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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. Genetic variation of the whole ICAM4 gene in Caucasians and African Americans

    PubMed Central

    Srivastava, Kshitij; Almarry, Noorah Salman; Flegel, Willy A.

    2014-01-01

    Background Landsteiner-Wiener (LW) is the human blood group system no. 16, which comprises 2 antithetical antigens, LWa and LWb and the high prevalence antigen LWab. LW is encoded by the Intracellular Adhesion Molecule 4 (ICAM4) gene. The ICAM4 protein is part of the Rhesus complex in the red cell membrane and is involved in cell-cell adhesion. Methods We developed a method to sequence the whole 1.9 kb ICAM4 gene from genomic DNA in 1 amplicon. We determined the nucleotide sequence of exons 1 to 3, the 2 introns and 402 bp 5′-UTR and 347 bp 3′-UTR in 97 Caucasian and 91 African American individuals. Results Seven variant ICAM4 alleles were found, distinct from the wild type ICAM4 allele (GenBank KF712272), known as LW*05 and encoding LWa. An effect of the LWa/LWb amino acid substitution on the protein structure was predicted by 2 of the 3 computational modeling programs used. Conclusions We describe a practical approach for sequencing and determining the ICAM4 alleles using genomic DNA. LW*05 is the ancestral allele, which had also been observed in a Neandertal sample. All 7 variant alleles are immediate derivatives of the prevalent LW*05 and caused by 1 single nucleotide polymorphism (SNP) in each allele. Our data were consistent with the NHLBI GO Exome Sequencing Project (ESP) and the dbSNP databases, as all SNPs had been observed before. Our study has the advantage over the other databases in that it adds haplotype (allele) information for the ICAM4 gene, clinically relevant in the field of transfusion medicine. PMID:24673173

  4. 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

  5. Fixman compensating potential for general branched molecules

    PubMed Central

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

    2013-01-01

    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. PMID:24387353

  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. Determination of interionic potentials in molecules

    SciTech Connect

    Conradson, S.D.; Leon, J.M.; Bridges, F.

    1996-04-01

    The rationale underlying materials by design is that properties are determined by structure so that if the relationships between structure and properties are understood, an appropriate material can be designed and fabricated to meet any set of criteria. Since ion-ion potentials determine state transformations and reactivity, they are essential to the entire concept of materials and molecules by design. Virtually all of the important state-to-state processes undergone by molecules (excitation, relaxation, ionization, dissociation, and combination) and the selection among these different pathways are determined by the ion-ion potentials and the resulting degree of overlap between molecular vibrational states for different electronic and atomic configurations. Although the depths of these potentials can be obtained from thermodynamic data and the separations between the vibronic states from spectroscopic measurements, the use of these potentials in the ab initio calculation of state-transformation outcomes is limited by the absence of any direct method for determining their extent and shape. The authors have recently developed a generalization of x-ray absorption fine structure (XAFS) and a related set of experimental and analysis procedures that, in principle, will allow them to obtain such potentials from XAFS data. They have undertaken the analysis of temperature-dependent XAFS data of Cu, Ag, and Au to test the accuracy of existing analytical forms (the Morse potential for metals) in predicting the details of pair distributions and to determine the range of validity of a temperature-independent effective pair-potential approximation. This is the final report of a three-year Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL).

  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. PMID:26476490

  9. Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

    PubMed Central

    Järveläinen, Hannu; Sainio, Annele; Koulu, Markku; Wight, Thomas N.; Penttinen, Risto

    2009-01-01

    The extracellular matrix (ECM) consists of numerous macromolecules classified traditionally into collagens, elastin, and microfibrillar proteins, proteoglycans including hyaluronan, and noncollagenous glycoproteins. In addition to being necessary structural components, ECM molecules exhibit important functional roles in the control of key cellular events such as adhesion, migration, proliferation, differentiation, and survival. Any structural inherited or acquired defect and/or metabolic disturbance in the ECM may cause cellular and tissue alterations that can lead to the development or progression of disease. Consequently, ECM molecules are important targets for pharmacotherapy. Specific agents that prevent theexcess accumulation of ECM molecules in the vascular system, liver, kidney, skin, and lung; alternatively, agents that inhibit the degradation of the ECM in degenerative diseases such as osteoarthritis would be clinically beneficial. Unfortunately, until recently, the ECM in drug discovery has been largely ignored. However, several of today's drugs that act on various primary targets affect the ECM as a byproduct of the drugs' actions, and this activity may in part be beneficial to the drugs' disease-modifying properties. In the future, agents and compounds targeting directly the ECM will significantly advance the treatment of various human diseases, even those for which efficient therapies are not yet available. PMID:19549927

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

    PubMed

    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. PMID:27387127

  11. Kohn-Sham potentials for fullerenes and spherical molecules

    SciTech Connect

    Pavlyukh, Y.; Berakdar, J.

    2010-04-15

    We present a procedure for the construction of accurate Kohn-Sham potentials of quasispherical molecules starting from the first-principles valence densities. The method is demonstrated for the case of icosahedral C{sub 20}{sup 2+} and C{sub 60} molecules. Provided the density is N representable the Hohenberg-Kohn theorem guarantees the uniqueness of the obtained potentials. The potential is iteratively built following the suggestion of R. van Leeuwen and E. J. Baerends [Phys. Rev. A 49, 2421 (1994)]. The high symmetry of the molecules allows a parametrization of the angular dependence of the densities and the potentials using a small number of symmetry-adapted spherical harmonics. The radial behavior of these quantities is represented on a grid and the density is reconstructed from the approximate potential by numerically solving the coupled-channel Kohn-Sham equations. Subsequently, the potential is updated and the procedure is continued until convergence is achieved.

  12. Coarse-grained interaction potentials for anisotropic molecules.

    PubMed

    Babadi, M; Everaers, R; Ejtehadi, M R

    2006-05-01

    We have proposed an efficient parametrization method for a recent variant of the Gay Berne potential for dissimilar and biaxial particles [Phys. Rev. E 67, 041710 (2003)] and demonstrated it for a set of small organic molecules. Compared with the previously proposed coarse-grained models, the new potential exhibits a superior performance in close contact and large distant interactions. The repercussions of thermal vibrations and elasticity have been studied through a statistical method. The study justifies that the potential of mean force is representable with the same functional form, extending the application of this coarse-grained description to a broader range of molecules. Moreover, the advantage of employing coarse-grained models over truncated atomistic summations with large distance cutoffs has been briefly studied. PMID:16689591

  13. 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.

  14. 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.

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

    PubMed

    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. PMID:25481132

  16. Contrastive studies of potential energy functions of some diatomic molecules

    NASA Astrophysics Data System (ADS)

    Abdallah, Hassan H.; Abdullah, Hewa Y.

    2016-03-01

    It was proposed that iron hydride, FeH, would be formed only on grains at the clouds through the reaction of the adsorbed H atoms or H2 molecules with the adsorbed Fe atoms on the grains. The importance of FeH in Astrophysics presents an additional motivation to study its energetic, spectroscopic constants and Potential Energy Curves. The structural optimization for ground state of FeH was calculated by different theoretical methods, namely, Hartree-Fock (HF), the density functional theory (DFT), B3LYP, MP2 method and QCISD(T) methods and compared with available data from the literature. The single ionized forms, cation and anion, were also obtained at the same level of calculations. Charges, dipole moment, geometrical parameters, molecular orbital energies and spectroscopic parameters were calculated and reported. In addition, the molecular ionization potential, electron affinity and dissociation energy were investigated.

  17. 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.

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

    PubMed

    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

  19. 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

  20. Rovibrational states of Wigner molecules in spherically symmetric confining potentials.

    PubMed

    Cioslowski, Jerzy

    2016-08-01

    The strong-localization limit of three-dimensional Wigner molecules, in which repulsively interacting particles are confined by a weak spherically symmetric potential, is investigated. An explicit prescription for computation of rovibrational wavefunctions and energies that are asymptotically exact at this limit is presented. The prescription is valid for systems with arbitrary angularly-independent interparticle and confining potentials, including those involving Coulombic and screened (i.e., Yukawa/Debye) interactions. The necessary derivations are greatly simplified by explicit constructions of the Eckart frame and the parity-adapted primitive wavefunctions. The performance of the new formalism is illustrated with the three- and four-electron harmonium atoms at their strong-correlation limits. In particular, the involvement of vibrational modes with the E symmetry is readily pinpointed as the origin of the "anomalous" weak-confinement behavior of the (1)S+ state of the four-electron species that is absent in its (1)D+ companion of the strong-confinement regime. PMID:27497548

  1. Rovibrational states of Wigner molecules in spherically symmetric confining potentials

    NASA Astrophysics Data System (ADS)

    Cioslowski, Jerzy

    2016-08-01

    The strong-localization limit of three-dimensional Wigner molecules, in which repulsively interacting particles are confined by a weak spherically symmetric potential, is investigated. An explicit prescription for computation of rovibrational wavefunctions and energies that are asymptotically exact at this limit is presented. The prescription is valid for systems with arbitrary angularly-independent interparticle and confining potentials, including those involving Coulombic and screened (i.e., Yukawa/Debye) interactions. The necessary derivations are greatly simplified by explicit constructions of the Eckart frame and the parity-adapted primitive wavefunctions. The performance of the new formalism is illustrated with the three- and four-electron harmonium atoms at their strong-correlation limits. In particular, the involvement of vibrational modes with the E symmetry is readily pinpointed as the origin of the "anomalous" weak-confinement behavior of the 1S+ state of the four-electron species that is absent in its 1D+ companion of the strong-confinement regime.

  2. 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

  3. 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.

  4. Canonical transient receptor potential 4 and its small molecule modulators

    PubMed Central

    FU, Jie; GAO, ZhaoBing; SHEN, Bing; ZHU, Michael X.

    2015-01-01

    Canonical transient receptor potential 4 (TRPC4) forms non-selective cation channels that contribute to phospholipase C-dependent Ca2+ entry into cells following stimulation of G protein coupled receptors and receptor tyrosine kinases. More-over, the channels are regulated by pertussis toxin-sensitive Gi/o proteins, lipids, and various other signaling mechanisms. TRPC4-containing channels participate in the regulation of a variety of physiological functions, including excitability of both gastrointestinal smooth muscles and brain neurons. This review is to present recent advances in the understanding of physiology and development of small molecular modulators of TRPC4 channels. PMID:25480324

  5. Non Coding RNA Molecules as Potential Biomarkers in Breast Cancer.

    PubMed

    De Leeneer, Kim; Claes, Kathleen

    2015-01-01

    The pursuit of minimally invasive biomarkers is a challenging but exciting area of research. Clearly, such markers would need to be sensitive and specific enough to aid in the detection of breast cancer at an early stage, would monitor progression of the disease, and could predict the individual patient's response to treatment. Unfortunately, to date, markers with such characteristics have not made it to the clinic for breast cancer. Past years, many studies indicated that the non-coding part of our genome (the so called 'junk' DNA), may be an ideal source for these biomarkers. In this chapter, the potential use of microRNAs and long non-coding RNAs as biomarkers will be discussed. PMID:26530371

  6. Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer's Disease.

    PubMed

    Thapa, Arjun; Chi, Eva Y

    2015-01-01

    Flavonoids are naturally occurring phytochemicals found in a variety of fruits and vegetables and offer color, flavor, aroma, nutritional and health benefits. Flavonoids have been found to play a neuroprotective role by inhibiting and/or modifying the self-assembly of the amyloid-β (Aβ) peptide into oligomers and fibrils, which are linked to the pathogenesis of Alzheimer's disease. The neuroprotective efficacy of flavonoids has been found to strongly depend on their structure and functional groups. Flavonoids may exist in monomeric, as well as di-, tri-, tetra- or polymeric form through C-C or C-O-C linkages. It has been shown that flavonoids containing two or more units, e.g., biflavonoids, exert greater biological activity than their respective monoflavonoids. For instance, biflavonoids have the ability to distinctly alter Aβ aggregation and more effectively reduce the toxicity of Aβ oligomers compared to the monoflavonoid moieties. Although the molecular mechanisms remain to be elucidated, flavonoids have been shown to alter the Aβ aggregation pathway to yield non-toxic, unstructured Aβ aggregates, as well as directly exerting a neuroprotective effect to cells. In this chapter, we review biflavonoid-mediated Aβ aggregation and toxicity, and highlight the beneficial roles biflavonoids can potentially play in the prevention and treatment of Alzheimer's disease. PMID:26092626

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

    PubMed

    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

    2016-08-19

    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

  8. Resonant transmission of a weakly bound molecule incident upon a step potential

    NASA Astrophysics Data System (ADS)

    Shegelski, Mark R. A.; Jones, George

    2016-08-01

    The case of a molecule with a single weakly bound state is considered. The molecule is incident in the bound state upon a step potential with an energy increase of V 0. We calculate the probability of reflection p R and transmission p T in the bound state and its dependence on the energy of the molecule. Three energy ranges are examined. For the highest range, resonant transmission occurs for all energies, a behaviour drastically different than that of a single particle. Other unexpected results are obtained and the physical reasons underlying the results are discussed.

  9. Scattering of a two-soliton molecule by Gaussian potentials in dipolar Bose–Einstein condensates

    NASA Astrophysics Data System (ADS)

    Umarov, B. A.; Aklan, N. A. B.; Baizakov, B. B.; Abdullaev, F. Kh

    2016-06-01

    Two bright solitons in a dipolar Bose–Einstein condensate (BEC) can form stable bound states, known as soliton molecules. In this paper we study the scattering of a two-soliton molecule by external potential, using the simplest and analytically tractable Gaussian potential barriers and wells, in one spatial dimension. Collisions of soliton molecules with single solitons are investigated, the latter playing the role of a localized defect. Due to the long-range character of dipolar forces solitons interact with each other even though their waveforms do not appreciably overlap. This is an essentially different feature of dipolar solitons compared to their counterparts in BECs with contact atomic interactions. The result of scattering significantly depends on the potential’s strength and velocity of collision. For weak potentials and/or low velocity the molecule preserves its coherence, meantime the internal modes are excited. Scattering by strong potentials at moderately high velocity ends up with dissociation of the molecule. The theoretical model is based on the variational approximation for the nonlocal Gross–Pitaevskii equation (GPE). Predictions of the mathematical model are compared with numerical simulations of the nonlocal GPE, and good qualitative agreement between them is demonstrated.

  10. Structures, Bonding, and Energetics of Potential Triatomic Circumstellar Molecules Containing Group 15 and 16 Elements.

    PubMed

    Turner, Walter E; Agarwal, Jay; Schaefer, Henry F

    2015-12-01

    The recent discovery of PN in the oxygen-rich shell of the supergiant star VY Canis Majoris points to the formation of several triatomic molecules involving oxygen, nitrogen, and phosphorus; these are also intriguing targets for main-group synthetic inorganic chemistry. In this research, high-level ab initio electronic structure computations were conducted on the potential circumstellar molecule OPN and several of its heavier group 15 and 16 congeners (SPN, SePN, TePN, OPP, OPAs, and OPSb). For each congener, four isomers were examined. Optimized geometries were obtained with coupled cluster theory [CCSD(T)] using large Dunning basis sets [aug-cc-pVQZ, aug-cc-pV(Q+d)Z, and aug-cc-pVQZ-PP], and relative energies were determined at the complete basis set limit of CCSDT(Q) from focal point analyses. The linear phosphorus-centered molecules were consistently the lowest in energy of the group 15 congeners by at least 6 kcal mol(-1), resulting from double-triple and single-double bond resonances within the molecule. The linear nitrogen-centered molecules were consistently the lowest in energy of the group 16 congeners by at least 5 kcal mol(-1), due to the electronegative central nitrogen atom encouraging electron delocalization throughout the molecule. For OPN, OPP, and SPN, anharmonic vibrational frequencies and vibrationally corrected rotational constants are predicted; good agreement with available experimental data is observed. PMID:26566183

  11. Quantum dynamics of a hydrogen molecule confined in a cylindrical potential

    NASA Astrophysics Data System (ADS)

    Yildirim, Taner; Harris, A. B.

    2003-06-01

    We study the coupled rotation-vibration levels of a hydrogen molecule in a confining potential with cylindrical symmetry. We include the coupling between rotations and translations and show how this interaction is essential to obtain the correct degeneracies of the energy level scheme. We applied our formalism to study the dynamics of H2 molecules inside a “smooth” carbon nanotube as a function of tube radius. The results are obtained both by numerical solution of the (2J+1)-component radial Schrödinger equation and by developing an effective Hamiltonian to describe the splitting of a manifold of states of fixed angular momentum J and number of phonons N. For nanotube radius smaller than ≈3.5 Å, the confining potential has a parabolic shape and the results can be understood in terms of a simple toy model. For larger radius, the potential has the “Mexican hat” shape and therefore the H2 molecule is off centered, yielding radial and tangential translational dynamics in addition to rotational dynamics of H2 molecule which we also describe by a simple model. Finally, we make several predictions for the the neutron scattering observation of various transitions between these levels.

  12. Permutation invariant polynomial neural network approach to fitting potential energy surfaces. III. Molecule-surface interactions

    NASA Astrophysics Data System (ADS)

    Jiang, Bin; Guo, Hua

    2014-07-01

    The permutation invariant polynomial-neural network (PIP-NN) method for constructing highly accurate potential energy surfaces (PESs) for gas phase molecules is extended to molecule-surface interaction PESs. The symmetry adaptation in the NN fitting of a PES is achieved by employing as the input symmetry functions that fulfill both the translational symmetry of the surface and permutation symmetry of the molecule. These symmetry functions are low-order PIPs of the primitive symmetry functions containing the surface periodic symmetry. It is stressed that permutationally invariant cross terms are needed to avoid oversymmetrization. The accuracy and efficiency are demonstrated in fitting both a model PES for the H2 + Cu(111) system and density functional theory points for the H2 + Ag(111) system.

  13. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

    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.

  15. 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

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

    NASA Astrophysics Data System (ADS)

    Fidiani, Elok

    2016-03-01

    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, H2 and O2. 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.

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

    NASA Astrophysics Data System (ADS)

    Tautz, Stefan

    2014-03-01

    Van der Waals (vdW) forces act ubiquitously in condensed matter. Their description as an inherently quantum mechanical phenomenon was developed for single atoms and homogeneous macroscopic bodies by London, Casimir, and Lifshitz. For intermediate-sized objects like organic molecules an atomistic description is required, but explicit first principles calculations are very difficult since correlations between many interacting electrons have to be considered. Hence, semi-empirical correction schemes are often used that simplify the vdW interaction to a sum over atom-pair potentials. A similar gap exists between successful measurements of vdW and Casimir forces for single atoms on the one hand and macroscopic bodies on the other, as comparable experiments for molecules are absent. I will present experiments in which long-range vdW potentials between a series of related molecules and a metal surface have been determined experimentally. The experiments rely on the extremely sensitive force detection of an atomic force microscope in combination with its molecular manipulation capabilities. The results allow us to confirm the asymptotic force law and to quantify the non-additive part of the vdW interaction which is particularly challenging for theory. In the present case, cooperative effects account for 10% of the total interaction. This effect is of general validity in molecules and thus relevant at the intersection of chemistry, physics, biology, and materials science.

  18. Theoretical and experimental electrostatic potential around the m-nitrophenol molecule.

    PubMed

    Drissi, Mokhtaria; Benhalima, Nadia; Megrouss, Youcef; Rachida, Rahmani; Chouaih, Abdelkader; Hamzaoui, Fodil

    2015-01-01

    This work concerns a comparison of experimental and theoretical results of the electron charge density distribution and the electrostatic potential around the m-nitrophenol molecule (m-NPH) known for its interesting physical characteristics. The molecular experimental results have been obtained from a high-resolution X-ray diffraction study. Theoretical investigations were performed using the Density Functional Theory at B3LYP level of theory at 6-31G* in the Gaussian program. The multipolar model of Hansen and Coppens was used for the experimental electron charge density distribution around the molecule, while we used the DFT methods for the theoretical calculations. The electron charge density obtained in both methods allowed us to find out different molecular properties such us the electrostatic potential and the dipole moment, which were finally subject to a comparison leading to a good match obtained between both methods. The intramolecular charge transfer has also been confirmed by an HOMO-LUMO analysis. PMID:25741898

  19. Current and potential uses of bioactive molecules from marine processing waste.

    PubMed

    Suleria, Hafiz Ansar Rasul; Masci, Paul; Gobe, Glenda; Osborne, Simone

    2016-03-15

    Food industries produce huge amounts of processing waste that are often disposed of incurring expenses and impacting upon the environment. For these and other reasons, food processing waste streams, in particular marine processing waste streams, are gaining popularity amongst pharmaceutical, cosmetic and nutraceutical industries as sources of bioactive molecules. In the last 30 years, there has been a gradual increase in processed marine products with a concomitant increase in waste streams that include viscera, heads, skins, fins, bones, trimmings and shellfish waste. In 2010, these waste streams equated to approximately 24 million tonnes of mostly unused resources. Marine processing waste streams not only represent an abundant resource, they are also enriched with structurally diverse molecules that possess a broad panel of bioactivities including anti-oxidant, anti-coagulant, anti-thrombotic, anti-cancer and immune-stimulatory activities. Retrieval and characterisation of bioactive molecules from marine processing waste also contributes valuable information to the vast field of marine natural product discovery. This review summarises the current use of bioactive molecules from marine processing waste in different products and industries. Moreover, this review summarises new research into processing waste streams and the potential for adoption by industries in the creation of new products containing marine processing waste bioactives. PMID:26332893

  20. 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

  1. Proteasome activation is a mechanism for pyrazolone small molecules displaying therapeutic potential in amyotrophic lateral sclerosis.

    PubMed

    Trippier, Paul C; Zhao, Kevin Tianmeng; Fox, Susan G; Schiefer, Isaac T; Benmohamed, Radhia; Moran, Jason; Kirsch, Donald R; Morimoto, Richard I; Silverman, Richard B

    2014-09-17

    Amyotrophic lateral sclerosis (ALS) is a progressive and ultimately fatal neurodegenerative disease. Pyrazolone containing small molecules have shown significant disease attenuating efficacy in cellular and murine models of ALS. Pyrazolone based affinity probes were synthesized to identify high affinity binding partners and ascertain a potential biological mode of action. Probes were confirmed to be neuroprotective in PC12-SOD1(G93A) cells. PC12-SOD1(G93A) cell lysates were used for protein pull-down, affinity purification, and subsequent proteomic analysis using LC-MS/MS. Proteomics identified the 26S proteasome regulatory subunit 4 (PSMC1), 26S proteasome regulatory subunit 6B (PSMC4), and T-complex protein 1 (TCP-1) as putative protein targets. Coincubation with appropriate competitors confirmed the authenticity of the proteomics results. Activation of the proteasome by pyrazolones was demonstrated in the absence of exogenous proteasome inhibitor and by restoration of cellular protein degradation of a fluorogenic proteasome substrate in PC12-SOD1(G93A) cells. Importantly, supplementary studies indicated that these molecules do not induce a heat shock response. We propose that pyrazolones represent a rare class of molecules that enhance proteasomal activation in the absence of a heat shock response and may have therapeutic potential in ALS. PMID:25001311

  2. Effective medium potentials for molecule-surface interactions: H2 on Cu and Ni surfaces

    NASA Astrophysics Data System (ADS)

    Nørskov, J. K.

    1989-06-01

    A new approximate method is developed for the calculation of the adiabatic potential energy surface for a molecule outside a metal surface. It is computationally fast enough to be useful in simulations of the dynamics of adsorbing and desorbing molecules. The method is characterized by the fact that the functional form of the total energy expression is derived from density functional theory, that each of the terms entering can be given a precise physical interpretation, and that most of the parameters entering can be calculated, within the local density approximation. The method is explicitly derived for H2 outside metal surfaces and the applicability is illustrated for H2 adsorbing on various Cu and Ni surfaces. Although very approximate, the calculated potentials seem to include a number of features observed experimentally: Ni is more active in dissociating H2 than Cu, and open surfaces are more active than close-packed ones. Moreover, the method is simple enough that one can contemplate studying variations in dissociation pathways over the surface unit cell. For the Cu surfaces these variations are substantial accounting for at least part of the variation of the sticking coefficient with the kinetic energy of the incoming molecule. Because of the transparent nature of the energy expression, all these trends can be given a simple physical interpretation.

  3. 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. PMID:25375470

  4. 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

  5. Modeling intermolecular interactions of physisorbed organic molecules using pair potential calculations

    SciTech Connect

    Kroeger, Ingo; Stadtmueller, Benjamin; Wagner, Christian; Weiss, Christian; Temirov, Ruslan; Tautz, F. Stefan; Kumpf, Christian

    2011-12-21

    The understanding and control of epitaxial growth of organic thin films is of crucial importance in order to optimize the performance of future electronic devices. In particular, the start of the submonolayer growth plays an important role since it often determines the structure of the first layer and subsequently of the entire molecular film. We have investigated the structure formation of 3,4,9,10-perylene-tetracarboxylic dianhydride and copper-phthalocyanine molecules on Au(111) using pair-potential calculations based on van der Waals and electrostatic intermolecular interactions. The results are compared with the fundamental lateral structures known from experiment and an excellent agreement was found for these weakly interacting systems. Furthermore, the calculations are even suitable for chemisorptive adsorption as demonstrated for copper-phthalocyanine/Cu(111), if the influence of charge transfer between substrate and molecules is known and the corresponding charge redistribution in the molecules can be estimated. The calculations are of general applicability for molecular adsorbate systems which are dominated by electrostatic and van der Waals interaction.

  6. Design, synthesis, and characterization of TPA-thiophene-based amide or imine functionalized molecule for potential optoelectronic devices

    NASA Astrophysics Data System (ADS)

    Sarswat, Prashant K.; Sathyapalan, Amarchand; Zhu, Yakun; Free, Michael L.

    2013-01-01

    New sets of molecules containing tri-phenyl-amine (TPA) core and thiophene unit with amide and imine functional groups are designed, synthesized, characterized, and compared. These are solution processable small molecules with high mobility. The newly designed molecules have better solubility due to the C=N (imine) and CONH2 (amide) moiety as compared to the established molecules with CH=CH (methine) for optoelectronic applications. They have an optimal energy band gap, which indicates their potential utility in a variety of optoelectronic applications. These molecules also show efficient intermolecular charge transfer mechanisms similar to conventional organic semiconducting molecules as evidenced by optical measurements. Density functional theory simulation results show that the localization of the frontier highest occupied molecular orbital is around the TPA core for molecules coupled with imine and amide, and is reasonably stable.

  7. 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

  8. Accurate Ionization Potentials and Electron Affinities of Acceptor Molecules IV: Electron-Propagator Methods.

    PubMed

    Dolgounitcheva, O; Díaz-Tinoco, Manuel; Zakrzewski, V G; Richard, Ryan M; Marom, Noa; Sherrill, C David; Ortiz, J V

    2016-02-01

    Comparison of ab initio electron-propagator predictions of vertical ionization potentials and electron affinities of organic, acceptor molecules with benchmark calculations based on the basis set-extrapolated, coupled cluster single, double, and perturbative triple substitution method has enabled identification of self-energy approximations with mean, unsigned errors between 0.1 and 0.2 eV. Among the self-energy approximations that neglect off-diagonal elements in the canonical, Hartree-Fock orbital basis, the P3 method for electron affinities, and the P3+ method for ionization potentials provide the best combination of accuracy and computational efficiency. For approximations that consider the full self-energy matrix, the NR2 methods offer the best performance. The P3+ and NR2 methods successfully identify the correct symmetry label of the lowest cationic state in two cases, naphthalenedione and benzoquinone, where some other methods fail. PMID:26730459

  9. CVRQD ab initio ground-state adiabatic potential energy surfaces for the water molecule.

    PubMed

    Barletta, Paolo; Shirin, Sergei V; Zobov, Nikolai F; Polyansky, Oleg L; Tennyson, Jonathan; Valeev, Edward F; Császár, Attila G

    2006-11-28

    The high accuracy ab initio adiabatic potential energy surfaces (PESs) of the ground electronic state of the water molecule, determined originally by Polyansky et al. [Science 299, 539 (2003)] and called CVRQD, are extended and carefully characterized and analyzed. The CVRQD potential energy surfaces are obtained from extrapolation to the complete basis set of nearly full configuration interaction valence-only electronic structure computations, augmented by core, relativistic, quantum electrodynamics, and diagonal Born-Oppenheimer corrections. We also report ab initio calculations of several quantities characterizing the CVRQD PESs, including equilibrium and vibrationally averaged (0 K) structures, harmonic and anharmonic force fields, harmonic vibrational frequencies, vibrational fundamentals, and zero-point energies. They can be considered as the best ab initio estimates of these quantities available today. Results of first-principles computations on the rovibrational energy levels of several isotopologues of the water molecule are also presented, based on the CVRQD PESs and the use of variational nuclear motion calculations employing an exact kinetic energy operator given in orthogonal internal coordinates. The variational nuclear motion calculations also include a simplified treatment of nonadiabatic effects. This sophisticated procedure to compute rovibrational energy levels reproduces all the known rovibrational levels of the water isotopologues considered, H(2) (16)O, H(2) (17)O, H(2) (18)O, and D(2) (16)O, to better than 1 cm(-1) on average. Finally, prospects for further improvement of the ground-state adiabatic ab initio PESs of water are discussed. PMID:17144700

  10. 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.

  11. 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

  12. Proline-rich peptides: multifunctional bioactive molecules as new potential therapeutic drugs.

    PubMed

    Vitali, Alberto

    2015-01-01

    Proline-rich peptides (PRPs) include a large and heterogeneous group of small-medium sized peptides characterized by the presence of proline residues often constituting peculiar sequences. This feature confers them a typical structure that determines the various biological functions endowed by these molecules. In particular the left-handed-polyproline-II helix is essential for the expression of the antimicrobial, immunomodulatory, antioxidant properties and to finely modulate protein-protein interactions, thus playing crucial roles in many cell signal transduction pathways. These peptides are widely diffuse in the animal kingdom and in humans, where they are present in many tissues and biological fluids. This review highlights the most relevant biological properties of these peptides, focusing on the potential therapeutic role that the PRPs may play as a promising source of new peptidebased novel drugs. PMID:25692951

  13. 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

  14. Benzofuran Small Molecules as Potential Inhibitors of Human Protein Kinases. A Review.

    PubMed

    Kwiecień, Halina; Goszczyńska, Agata; Rokosz, Paulina

    2016-01-01

    Kinases are known to regulate the majority of human cellular processes such as communication, division, metabolism, survival and apoptosis therefore they can be promising targets in cancer diseases, viral infection and in other disorders. Small molecules acting as selective human protein kinase inhibitors are very attractive pharmacological targets. This review presents a number of examples of biologically active natural and synthetic benzo[b]furans and their derivatives, such as benzo[b]furan-2- and 3-ones, benzo[b]furan-2- and 3-carboxylic acids, as well as benzo[c]furans as potential inhibitors of various human protein kinases. The pathways of function and implication of the inhibitors in cancer and other diseases are discussed. PMID:26648467

  15. Ground state of the polar alkali-metal-atom-strontium molecules: Potential energy curve and permanent dipole moment

    SciTech Connect

    Guerout, R.; Aymar, M.; Dulieu, O.

    2010-10-15

    In this study, we investigate the structure of the polar alkali-metal-atom-strontium diatomic molecules as possible candidates for the realization of samples of ultracold polar molecular species not yet investigated experimentally. Using a quantum chemistry approach based on effective core potentials and core polarization potentials, we model these systems as effective three-valence-electron systems, allowing for calculation of electronic properties with full configuration interaction. The potential curve and the permanent dipole moment of the {sup 2}{Sigma}{sup +} ground state are determined as functions of the internuclear distance for LiSr, NaSr, KSr, RbSr, and CsSr molecules. These molecules are found to exhibit a significant permanent dipole moment, though smaller than those of the alkali-metal-atom-Rb molecules.

  16. Very accurate potential energy curve of the LiH molecule

    NASA Astrophysics Data System (ADS)

    Tung, Wei-Cheng; Pavanello, Michele; Adamowicz, Ludwik

    2011-02-01

    We present very accurate calculations of the ground-state potential energy curve (PEC) of the LiH molecule performed with all-electron explicitly correlated Gaussian functions with shifted centers. The PEC is generated with the variational method involving simultaneous optimization of all Gaussians with an approach employing the analytical first derivatives of the energy with respect to the Gaussian nonlinear parameters (i.e., the exponents and the coordinates of the shifts). The LiH internuclear distance is varied between 1.8 and 40 bohrs. The absolute accuracy of the generated PEC is estimated as not exceeding 0.3 cm-1. The adiabatic corrections for the four LiH isotopologues, i.e., 7LiH, 6LiH, 7LiD, and 6LiD, are also calculated and added to the LiH PEC. The aforementioned PECs are then used to calculate the vibrational energies for these systems. The maximum difference between the computed and the experimental vibrational transitions is smaller than 0.9 cm-1. The contribution of the adiabatic correction to the dissociation energy of 7LiH molecule is 10.7 cm-1. The magnitude of this correction shows its importance in calculating the LiH spectroscopic constants. As the estimated contribution of the nonadiabatic and relativistic effects to the ground state dissociation energy is around 0.3 cm-1, their inclusion in the LiH PEC calculation seems to be the next most important contribution to evaluate in order to improve the accuracy achieved in this work.

  17. Very accurate potential energy curve of the LiH molecule.

    PubMed

    Tung, Wei-Cheng; Pavanello, Michele; Adamowicz, Ludwik

    2011-02-14

    We present very accurate calculations of the ground-state potential energy curve (PEC) of the LiH molecule performed with all-electron explicitly correlated Gaussian functions with shifted centers. The PEC is generated with the variational method involving simultaneous optimization of all Gaussians with an approach employing the analytical first derivatives of the energy with respect to the Gaussian nonlinear parameters (i.e., the exponents and the coordinates of the shifts). The LiH internuclear distance is varied between 1.8 and 40 bohrs. The absolute accuracy of the generated PEC is estimated as not exceeding 0.3 cm(-1). The adiabatic corrections for the four LiH isotopologues, i.e., (7)LiH, (6)LiH, (7)LiD, and (6)LiD, are also calculated and added to the LiH PEC. The aforementioned PECs are then used to calculate the vibrational energies for these systems. The maximum difference between the computed and the experimental vibrational transitions is smaller than 0.9 cm(-1). The contribution of the adiabatic correction to the dissociation energy of (7)LiH molecule is 10.7 cm(-1). The magnitude of this correction shows its importance in calculating the LiH spectroscopic constants. As the estimated contribution of the nonadiabatic and relativistic effects to the ground state dissociation energy is around 0.3 cm(-1), their inclusion in the LiH PEC calculation seems to be the next most important contribution to evaluate in order to improve the accuracy achieved in this work. PMID:21322671

  18. 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.

  19. 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.

  20. Prediction of physicochemical properties of organic molecules using van der Waals surface electrostatic potentials.

    PubMed

    Kim, Chan Kyung; Lee, Kyung A; Hyun, Kwan Hoon; Park, Heung Jin; Kwack, In Young; Kim, Chang Kon; Lee, Hai Whang; Lee, Bon-Su

    2004-12-01

    The generalized interaction properties function (GIPF) methodology developed by Politzer and coworkers, which calculated molecular surface electrostatic potential (MSESP) on a density envelope surface, was modified by calculating the MSESP on a much simpler van der Waals (vdW) surface of a molecule. In this work, vdW molecular surfaces were obtained from the fully optimized structures confirmed by frequency calculations at B3LYP/6-31G(d) level of theory. Multiple linear regressions for normal boiling point, heats of vaporization, heats of sublimation, heats of fusion, liquid density, and solid density were performed using GIPF variables from vdW model surface. Results from our model are compared with those from Politzer and coworkers. The surface-dependent beta (and gamma) values are dependent on the surface models but the surface-independent alpha and regression coefficients (r) are constant when vdW surface and density surface with 0.001 a.u. contour value are compared. This interesting phenomenon is explained by linear dependencies of GIPF variables. PMID:15484184

  1. 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

  2. Therapeutic potential of an orally effective small molecule inhibitor of plasminogen activator inhibitor for asthma.

    PubMed

    Liu, Rui-Ming; Eldridge, Stephanie; Watanabe, Nobuo; Deshane, Jessy; Kuo, Hui-Chien; Jiang, Chunsun; Wang, Yong; Liu, Gang; Schwiebert, Lisa; Miyata, Toshio; Thannickal, Victor J

    2016-02-15

    Asthma is one of the most common respiratory diseases. Although progress has been made in our understanding of airway pathology and many drugs are available to relieve asthma symptoms, there is no cure for chronic asthma. Plasminogen activator inhibitor 1 (PAI-1), a primary inhibitor of tissue-type and urokinase-type plasminogen activators, has pleiotropic functions besides suppression of fibrinolysis. In this study, we show that administration of TM5275, an orally effective small-molecule PAI-1 inhibitor, 25 days after ovalbumin (OVA) sensitization-challenge, significantly ameliorated airway hyperresponsiveness in an OVA-induced chronic asthma model. Furthermore, we show that TM5275 administration significantly attenuated OVA-induced infiltration of inflammatory cells (neutrophils, eosinophils, and monocytes), the increase in the levels of OVA-specific IgE and Th2 cytokines (IL-4 and IL-5), the production of mucin in the airways, and airway subepithelial fibrosis. Together, the results suggest that the PAI-1 inhibitor TM5275 may have therapeutic potential for asthma through suppressing eosinophilic allergic response and ameliorating airway remodeling. PMID:26702150

  3. 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

  4. Jellium model potentials for the C60 molecule and the photoionization of endohedral atoms, A@C60

    NASA Astrophysics Data System (ADS)

    Baltenkov, A. S.; Manson, S. T.; Msezane, A. Z.

    2015-09-01

    Approximating the C60 shell as a collection of carbon atoms, the potential experienced by a confined atom has been calculated within the framework of the self-consistent spherical jellium model. It has been found that the potential well in this model has a cusp-shaped Lorentz-like profile. The parameters of the model Lorentz-bubble potential (depth and thickness) have been selected so that in the potential well there would be an electronic level corresponding to the experimental electron affinity of the C60 molecule. The spatial distribution of the positive charge of the C-atomic nuclei and the negative charge of the electron clouds forming the electrostatic potential of C60, as a whole, has been analyzed using the Poisson equation. It is demonstrated that the often used radial square-well potential to approximate the C60 corresponds to a non-physical charge density for the C60 molecule. This analysis demonstrates that the phenomenological potentials simulating the C60 shell potential should belong to a family of potentials with a non-flat bottom and non-parallel potential walls similar to the Lorentz-bubble potential. The photoionization cross-sections of a hydrogen atom localized at the center of the C60 shell have been calculated as well. It is found that confinement oscillations in the cross-sections are exhibited within the framework of the cusp-shaped potential model and these oscillations are essentially the same as those in the case of the potential wells with well-defined borders (parallel walls), thereby demonstrating that the inherent characteristic distances of the potential, e.g., radii of the potential walls, or the distances between potential walls, are not necessary to produce confinement resonances; this should be a general result for atoms or molecules confined in near-spherical fullerenes.

  5. Local Spectroscopy of Image-Potential-Derived States: From Single Molecules to Monolayers of Benzene on Cu(111)

    NASA Astrophysics Data System (ADS)

    Dougherty, D. B.; Maksymovych, P.; Lee, J.; Yates, J. T., Jr.

    2006-12-01

    Stark-shifted image-potential states were measured with an STM tip for benzene adsorbed on a Cu(111) surface. A single benzene molecule locally shifts the position of the first image state toward the Fermi level by 0.2 eV relative to its position on the clean surface. The energetic position of this molecule-modified state shifts to lower energy with increasing coverage of benzene on the surface. This is attributed to local surface potential changes that are correlated with the lowering of the crystal work function due to adsorption of benzene.

  6. Potential function of the internal rotation of a methacrolein molecule in the ground ( S 0) electronic state

    NASA Astrophysics Data System (ADS)

    Koroleva, L. A.; Krasnoshchekov, S. V.; Matveev, V. K.; Pentin, Yu. A.

