel, Philippe; Lebrun, Anne; Heller, Christoph; Lavery, Richard; Viovy, Jean-Louis; Chatenay, Didier; Caron, Francois

    1996-02-01

    The force-displacement response of a single duplex DNA molecule was measured. The force saturates at a plateau around 70 piconewtons, which ends when the DNA has been stretched about 1.7 times its contour length. This behavior reveals a highly cooperative transition to a state here termed S-DNA. Addition of an intercalator suppresses this transition. Molecular modeling of the process also yields a force plateau and suggests a structure for the extended form. These results may shed light on biological processes involving DNA extension and open the route for mechanical studies on individual molecules in a previously unexplored range.

  4. Enzyme molecules as nanomotors.

    PubMed

    Sengupta, Samudra; Dey, Krishna K; Muddana, Hari S; Tabouillot, Tristan; Ibele, Michael E; Butler, Peter J; Sen, Ayusman

    2013-01-30

    Using fluorescence correlation spectroscopy, we show that the diffusive movements of catalase enzyme molecules increase in the presence of the substrate, hydrogen peroxide, in a concentration-dependent manner. Employing a microfluidic device to generate a substrate concentration gradient, we show that both catalase and urease enzyme molecules spread toward areas of higher substrate concentration, a form of chemotaxis at the molecular scale. Using glucose oxidase and glucose to generate a hydrogen peroxide gradient, we induce the migration of catalase toward glucose oxidase, thereby showing that chemically interconnected enzymes can be drawn together.

  5. Torsional and rotational couplings in nonrigid molecules

    NASA Astrophysics Data System (ADS)

    Omiste, Juan J.; Madsen, Lars Bojer

    2017-02-01

    We analyze theoretically the interplay between the torsional and the rotational motion of an aligned biphenyl-like molecule. To do so, we consider a transition between two electronic states with different internal torsional potentials, induced by means of a resonant laser pulse. The change in the internal torsional potential provokes the motion of the torsional wave packet in the excited electronic state, modifying the structure of the molecule, and hence, its inertia tensor. We find that this process has a strong impact on the rotational wave function, displaying different behavior depending on the electronic states involved and their associated torsional potentials. We describe the dynamics of the system by considering the degree of alignment and the expectation values of the angular momentum operators for the overall rotation of the molecule.

  6. Helminth-derived immunomodulatory molecules.

    PubMed

    Adisakwattana, Poom; Saunders, Sean P; Nel, Hendrik J; Fallon, Padraic G

    2009-01-01

    Infection of man with parasitic helminths leads to potent activation and modulation of the host immune response. This modulation of immunity by helminth infections may have bystander effects in altering, either suppressing or exacerbating, unrelated inflammatory processes. Various ongoing clinical trials are testing the therapeutic application of helminth infection of patients with inflammatory diseases, including inflammatory bowel disease and allergic disorders. Rather than the use of live helminth infection, with the potential for side effects, an alternative approach is to identify the immune modulatory molecules (IM) produced by helminths that can alter immune functions. In this review, we will focus on characterized helminth-derived IMs that may have potential to be developed as novel therapeutics for inflammatory diseases.

  7. Diversity in Biological Molecules

    ERIC Educational Resources Information Center

    Newbury, H. John

    2010-01-01

    One of the striking characteristics of fundamental biological processes, such as genetic inheritance, development and primary metabolism, is the limited amount of variation in the molecules involved. Natural selective pressures act strongly on these core processes and individuals carrying mutations and producing slightly sub-optimal versions of…

  8. Mighty Molecule Models

    ERIC Educational Resources Information Center

    Brown, Tom; Rushton, Greg; Bencomo, Marie

    2008-01-01

    As part of the SMATHematics Project: The Wonder of Science, The Power of Mathematics--a collaborative partnership between Kennesaw State University and two local school districts, fifth graders had the opportunity to puzzle out chemical formulas of propane, methanol, and other important molecules. In addition, they explored properties that…

  9. Diversity in Biological Molecules

    ERIC Educational Resources Information Center

    Newbury, H. John

    2010-01-01

    One of the striking characteristics of fundamental biological processes, such as genetic inheritance, development and primary metabolism, is the limited amount of variation in the molecules involved. Natural selective pressures act strongly on these core processes and individuals carrying mutations and producing slightly sub-optimal versions of…

  10. Mighty Molecule Models

    ERIC Educational Resources Information Center

    Brown, Tom; Rushton, Greg; Bencomo, Marie

    2008-01-01

    As part of the SMATHematics Project: The Wonder of Science, The Power of Mathematics--a collaborative partnership between Kennesaw State University and two local school districts, fifth graders had the opportunity to puzzle out chemical formulas of propane, methanol, and other important molecules. In addition, they explored properties that…

  11. Disentangling DNA molecules

    NASA Astrophysics Data System (ADS)

    Vologodskii, Alexander

    2016-09-01

    The widespread circular form of DNA molecules inside cells creates very serious topological problems during replication. Due to the helical structure of the double helix the parental strands of circular DNA form a link of very high order, and yet they have to be unlinked before the cell division. DNA topoisomerases, the enzymes that catalyze passing of one DNA segment through another, solve this problem in principle. However, it is very difficult to remove all entanglements between the replicated DNA molecules due to huge length of DNA comparing to the cell size. One strategy that nature uses to overcome this problem is to create the topoisomerases that can dramatically reduce the fraction of linked circular DNA molecules relative to the corresponding fraction at thermodynamic equilibrium. This striking property of the enzymes means that the enzymes that interact with DNA only locally can access their topology, a global property of circular DNA molecules. This review considers the experimental studies of the phenomenon and analyzes the theoretical models that have been suggested in attempts to explain it. We describe here how various models of enzyme action can be investigated computationally. There is no doubt at the moment that we understand basic principles governing enzyme action. Still, there are essential quantitative discrepancies between the experimental data and the theoretical predictions. We consider how these discrepancies can be overcome.

  12. Single molecules: Thermodynamic limits

    NASA Astrophysics Data System (ADS)

    Liphardt, Jan

    2012-09-01

    Technologies aimed at single-molecule resolution of non-equilibrium systems increasingly require sophisticated new ways of thinking about thermodynamics. An elegant extension to standard fluctuation theory grants access to the kinetic intermediate states of these systems -- as DNA-pulling experiments now demonstrate.

  13. Disentangling DNA molecules.

    PubMed

    Vologodskii, Alexander

    2016-09-01

    The widespread circular form of DNA molecules inside cells creates very serious topological problems during replication. Due to the helical structure of the double helix the parental strands of circular DNA form a link of very high order, and yet they have to be unlinked before the cell division. DNA topoisomerases, the enzymes that catalyze passing of one DNA segment through another, solve this problem in principle. However, it is very difficult to remove all entanglements between the replicated DNA molecules due to huge length of DNA comparing to the cell size. One strategy that nature uses to overcome this problem is to create the topoisomerases that can dramatically reduce the fraction of linked circular DNA molecules relative to the corresponding fraction at thermodynamic equilibrium. This striking property of the enzymes means that the enzymes that interact with DNA only locally can access their topology, a global property of circular DNA molecules. This review considers the experimental studies of the phenomenon and analyzes the theoretical models that have been suggested in attempts to explain it. We describe here how various models of enzyme action can be investigated computationally. There is no doubt at the moment that we understand basic principles governing enzyme action. Still, there are essential quantitative discrepancies between the experimental data and the theoretical predictions. We consider how these discrepancies can be overcome. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Sweeping molecules with light

    NASA Astrophysics Data System (ADS)

    Hutzler, Nicholas R.

    2017-03-01

    Many areas of physics—precision measurements, quantum information, and physical chemistry, to name a few—are starting to benefit from the enormous advantages offered by cold and ultracold polar molecules. Molecules have more states, more interactions, and more chemical properties compared to atoms, which make them exciting to study but difficult to tame. In particular, the powerful techniques of atomic laser cooling cannot be naïvely applied to molecules due to their complicated structure. Developments over the past few years have made directly laser cooled and trapped molecules a reality, and now much effort is focused on making these samples larger, denser, and colder—an important step to realizing many of their exciting applications. A careful experimental and numerical study by Truppe et al (2017 New J. Phys. 19 022001) demonstrates a significant improvement and advance in understanding of one of the most limiting steps in laser cooling and trapping of molecules—slowing them from a molecular beam to a near-standstill, with small enough kinetic energy that they can be loaded into a trap.

  15. Three new 'nonterrestrial' molecules

    NASA Astrophysics Data System (ADS)

    Thaddeus, P.; Guelin, M.; Linke, R. A.

    1981-05-01

    Eight new interstellar lines have been detected from three molecules not previously observed spectroscopically in space or in the laboratory. One is a linear or nearly linear molecule with microwave constants B0 equals 21,337.15 plus or minus 0.06 MHz, D0 equals 21.4 plus or minus 1.5 kHz. This is the thioformyl ion HCS(plus), first identified because B0 and D0 are close to those calculated, and now confirmed by laboratory detection of one of the present lines (Gudeman et al.). The second molecule, also linear or nearly so, has microwave constants B0 equals 10,691,406 plus or minus 0.043 MHz, D0 equals 1.84 plus or minus 0.91 kHz close to those expected for the isoelectronic systems HOCO(plus) and HOCN; a choice between the two cannot be made on the basis of the available astronomical data. The existence of a third molecule is deduced from an unidentified line at 85,338 MHz that has been found in many sources, is fairly intense in several, and may be self-absorbed in Sgr B2.

  16. Algebraic theory of molecules

    NASA Technical Reports Server (NTRS)

    Iachello, Franco

    1995-01-01

    An algebraic formulation of quantum mechanics is presented. In this formulation, operators of interest are expanded onto elements of an algebra, G. For bound state problems in nu dimensions the algebra G is taken to be U(nu + 1). Applications to the structure of molecules are presented.

  17. Controlling polar molecules in optical lattices

    SciTech Connect

    Kotochigova, S.; Tiesinga, E.

    2006-04-15

    We theoretically investigate the interaction of polar molecules with optical lattices and microwave fields. We demonstrate the existence of frequency windows in the optical domain where the complex internal structure of the molecule does not influence the trapping potential of the lattice. In such frequency windows the Franck-Condon factors are so small that near-resonant interaction of vibrational levels of the molecule with the lattice fields have a negligible contribution to the polarizability, and light-induced decoherences are kept to a minimum. In addition, we show that microwave fields can induce a tunable dipole-dipole interaction between ground-state rotationally symmetric (J=0) molecules. A combination of a carefully chosen lattice frequency and microwave-controlled interaction between molecules will enable trapping of polar molecules in a lattice and possibly realize molecular quantum logic gates. Our results are based on ab initio relativistic electronic structure calculations of the polar KRb and RbCs molecules combined with calculations of their rovibrational motion.

  18. Potentiometric Sensing of the Organic Molecules

    NASA Astrophysics Data System (ADS)

    Wang, Yantian; Jain, Vijay; Lee, Harriman; Levon, Kalle; Rafailovich, Miriam; Sokolov, Jonathan

    2006-03-01

    A prototype detector was constructed for the detection of complex biomolecules, such as viruses and complete chromosomes. The technology is based on ref. [1], where the technique was demonstrated for small molecules. A monolayer of 11-mercapto-1-undocanol (thiol) is co-absorbed with the organic molecules on a gold plated electrode. The thiolated molecules self assemble into a highly organized crystalline film chemically anchored to the surface. The bio-molecules which are not attached and can then be removed by washing in water, leaving behind templated regions, or cavities in the monolayer with specific size and shape. The electrochemical response between the modified electrode and the Ag/AgCl reference electrode was measured by the potentiometer. When the electrode was exposed to the solution containing the template molecules, in a concentration as low as 10-6M, a sharp potential response was observed, while very slight response was observed when exposed to other kind of molecules. This was attributed to the selective absorption of the molecules onto the electrode. Reference: [1]. Zhou Y., Yu B., Shiu E., Levon K., Anal. Chem. 2004, 76, 2689.

  19. OMG: Open Molecule Generator.

    PubMed

    Peironcely, Julio E; Rojas-Chertó, Miguel; Fichera, Davide; Reijmers, Theo; Coulier, Leon; Faulon, Jean-Loup; Hankemeier, Thomas

    2012-09-17

    Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck.

  20. OMG: Open Molecule Generator

    PubMed Central

    2012-01-01

    Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck. PMID:22985496

  1. Novel electrostatic trap for cold polar molecules

    NASA Astrophysics Data System (ADS)

    Xu, Xue-Yan; Ma, Hui; Yin, Jian-Ping

    2007-12-01

    We propose a novel scheme in which cold polar molecules are trapped by an electrostatic field generated by the combination of a pair of parallel transparent electrodes (i.e., two infinite transparent plates) and a ring electrode (i.e., a ring wire). The spatial distributions of the electrostatic fields from the above charged wire and the charged plates and the corresponding Stark potentials for cold CO molecules are calculated; the dependences of the trap centre position on the geometric parameters of the electrode are analysed. We also discuss the loading process of cold molecules from a cold molecular beam into our trap. This study shows that the proposed scheme is not only simple and convenient to trap, manipulate and control cold polar molecules in weak-field-seeking states, but also provides an opportunity to study cold collisions and collective quantum effects in a variety of cold molecular systems, etc.

  2. Dietary choline deficiency and excess induced intestinal inflammation and alteration of intestinal tight junction protein transcription potentially by modulating NF-κB, STAT and p38 MAPK signaling molecules in juvenile Jian carp.