    2016-08-01

    The structural parameters of s- trans- and s- cis-isomers of a methacrolein molecule in the ground ( S 0) electronic state are determined by means of MP2 method with the cc-pVTZ basis set. Kinematic factor F(φ) is expanded in a Fourier series. The potential function of internal rotation (PFIR) of methacrolein in this state is built using experimental frequencies of transitions of the torsional vibration of both isomers, obtained from an analysis of the vibrational structure of the high-resolution UV spectrum with allowance for the geometry and difference between the energy (Δ H) of the isomers. It is shown that the V n parameters of the potential function of internal rotation of the molecule, built using the frequencies of the transition of the torsional vibrations of s- trans- and s- cis-isomers of the methacrolein molecule, determined from vibrational structure of the high-resolution UV spectrum and the FTIR spectrum, are close.

  7. The movement of molecules and nanoparticles in potential field with the Casimir force in nano volumes with different optical boundaries

    NASA Astrophysics Data System (ADS)

    Uvarova, L. A.; Babarin, S. S.

    2014-09-01

    This work is devoted to the problem of dynamics of molecules and nanoparticles in fields in following potentials: the Casimir force, the van der Waals interactions, the Coulomb potential for charged particles, the potential energies for bonds, and the electric potential. In the general case, molecules or nanoparticles move in nano volumes with walls of different optical properties. In particular, the matter at boundary can be with zero refracted index (Vesseur E J R et al 2013 Phys. Rev. Lett. 110 013902; Uvarova L A 2005 AIP congress). Current model can be used to investigate dynamical and configuration properties of particle systems, and to determine influences of molecules interactions with the walls. It is accepted that the Casimir force affects the velocity distribution function, the total energy, and equilibrium properties that produce rise of temperature, pressure and energy deviations. In many-atom molecules or nanoparticles interactions with the Casimir force are more complex, but they give opportunity to control admixtures and modification of system under the influence of electromagnetic waves.

  8. 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

    2014-02-01

    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. PMID:23838574

  9. 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.

  10. 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

  11. Small Molecule Restores Itaconate Sensitivity in Salmonella enterica: A Potential New Approach to Treating Bacterial Infections.

    PubMed

    Hammerer, Fabien; Chang, Justin H; Duncan, Dustin; Castañeda Ruiz, Angel; Auclair, Karine

    2016-08-17

    In the context of increasing global antibiotic resistance, the need for alternative therapeutic targets is great. Although new antibiotics and resistance inhibitors provide temporary solutions, they are bound to become obsolete. In this work, we propose a new approach, coined "bacterio-modulation" that aims to restore macrophage potency towards bacterial strains that are able to survive in phagolysosomes. One key defense in the macrophage's arsenal is itaconate, an endogenous molecule with antimicrobial activity. Some intracellular pathogens have evolved to produce itaconate-degrading enzymes, which are required for intracellular proliferation and to promote pathogenicity. We herein present the first molecule able to resensitize Salmonella enterica to itaconate. PMID:27254798

  12. 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. PMID:26498990

  13. Cellular reprogramming for pancreatic β-cell regeneration: clinical potential of small molecule control

    PubMed Central

    2014-01-01

    Recent scientific breakthroughs in stem cell biology suggest that a sustainable treatment approach to cure diabetes mellitus (DM) can be achieved in the near future. However, the transplantation complexities and the difficulty in obtaining the stem cells from adult cells of pancreas, liver, bone morrow and other cells is a major concern. The epoch-making strategy of transcription-factor based cellular reprogramming suggest that these barriers could be overcome, and it is possible to reprogram any cells into functional β cells. Contemporary biological and analytical techniques help us to predict the key transcription factors needed for β-cell regeneration. These β cell-specific transcription factors could be modulated with diverse reprogramming protocols. Among cellular reprogramming strategies, small molecule approach gets proclaimed to have better clinical prospects because it does not involve genetic manipulation. Several small molecules targeting certain epigenetic enzymes and/or signaling pathways have been successful in helping to induce pancreatic β-cell specification. Recently, a synthetic DNA-based small molecule triggered targeted transcriptional activation of pancreas-related genes to suggest the possibility of achieving desired cellular phenotype in a precise mode. Here, we give a brief overview of treating DM by regenerating pancreatic β-cells from various cell sources. Through a comprehensive overview of the available transcription factors, small molecules and reprogramming strategies available for pancreatic β-cell regeneration, this review compiles the current progress made towards the generation of clinically relevant insulin-producing β-cells. PMID:24679123

  14. 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.

  15. Adiabatic potential-energy curves of long-range Rydberg molecules: Two-electron R -matrix approach

    NASA Astrophysics Data System (ADS)

    Tarana, Michal; Čurík, Roman

    2016-01-01

    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. Only diatomic molecules are considered. 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 put into a test by its application to a study of Rydberg states of the hydrogen molecule for internuclear distances R from 20 to 400 bohrs and energies corresponding to n from 3 to 22. The results are compared with previous quantum chemical calculations (lower quantum numbers n ) and computations based on contact-potential models (higher quantum numbers n ).

  16. Regulation of the Apelinergic System and Its Potential in Cardiovascular Disease: Peptides and Small Molecules as Tools for Discovery.

    PubMed

    Narayanan, Sanju; Harris, Danni L; Maitra, Rangan; Runyon, Scott P

    2015-10-22

    Apelin peptides and the apelin receptor represent a relatively new therapeutic axis for the potential treatment of cardiovascular disease. Several reports suggest apelin receptor activation with apelin peptides results in cardioprotection as noted through positive ionotropy, angiogenesis, reduction of mean arterial blood pressure, and apoptosis. Considering the potential therapeutic benefit attainable through modulation of the apelinergic system, research is expanding to develop novel therapies that limit the inherent rapid degradation of endogenous apelin peptides and produce metabolically stable small molecule agonists and antagonists to more rigorously interrogate the apelin receptor system. This review details the structure-activity relationships for chemically modified apelin peptides and recent disclosures of small molecule agonists and antagonists and summarizes the peer reviewed and patented literature. Development of metabolically stable ligands of apelin receptor and their effects in various models over the coming years will hopefully lead to establishment of this receptor as a validated target for cardiovascular indications. PMID:26102594

  17. A mixture of odorant molecules potentially indicating oestrus in mammals elicits penile erections in male rats.

    PubMed

    Nielsen, Birte L; Jerôme, Nathalie; Saint-Albin, Audrey; Thonat, Catherine; Briant, Christine; Boué, Franck; Rampin, Olivier; Maurin, Yves

    2011-12-01

    A common set of odorous molecules may indicate female receptiveness across species, as male rats display sexual arousal when exposed to the odour of oestrous faeces from rats, vixens and mares. More than 900 different compounds were identified by GC-MS analyses performed on faeces samples from di-oestrous and oestrous females and from males of the three species. Five carboxylic acids were found in lower concentrations in faeces from all oestrous females. We subjected 12 sexually trained male rats to a 30 min exposure to different dilutions of a mixture of these five molecules in the same proportions as found in female oestrous faeces. The behavioural responses of the rats were compared to those displayed when exposed to water (negative control) and faeces from oestrous female rats (positive control). Frequency of penile erections were found to be significantly dependent on mixture dilution, with two intermediate dilutions eliciting frequencies of penile erections that did not differ from those obtained during exposure to oestrous female rat faeces. Higher and lower dilutions did not elicit more penile erections than observed with water. These results support our hypothesis that a small set of odorous molecules may indicate sexual receptiveness in mammalian females. PMID:21884731

  18. On a Universal Potential Energy Function and the Importance of Ionic Structures for the Ground State of Molecules

    NASA Astrophysics Data System (ADS)

    Van Hooydonk, G.

    1982-09-01

    The Kratzer-Fues-Varshni-V-potential, applied to ionic dissociation energies, is shown to yield rather accurate potential energy curves in the bonding region for H2, HF, LiH, Li2 and LiF. Vibrational levels, calculated by this ionic approximation to the ground state of widely differing molecules, nearly coincide with RKR-data. At the repulsive side of the curve and up to 2re, the agreement with RKR-curves is even better than for Morse's curve, also for the "covalent" molecules H2 and Li2. Calculated spectroscopical constants αe and ωeχe are far better than those calculated with Morse's function. Even the existence of a maximum in the potential curve at larger r-values seems not in confict with an ionic approximation. From the universal character of the function used, it is concluded that a reasonable approximation for the ground state of all molecules considered is one in terms of ionic structures, even for H2 and especially for Li2. According to the present results, the term "covalent bonding" seems to be definitely superfluous, as the usually made distinction between ionic and covalent bonding is more appearant than real.

  19. 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.

  20. Rydberg-London potential for diatomic molecules and unbonded atom pairs.

    PubMed

    Cahill, Kevin; Parsegian, V Adrian

    2004-12-01

    We propose and test a pair potential that is accurate at all relevant distances and simple enough for use in large-scale computer simulations. A combination of the Rydberg potential from spectroscopy and the London inverse-sixth-power energy, the proposed form fits spectroscopically determined potentials better than the Morse, Varnshi, and Hulburt-Hirschfelder potentials and much better than the Lennard-Jones and harmonic potentials. At long distances, it goes smoothly to the London force appropriate for gases and preserves van der Waals's "continuity of the gas and liquid states," which is routinely violated by coefficients assigned to the Lennard-Jones 6-12 form. PMID:15634034

  1. Identification of Small Molecule Inhibitors of Tau Aggregation by Targeting Monomeric Tau As a Potential Therapeutic Approach for Tauopathies

    PubMed Central

    Pickhardt, Marcus; Neumann, Thomas; Schwizer, Daniel; Callaway, Kari; Vendruscolo, Michele; Schenk, Dale; St. George-Hyslop, Peter; Mandelkow, Eva M.; Dobson, Christopher M.; McConlogue, Lisa; Mandelkow, Eckhard; Tóth, Gergely

    2015-01-01

    A potential strategy to alleviate the aggregation of intrinsically disordered proteins (IDPs) is to maintain the native functional state of the protein by small molecule binding. However, the targeting of the native state of IDPs by small molecules has been challenging due to their heterogeneous conformational ensembles. To tackle this challenge, we applied a high-throughput chemical microarray surface plasmon resonance imaging screen to detect the binding between small molecules and monomeric full-length Tau, a protein linked with the onset of a range of Tauopathies. The screen identified a novel set of drug-like fragment and lead-like compounds that bound to Tau. We verified that the majority of these hit compounds reduced the aggregation of different Tau constructs in vitro and in N2a cells. These results demonstrate that Tau is a viable receptor of drug-like small molecules. The drug discovery approach that we present can be applied to other IDPs linked to other misfolding diseases such as Alzheimer’s and Parkinson’s diseases.

  2. Identification of small molecule inhibitors of Tau aggregation by targeting monomeric Tau as a potential therapeutic approach for Tauopathies

    PubMed Central

    Pickhardt, Marcus; Neumann, Thomas; Schwizer, Daniel; Callaway, Kari; Vendruscolo, Michele; Schenk, Dale; George-Hyslop, Peter; Mandelkow, Eva M.; Dobson, Christopher M.; McConlogue, Lisa; Mandelkow, Eckhard; Tóth, Gergely

    2016-01-01

    A potential strategy to alleviate the aggregation of intrinsically disordered proteins (IDPs) is to maintain the native functional state of the protein by small molecule binding. However, the targeting of the native state of IDPs by small molecules has been challenging due to their heterogeneous conformational ensembles. To tackle this challenge, we applied a high-throughput chemical microarray surface plasmon resonance imaging screen to detect the binding between small molecules and monomeric full-length Tau, a protein linked with the onset of a range of Tauopathies. The screen identified a novel set of drug-like fragment and lead-like compounds that bound to Tau. We verified that the majority of these hit compounds reduced the aggregation of different Tau constructs in vitro and in N2a cells. These results demonstrate that Tau is a viable receptor of drug-like small molecules. The drug discovery approach that we present can be applied to other IDPs linked to other misfolding diseases such as Alzheimer’s and Parkinson’s diseases. PMID:26510979

  3. 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.

  4. 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.

  5. 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.

  6. 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.

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

    PubMed

    Sharma, Charu; Sadek, Bassem; Goyal, Sameer N; Sinha, Satyesh; Kamal, Mohammad Amjad; 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 Δ(9)-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

  8. 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

  9. One-body potential theory of molecules and solids modified semiempirically for electron correlation

    NASA Astrophysics Data System (ADS)

    March, N. H.

    2010-10-01

    The study of Cordero, March and Alonso (CMA) for four spherical atoms, Be, Ne, Mg and Ar, semiempirically fine-tunes the Hartree-Fock (HF) ground-state electron density by inserting the experimentally determined ionization potentials. The present Letter, first of all, relates this approach to the very recent work of Bartlett ‘towards an exact correlated orbital theory for electrons’. Both methods relax the requirement of standard DFT that a one-body potential shall generate the exact ground-state density, though both work with high quality approximations. Unlike DFT, the CMA theory uses a modified HF non-local potential. It is finally stressed that this potential generates also an idempotent Dirac density matrix. The CMA approach is thereby demonstrated to relate, albeit approximately, to the DFT exchange-correlation potential.

  10. Application of the reduced-potential curve method for the detection of errors or inaccuracies in the analysis of spectra and for the construction of internuclear potentials of diatomic molecules: Alkali diatomic molecules

    NASA Astrophysics Data System (ADS)

    Jen, F.; Brandt, B. A.

    1989-05-01

    Errors in the Rydberg-Klein-Rees potentials for the ground and B-excited states of LiNa and LiK and in the ground-state potential of RbCs are detected using the reduced-potential curve (RPC) method and shown to be due to errors or inaccuracies in the analysis of the spectrum. Using the rules of the RPC scheme, estimates for the left limbs of the ground- and B-state potentials of LiNa and LiK are given which are quite accurate for the ground states. With the use of the RPC method, we also give estimates of the ground-state potentials of Rb2 and RbCs up to the dissociation limit. The RPC method is further employed for a calculation of accurate internuclear potentials from inaccurate theoretical ab initio potential curves for a series of molecules. These procedures could be useful for a prediction of the spectrum. The examples should illustrate the predictive and constructive power of the RPC method.

  11. Umbrella motion of the methyl cation, radical, and anion molecules. I. Potentials, energy levels and partition functions

    NASA Astrophysics Data System (ADS)

    Ragni, Mirco; Bitencourt, Ana Carla P.; Prudente, Frederico V.; Barreto, Patricia R. P.; Posati, Tamara

    2016-03-01

    A study of the umbrella motion of the methyl cation, radical, and anion molecules is presented. This is the floppiest mode of vibration of all three species and its characterization is of fundamental importance for understanding their reactivity. Minimum Energy Paths of the umbrella motions according to the hyperspherical treatment were obtained, by single point calculations, at the CCSD(T)/aug-cc-pVQT level of theory in the Born-Oppenheimer approximation. These energy profiles permit us to calculate the vibrational levels through the Hyperquantization algorithm, which is shown appropriated for the description of the umbrella motion of these three molecules. The adiabatic electron affinity and ionization potentials were estimated to good accuracy. Partition functions are also calculated in order to obtain information on the reaction rates involving these groups.

  12. Fucoidan and cancer: a multifunctional molecule with anti-tumor potential.

    PubMed

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

    2015-04-01

    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

  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. Potential and matrix elements of the hamiltonian of internal rotation in molecules in the basis set of Mathieu functions

    NASA Astrophysics Data System (ADS)

    Turovtsev, V. V.; Orlov, Yu. D.; Tsirulev, A. N.

    2015-08-01

    The advantages of the orthonormal basis set of 2π-periodic Mathieu functions compared to the trigonometric basis set in calculations of torsional states of molecules are substantiated. Explicit expressions are derived for calculating the Hamiltonian matrix elements of a one-dimensional torsional Schrödinger equation with a periodic potential of the general form in the basis set of Mathieu functions. It is shown that variation of a parameter of Mathieu functions allows the rotation potential and the structural function to be approximated with a good accuracy by a small number of series terms. The conditions for the best choice of this parameter are specified, and approximations are obtained for torsional potentials of n-butane upon rotation about the central C-C bond and of its univalent radical n-butyl C2H5C·H2 upon rotation of the C·H2 group. All algorithms are implemented in the Maple package.

  15. The inherent dynamics of a molecular liquid: Geodesic pathways through the potential energy landscape of a liquid of linear molecules

    NASA Astrophysics Data System (ADS)

    Jacobson, Daniel; Stratt, Richard M.

    2014-05-01

    Because the geodesic pathways that a liquid follows through its potential energy landscape govern its slow, diffusive motion, we suggest that these pathways are logical candidates for the title of a liquid's "inherent dynamics." Like their namesake "inherent structures," these objects are simply features of the system's potential energy surface and thus provide views of the system's structural evolution unobstructed by thermal kinetic energy. This paper shows how these geodesic pathways can be computed for a liquid of linear molecules, allowing us to see precisely how such molecular liquids mix rotational and translational degrees of freedom into their dynamics. The ratio of translational to rotational components of the geodesic path lengths, for example, is significantly larger than would be expected on equipartition grounds, with a value that scales with the molecular aspect ratio. These and other features of the geodesics are consistent with a picture in which molecular reorientation adiabatically follows translation—molecules largely thread their way through narrow channels available in the potential energy landscape.

  16. Analytical potential curves of some hydride molecules using algebraic and energy-consistent method

    NASA Astrophysics Data System (ADS)

    Fan, Qunchao; Sun, Weiguo; Feng, Hao; Zhang, Yi; Wang, Qi

    2014-01-01

    Based on the algebraic method (AM) and the energy consistent method (ECM), an AM-ECM protocol for analytical potential energy curves of stable diatomic electronic states is proposed as functions of the internuclear distance. Applications of the AM-ECM to the 6 hydride electronic states of HF-X1Σ+, DF-X1Σ+, D35Cl-X1Σ+, 6LiH-X1Σ+, 7LiH-X1Σ+, and 7LiD-X1Σ+ show that the AM-ECM potentials are in excellent agreement with the experimental RKR data and the full AM-RKR data, and that the AM-ECM can obtain reliable analytical potential energies in the molecular asymptotic and dissociation region for these molecular electronic states.

  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. 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)

  20. Investigation of potential molecular biomarkers and small molecule drugs for hepatocellular carcinoma transformed from cirrhosis

    PubMed Central

    XIE, FENG; ZHU, FANG; LU, ZAIMING; LIU, ZHENGRONG; WANG, HONGYAN

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China and the third leading cause of cancer-associated morality. The aim of the present study was to investigate and analyze differentially-expressed genes (DEGs) between cirrhosis and HCC, in order to screen the key genes involved in the transformation from cirrhosis to HCC and provide novel targets for the diagnosis and treatment of HCC in patients with cirrhosis. The gene expression profile, GSE17548, was obtained from Gene Expression Omnibus database and the DEGs were identified by LIMMA package in R language. Kyoto Encyclopedia of Genes and Genomes and gene ontology biology process analysis were performed for the DEGs. Differential co-expression network (DEN) analysis was conducted and the network was visualized using Cytoscape. Small molecule drugs were also screened from the Comparative Toxicogenomics Database for higher degree DEGs. A total of 95 DEGs were obtained, including 46 upregulated and 49 downregulated genes. The upregulated DEGs were primarily involved in biological processes and pathways associated with the cell cycle, while the downregulated DEGs were primarily involved in immune-associated biological processes. A total of 22 key DEGs were identified by DEN analysis, which distinguished HCC from cirrhosis samples. Furthermore, estradiol, benzo(a)pyrene, acetaminophen, copper sulfate and bisphenol A were identified as the five most associated chemicals to these 22 DEGs. In conclusion, the hub genes and chemicals identified by the present study may provide a theoretical basis for additional research on diagnosis and treatment of HCC transformed from cirrhosis. PMID:27347171

  1. Theory and simulation of central force model potentials: Application to homonuclear diatomic molecules

    NASA Astrophysics Data System (ADS)

    Bresme, Fernando; Abascal, José L. F.; Lomba, Enrique

    1996-12-01

    Structure and thermodynamics of fluids made of particles that interact via a central force model potential are studied by means of Monte Carlo simulations and integral equation theories. The Hamiltonian has two terms, an intramolecular component represented by a harmonic oscillatorlike potential and an intermolecular interaction of the Lennard-Jones type. The potential does not fulfill the steric saturation condition so it leads to a polydisperse system. First, we investigate the association (clustering) and thermodynamic properties as a function of the potential parameters, such as the intramolecular potential depth, force constant, and bond length. It is shown that the atomic hypernetted chain (HNC) integral equation provides a correct description of the model as compared with simulation results. The calculation of the HNC pseudospinodal curve indicates that the stability boundaries between the vapor and liquid phases are strongly dependent on the bond length and suggests that there might be a direct gas-solid transition for certain elongations. On the other hand, we have assessed the ability of the model to describe the thermodynamics and structure of diatomic liquids such as N2 and halogens. To this end we have devised a procedure to model the intramolecular potential depth to reproduce the complete association limit (i.e., an average number of bonds per particle equal to one). This constraint is imposed on the Ornstein-Zernike integral equation in a straightforward numerical way. The structure of the resulting fluid is compared with results from molecular theories. An excellent agreement between the HNC results for the associating fluid and the reference interaction site model (RISM)-HNC computations for the atom-atom model of the same fluid is obtained. There is also a remarkable coincidence between the simulation results for the molecular and the associating liquids, despite the polydisperse character of the latter. The stability boundaries in the complete

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Accurate potential energy curve of the LiH+ molecule calculated with explicitly correlated Gaussian functions.

    PubMed

    Tung, Wei-Cheng; Adamowicz, Ludwik

    2014-03-28

    Very accurate calculations of the ground-state potential energy curve (PEC) of the LiH(+) ion performed with all-electron explicitly correlated Gaussian functions with shifted centers are presented. The variational method is employed. The calculations involve optimization of nonlinear exponential parameters of the Gaussians performed with the aid of the analytical first derivatives of the energy determined with respect to the parameters. The diagonal adiabatic correction is also calculated for each PEC point. The PEC is then used to calculate the vibrational energies of the system. In that calculation, the non-adiabatic effects are accounted for by using an effective vibrational mass obtained by the minimization of the difference between the vibrational energies obtained from the calculations where the Born-Oppenheimer approximation was not assumed and the results of the present calculations. PMID:24697449

  8. Accurate potential energy curve of the LiH+ molecule calculated with explicitly correlated Gaussian functions

    NASA Astrophysics Data System (ADS)

    Tung, Wei-Cheng; Adamowicz, Ludwik

    2014-03-01

    Very accurate calculations of the ground-state potential energy curve (PEC) of the LiH+ ion performed with all-electron explicitly correlated Gaussian functions with shifted centers are presented. The variational method is employed. The calculations involve optimization of nonlinear exponential parameters of the Gaussians performed with the aid of the analytical first derivatives of the energy determined with respect to the parameters. The diagonal adiabatic correction is also calculated for each PEC point. The PEC is then used to calculate the vibrational energies of the system. In that calculation, the non-adiabatic effects are accounted for by using an effective vibrational mass obtained by the minimization of the difference between the vibrational energies obtained from the calculations where the Born-Oppenheimer approximation was not assumed and the results of the present calculations.

  9. Ab initio adiabatic and diabatic potential-energy curves of the LiH molecule

    NASA Astrophysics Data System (ADS)

    Boutalib, A.; Gadéa, F. X.

    1992-07-01

    For nearly all states below the ionic limit [i.e., Li(2s, 2p, 3s, 3p, 3d, 4s, and 4p)+H] we perform the first adiabatic and diabatic studies. This treatment involves a nonempirical pseudopotential for Li and a full configuration-interaction treatment of the valence-electron system. Core-valence correlation is taken into account according to a core-polarization-potential method. We present an analysis of the diabatic curves and introduce appropriate small corrections accounting for basis-set limitations. For the low-lying states, our vibrational level spacings and spectroscopic constants are in excellent agreement with the available experimental data and with the best all-electron results. Experimental suggestions are given for the higher states.

  10. 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. PMID:18822040

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

    PubMed

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

    2016-02-01

    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, and 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. We also describe the implementation of the self-consistent Coulomb hole with screened exchange method (COHSEX), which serves as one of the mean-field starting points. 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. PMID:26731609

  12. 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.

  13. Rhamnolipids as platform molecules for production of potential anti-zoospore agrochemicals.

    PubMed

    Miao, Shida; Dashtbozorg, Soroosh Soltani; Callow, Nicholas V; Ju, Lu-Kwang

    2015-04-01

    Rhamnolipid biosurfactants have potential applications in the control of zoosporic plant pathogens. However, rhamnolipids have not been closely investigated for the anti-zoospore mechanism or for developing new anti-zoospore chemicals. In this study, RhL-1 and RhL-3 groups of rhamnolipids were used to generate the corresponding RhL-2 and RhL-4 groups and the free diacids. Conversion of RhL-3 to RhL-1 was also accomplished in vitro with cellobiase as the catalyst. The anti-zoospore effects of RhL-1-RhL-4 and the diacids were investigated with zoospores of Phytophthora sojae. For RhL-1-RhL-4, approximately 20, 30, 40, and 40 mg/L, respectively, were found to be the lowest concentrations required to stop movement of all zoospores, which indicates that the anti-zoospore effect remains strong even after RhL-1 and RhL-3 are hydrolyzed into RhL-2 and RhL-4. The free diacids required a significantly higher critical concentration of about 125 mg/L. Rhamnose can be obtained as a co-product. PMID:25790115

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

    NASA Astrophysics Data System (ADS)

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

    2000-05-01

    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.

  15. Potential siRNA Molecules for Nucleoprotein and M2/L Overlapping Region of Respiratory Syncytial Virus: In Silico Design

    PubMed Central

    Shatizadeh Malekshahi, Somayeh; Arefian, Ehsan; Salimi, Vahid; Mokhtari Azad, Talat; Yavarian, Jila

    2016-01-01

    Background Human respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease in the pediatric population, elderly and in immunosuppressed individuals. Respiratory syncytial virus is also responsible for bronchiolitis, pneumonia, and chronic obstructive pulmonary infections in all age groups. With this high disease burden and the lack of an effective RSV treatment and vaccine, there is a clear need for discovery and development of novel, effective and safe drugs to prevent and treat RSV disease. The most innovative approach is the use of small interfering RNAs (siRNAs) which represent a revolutionary new concept in human therapeutics. The nucleoprotein gene of RSV which is known as the most conserved gene and the M2/L mRNA, which encompass sixty-eight overlapping nucleotides, were selected as suitable targets for siRNA design. Objectives The present study is aimed to design potential siRNAs for silencing nucleoprotein and an overlapping region of M2-L coding mRNAs by computational analysis. Materials and Methods Various computational methods (target alignment, similarity search, secondary structure prediction, and RNA interaction calculation) have been used for siRNA designing against different strains of RSV. Results In this study, seven siRNA molecules were rationally designed against the nucleoprotein gene and validated using various computational methods for silencing different strains of RSV. Additionally, three effective siRNA molecules targeting the overlapping region of M2/L mRNA were designed. Conclusions This approach provides insight and a validated strategy for chemical synthesis of an antiviral RNA molecule which meets many sequence features for efficient silencing and treatment at the genomic level. PMID:27303618

  16. Idalopirdine - a small molecule antagonist of 5-HT6 with therapeutic potential against obesity.

    PubMed

    Dudek, Magdalena; Marcinkowska, Monika; Bucki, Adam; Olczyk, Adrian; Kołaczkowski, Marcin

    2015-12-01

    5HT6 receptor antagonists offer the potential for safe and effective drugs against obesity, because they can reduce weight without causing serious side effects in the cardiovascular system. Also, their anorexic effect is associated with reduced food intake via an enhancement of satiety. In the present study we investigated the anorexic effect of idalopirdine (LuAE58054) in a model of obesity induced by high-fat diet. To induce obesity in rats, the animals were treated with feed with a fat content of 40 %. Body weight was controlled and the amount of food and water consumed was determined. The influence of the test compound on the lipid profile and glucose level was measured, as well as locomotor activity in home cages on the 20th day of the treatment. LuAE58054, at 5 mg kg(-1)/day i.p., was significantly anorectic in this model of obesity. Animals treated with LuAE58054 weighed 8 and 9.2 % less than the control obese animals on the 12th and 21st days, respectively. It significantly reduced food intake and the amount of peritoneal fat in animals, and reduced the level of triglycerides in plasma. LuAE58054 did not have a statistically significant effect on the spontaneous activity of diet-induced obese rats. The present study clearly demonstrates the effectiveness of LuAE58054 in reducing body weight. This compound is in phase III of clinical trials for the treatment of cognitive deficits associated with Alzheimer's disease and schizophrenia. It is a 5HT6 receptor antagonist and is, therefore, free of those unacceptable side effects that preclude chronic use of anti-obesity drugs with other mechanisms of action. The search for an effective and safe anti-obesity drug is essential for an increasingly obese population; therefore, the anorectic action of LuAE58054 is important and there is a need for more research in this direction. PMID:26419385

  17. Accurate Ionization Potentials and Electron Affinities of Acceptor Molecules II: Non-Empirically Tuned Long-Range Corrected Hybrid Functionals.

    PubMed

    Gallandi, Lukas; Marom, Noa; Rinke, Patrick; Körzdörfer, Thomas

    2016-02-01

    The performance of non-empirically tuned long-range corrected hybrid functionals for the prediction of vertical ionization potentials (IPs) and electron affinities (EAs) is assessed for a set of 24 organic acceptor molecules. Basis set-extrapolated coupled cluster singles, doubles, and perturbative triples [CCSD(T)] calculations serve as a reference for this study. Compared to standard exchange-correlation functionals, tuned long-range corrected hybrid functionals produce highly reliable results for vertical IPs and EAs, yielding mean absolute errors on par with computationally more demanding GW calculations. In particular, it is demonstrated that long-range corrected hybrid functionals serve as ideal starting points for non-self-consistent GW calculations. PMID:26731340

  18. A novel small-molecule agonist of PPAR-γ potentiates an anti-inflammatory M2 glial phenotype.

    PubMed

    Song, Gyun Jee; Nam, Youngpyo; Jo, Myungjin; Jung, Myungsu; Koo, Ja Young; Cho, Wansang; Koh, Minseob; Park, Seung Bum; Suk, Kyoungho

    2016-10-01

    Neuroinflammation is a key process for many neurodegenerative diseases. Activated microglia and astrocytes play an essential role in neuroinflammation by producing nitric oxide (NO), inflammatory cytokines, chemokines, and neurotoxins. Therefore, targeting glia-mediated neuroinflammation using small-molecules is a potential therapeutic strategy. In this study, we performed a phenotypic screen using microglia cell-based assay to identify a hit compound containing N-carbamoylated urethane moiety (SNU-BP), which inhibits lipopolysaccharide (LPS)-induced NO production in microglia. SNU-BP inhibited pro-inflammatory cytokines and inducible nitric oxide synthase in LPS-stimulated microglia, and potentiated interleukin-4-induced arginase-1 expression. PPAR-γ was identified as a molecular target of SNU-BP. The PPAR response element reporter assay revealed that SNU-BP specifically activated PPAR-γ, but not PPAR-δ or -α, confirming that PPAR-γ is the target protein of SNU-BP. The anti-inflammatory effect of SNU-BP was attenuated by genetic and pharmacological inhibition of PPAR-γ. In addition, SNU-BP induced an anti-inflammatory phenotype in astrocytes as well, by inhibiting pro-inflammatory NO and TNF-α, while increasing anti-inflammatory genes, such as arginase-1 and Ym-1. Finally, SNU-BP exhibited an anti-inflammatory effect in the LPS-injected mouse brain, demonstrating a protective potential for neuroinflammatory diseases. PMID:27288982

  19. 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. PMID:26243592

  20. microRNA-146a targets the L1 cell adhesion molecule and suppresses the metastatic potential of gastric cancer.

    PubMed

    Hou, Zhibo; Yin, Haitao; Chen, Cong; Dai, Xinzheng; Li, Xiaolin; Liu, Baorui; Fang, Xuefeng

    2012-09-01

    Recent studies have shown that microRNA-146a (miR-146a) is associated with cancer metastasis. However, the mechanisms underlying this process remain poorly understood. In this study, we aimed to investigate the potential role of miR-146a in gastric cancer metastasis. A wound-healing assay and a Transwell assay were used to investigate the impact of miR-146a on the migratory and invasive abilities of MKN-45 cells in vitro. MKN-45 cells stably expressing miR-146a or the negative control were transplanted into nude mice through the lateral tail vein to explore the effect of miR-146a on tumor metastasis in vivo. A luciferase reporter assay and western blot analysis were used to identify the potential target genes. Our results show that the overexpression of miR-146a inhibits the invasion and metastasis of MKN-45 cells in vitro and in vivo. Furthermore, the L1 cell adhesion molecule (L1CAM) was identified as a novel target of miR‑146a in gastric cancer. Taken together, our results provide evidence that miR-146a suppresses gastric cancer cell invasion and metastasis in vitro and in vivo, which may be in part due to the downregulation of L1CAM. miR-146a may have the therapeutic potential to suppress gastric cancer metastasis. PMID:22711166

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

    PubMed Central

    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. PMID:26243592

  2. Informatics calibration of a molecular descriptors database to predict solid dispersion potential of small molecule organic solids.

    PubMed

    Moore, Michael D; Wildfong, Peter L D

    2011-10-14

    The use of a novel, in silico method for making an intelligent polymer selection to physically stabilize small molecule organic (SMO) solid compounds formulated as amorphous molecular solid dispersions is reported. 12 compounds (75%, w/w) were individually co-solidified with polyvinyl pyrrolidone:vinyl acetate (PVPva) copolymer by melt-quenching. Co-solidified products were analyzed intact using differential scanning calorimetry (DSC) and the pair distribution function (PDF) transform of powder X-ray diffraction (PXRD) data to assess miscibility. Molecular descriptor indices were calculated for all twelve compounds using their reported crystallographic structures. Logistic regression was used to assess correlation between molecular descriptors and amorphous molecular solid dispersion potential. The final model was challenged with three compounds. Of the 12 compounds, 6 were miscible with PVPva (i.e. successful formation) and 6 were phase separated (i.e. unsuccessful formation). 2 of the 6 unsuccessful compounds exhibited detectable phase-separation using the PDF method, where DSC indicated miscibility. Logistic regression identified 7 molecular descriptors correlated to solid dispersion potential (α=0.001). The atomic mass-weighted third-order R autocorrelation index (R3m) was the only significant descriptor to provide completely accurate predictions of dispersion potential. The three compounds used to challenge the R3m model were also successfully predicted. PMID:21756988

  3. 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

  4. Non-adiabatic effects within a single thermally averaged potential energy surface: thermal expansion and reaction rates of small molecules.

    PubMed

    Alonso, J L; Castro, A; Clemente-Gallardo, J; Echenique, P; Mazo, J J; Polo, V; Rubio, A; Zueco, D

    2012-12-14

    At non-zero temperature and when a system has low-lying excited electronic states, the ground-state Born-Oppenheimer approximation breaks down and the low-lying electronic states are involved in any chemical process. In this work, we use a temperature-dependent effective potential for the nuclei which can accommodate the influence of an arbitrary number of electronic states in a simple way, while at the same time producing the correct Boltzmann equilibrium distribution for the electronic part. With the help of this effective potential, we show that thermally activated low-lying electronic states can have a significant effect in molecular properties for which electronic excitations are oftentimes ignored. We study the thermal expansion of the Manganese dimer, Mn(2), where we find that the average bond length experiences a change larger than the present experimental accuracy upon the inclusion of the excited states into the picture. We also show that, when these states are taken into account, reaction-rate constants are modified. In particular, we study the opening of the ozone molecule, O(3), and show that in this case the rate is modified as much as a 20% with respect to the ground-state Born-Oppenheimer prediction. PMID:23249070

  5. Small Molecule Docking Supports Broad and Narrow Spectrum Potential for the Inhibition of the Novel Antibiotic Target Bacterial Pth1

    PubMed Central

    Ferguson, Paul P.; Holloway, W. Blake; Setzer, William N.; McFeeters, Hana; McFeeters, Robert L.

    2016-01-01

    Peptidyl-tRNA hydrolases (Pths) play ancillary yet essential roles in protein biosynthesis by recycling peptidyl-tRNA. In E. coli, inhibition of bacterial Pth1 leads to accumulation of peptidyl-tRNA, depletion of aminoacyl-tRNA, and cell death. Eukaryotes have multiple Pths and Pth1 knock out was shown to have no effect on viability in yeast. Thereby, bacterial Pth1 is a promising target for novel antibiotic development. With the abundance of Pth1 structural data, molecular docking was used for virtual screening of existing, commercially available antibiotics to map potential interactions with Pth enzymes. Overall, 83 compounds were docked to eight different bacterial Pth1 and three different Pth2 structures. A variety of compounds demonstrated favorable docking with Pths. Whereas, some compounds interacted favorably with all Pths (potential broad spectrum inhibition), more selective interactions were observed for Pth1 or Pth2 and even specificity for individual Pth1s. While the correlation between computational docking and experimentation still remains unknown, these findings support broad spectrum inhibition, but also point to the possibility of narrow spectrum Pth1 inhibition. Also suggested is that Pth1 can be distinguished from Pth2 by small molecule inhibitors. The findings support continued development of Pth1 as an antibiotic target. PMID:27171117

  6. Small Molecule Docking Supports Broad and Narrow Spectrum Potential for the Inhibition of the Novel Antibiotic Target Bacterial Pth1.

    PubMed

    Ferguson, Paul P; Holloway, W Blake; Setzer, William N; McFeeters, Hana; McFeeters, Robert L

    2016-01-01

    Peptidyl-tRNA hydrolases (Pths) play ancillary yet essential roles in protein biosynthesis by recycling peptidyl-tRNA. In E. coli, inhibition of bacterial Pth1 leads to accumulation of peptidyl-tRNA, depletion of aminoacyl-tRNA, and cell death. Eukaryotes have multiple Pths and Pth1 knock out was shown to have no effect on viability in yeast. Thereby, bacterial Pth1 is a promising target for novel antibiotic development. With the abundance of Pth1 structural data, molecular docking was used for virtual screening of existing, commercially available antibiotics to map potential interactions with Pth enzymes. Overall, 83 compounds were docked to eight different bacterial Pth1 and three different Pth2 structures. A variety of compounds demonstrated favorable docking with Pths. Whereas, some compounds interacted favorably with all Pths (potential broad spectrum inhibition), more selective interactions were observed for Pth1 or Pth2 and even specificity for individual Pth1s. While the correlation between computational docking and experimentation still remains unknown, these findings support broad spectrum inhibition, but also point to the possibility of narrow spectrum Pth1 inhibition. Also suggested is that Pth1 can be distinguished from Pth2 by small molecule inhibitors. The findings support continued development of Pth1 as an antibiotic target. PMID:27171117

  7. A brief update on potential molecular mechanisms underlying antimicrobial and wound-healing potency of snake venom molecules.

    PubMed

    Samy, Ramar Perumal; Sethi, Gautam; Lim, Lina H K

    2016-09-01

    Infectious diseases remain a significant cause of morbidity and mortality worldwide. A wide range of diverse, novel classes of natural antibiotics have been isolated from different snake species in the recent past. Snake venoms contain diverse groups of proteins with potent antibacterial activity against a wide range of human pathogens. Some snake venom molecules are pharmacologically attractive, as they possess promising broad-spectrum antibacterial activities. Furthermore, snake venom proteins (SVPs)/peptides also bind to integrins with high affinity, thereby inhibiting cell adhesion and accelerating wound healing in animal models. Thus, SVPs are a potential alternative to chemical antibiotics. The mode of action for many antibacterial peptides involves pore formation and disruption of the plasma membrane. This activity often includes modulation of nuclear factor kappa B (NF-κB) activation during skin wound healing. The NF-κB pathway negatively regulates the transforming growth factor (TGF)-β1/Smad pathway by inducing the expression of Smad7 and eventually reducing in vivo collagen production at the wound sites. In this context, SVPs that regulate the NF-κB signaling pathway may serve as potential targets for drug development. PMID:26975619

  8. 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.

  9. Undulations of the potential-energy curves for highly excited electronic states in diatomic molecules related to the atomic orbital undulations

    NASA Astrophysics Data System (ADS)

    Yiannopoulou, Alexandra; Jeung, Gwang-Hi; Park, Su Jin; Lee, Hyo Sug; Lee, Yoon Sup

    1999-02-01

    We present potential-energy curves for highly excited electronic states of diatomic molecules showing spectacular undulations including multiple barriers and wells. Those undulations unrelated to avoided crossings are closely correlated with the oscillations of atomic radial electron density in the Rydberg states. The LiHe, LiNe, and LiH cases are examined with an accurate quantum chemical calculation. For the Σ+ states originating from the ns, np, nd, or nf states of lithium atom, n-2 potential barriers and the same number of potential wells exist. The 4 1Σ+g(F) state of Li2 also shows the energy barrier of the same origin. This spectroscopic property is supposed to be more general in diatomic molecules and other small molecules.

  10. LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential.

    PubMed

    Hong, Christopher S; Ho, Winson; Zhang, Chao; Yang, Chunzhang; Elder, J Bradley; Zhuang, Zhengping

    2015-01-01

    Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that plays a significant role in mitotic progression and cellular responses to DNA damage. While traditionally viewed as a tumor suppressor, inhibition of PP2A has recently come to attention as a novel therapeutic means of driving senescent cancer cells into mitosis and promoting cell death via mitotic catastrophe. These findings have been corroborated in numerous studies utilizing naturally produced compounds that selectively inhibit PP2A. To overcome the known human toxicities associated with these compounds, a water-soluble small molecule inhibitor, LB100, was recently developed to competitively inhibit the PP2A protein. This review summarizes the pre-clinical studies to date that have demonstrated the anti-cancer activity of LB100 via its chemo- and radio-sensitizing properties. These studies demonstrate the tremendous therapeutic potential of LB100 in a variety of cancer types. The results of an ongoing phase 1 trial are eagerly anticipated. PMID:25897893

  11. LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential

    PubMed Central

    Hong, Christopher S; Ho, Winson; Zhang, Chao; Yang, Chunzhang; Elder, J Bradley; Zhuang, Zhengping

    2015-01-01

    Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that plays a significant role in mitotic progression and cellular responses to DNA damage. While traditionally viewed as a tumor suppressor, inhibition of PP2A has recently come to attention as a novel therapeutic means of driving senescent cancer cells into mitosis and promoting cell death via mitotic catastrophe. These findings have been corroborated in numerous studies utilizing naturally produced compounds that selectively inhibit PP2A. To overcome the known human toxicities associated with these compounds, a water-soluble small molecule inhibitor, LB100, was recently developed to competitively inhibit the PP2A protein. This review summarizes the pre-clinical studies to date that have demonstrated the anti-cancer activity of LB100 via its chemo- and radio-sensitizing properties. These studies demonstrate the tremendous therapeutic potential of LB100 in a variety of cancer types. The results of an ongoing phase 1 trial are eagerly anticipated. PMID:25897893

  12. 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

  13. Reactions of oxygen-containing molecules on transition metal carbides: Surface science insight into potential applications in catalysis and electrocatalysis

    NASA Astrophysics Data System (ADS)

    Stottlemyer, Alan L.; Kelly, Thomas G.; Meng, Qinghe; Chen, Jingguang G.

    2012-09-01

    Historically the interest in the catalytic properties of transition metal carbides (TMC) has been inspired by their "Pt-like" properties in the transformation reactions of hydrocarbon molecules. Recent studies, however, have revealed that the reaction pathways of oxygen-containing molecules are significantly different between TMCs and Pt-group metals. Nonetheless, TMCs demonstrate intriguing catalytic properties toward oxygen-containing molecules, either as the catalyst or as the catalytically active substrate to support metal catalysts, in several important catalytic and electrocatalytic applications, including water electrolysis, alcohol electrooxidation, biomass conversion, and water gas shift reactions. In the current review we provide a summary of theoretical and experimental studies of the interaction of TMC surfaces with oxygen-containing molecules, including both inorganic (O2, H2O, CO and CO2) and organic (alcohols, aldehydes, acids and esters) molecules. We will discuss the general trends in the reaction pathways, as well as future research opportunities in surface science studies that would facilitate the utilization of TMCs as catalysts and electrocatalysts.

  14. Reactions of oxygen-containing molecules on transition metal carbides: Surface science insight into potential applications in catalysis and electrocatalysis

    NASA Astrophysics Data System (ADS)

    Stottlemyer, Alan L.; Kelly, Thomas G.; Meng, Qinghe; Chen, Jingguang G.

    2012-09-01

    Historically the interest in the catalytic properties of transition metal carbides (TMC) has been inspired by their “Pt-like” properties in the transformation reactions of hydrocarbon molecules. Recent studies, however, have revealed that the reaction pathways of oxygen-containing molecules are significantly different between TMCs and Pt-group metals. Nonetheless, TMCs demonstrate intriguing catalytic properties toward oxygen-containing molecules, either as the catalyst or as the catalytically active substrate to support metal catalysts, in several important catalytic and electrocatalytic applications, including water electrolysis, alcohol electrooxidation, biomass conversion, and water gas shift reactions. In the current review we provide a summary of theoretical and experimental studies of the interaction of TMC surfaces with oxygen-containing molecules, including both inorganic (O2, H2O, CO and CO2) and organic (alcohols, aldehydes, acids and esters) molecules. We will discuss the general trends in the reaction pathways, as well as future research opportunities in surface science studies that would facilitate the utilization of TMCs as catalysts and electrocatalysts.

  15. Molecular determinants mediating gating of Transient Receptor Potential Canonical (TRPC) channels by stromal interaction molecule 1 (STIM1).

    PubMed

    Lee, Kyu Pil; Choi, Seok; Hong, Jeong Hee; Ahuja, Malini; Graham, Sarabeth; Ma, Rong; So, Insuk; Shin, Dong Min; Muallem, Shmuel; Yuan, Joseph P

    2014-03-01

    Transient receptor potential canonical (TRPC) channels mediate a critical part of the receptor-evoked Ca(2+) influx. TRPCs are gated open by the endoplasmic reticulum Ca(2+) sensor STIM1. Here we asked which stromal interaction molecule 1 (STIM1) and TRPC domains mediate the interaction between them and how this interaction is used to open the channels. We report that the STIM1 Orai1-activating region domain of STIM1 interacts with the TRPC channel coiled coil domains (CCDs) and that this interaction is essential for opening the channels by STIM1. Thus, disruption of the N-terminal (NT) CCDs by triple mutations eliminated TRPC surface localization and reduced binding of STIM1 to TRPC1 and TRPC5 while increasing binding to TRPC3 and TRPC6. Single mutations in TRPC1 NT or C-terminal (CT) CCDs reduced interaction and activation of TRPC1 by STIM1. Remarkably, single mutations in the TRPC3 NT CCD enhanced interaction and regulation by STIM1. Disruption in the TRPC3 CT CCD eliminated regulation by STIM1 and the enhanced interaction caused by NT CCD mutations. The NT CCD mutations converted TRPC3 from a TRPC1-dependent to a TRPC1-independent, STIM1-regulated channel. TRPC1 reduced the FRET between BFP-TRPC3 and TRPC3-YFP and between CFP-TRPC3-YFP upon stimulation. Accordingly, knockdown of TRPC1 made TRPC3 STIM1-independent. STIM1 dependence of TRPC3 was reconstituted by the TRPC1 CT CCD alone. Knockout of Trpc1 and Trpc3 similarly inhibited Ca(2+) influx, and inhibition of Trpc3 had no further effect on Ca(2+) influx in Trpc1(-/-) cells. Cell stimulation enhanced the formation of Trpc1-Stim1-Trpc3 complexes. These findings support a model in which the TRPC3 NT and CT CCDs interact to shield the CT CCD from interaction with STIM1. The TRPC1 CT CCD dissociates this interaction to allow the STIM1 Orai1-activating region within STIM1 access to the TRPC3 CT CCD and regulation of TRPC3 by STIM1. These studies provide evidence that the TRPC channel CCDs participate in channel

  16. Molecular Determinants Mediating Gating of Transient Receptor Potential Canonical (TRPC) Channels by Stromal Interaction Molecule 1 (STIM1)*

    PubMed Central

    Lee, Kyu Pil; Choi, Seok; Hong, Jeong Hee; Ahuja, Malini; Graham, Sarabeth; Ma, Rong; So, Insuk; Shin, Dong Min; Muallem, Shmuel; Yuan, Joseph P.

    2014-01-01

    Transient receptor potential canonical (TRPC) channels mediate a critical part of the receptor-evoked Ca2+ influx. TRPCs are gated open by the endoplasmic reticulum Ca2+ sensor STIM1. Here we asked which stromal interaction molecule 1 (STIM1) and TRPC domains mediate the interaction between them and how this interaction is used to open the channels. We report that the STIM1 Orai1-activating region domain of STIM1 interacts with the TRPC channel coiled coil domains (CCDs) and that this interaction is essential for opening the channels by STIM1. Thus, disruption of the N-terminal (NT) CCDs by triple mutations eliminated TRPC surface localization and reduced binding of STIM1 to TRPC1 and TRPC5 while increasing binding to TRPC3 and TRPC6. Single mutations in TRPC1 NT or C-terminal (CT) CCDs reduced interaction and activation of TRPC1 by STIM1. Remarkably, single mutations in the TRPC3 NT CCD enhanced interaction and regulation by STIM1. Disruption in the TRPC3 CT CCD eliminated regulation by STIM1 and the enhanced interaction caused by NT CCD mutations. The NT CCD mutations converted TRPC3 from a TRPC1-dependent to a TRPC1-independent, STIM1-regulated channel. TRPC1 reduced the FRET between BFP-TRPC3 and TRPC3-YFP and between CFP-TRPC3-YFP upon stimulation. Accordingly, knockdown of TRPC1 made TRPC3 STIM1-independent. STIM1 dependence of TRPC3 was reconstituted by the TRPC1 CT CCD alone. Knockout of Trpc1 and Trpc3 similarly inhibited Ca2+ influx, and inhibition of Trpc3 had no further effect on Ca2+ influx in Trpc1−/− cells. Cell stimulation enhanced the formation of Trpc1-Stim1-Trpc3 complexes. These findings support a model in which the TRPC3 NT and CT CCDs interact to shield the CT CCD from interaction with STIM1. The TRPC1 CT CCD dissociates this interaction to allow the STIM1 Orai1-activating region within STIM1 access to the TRPC3 CT CCD and regulation of TRPC3 by STIM1. These studies provide evidence that the TRPC channel CCDs participate in channel gating

  17. 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.

  18. New hydrogen-bond potentials for use in determining energetically favorable binding sites on molecules of known structure.

    PubMed

    Boobbyer, D N; Goodford, P J; McWhinnie, P M; Wade, R C

    1989-05-01

    An empirical energy function designed to calculate the interaction energy of a chemical probe group, such as a carbonyl oxygen or an amine nitrogen atom, with a target molecule has been developed. This function is used to determine the sites where ligands, such as drugs, may bind to a chosen target molecule which may be a protein, a nucleic acid, a polysaccharide, or a small organic molecule. The energy function is composed of a Lennard-Jones, an electrostatic and a hydrogen-bonding term. The latter is dependent on the length and orientation of the hydrogen bond and also on the chemical nature of the hydrogen-bonding atoms. These terms have been formulated by fitting to experimental observations of hydrogen bonds in crystal structures. In the calculations, thermal motion of the hydrogen-bonding hydrogen atoms and lone-pair electrons may be taken into account. For example, in a alcoholic hydroxyl group, the hydrogen may rotate around the C-O bond at the observed tetrahedral angle. In a histidine residue, a hydrogen atom may be bonded to either of the two imidazole nitrogens and movement of this hydrogen will cause a redistribution of charge which is dependent on the nature of the probe group and the surrounding environment. The shape of some of the energy functions is demonstrated on molecules of pharmacological interest. PMID:2709375

  19. ESTIMATION OF MUTAGENIC/CARCINOGENIC POTENTIAL OF ENVIRONMENTAL CONTAMINANTS BY ION-MOLECULE REACTIONS AND TANDEM MASS SPECTROMETRY

    EPA Science Inventory

    The ability to produce and detect products of model DNA/carcinogen ion-molecule reactions is demonstrated in the ion source and the collision cell of a triple quadrupole tandem mass spectrometer. eaction between adenine and benzoyl chloride in the ion source is shown to produce t...

  20. Interactions of Hydrogen Molecules with Halogen-Containing Diatomics from Ab Initio Calculations: Spherical-Harmonics Representation and Characterization of the Intermolecular Potentials.

    PubMed

    Albernaz, Alessandra F; Aquilanti, Vincenzo; Barreto, Patricia R P; Caglioti, Concetta; Cruz, Ana Claudia P S; Grossi, Gaia; Lombardi, Andrea; Palazzetti, Federico

    2016-07-14

    For the prototypical diatomic-molecule-diatomic-molecule interactions H2-HX and H2-X2, where X = F, Cl, Br, quantum-chemical ab initio calculations are carried out on grids of the configuration space, which permit a spherical-harmonics representation of the potential energy surfaces (PESs). Dimer geometries are considered for sets of representative leading configurations, and the PESs are analyzed in terms of isotropic and anisotropic contributions. The leading configurations are individuated by selecting a minimal set of mutual orientations of molecules needed to build the spherical-harmonic expansion on geometrical and symmetry grounds. The terms of the PESs corresponding to repulsive and bonding dimer geometries and the averaged isotropic term, for each pair of interacting molecules, are compared with representations in terms of a potential function proposed by Pirani et al. (see Chem. Phys. Lett. 2004, 394, 37-44 and references therein). Connections of the involved parameters with molecular properties provide insight into the nature of the interactions. PMID:27043842

  1. The Yeast Three-Hybrid System as an Experimental Platform to Identify Proteins Interacting with Small Signaling Molecules in Plant Cells: Potential and Limitations

    PubMed Central

    Cottier, Stéphanie; Mönig, Timon; Wang, Zheming; Svoboda, Jiří; Boland, Wilhelm; Kaiser, Markus; Kombrink, Erich

    2011-01-01

    Chemical genetics is a powerful scientific strategy that utilizes small bioactive molecules as experimental tools to unravel biological processes. Bioactive compounds occurring in nature represent an enormous diversity of structures that can be used to dissect functions of biological systems. Once the bioactivity of a natural or synthetic compound has been critically evaluated the challenge remains to identify its molecular target and mode of action, which usually is a time-consuming and labor-intensive process. To facilitate this task, we decided to implement the yeast three-hybrid (Y3H) technology as a general experimental platform to scan the whole Arabidopsis proteome for targets of small signaling molecules. The Y3H technology is based on the yeast two-hybrid system and allows direct cloning of proteins that interact in vivo with a synthetic hybrid ligand, which comprises the biologically active molecule of interest covalently linked to methotrexate (Mtx). In yeast nucleus the hybrid ligand connects two fusion proteins: the Mtx part binding to dihydrofolate reductase fused to a DNA-binding domain (encoded in the yeast strain), and the bioactive molecule part binding to its potential protein target fused to a DNA-activating domain (encoded on a cDNA expression vector). During cDNA library screening, the formation of this ternary, transcriptional activator complex leads to reporter gene activation in yeast cells, and thereby allows selection of the putative targets of small bioactive molecules of interest. Here we present the strategy and experimental details for construction and application of a Y3H platform, including chemical synthesis of different hybrid ligands, construction of suitable cDNA libraries, the choice of yeast strains, and appropriate screening conditions. Based on the results obtained and the current literature we discuss the perspectives and limitations of the Y3H approach for identifying targets of small bioactive molecules. PMID:22639623

  2. 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.

  3. 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).

  4. 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.

  5. The determination of potential energy curve and dipole moment of the (5)0(+) electronic state of (85)Rb(133)Cs molecule by high resolution photoassociation spectroscopy.

    PubMed

    Yuan, Jinpeng; Zhao, Yanting; Ji, Zhonghua; Li, Zhonghao; Kim, Jin-Tae; Xiao, Liantuan; Jia, Suotang

    2015-12-14

    We present the formation of ultracold (85)Rb(133)Cs molecules in the (5)0(+) 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(+) 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(+) electronic state of (85)Rb(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(+) 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. PMID:26671380

  6. The determination of potential energy curve and dipole moment of the (5)0+ electronic state of 85Rb133Cs molecule by high resolution photoassociation spectroscopy

    NASA Astrophysics Data System (ADS)

    Yuan, Jinpeng; Zhao, Yanting; Ji, Zhonghua; Li, Zhonghao; Kim, Jin-Tae; Xiao, Liantuan; Jia, Suotang

    2015-12-01

    We present the formation of ultracold 85Rb133Cs molecules in the (5)0+ 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+ 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+ electronic state of 85Rb133Cs 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+ 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.

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

    PubMed Central

    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. PMID:22820909

  8. 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

  9. 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. PMID:23372815

  10. Investigation of parameter-free model polarization potentials for electron-molecule scattering calculations including the nuclear motion

    SciTech Connect

    Morrison, M.A.; Saha, B.C.

    1986-10-01

    A correlation-polarization potential originally introduced by O'Connell and Lane (Phys. Rev. A 27, 1893 (1983)) is used in e-H/sub 2/ scattering calculations in which the vibrational motion of the target is taken into account. Eigenphase sums (as a function of internuclear separation) and cross sections for elastic scattering and for rovibrational excitations are compared to their counterparts calculated using the ab initio nonadiabatic model polarization potential of Gibson and Morrison (Phys. Rev. A 29, 2497 (1984)). At low energies, these scattering quantities are found to be quite sensitive to the treatment of polarization. To assess these model potentials, theoretical total, momentum transfer, and rotational- and vibrational-excitation cross sections are compared to experimental data.

  11. The determination of potential energy curve and dipole moment of the (5) 0+ electronic state of 85 Rb133 Cs molecule by high resolution photoassociation spectroscopy

    NASA Astrophysics Data System (ADS)

    Yuan, Jinpeng; Zhao, Yanting; Ji, Zhonghua; Li, Zhonghao; Kim, Jin-Tae; Xiao, Liantuan; Jia, Suotang

    2016-05-01

    The creation and manipulation of ultracold polar molecules have attracted intensive attentions due to their permanent electric dipole moments interacting strongly with an external electric field and with long-range dipole-dipole force, which facilitate applications such as precision measurement, quantum control of cold chemical reactions, and quantum computation. The (5) 0+ state is a good candidate to produce ultracold ground state RbCs molecule through a short-range photoassociation (PA). We present the formation of ultracold 85 Rb133 Cs molecules in the (5) 0+ electronic state by PA and their detection via resonance-enhanced two-photon ionization. Up to v = 47 vibrational levels including the lowest v = 0 and lowest J = 0 levels are identified with high resolution. Precise Dunham coefficients and the Rydberg-Klein-Rees potential energy curve of the (5) 0+ state are determined The electric dipole moments with respect to the vibrational numbers of the (5) 0+ electronic state 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+ state are helpful to understand the molecular structure and discover suitable transition pathways for transferring to the lowest rovibrational level of the ground state.

  12. 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.

  13. 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).

  14. Ectopic expression of polysialylated neural cell adhesion molecule in adult macaque Schwann cells promotes their migration and remyelination potential in the central nervous system

    PubMed Central

    Bachelin, C.; Zujovic, V.; Buchet, D.; Mallet, J.

    2010-01-01

    Recent findings suggested that inducing neural cell adhesion molecule polysialylation in rodents is a promising strategy for promoting tissue repair in the injured central nervous system. Since autologous grafting of Schwann cells is one potential strategy to promote central nervous system remyelination, it is essential to show that such a strategy can be translated to adult primate Schwann cells and is of interest for myelin diseases. Adult macaque Schwann cells were transduced with a lentiviral vector encoding sialyltransferase, an enzyme responsible for neural cell adhesion molecule polysialylation. In vitro, we found that ectopic expression of polysialylate promoted adult macaque Schwann cell migration and improved their integration among astrocytes in vitro without modifying their antigenic properties as either non-myelinating or pro-myelinating. In addition, forced expression of polysialylate in adult macaque Schwann cells decreased their adhesion with sister cells. To investigate the ability of adult macaque Schwann cells to integrate and migrate in vivo, focally induced demyelination was targeted to the spinal cord dorsal funiculus of nude mice, and both control and sialyltransferase expressing Schwann cells overexpressing green fluorescein protein were grafted remotely from the lesion site. Analysis of the spatio-temporal distribution of the grafted Schwann cells performed in toto and in situ, showed that in both groups, Schwann cells migrated towards the lesion site. However, migration of sialyltransferase expressing Schwann cells was more efficient than that of control Schwann cells, leading to their accelerated recruitment by the lesion. Moreover, ectopic expression of polysialylated neural cell adhesion molecule promoted adult macaque Schwann cell interaction with reactive astrocytes when exiting the graft, and their ‘chain-like’ migration along the dorsal midline. The accelerated migration of sialyltransferase expressing Schwann cells to the

  15. 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.

  16. Zinc Chelation by a Small-Molecule Adjuvant Potentiates Meropenem Activity in Vivo against NDM-1-Producing Klebsiella pneumoniae.

    PubMed

    Falconer, Shannon B; Reid-Yu, Sarah A; King, Andrew M; Gehrke, Sebastian S; Wang, Wenliang; Britten, James F; Coombes, Brian K; Wright, Gerard D; Brown, Eric D

    2015-11-13

    The widespread emergence of antibiotic drug resistance has resulted in a worldwide healthcare crisis. In particular, the extensive use of β-lactams, a highly effective class of antibiotics, has been a driver for pervasive β-lactam resistance. Among the most important resistance determinants are the metallo-β-lactamases (MBL), which are zinc-requiring enzymes that inactivate nearly all classes of β-lactams, including the last-resort carbapenem antibiotics. The urgent need for new compounds targeting MBL resistance mechanisms has been widely acknowledged; however, the development of certain types of compounds-namely metal chelators-is actively avoided due to host toxicity concerns. The work herein reports the identification of a series of zinc-selective spiro-indoline-thiadiazole analogues that, in vitro, potentiate β-lactam antibiotics against an MBL-carrying pathogen by withholding zinc availability. This study demonstrates the ability of one such analogue to inhibit NDM-1 in vitro and, using a mouse model of infection, shows that combination treatment of the respective analogue with meropenem results in a significant decrease in bacterial burden in contrast to animals that received antibiotic treatment alone. These results support the therapeutic potential of these chelators in overcoming antibiotic resistance. PMID:27623408

  17. 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

  18. 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.

  19. Accurate potential energy curve of the LiH{sup +} molecule calculated with explicitly correlated Gaussian functions

    SciTech Connect

    Tung, Wei-Cheng; Adamowicz, Ludwik

    2014-03-28

    Very accurate calculations of the ground-state potential energy curve (PEC) of the LiH{sup +} ion performed with all-electron explicitly correlated Gaussian functions with shifted centers are presented. The variational method is employed. The calculations involve optimization of nonlinear exponential parameters of the Gaussians performed with the aid of the analytical first derivatives of the energy determined with respect to the parameters. The diagonal adiabatic correction is also calculated for each PEC point. The PEC is then used to calculate the vibrational energies of the system. In that calculation, the non-adiabatic effects are accounted for by using an effective vibrational mass obtained by the minimization of the difference between the vibrational energies obtained from the calculations where the Born-Oppenheimer approximation was not assumed and the results of the present calculations.

  20. 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

  1. Selection and Characterization of Single Chain Antibody Fragments Specific for Hsp90 as a Potential Cancer Targeting Molecule

    PubMed Central

    Petters, Edyta; Sokolowska-Wedzina, Aleksandra; Otlewski, Jacek

    2015-01-01

    Heat shock proteins play an essential role in facilitating malignant transformation and they have been recognized as important factors in human cancers. One of the key elements of the molecular chaperones machinery is Hsp90 and it has recently become a target for anticancer therapeutic approaches. The potential and importance of Hsp90-directed agents becomes apparent when one realizes that disruption of Hsp90 function may influence over 200 oncogenic client proteins. Here, we described the selection and characterization of Hsp90-specific antibody fragments from commercially available Tomlinson I and J phage display libraries. The affinities of Hsp90-binding scFv variants were measured using SPR method. Then, based on the best clone selected, we performed the affinity maturation procedure and obtained valuable Hsp90-specific clones. The selected binders were expressed and applied for immunostaining, ELISA and SPR analysis using model cancer cell lines. All performed experiments confirmed the ability of selected antibodies to interact with the Hsp90. Therefore, the presented Hsp90-specific scFv, might be a starting point for the development of a novel antibody-based strategy targeting cancer. PMID:26307975

  2. Selection and Characterization of Single Chain Antibody Fragments Specific for Hsp90 as a Potential Cancer Targeting Molecule.

    PubMed

    Petters, Edyta; Sokolowska-Wedzina, Aleksandra; Otlewski, Jacek

    2015-01-01

    Heat shock proteins play an essential role in facilitating malignant transformation and they have been recognized as important factors in human cancers. One of the key elements of the molecular chaperones machinery is Hsp90 and it has recently become a target for anticancer therapeutic approaches. The potential and importance of Hsp90-directed agents becomes apparent when one realizes that disruption of Hsp90 function may influence over 200 oncogenic client proteins. Here, we described the selection and characterization of Hsp90-specific antibody fragments from commercially available Tomlinson I and J phage display libraries. The affinities of Hsp90-binding scFv variants were measured using SPR method. Then, based on the best clone selected, we performed the affinity maturation procedure and obtained valuable Hsp90-specific clones. The selected binders were expressed and applied for immunostaining, ELISA and SPR analysis using model cancer cell lines. All performed experiments confirmed the ability of selected antibodies to interact with the Hsp90. Therefore, the presented Hsp90-specific scFv, might be a starting point for the development of a novel antibody-based strategy targeting cancer. PMID:26307975

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

    PubMed

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

    2015-01-21

    In this paper, we systematically investigate the electronic structure for the (2)Σ(+) 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. PMID:25612710

  4. 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.

  5. 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.

  6. Molecule nanoweaver

    DOEpatents

    Gerald, II; Rex E.; Klingler, Robert J.; Rathke, Jerome W.; Diaz, Rocio; Vukovic, Lela

    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.

  7. AB initio MRD CI potential curves, dipole moments and zero-field splittings for the X 2Π ground states of the CF and CCl molecules

    NASA Astrophysics Data System (ADS)

    Hess, Bernd A.; Buenker, Robert J.

    1986-01-01

    A series of ab initio MRD CI calculations at various levels of theoretical treatment is carried out for the X 2Π ground states of the CF and CCl molecules. The resulting potential energy curves lead to quite good agreement with known spectroscopic constants for these systems and also allow for the accurate computation of the corresponding vibrational wavefunctions. Particular attention is given to the dependence of the electric dipole moments and spin-orbit splittings on the choice of the one-electron basis in the CI calculations. Best agreement with experimental values for these quantities is obtained by employing the natural orbitals of X 2Π states, in which case errors of only 0.1-0.2 D and 2.0-4.0 cm -1 respectively in the computed dipole moments and zero-field splittings result.

  8. 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.

  9. Characterization of a Novel Small Molecule That Potentiates β-Lactam Activity against Gram-Positive and Gram-Negative Pathogens

    PubMed Central

    Nair, Dhanalakshmi R.; Monteiro, João M.; Memmi, Guido; Thanassi, Jane; Pucci, Michael; Schwartzman, Joseph; Pinho, Mariana G.

    2015-01-01

    In a loss-of-viability screen using small molecules against methicillin-resistant Staphylococcus aureus (MRSA) strain USA300 with a sub-MIC of a β-lactam, we found a small molecule, designated DNAC-1, which potentiated the effect of oxacillin (i.e., the MIC of oxacillin decreased from 64 to 0.25 μg/ml). Fluorescence microscopy indicated a disruption in the membrane structures within 15 min of exposure to DNAC-1 at 2× MIC. This permeabilization was accompanied by a rapid loss of membrane potential, as monitored by use of the DiOC2 (3,3′-diethyloxacarbocyanine iodide) dye. Macromolecular analysis showed the inhibition of staphylococcal cell wall synthesis by DNAC-1. Transmission electron microscopy of treated MRSA USA300 cells revealed a slightly thicker cell wall, together with mesosome-like projections into the cytosol. The exposure of USA300 cells to DNAC-1 was associated with the mislocalization of FtsZ accompanied by the localization of penicillin-binding protein 2 (PBP2) and PBP4 away from the septum, as well as mild activation of the vraRS-mediated cell wall stress response. However, DNAC-1 does not have any generalized toxicity toward mammalian host cells. DNAC-1 in combination with ceftriaxone is also effective against an assortment of Gram-negative pathogens. Using a murine subcutaneous coinjection model with 108 CFU of USA300 as a challenge inoculum, DNAC-1 alone or DNAC-1 with a sub-MIC of oxacillin resulted in a 6-log reduction in bacterial load and decreased abscess formation compared to the untreated control. We propose that DNAC-1, by exerting a bimodal effect on the cell membrane and cell wall, is a viable candidate in the development of combination therapy against many common bacterial pathogens. PMID:25583731

  10. Ionization Energies and Aqueous Redox Potentials of Organic Molecules: Comparison of DFT, Correlated ab Initio Theory and Pair Natural Orbital Approaches.

    PubMed

    Isegawa, Miho; Neese, Frank; Pantazis, Dimitrios A

    2016-05-10

    The calculation of redox potentials involves large energetic terms arising from gas phase ionization energies, thermodynamic contributions, and solvation energies of the reduced and oxidized species. In this work we study the performance of a wide range of wave function and density functional theory methods for the prediction of ionization energies and aqueous one-electron oxidation potentials of a set of 19 organic molecules. Emphasis is placed on evaluating methods that employ the computationally efficient local pair natural orbital (LPNO) approach, as well as several implementations of coupled cluster theory and explicitly correlated F12 methods. The electronic energies are combined with implicit solvation models for the solvation energies. With the exception of MP2 and its variants, which suffer from enormous errors arising at least partially from the poor Hartree-Fock reference, ionization energies can be systematically predicted with average errors below 0.1 eV for most of the correlated wave function based methods studies here, provided basis set extrapolation is performed. LPNO methods are the most efficient way to achieve this type of accuracy. DFT methods show in general larger errors and suffer from inconsistent behavior. The only exception is the M06-2X functional which is found to be competitive with the best LPNO-based approaches for ionization energies. Importantly, the limiting factor for the calculation of accurate redox potentials is the solvation energy. The errors in the predicted solvation energies by all continuum solvation models tested in this work dominate the final computed reduction potential, resulting in average errors typically in excess of 0.3 V and hence obscuring the gains that arise from choosing a more accurate electronic structure method. PMID:27065224

  11. 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.

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

    PubMed Central

    Wiersma, Valerie R; de Bruyn, Marco; Shi, Ce; Gooden, Marloes JM; Wouters, Maartje CA; 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. PMID:25760768

  13. 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

  14. Dysregulated co-stimulatory molecule expression in a Sjögren's syndrome mouse model with potential implications by microRNA-146a.

    PubMed

    Gauna, Adrienne E; Park, Yun-Jong; Nayar, Gautam; Onate, Marelys; Jin, Jun-o; Stewart, Carol M; Yu, Qing; Cha, Seunghee

    2015-12-01

    Sjögren's syndrome (SjS) is an autoimmune condition that primarily affects salivary and lacrimal glands, causing loss of secretion. We have previously shown that microRNA-146a (miR-146a) is over-expressed in the salivary glands and peripheral blood mononuclear cells (PBMC) of SjS-prone mice (C57BL/6.NOD-Aec1Aec2, B6DC) and in PBMC of SjS patients. The purpose of this research was to identify a target molecule of miR-146a and identify subpopulations of cells affected by altered miR-146a in the salivary glands of SjS-prone mice. In silico analyses identified costimulatory molecule CD80 as a potential target of miR-146a. Luciferase assay of the human CD80 3'untranslated region demonstrated miR-146a directly inhibited CD80 protein expression as indicated by reduced luciferase reporter expression and an examination of B6DC salivary glands revealed a reduction in CD80 protein. More interestingly, the specific reduction in CD80 protein was detected from the salivary gland epithelial cell population and in interstitial dendritic cells in the glands as well. The reduction in CD80 protein levels in salivary gland epithelial cells were negatively associated with elevated miR-146a expression. Therefore, this study provides the first indication that salivary gland epithelial cells may be critically involved in SjS progression by altering CD86:CD80 protein ratio in response to miR-146a upregulation. PMID:26505653

  15. 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

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

    2016-05-01

    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

  16. Effects of pyrethroid molecules on rat nerves in vitro: potential to reverse temperature-sensitive conduction block of demyelinated peripheral axons

    PubMed Central

    Lees, George

    1998-01-01

    neurotoxic actions and severely limit the clinical potential of this and related molecules. PMID:9504390

  17. 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

  18. Ab initio calculation of accurate dissociation energy, potential energy curve and dipole moment function for the A1Σ+ state 7LiH molecule

    NASA Astrophysics Data System (ADS)

    Shi, De-Heng; Liu, Yu-Fang; Sun, Jin-Feng; Yang, Xiang-Dong; Zhu, Zun-Lue

    2006-05-01

    The reasonable dissociation limit of the A1Σ+ state 7LiH molecule is obtained. The accurate dissociation energy and the equilibrium geometry of this state are calculated using a symmetry-adapted-cluster configuration-interaction method in complete active space for the first time. The whole potential energy curve and the dipole moment function for the A1Σ+ state are calculated over a wide internuclear separation range from about 0.1 to 1.4 nm. The calculated equilibrium geometry and dissociation energy of this potential energy curve are of Re=0.2487 nm and De=1.064 eV, respectively. The unusual negative values of the anharmonicity constant and the vibration-rotational coupling constant are of ωeχe=-4.7158cm-1 and αe=-0.08649cm-1, respectively. The vertical excitation energy from the ground to the A1Σ+ state is calculated and the value is of 3.613 eV at 0.15875 nm (the equilibrium position of the ground state). The highly anomalous shape of this potential energy curve, which is exceptionally flat over a wide radial range around the equilibrium position, is discussed in detail. The harmonic frequency value of 502.47cm-1 about this state is approximately estimated. Careful comparison of the theoretical determinations with those obtained by previous theories about the A1Σ+ state dissociation energy clearly shows that the present calculations are much closer to the experiments than previous theories, thus represents an improvement.

  19. 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.

  20. 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. PMID:23937300

  1. Interstellar molecules

    NASA Astrophysics Data System (ADS)

    Smith, D.

    1987-09-01

    Some 70 different molecular species have so far been detected variously in diffuse interstellar clouds, dense interstellar clouds, and circumstellar shells. Only simple (diatomic and triatomic) species exist in diffuse clouds because of the penetration of destructive UV radiations, whereas more complex (polyatomic) molecules survive in dense clouds as a result of the shielding against this UV radiation provided by dust grains. A current list of interstellar molecules is given together with a few other molecular species that have so far been detected only in circumstellar shells. Also listed are those interstellar species that contain rare isotopes of several elements. The gas phase ion chemistry is outlined via which the observed molecules are synthesized, and the process by which enrichment of the rare isotopes occurs in some interstellar molecules is described.

  2. 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)

  3. 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.

  4. 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

  5. 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.

  6. 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.

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

    PubMed

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

    2016-03-21

    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. PMID:27004887

  8. 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

  9. 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.

  10. Calculations of 21 Λ-S and 42 Ω states of BC molecule: Potential energy curves, spectroscopic parameters and spin-orbit coupling effect.

    PubMed

    Xing, Wei; Shi, Deheng; Sun, Jinfeng; Zhu, Zunlue

    2016-01-15

    The potential energy curves (PECs) were calculated for the 42 Ω states generated from the 21 Λ-S states (X(4)Σ(-), A(4)Π, B(4)Σ(-), a(2)Π, b(2)Σ(-), c(2)Δ, d(2)Σ(+), e(2)Π, 3(2)Π, 4(2)Π, 5(2)Π, 2(2)Σ(-), 3(2)Σ(-), 2(2)Σ(+), 3(2)Σ(+), 2(2)Δ, 3(2)Δ, 1(4)Σ(+), 2(4)Π, 1(4)Δ and 1(2)Φ), which originated from the lowest two dissociation channels, B((2)Pu)+C((3)Pg) and B((2)Pu)+C((1)Dg), of the BC molecule. The PECs were calculated for internuclear separations from 0.08 to 1.10 nm using the CASSCF method, which was followed by the icMRCI approach with the aug-cc-pV6Z basis set. Of these 21 Λ-S states, the e(2)Π, 2(2)Δ, 2(2)Σ(-), 4(2)Π, 1(2)Φ and 3(2)Δ possess the double wells. The A(4)Π, a(2)Π, c(2)Δ, 2(4)Π, 4(2)Π, 5(2)Π, 1(4)Δ and 1(2)Φ states are inverted with the spin-orbit coupling (SOC) effect taken into account. The first well of e(2)Π state and the second well of 4(2)Π and 2(2)Δ states do not have any vibrational states whether with or without the SOC effect included. All the Λ-S and Ω states involved in this paper are bound states. Scalar relativistic correction was included by the third-order Douglas-Kroll Hamiltonian approximation at the level of an aug-cc-pV5Z basis set. Core-valence correlation correction was included at the level of an aug-cc-pCV5Z basis set. The SOC effect was accounted for by the state interaction method with the Breit-Pauli Hamiltonian and the all-electron cc-pCV5Z basis set. The PECs of all the states were extrapolated to the complete basis set limit. The spectroscopic parameters were obtained. The vibrational properties of several Λ-S and Ω states with the relatively shallow wells were evaluated. The SOC effect on the spectroscopic parameters is not obvious for almost all the states. The spectroscopic properties reported in this paper can be expected to be reliably predicted ones. PMID:26476070

  11. A Potential Hydrogen-Storage Media: C2H4 and C5H5 Molecules Doped with Rare Earth Atoms

    NASA Astrophysics Data System (ADS)

    Lei, Hong-Wen; Zhang, Hong; Gong, Min; Wu, Wei-Dong

    2012-12-01

    Using first-principles calculations, we predict that a single C2H4 or C5H5 molecule can form a stable complex with two rare earth metals such as La, Eu, and Ho. The La2C2H4 complex then absorbs up to sixteen hydrogen molecules, reaching a gravimetric storage capacity of 9.5wt% by adding a rare-earth metal atom, The results show that Eu-4f electrons have little impact on the hydrogen adsorption. The nature of bonding between Eu and H2 is due to the hybridization of Eu-5d with the H-1s orbital.

  12. 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.

  13. 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.

  14. Accurate calculations on the 22 electronic states and 54 spin-orbit states of the O2 molecule: potential energy curves, spectroscopic parameters and spin-orbit coupling.

    PubMed

    Liu, Hui; Shi, Deheng; Sun, Jinfeng; Zhu, Zunlue; Shulin, Zhang

    2014-04-24

    The potential energy curves (PECs) of 54 spin-orbit states generated from the 22 electronic states of O2 molecule are investigated for the first time for internuclear separations from about 0.1 to 1.0nm. Of the 22 electronic states, the X(3)Σg(-), A(')(3)Δu, A(3)Σu(+), B(3)Σu(-), C(3)Πg, a(1)Δg, b(1)Σg(+), c(1)Σu(-), d(1)Πg, f(1)Σu(+), 1(5)Πg, 1(3)Πu, 2(3)Σg(-), 1(5)Σu(-), 2(1)Σu(-) and 2(1)Δg are found to be bound, whereas the 1(5)Σg(+), 2(5)Σg(+), 1(1)Πu, 1(5)Δg, 1(5)Πu and 2(1)Πu are found to be repulsive ones. The B(3)Σu(-) and d(1)Πg states possess the double well. And the 1(3)Πu, C(3)Πg, A'(3)Δu, 1(5)Δg and 2(5)Σg(+) states are the inverted ones when the spin-orbit coupling is included. The PEC calculations are done by the complete active space self-consistent field (CASSCF) method, which is followed by the internally contracted multireference configuration interaction (icMRCI) approach with the Davidson correction. Core-valence correlation and scalar relativistic corrections are taken into account. The convergence of present calculations is evaluated with respect to the basis set and level of theory. The vibrational properties are discussed for the 1(5)Πg, 1(3)Πu, d(1)Πg and 1(5)Σu(-) states and for the second well of the B(3)Σu(-) state. The spin-orbit coupling effect is accounted for by the state interaction method with the Breit-Pauli Hamiltonian. The PECs of all the electronic states and spin-orbit states are extrapolated to the complete basis set limit. The spectroscopic parameters are obtained, and compared with available experimental and other theoretical results. Analyses demonstrate that the spectroscopic parameters reported here can be expected to be reliably predicted ones. The conclusion is obtained that the effect of spin-orbit coupling on the spectroscopic parameters are small almost for all the electronic states involved in this paper except for the 1(5)Σu(-), 1(5)Πg and 1(3)Πu. PMID:24486866

  15. 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

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

    PubMed

    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

  17. 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.