    PubMed

    Wu, Pei; Jiang, Wei-Dan; Jiang, Jun; Zhao, Juan; Liu, Yang; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

    2016-11-01

    This study investigated the effects of choline on intestinal mucosal immune and the possible mechanisms in fish by feeding juvenile Jian carp (Cyprinus carpio var. Jian) with graded levels of dietary choline (165-1820 mg/kg diet) for 65 days. The results firstly showed that choline deficiency induced inflammatory infiltration in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) of fish. Meanwhile, compared with the optimal choline group, choline deficiency decreased the activities of lysozyme and acid phosphatase, contents of complement 3 and IgM in the intestine, downregulated the mRNA levels of antimicrobial peptides (liver-expressed antimicrobial peptide (LEAP) 2A and defensin-3 in the PI and MI, LEAP-2B and hepcidin in the PI, MI and DI), anti-inflammatory cytokines (interleukin (IL) 10 and transforming growth factor β2 in the PI, MI and DI), and signaling molecule IκB in the PI, MI and DI; while upregulated the mRNA levels of pro-inflammatory cytokines (IL-6a and tumor necrosis factor α in the MI and DI, interferon γ2b in the PI and MI, IL-1β and IL-6b in the PI, MI and DI), and signaling molecules (Toll-like receptor 4 in the MI, myeloid differentiation primary response 88 in the PI and MI, Janus kinase 3 and tyrosine kinase 2 in the MI and DI, nuclear factor kappa B (NF-κB), signal transducers and activators of transcription (STAT) 4 and STAT5 in the PI, MI and DI) of juvenile Jian carp, further indicating that choline deficiency caused inflammation and immunity depression in the intestine of fish. But choline deficiency decreased the PI IL-6a mRNA level, and increased the DI LEAP-2A and defensin-3 mRNA levels with unknown reasons. Furthermore, dietary choline deficiency downregulated mRNA levels of tight junction (TJ) proteins (claudin 3c in the PI and MI, claudin 7, claudin 11 and occludin in the PI, MI and DI) and signaling molecule mitogen-activated protein kinases p38 in the PI, MI and DI of juvenile Jian carp, whereas

  3. Bacterial invasion reconstructed molecule by molecule

    SciTech Connect

    Werner, James H

    2009-01-01

    We propose to visualize the initial stages of bacterial infection of a human host cell with unmatched spatial and temporal resolution. This work will develop a new capability for the laboratory (super-resolution optical imaging), will test unresolved scientific hypotheses regarding host-pathogen interaction dynamics, and leverages state of the art 3D molecular tracking instrumentation developed recently by our group. There is much to be gained by applying new single molecule tools to the important and familiar problem of pathogen entry into a host cell. For example, conventional fluorescence microscopy has identified key host receptors, such as CD44 and {alpha}5{beta}1 integrin, that aggregate near the site of Salmonella typhimurium infection of human cells. However, due to the small size of the bacteria ({approx} 2 {micro}m) and the diffraction of the emitted light, one just sees a fluorescent 'blob' of host receptors that aggregate at the site of attachment, making it difficult to determine the exact number of receptors present or whether there is any particular spatial arrangement of the receptors that facilitates bacterial adhesion/entry. Using newly developed single molecule based super-resolution imaging methods, we will visualize how host receptors are directed to the site of pathogen adhesion and whether host receptors adopt a specific spatial arrangement for successful infection. Furthermore, we will employ our 3D molecular tracking methods to follow the injection of virulence proteins, or effectors, into the host cell by the pathogen Type III secretion system (TTSS). We expect these studies to provide mechanistic insights into the early events of pathogen infection that have here-to-fore been technically beyond our reach. Our Research Goals are: Goal 1--Construct a super-resolution fluorescence microscope and use this new capability to image the spatial distribution of different host receptors (e.g. CD44, as {alpha}5{beta}1 integrin) at the point of

  4. Modelling water molecules inside cyclic peptide nanotubes

    NASA Astrophysics Data System (ADS)

    Tiangtrong, Prangsai; Thamwattana, Ngamta; Baowan, Duangkamon

    2016-03-01

    Cyclic peptide nanotubes occur during the self-assembly process of cyclic peptides. Due to the ease of synthesis and ability to control the properties of outer surface and inner diameter by manipulating the functional side chains and the number of amino acids, cyclic peptide nanotubes have attracted much interest from many research areas. A potential application of peptide nanotubes is their use as artificial transmembrane channels for transporting ions, biomolecules and waters into cells. Here, we use the Lennard-Jones potential and a continuum approach to study the interaction of a water molecule in a cyclo[(- D-Ala- L-Ala)_4-] peptide nanotube. Assuming that each unit of a nanotube comprises an inner and an outer tube and that a water molecule is made up of a sphere of two hydrogen atoms uniformly distributed over its surface and a single oxygen atom at the centre, we determine analytically the interaction energy of the water molecule and the peptide nanotube. Using this energy, we find that, independent of the number of peptide units, the water molecule will be accepted inside the nanotube. Once inside the nanotube, we show that a water molecule prefers to be off-axis, closer to the surface of the inner nanotube. Furthermore, our study of two water molecules inside the peptide nanotube supports the finding that water molecules form an array of a 1-2-1-2 file inside peptide nanotubes. The theoretical study presented here can facilitate thorough understanding of the behaviour of water molecules inside peptide nanotubes for applications, such as artificial transmembrane channels.

  5. Molecules in Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Berdyugina, Svetlana

    2015-08-01

    Molecules probe cool matter in the Universe and various astrophysical objects. Their ability to sense magnetic fields provides new insights into magnetic properties of these objects. During the past fifteen years we have carried out a theoretical study of molecular magnetic effects such as the Zeeman, Paschen-Back and Hanle effects and their applications for inferring magnetic structures and spatial inhomogeneities on the Sun, cool stars, brown dwarfs, and exoplanets from molecular spectro-polarimetry (e.g., Berdyugina 2011). Here, we present an overview of this study and compare our theoretical predictions with recent laboratory measurements of magnetic properties of some molecules. We present also a new web-based tool to compute molecular magnetic effects and polarized spectra which is supported by the ERC Advanced Grant HotMol.

  6. Single-molecule electrometry

    NASA Astrophysics Data System (ADS)

    Ruggeri, Francesca; Zosel, Franziska; Mutter, Natalie; Różycka, Mirosława; Wojtas, Magdalena; Ożyhar, Andrzej; Schuler, Benjamin; Krishnan, Madhavi

    2017-05-01

    Mass and electrical charge are fundamental properties of biological macromolecules. Although molecular mass has long been determined with atomic precision, a direct and precise determination of molecular charge remains an outstanding challenge. Here we report high-precision (<1e) measurements of the electrical charge of molecules such as nucleic acids, and globular and disordered proteins in solution. The measurement is based on parallel external field-free trapping of single macromolecules, permits the estimation of a dielectric coefficient of the molecular interior and can be performed in real time. Further, we demonstrate the direct detection of single amino acid substitution and chemical modifications in proteins. As the electrical charge of a macromolecule strongly depends on its three-dimensional conformation, this kind of high-precision electrometry offers an approach to probe the structure, fluctuations and interactions of a single molecule in solution.

  7. Strange skyrmion molecules

    NASA Astrophysics Data System (ADS)

    Kopeliovich, Vladimir B.; Stern, Boris E.

    1997-05-01

    Composed skyrmions with B=2, strangeness content close to 0.5 and the binding energy of several tens of Mev are described. These skyrmions are obtained starting from the system of two B=1 hedgehogs located in different SU(2) subgroups of SU(3) and have the mass and baryon number distribution of molecular (dipole) type. The quantization of zero modes of skyrmion molecules and physics consequences of their existence are discussed.

  8. Strange skyrmion molecules

    SciTech Connect

    Kopeliovich, Vladimir B.; Stern, Boris E.

    1997-05-20

    Composed skyrmions with B=2, strangeness content close to 0.5 and the binding energy of several tens of Mev are described. These skyrmions are obtained starting from the system of two B=1 hedgehogs located in different SU(2) subgroups of SU(3) and have the mass and baryon number distribution of molecular (dipole) type. The quantization of zero modes of skyrmion molecules and physics consequences of their existence are discussed.

  9. Characterization of dinaphthosulfoxide molecule

    NASA Astrophysics Data System (ADS)

    Uluçam, Gühergül; Okan, S. Erol; Aktaş, Şaban; Öğretmen, Gül Penbe

    2015-12-01

    Dinaphthosulfoxide has been synthesized, and confirmed by the experimental methods. The geometrical optimization of the two isomers of the molecule in their ground state was studied using density functional theory. Then, NMR and IR spectra were calculated for the optimized configurations. Analyzing the hydroxyl features in the NMR data and that of sulfoxide in IR spectra, the experimental observables are found to be in agreement with the properties of the syn isomer.

  10. Single Molecule Mechanochemistry

    NASA Astrophysics Data System (ADS)

    Li, Shaowei; Zhang, Yanxing; Ho, Wilson; Wu, Ruqian; Ruqian Wu, Yanxing Zhang Team; Wilson Ho, Shaowei Li Team

    Mechanical forces can be used to trigger chemical reactions through bending and stretching of chemical bonds. Using the reciprocating movement of the tip of a scanning tunneling microscope (STM), mechanical energy can be provided to a single molecule sandwiched between the tip and substrate. When the mechanical pulse center was moved to the outer ring feature of a CO molecule, the reaction rate was significantly increased compared with bare Cu surface and over Au atoms. First, DFT calculations show that the presence of CO makes the Cu cavity more attractive toward H2 Second, H2 prefers the horizontal adsorption geometry in the Cu-Cu and Au-Cu cavities and no hybridization occurs between the antibonding states of H2 and states of Cu atoms. While H2 loses electrons from its bonding state in all three cavities, the filling of its anti-bonding state only occurs in the CO-Cu cavity. Both make the CO-Cu cavity much more effectively to chop the H2 molecule. Work was supported by the National Science Foundation Center for Chemical Innovation on Chemistry at the Space-Time Limit (CaSTL) under Grant No. CHE-1414466.

  11. Photonic Molecule Lasers Revisited

    NASA Astrophysics Data System (ADS)

    Gagnon, Denis; Dumont, Joey; Déziel, Jean-Luc; Dubé, Louis J.

    2014-05-01

    Photonic molecules (PMs) formed by coupling two or more optical resonators are ideal candidates for the fabrication of integrated microlasers, photonic molecule lasers. Whereas most calculations on PM lasers have been based on cold-cavity (passive) modes, i.e. quasi-bound states, a recently formulated steady-state ab initio laser theory (SALT) offers the possibility to take into account the spectral properties of the underlying gain transition, its position and linewidth, as well as incorporating an arbitrary pump profile. We will combine two theoretical approaches to characterize the lasing properties of PM lasers: for two-dimensional systems, the generalized Lorenz-Mie theory will obtain the resonant modes of the coupled molecules in an active medium described by SALT. Not only is then the theoretical description more complete, the use of an active medium provides additional parameters to control, engineer and harness the lasing properties of PM lasers for ultra-low threshold and directional single-mode emission. We will extend our recent study and present new results for a number of promising geometries. The authors acknowledge financial support from NSERC (Canada) and the CERC in Photonic Innovations of Y. Messaddeq.

  12. Model molecules mimicking asphaltenes.

    PubMed

    Sjöblom, Johan; Simon, Sébastien; Xu, Zhenghe

    2015-04-01

    Asphalthenes are typically defined as the fraction of petroleum insoluble in n-alkanes (typically heptane, but also hexane or pentane) but soluble in toluene. This fraction causes problems of emulsion formation and deposition/precipitation during crude oil production, processing and transport. From the definition it follows that asphaltenes are not a homogeneous fraction but is composed of molecules polydisperse in molecular weight, structure and functionalities. Their complexity makes the understanding of their properties difficult. Proper model molecules with well-defined structures which can resemble the properties of real asphaltenes can help to improve this understanding. Over the last ten years different research groups have proposed different asphaltene model molecules and studied them to determine how well they can mimic the properties of asphaltenes and determine the mechanisms behind the properties of asphaltenes. This article reviews the properties of the different classes of model compounds proposed and present their properties by comparison with fractionated asphaltenes. After presenting the interest of developing model asphaltenes, the composition and properties of asphaltenes are presented, followed by the presentation of approaches and accomplishments of different schools working on asphaltene model compounds. The presentation of bulk and interfacial properties of perylene-based model asphaltene compounds developed by Sjöblom et al. is the subject of the next part. Finally the emulsion-stabilization properties of fractionated asphaltenes and model asphaltene compounds is presented and discussed.

  13. Small Molecule Organic Optoelectronic Devices

    NASA Astrophysics Data System (ADS)

    Bakken, Nathan

    Organic optoelectronics include a class of devices synthesized from carbon containing 'small molecule' thin films without long range order crystalline or polymer structure. Novel properties such as low modulus and flexibility as well as excellent device performance such as photon emission approaching 100% internal quantum efficiency have accelerated research in this area substantially. While optoelectronic organic light emitting devices have already realized commercial application, challenges to obtain extended lifetime for the high energy visible spectrum and the ability to reproduce natural white light with a simple architecture have limited the value of this technology for some display and lighting applications. In this research, novel materials discovered from a systematic analysis of empirical device data are shown to produce high quality white light through combination of monomer and excimer emission from a single molecule: platinum(II) bis(methyl-imidazolyl)toluene chloride (Pt-17). Illumination quality achieved Commission Internationale de L'Eclairage (CIE) chromaticity coordinates (x = 0.31, y = 0.38) and color rendering index (CRI) > 75. Further optimization of a device containing Pt-17 resulted in a maximum forward viewing power efficiency of 37.8 lm/W on a plain glass substrate. In addition, accelerated aging tests suggest high energy blue emission from a halogen-free cyclometalated platinum complex could demonstrate degradation rates comparable to known stable emitters. Finally, a buckling based metrology is applied to characterize the mechanical properties of small molecule organic thin films towards understanding the deposition kinetics responsible for an elastic modulus that is both temperature and thickness dependent. These results could contribute to the viability of organic electronic technology in potentially flexible display and lighting applications. The results also provide insight to organic film growth kinetics responsible for optical

  14. Spacer conformation in biologically active molecules. Part 2. Structure and conformation of 4-[2-(diphenylmethylamino)ethyl]-1-(2-methoxyphenyl) piperazine and its diphenylmethoxy analog—potential 5-HT 1A receptor ligands

    NASA Astrophysics Data System (ADS)

    Karolak-Wojciechowska, J.; Fruziński, A.; Czylkowski, R.; Paluchowska, M. H.; Mokrosz, M. J.

    2003-09-01

    As a part of studies on biologically active molecule structures with aliphatic linking chain, the structures of 4-[2-diphenylmethylamino)ethyl]-1-(2-methoxyphenyl)piperazine dihydrochloride ( 1) and 4-[2-diphenylmethoxy)ethyl]-1-(2-methoxyphenyl)piperazine fumarate ( 2) have been reported. In both compounds, four atomic non-all-carbons linking chains (N)C-C-X-C are present. The conformation of that linking spacer depends on the nature of the X-atom. The preferred conformation for chain with XNH has been found to be fully extended while for that with XO—the bend one. It was confirmed by conformational calculations (strain energy distribution and random search) and crystallographic data, including statistics from CCDC.

  15. Evidence of water molecules--a statistical evaluation of water molecules based on electron density.

    PubMed

    Nittinger, Eva; Schneider, Nadine; Lange, Gudrun; Rarey, Matthias

    2015-04-27

    Water molecules play important roles in many biological processes, especially when mediating protein-ligand interactions. Dehydration and the hydrophobic effect are of central importance for estimating binding affinities. Due to the specific geometric characteristics of hydrogen bond functions of water molecules, meaning two acceptor and two donor functions in a tetrahedral arrangement, they have to be modeled accurately. Despite many attempts in the past years, accurate prediction of water molecules-structurally as well as energetically-remains a grand challenge. One reason is certainly the lack of experimental data, since energetic contributions of water molecules can only be measured indirectly. However, on the structural side, the electron density clearly shows the positions of stable water molecules. This information has the potential to improve models on water structure and energy in proteins and protein interfaces. On the basis of a high-resolution subset of the Protein Data Bank, we have conducted an extensive statistical analysis of 2.3 million water molecules, discriminating those water molecules that are well resolved and those without much evidence of electron density. In order to perform this classification, we introduce a new measurement of electron density around an individual atom enabling the automatic quantification of experimental support. On the basis of this measurement, we present an analysis of water molecules with a detailed profile of geometric and structural features. This data, which is freely available, can be applied to not only modeling and validation of new water models in structural biology but also in molecular design.

  16. Negative ions of polyatomic molecules.

    PubMed

    Christophorou, L G

    1980-06-01

    In this paper general concepts relating to, and recent advances in, the study of negative ions of polyatomic molecules area discussed with emphasis on halocarbons. The topics dealt with in the paper are as follows: basic electron attachment processes, modes of electron capture by molecules, short-lived transient negative ions, dissociative electron attachment to ground-state molecules and to "hot" molecules (effects of temperature on electron attachment), parent negative ions, effect of density, nature, and state of the medium on electron attachment, electron attachment to electronically excited molecules, the binding of attached electrons to molecules ("electron affinity"), and the basic and the applied significance of negative-ion studies.

  17. Watching single molecules dance

    NASA Astrophysics Data System (ADS)

    Mehta, Amit Dinesh

    Molecular motors convert chemical energy, from ATP hydrolysis or ion flow, into mechanical motion. A variety of increasingly precise mechanical probes have been developed to monitor and perturb these motors at the single molecule level. Several outstanding questions can be best approached at the single molecule level. These include: how far does a motor progress per energy quanta consumed? how does its reaction cycle respond to load? how many productive catalytic cycles can it undergo per diffusional encounter with its track? and what is the mechanical stiffness of a single molecule connection? A dual beam optical trap, in conjunction with in vitro ensemble motility assays, has been used to characterize two members of the myosin superfamily: muscle myosin II and chick brain myosin V. Both move the helical polymer actin, but myosin II acts in large ensembles to drive muscle contraction or cytokinesis, while myosin V acts in small numbers to transport vesicles. An optical trapping apparatus was rendered sufficiently precise to identify a myosin working stroke with 1nm or so, barring systematic errors such as those perhaps due to random protein orientations. This and other light microscopic motility assays were used to characterize myosin V: unlike myosin II this vesicle transport protein moves through many increments of travel while remaining strongly bound to a single actin filament. The step size, stall force, and travel distance of myosin V reveal a remarkably efficient motor capable of moving along a helical track for over a micrometer without significantly spiraling around it. Such properties are fully consistent with the putative role of an organelle transport motor, present in small numbers to maintain movement over long ranges relative to cellular size scales. The contrast between myosin II and myosin V resembles that between a human running on the moon and one walking on earth, where the former allows for faster motion when in larger ensembles but for less

  18. Molecules in crystals

    NASA Astrophysics Data System (ADS)

    Spackman, Mark A.

    2013-04-01

    Hirshfeld surface analysis has developed from the serendipitous discovery of a novel partitioning of the crystal electron density into discrete molecular fragments, to a suite of computational tools used widely for the identification, analysis and discussion of intermolecular interactions in molecular crystals. The relationship between the Hirshfeld surface and very early ideas on the internal structure of crystals is outlined, and applications of Hirshfeld surface analysis are presented for three molecules of historical importance in the development of modern x-ray crystallography: hexamethylbenzene, hexamethylenetetramine and diketopiperazine.

  19. Addition of nucleophiles on cyanoacetylene N≡CCH=CH-X (X = NH2, OH, SH, …). Synthesis and Physico-chemical Properties of Potential Prebiotic Compounds or Interstellar Molecules.

    NASA Astrophysics Data System (ADS)

    Guillemin, Jean-Claude

    Among the molecules detected to date in the interstellar medium (ISM), cyanopolyynes constitute a rich and important subset. These robust compounds exhibit special properties with respect to their reactivity and kinetic stability, and some have been found in other astrochemical environments, such as comets or in lab simulations of planetary atmospheres.[1] These systems are supposed to be good starting materials for the formation of new, more complex, astrochemical species, or amino acids on primitive Earth. The formal addition of water, hydrogen sulfur or ammonia on cyanoacetylene (H-C≡C-C≡N) gives the corresponding heterosubstitued acrylonitriles. We have extensively investigated the study of such adducts. With water, the formed cyanovinylalcohol (NC-CH=CH-OH) is in a tautomeric equilibrium with the kinetically more stable cyanoacetaldehyde (NC-CH2 CH(=O)). Isolation of these compounds in pure form is challenging but the gas phase infrared spectrum has been recorded. Reaction of ammonia with cyanoacetylene gives aminoacrylonitrile (H2 N-CH=CH-CN), a stable enamine; microwave and infrared spectra were obtained.[2] Similarly the MW spectrum of 3-mercapto-2-propenenitrile (HS-CH=CH-CN) has been recorded.[3] Attempts to detect both species in the ISM have been performed. A combined experimental and theoretical study on the gas-phase basicity and acidity of a series of cyanovinyl derivatives is also presented.[4] We will demonstrate that many particular physicochemical properties are associated to these simple adducts of cyanoacetylene, compounds often proposed as prebiotic molecules or components of the ISM. 1] S. W. Fow, K. Dose, Molecular Evolution and the Origin of Life, Marcel Dekker, Stateplace- New York, metricconverterProductID1977. A1977. A. Coustenis, T. Encrenaz, B. BJzard, B. Bjoraker, G. Graner, G. Dang-Nhu, E. AriJ, Icarus 1993, 102, 240 - 269. [2] Benidar, A. ; Guillemin, J.-C. ; M—, O. ; Y‡-ez, M. J. Phys. Chem. A. 2005, 109, 4705-4712. E

  20. Theoretical spectra of floppy molecules

    NASA Astrophysics Data System (ADS)

    Chen, Hua

    2000-09-01

    Detailed studies of the vibrational dynamics of floppy molecules are presented. Six-D bound-state calculations of the vibrations of rigid water dimer based on several anisotropic site potentials (ASP) are presented. A new sequential diagonalization truncation approach was used to diagonalize the angular part of the Hamiltonian. Symmetrized angular basis and a potential optimized discrete variable representation for intermonomer distance coordinate were used in the calculations. The converged results differ significantly from the results presented by Leforestier et al. [J. Chem. Phys. 106 , 8527 (1997)]. It was demonstrated that ASP-S potential yields more accurate tunneling splittings than other ASP potentials used. Fully coupled 4D quantum mechanical calculations were performed for carbon dioxide dimer using the potential energy surface given by Bukowski et al [J. Chem. Phys., 110, 3785 (1999)]. The intermolecular vibrational frequencies and symmetry adapted force constants were estimated and compared with experiments. The inter-conversion tunneling dynamics was studied using the calculated virtual tunneling splittings. Symmetrized Radau coordinates and the sequential diagonalization truncation approach were formulated for acetylene. A 6D calculation was performed with 5 DVR points for each stretch coordinate, and an angular basis that is capable of converging the angular part of the Hamiltonian to 30 cm-1 for internal energies up to 14000 cm-1. The probability at vinylidene configuration were evaluated. It was found that the eigenstates begin to extend to vinylidene configuration from about 10000 cm-1, and the ra, coordinate is closely related to the vibrational dynamics at high energy. Finally, a direct product DVR was defined for coupled angular momentum operators, and the SDT approach were formulated. They were applied in solving the angular part of the Hamiltonian for carbon dioxide dimer problem. The results show the method is capable of giving very accurate

  1. Ultra-cold molecule production.

    SciTech Connect

    Ramirez-Serrano, Jamie; Chandler, David W.; Strecker, Kevin; Rahn, Larry A.

    2005-12-01

    The production of Ultra-cold molecules is a goal of many laboratories through out the world. Here we are pursuing a unique technique that utilizes the kinematics of atomic and molecular collisions to achieve the goal of producing substantial numbers of sub Kelvin molecules confined in a trap. Here a trap is defined as an apparatus that spatially localizes, in a known location in the laboratory, a sample of molecules whose temperature is below one degree absolute Kelvin. Further, the storage time for the molecules must be sufficient to measure and possibly further cool the molecules. We utilize a technique unique to Sandia to form cold molecules from near mass degenerate collisions between atoms and molecules. This report describes the progress we have made using this novel technique and the further progress towards trapping molecules we have cooled.

  2. Depth: a web server to compute depth, cavity sizes, detect potential small-molecule ligand-binding cavities and predict the pKa of ionizable residues in proteins

    PubMed Central

    Tan, Kuan Pern; Nguyen, Thanh Binh; Patel, Siddharth; Varadarajan, Raghavan; Madhusudhan, M. S.

    2013-01-01

    Residue depth accurately measures burial and parameterizes local protein environment. Depth is the distance of any atom/residue to the closest bulk water. We consider the non-bulk waters to occupy cavities, whose volumes are determined using a Voronoi procedure. Our estimation of cavity sizes is statistically superior to estimates made by CASTp and VOIDOO, and on par with McVol over a data set of 40 cavities. Our calculated cavity volumes correlated best with the experimentally determined destabilization of 34 mutants from five proteins. Some of the cavities identified are capable of binding small molecule ligands. In this study, we have enhanced our depth-based predictions of binding sites by including evolutionary information. We have demonstrated that on a database (LigASite) of ∼200 proteins, we perform on par with ConCavity and better than MetaPocket 2.0. Our predictions, while less sensitive, are more specific and precise. Finally, we use depth (and other features) to predict pKas of GLU, ASP, LYS and HIS residues. Our results produce an average error of just <1 pH unit over 60 predictions. Our simple empirical method is statistically on par with two and superior to three other methods while inferior to only one. The DEPTH server (http://mspc.bii.a-star.edu.sg/depth/) is an ideal tool for rapid yet accurate structural analyses of protein structures. PMID:23766289

  3. Heteropentameric Cholera Toxin B Subunit Chimeric Molecules Genetically Fused to a Vaccine Antigen Induce Systemic and Mucosal Immune Responses: a Potential New Strategy To Target Recombinant Vaccine Antigens to Mucosal Immune Systems

    PubMed Central

    Harakuni, Tetsuya; Sugawa, Hideki; Komesu, Ai; Tadano, Masayuki; Arakawa, Takeshi

    2005-01-01

    Noninvasive mucosal vaccines are attractive alternatives to parenteral vaccines. Although the conjugation of vaccine antigens with the B subunit of cholera toxin (CTB) is one of the most promising strategies for vaccine delivery to mucosal immune systems, the molecule cannot tolerate large-protein fusion, as it severely impairs pentamerization and loses affinity for GM1-ganglioside. Here we report a new strategy, in which steric hindrance between CTB-antigen fusion subunits is significantly reduced through the integration of unfused CTB “molecular buffers” into the pentamer unit, making them more efficiently self-assemble into biologically active pentamers. In addition, the chimeric protein took a compact configuration, becoming small enough to be secreted, and one-step affinity-purified proteins, when administered through a mucosal route, induced specific immune responses in mice. Since our results are not dependent on the use of a particular expression system or vaccine antigen, this strategy could be broadly applicable to bacterial enterotoxin-based vaccine design. PMID:16113283

  4. Covalent Chemistry beyond Molecules.

    PubMed

    Jiang, Juncong; Zhao, Yingbo; Yaghi, Omar M

    2016-03-16

    Linking molecular building units by covalent bonds to make crystalline extended structures has given rise to metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), thus bringing the precision and versatility of covalent chemistry beyond discrete molecules to extended structures. The key advance in this regard has been the development of strategies to overcome the "crystallization problem", which is usually encountered when attempting to link molecular building units into covalent solids. Currently, numerous MOFs and COFs are made as crystalline materials in which the large size of the constituent units provides for open frameworks. The molecular units thus reticulated become part of a new environment where they have (a) lower degrees of freedom because they are fixed into position within the framework; (b) well-defined spatial arrangements where their properties are influenced by the intricacies of the pores; and (c) ordered patterns onto which functional groups can be covalently attached to produce chemical complexity. The notion of covalent chemistry beyond molecules is further strengthened by the fact that covalent reactions can be carried out on such frameworks, with full retention of their crystallinity and porosity. MOFs are exemplars of how this chemistry has led to porosity with designed metrics and functionality, chemically-rich sequences of information within their frameworks, and well-defined mesoscopic constructs in which nanoMOFs enclose inorganic nanocrystals and give them new levels of spatial definition, stability, and functionality.