  18. IL-2 or IL-4 mRNA as a potential flow cytometric marker molecule for selective collection of living T helper 1 or T helper 2 lymphocytes.

    PubMed

    Ishibashi, Kaname; Tsuji, Akihiko

    2003-06-01

    Flow cytometry has been widely used to analyze and sort out particular types of living cells that have specific marker molecules. In many cases, marker proteins are present on the cell surface and are detected by monoclonal antibodies against them. However, there are some cases in which cells do not have specific marker molecules on their surface. In this situation, it would be useful if mRNA that is expressed specifically in the particular cell could be used as a marker molecule. We previously reported that mRNA can be detected in living cells by hybridizing a pair of fluoreophore (donor or acceptor)-labeled oligonucleotides to adjacent locations on the target mRNA in the cytoplasm of cells (Tsuji, A.; Koshimoto, H.; Sato, Y.; Hirano, M.; Sei-Iida, Y.; Kondo, S.; Ishibashi, K. Biophys. J. 2000, 78, 3260-3274). On the formed hybrid of the two fluorescent oligonucleotides with the target mRNA, the distance between the two fluorophores becomes very close, which results in fluorescence resonance energy transfer (FRET). Combining this fluorescent labeling method for mRNA with flow cytometry, we have examined the isolation of living CD4+ T helper lymphocytes expressing IL-2 mRNA (Th1) or IL-4 mRNA (Th2). A pair of fluorescent oligonucleotides for hybridizing to IL-2 or IL-4 mRNA were introduced into activated CD4+ T lymphocytes by electroporation. The cells were applied to FACS and analyzed by FRET signals. Th1 or Th2 lymphocytes were exclusively sorted from their mixed populations in activated CD4+ T cells. Our results demonstrate that it is possible to use mRNA as marker molecules to analyze and isolate living cells in flow cytometry. PMID:12948141

  19. Identification of EPAC (Exchange Protein Activated by cAMP) bioinformatically as a potential signalling biomarker in Cardiovascular Disease (CVD) and its molecular docking by a lead molecule.

    PubMed

    Bala, Saranya; Pathak, Ravi Kant; Mishra, Vachaspati

    2011-01-01

    The present work delineates the combinatorial approach of firstly, creation of a centralized data-set comprising signalling proteins identified on the basis of altered expression, such as over-expression or repression of a set of signalling protein(s) leading to the cause of the disease, which is based on published reports screened through Pubmed and secondly, in the in silico creation of novel lead (drug) molecules and docking of identified signalling biomarkers using such drugs to investigate possibility of their future application in the model systems eventually. EPAC (Exchange Protein Activated by cAMP) emerges as a signalling biomarker in cases studied presently. Brefeldin, the known inhibitor of EPAC, though the mechanism yet unexplored, has been the molecule used as the pharmacophore for creation of lead drug molecule. Various modifications have been incorporated into the pharmacophore to increase the hydrophobic interactions for increasing the binding efficiency of the generated lead molecule. Side-chain modifications of the pharmacophore and refinement of data through firedock upon docking of EPAC with the modified pharmacophore yielded best results on the bases of atomic contact energy, van der Waal and partial electrostatic interactions as well as additional estimations of the binding free energy. Modifications of CH3 at C15 with COOH and H at C2 with OH in brefeldin showed the best docking results on the basis of protein-drug interaction parameters. The present work provides a clue in rational design of EPAC inhibitors which could be developed as drug lead in combating CVD. PMID:21738308

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

    PubMed

    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

  1. 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.

  2. 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

  3. 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

  4. Single-molecule bioelectronics.

    PubMed

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

    2015-01-01

    Experimental techniques that 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. In this study, we review several technologies that 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

  5. 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

  6. Comment on ``On the role of dissipation on the Casimir-Polder potential between molecules in dielectric media'' [J. Chem. Phys. 133, 164501 (2010)

    NASA Astrophysics Data System (ADS)

    Dalvit, D. A. R.; Milonni, P. W.

    2011-07-01

    J. J. Rodriguez and A. Salam [J. Chem. Phys. 133, 164501 (2010)], 10.1063/1.3495954 find discrepancies between their calculation and a previously published one [S. Spagnolo, D. A. R. Dalvit, and P. W. Milonni, Phys. Rev. A 75, 052117 (2007)], 10.1103/PhysRevA.75.052117 for the van der Waals interaction of two guest molecules in a host dielectric medium. We trace these discrepancies to what we regard as fundamental errors in the calculation by Rodriguez and Salam.

  7. 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.

  8. Enteral n-3 fatty acids and micronutrients enhance percentage of positive neutrophil and lymphocyte adhesion molecules: a potential mediator of pressure ulcer healing in critically ill patients.

    PubMed

    Theilla, Miriam; Schwartz, Betty; Zimra, Yael; Shapiro, Haim; Anbar, Ronit; Rabizadeh, Esther; Cohen, Jonathan; Singer, Pierre

    2012-04-01

    n-3 Fatty acids are recognised as influencing both wound healing and immunity. We assessed the impact of a fish oil- and micronutrient-enriched formula (study formula) on the healing of pressure ulcers and on immune function in critically ill patients in an intensive care unit. A total of forty patients with pressure ulcers and receiving nutritional support were enrolled (intervention group, n 20, received study formula; and a control group, n 20, received an isoenergetic formula). Total and differential leucocyte count and percentage of adhesion molecule positive granulocyte and lymphocyte cells (CD11a, CD11b, CD18 and CD49b) were measured on days 0, 7 and 14. Percentage of positive lymphocytes for CD54, CD49b, CD49d and CD8 were also measured on days 0, 7 and 14. The state of pressure ulcers was assessed by using the pressure ulcer scale for healing tool score on days 7, 14 and 28 of treatment. No between-group differences in patient demographics, anthropometry or diagnostic class were observed. Patients who received the study formula showed significant increases in the percentage of positive CD18 and CD11a lymphocytes and of CD49b granulocytes as compared to controls (P < 0·05). While the severity of pressure ulcers was not significantly different between the two groups on admission, severity increased significantly over time for the control group (P < 0·05), but not for the study group. The present study suggests that a fish oil- and micronutrient-enriched formula may prevent worsening of pressure ulcers and that this effect may be mediated by an effect on adhesion molecule expression. PMID:22040465

  9. Structure-Based Screen Identifies a Potent Small Molecule Inhibitor of Stat5a/b with Therapeutic Potential for Prostate Cancer and Chronic Myeloid Leukemia.

    PubMed

    Liao, Zhiyong; Gu, Lei; Vergalli, Jenny; Mariani, Samanta A; De Dominici, Marco; Lokareddy, Ravi K; Dagvadorj, Ayush; Purushottamachar, Puranik; McCue, Peter A; Trabulsi, Edouard; Lallas, Costas D; Gupta, Shilpa; Ellsworth, Elyse; Blackmon, Shauna; Ertel, Adam; Fortina, Paolo; Leiby, Benjamin; Xia, Guanjun; Rui, Hallgeir; Hoang, David T; Gomella, Leonard G; Cingolani, Gino; Njar, Vincent; Pattabiraman, Nagarajan; Calabretta, Bruno; Nevalainen, Marja T

    2015-08-01

    Bypassing tyrosine kinases responsible for Stat5a/b phosphorylation would be advantageous for therapy development for Stat5a/b-regulated cancers. Here, we sought to identify small molecule inhibitors of Stat5a/b for lead optimization and therapy development for prostate cancer and Bcr-Abl-driven leukemias. In silico screening of chemical structure databases combined with medicinal chemistry was used for identification of a panel of small molecule inhibitors to block SH2 domain-mediated docking of Stat5a/b to the receptor-kinase complex and subsequent phosphorylation and dimerization. We tested the efficacy of the lead compound IST5-002 in experimental models and patient samples of two known Stat5a/b-driven cancers, prostate cancer and chronic myeloid leukemia (CML). The lead compound inhibitor of Stat5-002 (IST5-002) prevented both Jak2 and Bcr-Abl-mediated phosphorylation and dimerization of Stat5a/b, and selectively inhibited transcriptional activity of Stat5a (IC50 = 1.5μmol/L) and Stat5b (IC50 = 3.5 μmol/L). IST5-002 suppressed nuclear translocation of Stat5a/b, binding to DNA and Stat5a/b target gene expression. IST5-002 induced extensive apoptosis of prostate cancer cells, impaired growth of prostate cancer xenograft tumors, and induced cell death in patient-derived prostate cancers when tested ex vivo in explant organ cultures. Importantly, IST5-002 induced robust apoptotic death not only of imatinib-sensitive but also of imatinib-resistant CML cell lines and primary CML cells from patients. IST5-002 provides a lead structure for further chemical modifications for clinical development for Stat5a/b-driven solid tumors and hematologic malignancies. PMID:26026053

  10. Experimental and theoretical investigation of the molecular structure, conformational stability, hyperpolarizability, electrostatic potential, thermodynamic properties and NMR spectra of pharmaceutical important molecule: 4'-methylpropiophenone.

    PubMed

    Karunakaran, V; Balachandran, V

    2014-07-15

    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 (1)H and (13)C 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. PMID:24657464

  11. 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.

  12. Generalizing the Concept of Specific Compound Formulation Additives towards Non-Fluorescent Drugs: A Solubilization Study on Potential Anti-Alzheimer-Active Small-Molecule Compounds.

    PubMed

    Lawatscheck, Carmen; Pickhardt, Marcus; Wieczorek, Sebastian; Grafmüller, Andrea; Mandelkow, Eckhard; Börner, Hans G

    2016-07-18

    Tailor-made compound formulation additives enable the testing of potential drugs with undesirable pharmacological profiles. A combinatorial approach using Raman microscopy as the readout method is presented to select peptide sequences from large one-bead-one-compound libraries. The resulting peptide-PEG conjugates solubilize potential prophylactic and therapeutic anti-Alzheimer compounds and can be used as specific additives not only for fluorescent but also for non-fluorescent compounds. PMID:27282127

  13. 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%.

  14. 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

  15. 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

    Costantini, Claudio; Micheletti, Alessandra; Calzetti, Federica; Perbellini, Omar; Tamassia, Nicola; Albanesi, Cristina; Vermi, William; Cassatella, Marco A

    2011-10-01

    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

  16. 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.

  17. 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

  18. 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. PMID:26389789

  19. 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

  20. Response to ``Comment on `On the role of dissipation on the Casimir-Polder potential between molecules in dielectric media''' [J. Chem. Phys. 135, 047101 (2011)

    NASA Astrophysics Data System (ADS)

    Rodriguez, Justo J.; Salam, A.

    2011-07-01

    In this Response to the Comment by Dalvit and Milonni, we go into further details as to why the dispersion interaction potential appearing in each of our works differs, and why the form given by Rodriguez and Salam correctly accounts for absorption in the dielectric medium. We also point out and address a number of fallacies raised in the Comment.

  1. The c.503T>C Polymorphism in the Human KLRB1 Gene Alters Ligand Binding and Inhibitory Potential of CD161 Molecules

    PubMed Central

    Rother, Sascha; Hundrieser, Joachim; Pokoyski, Claudia; Kollrich, Sonja; Borns, Katja; Blasczyk, Rainer; Poehnert, Daniel; Klempnauer, Jürgen; Schwinzer, Reinhard

    2015-01-01

    Studying genetic diversity of immunologically relevant molecules can improve our knowledge on their functional spectrum in normal immune responses and may also uncover a possible role of different variants in diseases. We characterized the c.503T>C polymorphism in the human KLRB1 gene (Killer cell lectin-like receptor, subfamily B, member 1) coding for the cell surface receptor CD161. CD161 is expressed by subsets of CD4+ and CD8+ T cells and the great majority of CD56+ natural killer (NK) cells, acting as inhibitory receptor in the latter population. Genotyping a cohort of 118 healthy individuals revealed 40% TT homozygotes, 46% TC heterozygotes, and 14% carriers of CC. There was no difference in the frequency of CD161 expressing CD4+ and CD8+ T cells between the different genotypes. However, the frequency of CD161+ NK cells was significantly decreased in CC carriers as compared to TT homozygotes. c.503T>C causes an amino acid exchange (p.Ile168Thr) in an extracellular loop of the CD161 receptor, which is regarded to be involved in binding of its ligand Lectin-like transcript 1 (LLT1). Binding studies using soluble LLT1-Fc on 293 transfectants over-expressing CD161 receptors from TT or CC carriers suggested diminished binding to the CC variant. Furthermore, triggering of CD161 either by LLT1 or anti-CD161 antibodies inhibited NK cell activation less effectively in cells from CC individuals than cells from TT carriers. These data suggest that the c.503T>C polymorphism is associated with structural alterations of the CD161 receptor. The regulation of NK cell homeostasis and activation apparently differs between carriers of the CC and TT variant of CD161. PMID:26309225

  2. 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

  3. 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.

  4. 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.

  5. Nonsequential double ionization of molecules

    SciTech Connect

    Prauzner-Bechcicki, Jakub S.; Sacha, Krzysztof; Zakrzewski, Jakub; Eckhardt, Bruno

    2005-03-01

    Double ionization of diatomic molecules by short linearly polarized laser pulses is analyzed. We consider the final stage of the ionization process, that is the decay of a highly excited two electron molecule, which is formed after rescattering. The saddles of the effective adiabatic potential energy close to which simultaneous escape of electrons takes place are identified. Numerical simulations of the ionization of molecules show that the process can be dominated by either sequential or nonsequential events. In order to increase the ratio of nonsequential to sequential ionizations very short laser pulses should be applied.

  6. Accurate Ionization Potentials and Electron Affinities of Acceptor Molecules I. Reference Data at the CCSD(T) Complete Basis Set Limit.

    PubMed

    Richard, Ryan M; Marshall, Michael S; Dolgounitcheva, O; Ortiz, J V; Brédas, Jean-Luc; Marom, Noa; Sherrill, C David

    2016-02-01

    In designing organic materials for electronics applications, particularly for organic photovoltaics (OPV), the ionization potential (IP) of the donor and the electron affinity (EA) of the acceptor play key roles. This makes OPV design an appealing application for computational chemistry since IPs and EAs are readily calculable from most electronic structure methods. Unfortunately reliable, high-accuracy wave function methods, such as coupled cluster theory with single, double, and perturbative triples [CCSD(T)] in the complete basis set (CBS) limit are too expensive for routine applications to this problem for any but the smallest of systems. One solution is to calibrate approximate, less computationally expensive methods against a database of high-accuracy IP/EA values; however, to our knowledge, no such database exists for systems related to OPV design. The present work is the first of a multipart study whose overarching goal is to determine which computational methods can be used to reliably compute IPs and EAs of electron acceptors. This part introduces a database of 24 known organic electron acceptors and provides high-accuracy vertical IP and EA values expected to be within ±0.03 eV of the true non-relativistic, vertical CCSD(T)/CBS limit. Convergence of IP and EA values toward the CBS limit is studied systematically for the Hartree-Fock, MP2 correlation, and beyond-MP2 coupled cluster contributions to the focal point estimates. PMID:26731487

  7. 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.

  8. 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.

  9. 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. PMID:25904053

  10. 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.

  11. 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. PMID:22687516

  12. 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.

  13. 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 ...

  14. Nanochannel Based Single Molecule Recycling

    PubMed Central

    Lesoine, John F.; Venkataraman, Prahnesh A.; Maloney, Peter C.; Dumont, Mark

    2012-01-01

    We present a method for measuring the fluorescence from a single molecule hundreds of times without surface immobilization. The approach is based on the use of electroosmosis to repeatedly drive a single target molecule in a fused silica nanochannel through a stationary laser focus. Single molecule fluorescence detected during the transit time through the laser focus is used to repeatedly reverse the electrical potential controlling the flow direction. Our method does not rely on continuous observation and therefore is less susceptible to fluorescence blinking than existing fluorescence-based trapping schemes. The variation in the turnaround times can be used to measure the diffusion coefficient on a single molecule level. We demonstrate the ability to recycle both proteins and DNA in nanochannels and show that the procedure can be combined with single-pair Förster energy transfer. Nanochannel-based single molecule recycling holds promise for studying conformational dynamics on the same single molecule in solution and without surface tethering. PMID:22662745

  15. Electrochromic graphene molecules.

    PubMed

    Ji, Zhiqiang; Doorn, Stephen K; Sykora, Milan

    2015-04-28

    Polyclic aromatic hydrocarbons also called Graphene Molecules (GMs), with chemical composition C132H36(COOH)2 were synthesized in situ on the surface of transparent nanocrystalline indium tin oxide (nc-ITO) electrodes and 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 a 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 nonideal. The nonideality factors associated with the oxidation and reduction processes are attributed to 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. PMID:25768313

  16. Electrochromic Graphene Molecules

    DOE PAGESBeta

    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

  17. 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.

  18. 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.

  19. Small Molecule based Musculoskeletal Regenerative Engineering

    PubMed Central

    Lo, Kevin W.-H.; Jiang, Tao; Gagnon, Keith A.; Nelson, Clarke; Laurencin, Cato T.

    2014-01-01

    Clinicians and scientists working in the field of regenerative engineering are actively investigating a wide range of methods to promote musculoskeletal tissue regeneration. Small molecule-mediated tissue regeneration is emerging as a promising strategy for regenerating various musculoskeletal tissues and a large number of small molecule compounds have been recently discovered as potential bioactive molecules for musculoskeletal tissue repair and regeneration. In this review, we summarize the recent literature encompassing the past four years in the area of small bioactive molecule for promoting repair and regeneration of various musculoskeletal tissues including bone, muscle, cartilage, tendon, and nerve. PMID:24405851

  20. 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. PMID:26136234

  1. 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.

  2. Quantifying molecule-surface interactions using AFM-based single-molecule manipulation

    NASA Astrophysics Data System (ADS)

    Tautz, F. S.; Wagner, C.; Temirov, R.; Fournier, N.; Green, M.; Esat, T.; Leinen, P.; Groetsch, A.; Ruiz, V. G.; Tkatchenko, A.; Li, C.; Muellen, K.; Rohlfing, M.

    2015-03-01

    Scanning probe microscopy plays an important role in the investigation of molecular adsorption. Promising, is the possibility to probe the molecule-surface interaction while tuning its strength through AFM tip-induced single-molecule manipulation. Here, we outline a strategy to achieve quantitative understanding of such manipulation experiments. The example of qPlus sensor based PTCDA molecule lifting experiments is used to demonstrate how different aspects of the molecule-surface interaction, namely the short-range adsorption potential, the asymptotic van der Waals potential, local chemical bonds which are the source of the surface corrugation, and molecule-molecule interactions can be measured with SPM and interpreted by the help of force-field simulations.

  3. 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

  4. 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.

  5. Adhesion molecules and receptors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adhesion molecules are necessary for leukocyte trafficking and differentiation. They serve to initiate cell-cell interactions under conditions of shear, and they sustain the cell-cell and cell-matrix interactions needed for cellular locomotion. They also can serve directly as signaling molecules act...

  6. 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)

  7. Functional molecules in electronic circuits.

    PubMed

    Weibel, Nicolas; Grunder, Sergio; Mayor, Marcel

    2007-08-01

    Molecular electronics is a fascinating field of research contributing to both fundamental science and future technological achievements. A promising starting point for molecular devices is to mimic existing electronic functions to investigate the potential of molecules to enrich and complement existing electronic strategies. Molecules designed and synthesized to be integrated into electronic circuits and to perform an electronic function are presented in this article. The focus is set in particular on rectification and switching based on molecular devices, since the control over these two parameters enables the assembly of memory units, likely the most interesting and economic application of molecular based electronics. Both historical and contemporary solutions to molecular rectification are discussed, although not exhaustively. Several examples of integrated molecular switches that respond to light are presented. Molecular switches responding to an electrochemical signal are also discussed. Finally, supramolecular and molecular systems with intuitive application potential as memory units due to their hysteretic switching are highlighted. Although a particularly attractive feature of molecular electronics is its close cooperation with neighbouring disciplines, this article is written from the point of view of a chemist. Although the focus here is largely on molecular considerations, innovative contributions from physics, electro engineering, nanotechnology and other scientific disciplines are equally important. However, the ability of the chemist to correlate function with structure, to design and to provide tailor-made functional molecules is central to molecular electronics. PMID:17637951

  8. Ultracold polar KRb molecules

    NASA Astrophysics Data System (ADS)

    Neyenhuis, Brian; Chotia, Amodsen; Moses, Steven; Ye, Jun; Jin, Deborah

    2011-05-01

    Ultracold polar molecules in the quantum degenerate regime open the possibility of realizing quantum gases with long-range, and spatially anisotropic, interparticle interactions. Currently, we can create a gas of ultracold fermionic ground-state KRb molecules in with a peak density of 1012 cm-3 and a temperature just 1.4 times the Fermi temperature. We will report on efforts to further cool this gas of molecules. One possibility is to evaporatively cool a spin-polarized molecular Fermi gas confined in quasi-2D, where we would rely on dipole-dipole interactions for rethermalization. We acknowledge funding from NIST, NSF, and AFOSR-MURI.

  9. Poisson's spot with molecules

    SciTech Connect

    Reisinger, Thomas; Holst, Bodil; Patel, Amil A.; Smith, Henry I.; Reingruber, Herbert; Fladischer, Katrin; Ernst, Wolfgang E.; Bracco, Gianangelo

    2009-05-15

    In the Poisson-spot experiment, waves emanating from a source are blocked by a circular obstacle. Due to their positive on-axis interference an image of the source (the Poisson spot) is observed within the geometrical shadow of the obstacle. In this paper we report the observation of Poisson's spot using a beam of neutral deuterium molecules. The wavelength independence and the weak constraints on angular alignment and position of the circular obstacle make Poisson's spot a promising candidate for applications ranging from the study of large molecule diffraction to patterning with molecules.

  10. Poisson's spot with molecules

    NASA Astrophysics Data System (ADS)

    Reisinger, Thomas; Patel, Amil A.; Reingruber, Herbert; Fladischer, Katrin; Ernst, Wolfgang E.; Bracco, Gianangelo; Smith, Henry I.; Holst, Bodil

    2009-05-01

    In the Poisson-spot experiment, waves emanating from a source are blocked by a circular obstacle. Due to their positive on-axis interference an image of the source (the Poisson spot) is observed within the geometrical shadow of the obstacle. In this paper we report the observation of Poisson’s spot using a beam of neutral deuterium molecules. The wavelength independence and the weak constraints on angular alignment and position of the circular obstacle make Poisson’s spot a promising candidate for applications ranging from the study of large molecule diffraction to patterning with molecules.

  11. 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.

  12. 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)

  13. Spin polarization effect for Fe2 molecule

    NASA Astrophysics Data System (ADS)

    Yan, Shi-Ying; Zhu, Zheng-He

    2006-07-01

    This paper uses the density functional theory (DFT)(B3p86) of Gaussian03 to optimize the structure of Fe2 molecule. The result shows that the ground state for Fe2 molecule is a 9-multiple state, which shows spin polarization effect of Fe2 molecule of transition metal elements for the first time. Meanwhile, we have not found any spin pollution because the wavefunction of the ground state does not mingle with wavefunctions with higher energy states. So, that the ground state for Fe2 molecule is a 9-multiple state is indicative of the spin polarization effect of Fe2 molecule of transition metal elements. That is, there exist 8 parallel spin electrons. The non-conjugated electron is greatest in number. These electrons occupy different spacious tracks, so that the energy of the Fe2 molecule is minimized. It can be concluded that the effect of parallel spin of the Fe2 molecule is larger than the effect of the conjugated molecule, which is obviously related to the effect of electron d delocalization. In addition, the Murrell-Sorbie potential functions with the parameters for the ground state and other states of Fe2 molecule are derived. Dissociation energy De for the ground state of Fe2 molecule is 2.8586ev, equilibrium bond length Re is 0.2124nm, vibration frequency ωe is 336.38 cm-1. Its force constants f2, f3, and f4 are 1.8615aJ.nm-2, -8.6704aJ.nm-3, 29.1676aJ.nm-4 respectively. The other spectroscopic data for the ground state of Fe2 molecule ωeχe,Be, αe are 1.5461 cm-1, 0.1339 cm-1, 7.3428×10-4 cm-1 respectively.

  14. Ultralong-range polyatomic Rydberg molecules

    NASA Astrophysics Data System (ADS)

    Gonzalez-Ferez, Rosario

    2016-05-01

    Ultralong-range polyatomic Rydberg molecules are formed when a ground-state atom is bound to a Rydberg atom. The binding mechanism of these Rydberg molecules is based on the low-energy collisions between a Rydberg electron and a ground-state atom and leads to the unusual oscillatory behavior of the adiabatic potential energy curves. If the ground-state atom immersed into the Rydberg wave function is replaced by a heteronuclear diatomic molecule another type of polyatomic Rydberg molecules can form. In this case, the Rydberg electron is coupled to the internal states of the polar ground-state molecule. In this talk, we will explore the electronic structure and rovibrational properties of these ultralong-range polyatomic Rydberg molecule. For the second type of Rydberg molecules, the polar dimer is allowed to rotate in the electric fields generated by the Rydberg electron and Rydberg core as well as an additional external field. We will investigate the metamorphosis of the Born-Oppenheimer potential curves, essential for the binding mechanism, with varying electric field and analyze the resulting properties such as the vibrational structure and the alignment and orientation of the polar dimer.

  15. Entropy bottlenecks in ion-molecule reactions

    NASA Technical Reports Server (NTRS)

    Dodd, J. A.; Brauman, J. I.; Golden, D. M.

    1984-01-01

    The significance of entropy bottlenecks in dissociation and recombination pathways in the prototype ionic system CH3 + CH3(+) has been investigated. Ion-molecule systems are shown to react through an entirely different dynamics than neutral systems, due to intrinsic differences in the shapes of the relevant potential surfaces. Consequences with regard to the interpretation of experimental rate parameters in the ion-molecule area are discussed.

  16. Positron binding to molecules

    NASA Astrophysics Data System (ADS)

    Danielson, J. R.

    2011-05-01

    While there is theoretical evidence that positrons can bind to atoms, calculations for molecules are much less precise. Unfortunately, there have been no measurements of positron-atom binding, due primarily to the difficulty in forming positron-atom bound states in two-body collisions. In contrast, positrons attach to molecules via Feshbach resonances (VFR) in which a vibrational mode absorbs the excess energy. Using a high-resolution positron beam, this VFR process has been studied to measure binding energies for more than 40 molecules. New measurements will be described in two areas: positron binding to relatively simple molecules, for which theoretical calculations appear to be possible; and positron binding to molecules with large permanent dipole moments, which can be compared to analogous, weakly bound electron-molecule (negative-ion) states. Binding energies range from 75 meV for CS2 (no dipole moment) to 180 meV for acetonitrile (CH3CN). Other species studied include aldehydes and ketones, which have permanent dipole moments in the range 2.5 - 3.0 debye. The measured binding energies are surprisingly large (by a factor of 10 to 100) compared to those for the analogous negative ions, and these differences will be discussed. New theoretical calculations for positron-molecule binding are in progress, and a recent result for acetonitrile will be discussed. This ability to compare theory and experiment represents a significant step in attempts to understand positron binding to matter. In collaboration with A. C. L. Jones, J. J. Gosselin, and C. M. Surko, and supported by NSF grant PHY 07-55809.

  17. Low energy positron interactions with biological molecules

    NASA Astrophysics Data System (ADS)

    Wanniarachchi, Indika L.

    Calculations of the positron density distribution which can be used for positrons bound to midsize and larger molecules have been tested for smaller molecules and subsequently applied to investigate the most likely e +e-- annihilation sites for positrons interacting with biological molecules containing C, H, O, and N. In order to allow consideration of positrons bound to extended molecules with regions of different character and no particular symmetry, atom-centered positron basis sets of Gaussian-type functions were developed for positrons bound to molecules containing O, N, C, H, Li, Na, and Be. Testing shows that there is no need to scale the positron basis functions to take into account different effective charges on the atoms in different molecules. Even at the HF level of theory the calculated positron and the contact density of e+LiH system is in qualitative agreement with the most accurate calculation was done in ECG method. Also it has been found that for larger biological molecules such as derivation of formaldehyde can leave out positron basis sets centered on H atoms and still get qualitatively acceptable contact density distribution. According to our results, the electronic and positronic wavefunctions have the most overlap in the regions of most negative electrostatic potential in the parent molecule, and we can expect that a positron bound to the molecule will be more likely to annihilate with one of the electrons in these regions. Also we find that the highest energy occupied electronic orbital often does not make the largest contribution to e+e -- annihilation, and that the energy liberated by subsequent electronic relaxation is sufficient to break the backbone in several places in di-peptides and other organic molecules.

  18. Molecules on ice

    SciTech Connect

    Clary, D.C.

    1996-03-15

    The ozone hole that forms in the spring months over the Antarctic is thought to be produced through a network of chemical reactions catalyzed by the surfaces of ice crystals in polar stratospheric clouds (PSCs). A reaction between chlorine reservoir molecules, such as HCl + ClONO{sub 2} > HNO{sub 3} + Cl{sub 2}, is kinetically forbidden in the gas phase but proceeds quickly on the surface of ice and produces Cl{sub 2} molecules that are photodissociated by sunlight to yield the Cl atoms that destroy ozone. This destructive chain of events begins when HCl molecules stick to the ice crystals, and the mechanism for this crucial sticking process has been the subject of much debate. Recent work describes a mechanism that explains how HCl sticks to ice. This article goes on to detail research focusing surface reactions in stratospheric chemistry. 9 refs., 1 fig.

  19. 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.

  20. Atomic branching in molecules

    NASA Astrophysics Data System (ADS)

    Estrada, Ernesto; Rodríguez-Velázquez, Juan A.; Randić, Milan

    A graph theoretic measure of extended atomic branching is defined that accounts for the effects of all atoms in the molecule, giving higher weight to the nearest neighbors. It is based on the counting of all substructures in which an atom takes part in a molecule. We prove a theorem that permits the exact calculation of this measure based on the eigenvalues and eigenvectors of the adjacency matrix of the graph representing a molecule. The definition of this measure within the context of the Hückel molecular orbital (HMO) and its calculation for benzenoid hydrocarbons are also studied. We show that the extended atomic branching can be defined using any real symmetric matrix, as well as any Hermitian (self-adjoint) matrix, which permits its calculation in topological, geometrical, and quantum chemical contexts.

  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. Molecules in η Carinae

    NASA Astrophysics Data System (ADS)

    Loinard, Laurent; Menten, Karl M.; Güsten, Rolf; Zapata, Luis A.; Rodríguez, Luis F.

    2012-04-01

    We report the detection toward η Carinae of six new molecules, CO, CN, HCO+, HCN, HNC, and N2H+, and of two of their less abundant isotopic counterparts, 13CO and H13CN. The line profiles are moderately broad (~100 km s-1), indicating that the emission originates in the dense, possibly clumpy, central arcsecond of the Homunculus Nebula. Contrary to previous claims, CO and HCO+ do not appear to be underabundant in η Carinae. On the other hand, molecules containing nitrogen or the 13C isotope of carbon are overabundant by about one order of magnitude. This demonstrates that, together with the dust responsible for the dimming of η Carinae following the Great Eruption, the molecules detected here must have formed in situ out of CNO-processed stellar material.

  3. Poisson's Spot with Molecules

    NASA Astrophysics Data System (ADS)

    Reisinger, Thomas; Patel, Amil; Reingruber, Herbert; Fladischer, Katrin; Ernst, Wolfgang E.; Bracco, Gianangelo; Smith, Henry I.; Holst, Bodil

    2009-03-01

    In the Poisson-Spot experiment, waves emanating from a source are blocked by a circular obstacle. Due to their positive on-axis interference an image of the source (the Poisson spot) is observed within the geometrical shadow of the obstacle. The Poisson spot is the last of the classical optics experiments to be realized with neutral matter waves. In this paper we report the observation of Poisson's Spot using a beam of neutral deuterium molecules. The wavelength-independence and the weak constraints on angular alignment and position of the circular obstacle make Poisson's spot a promising candidate for applications ranging from the study of large-molecule diffraction and coherence in atom-lasers to patterning with large molecules.

  4. 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.

  5. Towards single molecule switches.

    PubMed

    Zhang, Jia Lin; Zhong, Jian Qiang; Lin, Jia Dan; Hu, Wen Ping; Wu, Kai; Xu, Guo Qin; Wee, Andrew T S; Chen, Wei

    2015-05-21

    The concept of using single molecules as key building blocks for logic gates, diodes and transistors to perform basic functions of digital electronic devices at the molecular scale has been explored over the past decades. However, in addition to mimicking the basic functions of current silicon devices, molecules often possess unique properties that have no parallel in conventional materials and promise new hybrid devices with novel functions that cannot be achieved with equivalent solid-state devices. The most appealing example is the molecular switch. Over the past decade, molecular switches on surfaces have been intensely investigated. A variety of external stimuli such as light, electric field, temperature, tunneling electrons and even chemical stimulus have been used to activate these molecular switches between bistable or even multiple states by manipulating molecular conformations, dipole orientations, spin states, charge states and even chemical bond formation. The switching event can occur either on surfaces or in break junctions. The aim of this review is to highlight recent advances in molecular switches triggered by various external stimuli, as investigated by low-temperature scanning tunneling microscopy (LT-STM) and the break junction technique. We begin by presenting the molecular switches triggered by various external stimuli that do not provide single molecule selectivity, referred to as non-selective switching. Special focus is then given to selective single molecule switching realized using the LT-STM tip on surfaces. Single molecule switches operated by different mechanisms are reviewed and discussed. Finally, molecular switches embedded in self-assembled monolayers (SAMs) and single molecule junctions are addressed. PMID:25757483

  6. Plasmonic nanostructures: artificial molecules.

    PubMed

    Wang, Hui; Brandl, Daniel W; Nordlander, Peter; Halas, Naomi J

    2007-01-01

    This Account describes a new paradigm for the relationship between the geometry of metallic nanostructures and their optical properties. While the interaction of light with metallic nanoparticles is determined by their collective electronic or plasmon response, a compelling analogy exists between plasmon resonances of metallic nanoparticles and wave functions of simple atoms and molecules. Based on this insight, an entire family of plasmonic nanostructures, artificial molecules, has been developed whose optical properties can be understood within this picture: nanoparticles (nanoshells, nanoeggs, nanomatryushkas, nanorice), multi-nanoparticle assemblies (dimers, trimers, quadrumers), and a nanoparticle-over-metallic film, an electromagnetic analog of the spinless Anderson model. PMID:17226945

  7. Single-molecule junctions beyond electronic transport

    NASA Astrophysics Data System (ADS)

    Aradhya, Sriharsha V.; Venkataraman, Latha

    2013-06-01

    The idea of using individual molecules as active electronic components provided the impetus to develop a variety of experimental platforms to probe their electronic transport properties. Among these, single-molecule junctions in a metal-molecule-metal motif have contributed significantly to our fundamental understanding of the principles required to realize molecular-scale electronic components from resistive wires to reversible switches. The success of these techniques and the growing interest of other disciplines in single-molecule-level characterization are prompting new approaches to investigate metal-molecule-metal junctions with multiple probes. Going beyond electronic transport characterization, these new studies are highlighting both the fundamental and applied aspects of mechanical, optical and thermoelectric properties at the atomic and molecular scales. Furthermore, experimental demonstrations of quantum interference and manipulation of electronic and nuclear spins in single-molecule circuits are heralding new device concepts with no classical analogues. In this Review, we present the emerging methods being used to interrogate multiple properties in single molecule-based devices, detail how these measurements have advanced our understanding of the structure-function relationships in molecular junctions, and discuss the potential for future research and applications.

  8. Small molecule TSHR agonists and antagonists.

    PubMed

    Neumann, S; Gershengorn, M C

    2011-04-01

    TSH activates the TSH receptor (TSHR) thereby stimulating the function of thyroid follicular cells (thyrocytes) leading to biosynthesis and secretion of thyroid hormones. Because TSHR is involved in several thyroid pathologies, there is a strong rationale for the design of small molecule "drug-like" ligands. Recombinant human TSH (rhTSH, Thyrogen(®)) has been used in the follow-up of patients with thyroid cancer to increase the sensitivity for detection of recurrence or metastasis. rhTSH is difficult to produce and must be administered by injection. A small molecule TSHR agonist could produce the same beneficial effects as rhTSH but with greater ease of oral administration. We developed a small molecule ligand that is a full agonist at TSHR. Importantly for its clinical potential, this agonist elevated serum thyroxine and stimulated thyroidal radioiodide uptake in mice after its absorption from the gastrointestinal tract following oral administration. Graves' disease (GD) is caused by persistent, unregulated stimulation of thyrocytes by thyroid-stimulating antibodies (TSAbs) that activate TSHR. We identified the first small molecule TSHR antagonists that inhibited TSH- and TSAb-stimulated signalling in primary cultures of human thyrocytes. Our results provide proof-of-principle for effectiveness of small molecule agonists and antagonists for TSHR. We suggest that these small molecule ligands are lead compounds for the development of higher potency ligands that can be used as probes of TSHR biology with therapeutic potential. PMID:21511239

  9. Prebiologically Important Interstellar Molecules

    NASA Astrophysics Data System (ADS)

    Kuan, Y.-J.; Huang, H.-C.; Charnley, S. B.; Tseng, W.-L.; Snyder, L. E.; Ehrenfreund, P.; Kisiel, Z.; Thorwirth, S.; Bohn, R. K.; Wilson, T. L.

    2004-06-01

    Understanding the organic chemistry of molecular clouds, particularly the formation of biologically important molecules, is fundamental to the study of the processes which lead to the origin, evolution and distribution of life in the Galaxy. Determining the level of molecular complexity attainable in the clouds, and the nature of the complex organic material available to protostellar disks and the planetary systems that form from them, requires an understanding of the possible chemical pathways and is therefore a central question in astrochemistry. We have thus searched for prebiologically important molecules in the hot molecular cloud cores: Sgr B2(N-LMH), W51 e1/e2 and Orion-KL. Among the molecules searched: Pyrimidine is the unsubstituted ring analogue for three of the DNA and RNA bases. 2H-Azirine and Aziridine are azaheterocyclic compounds. And Glycine is the simplest amino acid. Detections of these interstellar organic molecular species will thus have important implications for Astrobiology. Our preliminary results indicate a tentative detection of interstellar glycine. If confirmed, this will be the first detection of an amino acid in interstellar space and will greatly strengthen the thesis that interstellar organic molecules could have played a pivotal role in the prebiotic chemistry of the early Earth.

  10. 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.

  11. 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…

  12. 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…

  13. The Science of Molecules

    ERIC Educational Resources Information Center

    Flory, Paul J.

    1974-01-01

    The author maintains that chemistry has a key role as the science of molecules and rejects the concept of chemistry as a branch of physics. The scope of chemistry, the philosophies underlying its practice, and the teaching of the subject also are discussed. (DT)

  14. 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.