  5. Cavity sideband cooling of trapped molecules

    SciTech Connect

    Kowalewski, Markus; Vivie-Riedle, Regina de; Morigi, Giovanna; Pinkse, Pepijn W. H.

    2011-09-15

    The efficiency of cavity sideband cooling of trapped molecules is theoretically investigated for the case in which the infrared transition between two rovibrational states is used as a cycling transition. The molecules are assumed to be trapped either by a radiofrequency or optical trapping potential, depending on whether they are charged or neutral, and confined inside a high-finesse optical resonator that enhances radiative emission into the cavity mode. Using realistic experimental parameters and COS as a representative molecular example, we show that in this setup, cooling to the trap ground state is feasible.

  6. Small molecule inhibitors of ebola virus infection.

    PubMed

    Picazo, Edwige; Giordanetto, Fabrizio

    2015-02-01

    Ebola viruses are extremely virulent and highly transmissible. They are responsible for sporadic outbreaks of severe hemorrhagic fevers with human mortality rates of up to 90%. No prophylactic or therapeutic treatments in the form of vaccine, biologicals or small molecule, currently exist. Yet, a wealth of antiviral research on ebola virus is being generated and potential inhibitors have been identified in biological screening and medicinal chemistry programs. Here, we detail the state-of-the-art in small molecule inhibitors of ebola virus infection, with >60 examples, including approved drugs, compounds currently in clinical trials, and more exploratory leads, and summarize the associated in vitro and in vivo evidence for their effectiveness.

  7. Enhancing single-molecule fluorescence with nanophotonics.

    PubMed

    Acuna, Guillermo; Grohmann, Dina; Tinnefeld, Philip

    2014-10-01

    Single-molecule fluorescence spectroscopy has become an important research tool in the life sciences but a number of limitations hinder the widespread use as a standard technique. The limited dynamic concentration range is one of the major hurdles. Recent developments in the nanophotonic field promise to alleviate these restrictions to an extent that even low affinity biomolecular interactions can be studied. After motivating the need for nanophotonics we introduce the basic concepts of nanophotonic devices such as zero mode waveguides and nanoantennas. We highlight current applications and the future potential of nanophotonic approaches when combined with biological systems and single-molecule spectroscopy.

  8. Molecules Best Paper Award 2013.

    PubMed

    McPhee, Derek J

    2013-02-05

    Molecules has started to institute a "Best Paper" award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published in Molecules. We are pleased to announce the second "Molecules Best Paper Award" for 2013.

  9. Deceleration of neutral molecules in macroscopic traveling traps

    SciTech Connect

    Osterwalder, Andreas; Meek, Samuel A.; Hammer, Georg; Haak, Henrik; Meijer, Gerard

    2010-05-15

    A decelerator is presented where polar neutral molecules are guided and decelerated using the principle of traveling electric potential wells, such that molecules are confined in stable three-dimensional traps throughout. We compare this decelerator with that of Scharfenberg et al. [Phys. Rev. A 79, 023410 (2009)] and we show that the current decelerator provides a substantially larger phase-space acceptance, even at higher acceleration. The mode of operation is described and experimentally demonstrated by guiding and decelerating CO molecules.

  10. Hydrogen sulfide and polysulfides as signaling molecules

    PubMed Central

    KIMURA, Hideo

    2015-01-01

    Hydrogen sulfide (H2S) is a familiar toxic gas that smells of rotten eggs. After the identification of endogenous H2S in the mammalian brain two decades ago, studies of this molecule uncovered physiological roles in processes such as neuromodulation, vascular tone regulation, cytoprotection against oxidative stress, angiogenesis, anti-inflammation, and oxygen sensing. Enzymes that produce H2S, such as cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase have been studied intensively and well characterized. Polysulfides, which have a higher number of inner sulfur atoms than that in H2S, were recently identified as potential signaling molecules that can activate ion channels, transcription factors, and tumor suppressors with greater potency than that of H2S. This article focuses on our contribution to the discovery of these molecules and their metabolic pathways and mechanisms of action. PMID:25864468

  11. Small molecule modifiers of circadian clocks.

    PubMed

    Chen, Zheng; Yoo, Seung-Hee; Takahashi, Joseph S

    2013-08-01

    Circadian clocks orchestrate 24-h oscillations of essential physiological and behavioral processes in response to daily environmental changes. These clocks are remarkably precise under constant conditions yet highly responsive to resetting signals. With the molecular composition of the core oscillator largely established, recent research has increasingly focused on clock-modifying mechanisms/molecules. In particular, small molecule modifiers, intrinsic or extrinsic, are emerging as powerful tools for understanding basic clock biology as well as developing putative therapeutic agents for clock-associated diseases. In this review, we will focus on synthetic compounds capable of modifying the period, phase, or amplitude of circadian clocks, with particular emphasis on the mammalian clock. We will discuss the potential of exploiting these small molecule modifiers in both basic and translational research.

  12. Molecules in the Spotlight

    SciTech Connect

    Cryan, James

    2010-01-26

    SLAC has just unveiled the world's first X-ray laser, the LCLS. This machine produces pulses of X-rays that are ten billion times brighter than those from conventional sources. One of the goals of this machine is to make movies of chemical reactions, including reactions necessary for life and reactions that might power new energy technologies. This public lecture will show the first results from the LCLS. As a first target, we have chosen nitrogen gas, the main component of the air we breathe. Using the unprecedented power of the LCLS X-rays as a blasting torch, we have created new forms of this molecule and with unique electronic arrangements. Please share with us the first insights from this new technology.

  13. Biochips - Can molecules compute?

    NASA Astrophysics Data System (ADS)

    Tucker, J. B.

    1984-02-01

    In recent years the possibility has been considered to build 'biochip' computers, in which the silicon transistors of present machines would be replaced by large organic molecules or genetically engineered proteins. Two major advantages of such biochips over current devices would be related to vastly increased densities of computing elements, and entirely new styles of data processing, suited to such high-level tasks as pattern recognition and context-dependent analysis. The limitations of the semiconductor chip with respect to the density of elementary units due to size considerations and heat development could be overcome by making use of molecular switches. Attention is given to soliton switching, soliton logic, bulk molecular devices, analog biochips, 'intelligent' switches based on the employment of enzymes, robot vision, questions of biochip fabrication, protein engineering, and a strategy for the development of biochips.

  14. Fiber-mesh photonic molecule

    NASA Astrophysics Data System (ADS)

    Mishra, Subodha; Satpathy, Sashi

    2008-03-01

    Analogous to the photonic crystal, we introduce the concept of a fiber-mesh photonic molecule made up of optical fibers and study its transmission characteristics. We consider a specific example of a photonic molecule, inspired by the well-known C60 molecule, with the arms of the molecule formed out of single-moded optical fibers. The transmittance consists of sharp peaks determined by the pole structure of the scattering matrix in the complex energy plane. A molecule can be designed to control the positions and the widths of the transmission peaks, opening up the possibility of building new photonic devices such as high quality band-pass filters.

  15. Source of polarized hydrogen molecules

    NASA Astrophysics Data System (ADS)

    Toporkov, D. K.; Gramolin, A. V.; Nikolenko, D. M.; Rachek, I. A.; Sadykov, R. Sh.; Shestakov, Yu. V.; Yurchenko, A. V.; Zevakov, S. A.

    2017-10-01

    A novel source of polarized hydrogen and deuterium molecules has been tested. The use of sextupole superconducting magnets allows us to select molecules with the nuclear spin projection -1 for hydrogen and -2 for deuterium. The measured beam intensity of polarized hydrogen molecules for the nozzle temperature range of 6.5-30 K and a gas flow rate up to 5 ṡ 10-2 Torr ṡ l / s is presented. The measured flux of polarized hydrogen molecules of ≈ 3 ṡ 1012 mol / s is in reasonable agreement with estimations. The obtained results can be used as a basis for the development of a high-intensity source of polarized molecules.

  16. Connexin Channel Permeability to Cytoplasmic Molecules

    PubMed Central

    Harris, Andrew L.

    2007-01-01

    Connexin channels are known to be permeable to a variety of cytoplasmic molecules. The first observation of second messenger junctional permeability, made ∼30 years ago, sparked broad interest in gap junction channels as mediators of intercellular molecular signaling. Since then, much has been learned about the diversity of connexin channels with regard to isoform diversity, tissue and developmental distribution, modes of channel regulation, assembly and expression, biochemical modification and permeability, all of which appear to be dynamically regulated. This information has expanded the potential roles of connexin channels in development, physiology and disease, and made their elucidation much more complex - 30 years ago such an orchestra of junctional dynamics was unanticipated. Only recently, however, have investigators been able to directly address, in this more complex framework, the key issue: What specific biological molecules, second messengers and others, are able to permeate the various types of connexin channels, and how well? An important related issue, given the ever-growing list of connexin-related pathologies, is how these permeabilities are altered by disease-causing connexin mutations. Together, many studies show that a variety of cytoplasmic molecules can permeate the different types of connexin channels. A few studies reveal differences in permeation by different molecules through a particular type of connexin channel, and differences in permeation by a particular molecule through different types of connexin channels. This article describes and evaluates the various methods used to obtain these data, presents an annotated compilation of the results, and discusses the findings in the context of what can be inferred about mechanism of selectivity and potential relevance to signaling. The data strongly suggest that highly specific interactions take place between connexin pores and specific biological molecular permeants, and that those

  17. Proteasome Activation by Small Molecules.

    PubMed

    Leestemaker, Yves; de Jong, Annemieke; Witting, Katharina F; Penning, Renske; Schuurman, Karianne; Rodenko, Boris; Zaal, Esther A; van de Kooij, Bert; Laufer, Stefan; Heck, Albert J R; Borst, Jannie; Scheper, Wiep; Berkers, Celia R; Ovaa, Huib

    2017-06-22

    Drugs that increase 26S proteasome activity have potential therapeutic applications in the treatment of neurodegenerative diseases. A chemical genetics screen of over 2,750 compounds using a proteasome activity probe as a readout in a high-throughput live-cell fluorescence-activated cell sorting-based assay revealed more than ten compounds that increase proteasome activity, with the p38 MAPK inhibitor PD169316 being one of the most potent ones. Genetic and chemical inhibition of either p38 MAPK, its upstream regulators, ASK1 and MKK6, and downstream target, MK2, enhance proteasome activity. Chemical activation of the 26S proteasome increases PROTAC-mediated and ubiquitin-dependent protein degradation and decreases the levels of both overexpressed and endogenous α-synuclein, without affecting the overall protein turnover. In addition, survival of cells overexpressing toxic α-synuclein assemblies is increased in the presence of p38 MAPK inhibitors. These findings highlight the potential of activation of 26S proteasome activity and that this can be achieved through multiple mechanisms by distinct molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The bound states of ultracold KRb molecules

    NASA Astrophysics Data System (ADS)

    Julienne, Paul; Hanna, Thomas

    2009-03-01

    Recently ultracold vibrational ground state ^40K^87Rb polar molecules have been made using magnetoassociation of two cold atoms to a weakly bound Feshbach molecule, followed by a two-color optical STIRAP process to transfer molecules to the molecular ground state [1]. We have used accurate potential energy curves for the singlet and triplet states of the KRb molecule [2] with coupled channels calculations to calculate all of the bound states of the ^40K^87Rb molecule as a function of magnetic field from the cold atom collision threshold to the v=0 ground state. We have also developed approximate models for understanding the changing properties of the molecular bound states as binding energy increases. Some overall conclusions from these calculations will be presented. [1] K.-K. Ni, S. Ospelkaus, M. H. G. de Miranda, A. Peer, B. Neyenhuis, J. J. Zirbel, S. Kotochigova, P. S. Julienne, D. S. Jin, and J. Ye, Science, 2008, 322, 231--235. [2] A. Pashov, O. Docenko, M. Tamanis, R. Ferber, H. Kn"ockel, and E. Tiemann, Phys. Rev. A, 2007, 76, 022511.

  19. Structural variations in (CuL)2Ln complexes of a series of lanthanide ions with a salen-type unsymmetrical Schiff base(H2L): Dy and Tb derivatives as potential single-molecule magnets.

    PubMed

    Mahapatra, Prithwish; Ghosh, Soumavo; Koizumi, Naoki; Kanetomo, Takuya; Ishida, Takayuki; Drew, Michael G B; Ghosh, Ashutosh

    2017-09-28

    A new series of heterometallic trinuclear Cu2Ln complexes [lanthanide ions Ln = Gd (1), Tb (2), Dy (3), Ho (4) and Er (5)] has been synthesized using a Cu(ii)-metalloligand derived from a N2O2 donor unsymmetrical Schiff base, H2L (where H2L = N-α-methylsalicylidene-N'-salicylidene-1,3-propanediamine), and structurally characterized. Among these complexes, [(CuL)2Gd(NO3)3(CH3CN)2] (1), [(CuL)2Tb(NO3)3(CH3CN)2] (2) and [(CuL)2Dy(NO3)3(CH3CN)2] (3) are isomorphic and isostructural. In these complexes two metalloligands coordinate to the central Ln(iii) (Ln = Gd, Tb and Dy respectively) ion in a transoid fashion viaμ2-phenoxido oxygen atoms. The Ln(iii) ions are deca-coordinated with a distorted tetradecahedron geometry. The two terminal Cu(ii) ions of the complexes possess a hexa-coordinated distorted octahedral geometry. In contrast, in complexes [(CuL)2Ho(NO3)3(CH3CN)], (4) and [(CuL)2Er(NO3)3(CH3CN)]·0.5(CH3CN) (5), the two metalloligands coordinated to the Ln(iii) ions in a cisoid fashion. The Ho(iii) ion in 4 is nona-coordinated with a distorted tricapped trigonal prismatic geometry and the Er(iii) ion in 5 is octa-coordinated with a distorted square antiprismatic geometry. The two terminal Cu(ii) ions in complexes 4 and 5 are penta-coordinated with a distorted square-pyramidal geometry. The dc magnetic susceptibilities and field dependent magnetization measurement of complex 1 reveal the occurrence of ferromagnetic interactions between Cu(ii) and Gd(iii) ions as well as intermolecular antiferromagnetic interactions. Both complexes 2 and 3 show ferromagnetic interactions between Cu(ii) and Ln(iii) ions. The ac magnetic susceptibilities of all the complexes were also recorded and it was found that only complexes 2 and 3 exhibit slow relaxation of magnetization reorientation below 10 K at 2000 Oe applied dc field, this being characteristic of single molecule magnets.