  15. 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

  16. OMG: Open Molecule Generator.

    PubMed

    Peironcely, Julio E; Rojas-Chertó, Miguel; Fichera, Davide; Reijmers, Theo; Coulier, Leon; Faulon, Jean-Loup; Hankemeier, Thomas

    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

  17. Single Chain Recombinant HLA-DQ2.5/peptide Molecules Block α2-gliadin-Specific Pathogenic CD4+ T Cell Proliferation and Attenuate Production of Inflammatory Cytokines: A Potential Therapy for Celiac Disease

    PubMed Central

    Huan, J; Meza-Romero, R; Mooney, J L; Vandenbark, A A; Offner, H; Burrows, G G

    2010-01-01

    Celiac disease (CD) is a disorder of the small intestine caused by intolerance to wheat gluten and related proteins in barley and rye. CD4+ T cells play a central role in CD, recognizing and binding complexes of HLA-DQ2.5 bearing gluten peptides that have survived digestion and that are deamidated by tissue transglutaminase (TG2), propagating a cascade of inflammatory processes that damage and eventually destroy the villous tissue structures of the small intestine. Here we present data showing that recombinant DQ2.5-derived molecules bearing covalently tethered α2-gliadin-61-71 peptide have a remarkable ability to block antigen-specific T cell proliferation and inhibited pro-inflammatory cytokine secretion in human DQ2.5-restricted α2-gliadin specific T cell clones obtained from patients with celiac disease. The results from our in vitro studies suggest that HLA-DQ2.5 derived molecules could significantly inhibit and perhaps reverse the intestinal pathology caused by T cell mediated inflammation and the associated production of proinflammatory cytokines. PMID:20736999

  18. Bringing single-molecule spectroscopy to macromolecular protein complexes

    PubMed Central

    Joo, Chirlmin; Fareh, Mohamed; Kim, V. Narry

    2013-01-01

    Single-molecule fluorescence spectroscopy offers real-time, nanometer-resolution information. Over the past two decades, this emerging single-molecule technique has been rapidly adopted to investigate the structural dynamics and biological functions of proteins. Despite this remarkable achievement, single-molecule fluorescence techniques must be extended to macromolecular protein complexes that are physiologically more relevant for functional studies. In this review, we present recent major breakthroughs for investigating protein complexes within cell extracts using single-molecule fluorescence. We outline the challenges, future prospects and potential applications of these new single-molecule fluorescence techniques in biological and clinical research. PMID:23200186

  19. Spin Hall separation of ultracold atom-molecule mixed gases

    NASA Astrophysics Data System (ADS)

    Ye, Chong; Fu, Li-Bin; Liu, Jie

    2016-05-01

    We propose a theoretical scheme to separate a molecular cloud from atoms in analogy to the spin Hall effect and to completely transfer Feshbach molecules to the ground state by applying a spatially modulated laser field to an atom-molecule mixed gas. In particular, the laser-molecule interaction induces a synthetic U(1) gauge potential for the dressed molecular dark state. Through numerical simulation, we demonstrate that such a gauge field leads to a spin Hall separation of atoms and molecules. In such a process, molecules can be transformed into the ground state completely.

  20. 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

  1. Single-molecule electrophoresis

    SciTech Connect

    Castro, A.; Shera, E.B.

    1995-09-15

    A novel method for the detection and identification of single molecules in solution has been devised, computer simulated, and experimentally achieved. The technique involves the determination of electrophoretic velocities by measuring the time required for individual molecules to travel a fixed distance between two laser beams. Computer simulations of the process were performed before-hand in order to estimate the experimental feasibility of the method and to determine the optimum values for the various experimental parameters. Examples of the use of the technique for the ultrasensitive detection and identification of rhodamine-6G, a mixture of DNA restriction fragments, and a mixture of proteins in aqueous solution are presented. 20 refs., 8 figs.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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. PMID:25638443

  7. 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.

  8. Molecules in interstellar clouds

    NASA Astrophysics Data System (ADS)

    Irvine, W. M.; Hjalmarson, A.; Rydbeck, O. E. H.

    The physical conditions and chemical compositions of the gas in interstellar clouds are reviewed in light of the importance of interstellar clouds for star formation and the origin of life. The Orion A region is discussed as an example of a giant molecular cloud where massive stars are being formed, and it is pointed out that conditions in the core of the cloud, with a kinetic temperature of about 75 K and a density of 100,000-1,000,000 molecules/cu cm, may support gas phase ion-molecule chemistry. The Taurus Molecular Clouds are then considered as examples of cold, dark, relatively dense interstellar clouds which may be the birthplaces of solar-type stars and which have been found to contain the heaviest interstellar molecules yet discovered. The molecular species identified in each of these regions are tabulated, including such building blocks of biological monomers as H2O, NH3, H2CO, CO, H2S, CH3CN and H2, and more complex species such as HCOOCH3 and CH3CH2CN.

  9. Epithelial Cell Adhesion Molecule

    PubMed Central

    Trzpis, Monika; McLaughlin, Pamela M.J.; de Leij, Lou M.F.H.; Harmsen, Martin C.

    2007-01-01

    The epithelial cell adhesion molecule (EpCAM, CD326) is a glycoprotein of ∼40 kd that was originally identified as a marker for carcinoma, attributable to its high expression on rapidly proliferating tumors of epithelial origin. Normal epithelia express EpCAM at a variable but generally lower level than carcinoma cells. In early studies, EpCAM was proposed to be a cell-cell adhesion molecule. However, recent insights revealed a more versatile role for EpCAM that is not limited only to cell adhesion but includes diverse processes such as signaling, cell migration, proliferation, and differentiation. Cell surface expression of EpCAM may actually prevent cell-cell adhesion. Here, we provide a comprehensive review of the current knowledge on EpCAM biology in relation to other cell adhesion molecules. We discuss the implications of the newly identified functions of EpCAM in view of its prognostic relevance in carcinoma, inflammatory pathophysiology, and tissue development and regeneration as well as its role in normal epithelial homeostasis. PMID:17600130

  10. Selective functionalization: Shields for small molecules

    NASA Astrophysics Data System (ADS)

    Silverman, Scott K.

    2012-10-01

    Nucleic acid aptamers have been employed to shield small molecules so that one among many similar reactive functional groups can be modified. This provides access to new chemical entities with potentially interesting properties while avoiding the use of covalent protecting groups.

  11. Bipolar Conductance Switching of Single Anthradithiophene Molecules.

    PubMed

    Borca, Bogdana; Schendel, Verena; Pétuya, Rémi; Pentegov, Ivan; Michnowicz, Tomasz; Kraft, Ulrike; Klauk, Hagen; Arnau, Andrés; Wahl, Peter; Schlickum, Uta; Kern, Klaus

    2015-12-22

    Single molecular switches are basic device elements in organic electronics. The pentacene analogue anthradithiophene (ADT) shows a fully reversible binary switching between different adsorption conformations on a metallic surface accompanied by a charge transfer. These transitions are activated locally in single molecules in a low-temperature scanning tunneling microscope . The switching induces changes between bistable orbital structures and energy level alignment at the interface. The most stable geometry, the "off" state, which all molecules adopt upon evaporation, corresponds to a short adsorption distance at which the electronic interactions of the acene rings bend the central part of the molecule toward the surface accompanied by a significant charge transfer from the metallic surface to the ADT molecules. This leads to a shift of the lowest unoccupied molecular orbital down to the Fermi level (EF). In the "on" state the molecule has a flat geometry at a larger distance from the surface; consequently the interaction is weaker, resulting in a negligible charge transfer with an orbital structure resembling the highest occupied molecular orbital when imaged close to EF. The potential barrier between these two states can be overcome reversibly by injecting charge carriers locally into individual molecules. Voltage-controlled current traces show a hysteresis characteristic of a bipolar switching behavior. The interpretation is supported by first-principles calculations. PMID:26580569

  12. Clusters of mobile molecules in supercooled water

    NASA Astrophysics Data System (ADS)

    Giovambattista, Nicolas; Buldyrev, Sergey V.; Stanley, H. Eugene; Starr, Francis W.

    2005-07-01

    We study the spatially heterogeneous dynamics in water via molecular dynamics simulations using the extended simple point charge potential. We identify clusters formed by mobile molecules and study their properties. We find that these clusters grow in size and become more compact as temperature decreases. We analyze the probability density function of cluster size, and we study the cluster correlation length. We find that clusters appear to be characterized by a fractal dimension consistent with that of lattice animals. We relate the cluster size and correlation length to the configurational entropy, Sconf . We find that these quantities depend weakly on 1/Sconf . In particular, the linearity found between the cluster mass n* and 1/Sconf suggests that n* may be interpreted as the mass of the cooperatively rearranging regions that form the basis of the Adam-Gibbs approach to the dynamics of supercooled liquids. We study the motion of molecules within a cluster, and find that each molecule preferentially follows a neighboring molecule in the same cluster. Based on this finding we hypothesize that stringlike cooperative motion may be a general mechanism for molecular rearrangement of complex, as well as simple liquids. By mapping each equilibrium configuration onto its corresponding local potential energy minimum or inherent structure (IS), we are able to compare the mobile molecule clusters in the equilibrium system with the molecules forming the clusters identified in the transitions between IS. We find that (i) mobile molecule clusters obtained by comparing different system configurations and (ii) clusters obtained by comparing the corresponding IS are completely different for short time scales, but are the same on the longer time scales of diffusive motion.

  13. Negative ions of polyatomic molecules.

    PubMed Central

    Christophorou, L G

    1980-01-01

    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. PMID:7428744

  14. Using small molecules to study big questions in cellular microbiology.

    PubMed

    Ward, Gary E; Carey, Kimberly L; Westwood, Nicholas J

    2002-08-01

    High-throughput screening of small molecules is used extensively in pharmaceutical settings for the purpose of drug discovery. In the case of antimicrobials, this involves the identification of small molecules that are significantly more toxic to the microbe than to the host. Only a small percentage of the small molecules identified in these screens have been studied in sufficient detail to explain the molecular basis of their antimicrobial effect. Rarer still are small molecule screens undertaken with the explicit goal of learning more about the biology of a particular microbe or the mechanism of its interaction with its host. Recent technological advances in small molecule synthesis and high-throughput screening have made such mechanism-directed small molecule approaches a powerful and accessible experimental option. In this article, we provide an overview of the methods and technical requirements and we discuss the potential of small molecule approaches to address important and often otherwise experimentally intractable problems in cellular microbiology. PMID:12174082

  15. Single-Molecule Sensors: Challenges and Opportunities for Quantitative Analysis.

    PubMed

    Gooding, J Justin; Gaus, Katharina

    2016-09-12

    Measurement science has been converging to smaller and smaller samples, such that it is now possible to detect single molecules. This Review focuses on the next generation of analytical tools that combine single-molecule detection with the ability to measure many single molecules simultaneously and/or process larger and more complex samples. Such single-molecule sensors constitute a new type of quantitative analytical tool, as they perform analysis by molecular counting and thus potentially capture the heterogeneity of the sample. This Review outlines the advantages and potential of these new, quantitative single-molecule sensors, the measurement challenges in making single-molecule devices suitable for analysis, the inspiration biology provides for overcoming these challenges, and some of the solutions currently being explored. PMID:27444661

  16. 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

  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. Leucocyte cellular adhesion molecules.

    PubMed

    Yong, K; Khwaja, A

    1990-12-01

    Leucocytes express adhesion promoting receptors which mediate cell-cell and cell-matrix interactions. These adhesive interactions are crucial to the regulation of haemopoiesis and thymocyte maturation, the direction and control of leucocyte traffic and migration through tissues, and in the development of immune and non-immune inflammatory responses. Several families of adhesion receptors have been identified (Table). The leucocyte integrin family comprises 3 alpha beta heterodimeric membrane glycoproteins which share a common beta subunit, designated CD18. The alpha subunits of each of the 3 members, lymphocyte function associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1) and p150,95 are designated CD11a, b and c respectively. These adhesion molecules play a critical part in the immune and inflammatory responses of leucocytes. The leucocyte integrin family is, in turn, part of the integrin superfamily, members of which are evolutionally, structurally and functionally related. Another Integrin subfamily found on leucocytes is the VLA group, so-called because the 'very late activation antigens' VLA-1 and VLA-2 were originally found to appear late in T-cell activation. Members of this family function mainly as extracellular matrix adhesion receptors and are found both on haemopoietic and non-haemopoietic cells. They play a part in diverse cellular functions including tissue organisation, lymphocyte recirculation and T-cell immune responses. A third integrin subfamily, the cytoadhesins, are receptors on platelets and endothelial cells which bind extracellular matrix proteins. A second family of adhesion receptors is the immunoglobulin superfamily, members of which include CD2, LFA-3 and ICAM-1, which participate in T-cell adhesive interactions, and the antigen-specific receptors of T and B cells, CD4, CD8 and the MHC Class I and II molecules. A recently recognised family of adhesion receptors is the selectins, characterised by a common lectin domain. Leucocyte

  19. Single Molecule Transcription Elongation

    PubMed Central

    Galburt, Eric A.; Grill, Stephan W.; Bustamante, Carlos

    2009-01-01

    Single molecule optical trapping assays have now been applied to a great number of macromolecular systems including DNA, RNA, cargo motors, restriction enzymes, DNA helicases, chromosome remodelers, DNA polymerases and both viral and bacterial RNA polymerases. The advantages of the technique are the ability to observe dynamic, unsynchronized molecular processes, to determine the distributions of experimental quantities and to apply force to the system while monitoring the response over time. Here, we describe the application of these powerful techniques to study the dynamics of transcription elongation by RNA polymerase II from Saccharomyces cerevisiae. PMID:19426807

  20. Electrostatic propulsion using C60 molecules

    NASA Technical Reports Server (NTRS)

    Leifer, Stephanie D.; Rapp, Donald; Saunders, Winston A.

    1992-01-01

    An evaluation is made of the potential benefits of C60 molecules as a basis for ion propulsion. Because C60 is storable, its use may result in a larger usable propellant fraction than previous methods of cluster ion propulsion. C60 may also relax such engineering constraints as grid spacing, which restrict the performance of noble gas ion propulsion. The behavior of C60 in a plasma discharge environment, as well as various electron impact cross sections of the molecule, will greatly afftect the feasibility of the concept.

  1. 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.

  2. 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.

  3. 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. PMID:26863450

  4. Detecting and identifying small molecules in a nanopore flux capacitor

    NASA Astrophysics Data System (ADS)

    Bearden, Samuel; McClure, Ethan; Zhang, Guigen

    2016-02-01

    A new method of molecular detection in a metallic-semiconductor nanopore was developed and evaluated with experimental and computational methods. Measurements were made of the charging potential of the electrical double layer (EDL) capacitance as charge-carrying small molecules translocated the nanopore. Signals in the charging potential were found to be correlated to the physical properties of analyte molecules. From the measured signals, we were able to distinguish molecules with different valence charge or similar valence charge but different size. The relative magnitude of the signals from different analytes was consistent over a wide range of experimental conditions, suggesting that the detected signals are likely due to single molecules. Computational modeling of the nanopore system indicated that the double layer potential signal may be described in terms of disruption of the EDL structure due to the size and charge of the analyte molecule, in agreement with Huckel and Debye’s analysis of the electrical atmosphere of electrolyte solutions.

  5. Analytic Empirical Potentials for BeH^+, BeD^+, and BeT^+ Including up to 4TH Order QED in the Long-Range and Predictions for the Halo Nucleonic Molecules 11BeH^+ and 14BeH^+.

    NASA Astrophysics Data System (ADS)

    Li Chun Fong, Lena C. M.; Lach, Grzegorz; Le Roy, Robert J.; Dattani, Nikesh S.

    2015-06-01

    The 13.81(8)s half-life of the halo nucleonic atom 11Be is orders of magnitude longer than those for any other halo nucleonic atom known, and makes Be-based diatomics the most promising candidates for the formation of the first halo nucleonic molecules. However, the 4e^- species LiH and BeH^+ are some of the first molecules for which the highest accuracy ab initio methods are not accessible, so empirical potential energy functions will be important for making predictions and for benchmarking how ab initio calculations break down at this transition from 3e^- to 4e^-. BeH^+ is also very light, and has one of the most extensive data sets involving a tritium isotopologue, making it a very useful benchmark for studying Born-Oppenheimer breakdown. We therefore seek to determine an empirical analytic potential energy function for BeH^+ that has as much precision as possible. To this end, all available spectroscopic data for all stable isotopologues of BeH^+ are analyzed in a standard direct-potential-fit procedure that uses least-squares fits to optimize the parameters defining an analytic potential. The ``Morse/Long-range'' (MLR) model used for the potential energy function incorporates the inverse-power long-range tail required by theory, and the calculation of the leading long-range coefficients C_4, C_6, C_7, and C_8 include non-adiabatic terms, and up to 4th order QED corrections. As a by-product, we have calculated some fundamental properties of 1e^- systems with unprecedented precision, such as the dipole, quadrupole, octupole, non-adiabatic, and mixed higher order polarizabilities of hydrogen, deuterium, and tritium. We provide good first estimates for the transition energies for the halo nucleonic species 11BeH^+ and 14BeH^+.

  6. X(3872) boson: Molecule or charmonium

    SciTech Connect

    Suzuki, Mahiko

    2005-12-01

    It has been argued that the mystery boson X(3872) is a molecule state consisting of primarily D{sup 0}D*{sup 0}+D{sup 0}D*{sup 0}. In contrast, apparent puzzles and potential difficulties have been pointed out for the charmonium assignment of X(3872). We examine several aspects of these alternatives by semiquantitative methods since quantitatively accurate results are often hard to reach on them. We 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 cc with DD*+DD* is taken into account.

  7. Hydrogen sulfide and polysulfides as signaling molecules.

    PubMed

    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

  8. 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

  9. Small Molecules in the Treatment of Psoriasis.

    PubMed

    Torres, Tiago; Filipe, Paulo

    2015-08-01

    Preclinical Research Psoriasis is an inflammatory systemic skin disease that affects various parts of the body requiring long-term management due to its chronic nature. Available treatment options include topical, systemic or biological therapies, which have long-term limitations associated to toxicity, tolerability and risk for adverse effects requiring its intermittent use and close monitoring. Small molecules modulate proinflammatory cytokines, selectively inhibit signaling pathways and showing potential to treat inflammatory diseases in patients not responding to conventional treatments. Presently, small molecules available are phosphodiesterase 4 inhibitors or Janus kinase inhibitors. Other small molecules under development for psoriasis include fumaric acid esters, amygdalin analogs, protein kinase C inhibitors, mitogen-activated protein kinase inhibitors, spleen protein kinase inhibitors, other tyrosine kinase inhibitors, sphingosine 1-phosphate receptor agonists, and A3 adenosine receptor agonists. These new treatment options represent important advances in the development of specific drugs to respond to the goals of treatment and improve patient quality of life. PMID:26255795

  10. 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.

  11. Connexin channel permeability to cytoplasmic molecules.

    PubMed

    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 approximately 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, 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

  12. 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.

  13. Ultracold molecules from the bottom-up

    NASA Astrophysics Data System (ADS)

    Zhang, Jessie T.; Hutzler, Nicholas R.; Liu, Lee R.; Yu, Yichao; Ni, Kang-Kuen

    2016-05-01

    Ultracold polar molecules exhibit strong, long-range, and tunable dipole-dipole interactions that may be utilized for a wide range of studies in quantum simulation and quantum information processing. To realize the full potential of these studies, it is desirable to have a low entropy sample of ultracold polar molecules with full control over both internal and external states, as well as inter-particle interactions. We work toward this goal with a new, bottom-up approach using the highly polar NaCs molecule. The key steps of our scheme are trapping single Na and Cs atoms in optical dipole traps, cooling the atoms to their motional ground state using Raman sideband cooling, and finally coherently transferring them to ground state NaCs molecules via a two-photon process. This approach should enable creation of low entropy samples with full control over all degrees of freedom, as well as realizing the possibility of single-site read-out and manipulation of molecules.

  14. Ultracold polar molecules near quantum degeneracy.

    PubMed

    Ospelkaus, S; Ni, K K; de Miranda, M H G; Neyenhuis, B; Wang, D; Kotochigova, S; Julienne, P S; Jin, D S; Ye, J

    2009-01-01

    We report the creation and characterization of a near quantum-degenerate gas of polar 40K-87Rb molecules in their absolute rovibrational ground state. Starting from weakly bound heteronuclear KRb Feshbach molecules, we implement precise control of the molecular electronic, vibrational, and rotational degrees of freedom with phase-coherent laser fields. In particular, we coherently transfer these weakly bound molecules across a 125 THz frequency gap in a single step into the absolute rovibrational ground state of the electronic ground potential. Phase coherence between lasers involved in the transfer process is ensured by referencing the lasers to two single components of a phase-stabilized optical frequency comb. Using these methods, we prepare a dense gas of 4 x 10(4) polar molecules at a temperature below 400 nK. This fermionic molecular ensemble is close to quantum degeneracy and can be characterized by a degeneracy parameter of T/T(F) = 3. We have measured the molecular polarizability in an optical dipole trap where the trap lifetime gives clues to interesting decay mechanisms. Given the large measured dipole moment of the KRb molecules of 0.5 Debye, the study of quantum degenerate molecular gases interacting via strong dipolar interactions is now within experimental reach. PACS numbers: 37.10.Mn, 37.10.Pq. PMID:20151553

  15. 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.

  16. Emerging small molecule drugs.

    PubMed

    Colin, Sophie; Chinetti-Gbaguidi, Giulia; Kuivenhoven, Jan A; Staels, Bart

    2015-01-01

    Dyslipidaemia is a major risk factor for cardiovascular diseases. Pharmacological lowering of LDL-C levels using statins reduces cardiovascular risk. However, a substantial residual risk persists especially in patients with type 2 diabetes mellitus. Because of the inverse association observed in epidemiological studies of HDL-C with the risk for cardiovascular diseases, novel therapeutic strategies to raise HDL-C levels or improve HDL functionality are developed as complementary therapy for cardiovascular diseases. However, until now most therapies targeting HDL-C levels failed in clinical trials because of side effects or absence of clinical benefits. This chapter will highlight the emerging small molecules currently developed and tested in clinical trials to pharmacologically modulate HDL-C and functionality including new CETP inhibitors (anacetrapib, evacetrapib), novel PPAR agonists (K-877, CER-002, DSP-8658, INT131 and GFT505), LXR agonists (ATI-111, LXR-623, XL-652) and RVX-208. PMID:25523004

  17. 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.

  18. Forces in molecules.

    PubMed

    Hernández-Trujillo, Jesús; Cortés-Guzmán, Fernando; Fang, De-Chai; Bader, Richard F W

    2007-01-01

    Chemistry is determined by the electrostatic forces acting within a collection of nuclei and electrons. The attraction of the nuclei for the electrons is the only attractive force in a molecule and is the force responsible for the bonding between atoms. This is the attractive force acting on the electrons in the Ehrenfest force and on the nuclei in the Feynman force, one that is countered by the repulsion between the electrons in the former and by the repulsion between the nuclei in the latter. The virial theorem relates these forces to the energy changes resulting from interactions between atoms. All bonding, as signified by the presence of a bond path, has a common origin in terms of the mechanics determined by the Ehrenfest, Feynman and virial theorems. This paper is concerned in particular with the mechanics of interaction encountered in what are classically described as 'nonbonded interactions'--are atoms that 'touch' bonded or repelling one another? PMID:17328425

  19. Manipulating transport through a single-molecule junction

    SciTech Connect

    Sotthewes, Kai; Heimbuch, René; Zandvliet, Harold J. W.

    2013-12-07

    Molecular Electronics deals with the realization of elementary electronic devices that rely on a single molecule. For electronic applications, the most important property of a single molecule is its conductance. Here we show how the conductance of a single octanethiol molecule can be measured and manipulated by varying the contact's interspace. This mechanical gating of the single molecule junction leads to a variation of the conductance that can be understood in terms of a tunable image charge effect. The image charge effect increases with a decrease of the contact's interspace due to a reduction of the effective potential barrier height of 1.5 meV/pm.

  20. Lesser-Known Molecules in Ovarian Carcinogenesis

    PubMed Central

    Lozneanu, Ludmila; Cojocaru, Elena; Giuşcă, Simona Eliza; Cărăuleanu, Alexandru; Căruntu, Irina-Draga

    2015-01-01

    Currently, the deciphering of the signaling pathways brings about new advances in the understanding of the pathogenic mechanism of ovarian carcinogenesis, which is based on the interaction of several molecules with different biochemical structure that, consequently, intervene in cell metabolism, through their role as regulators in proliferation, differentiation, and cell death. Given that the ensemble of biomarkers in OC includes more than 50 molecules the interest of the researchers focuses on the possible validation of each one's potential as prognosis markers and/or therapeutic targets. Within this framework, this review presents three protein molecules: ALCAM, c-FLIP, and caveolin, motivated by the perspectives provided through the current limited knowledge on their role in ovarian carcinogenesis and on their potential as prognosis factors. Their structural stability, once altered, triggers the initiation of the sequences characteristic for ovarian carcinogenesis, through their role as modulators for several signaling pathways, contributing to the disruption of cellular junctions, disturbance of pro-/antiapoptotic equilibrium, and alteration of transmission of the signals specific for the molecular pathways. For each molecule, the text is built as follows: (i) general remarks, (ii) structural details, and (iii) particularities in expression, from different tumors to landmarks in ovarian carcinoma. PMID:26339605

  1. Geranyl diphosphate synthase molecules, and nucleic acid molecules encoding same

    SciTech Connect

    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.

  2. Formation and analysis of ultracold polar molecules

    NASA Astrophysics Data System (ADS)

    Juarros, Elizabeth Ann

    Alkali hydride molecules are polar, exhibiting large ground-state dipole moments. As ultracold sources of alkali atoms, as well as hydrogen, have been created in the laboratory, we explore theoretically the feasibility of forming such molecules from a mixture of the ultracold atomic gases, employing various photoassociation schemes. In this work we use lithium and sodium hydride as benchmark systems to calculate molecule formation rates through stimulated one-photon radiative association directly from the continuum as well as two-photon stimulated radiative association (Raman transfer) and excitation to bound levels of an excited state followed by spontaneous emission to the ground state. Using accurate molecular potential energy curves and dipole transition moments and with laser intensities and MOT densities that are easily attainable experimentally, we have found that substantial molecule formation rates can be realized even after the effect of back-stimulation has been accounted for. We examine the spontaneous emission cascade which takes place from the upper vibrational levels of the singlet ground state on a time scale of milliseconds. Because photon emission in the cascade process does not contribute to trap loss, a sizable population of molecules in the lowest vibrational level can be achieved. The triplet ground electronic state is of particular interest for experimental efforts since, although it has never been observed experimentally, molecular structure calculations of the a3Sigma+ state for LiH and NaH predict a small van der Waals attraction, with a potential energy well so shallow that it can support only one bound rotational-vibrational level. Any molecule formed in the triplet ground state would then be immediately in the lowest and most stable level of that state and would be quite long-lived, unlike molecules in high vibrational levels which have significantly shorter lifetimes. As an analysis of our method of calculating molecule formation rates

  3. Theory of Long-Range Ultracold Atom-Molecule Photoassociation

    NASA Astrophysics Data System (ADS)

    Pérez-Ríos, Jesús; Lepers, Maxence; Dulieu, Olivier

    2015-08-01

    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 Cs2 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 Cs3 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.

  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. 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.

  6. Tunneling, diffusion, and dissociation of Feshbach molecules in optical lattices

    NASA Astrophysics Data System (ADS)

    Bailey, Taylor; Bertulani, Carlos A.; Timmermans, Eddy

    2012-03-01

    The quantum dynamics of an ultracold diatomic molecule tunneling and diffusing in a one-dimensional optical lattice exhibits unusual features. While it is known that the process of quantum tunneling through potential barriers can break up a bound-state molecule into a pair of dissociated atoms, interference and reassociation produce intricate patterns in the time-evolving site-dependent probability distribution for finding atoms and bound-state molecules. We find that the bound-state molecule is unusually resilient against break up at ultralow binding energy Eb (Eb much smaller than the barrier height of the lattice potential). After an initial transient, the bound-state molecule spreads with a width that grows as the square root of time. Surprisingly, the width of the probability of finding dissociated atoms does not increase with time as a power law.

  7. Reactions of oriented molecules.

    PubMed

    Brooks, P R

    1976-07-01

    Beams of oriented molecules have been used to directly study geometrical requirements in chemical reactions. These studies have shown that reactivity is much greater in some orientations than others and demonstrated the existence of steric effects. For some reactions portions of the orientation results are in good accord with traditional views of steric hindrance, but for others it is clear that our chemical intuition needs recalibrating. Indeed, the information gained from simultaneously orienting the reactants and observing the scattering angle of the products may lead to new insights about the detailed mechanism of certain reactions. Further work must be done to extend the scope and detail of the studies described here. More detailed information is needed on the CH(3)I reaction and the CF(3)I reaction. The effects of alkyl groups of various sizes and alkali metals of various sizes are of interest. In addition, reactions where a long-lived complex is formed should be studied to see if orientation is important. Finally, it would be of interest to apply the technique to the sort of reactions that led to our interest in the first place: the S(N)2 displacements in alkyl halides where the fascinating Walden inversion occurs. PMID:17793988

  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. Energy Transfer Involving Diatomic Molecules.

    NASA Astrophysics Data System (ADS)

    Gibbons, John Paul

    three colliding pairs, the experimental results lie between the results calculated for the same two sets of potential parameters. These parameters were those calculated to match the short range Lennard-Jones potential and a set obtained by a theoretical Thomas-Fermi treatment of the molecules.

  11. 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.

  12. Strongly interacting ultracold polar molecules

    NASA Astrophysics Data System (ADS)

    Gadway, Bryce; Yan, Bo

    2016-08-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole–dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  13. Adsorption kinetics of diatomic molecules.

    PubMed

    Burde, Jared T; Calbi, M Mercedes

    2014-05-01

    The adsorption dynamics of diatomic molecules on solid surfaces is examined by using a Kinetic Monte Carlo algorithm. Equilibration times at increasing loadings are obtained, and explained based on the elementary processes that lead to the formation of the adsorbed film. The ability of the molecules to change their orientation accelerates the overall uptake and leads to competitive kinetic behaviour between the different orientations. The dependence of the equilibration time on coverage follows the same decreasing trend obtained experimentally for ethane adsorption on closed-end carbon nanotube bundles. The exploration of molecule-molecule interaction effects on this trend provides relevant insights to understand the kinetic behaviour of other species, from simpler molecules to larger polyatomic molecules, adsorbing on surfaces with different binding strength. PMID:24654004

  14. Part I. Evaluation of thermodynamic and kinetic parameters for electron transfer and following chemical reaction from a global analysis of current-potential-time data. Part II. Electro-catalytic detection in high-performance liquid chromatography of vitamin B[sub 12] and other molecules of biological and environmental interest

    SciTech Connect

    Kumar, V.T.

    1992-01-01

    Simultaneous evaluation of electron transfer rate constant, k[sup 0], following chemical reaction rate constant, k[sub f], electron transfer coefficient, [alpha] and standard potential, E[sup 0][prime] for an electrochemical reaction following the EC mechanism is described. A mathematical model for the current response to a potential step is developed, starting with the Butler-Volmer equation for electrode kinetics and concentration expressions for the redox couple. The resulting integral equations are solved numerically via the Step Function method. Current-potential and current-time curves are simulated and tested under limiting conditions. The four parameters of the system are evaluated by fitting simulated current-voltage-time (i-E-t) surface to the theoretical equation. The method is applied to study an important biological molecule, viz., methyl cobalamin, in DMSO. Included in the discussion part is the use of kinetic zone diagrams to depict chronoamperometric current response as a function of dimensionless rate constants for the EC reaction scheme. This compact display of the influence of the two rate constants on current in all time windows can be used to select the best data for analysis. Theoretical limits of measurable rate constants can be estimated from the zone diagram. The development of a dropping mercury electrode detector for High Performance Liquid Chromatography (HPLC) and its application to analysis of B[sub 12] and other vitamins is described. This EC detector is able to achieve high levels of sensitivity by exploiting the catalytic hydrogen evolution undergone by many nitrogenous organic molecules. Vitamin B[sub 12], thiamine, riboflavin and niacinamide were analyzed individually and in mixtures on reverse phase C18 column. Preliminary results from the analysis of commercial multivitamin preparations are also discussed.

  15. Trapping Single Molecules by Dielectrophoresis

    NASA Astrophysics Data System (ADS)

    Hölzel, Ralph; Calander, Nils; Chiragwandi, Zackary; Willander, Magnus; Bier, Frank F.

    2005-09-01

    We have trapped single protein molecules of R-phycoerythrin in an aqueous solution by an alternating electric field. A radio frequency voltage is applied to sharp nanoelectrodes and hence produces a strong electric field gradient. The resulting dielectrophoretic forces attract freely diffusing protein molecules. Trapping takes place at the electrode tips. Switching off the field immediately releases the molecules. The electric field distribution is computed, and from this the dielectrophoretic response of the molecules is calculated using a standard polarization model. The resulting forces are compared to the impact of Brownian motion. Finally, we discuss the experimental observations on the basis of the model calculations.

  16. 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.

  17. 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).

  18. Coordination programming of photofunctional molecules.

    PubMed

    Sakamoto, Ryota; Kusaka, Shinpei; Hayashi, Mikihiro; Nishikawa, Michihiro; Nishihara, Hiroshi

    2013-01-01

    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. PMID:23563859

  19. Adhesion molecules in cutaneous inflammation.

    PubMed

    Barker, J N

    1995-01-01

    As in other organs, leukocyte adhesion molecules and their ligands play a major role in cutaneous inflammatory events both by directing leukocyte trafficking and by their effects on antigen presentation. Skin biopsies of inflamed skin from patients with diseases such as as psoriasis or atopic dermatitis reveal up-regulation of endothelial cell expression of P- and E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1. Studies of evolving lesions following UVB irradiation, Mantoux reaction or application of contact allergen, demonstrate that expression of these adhesion molecules parallels leukocyte infiltration into skin. When cutaneous inflammation is widespread (e.g. in erythroderma), soluble forms of these molecules are detectable in serum. In vitro studies predict that peptide mediators are important regulatory factors for endothelial adhesion molecules. Intradermal injection of the cytokines interleukin 1, tumour necrosis factor alpha and interferon gamma into normal human skin leads to induction of endothelial adhesion molecules with concomitant infiltration of leukocytes. In addition, neuropeptides rapidly induce P-selectin translocation to the cell membrane and expression of E-selectin. Adhesion molecules also play a crucial role as accessory molecules in the presentation of antigen to T lymphocytes by Langerhans' cells. Expression of selectin ligands by Langerhans' cells is up-regulated by various inflammatory stimuli, suggesting that adhesion molecules may be important in Langerhans' cell migration. The skin, because of its accessibility, is an ideal organ in which to study expression of adhesion molecules and their relationship to inflammatory events. Inflammatory skin diseases are common and inhibition of lymphocyte accumulation in skin is likely to prove of great therapeutic benefit. PMID:7587640

  20. Clusterization of water molecules as deduced from statistical mechanical approach

    NASA Astrophysics Data System (ADS)

    Krasnoholovets, Volodymyr

    2004-12-01

    Using the methods of statistical mechanics we have shown that a homogeneous water network is unstable and spontaneously disintegrates to the nonhomogeneous state (i.e. peculiar clusters), which can be treated as an ordinary state of liquid water. The major peculiarity of the concept is that it separates the paired potential into two independent components—the attractive potential and the repulsive one, which in turn should feature a very different dependence on the distance from the particle (a water molecule in the present case). We choose the interaction potential as a combination of the ionic crystal potential and the vibratory potential associated with the elastic properties of the water system as a whole. The number ℵ of water molecules that enters a cluster is calculated as a function of several parameters, such as the dielectric constant, the mass of a water molecule, the distance between nearest molecules, and the vibrations of nearest molecules in their nodes. The number of H2O molecules that comprise a cluster is estimated as about ℵ ≈ 900, which agrees with the available experimental data.

  1. 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.

  2. 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.

  3. Proregenerative Properties of ECM Molecules

    PubMed Central

    Plantman, Stefan

    2013-01-01

    After traumatic injuries to the nervous system, regrowing axons encounter a complex microenvironment where mechanisms that promote regeneration compete with inhibitory processes. Sprouting and axonal regrowth are key components of functional recovery but are often counteracted by inhibitory molecules. This review covers extracellular matrix molecules that support neuron axonal outgrowth. PMID:24195084

  4. 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)

  5. Enzyme molecules in solitary confinement.

    PubMed

    Liebherr, Raphaela B; Gorris, Hans H

    2014-01-01

    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. PMID:25221867

  6. 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.

  7. 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.

  8. 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. PMID:23836648

  9. Cold molecules, collisions and reactions

    NASA Astrophysics Data System (ADS)

    Hecker Denschlag, Johannes

    2016-05-01

    I will report on recent experiments of my group where we have been studying the formation of ultracold diatomic molecules and their subsequent inelastic/reactive collisions. For example, in one of these experiments we investigate collisions of triplet Rb2 molecules in the rovibrational ground state. We observe fast molecular loss and compare the measured loss rates to predictions based on universality. In another set of experiments we investigate the formation of (BaRb)+ molecules after three-body recombination of a single Ba+ ion with two Rb atoms in an ultracold gas of Rb atoms. Our investigations indicate that the formed (BaRb)+ molecules are weakly bound and that several secondary processes take place ranging from photodissociation of the (BaRb)+ molecule to reactive collisions with Rb atoms. I will explain how we can experimentally distinguish these processes and what the typical reaction rates are. Support from the German Research foundation DFG and the European Community is acknowledged.

  10. 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

  11. 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

  12. 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.

  13. Multichannel quantum defect theory for polar molecules

    NASA Astrophysics Data System (ADS)

    Elfimov, Sergei V.; Dorofeev, Dmitrii L.; Zon, Boris A.

    2014-02-01

    Our work is devoted to developing a general approach for nonpenetrating Rydberg states of polar molecules. We propose a method to estimate the accuracy of calculation of their wave functions and quantum defects. Basing on this method we estimate the accuracy of Born-Oppenheimer (BO) and inverse Born-Oppenheimer (IBO) approximations for these states. This estimation enables us to determine the space and energy regions where BO and IBO approximations are valid. It depends on the interplay between l coupling (due to dipole potential of the core) and l uncoupling (due to rotation the core). Next we consider the intermediate region where both BO and IBO are not valid. For this intermediate region we propose a modification of Fano's multichannel quantum defect theory to match BO and IBO wave functions and show that it gives more reliable results. They are demonstrated on the example of SO molecule.

  14. Single-molecule Studies of Riboswitch Folding

    PubMed Central

    Savinov, Andrew; Perez, Christian F.; Block, Steven M.

    2014-01-01

    The folding dynamics of riboswitches are central to their ability to modulate gene expression in response to environmental cues. In most cases, a structural competition between the formation of a ligand-binding aptamer and an expression platform (or some other competing off-state) determines the regulatory outcome. Here, we review single-molecule studies of riboswitch folding and function, predominantly carried out using single-molecule FRET or optical trapping approaches. Recent results have supplied new insights into riboswitch folding energy landscapes, the mechanisms of ligand binding, the roles played by divalent ions, the applicability of hierarchical folding models, and kinetic vs. thermodynamic control schemes. We anticipate that future work, based on improved data sets and potentially combining multiple experimental techniques, will enable the development of more complete models for complex RNA folding processes. PMID:24727093

  15. Friction mediated by redox-active supramolecular connector molecules.

    PubMed

    Bozna, B L; Blass, J; Albrecht, M; Hausen, F; Wenz, G; Bennewitz, R

    2015-10-01

    We report on a friction study at the nanometer scale using atomic force microscopy under electrochemical control. Friction arises from the interaction between two surfaces functionalized with cyclodextrin molecules. The interaction is mediated by connector molecules with (ferrocenylmethyl)ammonium end groups forming supramolecular complexes with the cyclodextrin molecules. With ferrocene connector molecules in solution, the friction increases by a factor of up to 12 compared to control experiments without connector molecules. The electrochemical oxidation of ferrocene to ferrocenium causes a decrease in friction owing to the lower stability of ferrocenium-cyclodextrin complex. Upon switching between oxidative and reduction potentials, a change in friction by a factor of 1.2-1.8 is observed. Isothermal titration calorimetry reveals fast dissociation and rebinding kinetics and thus an equilibrium regime for the friction experiments. PMID:26367352

  16. Static trapping of polar molecules in a traveling wave decelerator.

    PubMed

    Quintero-Pérez, Marina; Jansen, Paul; Wall, Thomas E; van den Berg, Joost E; Hoekstra, Steven; Bethlem, Hendrick L

    2013-03-29

    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. PMID:23581314

  17. 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)

  18. 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.