  20. Liquid Catholyte Molecules for Nonaqueous Redox Flow Batteries

    SciTech Connect

    Huang, Jinhua; Cheng, Lei; Assary, Rajeev S.; Wang, Peiqi; Xue, Zheng; Burrell, Anthony K.; Curtiss, Larry A.; Zhang, Lu

    2014-11-25

    A series of dimethoxybenzene-based catholyte molecules, which are electrochemically reversible at high potential (4.0 V vs Li/Li+) and in the form of liquid, is developed. The liquid nature offers the molecules the possibility of being a solo or co-solvent for nonaqueous redox flow batteries. This could dramatically improve the energy density.

  1. Spectroscopic probes of vibrationally excited molecules at chemically significant energies

    SciTech Connect

    Rizzo, T.R.

    1993-12-01

    This project involves the application of multiple-resonance spectroscopic techniques for investigating energy transfer and dissociation dynamics of highly vibrationally excited molecules. Two major goals of this work are: (1) to provide information on potential energy surfaces of combustion related molecules at chemically significant energies, and (2) to test theoretical modes of unimolecular dissociation rates critically via quantum-state resolved measurements.

  2. Discovery of RNA Binding Small Molecules Using Small Molecule Microarrays.

    PubMed

    Connelly, Colleen M; Abulwerdi, Fardokht A; Schneekloth, John S

    2017-01-01

    New methods to identify RNA-binding small molecules open yet unexplored opportunities for the pharmacological modulation of RNA-driven biology and disease states. One such approach is the use of small molecule microarrays (SMMs). Typically, SMMs are generated by spatially arraying and covalently linking a library of small molecules to a glass surface. Next, incubation of the arrays with a fluorescently labeled RNA reveals binding interactions that are detected upon slide imaging. The relative ease with which SMMs are manufactured enables the screening of multiple oligonucleotides in parallel against tens of thousands of small molecules, providing information about both binding and selectivity of identified RNA-small molecule interactions. This approach is useful for screening a broad variety of structurally and functionally diverse RNAs. Here, we present a general method for the preparation and use of SMMs to rapidly identify small molecules that selectively bind to an RNA of interest.

  3. Geranyl diphosphate synthase molecules, and nucleic acid molecules encoding same

    DOEpatents

    Croteau, Rodney Bruce; Burke, Charles Cullen

    2008-06-24

    In one aspect, the present invention provides isolated nucleic acid molecules that each encode a geranyl diphosphate synthase protein, wherein each isolated nucleic acid molecule hybridizes to a nucleic acid molecule consisting of the sequence set forth in SEQ ID NO:1 under conditions of 5.times.SSC at 45.degree. C. for one hour. The present invention also provides isolated geranyl diphosphate synthase proteins, and methods for altering the level of expression of geranyl diphosphate synthase protein in a host cell.

  4. Organic Molecules in Meteorites

    NASA Astrophysics Data System (ADS)

    Martins, Zita

    2015-08-01

    Carbonaceous meteorites are primitive samples from the asteroid belt, containing 3-5wt% organic carbon. The exogenous delivery of organic matter by carbonaceous meteorites may have contributed to the organic inventory of the early Earth. The majority (>70%) of the meteoritic organic material consist of insoluble organic matter (IOM) [1]. The remaining meteoritic organic material (<30%) consists of a rich organic inventory of soluble organic compounds, including key compounds important in terrestrial biochemistry [2-4]. Different carbonaceous meteorites contain soluble organic molecules with different abundances and distributions, which may reflect the extension of aqueous alteration or thermal metamorphism on the meteorite parent bodies. Extensive aqueous alteration on the meteorite parent body may result on 1) the decomposition of α-amino acids [5, 6]; 2) synthesis of β- and γ-amino acids [2, 6-9]; 3) higher relative abundances of alkylated polycyclic aromatic hydrocarbons (PAHs) [6, 10]; and 4) higher L-enantiomer excess (Lee) value of isovaline [6, 11, 12].The soluble organic content of carbonaceous meteorites may also have a contribution from Fischer-Tropsch/Haber-Bosch type gas-grain reactions after the meteorite parent body cooled to lower temperatures [13, 14].The analysis of the abundances and distribution of the organic molecules present in meteorites helps to determine the physical and chemical conditions of the early solar system, and the prebiotic organic compounds available on the early Earth.[1] Cody and Alexander (2005) GCA 69, 1085. [2] Cronin and Chang (1993) in: The Chemistry of Life’s Origin. pp. 209-258. [3] Martins and Sephton (2009) in: Amino acids, peptides and proteins in organic chemistry. pp. 1-42. [4] Martins (2011) Elements 7, 35. [5] Botta et al. (2007) MAPS 42, 81. [6] Martins et al. (2015) MAPS, in press. [7] Cooper and Cronin (1995) GCA 59, 1003. [8] Glavin et al. (2006) MAPS. 41, 889. [9] Glavin et al. (2011) MAPS 45, 1948. [10

  5. Electron-excited molecule interactions

    SciTech Connect

    Christophorou, L.G. Tennessee Univ., Knoxville, TN . Dept. of Physics)

    1991-01-01

    In this paper the limited but significant knowledge to date on electron scattering from vibrationally/rotationally excited molecules and electron scattering from and electron impact ionization of electronically excited molecules is briefly summarized and discussed. The profound effects of the internal energy content of a molecule on its electron attachment properties are highlighted focusing in particular on electron attachment to vibrationally/rotationally and to electronically excited molecules. The limited knowledge to date on electron-excited molecule interactions clearly shows that the cross sections for certain electron-molecule collision processes can be very different from those involving ground state molecules. For example, optically enhanced electron attachment studies have shown that electron attachment to electronically excited molecules can occur with cross sections 10{sup 6} to 10{sup 7} times larger compared to ground state molecules. The study of electron-excited molecule interactions offers many experimental and theoretical challenges and opportunities and is both of fundamental and technological significance. 54 refs., 15 figs.

  6. Quantitative analysis of single-molecule superresolution images

    PubMed Central

    Coltharp, Carla; Yang, Xinxing; Xiao, Jie

    2014-01-01

    This review highlights the quantitative capabilities of single-molecule localization-based superresolution imaging methods. In addition to revealing fine structural details, the molecule coordinate lists generated by these methods provide the critical ability to quantify the number, clustering, and colocalization of molecules with 10 – 50 nm resolution. Here we describe typical workflows and precautions for quantitative analysis of single-molecule superresolution images. These guidelines include potential pitfalls and essential control experiments, allowing critical assessment and interpretation of superresolution images. PMID:25179006

  7. Atmospheric trace molecule spectroscopy

    NASA Technical Reports Server (NTRS)

    Farmer, C. B.

    1982-01-01

    The Spacelab investigation entitled Atmospheric Trace Molecule Spectroscopy (ATMOS) is designed to obtain fundamental information related to the chemistry and physics of the Earth's upper atmosphere using the techniques of infrared absorption spectroscopy. There are two principal objectives to be met. The first is the determination, on a global scale, of the compositional structure of the upper atmosphere and its spatial variability. The establishment of this variability represents the first step toward determining the characteristic residence times for the upper atmospheric constituents; the magnitudes of their sources and sinks; and, ultimately, an understanding of their effects on the stability of the stratosphere. The second objective is to provide the high-resolution, calibrated spectral information which is essential for the detailed design of advanced instrumentation for subsequent global monitoring of specific species found to be critical to atmospheric stability. This information will be disseminated in the form of a three dimensional atlas of solar absorption spectra obtained over a range of latitudes, longitudes, and altitudes.

  8. Single molecule tracking

    DOEpatents

    Shera, E. Brooks

    1988-01-01

    A detection system is provided for identifying individual particles or molecules having characteristic emission in a flow train of the particles in a flow cell. A position sensitive sensor is located adjacent the flow cell in a position effective to detect the emissions from the particles within the flow cell and to assign spatial and temporal coordinates for the detected emissions. A computer is then enabled to predict spatial and temporal coordinates for the particle in the flow train as a function of a first detected emission. Comparison hardware or software then compares subsequent detected spatial and temporal coordinates with the predicted spatial and temporal coordinates to determine whether subsequently detected emissions originate from a particle in the train of particles. In one embodiment, the particles include fluorescent dyes which are excited to fluoresce a spectrum characteristic of the particular particle. Photones are emitted adjacent at least one microchannel plate sensor to enable spatial and temporal coordinates to be assigned. The effect of comparing detected coordinates with predicted coordinates is to define a moving sample volume which effectively precludes the effects of background emissions.

  9. Single molecule tracking

    DOEpatents

    Shera, E.B.

    1987-10-07

    A detection system is provided for identifying individual particles or molecules having characteristic emission in a flow train of the particles in a flow cell. A position sensitive sensor is located adjacent the flow cell in a position effective to detect the emissions from the particles within the flow cell and to assign spatial and temporal coordinates for the detected emissions. A computer is then enabled to predict spatial and temporal coordinates for the particle in the flow train as a function of a first detected emission. Comparison hardware or software then compares subsequent detected spatial and temporal coordinates with the predicted spatial and temporal coordinates to determine whether subsequently detected emissions originate from a particle in the train of particles. In one embodiment, the particles include fluorescent dyes which are excited to fluoresce a spectrum characteristic of the particular particle. Photons are emitted adjacent at least one microchannel plate sensor to enable spatial and temporal coordinates to be assigned. The effect of comparing detected coordinates with predicted coordinates is to define a moving sample volume which effectively precludes the effects of background emissions. 3 figs.

  10. Single-Molecule Plasmon Sensing: Current Status and Future Prospects.

    PubMed

    Taylor, Adam B; Zijlstra, Peter

    2017-08-25

    Single-molecule detection has long relied on fluorescent labeling with high quantum-yield fluorophores. Plasmon-enhanced detection circumvents the need for labeling by allowing direct optical detection of weakly emitting and completely nonfluorescent species. This review focuses on recent advances in single molecule detection using plasmonic metal nanostructures as a sensing platform, particularly using a single particle-single molecule approach. In the past decade two mechanisms for plasmon-enhanced single-molecule detection have been demonstrated: (1) by plasmonically enhancing the emission of weakly fluorescent biomolecules, or (2) by monitoring shifts of the plasmon resonance induced by single-molecule interactions. We begin with a motivation regarding the importance of single molecule detection, and advantages plasmonic detection offers. We describe both detection mechanisms and discuss challenges and potential solutions. We finalize by highlighting the exciting possibilities in analytical chemistry and medical diagnostics.

  11. Single-Molecule Plasmon Sensing: Current Status and Future Prospects

    PubMed Central

    2017-01-01

    Single-molecule detection has long relied on fluorescent labeling with high quantum-yield fluorophores. Plasmon-enhanced detection circumvents the need for labeling by allowing direct optical detection of weakly emitting and completely nonfluorescent species. This review focuses on recent advances in single molecule detection using plasmonic metal nanostructures as a sensing platform, particularly using a single particle–single molecule approach. In the past decade two mechanisms for plasmon-enhanced single-molecule detection have been demonstrated: (1) by plasmonically enhancing the emission of weakly fluorescent biomolecules, or (2) by monitoring shifts of the plasmon resonance induced by single-molecule interactions. We begin with a motivation regarding the importance of single molecule detection, and advantages plasmonic detection offers. We describe both detection mechanisms and discuss challenges and potential solutions. We finalize by highlighting the exciting possibilities in analytical chemistry and medical diagnostics. PMID:28762723

  12. Theory of Long-Range Ultracold Atom-Molecule Photoassociation.

    PubMed

    Pérez-Ríos, Jesús; Lepers, Maxence; Dulieu, Olivier

    2015-08-14

    The creation of ultracold molecules is currently limited to diatomic species. In this Letter, we present a theoretical description of the photoassociation of ultracold atoms and molecules to create ultracold excited triatomic molecules, thus being a novel example of a light-assisted ultracold chemical reaction. The calculation of the photoassociation rate of an ultracold Cs_{2} molecule in its rovibrational ground state with an ultracold Cs atom at frequencies close to its resonant excitation is reported, based on the solution of the quantum dynamics involving the atom-molecule long-range interactions and assuming a model potential for the short-range physics. The rate for the formation of excited Cs_{3} molecules is predicted to be comparable with currently observed atom-atom photoassociation rates. We formulate an experimental proposal to observe this process relying on the available techniques of optical lattices and standard photoassociation spectroscopy.

  13. Water Molecule Hops on Ceres

    NASA Image and Video Library

    2016-12-15

    This graphic shows a theoretical path of a water molecule on Ceres. Some water molecules fall into cold, dark craters at high latitudes called "cold traps," where very little of the ice turns into vapor, even over the course of a billion years. Other water molecules that do not land in cold traps are lost to space as they hop around the dwarf planet. http://photojournal.jpl.nasa.gov/catalog/PIA21083

  14. Aromatic molecules as spintronic devices

    SciTech Connect

    Ojeda, J. H.; Orellana, P. A.; Laroze, D.