  19. Organic heterocyclic molecules become superalkalis.

    PubMed

    Reddy, G Naaresh; Giri, Santanab

    2016-09-21

    An organic molecule which behaves like a superalkali has been designed from an aromatic heterocyclic molecule, pyrrole. Using first-principles calculation and a systematic two-step approach, we can have superalkali molecules with a low ionization energy, even lower than that of Cs. Couple cluster (CCSD) calculation reveals that a new heterocycle, C3N2(CH3)5 derived from a well-known aromatic heterocycle, pyrrole (C4H5N) has an ionization energy close to 3.0 eV. A molecular dynamics calculation on C3N2(CH3)5 reveals that the structure is dynamically stable. PMID:27530344

  20. 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

  1. 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.

  2. 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

  3. Halogen bonds in biological molecules.

    PubMed

    Auffinger, Pascal; Hays, Franklin A; Westhof, Eric; Ho, P Shing

    2004-11-30

    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 C-X...O-Y interaction (C-X is a carbon-bonded chlorine, bromine, or iodine, and O-Y 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 A for Cl...O, 3.37 A for Br...O, and 3.50 A for I...O) and can conform to the geometry seen in small molecules, with the C-X...O angle approximately 165 degrees (consistent with a strong directional polarization of the halogen) and the X...O-Y angle approximately 120 degrees . 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 pi -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

  4. 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

  5. Sperm specific proteins-potential candidate molecules for fertility control

    PubMed Central

    Suri, Anil

    2004-01-01

    The increase in population growth rate warrants the development of additional contraceptive methods that are widely acceptable, free from side effects and less expensive. Immunocontraception, and in particular the targeting of antibodies to gamete-specific antigens implicated in sperm egg binding and fertilization, offers an attractive approach to control fertility. The development of a contraceptive vaccine based on sperm antigen represents a promising approach to contraception. In mammals, fertilization is completed by the direct interaction of sperm and egg, a process mediated primarily by sperm surface proteins. Sperm have proteins that are unique, cell specific, immunogenic and accessible to antibodies. A few of the sperm specific proteins have been isolated and characterized. The antibodies raised against the sperm specific antigens have proved to be extremely effective at reducing sperm-egg interaction in vitro; fertility trials in sub-human primates would eventually prove the effectiveness of the sperm antigens in terms of contraceptive efficacy. PMID:15012833

  6. 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)

  7. Surface chemistry of deuterated molecules

    NASA Astrophysics Data System (ADS)

    Tielens, A. G. G. M.

    1983-03-01

    The chemical composition of grain mantles is calculated in order to determine the concentration of deuterated molecules relative to their hydrogenated counterparts in grain mantles. The computation takes into account reactions involving deuterium in the gas phase and on grain surfaces. The results show that the abundance of deuterium molecules in grain mantles is much higher than expected on the basis of the cosmic abundance ratio of D to H. HDCO has a relatively high abundance in grain mantles as compared to other deuterated molecules, due to the fact that H abstraction from HDCO has a lower activation barrier than D abstraction. The infrared characteristics of the calculated grain mantles are discussed and observational tests of the model calcultions are suggested. The contribution of grain surface chemistry to the concentration of molecules in the gas phase is briefly considered.

  8. Cobalt single-molecule magnet

    NASA Astrophysics Data System (ADS)

    Yang, En-Che; Hendrickson, David N.; Wernsdorfer, Wolfgang; Nakano, Motohiro; Zakharov, Lev N.; Sommer, Roger D.; Rheingold, Arnold L.; Ledezma-Gairaud, Marisol; Christou, George

    2002-05-01

    A cobalt molecule that functions as a single-molecule magnet, [Co4(hmp)4(MeOH)4Cl4], where hmp- is the anion of hydroxymethylpyridine, is reported. The core of the molecule consists of four Co(II) cations and four hmp- oxygen atom ions at the corners of a cube. Variable-field and variable-temperature magnetization data have been analyzed to establish that the molecule has a S=6 ground state with considerable negative magnetoanisotropy. Single-ion zero-field interactions (DSz2) at each cobalt ion are the origin of the negative magnetoanisotropy. A single crystal of the compound was studied by means of a micro-superconducting quantum interference device magnetometer in the range of 0.040-1.0 K. Hysteresis was found in the magnetization versus magnetic field response of this single crystal.

  9. Spin tunneling in magnetic molecules

    NASA Astrophysics Data System (ADS)

    Kececioglu, Ersin

    In this thesis, we will focus on spin tunneling in a family of systems called magnetic molecules such as Fe8 and Mn12. This is comparatively new, in relation to other tunneling problems. Many issues are not completely solved and/or understood yet. The magnetic molecule Fe 8 has been observed to have a rich pattern of degeneracies in its magnetic spectrum. We focus on these degeneracies from several points of view. We start with the simplest anisotropy Hamiltonian to describe the Fe 8 molecule and extend our discussion to include higher order anisotropy terms. We give analytical expressions as much as we can, for the degeneracies in the semi-classical limit in both cases. We reintroduce jump instantons to the instanton formalism. Finally, we discuss the effect of the environment on the molecule. Our results, for all different models and techniques, agree well with both experimental and numerical results.

  10. 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

  11. Single-Molecule DNA Analysis

    NASA Astrophysics Data System (ADS)

    Efcavitch, J. William; Thompson, John F.

    2010-07-01

    The ability to detect single molecules of DNA or RNA has led to an extremely rich area of exploration of the single most important biomolecule in nature. In cases in which the nucleic acid molecules are tethered to a solid support, confined to a channel, or simply allowed to diffuse into a detection volume, novel techniques have been developed to manipulate the DNA and to examine properties such as structural dynamics and protein-DNA interactions. Beyond the analysis of the properties of nucleic acids themselves, single-molecule detection has enabled dramatic improvements in the throughput of DNA sequencing and holds promise for continuing progress. Both optical and nonoptical detection methods that use surfaces, nanopores, and zero-mode waveguides have been attempted, and one optically based instrument is already commercially available. The breadth of literature related to single-molecule DNA analysis is vast; this review focuses on a survey of efforts in molecular dynamics and nucleic acid sequencing.

  12. 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.

  13. Collisional decoherence of polar molecules

    NASA Astrophysics Data System (ADS)

    Walter, Kai; Stickler, Benjamin A.; Hornberger, Klaus

    2016-06-01

    The quantum state of motion of a large and rotating polar molecule can lose coherence through the collisions with gas atoms. We show how the associated quantum master equation for the center of mass can be expressed in terms of the orientationally averaged differential and total scattering cross sections, for which we provide approximate analytic expressions. The master equation is then utilized to quantify collisional decoherence in a interference experiment with polar molecules.

  14. Challenges and Opportunities for Small Molecule Aptamer Development

    PubMed Central

    McKeague, Maureen; DeRosa, Maria C.

    2012-01-01

    Aptamers are single-stranded oligonucleotides that bind to targets with high affinity and selectivity. Their use as molecular recognition elements has emerged as a viable approach for biosensing, diagnostics, and therapeutics. Despite this potential, relatively few aptamers exist that bind to small molecules. Small molecules are important targets for investigation due to their diverse biological functions as well as their clinical and commercial uses. Novel, effective molecular recognition probes for these compounds are therefore of great interest. This paper will highlight the technical challenges of aptamer development for small molecule targets, as well as the opportunities that exist for their application in biosensing and chemical biology. PMID:23150810

  15. Toward Triplet Ground State LiNa Molecules

    NASA Astrophysics Data System (ADS)

    Jamison, Alan; Rvachov, Timur; Jing, Li; Jiang, Yijun; Zwierlein, Martin; Ketterle, Wolfgang

    2015-05-01

    We present progress toward creation of ultracold ground-state triplet LiNa molecules. This molecule is expected to have a long lifetime in the triplet ground state due to its fermionic nature, large rotational constant, and weak spin-orbit coupling. The triplet state has both electric and magnetic dipole moments, affording unique opportunities in quantum simulation and ultracold chemistry. Our progress includes the first observation of triplet excited states in this molecule, achieved through photoassociation of ultracold mixtures of 6-Li and Na. We compare experimental results to a variety of near-dissociation expansions as well as ab initio potentials.

  16. Ultrasensitive detection and characterization of molecules with infrared plasmonic metamaterials

    PubMed Central

    Cheng, Fei; Yang, Xiaodong; Gao, Jie

    2015-01-01

    Infrared vibrational spectroscopy is an effective technique which enables the direct probe of molecular fingerprints, and such detection can be further enhanced by the emerging engineered plasmonic metamaterials. Here we experimentally demonstrate ultrasensitive detection and characterization of polymer molecules based on an asymmetric infrared plasmonic metamaterial, and quantitatively analyze the molecule detection sensitivity and molecule-structure interactions. A sharp, non-radiative Fano resonance supported by the plasmonic metamaterial exhibits strongly enhanced near-field, and the resonance frequency is tailored to match the vibrational fingerprint of the target molecule. By utilizing the near-field nature of the plasmonic excitation, significantly enhanced absorption signal of molecules in the infrared spectroscopy are obtained, enabling ultrasensitive detection of only minute quantities of organic molecules. The enhancement of molecular absorption up to 105 fold is obtained, and sensitive detection of molecules at zeptomole levels (corresponding to a few tens of molecules within a unit cell) is achieved with high signal-to-noise ratio in our experiment. The demonstrated infrared plasmonic metamaterial sensing platform offers great potential for improving the specificity and sensitivity of label-free, biochemical detection. PMID:26388404

  17. Photoionization of atoms and molecules. [of hydrogen, helium, and xenon

    NASA Technical Reports Server (NTRS)

    Samson, J. A. R.

    1976-01-01

    A literature review on the present state of knowledge in photoionization is presented. Various experimental techniques that have been developed to study photoionization, such as fluorescence and photoelectron spectroscopy, mass spectroscopy, are examined. Various atoms and molecules were chosen to illustrate these techniques, specifically helium and xenon atoms and hydrogen molecules. Specialized photoionization such as in positive and negative ions, excited states, and free radicals is also treated. Absorption cross sections and ionization potentials are also discussed.

  18. Non-adiabatic Dynamics of Molecules in Optical Cavities

    NASA Astrophysics Data System (ADS)

    Kowalewski, Markus; Bennett, Kochise; Mukamel, Shaul

    Molecular systems coupled to optical cavities are promising candidates for a novel kind of photo chemistry. Strong coupling to the vacuum field of the cavity can modify the potential energy surfaces opening up new reaction pathways. We present a derivation of the non-adiabatic couplings for single molecules in the strong coupling regime. The possibilities for photo chemistry are demonstrated for a set of model systems representing typical situations found in molecules. Supported by the Alexander von Humboldt Foundation.

  19. J-factors of short DNA molecules.

    PubMed

    Zoli, Marco

    2016-06-01

    The propensity of short DNA sequences to convert to the circular form is studied by a mesoscopic Hamiltonian method which incorporates both the bending of the molecule axis and the intrinsic twist of the DNA strands. The base pair fluctuations with respect to the helix diameter are treated as path trajectories in the imaginary time path integral formalism. The partition function for the sub-ensemble of closed molecules is computed by imposing chain end boundary conditions both on the radial fluctuations and on the angular degrees of freedom. The cyclization probability, the J-factor, proves to be highly sensitive to the stacking potential, mostly to its nonlinear parameters. We find that the J-factor generally decreases by reducing the sequence length (N) and, more significantly, below N = 100 base pairs. However, even for very small molecules, the J-factors remain sizeable in line with recent experimental indications. Large bending angles between adjacent base pairs and anharmonic stacking appear as the causes of the helix flexibility at short length scales. PMID:27276942

  20. Quantum Optics of Ultra-Cold Molecules

    NASA Astrophysics Data System (ADS)

    Meiser, D.; Miyakawa, T.; Uys, H.; Meystre, P.

    Quantum optics has been a major driving force behind the rapid experimental developments that have led from the first laser cooling schemes to the Bose-Einstein condensation (BEC) of dilute atomic and molecular gases. Not only has it provided experimentalists with the necessary tools to create ultra-cold atomic systems, but it has also provided theorists with a formalism and framework to describe them: many effects now being studied in quantum-degenerate atomic and molecular systems find a very natural explanation in a quantum optics picture. This article briefly reviews three such examples that find their direct inspiration in the trailblazing work carried out over the years by Herbert Walther, one of the true giants of that field. Specifically, we use an analogy with the micromaser to analyze ultra-cold molecules in a double-well potential; study the formation and dissociation dynamics of molecules using the passage time statistics familiar from superradiance and superfluorescence studies; and show how molecules can be used to probe higher-order correlations in ultra-cold atomic gases, in particular bunching and antibunching.

  1. Signaling Molecules: Hydrogen Sulfide and Polysulfide

    PubMed Central

    2015-01-01

    Abstract Significance: Hydrogen sulfide (H2S) has been recognized as a signaling molecule as well as a cytoprotectant. It modulates neurotransmission, regulates vascular tone, and protects various tissues and organs, including neurons, the heart, and kidneys, from oxidative stress and ischemia-reperfusion injury. H2S is produced from l-cysteine by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase. Recent Advances: In addition to these enzymes, we recently identified a novel pathway to produce H2S from d-cysteine, which involves d-amino acid oxidase (DAO) along with 3MST. These enzymes are localized in the cytoplasm, mitochondria, and peroxisomes. However, some enzymes translocate to organelles under specific conditions. Moreover, H2S-derived potential signaling molecules such as polysulfides and HSNO have been identified. Critical Issues: The physiological stimulations, which trigger the production of H2S and its derivatives and maintain their local levels, remain unclear. Future Directions: Understanding the regulation of the H2S production and H2S-derived signaling molecules and the specific stimuli that induce their release will provide new insights into the biology of H2S and therapeutic development in diseases involving these substances. Antioxid. Redox Signal. 22, 362–376. PMID:24800864

  2. Combining single-molecule manipulation and single-molecule detection.

    PubMed

    Cordova, Juan Carlos; Das, Dibyendu Kumar; Manning, Harris W; Lang, Matthew J

    2014-10-01

    Single molecule force manipulation combined with fluorescence techniques offers much promise in revealing mechanistic details of biomolecular machinery. Here, we review force-fluorescence microscopy, which combines the best features of manipulation and detection techniques. Three of the mainstay manipulation methods (optical traps, magnetic traps and atomic force microscopy) are discussed with respect to milestones in combination developments, in addition to highlight recent contributions to the field. An overview of additional strategies is discussed, including fluorescence based force sensors for force measurement in vivo. Armed with recent exciting demonstrations of this technology, the field of combined single-molecule manipulation and single-molecule detection is poised to provide unprecedented views of molecular machinery. PMID:25255052

  3. Raman Optical Activity Spectra for Large Molecules through Molecules-in-Molecules Fragment-Based Approach.

    PubMed

    Jovan Jose, K V; Raghavachari, Krishnan

    2016-02-01

    We present an efficient method for the calculation of the Raman optical activity (ROA) spectra for large molecules through the molecules-in-molecules (MIM) fragment-based method. The relevant higher energy derivatives from smaller fragments are used to build the property tensors of the parent molecule to enable the extension of the MIM method for evaluating ROA spectra (MIM-ROA). Two factors were found to be particularly important in yielding accurate results. First, the link-atom tensor components are projected back onto the corresponding host and supporting atoms through the Jacobian projection method, yielding a mathematically rigorous method. Second, the long-range interactions between fragments are taken into account by using a less computationally expensive lower level of theory. The performance of the MIM-ROA model is calibrated on the enantiomeric pairs of 10 carbohydrate benchmark molecules, with strong intramolecular interactions. The vibrational frequencies and ROA intensities are accurately reproduced relative to the full, unfragmented, results for these systems. In addition, the MIM-ROA method is employed to predict the ROA spectra of d-maltose, α-D-cyclodextrin, and cryptophane-A, yielding spectra in excellent agreement with experiment. The accuracy and performance of the benchmark systems validate the MIM-ROA model for exploring ROA spectra of large molecules. PMID:26760444

  4. Measuring an antibody affinity distribution molecule by molecule

    SciTech Connect

    Bradbury, Andrew M; Werner, James H; Temirov, Jamshid

    2008-01-01

    Single molecule fluorescence mIcroscopy was used to observe the binding and unbinding of hapten decorated quantum dots with individual surface immobilized antibodies. The fluorescence time history from an individual antibody site can be used to calculate its binding affinity. While quantum dot blinking occurs during these measurements, we describe a simple empirical method to correct the apparent/observed affinity to account for the blinking contribution. The combination of many single molecule affinity measurements from different antibodies yields not only the average affinity, it directly measures the full shape and character of the surface affinity distribution function.

  5. Electron Collisions with Large Molecules

    NASA Astrophysics Data System (ADS)

    McKoy, Vincent

    2006-10-01

    In recent years, interest in electron-molecule collisions has increasingly shifted to large molecules. Applications within the semiconductor industry, for example, require electron collision data for molecules such as perfluorocyclobutane, while almost all biological applications involve macromolecules such as DNA. A significant development in recent years has been the realization that slow electrons can directly damage DNA. This discovery has spurred studies of low-energy collisions with the constituents of DNA, including the bases, deoxyribose, the phosphate, and larger moieties assembled from them. In semiconductor applications, a key goal is development of electron cross section sets for plasma chemistry modeling, while biological studies are largely focused on understanding the role of localized resonances in inducing DNA strand breaks. Accurate calculations of low-energy electron collisions with polyatomic molecules are computationally demanding because of the low symmetry and inherent many-electron nature of the problem; moreover, the computational requirements scale rapidly with the size of the molecule. To pursue such studies, we have adapted our computational procedure, known as the Schwinger multichannel method, to run efficiently on highly parallel computers. In this talk, we will present some of our recent results for fluorocarbon etchants used in the semiconductor industry and for constituents of DNA and RNA. In collaboration with Carl Winstead, California Institute of Technology.

  6. Spectroscopic modeling of water molecule

    NASA Astrophysics Data System (ADS)

    Danylo, R. I.; Okhrimenko, B. A.

    2013-12-01

    This research is devoted to the vibrational spectroscopy inverse problem solution that gives a possibility to design a molecule and make conclusions about its geometry. The valence angle finding based on the usage of inverse spectral vibrational spectroscopy problem is a well-known task. 3N-matrix method was chosen to solve the proposed task. The usage of this method permits to make no assumptions about the molecule force field, besides it can be applied to molecules of matter in liquid state. Anharmonicity constants assessment is an important part of the valence angle finding. The reduction to zero vibrations is necessary because used matrix analytical expression were found in the harmonic approach. In order to find the single-valued inverse spectral problem of vibrational spectroscopy solution a shape parameter characterizing "mixing" of ω1 and ω2 vibrations forms must be found. The minimum of such a function Υ called a divergence parameter was found. This function characterizes method's accuracy. The valence angle assessment was reduced to the divergence parameter minimization. The β value concerning divergence parameter minimum was interpreted as the desired valence angle. The proposed method was applied for water molecule in liquid state: β = (88,8 ±1,7)° . The found angle fits the water molecule nearest surrounding tetrahedral model including hydrogen bond curvature in the first approximation.

  7. A quantum gas of polar molecules in an optical lattice

    NASA Astrophysics Data System (ADS)

    Moses, Steven A.

    Ultracold polar molecules, because of their long-range, spatially anisotropic interactions, are a new quantum system in which to study novel many-body phenomena. In our lab, we have produced the first quantum gas of 40K 87Rb polar molecules. These molecules were found to undergo exothermic chemical reactions, and this led to interesting studies of chemistry near absolute zero. By creating the molecules at individual sites of a 3D optical lattice, we completely suppress these chemical reactions, and the polar molecule gas becomes stable and lives for tens of seconds. This thesis documents our efforts to explore coherent, many-body phenomena resulting from long-range dipolar interactions in the lattice. By encoding a spin-1/2 system in the rotational states of the molecules, we were able to realize spin-exchange interactions based on a spin Hamiltonian, which is one of the first steps in studying quantum magnetism with polar molecules. While this study was the first realization of such coherent dipolar interactions with polar molecules in a lattice, its full potential was limited by the low lattice filling fractions. Using our ability to exquisitely control the initial atomic gas mixture, we loaded a Mott insulator of Rb and a band insulator of K into the lattice. This quantum synthesis approach led to significantly higher molecular filling fractions and represents the first fully connected system of polar molecules in an optical lattice. This low-entropy quantum gas of polar molecules opens the door to interesting quantum simulations, which should be attainable in the next generation of the experiment.

  8. Room temperature single molecule microscopes

    SciTech Connect

    Ambrose, W.P.; Goodwin, P.M.; Enderlein, G.; Semin, D.J.; Keller, R.A.

    1997-12-31

    We have developed three capabilities to image the locations of and interrogate immobilized single fluorescent molecules: near-field scanning optical, confocal scanning optical, and wide-field epi-fluorescence microscopy. Each microscopy has its own advantages. Near-field illumination can beat the diffraction limit. Confocal microscopy has high brightness and temporal resolution. Wide-field has the quickest (parallel) imaging capability. With confocal microscopy, we have verified that single fluorescent spots in our images are due to single molecules by observing photon antibunching. Using all three microscopies, we have observed that xanthene molecules dispersed on dry silica curiously exhibit intensity fluctuations on millisecond to minute time scales. We are exploring the connection between the intensity fluctuations and fluctuations in individual photophysical parameters. The fluorescence lifetimes of Rhodamine 6G on silica fluctuate. The complex nature of the intensity and lifetime fluctuations is consistent with a mechanism that perturbs more than one photophysical parameter.

  9. Guidance molecules in lung cancer

    PubMed Central

    Nasarre, Patrick; Potiron, Vincent; Drabkin, Harry

    2010-01-01

    Guidance molecules were first described in the nervous system to control axon outgrowth direction. They are also widely expressed outside the nervous system where they control cell migration, tissue development and establishment of the vascular network. In addition, they are involved in cancer development, tumor angiogenesis and metastasis. This review is primarily focused on their functions in lung cancer and their involvement in lung development is also presented. Five guidance molecule families and their corresponding receptors are described, including the semaphorins/neuropilins/plexins, ephrins and Eph receptors, netrin/DCC/UNC5, Slit/Robo and Notch/Delta. In addition, the possibility to target these molecules as a therapeutic approach in cancer is discussed. PMID:20139699

  10. Orbital molecules in electronic materials

    SciTech Connect

    Attfield, J. Paul

    2015-04-01

    Orbital molecules are made up of coupled orbital states on several metal ions within an orbitally ordered (and sometimes also charge-ordered) solid such as a transition metal oxide. Spin-singlet dimers are known in many materials, but recent discoveries of more exotic species such as 18-electron heptamers in AlV{sub 2}O{sub 4} and magnetic 3-atom trimerons in magnetite (Fe{sub 3}O{sub 4}) have shown that orbital molecules constitute a general new class of quantum electronic states in solids.

  11. Dipolar molecules in optical lattices.

    PubMed

    Sowiński, Tomasz; Dutta, Omjyoti; Hauke, Philipp; Tagliacozzo, Luca; Lewenstein, Maciej

    2012-03-16

    We study the extended Bose-Hubbard model describing an ultracold gas of dipolar molecules in an optical lattice, taking into account all on-site and nearest-neighbor interactions, including occupation-dependent tunneling and pair tunneling terms. Using exact diagonalization and the multiscale entanglement renormalization ansatz, we show that these terms can destroy insulating phases and lead to novel quantum phases. These considerable changes of the phase diagram have to be taken into account in upcoming experiments with dipolar molecules. PMID:22540482

  12. Piezoresistivity in single DNA molecules

    PubMed Central

    Bruot, Christopher; Palma, Julio L.; Xiang, Limin; Mujica, Vladimiro; Ratner, Mark A.; Tao, Nongjian

    2015-01-01

    Piezoresistivity is a fundamental property of materials that has found many device applications. Here we report piezoresistivity in double helical DNA molecules. By studying the dependence of molecular conductance and piezoresistivity of single DNA molecules with different sequences and lengths, and performing molecular orbital calculations, we show that the piezoresistivity of DNA is caused by force-induced changes in the π–π electronic coupling between neighbouring bases, and in the activation energy of hole hopping. We describe the results in terms of thermal activated hopping model together with the ladder-based mechanical model for DNA proposed by de Gennes. PMID:26337293

  13. Piezoresistivity in single DNA molecules

    NASA Astrophysics Data System (ADS)

    Bruot, Christopher; Palma, Julio L.; Xiang, Limin; Mujica, Vladimiro; Ratner, Mark A.; Tao, Nongjian

    2015-09-01

    Piezoresistivity is a fundamental property of materials that has found many device applications. Here we report piezoresistivity in double helical DNA molecules. By studying the dependence of molecular conductance and piezoresistivity of single DNA molecules with different sequences and lengths, and performing molecular orbital calculations, we show that the piezoresistivity of DNA is caused by force-induced changes in the π-π electronic coupling between neighbouring bases, and in the activation energy of hole hopping. We describe the results in terms of thermal activated hopping model together with the ladder-based mechanical model for DNA proposed by de Gennes.

  14. Piezoresistivity in single DNA molecules.

    PubMed

    Bruot, Christopher; Palma, Julio L; Xiang, Limin; Mujica, Vladimiro; Ratner, Mark A; Tao, Nongjian

    2015-01-01

    Piezoresistivity is a fundamental property of materials that has found many device applications. Here we report piezoresistivity in double helical DNA molecules. By studying the dependence of molecular conductance and piezoresistivity of single DNA molecules with different sequences and lengths, and performing molecular orbital calculations, we show that the piezoresistivity of DNA is caused by force-induced changes in the π-π electronic coupling between neighbouring bases, and in the activation energy of hole hopping. We describe the results in terms of thermal activated hopping model together with the ladder-based mechanical model for DNA proposed by de Gennes. PMID:26337293

  15. Circulating adhesion molecules in obstructive sleep apnea and cardiovascular disease

    PubMed Central

    Pak, Victoria M.; Grandner, Michael A.; Pack, Allan I.

    2013-01-01

    SUMMARY Over 20 years of evidence indicates a strong association between obstructive sleep apnea (OSA) and cardiovascular disease. Although inflammatory processes have been heavily implicated as an important link between the two, the mechanism for this has not been conclusively established. Atherosclerosis may be one of the mechanisms linking OSA to cardiovascular morbidity. This review addresses the role of circulating adhesion molecules in patients with OSA, and how these may be part of the link between cardiovascular disease and OSA. There is evidence for the role of adhesion molecules in cardiovascular disease risk. Some studies, albeit with small sample sizes, also show higher levels of adhesion molecules in patients with OSA compared to controls. There are also studies that show that levels of adhesion molecules diminish with continuous positive airway pressure therapy. Limitations of these studies include small sample sizes, cross-sectional sampling, and inconsistent control for confounding variables known to influence adhesion molecule levels. There are potential novel therapies to reduce circulating adhesion molecules in patients with OSA to diminish cardiovascular disease. Understanding the role of cell adhesion molecules generated in OSA will help elucidate one mechanistic link to cardiovascular disease in patients with OSA. PMID:23618532

  16. Comets as a possible source of prebiotic molecules

    NASA Technical Reports Server (NTRS)

    Huebner, W. F.; Boice, D. C.

    1992-01-01

    Prebiotic molecules derive from abiotic organic molecules, radicals, and ions that pervade the universe at temperatures as high as several 1000 K. Here we review the role of organic molecules that condensed at low temperatures before or during comet formation in the early history of the Solar System. Recent spacecraft encounters and ground-based observations of carbon-rich volatile and dust components of comet comae provide a broad database for the investigation of these organic molecules. New laboratory data for some potential cometary organics are presented. Probable icy organic constituents of the nucleus and CHON particles as likely candidates for the distributed sources of gas-phase organic species in the coma are discussed. There is broad agreement that many organic molecules observed in the coma originate from the dust that must have existed in the solar nebula at the time and place of comet formation. We conclude that complex organic molecules found in comets may be a source of prebiotic molecules that led to the origins of life.

  17. Modeling sympathetic cooling of molecules by ultracold atoms

    NASA Astrophysics Data System (ADS)

    Lim, Jongseok; Frye, Matthew D.; Hutson, Jeremy M.; Tarbutt, M. R.

    2015-11-01

    We model sympathetic cooling of ground-state CaF molecules by ultracold Li and Rb atoms. The molecules are moving in a microwave trap, while the atoms are trapped magnetically. We calculate the differential elastic cross sections for CaF-Li and CaF-Rb collisions, using model Lennard-Jones potentials adjusted to give typical values for the s -wave scattering length. Together with trajectory calculations, these differential cross sections are used to simulate the cooling of the molecules, the heating of the atoms, and the loss of atoms from the trap. We show that a hard-sphere collision model based on an energy-dependent momentum transport cross section accurately predicts the molecule cooling rate but underestimates the rates of atom heating and loss. Our simulations suggest that Rb is a more effective coolant than Li for ground-state molecules, and that the cooling dynamics is less sensitive to the exact value of the s -wave scattering length when Rb is used. Using realistic experimental parameters, we find that molecules can be sympathetically cooled to 100 μ K in about 10 s. By applying evaporative cooling to the atoms, the cooling rate can be increased and the final temperature of the molecules can be reduced to 1 μ K within 30 s.

  18. Spectroscopy, reaction, and photodissociation in highly vibrationally excited molecules

    SciTech Connect

    Not Available

    1991-01-01

    Highly vibrationally excited molecules often control the course of chemical reactions in the atmosphere, combustion, plasmas, and many other environments. The research described in this Progress Report uses laser excitation and interrogation techniques to study and control the dynamics of highly vibrationally excited molecules. In particular, they show that it is possible to unravel the details and influence the course of photodissociation and bimolecular reaction. The experiments use laser excitation of overtone vibrations to prepare highly vibrationally excited molecules, frequently with single quantum state resolution, and laser spectroscopy to monitor the subsequent behavior of the excited molecule. We have studied the vibrationally mediated photodissociation and the bond- and state-selected bimolecular reaction of highly vibrationally excited molecules. In the first process, one photon creates a highly excited molecule, a second photon from another laser dissociates it, and light from a third laser detects the population of individual product quantum states. This approach allows us to explore otherwise inaccessible regions of the ground and excited state potential energy surface and, by exciting to the proper regions of the surface, to control the breaking of a selected chemical bond. In the second process, the highly vibrationally excited molecule reacts with an atom formed either in a microwave discharge or by photolysis and another laser interrogates the products. We have used this approach to demonstrate mode- and bond-selected bimolecular reactions in which the initial excitation controls the subsequent chemistry. 30 refs., 8 figs.

  19. Ultralong-range triatomic Rydberg molecules in an electric field

    NASA Astrophysics Data System (ADS)

    Aguilera Fernández, Javier; Schmelcher, Peter; González-Férez, Rosario

    2016-06-01

    We investigate the electronic structure of a triatomic Rydberg molecule formed by a Rydberg atom and two neutral ground-state atoms. Taking into account the s-wave and p-wave interactions, we perform electronic structure calculations and analyze the adiabatic electronic potentials evolving from the Rb (n=35,l≥slant 3) Rydberg degenerate manifold. We hereby focus on three different classes of geometries of the Rydberg molecules, including symmetric, asymmetric and planar configurations. The metamorphosis of these potential energy surfaces in the presence of an external electric field is explored.

  20. Diatomic molecules in optical and microwave dipole traps

    SciTech Connect

    Lysebo, Marius; Veseth, Leif

    2011-03-15

    The dipole forces on rotating diatomic molecules are worked out in detail for optical as well as microwave radiation fields. The objective is in particular to investigate how the dipole forces and potentials depend on the subtle internal structure of the molecule, with special emphasis on hyperfine and Zeeman states. Dipole potentials are obtained from computations of the real part of the complex molecular polarizability, whereas the imaginary part yields the scattering force. Numerical examples are presented for {sup 23}Na{sub 2} and OH for optical (laser) fields related to strong electronic transitions and for microwave fields for the {Lambda} doubling in the OH ground state.

  1. Control of vascular permeability by adhesion molecules.

    PubMed

    Sarelius, Ingrid H; Glading, Angela J

    2015-01-01

    Vascular permeability is a vital function of the circulatory system that is regulated in large part by the limited flux of solutes, water, and cells through the endothelial cell layer. One major pathway through this barrier is via the inter-endothelial junction, which is driven by the regulation of cadherin-based adhesions. The endothelium also forms attachments with surrounding proteins and cells via 2 classes of adhesion molecules, the integrins and IgCAMs. Integrins and IgCAMs propagate activation of multiple downstream signals that potentially impact cadherin adhesion. Here we discuss the known contributions of integrin and IgCAM signaling to the regulation of cadherin adhesion stability, endothelial barrier function, and vascular permeability. Emphasis is placed on known and prospective crosstalk signaling mechanisms between integrins, the IgCAMs- ICAM-1 and PECAM-1, and inter-endothelial cadherin adhesions, as potential strategic signaling nodes for multipartite regulation of cadherin adhesion. PMID:25838987

  2. Rotational transitions in compound muonic molecules

    SciTech Connect

    Padial, N.T.; Cohen, J.S.; Walker, R.B.

    1988-01-15

    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 H/sub 2/-H/sub 2/ potential, and the R-matrix propagation method is used to solve the set of coupled collisional equations for the systems D/sub 2/+((dt..mu..)dee), D/sub 2/+((dd..mu..)dee), T/sub 2/+((dt..mu..)dee), D/sub 2/+((dt..mu..)tee), and H/sub 2/+((dd..mu..)pee). Calculations are also done on H/sub 2/+HD and D/sub 2/+HD for comparison with previous work.

  3. Toroidal nanotraps for cold polar molecules

    DOE PAGESBeta

    Salhi, Marouane; Passian, Ali; Siopsis, George

    2015-09-14

    Electronic excitations in metallic nanoparticles in the optical regime that have been of great importance in surface-enhanced spectroscopy and emerging applications of molecular plasmonics, due to control and confinement of electromagnetic energy, may also be of potential to control the motion of nanoparticles and molecules. Here, we propose a concept for trapping polarizable particles and molecules using toroidal metallic nanoparticles. Specifically, gold nanorings are investigated for their scattering properties and field distribution to computationally show that the response of these optically resonant particles to incident photons permit the formation of a nanoscale trap when proper aspect ratio, photon wavelength, andmore » polarization are considered. However, interestingly the resonant plasmonic response of the nanoring is shown to be detrimental to the trap formation. The results are in good agreement with analytic calculations in the quasistatic limit within the first-order perturbation of the scalar electric potential. The possibility of extending the single nanoring trapping properties to two-dimensional arrays of nanorings is suggested by obtaining the field distribution of nanoring dimers and trimers.« less

  4. Toroidal nanotraps for cold polar molecules

    NASA Astrophysics Data System (ADS)

    Salhi, Marouane; Passian, Ali; Siopsis, George

    2015-09-01

    Electronic excitations in metallic nanoparticles in the optical regime that have been of great importance in surface-enhanced spectroscopy and emerging applications of molecular plasmonics, due to control and confinement of electromagnetic energy, may also be of potential to control the motion of nanoparticles and molecules. Here, we propose a concept for trapping polarizable particles and molecules using toroidal metallic nanoparticles. Specifically, gold nanorings are investigated for their scattering properties and field distribution to computationally show that the response of these optically resonant particles to incident photons permit the formation of a nanoscale trap when proper aspect ratio, photon wavelength, and polarization are considered. However, interestingly the resonant plasmonic response of the nanoring is shown to be detrimental to the trap formation. The results are in good agreement with analytic calculations in the quasistatic limit within the first-order perturbation of the scalar electric potential. The possibility of extending the single nanoring trapping properties to two-dimensional arrays of nanorings is suggested by obtaining the field distribution of nanoring dimers and trimers.

  5. Toroidal nanotraps for cold polar molecules

    SciTech Connect

    Salhi, Marouane; Passian, Ali; Siopsis, George

    2015-09-14

    Electronic excitations in metallic nanoparticles in the optical regime that have been of great importance in surface-enhanced spectroscopy and emerging applications of molecular plasmonics, due to control and confinement of electromagnetic energy, may also be of potential to control the motion of nanoparticles and molecules. Here, we propose a concept for trapping polarizable particles and molecules using toroidal metallic nanoparticles. Specifically, gold nanorings are investigated for their scattering properties and field distribution to computationally show that the response of these optically resonant particles to incident photons permit the formation of a nanoscale trap when proper aspect ratio, photon wavelength, and polarization are considered. However, interestingly the resonant plasmonic response of the nanoring is shown to be detrimental to the trap formation. The results are in good agreement with analytic calculations in the quasistatic limit within the first-order perturbation of the scalar electric potential. The possibility of extending the single nanoring trapping properties to two-dimensional arrays of nanorings is suggested by obtaining the field distribution of nanoring dimers and trimers.

  6. Spin-crossover molecule based thermoelectric junction

    SciTech Connect

    Ghosh, Dibyajyoti; Parida, Prakash; Pati, Swapan K.

    2015-05-11

    Using ab-initio numerical methods, we explore the spin-dependent transport and thermoelectric properties of a spin-crossover molecule (i.e., iron complex of 2-(1H-pyrazol-1-yl)-6-(1H-tetrazole-5-yl)pyridine) based nano-junction. We demonstrate a large magnetoresistance, efficient conductance-switching, and spin-filter activity in this molecule-based two-terminal device. The spin-crossover process also modulates the thermoelectric entities. It can efficiently switch the magnitude as well as spin-polarization of the thermocurrent. We find that thermocurrent is changed by ∼4 orders of magnitude upon spin-crossover. Moreover, it also substantially affects the thermopower and consequently, the device shows extremely efficient spin-crossover magnetothermopower generation. Furthermore, by tuning the chemical potential of electrodes into a certain range, a pure spin-thermopower can be achieved for the high-spin state. Finally, the reasonably large values of figure-of-merit in the presence and absence of phonon demonstrate a large heat-to-voltage conversion efficiency of the device. We believe that our study will pave an alternative way of tuning the transport and thermoelectric properties through the spin-crossover process and can have potential applications in generation of spin-dependent current, information storage, and processing.

  7. Quantum monodromy and quantum phase transitions in floppy molecules

    NASA Astrophysics Data System (ADS)

    Larese, Danielle

    2012-10-01

    A simple algebraic Hamiltonian has been used to explore the vibrational and rotational spectra of the skeletal bending modes of HCNO, BrCNO, NCNCS, and other "floppy" (quasi-linear or quasi-bent) molecules. These molecules have large-amplitude, low-energy bending modes and champagne-bottle potential surfaces, making them good candidates for observing quantum phase transitions (QPT). We describe the geometric phase transitions from bent to linear in these and other non-rigid molecules, quantitatively analyzing the spectroscopic signatures of ground state QPT, excited state QPT, and quantum monodromy. The algebraic framework is ideal for this work because of its small calculational effort yet robust results. Although these methods have historically found success with tri-and four-atomic molecules, we now address five-atomic and simple branched molecules such as CH3NCO and GeH3NCO. Extraction of potential functions are completed for several molecules, resulting in predictions of barriers to linearity and equilibrium bond angles.

  8. Towards inclusion of excited vibrational states in ultracold molecule-molecule quantum scattering calculations

    NASA Astrophysics Data System (ADS)

    Ticknor, Christopher; Kendrick, Brian

    2016-05-01

    We report progress towards including excited vibrational states in quantum scattering calculations of NaK-NaK at ultracold temperatures. We systematically use all pair potentials to build a complete 4 body potential energy surface. We study this 4-body potential and the asymptotic ro-vibrational 2-body basis. This allows for a more complete interaction as two molecules approach each other. We study where and how vibrationally excited states influence the asymptotic 2-body ro-vibrational scattering potentials. This work is an intermediate step in performing the complete scattering calculations as we develop tools to bring together the long range, ultracold 2-body scattering problem and the short range 4-body quantum chemistry problem.

  9. One-photon-assisted formation of ultracold polar molecules

    NASA Astrophysics Data System (ADS)

    Juarros, Elizabeth; Pellegrini, Philippe; Kirby, Kate; Côté, Robin

    2006-04-01

    Alkali-metal hydride molecules have large dipole moments in their ground electronic states. We explore the possibility of forming such molecules from a mixture of the ultracold atomic gases, employing a one-photon stimulated radiative association process. Using accurate molecular potential-energy curves and dipole moments, we have calculated the rate coefficients for populating each of the vibrational levels of the XΣ+1 states of LiH and NaH. We have found that significant molecule formation rates into the upper vibrational levels can be realized with laser intensities and atomic densities that are easily attainable experimentally. We examine the spontaneous emission cascade which takes place from these upper vibrational levels on a time scale of milliseconds, and calculate the resulting rotational populations in v=0 . We show that photon emission in the cascade process does not contribute to trap loss and that a large population of molecules in v=0 can be achieved.

  10. Anisotropic behavior of organic molecules on prepatterned surfaces

    NASA Astrophysics Data System (ADS)

    Hopp, Stefan Frieder; Heuer, Andreas

    2012-04-01

    The nucleation of organic molecules on surfaces, prepatterned with stripes, is investigated with emphasis on anisotropy effects. Representing the molecules as ellipsoids, the related particle-particle interaction is modeled by means of a generalized Gay-Berne potential for similar biaxial particles. The orientation behavior of these ellipsoidal molecules induced by the stripe pattern is studied for the first monolayer by performing kinetic Monte Carlo simulations. It is shown how the properties of the particle alignment depend on energy scales, temperature, and flux. Based on the fact the particles strictly arrange in rows, it is furthermore instructive to analyze the orientation behavior within the different rows. Finally, the transfer of orientation from a preset row of molecules with fixed orientation to other nucleating particles is examined.

  11. Cell Adhesion Molecules and Ubiquitination—Functions and Significance

    PubMed Central

    Homrich, Mirka; Gotthard, Ingo; Wobst, Hilke; Diestel, Simone

    2015-01-01

    Cell adhesion molecules of the immunoglobulin (Ig) superfamily represent the biggest group of cell adhesion molecules. They have been analyzed since approximately 40 years ago and most of them have been shown to play a role in tumor progression and in the nervous system. All members of the Ig superfamily are intensively posttranslationally modified. However, many aspects of their cellular functions are not yet known. Since a few years ago it is known that some of the Ig superfamily members are modified by ubiquitin. Ubiquitination has classically been described as a proteasomal degradation signal but during the last years it became obvious that it can regulate many other processes including internalization of cell surface molecules and lysosomal sorting. The purpose of this review is to summarize the current knowledge about the ubiquitination of cell adhesion molecules of the Ig superfamily and to discuss its potential physiological roles in tumorigenesis and in the nervous system. PMID:26703751

  12. Anisotropic behavior of organic molecules on prepatterned surfaces.

    PubMed

    Hopp, Stefan Frieder; Heuer, Andreas

    2012-04-21

    The nucleation of organic molecules on surfaces, prepatterned with stripes, is investigated with emphasis on anisotropy effects. Representing the molecules as ellipsoids, the related particle-particle interaction is modeled by means of a generalized Gay-Berne potential for similar biaxial particles. The orientation behavior of these ellipsoidal molecules induced by the stripe pattern is studied for the first monolayer by performing kinetic Monte Carlo simulations. It is shown how the properties of the particle alignment depend on energy scales, temperature, and flux. Based on the fact the particles strictly arrange in rows, it is furthermore instructive to analyze the orientation behavior within the different rows. Finally, the transfer of orientation from a preset row of molecules with fixed orientation to other nucleating particles is examined. PMID:22519314

  13. From dipolar to multipolar interactions between ultracold Feshbach molecules

    NASA Astrophysics Data System (ADS)

    Quéméner, Goulven; Lepers, Maxence; Luc-Koenig, Eliane; Dulieu, Olivier

    2016-05-01

    Using the multipolar expansion of electrostatic and magnetostatic potential energies, we characterize the long-range interactions between two weakly-bound diatomic molecules, taking as an example the paramagnetic Er2 Feshbach molecules which were produced recently. The interaction between atomic magnetic dipoles gives rise to the usual R-3 leading term of the multipolar expansion, where R is the intermolecular distance. We show that additional terms scaling as R-5, R-7 and so on also appear, which are strongly anisotropic with respect to the orientation of the molecules. These terms can be seen as effective molecular multipole moments reflecting the spatial extension of the molecules which is non-negligible compared to R. We acknowledge the financial support of the COPOMOL project (ANR-13-IS04-0004) from Agence Nationale de la Recherche.

  14. Structure factor and rheology of chain molecules from molecular dynamics

    NASA Astrophysics Data System (ADS)

    Castrejón-González, Omar; Castillo-Tejas, Jorge; Manero, Octavio; Alvarado, Juan F. J.

    2013-05-01

    Equilibrium and non-equilibrium molecular dynamics were performed to determine the relationship between the static structure factor, the molecular conformation, and the rheological properties of chain molecules. A spring-monomer model with Finitely Extensible Nonlinear Elastic and Lennard-Jones force field potentials was used to describe chain molecules. The equations of motion were solved for shear flow with SLLOD equations of motion integrated with Verlet's algorithm. A multiple time scale algorithm extended to non-equilibrium situations was used as the integration method. Concentric circular patterns in the structure factor were obtained, indicating an isotropic Newtonian behavior. Under simple shear flow, some peaks in the structure factor were emerged corresponding to an anisotropic pattern as chains aligned along the flow direction. Pure chain molecules and chain molecules in solution displayed shear-thinning regions. Power-law and Carreau-Yasuda models were used to adjust the generated data. Results are in qualitative agreement with rheological and light scattering experiments.

  15. Quantum Behavior of Water Molecules Confined to Nanocavities in Gemstones.

    PubMed

    Gorshunov, Boris P; Zhukova, Elena S; Torgashev, Victor I; Lebedev, Vladimir V; Shakurov, Gil'man S; Kremer, Reinhard K; Pestrjakov, Efim V; Thomas, Victor G; Fursenko, Dimitry A; Dressel, Martin

    2013-06-20

    When water is confined to nanocavities, its quantum mechanical behavior can be revealed by terahertz spectroscopy. We place H2O molecules in the nanopores of a beryl crystal lattice and observe a rich and highly anisotropic set of absorption lines in the terahertz spectral range. Two bands can be identified, which originate from translational and librational motions of the water molecule isolated within the cage; they correspond to the analogous broad bands in liquid water and ice. In the present case of well-defined and highly symmetric nanocavities, the observed fine structure can be explained by macroscopic tunneling of the H2O molecules within a six-fold potential caused by the interaction of the molecule with the cavity walls. PMID:26283245

  16. A New Approach to the Architecture of Diatomic Molecules

    NASA Astrophysics Data System (ADS)

    Yarman, Tolga

    2001-05-01

    In our previous work, we established that, in an atomic or molecular wave-like description embodying a potential energy term made of Coulomb Potentials, if the mass M of the object (or different masses the object involves) is multiplied by the hypothetical number γ, then the size of space R in which this object is installed, shrinks as much, and the total energy E of the object, is increased as much [1]. This occurance yields at once the “quantum mechanical invariance” of the quantity EMR^2; furthermore this quantity happens to be girdled to h^2, so that we end up with the relationship EMR^2 h^2 [1]. Note that this is in no way a “dimension analysis”. Anyhow, the occurance we disclose would not work, if the wave-like description embodies other potentials than Coulomb Potentials, though of course, there still would be no problem in regards to a dimension analysis. Herein, we consider the above relationship, together with the equation related to the electronic motion of the molecule (for fixed nuclei), obtained through the Born and Oppenheimer Approximation [2], when this is applied to the Schrodinger description of a diatomic molecule. Our approach thus leads to an essential relationship for the vibrational period of the diatomic molecule in hand, namely T=4π ^2/[h(n_in_j)^1/2][gM_redm_e]^1/2R^2, where M_red is the reduced mass of the nuclei of the diatomic molecule of concern, me the mass of the electron, and g, a dimensionless coefficient; ni and nj (essentially on the basis of the study of the hydrogen molecule vibrational excited electronic data together with the study of the ground state vibrational data related to alkali hydrides and alkali molecules), are disclosed to be the numbers identifying the rows of The Periodic Table of The Elements, to which the atoms making up the molecule belong; this finding is further checked throughout the entire body of diatomic molecules. From the above relationship, it appears immediately that g, necessesarily

  17. Interactions Between Ground-State Nitrogen Atoms and Molecules

    NASA Technical Reports Server (NTRS)

    Vanderslice, Joseph T.; Mason, Edward A.; Lippincott, Ellis R.

    1959-01-01

    Potential-energy curves for nitrogen atom (N-N) interactions corresponding to the X (1)Sigma(sup +, sub g), A (3)Sigma(sup +, sub u), (5)Sigma(sup +, sub g), (7)Sigma(sup +, sub u), B (3) Pi(sub g), C (3)(Pi(su u)and a (1)Pi(sub g) states of the nitrogen molecule N2 as well as curves for the atom-molecules (N-N2) and molecule-molecule (N2-N2) interactions have been calculated. All calculations have been based as nearly as possible on experimental data, including spectroscopically determined vibrational energy levels, scattering cross sections of atomic beams in gases, and measured vibrational relaxation times. In cases where experimental data were not available, approximate quantum-mechanical calculations have been made. Results obtained by these various methods are remarkably consistent with one another and are believed to have good accuracy.

  18. A guest molecule-host cavity fitting algorithm to mine PDB for small molecule targets.

    PubMed

    Byrem, William C; Armstead, Stephen C; Kobayashi, Shunji; Eckenhoff, Roderic G; Eckmann, David M

    2006-08-01

    Inhaled anesthetic molecule occupancy of a protein internal cavity depends in part on the volumes of the guest molecule and the host site. Current algorithms to determine volume and surface area of cavities in proteins whose structures have been determined and cataloged make no allowance for shape or small degrees of shape adjustment to accommodate a guest. We developed an algorithm to determine spheroid dimensions matching cavity volume and surface area and applied it to screen the cavities of 6,658 nonredundant structures stored in the Protein Data Bank (PDB) for potential targets of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane). Our algorithm determined sizes of prolate and oblate spheroids matching dimensions of each cavity found. If those spheroids could accommodate halothane (radius 2.91 A) as a guest, we determined the packing coefficient. 394,766 total cavities were identified. Of 58,681 cavities satisfying the fit criteria for halothane, 11,902 cavities had packing coefficients in the range of 0.46-0.64. This represents 20.3% of cavities large enough to hold halothane, 3.0% of all cavities processed, and found in 2,432 protein structures. Our algorithm incorporates shape dependence to screen guest-host relationships for potential small molecule occupancy of protein cavities. Proteins with large numbers of such cavities are more likely to be functionally altered by halothane. PMID:16904958

  19. Monitoring Molecules: Insights and Progress

    PubMed Central

    2015-01-01

    In August, 2014, neuroscientists and physical scientists gathered together on the campus of the University of California, Los Angeles to discuss how to monitor molecules in neuroscience. This field has seen significant growth since its inception in the 1970s. Here, the advances in this field are documented, including its advance into understanding the actions that specific neurotransmitters mediate during behavior. PMID:25514501

  20. Nucleic Acids as Information Molecules.

    ERIC Educational Resources Information Center

    McInerney, Joseph D.

    1996-01-01

    Presents an activity that aims at enabling students to recognize that DNA and RNA are information molecules whose function is to store, copy, and make available the information in biological systems, without feeling overwhelmed by the specialized vocabulary and the minutia of the central dogma. (JRH)

  1. Nanodevices for Single Molecule Studies

    NASA Astrophysics Data System (ADS)

    Craighead, H. G.; Stavis, S. M.; Samiee, K. T.

    During the last two decades, biotechnology research has resulted in progress in fields as diverse as the life sciences, agriculture and healthcare. While existing technology enables the analysis of a variety of biological systems, new tools are needed for increasing the efficiency of current methods, and for developing new ones altogether. Interest has grown in single molecule analysis for these reasons.

  2. Dialkylresorcinols as bacterial signaling molecules

    PubMed Central

    Brameyer, Sophie; Kresovic, Darko; Bode, Helge B.; Heermann, Ralf

    2015-01-01

    It is well recognized that bacteria communicate via small diffusible molecules, a process termed quorum sensing. The best understood quorum sensing systems are those that use acylated homoserine lactones (AHLs) for communication. The prototype of those systems consists of a LuxI-like AHL synthase and a cognate LuxR receptor that detects the signal. However, many proteobacteria possess LuxR receptors, yet lack any LuxI-type synthase, and thus these receptors are referred to as LuxR orphans or solos. In addition to the well-known AHLs, little is known about the signaling molecules that are sensed by LuxR solos. Here, we describe a novel cell–cell communication system in the insect and human pathogen Photorhabdus asymbiotica. We identified the LuxR homolog PauR to sense dialkylresorcinols (DARs) and cyclohexanediones (CHDs) instead of AHLs as signals. The DarABC synthesis pathway produces the molecules, and the entire system emerged as important for virulence. Moreover, we have analyzed more than 90 different Photorhabdus strains by HPLC/MS and showed that these DARs and CHDs are specific to the human pathogen P. asymbiotica. On the basis of genomic evidence, 116 other bacterial species are putative DAR producers, among them many human pathogens. Therefore, we discuss the possibility of DARs as novel and widespread bacterial signaling molecules and show that bacterial cell–cell communication goes far beyond AHL signaling in nature. PMID:25550519

  3. Engineering crystals of dendritic molecules.

    PubMed

    Lukin, Oleg; Schubert, Dirk; Müller, Claudia M; Schweizer, W Bernd; Gramlich, Volker; Schneider, Julian; Dolgonos, Grygoriy; Shivanyuk, Alexander

    2009-07-01

    A detailed single-crystal X-ray study of conformationally flexible sulfonimide-based dendritic molecules with systematically varied molecular architectures was undertaken. Thirteen crystal structures reported in this work include 9 structures of the second-generation dendritic sulfonimides decorated with different aryl groups, 2 compounds bearing branches of both second and first generation, and 2 representatives of the first generation. Analysis of the packing patterns of 9 compounds bearing second-generation branches shows that despite their lack of strong directive functional groups there is a repeatedly reproduced intermolecular interaction mode consisting in an anchor-type packing of complementary second-generation branches of neighbouring molecules. The observed interaction tolerates a wide range of substituents in meta- and para-positions of the peripheral arylsulfonyl rings. Quantum chemical calculations of the molecule-molecule interaction energies agree at the qualitative level with the packing preferences found in the crystalline state. The calculations can therefore be used as a tool to rationalize and predict molecular structures with commensurate and non-commensurate branches for programming of different packing modes in crystal. PMID:19549870

  4. Engineering crystals of dendritic molecules

    PubMed Central

    Lukin, Oleg; Schubert, Dirk; Müller, Claudia M.; Schweizer, W. Bernd; Gramlich, Volker; Schneider, Julian; Dolgonos, Grygoriy; Shivanyuk, Alexander

    2009-01-01

    A detailed single-crystal X-ray study of conformationally flexible sulfonimide-based dendritic molecules with systematically varied molecular architectures was undertaken. Thirteen crystal structures reported in this work include 9 structures of the second-generation dendritic sulfonimides decorated with different aryl groups, 2 compounds bearing branches of both second and first generation, and 2 representatives of the first generation. Analysis of the packing patterns of 9 compounds bearing second-generation branches shows that despite their lack of strong directive functional groups there is a repeatedly reproduced intermolecular interaction mode consisting in an anchor-type packing of complementary second-generation branches of neighbouring molecules. The observed interaction tolerates a wide range of substituents in meta- and para-positions of the peripheral arylsulfonyl rings. Quantum chemical calculations of the molecule-molecule interaction energies agree at the qualitative level with the packing preferences found in the crystalline state. The calculations can therefore be used as a tool to rationalize and predict molecular structures with commensurate and non-commensurate branches for programming of different packing modes in crystal. PMID:19549870

  5. Effective multipoles and Yukawa electrostatics in dressed molecule theory

    NASA Astrophysics Data System (ADS)

    Ramirez, Rosa; Kjellander, Roland

    2006-10-01

    In this paper we derive the multipolar expansion of the screened Coulomb potential in electrolyte solutions with molecular solvent. The solute and solvent molecules can have arbitrary sizes, shapes, and internal charge distributions. We use the exact statistical mechanical definition of renormalized charge distributions coming from "dressed molecule theory" to determine the effective multipoles of a molecule immersed in an electrolyte. The effects of many-body correlations are fully included in our formally exact theory. We restrict ourselves to sufficiently dilute solutions so the screened Coulomb potential decays for large distances like a Yukawa function, exp(-κr )/r, where r is the distance and 1/κ is the decay length (it is normally different from the Debye length). The resulting "Yukawa electrostatics" differ in many respects from ordinary, unscreened electrostatics. The "Yukawa charge" of a molecule (the lowest order moment in the multipolar expansion) is in general not equal to its Coulombic charge and it is not the integral of the renormalized charge distribution of the molecule. Moreover, as shown in this paper, the multipolar expansion of the Yukawa potential does not correspond, contrary to the case of the Coulomb potential, to its asymptotic expansion for large r. As a consequence, the charge term in the multipolar expansion is not the leading term in the asymptotic expansion. Instead, for large r values, multipoles of all orders contribute to the leading asymptotic term. Thus, the electrostatic potential from, for example, an electroneutral solvent molecule in an electrolyte solution has generally the same range as that from an ion. The proper asymptotic expansion for electrostatic interactions in electrolytes is derived. It is briefly shown how the multipole expansion formalism can also be applied in the Poisson-Boltzmann approximation for primitive model electrolytes.

  6. Effective multipoles and Yukawa electrostatics in dressed molecule theory.

    PubMed

    Ramirez, Rosa; Kjellander, Roland

    2006-10-14

    In this paper we derive the multipolar expansion of the screened Coulomb potential in electrolyte solutions with molecular solvent. The solute and solvent molecules can have arbitrary sizes, shapes, and internal charge distributions. We use the exact statistical mechanical definition of renormalized charge distributions coming from "dressed molecule theory" to determine the effective multipoles of a molecule immersed in an electrolyte. The effects of many-body correlations are fully included in our formally exact theory. We restrict ourselves to sufficiently dilute solutions so the screened Coulomb potential decays for large distances like a Yukawa function, exp(-kappa r)/r, where r is the distance and 1/kappa is the decay length (it is normally different from the Debye length). The resulting "Yukawa electrostatics" differ in many respects from ordinary, unscreened electrostatics. The "Yukawa charge" of a molecule (the lowest order moment in the multipolar expansion) is in general not equal to its Coulombic charge and it is not the integral of the renormalized charge distribution of the molecule. Moreover, as shown in this paper, the multipolar expansion of the Yukawa potential does not correspond, contrary to the case of the Coulomb potential, to its asymptotic expansion for large r. As a consequence, the charge term in the multipolar expansion is not the leading term in the asymptotic expansion. Instead, for large r values, multipoles of all orders contribute to the leading asymptotic term. Thus, the electrostatic potential from, for example, an electroneutral solvent molecule in an electrolyte solution has generally the same range as that from an ion. The proper asymptotic expansion for electrostatic interactions in electrolytes is derived. It is briefly shown how the multipole expansion formalism can also be applied in the Poisson-Boltzmann approximation for primitive model electrolytes. PMID:17042582

  7. An ab initio molecular orbital study of the argon hydride molecule-ions, ArH + and ArD +, at the MP4(SDQ)/6-311++G(3df,3dp) level. II. The changes in bonding MOs during the Born-Oppenheimer stepwise scan of the internuclear potential energy of the X 1Σ+ ground state of the 40Ar1H+ molecule-ion

    NASA Astrophysics Data System (ADS)

    Schutte, C. J. H.

    2001-12-01

    An analysis of the shapes of the MOs obtained during a Born-Oppenheimer scan of the PE of ArH + by MP4/6-311++G(3df,3dp) MO calculations, allows the successive disengagement of bonding orbitals to be determined. This clearly shows how the different MOs influence the vibrational-rotational properties of ArH + and underlines the importance of the concept of orbital following for molecular spectroscopy and the understanding of chemical bonds in molecules. From this follows an explanation why the first excited state of ArH + and the ground state of ArH are unstable.

  8. Combining small molecules for cell reprogramming through an interatomic analysis.

    PubMed

    Feltes, Bruno César; Bonatto, Diego

    2013-11-01

    The knowledge available about the application and generation of induced pluripotent stem cells (iPSC) has grown since their discovery, and new techniques to enhance the reprogramming process have been described. Among the new approaches to induce iPSC that have gained great attention is the use of small molecules for reprogramming. The application of small molecules, unlike genetic manipulation, provides for control of the reprogramming process through the shifting of concentrations and the combination of different molecules. However, different researchers have reported the use of "reprogramming cocktails" with variable results and drug combinations. Thus, the proper combination of small molecules for successful and enhanced reprogramming is a matter for discussion. However, testing all potential drug combinations in different cell lineages is very costly and time-consuming. Therefore, in this article, we discuss the use of already employed molecules for iPSC generation, followed by the application of systems chemo-biology tools to create different data sets of protein-protein (PPI) and chemical-protein (CPI) interaction networks based on the knowledge of already used and new reprogramming cocktail combinations. We further analyzed the biological processes associated with PPI-CPI networks and provided new potential protein targets to be inhibited or expressed for stem cell reprogramming. In addition, we applied a new interference analysis to prospective targets that could negatively affect the classical pluripotency-associated factors (SOX2, NANOG, KLF4 and OCT4) and thus potentially improve reprogramming protocols. PMID:24056910

  9. EDITORIAL: Focus on Cold and Ultracold Molecules FOCUS ON COLD AND ULTRACOLD MOLECULES

    NASA Astrophysics Data System (ADS)

    Carr, Lincoln D.; Ye, Jun

    2009-05-01

    öhlich, A Griesmaier, T Pfau, H Saito, Y Kawaguchi and M Ueda High-energy-resolution molecular beams for cold collision studies L P Parazzoli, N Fitch, D S Lobser and H J Lewandowski Collisional effects in the formation of cold guided beams of polar molecules M Motsch, C Sommer, M Zeppenfeld, L D van Buuren, P W H Pinkse and G Rempe Towards sympathetic cooling of large molecules: cold collisions between benzene and rare gas atoms P Barletta, J Tennyson and P F Barker Efficient formation of ground-state ultracold molecules via STIRAP from the continuum at a Feshbach resonance Elena Kuznetsova, Marko Gacesa, Philippe Pellegrini, Susanne F Yelin and Robin Côté Emergent timescales in entangled quantum dynamics of ultracold molecules in optical lattices M L Wall and L D Carr Rotational state resolved photodissociation spectroscopy of translationally and vibrationally cold MgH+ ions: toward rotational cooling of molecular ions K Højbjerre, A K Hansen, P S Skyt, P F Staanum and M Drewsen Collective transverse cavity cooling of a dense molecular beam Thomas Salzburger and Helmut Ritsch A Stark decelerator on a chip Samuel A Meek, Horst Conrad and Gerard Meijer Deceleration of molecules by dipole force potential: a numerical simulation Susumu Kuma and Takamasa Momose Ultracold molecules: vehicles to scalable quantum information processing Kathy-Anne Brickman Soderberg, Nathan Gemelke and Cheng Chin Magnetic field modification of ultracold molecule-molecule collisions T V Tscherbul, Yu V Suleimanov, V Aquilanti and R V Krems Spectroscopy of 39K85Rb triplet excited states using ultracold a 3Σ+ state molecules formed by photoassociation J T Kim, D Wang, E E Eyler, P L Gould and W C Stwalley Pumping vortex into a Bose-Einstein condensate of heteronuclear molecules Z F Xu, R Q Wang and L You Intense atomic and molecular beams via neon buffer-gas cooling David Patterson, Julia Rasmussen and John M Doyle Dynamical properties of dipolar Fermi gases T Sogo, L He, T Miyakawa, S Yi, H Lu

  10. MHCcluster, a method for functional clustering of MHC molecules.

    PubMed

    Thomsen, Martin; Lundegaard, Claus; Buus, Søren; Lund, Ole; Nielsen, Morten

    2013-09-01

    The identification of peptides binding to major histocompatibility complexes (MHC) is a critical step in the understanding of T cell immune responses. The human MHC genomic region (HLA) is extremely polymorphic comprising several thousand alleles, many encoding a distinct molecule. The potentially unique specificities remain experimentally uncharacterized for the vast majority of HLA molecules. Likewise, for nonhuman species, only a minor fraction of the known MHC molecules have been characterized. Here, we describe a tool, MHCcluster, to functionally cluster MHC molecules based on their predicted binding specificity. The method has a flexible web interface that allows the user to include any MHC of interest in the analysis. The output consists of a static heat map and graphical tree-based visualizations of the functional relationship between MHC variants and a dynamic TreeViewer interface where both the functional relationship and the individual binding specificities of MHC molecules are visualized. We demonstrate that conventional sequence-based clustering will fail to identify the functional relationship between molecules, when applied to MHC system, and only through the use of the predicted binding specificity can a correct clustering be found. Clustering of prevalent HLA-A and HLA-B alleles using MHCcluster confirms the presence of 12 major specificity groups (supertypes) some however with highly divergent specificities. Importantly, some HLA molecules are shown not to fit any supertype classification. Also, we use MHCcluster to show that chimpanzee MHC class I molecules have a reduced functional diversity compared to that of HLA class I molecules. MHCcluster is available at www.cbs.dtu.dk/services/MHCcluster-2.0. PMID:23775223

  11. Molecular electrostatic potentials by systematic molecular fragmentation

    SciTech Connect

    Reid, David M.; Collins, Michael A.

    2013-11-14

    A simple method is presented for estimating the molecular electrostatic potential in and around molecules using systematic molecular fragmentation. This approach estimates the potential directly from the electron density. The accuracy of the method is established for a set of organic molecules and ions. The utility of the approach is demonstrated by estimating the binding energy of a water molecule in an internal cavity in the protein ubiquitin.

  12. Adiabatic Field-Free Alignment of Asymmetric Top Molecules with an Optical Centrifuge

    NASA Astrophysics Data System (ADS)

    Korobenko, A.; Milner, V.

    2016-05-01

    We use an optical centrifuge to align asymmetric top SO2 molecules by adiabatically spinning their most polarizable O-O axis. The effective centrifugal potential in the rotating frame confines the sulfur atoms to the plane of the laser-induced rotation, leading to the planar molecular alignment that persists after the molecules are released from the centrifuge. The periodic appearance of the full three-dimensional alignment, typically observed only with linear and symmetric top molecules, is also detected. Together with strong in-plane centrifugal forces, which bend the molecules by up to 10 deg, permanent field-free alignment offers new ways of controlling molecules with laser light.

  13. Delocalized π state between molecules through a surface confined pseudodihydrogen bond.

    PubMed

    Chen, Lan; Li, Hui; Wee, Andrew Thye Shen

    2010-11-26

    When 3,4,9,10-perylene-tetracarboxylic-dianhydride (PTCDA) and coronene molecules coadsorb on the Ag(111) surface, one-dimensional PTCDA molecular oligomers with efficient electronic connection via noncovalent bonds are observed by low temperature scanning tunneling microscopy. Density functional theory calculations indicate the neighboring PTCDA molecules form oligomers due to strong PTCDA-metal interactions, which result in overlapping of π orbitals and pseudodihydrogen surface bonds between molecules. Our results provide a potential approach for electron transport from molecule to molecule directly through noncovalent bond. PMID:21231400

  14. Molecule-optimized basis sets and Hamiltonians for accelerated electronic structure calculations of atoms and molecules.

    PubMed

    Gidofalvi, Gergely; Mazziotti, David A

    2014-01-16

    Molecule-optimized basis sets, based on approximate natural orbitals, are developed for accelerating the convergence of quantum calculations with strongly correlated (multireferenced) electrons. We use a low-cost approximate solution of the anti-Hermitian contracted Schrödinger equation (ACSE) for the one- and two-electron reduced density matrices (RDMs) to generate an approximate set of natural orbitals for strongly correlated quantum systems. The natural-orbital basis set is truncated to generate a molecule-optimized basis set whose rank matches that of a standard correlation-consistent basis set optimized for the atoms. We show that basis-set truncation by approximate natural orbitals can be viewed as a one-electron unitary transformation of the Hamiltonian operator and suggest an extension of approximate natural-orbital truncations through two-electron unitary transformations of the Hamiltonian operator, such as those employed in the solution of the ACSE. The molecule-optimized basis set from the ACSE improves the accuracy of the equivalent standard atom-optimized basis set at little additional computational cost. We illustrate the method with the potential energy curves of hydrogen fluoride and diatomic nitrogen. Relative to the hydrogen fluoride potential energy curve from the ACSE in a polarized triple-ζ basis set, the ACSE curve in a molecule-optimized basis set, equivalent in size to a polarized double-ζ basis, has a nonparallelity error of 0.0154 au, which is significantly better than the nonparallelity error of 0.0252 au from the polarized double-ζ basis set. PMID:24387056

  15. Designing a small molecule erythropoietin mimetic.

    PubMed

    Guarnieri, Frank

    2015-01-01

    the stem cells into red blood cells. Researchers at Amgen published a co-crystal structure of EPO bound to the EPO receptor, which has a beautiful twofold symmetry-it was argued that this is the active state of the receptor. Activating the EPO receptor with EPO induces an almost instantaneous shutdown mechanism to sharply curtail any proliferative signal transduction, and thus, my hypotheses lead to the conclusion that the Amgen co-crystal is actually the state after receptor downregulation and thus an off-state. To put these hypotheses to the test, my computational method of Simulated Annealing of Chemical Potential was run using the co-crystal created at RWJ, which is the receptor trapped in a partial agonist state. The simulations predicted a previously unknown high affinity binding site at the pivot point where the two halves of the dimeric receptor meet, and detailed analysis of the fragment patterns led to the prediction of a molecule less than 300 MW that is basically twofold symmetric with a chiral center on one side and not the other. Thus, to the degree that computer simulations can be taken seriously, these results support my hypotheses on small molecule receptor activation. When this small molecule was synthesized and tested it indeed induced human hematopoietic stems cells to become red blood cells. When the predicted chiral center of this molecule was removed eliminating its one asymmetric feature, the resulting molecule was an antagonist-it could potently displace hot EPO but could no longer induce stem cell proliferation and differentiation. These results provided strong support for my theories on how to create potent small molecule EPO agonists and were used to launch the new company Locus Pharmaceuticals. These molecules, however, required significant chemical changes in order to make them stable in other in vitro assays and to be in vivo active, but these alterations had to be done in a way that maintained the symmetry-asymmetry considerations that

  16. Cold collisions between boson or fermion molecules

    SciTech Connect

    Kajita, Masatoshi

    2004-01-01

    We theoretically investigate collisions between electrostatically trapped cold polar molecules and compare boson and fermion isotopes. Evaporative cooling seems possible for fermion molecules as the ratio of the collision loss cross section to the elastic collision cross section (R) gets smaller as the molecular temperature T lowers. With boson molecules, R gets larger as T lowers, which makes evaporative cooling difficult. The elastic collision cross section between fermion molecules can be larger than that for boson molecules with certain conditions.

  17. Dissociation energy of molecules in dense gases

    NASA Technical Reports Server (NTRS)

    Kunc, J. A.

    1992-01-01

    A general approach is presented for calculating the reduction of the dissociation energy of diatomic molecules immersed in a dense (n = less than 10 exp 22/cu cm) gas of molecules and atoms. The dissociation energy of a molecule in a dense gas differs from that of the molecule in vacuum because the intermolecular forces change the intramolecular dynamics of the molecule, and, consequently, the energy of the molecular bond.

  18. Non-adiabatic dynamics of molecules in optical cavities

    NASA Astrophysics Data System (ADS)

    Kowalewski, Markus; Bennett, Kochise; Mukamel, Shaul

    2016-02-01

    Strong coupling of molecules to the vacuum field of micro cavities can modify the potential energy surfaces thereby opening new photophysical and photochemical reaction pathways. While the influence of laser fields is usually described in terms of classical field, coupling to the vacuum state of a cavity has to be described in terms of dressed photon-matter states (polaritons) which require quantized fields. We present a derivation of the non-adiabatic couplings for single molecules in the strong coupling regime suitable for the calculation of the dressed state dynamics. The formalism allows to use quantities readily accessible from quantum chemistry codes like the adiabatic potential energy surfaces and dipole moments to carry out wave packet simulations in the dressed basis. The implications for photochemistry are demonstrated for a set of model systems representing typical situations found in molecules.

  19. Observation of ultralong range Rydberg molecules

    NASA Astrophysics Data System (ADS)

    Shaffer, James

    2009-05-01

    In 1934, Enrico Fermi described the scattering of a low energy electron from a neutral atom by using the ideas of scattering length and pseudopotential. Although the long range potential for an electron-atom interaction is always attractive, Fermi realized that the s-wave scattering length that characterizes the low energy collision can be either positive or negative. For a positive scattering length, the wavefunction of the electron is shifted away from the atom, the electron is repelled; whereas for a negative scattering length, the wavefunction of the electron is shifted to the atom, the electron is attracted. Based on Fermi's approach, Greene and co-workers predicted a novel molecular binding mechanism where a low energy Rydberg electron is scattered from a ground state atom in the case of negative scattering length. In this situation, the interaction between the electron and ground state atom is attractive and results in the formation of bound states of the ground state atom and the Rydberg atom. Molecules bound by electron scattering can have an internuclear separation of several thousand Bohr radii and are very different from molecules formed by 2 Rydberg atoms where the binding is the result of multipolar forces between the atoms alone. In this talk, we present experimental data on the observation of these exotic molecular states for Rb Rydberg atoms in S states for principal quantum numbers n between 34 and 40. The spectroscopic results for the vibrational ground and first excited state of the dimer Rb(5S)-Rb(nS) are presented and the s-wave scattering length for electron-Rb(5S) scattering in the low energy regime where the kinetic energy is less than 100 meV. Finally, we discuss and present data on the lifetimes and decay mechanisms of these molecules in a magnetic trap.

  20. X(3872): charmonium or molecule?

    SciTech Connect

    Nefediev, A. V.

    2011-05-23

    A theoretical analysis of the recent experimental data from the Belle and BABAR Collaborations on the charmonium state X(3872) is performed. The analysis takes into account the proximity of an S-wave mesonic threshold and a possible presence of molecule component in the resonance wave function, finite width of the molecule constituents, and a possible interference in the final state. In particular, a model-independent approach is formulated, based on the Flatte parametrisation of near-threshold observables as well as on the Weinberg analysis of the nature of weakly bound systems generalised to the case of unstable constituents. Conclusion is made that the X(3872) is generated dynamically by a strong coupling of the bare {chi}{sub c1} charmonium to the DD-bar* hadronic channel, with a large admixture of the DD-bar* molecular component.

  1. Electrochemical detection of single molecules.

    PubMed

    Fan, F R; Bard, A J

    1995-02-10

    The electrochemical behavior of a single molecule can be observed by trapping a small volume of a dilute solution of the electroactive species between an ultramicroelectrode tip with a diameter of approximately 15 nanometers and a conductive substrate. A scanning electrochemical microscope was used to adjust the tip-substrate distance ( approximately 10 nanometers), and the oxidation of [(trimethylammonio)methyl] ferrocene (Cp(2)FeTMA(+)) to Cp(2)FeTMA(2+) was carried out. The response was stochastic, and anodic current peaks were observed as the molecule moved into and out of the electrode-substrate gap. Similar experiments were performed with a solution containing two redox species, ferrocene carboxylate (Cp(2)FeCOO(-)) and Os(bpy)(3)(2+) (bpy is 2,2'-bipyridyl). PMID:17813918

  2. Bioactive molecules from sea hares.

    PubMed

    Kamiya, H; Sakai, R; Jimbo, M

    2006-01-01

    Sea hares, belonging to the order Opisthobranchia, subclass Gastropoda, are mollusks that have attracted many researchers who are interested in the chemical defense mechanisms of these soft and "shell-less" snails. Numbers of small molecules of dietary origin have been isolated from sea hares and some have ecologically relevant activities, such as fish deterrent activity or toxicity. Recently, however, greater attention has been paid to biomedically interesting sea hare isolates such as dolastatins, a series of antitumor peptide/macrolides isolated from Dolabella auricularia. Another series of bioactive peptide/macrolides, as represented by aplyronines, have been isolated from sea hares in Japanese waters. Although earlier studies indicated the potent antitumor activity of aplyronines, their clinical development has never been conducted because of the minute amount of compound available from the natural source. Recent synthetic studies, however, have made it possible to prepare these compounds and analogs for a structure-activity relationship study, and started to uncover their unique action mechanism towards their putative targets, microfilaments. Here, recent findings of small antitumor molecules isolated from Japanese sea hares are reviewed. Sea hares are also known to produce cytotoxic and antimicrobial proteins. In contrast to the small molecules of dietary origin, proteins are the genetic products of sea hares and they are likely to have some primary physiological functions in addition to ecological roles in the sea hare. Based on the biochemical properties and phylogenetic analysis of these proteins, we propose that they belong to one family of molecule, the "Aplysianin A family," although their molecular weights are apparently divided into two groups. Interestingly, the active principles in Aplysia species and Dolabella auricularia were shown to be L-amino acid oxidase (LAAO), a flavin enzyme that oxidizes an alpha-amino group of the substrate with

  3. Simple molecules as complex systems.

    PubMed

    Furtenbacher, Tibor; Arendás, Péter; Mellau, Georg; Császár, Attila G

    2014-01-01

    For individual molecules quantum mechanics (QM) offers a simple, natural and elegant way to build large-scale complex networks: quantized energy levels are the nodes, allowed transitions among the levels are the links, and transition intensities supply the weights. QM networks are intrinsic properties of molecules and they are characterized experimentally via spectroscopy; thus, realizations of QM networks are called spectroscopic networks (SN). As demonstrated for the rovibrational states of H2(16)O, the molecule governing the greenhouse effect on earth through hundreds of millions of its spectroscopic transitions (links), both the measured and first-principles computed one-photon absorption SNs containing experimentally accessible transitions appear to have heavy-tailed degree distributions. The proposed novel view of high-resolution spectroscopy and the observed degree distributions have important implications: appearance of a core of highly interconnected hubs among the nodes, a generally disassortative connection preference, considerable robustness and error tolerance, and an "ultra-small-world" property. The network-theoretical view of spectroscopy offers a data reduction facility via a minimum-weight spanning tree approach, which can assist high-resolution spectroscopists to improve the efficiency of the assignment of their measured spectra. PMID:24722221

  4. Molecules in the early universe

    SciTech Connect

    Lepp, S.; Shull, J.M.

    1984-05-15

    We present calculations of the formation of astrophysically interesting molecules (H/sub 2/, HD, LiH, and HeH/sup +/) by gas-phase reactions during the postrecombination epoch (redshifts z = 300-30). In standard Friedmann cosmological models, H/sub 2//Hroughly-equal10/sup -6/, HD/H/sub 2/roughly-equal10/sup -4.5/, and LiH/H/sub 2/roughly-equal10/sup -6.5/. These molecules may dominate the cooling and trigger the collapse of primordial gas clouds. The dipole rotational transitions of HD and LiH are particularly important at high density and low temperature. Additional molecules form during spherical collapse of these clouds, their rotational cooling keeps the gas temperature between 400 and 1500 K over 12 decades of density increase until the H/sub 2/ lines become optically thick. The existence of molecular coolants at high redshift has significant implications for the first generation of stars and for thermal instabilities in intergalactic matter.