    2014-03-14

    In this paper, we study the spin-dependent electron transport through aromatic molecular chains attached to two semi-infinite leads. We model this system taking into account different geometrical configurations which are all characterized by a tight binding Hamiltonian. Based on the Green's function approach with a Landauer formalism, we find spin-dependent transport in short aromatic molecules by applying external magnetic fields. Additionally, we find that the magnetoresistance of aromatic molecules can reach different values, which are dependent on the variations in the applied magnetic field, length of the molecules, and the interactions between the contacts and the aromatic molecule.

  15. Vibrational autoionization in polyatomic molecules.

    PubMed

    Pratt, S T

    2005-01-01

    The vibrationally autoionizing Rydberg states of small polyatomic molecules provide a fascinating laboratory in which to study fundamental nonadiabatic processes. In this review, recent results on the vibrational mode dependence of vibrational autoionization are discussed. In general, autoionization rates depend strongly on the character of the normal mode driving the process and on the electronic character of the Rydberg electron. Although quantitative calculations based on multichannel quantum defect theory are available for some polyatomic molecules, including H3, only qualitative information exists for most molecules. This review shows how qualitative information, such as Walsh diagrams along different normal coordinates of the molecule, can provide insight into the vibrational autoionization rates.

  16. Electrical Transport through Organic Molecules

    NASA Astrophysics Data System (ADS)

    Lau, C. N.; Chang, Shun-Chi; Williams, Stan

    2003-03-01

    We investigate electrical transport properties of single organic molecules using electromigration break junctions[1]. A self-assembled monolayer of various organic molecules such as 1,4-di(phenylethynyl-4'-methanethiol)benzene was grown on narrow metal wires, and single or a few molecules were incorporated into the junctions which were created by applying a large voltage and breaking the wires. The transport properties of these molecules were then measured at low temperatures. Latest experimental results will be discussed. [1] Park, J. et al, Nature, 417, 722 (2002); Liang W. et al, Nature, 417, 725 (2002).

  17. Collision integrals for isotopic hydrogen molecules.

    NASA Technical Reports Server (NTRS)

    Brown, N. J.; Munn, R. J.

    1972-01-01

    The study was undertaken to determine the effects of reduced mass and differences in asymmetry on the collision integrals and thermal diffusion factors of isotopic hydrogen systems. Each system selected for study consisted of two diatoms, one in the j = 0 rotation state and the other in the j = 1 state. The molecules interacted with a Lennard-Jones type potential modified to include angular terms. A set of cross sections and collision integrals were obtained for each system.

  18. Collision integrals for isotopic hydrogen molecules.

    NASA Technical Reports Server (NTRS)

    Brown, N. J.; Munn, R. J.

    1972-01-01

    The study was undertaken to determine the effects of reduced mass and differences in asymmetry on the collision integrals and thermal diffusion factors of isotopic hydrogen systems. Each system selected for study consisted of two diatoms, one in the j = 0 rotation state and the other in the j = 1 state. The molecules interacted with a Lennard-Jones type potential modified to include angular terms. A set of cross sections and collision integrals were obtained for each system.

  19. Micro injector sample delivery system for charged molecules

    DOEpatents

    Davidson, James C.; Balch, Joseph W.

    1999-11-09

    A micro injector sample delivery system for charged molecules. The injector is used for collecting and delivering controlled amounts of charged molecule samples for subsequent analysis. The injector delivery system can be scaled to large numbers (>96) for sample delivery to massively parallel high throughput analysis systems. The essence of the injector system is an electric field controllable loading tip including a section of porous material. By applying the appropriate polarity bias potential to the injector tip, charged molecules will migrate into porous material, and by reversing the polarity bias potential the molecules are ejected or forced away from the tip. The invention has application for uptake of charged biological molecules (e.g. proteins, nucleic acids, polymers, etc.) for delivery to analytical systems, and can be used in automated sample delivery systems.

  20. Anti-inflammatory Potential of Quercetin-3-O-β-D-("2"-galloyl)-glucopyranoside and Quercetin Isolated from Diospyros kaki calyx via Suppression of MAP Signaling Molecules in LPS-induced RAW 264.7 Macrophages.

    PubMed

    Cho, Yong-Hun; Kim, Na-Hyung; Khan, Imran; Yu, Jae Myo; Jung, Hyun Gug; Kim, Han Hyuk; Jang, Jae Yoon; Kim, Hyeon Jeong; Kim, Dong-In; Kwak, Jae-Hoon; Kang, Sun Chul; An, Bong Jeun

    2016-10-01

    Diospyros kaki (DK) contains an abundance of flavonoids and has been used in folk medicine in Korea for centuries. Here, we report for the first time the anti-inflammatory activities of Quercetin (QCT) and Quercetin 3-O-β-("2"-galloyl)-glucopyranoside (Q32G) isolated from DK. We have determine the no cytotoxicity of Q32G and QCT against RAW 264.7 cells up to concentration of 50 μM. QCT and Q32G demonstrated potent anti-inflammatory activities by reducing expression of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and mitogen-activated protein kinase (MAPKs) in mouse RAW 264.7 macrophages activated with lipopolysaccharide (LPS). Both QCT or Q32G could decrease cellular protein levels of COX-2 and iNOS as well as secreted protein levels of NO, PGE2 , and cytokines (TNF-α, IL-1β, and IL-6) in culture medium of LPS-stimulated RAW 264.7 macrophages. Immunoblot analysis showed that QCT and Q32G suppressed LPS-induced MAP kinase pathway proteins p-p38, ERK, and JNK. This study revealed that QCT and Q32G have anti-inflammatory potential, however Q32G possess comparable activity as that of QCT and could be use as adjuvant to treat inflammatory diseases. © 2016 Institute of Food Technologists®.

  1. Evaluating enzymatic synthesis of small molecule drugs.

    PubMed

    Moura, Matthew; Finkle, Justin; Stainbrook, Sarah; Greene, Jennifer; Broadbelt, Linda J; Tyo, Keith E J

    2016-01-01

    There have been many achievements in applying biochemical synthetic routes to the synthesis of commodity chemicals. However, most of these endeavors have focused on optimizing and increasing the yields of naturally existing pathways. We sought to evaluate the potential for biosynthesis beyond the limits of known biochemistry towards the production of small molecule drugs that do not exist in nature. Because of the potential for improved yields compared to total synthesis, and therefore lower manufacturing costs, we focused on drugs for diseases endemic to many resource poor regions, like tuberculosis and HIV. Using generalized biochemical reaction rules, we were able to design biochemical pathways for the production of eight small molecule drugs or drug precursors and identify potential enzyme-substrate pairs for nearly every predicted reaction. All pathways begin from native metabolites, abrogating the need for specialized precursors. The simulated pathways showed several trends with the sequential ordering of reactions as well as the types of chemistries used. For some compounds, the main obstacles to finding feasible biochemical pathways were the lack of appropriate, natural starting compounds and a low diversity of biochemical coupling reactions necessary to synthesize molecules with larger molecular size. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  2. Coordination programming of photofunctional molecules.

    PubMed

    Sakamoto, Ryota; Kusaka, Shinpei; Hayashi, Mikihiro; Nishikawa, Michihiro; Nishihara, Hiroshi

    2013-04-05

    Our recent achievements relating to photofunctional molecules are addressed. Section 1 discloses a new concept of photoisomerization. Pyridylpyrimidine-copper complexes undergo a ring inversion that can be modulated by the redox state of the copper center. In combination with an intermolecular photoelectron transfer (PET) initiated by the metal-to-ligand charge transfer (MLCT) transition of the Cu(I) state, we realize photonic regulation of the ring inversion. Section 2 reports on the first examples of heteroleptic bis(dipyrrinato)zinc(II) complexes. Conventional homoleptic bis(dipyrrinato)zinc(II) complexes suffered from low fluorescence quantum yields, whereas the heteroleptic ones feature bright fluorescence even in polar solvents. Section 3 describes our new findings on Pechmann dye, which was first synthesized in 1882. New synthetic procedures for Pechmann dye using dimethyl bis(arylethynyl)fumarate as a starting material gives rise to its new structural isomer. We also demonstrate potentiality of a donor-acceptor-donor type of Pechmann dye in organic electronics.

  3. Rotational transitions in compound muonic molecules

    NASA Astrophysics Data System (ADS)

    Padial, N. T.; Cohen, James S.; Walker, Robert B.

    1988-01-01

    Cross sections and rate constants are calculated for collision-induced rotational transitions of compound muonic molecules, which determine relaxation rates important to muon-catalyzed fusion processes. The interaction potential is derived from the H2-H2 potential, and the R-matrix propagation method is used to solve the set of coupled collisional equations for the systems D2+[(dtμ)dee], D2+[(ddμ)dee], T2+[(dtμ)dee], D2+[(dtμ)tee], and H2+[(ddμ)pee]. Calculations are also done on H2+HD and D2+HD for comparison with previous work.

  4. Micro-Kelvin cold molecules.

    SciTech Connect

    Strecker, Kevin E.; Chandler, David W.

    2009-10-01

    We have developed a novel experimental technique for direct production of cold molecules using a combination of techniques from atomic optical and molecular physics and physical chemistry. The ability to produce samples of cold molecules has application in a broad spectrum of technical fields high-resolution spectroscopy, remote sensing, quantum computing, materials simulation, and understanding fundamental chemical dynamics. Researchers around the world are currently exploring many techniques for producing samples of cold molecules, but to-date these attempts have offered only limited success achieving milli-Kelvin temperatures with low densities. This Laboratory Directed Research and Development project is to develops a new experimental technique for producing micro-Kelvin temperature molecules via collisions with laser cooled samples of trapped atoms. The technique relies on near mass degenerate collisions between the molecule of interest and a laser cooled (micro-Kelvin) atom. A subset of collisions will transfer all (nearly all) of the kinetic energy from the 'hot' molecule, cooling the molecule at the expense of heating the atom. Further collisions with the remaining laser cooled atoms will thermally equilibrate the molecules to the micro-Kelvin temperature of the laser-cooled atoms.

  5. Loosely-Bound Diatomic Molecules.

    ERIC Educational Resources Information Center

    Balfour, W. J.

    1979-01-01

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

  6. Featured Molecules: Sucrose and Vanillin

    NASA Astrophysics Data System (ADS)

    Coleman, William F.; Wildman, Randall J.

    2003-04-01

    The WebWare molecules of the month for April relate to the sense of taste. Apple Fool, the JCE Classroom Activity, mentions sucrose and vanillin and their use as flavorings. Fully manipulable (Chime) versions of these and other molecules are available at Only@JCE Online.

  7. Loosely-Bound Diatomic Molecules.

    ERIC Educational Resources Information Center

    Balfour, W. J.

    1979-01-01

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

  8. Triatomic molecules laser-cooled

    NASA Astrophysics Data System (ADS)

    2017-06-01

    Molecules containing three atoms have been laser-cooled to ultracold temperatures for the first time. John Doyle and colleagues at Harvard University in the US used a technique called Sisyphus cooling to chill an ensemble of about a million strontium-monohydroxide molecules to 750 μK.

  9. Collisional Transitions in Interstellar Asymmetric Top Molecules

    NASA Astrophysics Data System (ADS)

    Chandra, Suresh

    2012-07-01

    known interaction potential. As an example, we shall discuss collisional rates for rotational transitions in H_2CS molecule.

  10. Tracking Nanocars Using Single Molecule Spectroscopy

    NASA Astrophysics Data System (ADS)

    Link, Stephan; Khatua, Saumyakanti; Claytor, Kevin; Guerrero, Jason; Tour, James

    2008-03-01

    Nanocars belong to an exciting new class of molecules known as molecular machines. They consist of four fullerene or carborane wheels attached to a chassis consisting of a stiff aromatic backbone. The nanocars are designed to roll over a solid surface making them potential candidates for nano-cargo transporters. Here, we present our results on tracking of nanocars by single molecule fluorescence spectroscopy. By attaching the fluorescent tag tetramethylrhodamin isothiocyanate to the nanocars, we were able to visualize and track individual nanocars using confocal sample scanning microscopy. Fluorescence images were analyzed for directional movement as opposed to random diffusion or stage drift. We had to overcome 2 major problems in our image analysis: 1) fluorescence photo-blinking and 2) photo-bleaching. We developed routines that are capable of tracking individual fluorescent molecules while accounting for photo-blinking and photo-bleaching. The ability to track individual nanocars is checked independently by simulations. Our method is not limited to tracking of nanocars however, and can be extended to follow individual molecules in biological or mechanical systems as well.

  11. Single-molecule techniques for drug discovery.

    PubMed

    Skinner, Gary M; Visscher, Koen

    2004-08-01

    Single-molecule techniques offer a number of key benefits over conventional in vitro assay methods for drug screening, as they use less material and unlock the ability to observe transient states. By observing such states, it should be possible to screen for chemical compounds that isolate these steps. The benefit of this is twofold: (a) inhibitors can be found that target key phases in biochemical processes, e.g., transcription initiation; and (b) the total number of drug targets increases as many biochemical processes consist of many transient steps, e.g., transcription promoter binding, initiation, elongation, and termination. Although single-molecule methods offer exciting opportunities for new ways of discovering drugs, there are a number of obstacles to their adoption for drug screening. The main hurdle is to develop robust apparatus that will allow many thousands of individual single molecule experiments to be performed in parallel. By using recently developed integrated microfluidics technology, this hurdle may be overcome. Here, a number of potential single-molecule approaches to drug screening are presented along with a discussion of the benefits and technical obstacles that must be overcome.

  12. System-wide detection of protein-small molecule complexes suggests extensive metabolite regulation in plants

    PubMed Central

    Veyel, Daniel; Kierszniowska, Sylwia; Kosmacz, Monika; Sokolowska, Ewelina Maria; Michaelis, Aenne; Luzarowski, Marcin; Szlachetko, Jagoda; Willmitzer, Lothar; Skirycz, Aleksandra

    2017-01-01

    Protein small molecule interactions are at the core of cell regulation controlling metabolism and development. We reasoned that due to the lack of system wide approaches only a minority of those regulatory molecules are known. In order to see whether or not this assumption is true we developed an effective approach for the identification of small molecules having potential regulatory role that obviates the need of protein or small molecule baits. At the core of this approach is a simple biochemical co-fractionation taking advantage of size differences between proteins and small molecules. Metabolomics based analysis of small molecules co-fractionating with proteins identified a multitude of small molecules in Arabidopsis suggesting the existence of numerous, small molecules/metabolites bound to proteins representing potential regulatory molecules. The approach presented here uses Arabidopsis cell cultures, but is generic and hence applicable to all biological systems. PMID:28205532

  13. Enzyme molecules in solitary confinement.

    PubMed

    Liebherr, Raphaela B; Gorris, Hans H

    2014-09-12

    Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme molecules in microwells does not require any surface immobilization step and enables the kinetic investigation of enzymes free in solution. This review describes various microwell array formats and explores their applications for the detection and investigation of single enzyme molecules. The development of new fabrication techniques and sensitive detection methods drives the field of single molecule enzymology. Here, we introduce recent progress in single enzyme molecule analysis in microwell arrays and discuss the challenges and opportunities.

  14. Molecule-hugging graphene nanopores.

    PubMed

    Garaj, Slaven; Liu, Song; Golovchenko, Jene A; Branton, Daniel

    2013-07-23

    It has recently been recognized that solid-state nanopores in single-atomic-layer graphene membranes can be used to electronically detect and characterize single long charged polymer molecules. We have now fabricated nanopores in single-layer graphene that are closely matched to the diameter of a double-stranded DNA molecule. Ionic current signals during electrophoretically driven translocation of DNA through these nanopores were experimentally explored and theoretically modeled. Our experiments show that these nanopores have unusually high sensitivity (0.65 nA/Å) to extremely small changes in the translocating molecule's outer diameter. Such atomically short graphene nanopores can also resolve nanoscale-spaced molecular structures along the length of a polymer, but do so with greatest sensitivity only when the pore and molecule diameters are closely matched. Modeling confirms that our most closely matched pores have an inherent resolution of ≤ 0.6 nm along the length of the molecule.

  15. Magnetoassociation of KRb Feshbach molecules

    NASA Astrophysics Data System (ADS)

    Cumby, Tyler; Perreault, John; Shewmon, Ruth; Jin, Deborah

    2010-03-01

    I will discuss experiments in which we study the creation of ^40K^87Rb Feshbach molecules via magnetoassociation. We measure the molecule number as a function of the magnetic-field sweep rate through the interspecies Feshbach resonance and explore the dependence of association on the initial atom gas conditions. This study of the Feshbach molecule creation process may be relevant to the production of ultracold polar molecules, where magnetoassociated Feshbach molecules can be a crucial first step [1].[4pt] [1] K.-K. Ni, S. Ospelkaus, M. H. G. de Miranda, A. Peer, B. Neyenhuis, J. J. Zirbel, S. Kotochigova, P. S. Julienne, D. S. Jin, and J. Ye, Science, 2008, 322, 231-235.

  16. Magnetoassociation of KRb Feshbach molecules

    NASA Astrophysics Data System (ADS)

    Cumby, Tyler; Perreault, John; Shewmon, Ruth; Jin, Deborah

    2010-03-01

    I will discuss experiments in which we study the creation of ^40K^87Rb Feshbach molecules via magnetoassociation. We measure the molecule number as a function of the magnetic-field sweep rate through the interspecies Feshbach resonance and explore the dependence of association on the initial atom gas conditions. This study of the Feshbach molecule creation process may be relevant to the production of ultracold polar molecules, where magnetoassociated Feshbach molecules can be a crucial first step [1].[4pt] [1] K.-K. Ni, S. Ospelkaus, M. H. G. de Miranda, A. Peer, B. Neyenhuis, J. J. Zirbel, S. Kotochigova, P. S. Julienne, D. S. Jin, and J. Ye, Science, 2008, 322, 231- 235.

  17. Generalized Stern-Gerlach Effect for Chiral Molecules

    NASA Astrophysics Data System (ADS)

    Li, Yong; Bruder, C.; Sun, C. P.

    2007-09-01

    The Stern-Gerlach effect is well known as spin-dependent splitting of a beam of atoms with magnetic moments by a magnetic-field gradient. Here, we show that an induced gauge potential may lead to a similar effect for chiral molecules. In the presence of three inhomogeneous light fields, the center of mass of a three-level chiral molecule is subject to an optically induced gauge potential, and the internal dynamics of the molecule can be described as an adiabatic evolution in the reduced pseudospin subspace of the two lowest energy levels. We demonstrate numerically that such an induced gauge potential can lead to observable pseudospin-dependent and chirality-dependent generalized Stern-Gerlach effects for mixed left- and right-handed chiral molecules under realistic conditions.

  18. Generalized Stern-Gerlach effect for chiral molecules.

    PubMed

    Li, Yong; Bruder, C; Sun, C P

    2007-09-28

    The Stern-Gerlach effect is well known as spin-dependent splitting of a beam of atoms with magnetic moments by a magnetic-field gradient. Here, we show that an induced gauge potential may lead to a similar effect for chiral molecules. In the presence of three inhomogeneous light fields, the center of mass of a three-level chiral molecule is subject to an optically induced gauge potential, and the internal dynamics of the molecule can be described as an adiabatic evolution in the reduced pseudospin subspace of the two lowest energy levels. We demonstrate numerically that such an induced gauge potential can lead to observable pseudospin-dependent and chirality-dependent generalized Stern-Gerlach effects for mixed left- and right-handed chiral molecules under realistic conditions.

  19. Can octupolar molecules be poled by an external electric field?

    PubMed

    Tu, Yaoquan; Luo, Yi; Agren, Hans

    2005-09-08

    Octupolar molecules are generally believed to be of potential use in developing nonlinear optical materials owing to the fact that they do not easily form molecular aggregates. This is often put against the conjectured drawback that electric fields have no poling, or ordering, effect for this class of molecules because of the lack of a permanent ground state dipole moment. In this paper, we analyze this notion in some detail and present results from molecular dynamics computer simulations of an ensemble of a prototypical octupolar molecule, the 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) molecule, dissolved in chloroform. It is found that TATB molecules indeed show rather significant dipole moments in solutions because of the dual action of the thermal motions of the atoms and the strong intermolecular interactions. Applied electric fields accordingly show significant effects on the orientations of the molecular dipole moments. We also find that TATB molecules can aggregate because of the strong hydrogen-bonding interactions between the molecules, though they lack a static permanent dipole moment. Thus, the simulation results for TATB molecules in solution present us with a totally different notion about the collective properties of octupolar molecules. Taking account of quantum chemistry results, we found that the collective molecular nonlinear optical (NLO) properties are enhanced after the onset of the electric field, showing significant anisotropic characteristics.

  20. Single Molecule Electronics and Devices

    PubMed Central

    Tsutsui, Makusu; Taniguchi, Masateru

    2012-01-01

    The manufacture of integrated circuits with single-molecule building blocks is a goal of molecular electronics. While research in the past has been limited to bulk experiments on self-assembled monolayers, advances in technology have now enabled us to fabricate single-molecule junctions. This has led to significant progress in understanding electron transport in molecular systems at the single-molecule level and the concomitant emergence of new device concepts. Here, we review recent developments in this field. We summarize the methods currently used to form metal-molecule-metal structures and some single-molecule techniques essential for characterizing molecular junctions such as inelastic electron tunnelling spectroscopy. We then highlight several important achievements, including demonstration of single-molecule diodes, transistors, and switches that make use of electrical, photo, and mechanical stimulation to control the electron transport. We also discuss intriguing issues to be addressed further in the future such as heat and thermoelectric transport in an individual molecule. PMID:22969345

  1. Adhesion molecules in vernal keratoconjunctivitis

    PubMed Central

    El-Asrar, A.; Geboes, K.; Al-Kharashi, S.; Tabbara, K.; Missotten, L.; Desmet, V.

    1997-01-01

    AIMS/BACKGROUND—Adhesion molecules play a key role in the selective recruitment of different leucocyte population to inflammatory sites. The purpose of the present study was to investigate the presence and distribution of adhesion molecules in the conjunctiva of patients with vernal keratoconjunctivitis (VKC).
METHODS—The presence and distribution of adhesion molecules were studied in 14 conjunctival biopsy specimens from seven patients with active VKC and in four normal conjunctival biopsy specimens. We used a panel of specific monoclonal antibodies (mAbs) directed against intercellular adhesion molecule-1 (ICAM-1), intercellular adhesion molecule-3 (ICAM-3), lymphocyte function associated antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leucocyte adhesion molecule-1 (ELAM-1). In addition, a panel of mAbs were used to characterise the composition of the inflammatory infiltrate.
RESULTS—In the normal conjunctiva, ICAM-1 was expressed on the vascular endothelium only, LFA-1 and ICAM-3 on epithelial and stromal mononuclear cells , and VLA-4 on stromal mononuclear cells. The expression of VCAM-1 and ELAM-1 was absent. The number of cells expressing adhesion molecules was found to be markedly increased in all VKC specimens. This was concurrent with a heavy inflammatory infiltrate. Strong ICAM-1 expression was induced on the basal epithelial cells, and vascular endothelial cells. Furthermore, ICAM-1 was expressed on stromal mononuclear cells. LFA-1 and ICAM-3 were expressed on the majority of epithelial and stromal infiltrating mononuclear cells. VLA-4 expression was noted on stromal mononuclear cells. Compared with controls, VKC specimens showed significantly more ICAM-3+, LFA-1+, and VLA-4+ cells. VCAM-1 and ELAM-1 were induced on the vascular endothelial cells.
CONCLUSIONS—Increased expression of adhesion molecules may play an important role in the pathogenesis of VKC.

 PMID

  2. Molecules for Fluorescence Detection of Specific Chemicals

    NASA Technical Reports Server (NTRS)

    Fedor, Steve

    2008-01-01

    A family of fluorescent dye molecules has been developed for use in on-off fluorescence detection of specific chemicals. By themselves, these molecules do not fluoresce. However, when exposed to certain chemical analytes in liquid or vapor forms, they do fluoresce (see figure). These compounds are amenable to fixation on or in a variety of substrates for use in fluorescence-based detection devices: they can be chemically modified to anchor them to porous or non-porous solid supports or can be incorporated into polymer films. Potential applications for these compounds include detection of chemical warfare agents, sensing of acidity or alkalinity, and fluorescent tagging of proteins in pharmaceutical research and development. These molecules could also be exploited for use as two-photon materials for photodynamic therapy in the treatment of certain cancers and other diseases. A molecule in this family consists of a fluorescent core (such as an anthracene or pyrene) attached to two end groups that, when the dye is excited by absorption of light, transfer an electron to the core, thereby quenching the fluorescence. The end groups can be engineered so that they react chemically with certain analytes. Upon reaction, electrons on the end groups are no longer available for transfer to the core and, consequently, the fluorescence from the core is no longer quenched. The chemoselectivity of these molecules can be changed by changing the end groups. For example, aniline end groups afford a capability for sensing acids or acid halides (including those contained in chemical warfare agents). Pyridine or bipyridyl end groups would enable sensing of metal ions. Other chemicals that can be selectively detected through suitable choice of end groups include glucose and proteins. Moreover, the fluorescent cores can be changed to alter light-absorption and -emission characteristics: anthracene cores fluoresce at wavelengths around 500 nm, whereas perylene cores absorb and emit at

  3. Resolving metal-molecule interfaces at single-molecule junctions

    NASA Astrophysics Data System (ADS)

    Komoto, Yuki; Fujii, Shintaro; Nakamura, Hisao; Tada, Tomofumi; Nishino, Tomoaki; Kiguchi, Manabu

    2016-05-01

    Electronic and structural detail at the electrode-molecule interface have a significant influence on charge transport across molecular junctions. Despite the decisive role of the metal-molecule interface, a complete electronic and structural characterization of the interface remains a challenge. This is in no small part due to current experimental limitations. Here, we present a comprehensive approach to obtain a detailed description of the metal-molecule interface in single-molecule junctions, based on current-voltage (I-V) measurements. Contrary to conventional conductance studies, this I-V approach provides a correlated statistical description of both, the degree of electronic coupling across the metal-molecule interface, and the energy alignment between the conduction orbital and the Fermi level of the electrode. This exhaustive statistical approach was employed to study single-molecule junctions of 1,4-benzenediamine (BDA), 1,4-butanediamine (C4DA), and 1,4-benzenedithiol (BDT). A single interfacial configuration was observed for both BDA and C4DA junctions, while three different interfacial arrangements were resolved for BDT. This multiplicity is due to different molecular adsorption sites on the Au surface namely on-top, hollow, and bridge. Furthermore, C4DA junctions present a fluctuating I-V curve arising from the greater conformational freedom of the saturated alkyl chain, in sharp contrast with the rigid aromatic backbone of both BDA and BDT.

  4. Resolving metal-molecule interfaces at single-molecule junctions

    PubMed Central

    Komoto, Yuki; Fujii, Shintaro; Nakamura, Hisao; Tada, Tomofumi; Nishino, Tomoaki; Kiguchi, Manabu

    2016-01-01

    Electronic and structural detail at the electrode-molecule interface have a significant influence on charge transport across molecular junctions. Despite the decisive role of the metal-molecule interface, a complete electronic and structural characterization of the interface remains a challenge. This is in no small part due to current experimental limitations. Here, we present a comprehensive approach to obtain a detailed description of the metal-molecule interface in single-molecule junctions, based on current-voltage (I-V) measurements. Contrary to conventional conductance studies, this I-V approach provides a correlated statistical description of both, the degree of electronic coupling across the metal-molecule interface, and the energy alignment between the conduction orbital and the Fermi level of the electrode. This exhaustive statistical approach was employed to study single-molecule junctions of 1,4-benzenediamine (BDA), 1,4-butanediamine (C4DA), and 1,4-benzenedithiol (BDT). A single interfacial configuration was observed for both BDA and C4DA junctions, while three different interfacial arrangements were resolved for BDT. This multiplicity is due to different molecular adsorption sites on the Au surface namely on-top, hollow, and bridge. Furthermore, C4DA junctions present a fluctuating I-V curve arising from the greater conformational freedom of the saturated alkyl chain, in sharp contrast with the rigid aromatic backbone of both BDA and BDT. PMID:27221947

  5. Relative Sizes of Organic Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This computer graphic depicts the relative complexity of crystallizing large proteins in order to study their structures through x-ray crystallography. Insulin is a vital protein whose structure has several subtle points that scientists are still trying to determine. Large molecules such as insuline are complex with structures that are comparatively difficult to understand. For comparison, a sugar molecule (which many people have grown as hard crystals in science glass) and a water molecule are shown. These images were produced with the Macmolecule program. Photo credit: NASA/Marshall Space Flight Center (MSFC)

  6. Quantum transport through aromatic molecules

    SciTech Connect

    Ojeda, J. H.; Rey-González, R. R.; Laroze, D.

    2013-12-07

    In this paper, we study the electronic transport properties through aromatic molecules connected to two semi-infinite leads. The molecules are in different geometrical configurations including arrays. Using a nearest neighbor tight-binding approach, the transport properties are analyzed into a Green's function technique within a real-space renormalization scheme. We calculate the transmission probability and the Current-Voltage characteristics as a function of a molecule-leads coupling parameter. Our results show different transport regimes for these systems, exhibiting metal-semiconductor-insulator transitions and the possibility to employ them in molecular devices.

  7. Relative Sizes of Organic Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This computer graphic depicts the relative complexity of crystallizing large proteins in order to study their structures through x-ray crystallography. Insulin is a vital protein whose structure has several subtle points that scientists are still trying to determine. Large molecules such as insuline are complex with structures that are comparatively difficult to understand. For comparison, a sugar molecule (which many people have grown as hard crystals in science glass) and a water molecule are shown. These images were produced with the Macmolecule program. Photo credit: NASA/Marshall Space Flight Center (MSFC)

  8. Continuous centrifuge decelerator for polar molecules.

    PubMed

    Chervenkov, S; Wu, X; Bayerl, J; Rohlfes, A; Gantner, T; Zeppenfeld, M; Rempe, G

    2014-01-10

    Producing large samples of slow molecules from thermal-velocity ensembles is a formidable challenge. Here we employ a centrifugal force to produce a continuous molecular beam with a high flux at near-zero velocities. We demonstrate deceleration of three electrically guided molecular species, CH3F, CF3H, and CF3CCH, with input velocities of up to 200  m s(-1) to obtain beams with velocities below 15  m s(-1) and intensities of several 10(9)  mm(-2) s(-1). The centrifuge decelerator is easy to operate and can, in principle, slow down any guidable particle. It has the potential to become a standard technique for continuous deceleration of molecules.

  9. The X(3872) boson: Molecule or charmonium

    SciTech Connect

    Suzuki, Mahiko

    2005-08-01

    It has been argued that the mystery boson X(3872) is a molecular state consisting of primarily D{sup 0}{bar D}*{sup 0} + {bar D}{sup 0}D*{sup 0}. In contrast, apparent puzzles and potential difficulties have been pointed out for the charmonium assignment of X(3872). They examine several aspects of these alternatives by semi-quantitative methods since quantitatively accurate results are often hard to reach on them. they point out that some of the observed properties of X(3872), in particular, the binding and the production rates are incompatible with the molecule interpretation. Despite puzzles and obstacles, X(3872) may fit more likely to the excited {sup 3}P{sub 1} charmonium than to the molecule after the mixing of c{bar c} with D{bar D}* + {bar D}D* is taken into account.

  10. Single-Molecule Localization Microscopy in Eukaryotes.

    PubMed

    Sauer, Markus; Heilemann, Mike

    2017-06-14

    Super-resolution fluorescence imaging by photoactivation or photoswitching of single fluorophores and position determination (single-molecule localization microscopy, SMLM) provides microscopic images with subdiffraction spatial resolution. This technology has enabled new insights into how proteins are organized in a cellular context, with a spatial resolution approaching virtually the molecular level. A unique strength of SMLM is that it delivers molecule-resolved information, along with super-resolved images of cellular structures. This allows quantitative access to cellular structures, for example, how proteins are distributed and organized and how they interact with other biomolecules. Ultimately, it is even possible to determine protein numbers in cells and the number of subunits in a protein complex. SMLM thus has the potential to pave the way toward a better understanding of how cells function at the molecular level. In this review, we describe how SMLM has contributed new knowledge in eukaryotic biology, and we specifically focus on quantitative biological data extracted from SMLM images.

  11. Targeted Protein Degradation by Small Molecules.

    PubMed

    Bondeson, Daniel P; Crews, Craig M

    2017-01-06

    Protein homeostasis networks are highly regulated systems responsible for maintaining the health and productivity of cells. Whereas therapeutics have been developed to disrupt protein homeostasis, more recently identified techniques have been used to repurpose homeostatic networks to effect degradation of disease-relevant proteins. Here, we review recent advances in the use of small molecules to degrade proteins in a selective manner. First, we highlight all-small-molecule techniques with direct clinical application. Second, we describe techniques that may find broader acceptance in the biomedical research community that require little or no synthetic chemistry. In addition to serving as innovative research tools, these new approaches to control intracellular protein levels offer the potential to develop novel therapeutics targeting proteins that are not currently pharmaceutically vulnerable.

  12. Forskolin: upcoming antiglaucoma molecule.

    PubMed

    Wagh, V D; Patil, P N; Surana, S J; Wagh, K V

    2012-01-01

    Forskolin is the first pharmaceutical drug and product derived from a plant to be approved in India by the DCGI in 2006. Forskolin (7beta-acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one) is a diterpenoid isolated from plant Coleus forskohlii (Lamiaceae). It is a lipid-soluble compound that can penetrate cell membranes and stimulates the enzyme adenylate cyclase which, in turn, stimulates ciliary epithelium to activate cyclic adenosine monophosphate, which decreases intraocular pressure (IOP) by reducing aqueous humor inflow. The topical application of forskolin is capable of reducing IOP in rabbits, monkeys, and humans. In its drug interactions, forskolin may act synergistically with epinephrine, ephedrine and pseudoephedrine. Whereas the effects of anti-clotting medications like warfarin, clopidogre, aspirin, anoxaparin, etc., may be enhanced by forskolin. Forskolin is contraindicated in the medications for people with ulcers as forskolin may increase acid level. Forskolin has a very good shelf-life of five years. Recently, its Ophthalmic inserts and in situ gels for sustained and delayed-release drug delivery systems were tested in New Zealand Albino Rabbits for its antiglaucoma efficacy. This drug review explains Forskolin as a drug, its antiglaucoma potential and recent findings of forskolin as an antiglaucoma agent. The literature search method used for this review was different databases and search engines like PubMed, International Pharmaceutical Abstracts, Google, Medicinal and Aromatic Plants (MAPA).

  13. Halogen bonds in biological molecules

    PubMed Central

    Auffinger, Pascal; Hays, Franklin A.; Westhof, Eric; Ho, P. Shing

    2004-01-01

    Short oxygen–halogen interactions have been known in organic chemistry since the 1950s and recently have been exploited in the design of supramolecular assemblies. The present survey of protein and nucleic acid structures reveals similar halogen bonds as potentially stabilizing inter- and intramolecular interactions that can affect ligand binding and molecular folding. A halogen bond in biomolecules can be defined as a short CX···OY interaction (CX is a carbon-bonded chlorine, bromine, or iodine, and OY is a carbonyl, hydroxyl, charged carboxylate, or phosphate group), where the X···O distance is less than or equal to the sums of the respective van der Waals radii (3.27 Å for Cl···O, 3.37Å for Br···O, and 3.50 Å for I···O) and can conform to the geometry seen in small molecules, with the CX···O angle ≈165° (consistent with a strong directional polarization of the halogen) and the X···OY angle ≈120°. Alternative geometries can be imposed by the more complex environment found in biomolecules, depending on which of the two types of donor systems are involved in the interaction: (i) the lone pair electrons of oxygen (and, to a lesser extent, nitrogen and sulfur) atoms or (ii) the delocalized π -electrons of peptide bonds or carboxylate or amide groups. Thus, the specific geometry and diversity of the interacting partners of halogen bonds offer new and versatile tools for the design of ligands as drugs and materials in nanotechnology. PMID:15557000

  14. Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials

    PubMed Central

    Scaggiante, Bruna; Kazemi, Maryam; Pozzato, Gabriele; Dapas, Barbara; Farra, Rosella; Grassi, Mario; Zanconati, Fabrizio; Grassi, Gabriele

    2014-01-01

    Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the sixth most common cancer worldwide and the third leading cause of cancer-related death. The difficulty to diagnose early cancer stages, the aggressive behaviors of HCC, and the poor effectiveness of therapeutic treatments, represent the reasons for the quite similar deaths per year and incidence number. Considering the fact that the diagnosis of HCC typically occurs in the advanced stages of the disease when the therapeutic options have only modest efficacy, the possibility to identify early diagnostic markers could be of significant benefit. So far, a large number of biomarkers have been associated to HCC progression and aggressiveness, but many of them turned out not to be of practical utility. This is the reason why active investigations are ongoing in this field. Given the huge amount of published works aimed at the identification of HCC biomarkers, in this review we mainly focused on the data published in the last year, with particular attention to the role of (1) molecular and biochemical cellular markers; (2) micro-interfering RNAs; (3) epigenetic variations; and (4) tumor stroma. It is worth mentioning that a significant number of the HCC markers described in the present review may be utilized also as targets for novel therapeutic approaches, indicating the tight relation between diagnosis and therapy. In conclusion, we believe that integrated researches among the different lines of investigation indicated above should represent the winning strategies to identify effective HCC markers and therapeutic targets. PMID:24574801

  15. Static Trapping of Polar Molecules in a Traveling Wave Decelerator

    NASA Astrophysics Data System (ADS)

    Quintero-Pérez, Marina; Jansen, Paul; Wall, Thomas E.; van den Berg, Joost E.; Hoekstra, Steven; Bethlem, Hendrick L.

    2013-03-01

    We present experiments on decelerating and trapping ammonia molecules using a combination of a Stark decelerator and a traveling wave decelerator. In the traveling wave decelerator, a moving potential is created by a series of ring-shaped electrodes to which oscillating high voltages (HV) are applied. By lowering the frequency of the applied voltages, the molecules confined in the moving trap are decelerated and brought to a standstill. As the molecules are confined in a true 3D well, this kind of deceleration has practically no losses, resulting in a great improvement on the usual Stark deceleration techniques. The necessary voltages are generated by amplifying the output of an arbitrary wave generator using fast HV amplifiers, giving us great control over the trapped molecules. We illustrate this by experiments in which we adiabatically cool trapped NH3 and ND3 molecules and resonantly excite their motion.

  16. Observations of molecules in comets

    NASA Technical Reports Server (NTRS)

    Feldman, P. D.

    1987-01-01

    Ultraviolet and visible spectroscopy of comets has identified a large number of species in the coma, most of which appear to be the photodissociation and photoionization products of the 'parent' molecules evaporated directly from the cometary nucleus. Analyses of cometary spectra support the icy conglomerate model of the nucleus with H2O as the dominant ice species. Two molecules detected in the ultraviolet, CO and S2, are of particular interest to the study of the cosmogonic evolution of cometary grains. CO appears to be a highly variable constituent from comet to comet, while S2, first observed in comet IRAS-Araki-Alcock in 1983, is found in no other celestial source. Both of these molecules appear to be parent molecules.

  17. Molecule-hugging graphene nanopores

    PubMed Central

    Garaj, Slaven; Liu, Song; Golovchenko, Jene A.; Branton, Daniel

    2013-01-01

    It has recently been recognized that solid-state nanopores in single-atomic-layer graphene membranes can be used to electronically detect and characterize single long charged polymer molecules. We have now fabricated nanopores in single-layer graphene that are closely matched to the diameter of a double-stranded DNA molecule. Ionic current signals during electrophoretically driven translocation of DNA through these nanopores were experimentally explored and theoretically modeled. Our experiments show that these nanopores have unusually high sensitivity (0.65 nA/Å) to extremely small changes in the translocating molecule’s outer diameter. Such atomically short graphene nanopores can also resolve nanoscale-spaced molecular structures along the length of a polymer, but do so with greatest sensitivity only when the pore and molecule diameters are closely matched. Modeling confirms that our most closely matched pores have an inherent resolution of ≤0.6 nm along the length of the molecule. PMID:23836648

  18. Fluorescence Microscopy of Single Molecules

    ERIC Educational Resources Information Center

    Zimmermann, Jan; van Dorp, Arthur; Renn, Alois

    2004-01-01

    The investigation of photochemistry and photophysics of individual quantum systems is described with the help of a wide-field fluorescence microscopy approach. The fluorescence single molecules are observed in real time.

  19. Fluorescence Microscopy of Single Molecules

    ERIC Educational Resources Information Center

    Zimmermann, Jan; van Dorp, Arthur; Renn, Alois

    2004-01-01

    The investigation of photochemistry and photophysics of individual quantum systems is described with the help of a wide-field fluorescence microscopy approach. The fluorescence single molecules are observed in real time.

  20. Moving Molecules and Mothball Madness.

    ERIC Educational Resources Information Center

    Strain, John

    1993-01-01

    Describes concrete demonstrations on the states of matter. In the first demonstration, students represent molecules; and, in the second demonstration, moth balls are heated to produce a change of state. (PR)