  5. Simple molecules as complex systems

    PubMed Central

    Furtenbacher, Tibor; Árendás, Péter; Mellau, Georg; Császár, Attila G.

    2014-01-01

    For individual molecules quantum mechanics (QM) offers a simple, natural and elegant way to build large-scale complex networks: quantized energy levels are the nodes, allowed transitions among the levels are the links, and transition intensities supply the weights. QM networks are intrinsic properties of molecules and they are characterized experimentally via spectroscopy; thus, realizations of QM networks are called spectroscopic networks (SN). As demonstrated for the rovibrational states of H216O, the molecule governing the greenhouse effect on earth through hundreds of millions of its spectroscopic transitions (links), both the measured and first-principles computed one-photon absorption SNs containing experimentally accessible transitions appear to have heavy-tailed degree distributions. The proposed novel view of high-resolution spectroscopy and the observed degree distributions have important implications: appearance of a core of highly interconnected hubs among the nodes, a generally disassortative connection preference, considerable robustness and error tolerance, and an “ultra-small-world” property. The network-theoretical view of spectroscopy offers a data reduction facility via a minimum-weight spanning tree approach, which can assist high-resolution spectroscopists to improve the efficiency of the assignment of their measured spectra. PMID:24722221

  6. A single-molecule diode

    PubMed Central

    Elbing, Mark; Ochs, Rolf; Koentopp, Max; Fischer, Matthias; von Hänisch, Carsten; Weigend, Florian; Evers, Ferdinand; Weber, Heiko B.; Mayor, Marcel

    2005-01-01

    We have designed and synthesized a molecular rod that consists of two weakly coupled electronic π -systems with mutually shifted energy levels. The asymmetry thus implied manifests itself in a current–voltage characteristic with pronounced dependence on the sign of the bias voltage, which makes the molecule a prototype for a molecular diode. The individual molecules were immobilized by sulfur–gold bonds between both electrodes of a mechanically controlled break junction, and their electronic transport properties have been investigated. The results indeed show diode-like current–voltage characteristics. In contrast to that, control experiments with symmetric molecular rods consisting of two identical π -systems did not show significant asymmetries in the transport properties. To investigate the underlying transport mechanism, phenomenological arguments are combined with calculations based on density functional theory. The theoretical analysis suggests that the bias dependence of the polarizability of the molecule feeds back into the current leading to an asymmetric shape of the current–voltage characteristics, similar to the phenomena in a semiconductor diode. PMID:15956208

  7. Small Molecules Take A Big Step Against Clostridium difficile.

    PubMed

    Beilhartz, Greg L; Tam, John; Melnyk, Roman A

    2015-12-01

    Effective treatment of Clostridium difficile infections demands a shift away from antibiotics towards toxin-neutralizing agents. Work by Bender et al., using a drug that attenuates toxin action in vivo without affecting bacterial survival, demonstrates the exciting potential of small molecules as a new modality in the fight against C. difficile. PMID:26547239

  8. Femtosecond spectroscopy of molecules and clusters

    SciTech Connect

    Baumert, T.; Gerber, G.

    1995-12-31

    In the molecular physics section of this report we first discuss the evolution of a vibrational wavepacket in a double minimum potential well. Second, we will focus on the dynamics of multiphoton ionization (MPI) in a diatomic, and we will see how the unexpected results give new input into the challenging field of controlling chemical reactions by means of time-resolved laser techniques. As high laser intensities are achieved in focused ultrashort light pulses, their interaction with molecules is of particular interest and will be treated next. For all these experiments we have chosen the Na{sub 2} molecule as a model system, as there is a wealth of spectroscopic and theoretical information available, which facilitates the interpretation of the time domain results considerably. In the cluster section of this chapter we report the first experiments in cluster physics employing ultrashort laser pulses to time-resolved studies of cluster ionization and fragmentation processes. Clusters and in particular metal clusters have been the fascinating subject of many experimental and theoretical studies. Clusters form the link between solid-state physics and molecular physics. Metal clusters exhibit distinct features ranging from molecular properties seen in small particles to the solid state like behavior of larger aggregates. Studies of cluster properties like geometric structures, the evolution of the electronic states from localized to delocalized in nature, and the real-time dynamics of ionization and fragmentation have not yet been performed in detail as a function of cluster size.

  9. Proteinaceous Molecules Mediating Bifidobacterium-Host Interactions.

    PubMed

    Ruiz, Lorena; Delgado, Susana; Ruas-Madiedo, Patricia; Margolles, Abelardo; Sánchez, Borja

    2016-01-01

    Bifidobacteria are commensal microoganisms found in the gastrointestinal tract. Several strains have been attributed beneficial traits at local and systemic levels, through pathogen exclusion or immune modulation, among other benefits. This has promoted a growing industrial and scientific interest in bifidobacteria as probiotic supplements. However, the molecular mechanisms mediating this cross-talk with the human host remain unknown. High-throughput technologies, from functional genomics to transcriptomics, proteomics, and interactomics coupled to the development of both in vitro and in vivo models to study the dynamics of the intestinal microbiota and their effects on host cells, have eased the identification of key molecules in these interactions. Numerous secreted or surface-associated proteins or peptides have been identified as potential mediators of bifidobacteria-host interactions and molecular cross-talk, directly participating in sensing environmental factors, promoting intestinal colonization, or mediating a dialogue with mucosa-associated immune cells. On the other hand, bifidobacteria induce the production of proteins in the intestine, by epithelial or immune cells, and other gut bacteria, which are key elements in orchestrating interactions among bifidobacteria, gut microbiota, and host cells. This review aims to give a comprehensive overview on proteinaceous molecules described and characterized to date, as mediators of the dynamic interplay between bifidobacteria and the human host, providing a framework to identify knowledge gaps and future research needs. PMID:27536282

  10. Single Molecule and Single Cell Epigenomics

    PubMed Central

    Hyun, Byung-Ryool; McElwee, John L.; Soloway, Paul D.

    2014-01-01

    Dynamically regulated changes in chromatin states are vital for normal development and can produce disease when they go awry. Accordingly, much effort has been devoted to characterizing these states under normal and pathological conditions. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is the most widely used method to characterize where in the genome transcription factors, modified histones, modified nucleotides and chromatin binding proteins are found; bisulfite sequencing (BS-seq) and its variants are commonly used to characterize the locations of DNA modifications. Though very powerful, these methods are not without limitations. Notably, they are best at characterizing one chromatin feature at a time, yet chromatin features arise and function in combination. Investigators commonly superimpose separate ChIP-seq or BS-seq datasets, and then infer where chromatin features are found together. While these inferences might be correct, they can be misleading when the chromatin source has distinct cell types, or when a given cell type exhibits any cell to cell variation in chromatin state. These ambiguities can be eliminated by robust methods that directly characterize the existence and genomic locations of combinations of chromatin features in very small inputs of cells or ideally, single cells. Here we review single molecule epigenomic methods under development to overcome these limitations, the technical challenges associated with single molecule methods and their potential application to single cells. PMID:25204781

  11. Proteinaceous Molecules Mediating Bifidobacterium-Host Interactions

    PubMed Central

    Ruiz, Lorena; Delgado, Susana; Ruas-Madiedo, Patricia; Margolles, Abelardo; Sánchez, Borja

    2016-01-01

    Bifidobacteria are commensal microoganisms found in the gastrointestinal tract. Several strains have been attributed beneficial traits at local and systemic levels, through pathogen exclusion or immune modulation, among other benefits. This has promoted a growing industrial and scientific interest in bifidobacteria as probiotic supplements. However, the molecular mechanisms mediating this cross-talk with the human host remain unknown. High-throughput technologies, from functional genomics to transcriptomics, proteomics, and interactomics coupled to the development of both in vitro and in vivo models to study the dynamics of the intestinal microbiota and their effects on host cells, have eased the identification of key molecules in these interactions. Numerous secreted or surface-associated proteins or peptides have been identified as potential mediators of bifidobacteria-host interactions and molecular cross-talk, directly participating in sensing environmental factors, promoting intestinal colonization, or mediating a dialogue with mucosa-associated immune cells. On the other hand, bifidobacteria induce the production of proteins in the intestine, by epithelial or immune cells, and other gut bacteria, which are key elements in orchestrating interactions among bifidobacteria, gut microbiota, and host cells. This review aims to give a comprehensive overview on proteinaceous molecules described and characterized to date, as mediators of the dynamic interplay between bifidobacteria and the human host, providing a framework to identify knowledge gaps and future research needs. PMID:27536282

  12. Experimental and theoretical studies of plasmon-molecule interactions.

    PubMed

    Chen, Hanning; Schatz, George C; Ratner, Mark A

    2012-09-01

    Plasmon-molecule interactions are widely believed to involve photo-induced interferences between the localized excitation of individual electrons in molecules and the large collective excitation of conduction electrons in metal particles. The intrinsic multi-scale characteristics of plasmon-molecule interactions not only offer great opportunities for realizing precise top-down control of the optical properties of individual molecules, but also allow for accurate bottom-up manipulation of light polarization and propagation as a result of molecular excitation. However, the temporal and spatial complexity of plasmon-molecule experiments severely limits our interpretation and understanding of interactions that have important applications in dye-sensitized solar cells, single-molecule detectors, photoconductive molecular electronics, all-optical switching and photo-catalytic water splitting. This review aims to outline recent progress in experimental practice and theory for probing and exploiting the subtle coupling between discrete molecular orbitals and continuous metallic bands. For each experimental technique or theoretical model, the fundamental mechanisms and relevant applications are discussed in detail with specific examples. In addition, the experimental validation of theoretical models and the computational design of functional devices are both highlighted. Finally, a brief summary is presented together with an outlook for potential future directions of this emerging interdisciplinary research field. PMID:22935744

  13. Towards Hybrid Quantum Information Processing with Polar Molecules

    NASA Astrophysics Data System (ADS)

    Rabl, Peter

    2008-05-01

    With the ongoing miniaturization of on-chip traps for atoms and ions it is timely to think about coherent interfaces between AMO and solid state systems with potential applications for new hybrid implementations for quantum computers. In this talk I will discuss a potential scenario, where ensembles of polar molecules serve as long-lived quantum memories for superconducting qubits and quantum information is transmitted via a high-Q microwave cavity. Polar molecules combine the exceptional features of a large electric dipole moment and long-lived rotational states with level splittings in the GHz regime. When trapped close to the surface of a chip this combination allows strong interactions with coherent solid state devices, e.g., superconducting microwave cavities or Josephson qubits. I will first introduce the system consisting of a single polar molecule coupled to a stripline cavity which realizes a cavity QED system in the microwave regime and discuss applications for quantum information processing, state detection and new cavity-assisted cooling schemes for polar molecules. I will then switch to molecular ensemble qubits where quantum information is encoded in collective spin or rotational excitations of an ensemble of N molecules. Ensemble qubits benefit from a collectively enhanced coupling ˜√N which allows quantum state transfer between the molecules and, e.g., a charge qubit on a timescale that is compatible with typical coherence times in a solid state environment. With the goal to protect ensemble qubits from collisions, I will finally discuss a scenario, where molecules are prepared in a crystalline phase under 1D trapping conditions and dipole moments aligned by an external field.

  14. Microemulsions as carriers for therapeutic molecules.

    PubMed

    Mehta, Surinder K; Kaur, Gurpreet

    2010-01-01

    The thrust for finding newer drug delivery systems for exiting therapeutic molecules has opened a wide window for colloidal systems. Due to the presence of different domains of variable polarity in the microemulsion systems, they show a huge potential to be used as drug delivery vehicles for a variety of drugs. The use of microemulsion as drug delivery vehicles through a number of routes has engaged a large number of research groups in this area. Microemulsion media finds several applications ranging from drug delivery to drug nanoparticle templating due to its ability to enhance solubility, stability and bioavailability. This review on patent articles recounts the patent literature dealing with different kind of microemulsion carriers used via different routes, solubility and permeability enhancement and its use as a template for nanoparticle synthesis. PMID:19807681

  15. New antimicrobial molecules and new antibiotic strategies.

    PubMed

    Rodríguez de Castro, Felipe; Naranjo, Olga Rajas; Marco, Javier Aspa; Violán, Jordi Solé

    2009-04-01

    Drug options for treatment of infections are increasingly limited. The pharmaceutical industry has found it difficult to discover new antimicrobial agents, and only two novel classes of antibiotics, the oxazolidinones and the cyclic lipopeptides, have entered the market since the late 1960s. Few new agents have reached the market in the last decade with potential interest for community-acquired pneumonia (CAP) treatment, including linezolid (the first oxazolidinone in clinical use), new fluoroquinolones, cefditoren, ertapenem, and telithromycin. Agents currently in clinical development include other novel quinolones and ketolides, broad-spectrum cephalosporin derivatives, faropenem, several glycopeptides, and iclaprim. Other molecules are considered to be promising candidates for the future. In addition to the foregoing agents, alternative treatment approaches have also been introduced into clinical practice, which include the administration of the appropriate antimicrobials in a timely manner and the consideration of the pharmacokinetic-pharmacodynamic properties of the agent(s). PMID:19296416

  16. Single-Molecule Observations of Ribosome Function

    PubMed Central

    Blanchard, Scott C.

    2009-01-01

    Summary of Recent Advances Single-molecule investigations promise to greatly advance our understanding of basic and regulated ribosome functions during the process of translation. Here, recent progress towards directly imaging the elemental translation elongation steps using fluorescence resonance energy transfer (FRET)-based imaging methods is discussed, which provide striking evidence of the highly dynamic nature of the ribosome. In this view, global rates and fidelities of protein synthesis reactions may be regulated by interactions of the ribosome with mRNA, tRNA, translation factors, and potentially many other cellular ligands, that modify intrinsic conformational equilibria in the translating particle. Future investigations probing this model must aim to visualize translation processes from multiple structural and kinetic perspectives simultaneously, to provide direct correlations between factor binding and conformational events. PMID:19223173

  17. Small-Molecule Inhibitors of Urea Transporters

    PubMed Central

    Verkman, Alan S.; Esteva-Font, Cristina; Cil, Onur; Anderson, Marc O.; Li, Fei; Li, Min; Lei, Tianluo; Ren, Huiwen; Yang, Baoxue

    2015-01-01

    Urea transporter (UT) proteins, which include isoforms of UT-A in kidney tubule epithelia and UT-B in vasa recta endothelia and erythrocytes, facilitate urinary concentrating function. Inhibitors of urea transporter function have potential clinical applications as sodium-sparing diuretics, or ‘urearetics,’ in edema from different etiologies, such as congestive heart failure and cirrhosis, as well as in syndrome of inappropriate antidiuretic hormone (SIADH). High-throughput screening of drug-like small molecules has identified UT-A and UT-B inhibitors with nanomolar potency. Inhibitors have been identified with different UT-A versus UT-B selectivity profiles and putative binding sites on UT proteins. Studies in rodent models support the utility of UT inhibitors in reducing urinary concentration, though testing in clinically relevant animal models of edema has not yet been done. PMID:25298345

  18. Oligomer Molecules for Efficient Organic Photovoltaics.

    PubMed

    Lin, Yuze; Zhan, Xiaowei

    2016-02-16

    Solar cells, a renewable, clean energy technology that efficiently converts sunlight into electricity, are a promising long-term solution for energy and environmental problems caused by a mass of production and the use of fossil fuels. Solution-processed organic solar cells (OSCs) have attracted much attention in the past few years because of several advantages, including easy fabrication, low cost, lightweight, and flexibility. Now, OSCs exhibit power conversion efficiencies (PCEs) of over 10%. In the early stage of OSCs, vapor-deposited organic dye materials were first used in bilayer heterojunction devices in the 1980s, and then, solution-processed polymers were introduced in bulk heterojunction (BHJ) devices. Relative to polymers, vapor-deposited small molecules offer potential advantages, such as a defined molecular structure, definite molecular weight, easy purification, mass-scale production, and good batch-to-batch reproducibility. However, the limited solubility and high crystallinity of vapor-deposited small molecules are unfavorable for use in solution-processed BHJ OSCs. Conversely, polymers have good solution-processing and film-forming properties and are easily processed into flexible devices, whereas their polydispersity of molecular weights and difficulty in purification results in batch to batch variation, which may hamper performance reproducibility and commercialization. Oligomer molecules (OMs) are monodisperse big molecules with intermediate molecular weights (generally in the thousands), and their sizes are between those of small molecules (generally with molecular weights <1000) and polymers (generally with molecular weights >10000). OMs not only overcome shortcomings of both vapor-deposited small molecules and solution-processed polymers, but also combine their advantages, such as defined molecular structure, definite molecular weight, easy purification, mass-scale production, good batch-to-batch reproducibility, good solution processability

  19. Quantum Monte Carlo for vibrating molecules

    SciTech Connect

    Brown, W.R. |

    1996-08-01

    Quantum Monte Carlo (QMC) has successfully computed the total electronic energies of atoms and molecules. The main goal of this work is to use correlation function quantum Monte Carlo (CFQMC) to compute the vibrational state energies of molecules given a potential energy surface (PES). In CFQMC, an ensemble of random walkers simulate the diffusion and branching processes of the imaginary-time time dependent Schroedinger equation in order to evaluate the matrix elements. The program QMCVIB was written to perform multi-state VMC and CFQMC calculations and employed for several calculations of the H{sub 2}O and C{sub 3} vibrational states, using 7 PES`s, 3 trial wavefunction forms, two methods of non-linear basis function parameter optimization, and on both serial and parallel computers. In order to construct accurate trial wavefunctions different wavefunctions forms were required for H{sub 2}O and C{sub 3}. In order to construct accurate trial wavefunctions for C{sub 3}, the non-linear parameters were optimized with respect to the sum of the energies of several low-lying vibrational states. In order to stabilize the statistical error estimates for C{sub 3} the Monte Carlo data was collected into blocks. Accurate vibrational state energies were computed using both serial and parallel QMCVIB programs. Comparison of vibrational state energies computed from the three C{sub 3} PES`s suggested that a non-linear equilibrium geometry PES is the most accurate and that discrete potential representations may be used to conveniently determine vibrational state energies.

  20. Hexapole-Oriented Molecule Beams Scattered by Single Crystal Surfaces.

    NASA Astrophysics Data System (ADS)

    Curtiss, Thomas J.

    Cl from this surface. From the body of experimental data on the orientation dependence of the scattering (both direct and trapping/desorption) of polyatomic molecules by graphite, it appears that the origin of the steric effect is the anisotropic molecule -graphite interaction potential, which is, in turn, governed by the charge density distribution of the molecule.

  1. Electron transport in single molecules: from benzene to graphene.

    PubMed

    Chen, F; Tao, N J

    2009-03-17

    Electron movement within and between molecules--that is, electron transfer--is important in many chemical, electrochemical, and biological processes. Recent advances, particularly in scanning electrochemical microscopy (SECM), scanning-tunneling microscopy (STM), and atomic force microscopy (AFM), permit the study of electron movement within single molecules. In this Account, we describe electron transport at the single-molecule level. We begin by examining the distinction between electron transport (from semiconductor physics) and electron transfer (a more general term referring to electron movement between donor and acceptor). The relation between these phenomena allows us to apply our understanding of single-molecule electron transport between electrodes to a broad range of other electron transfer processes. Electron transport is most efficient when the electron transmission probability via a molecule reaches 100%; the corresponding conductance is then 2e(2)/h (e is the charge of the electron and h is the Planck constant). This ideal conduction has been observed in a single metal atom and a string of metal atoms connected between two electrodes. However, the conductance of a molecule connected to two electrodes is often orders of magnitude less than the ideal and strongly depends on both the intrinsic properties of the molecule and its local environment. Molecular length, means of coupling to the electrodes, the presence of conjugated double bonds, and the inclusion of possible redox centers (for example, ferrocene) within the molecular wire have a pronounced effect on the conductance. This complex behavior is responsible for diverse chemical and biological phenomena and is potentially useful for device applications. Polycyclic aromatic hydrocarbons (PAHs) afford unique insight into electron transport in single molecules. The simplest one, benzene, has a conductance much less than 2e(2)/h due to its large LUMO-HOMO gap. At the other end of the spectrum, graphene

  2. DUO: Spectra of diatomic molecules

    NASA Astrophysics Data System (ADS)

    Yurchenko, Sergei N.; Lodi, Lorenzo; Tennyson, Jonathan; Stolyarov, Andrey V.

    2016-05-01

    Duo computes rotational, rovibrational and rovibronic spectra of diatomic molecules. The software, written in Fortran 2003, solves the Schrödinger equation for the motion of the nuclei for the simple case of uncoupled, isolated electronic states and also for the general case of an arbitrary number and type of couplings between electronic states. Possible couplings include spin–orbit, angular momenta, spin-rotational and spin–spin. Introducing the relevant couplings using so-called Born–Oppenheimer breakdown curves can correct non-adiabatic effects.

  3. XUV ionization of aligned molecules

    SciTech Connect

    Kelkensberg, F.; Siu, W.; Gademann, G.; Rouzee, A.; Vrakking, M. J. J.; Johnsson, P.; Lucchini, M.; Lucchese, R. R.

    2011-11-15

    New extreme-ultraviolet (XUV) light sources such as high-order-harmonic generation (HHG) and free-electron lasers (FELs), combined with laser-induced alignment techniques, enable novel methods for making molecular movies based on measuring molecular frame photoelectron angular distributions. Experiments are presented where CO{sub 2} molecules were impulsively aligned using a near-infrared laser and ionized using femtosecond XUV pulses obtained by HHG. Measured electron angular distributions reveal contributions from four orbitals and the onset of the influence of the molecular structure.

  4. Nanoelectronics of a DNA molecule

    NASA Astrophysics Data System (ADS)

    Albuquerque, E. L.; Fulco, U. L.; Caetano, E. W. S.; Freire, V. N.; Lyra, M. L.; Moura, F. A. B. F.

    2014-03-01

    We investigate the nanoelectronic properties of a double-strand quasiperiodic DNA molecule, modeled by a tight-binding effective Hamiltonian, which includes contributions from the nucleobasis system as well as the sugar-phosphate backbone. Our theoretical approach makes use of Dyson's equation together with a transfer-matrix treatment, to investigate the electronic density of states, the electronic transmissivity, and the current-voltage characteristic curves of sequences of a DNA finite segment.We compared the electronic transport found for the quasiperiodic structure to those using a sequence of natural DNA, as part of the human chromosome Ch22.

  5. A simple model for electronic properties of surface adsorbed molecules

    NASA Astrophysics Data System (ADS)

    Dhakal, Rajesh; Schwalm, William

    We adapt a minimal approximation to one electron quantum theory of molecules referred as Fast Accurate Kinetic Energy method. This in principle handles large complex molecular structures with less computational effort to compute electronic properties of adsorbed molecules. Kinetic energy integrals are calculated accurately but multi-electron potential energy integrals are approximated. The neighboring atom interactions are included also. For layers of isopthalic acids formed on pyrolytic graphite the configuration changes as a function of length of hydrocarbon tails. We study properties of this system as a function of tail length.

  6. Critical analysis and extension of the Hirshfeld atoms in molecules.

    PubMed

    Bultinck, Patrick; Van Alsenoy, Christian; Ayers, Paul W; Carbó-Dorca, Ramon

    2007-04-14

    The computational approach to the Hirshfeld [Theor. Chim. Acta 44, 129 (1977)] atom in a molecule is critically investigated, and several difficulties are highlighted. It is shown that these difficulties are mitigated by an alternative, iterative version, of the Hirshfeld partitioning procedure. The iterative scheme ensures that the Hirshfeld definition represents a mathematically proper information entropy, allows the Hirshfeld approach to be used for charged molecules, eliminates arbitrariness in the choice of the promolecule, and increases the magnitudes of the charges. The resulting "Hirshfeld-I charges" correlate well with electrostatic potential derived atomic charges. PMID:17444705

  7. Critical analysis and extension of the Hirshfeld atoms in molecules

    NASA Astrophysics Data System (ADS)

    Bultinck, Patrick; Van Alsenoy, Christian; Ayers, Paul W.; Carbó-Dorca, Ramon

    2007-04-01

    The computational approach to the Hirshfeld [Theor. Chim. Acta 44, 129 (1977)] atom in a molecule is critically investigated, and several difficulties are highlighted. It is shown that these difficulties are mitigated by an alternative, iterative version, of the Hirshfeld partitioning procedure. The iterative scheme ensures that the Hirshfeld definition represents a mathematically proper information entropy, allows the Hirshfeld approach to be used for charged molecules, eliminates arbitrariness in the choice of the promolecule, and increases the magnitudes of the charges. The resulting "Hirshfeld-I charges" correlate well with electrostatic potential derived atomic charges.

  8. Toward Triplet Ground State NaLi Molecules

    NASA Astrophysics Data System (ADS)

    Ebadi, Sepehr; Jamison, Alan; Rvachov, Timur; Jing, Li; Son, Hyungmok; Jiang, Yijun; Zwierlein, Martin; Ketterle, Wolfgang

    2016-05-01

    The NaLi molecule is expected to have a long lifetime in the triplet ground-state due to its fermionic nature, large rotational constant, and weak spin-orbit coupling. The triplet state has both electric and magnetic dipole moments, affording unique opportunities in quantum simulation and ultracold chemistry. We have mapped the excited state NaLi triplet potential by means of photoassociation spectroscopy. We report on this and our further progress toward the creation of the triplet ground-state molecules using STIRAP. NSF, ARO-MURI, Samsung, NSERC.

  9. Fractal scattering dynamics of the three-dimensional HOCl molecule

    NASA Astrophysics Data System (ADS)

    Lin, Yi-Der; Barr, Alex M.; Reichl, L. E.; Jung, Christof

    2013-01-01

    We compare the 2D and 3D classical fractal scattering dynamics of Cl and HO for energies just above dissociation of the HOCl molecule, using a realistic potential energy surface for the HOCl molecule and techniques developed to analyze 3D chaotic scattering processes. For parameter regimes where the HO dimer initially has small vibrational energy, only small intervals of initial conditions show fractal scattering behavior and the scattering process is well described by a 2D model. For parameter regimes where the HO dimer initially has large vibrational energy, the scattering process is fully 3D and is dominated by fractal behavior.

  10. Dual band metamaterial perfect absorber based on artificial dielectric "molecules".

    PubMed

    Liu, Xiaoming; Lan, Chuwen; Li, Bo; Zhao, Qian; Zhou, Ji

    2016-01-01

    Dual band metamaterial perfect absorbers with two absorption bands are highly desirable because of their potential application areas such as detectors, transceiver system, and spectroscopic imagers. However, most of these dual band metamaterial absorbers proposed were based on resonances of metal patterns. Here, we numerically and experimentally demonstrate a dual band metamaterial perfect absorber composed of artificial dielectric "molecules" with high symmetry. The artificial dielectric "molecule" consists of four "atoms" of two different sizes corresponding to two absorption bands with near unity absorptivity. Numerical and experimental absorptivity verify that the dual-band metamaterial absorber is polarization insensitive and can operate in wide-angle incidence. PMID:27406699

  11. Hyperfine-structure-induced purely long-range molecules.

    PubMed

    Enomoto, Katsunari; Kitagawa, Masaaki; Tojo, Satoshi; Takahashi, Yoshiro

    2008-03-28

    We have experimentally observed and theoretically identified a novel class of purely long-range molecules. This novel purely long-range state is formed due to a very weak hyperfine interaction that is usually treated only as a small perturbation in molecular spectra. Photoassociation spectroscopy of ultracold ytterbium (171Yb) atoms with the 1S0-3P1 intercombination transition presents clear identification of molecular states and the shallowest molecular potential depth of about 750 MHz among the purely long-range molecules ever observed. PMID:18517858

  12. Single-molecule imaging of non-equilibrium molecular ensembles on the millisecond timescale.

    PubMed

    Juette, Manuel F; Terry, Daniel S; Wasserman, Michael R; Altman, Roger B; Zhou, Zhou; Zhao, Hong; Blanchard, Scott C

    2016-04-01

    Single-molecule fluorescence microscopy is uniquely suited for detecting transient molecular recognition events, yet achieving the time resolution and statistics needed to realize this potential has proven challenging. Here we present a single-molecule imaging and analysis platform using scientific complementary metal-oxide semiconductor (sCMOS) detectors that enables imaging of 15,000 individual molecules simultaneously at millisecond rates. This system enabled the detection of previously obscured processes relevant to the fidelity mechanism in protein synthesis. PMID:26878382

  13. Hydrophobic Porous Material Adsorbs Small Organic Molecules

    NASA Technical Reports Server (NTRS)

    Sharma, Pramod K.; Hickey, Gregory S.

    1994-01-01

    Composite molecular-sieve material has pore structure designed specifically for preferential adsorption of organic molecules for sizes ranging from 3 to 6 angstrom. Design based on principle that contaminant molecules become strongly bound to surface of adsorbent when size of contaminant molecules is nearly same as that of pores in adsorbent. Material used to remove small organic contaminant molecules from vacuum systems or from enclosed gaseous environments like closed-loop life-support systems.

  14. Spin squeezing a cold molecule

    NASA Astrophysics Data System (ADS)

    Bhattacharya, M.

    2015-12-01

    In this article we present a concrete proposal for spin squeezing the cold ground-state polar paramagnetic molecule OH, a system currently under fine control in the laboratory. In contrast to existing work, we consider a single, noninteracting molecule with angular momentum greater than 1 /2 . Starting from an experimentally relevant effective Hamiltonian, we identify an adiabatic regime where different combinations of static electric and magnetic fields can be used to realize the single-axis twisting Hamiltonian of Kitagawa and Ueda [M. Kitagawa and M. Ueda, Phys. Rev. A 47, 5138 (1993), 10.1103/PhysRevA.47.5138], the uniform field Hamiltonian proposed by Law et al. [C. K. Law, H. T. Ng, and P. T. Leung, Phys. Rev. A 63, 055601 (2001), 10.1103/PhysRevA.63.055601], and a model of field propagation in a Kerr medium considered by Agarwal and Puri [G. S. Agarwal and R. R. Puri, Phys. Rev. A 39, 2969 (1989), 10.1103/PhysRevA.39.2969]. We then consider the situation in which nonadiabatic effects are quite large and show that the effective Hamiltonian supports spin squeezing even in this case. We provide analytical expressions as well as numerical calculations, including optimization of field strengths and accounting for the effects of field misalignment. Our results have consequences for applications such as precision spectroscopy, techniques such as magnetometry, and stereochemical effects such as the orientation-to-alignment transition.

  15. Electronic spectroscopy of diatomic molecules

    NASA Technical Reports Server (NTRS)

    Partridge, Harry; Langhoff, Stephen R.; Bauschlicher, Charles W., Jr.

    1994-01-01

    This article provides an overview of the principal computational approaches and their accuracy for the study of electronic spectroscopy of diatomic molecules. We include a number of examples from our work that illustrate the range of application. We show how full configuration interaction benchmark calculations were instrumental in improving the understanding of the computational requirements for obtaining accurate results for diatomic spectroscopy. With this understanding it is now possible to compute radiative lifetimes accurate to within 10% for systems involving first- and second-row atoms. We consider the determination of the infrared vibrational transition probabilities for the ground states of SiO and NO, based on a globally accurate dipole moment function. We show how we were able to assign the a(sup "5)II state of CO as the upper state in the recently observed emission bands of CO in an Ar matrix. We next discuss the assignment of the photoelectron detachment spectra of NO and the alkali oxide negative ions. We then present several examples illustrating the state-of-the-art in determining radiative lifetimes for valence-valence and valence-Rydberg transitions. We next compare the molecular spectroscopy of the valence isoelectronic B2, Al2, and AlB molecules. The final examples consider systems involving transition metal atoms, which illustrate the difficulty in describing states with different numbers of d electrons.

  16. Characterization of Interstellar Organic Molecules

    SciTech Connect

    Gencaga, Deniz; Knuth, Kevin H.; Carbon, Duane F.

    2008-11-06

    Understanding the origins of life has been one of the greatest dreams throughout history. It is now known that star-forming regions contain complex organic molecules, known as Polycyclic Aromatic Hydrocarbons (PAHs), each of which has particular infrared spectral characteristics. By understanding which PAH species are found in specific star-forming regions, we can better understand the biochemistry that takes place in interstellar clouds. Identifying and classifying PAHs is not an easy task: we can only observe a single superposition of PAH spectra at any given astrophysical site, with the PAH species perhaps numbering in the hundreds or even thousands. This is a challenging source separation problem since we have only one observation composed of numerous mixed sources. However, it is made easier with the help of a library of hundreds of PAH spectra. In order to separate PAH molecules from their mixture, we need to identify the specific species and their unique concentrations that would provide the given mixture. We develop a Bayesian approach for this problem where sources are separated from their mixture by Metropolis Hastings algorithm. Separated PAH concentrations are provided with their error bars, illustrating the uncertainties involved in the estimation process. The approach is demonstrated on synthetic spectral mixtures using spectral resolutions from the Infrared Space Observatory (ISO). Performance of the method is tested for different noise levels.

  17. Computational analysis of the reactive properties of some nitrosoaromatic molecules

    SciTech Connect

    Politzer, P.; Bar-Adon, R.

    1987-04-09

    The interactions of a nitroso (NO) substituent with an aromatic ring and with an amino group on that ring, and the manner in which these affect the overall molecular reactivity, have been studied by ab initio SCF molecular orbital calculations. The Gaussian 82 program was used to first optimize the structures of nitrosobenzene and the three isomeric nitrosoanilines, at the 3-21G level, and then to compute the STO-5G molecular electrostatic potentials. The NO was found to deactivate the ring toward electrophilic attack, even in the presence of NH/sub 2/, although the directing properties of the latter are evident. For each molecule, the strongest negative potential is associated with the lone pair of the nitroso nitrogen. All the molecules show buildups of positive potential above the C-NO portions, within the C-N-O angles; these are interpreted as possible routes for nucleophilic attack.

  18. Time scales for molecule formation by ion-molecule reactions

    NASA Technical Reports Server (NTRS)

    Langer, W. D.; Glassgold, A. E.

    1976-01-01

    Analytical solutions are obtained for nonlinear differential equations governing the time-dependence of molecular abundances in interstellar clouds. Three gas-phase reaction schemes are considered separately for the regions where each dominates. The particular case of CO, and closely related members of the Oh and CH families of molecules, is studied for given values of temperature, density, and the radiation field. Nonlinear effects and couplings with particular ions are found to be important. The time scales for CO formation range from 100,000 to a few million years, depending on the chemistry and regime. The time required for essentially complete conversion of C(+) to CO in the region where the H3(+) chemistry dominates is several million years. Because this time is longer than or comparable to dynamical time scales for dense interstellar clouds, steady-state abundances may not be observed in such clouds.

  19. Ultrafast electron diffraction from aligned molecules

    SciTech Connect

    Centurion, Martin

    2015-08-17

    The aim of this project was to record time-resolved electron diffraction patterns of aligned molecules and to reconstruct the 3D molecular structure. The molecules are aligned non-adiabatically using a femtosecond laser pulse. A femtosecond electron pulse then records a diffraction pattern while the molecules are aligned. The diffraction patterns are then be processed to obtain the molecular structure.

  20. Mechanical studies on single molecules: general considerations

    NASA Astrophysics Data System (ADS)

    Bensimon, David; Croquette, Vincent

    2015-10-01

    The following sections are included: * Elements of molecular biology * Advantages and drawbacks of single molecule studies * Order of magnitude of the relevant parameters at the single molecule level * Single molecule manipulation techniques * Comparison of the different techniques * DNA mechanical properties * Conclusion * Bibliography

  1. Single-molecule decoding of combinatorially modified nucleosomes.

    PubMed

    Shema, Efrat; Jones, Daniel; Shoresh, Noam; Donohue, Laura; Ram, Oren; Bernstein, Bradley E

    2016-05-01

    Different combinations of histone modifications have been proposed to signal distinct gene regulatory functions, but this area is poorly addressed by existing technologies. We applied high-throughput single-molecule imaging to decode combinatorial modifications on millions of individual nucleosomes from pluripotent stem cells and lineage-committed cells. We identified definitively bivalent nucleosomes with concomitant repressive and activating marks, as well as other combinatorial modification states whose prevalence varies with developmental potency. We showed that genetic and chemical perturbations of chromatin enzymes preferentially affect nucleosomes harboring specific modification states. Last, we combined this proteomic platform with single-molecule DNA sequencing technology to simultaneously determine the modification states and genomic positions of individual nucleosomes. This single-molecule technology has the potential to address fundamental questions in chromatin biology and epigenetic regulation. PMID:27151869

  2. Chemical materials and their regulation of the movement of molecules.

    PubMed

    Langer, Robert

    2015-11-01

    Materials chemistry has been fundamental to the enormous field that encompasses the delivery of molecules both to desired sites and/or at desired rates and durations. The field encompasses the delivery of molecules including fertilizers, pesticides, herbicides, food ingredients, fragrances and biopharmaceuticals. A personal perspective is provided on our early work in this field that has enabled the controlled release of ionic substances and macromolecules. Also discussed are new paradigms in creating biomaterials for human use, the non-invasive delivery of molecules through the skin and lungs, the development of intelligent delivery systems and extensions to nanomedicine. With the advent of potentially newer biopharmaceutics such as siRNA, mRNA and gene editing approaches and their use being limited by delivery, future research in this field may be more critical than ever before. PMID:26537401

  3. Proposal for the formation of ultracold paramagnetic polar molecules

    NASA Astrophysics Data System (ADS)

    Dulieu, Olivier; Borsalino, Dimitri; Luc, Eliane; Bouloufa-Maafa, Nadia; Zuchowski, Piotr

    2016-05-01

    Alkali-alkaline-earth dimers, such as RbCa and RbSr, possess (in their ground electronic state) both a permanent magnetic and electric dipole moment in the molecular frame, allowing their manipulation with external fields at ultracold temperatures. Such molecules have been proposed as candidates for quantum simulators. We propose an efficient method combining a photoassociation step and a stimulated Raman process to create ultracold RbSr and RbCa molecules in their absolute ground state, suitable for studying dipolar interactions in quantum gases. Our model is based on new accurate quantum chemistry computations of potential energy surfaces of ground and excited molecular states and of relevant transition dipole moments of these molecules. The results are in good agreement with recent low-resolution spectroscopic data recorded with Helium nanodroplets.

  4. Stochastic electrotransport selectively enhances the transport of highly electromobile molecules.

    PubMed

    Kim, Sung-Yon; Cho, Jae Hun; Murray, Evan; Bakh, Naveed; Choi, Heejin; Ohn, Kimberly; Ruelas, Luzdary; Hubbert, Austin; McCue, Meg; Vassallo, Sara L; Keller, Philipp J; Chung, Kwanghun

    2015-11-17

    Nondestructive chemical processing of porous samples such as fixed biological tissues typically relies on molecular diffusion. Diffusion into a porous structure is a slow process that significantly delays completion of chemical processing. Here, we present a novel electrokinetic method termed stochastic electrotransport for rapid nondestructive processing of porous samples. This method uses a rotational electric field to selectively disperse highly electromobile molecules throughout a porous sample without displacing the low-electromobility molecules that constitute the sample. Using computational models, we show that stochastic electrotransport can rapidly disperse electromobile molecules in a porous medium. We apply this method to completely clear mouse organs within 1-3 days and to stain them with nuclear dyes, proteins, and antibodies within 1 day. Our results demonstrate the potential of stochastic electrotransport to process large and dense tissue samples that were previously infeasible in time when relying on diffusion. PMID:26578787

  5. On the Several Molecules and Nanostructures of Water

    PubMed Central

    Whitney, Cynthia Kolb

    2012-01-01

    This paper investigates the water molecule from a variety of viewpoints. Water can involve different isotopes of Hydrogen and Oxygen, it can form differently shaped isomer molecules, and, when frozen, it occupies space differently than most other substances do. The tool for conducting the investigation of all this is called ‘Algebraic Chemistry’. This tool is a quantitative model for predicting the energy budget for all sorts of changes between different ionization states of atoms that are involved in chemical reactions and in changes of physical state. The model is based on consistent patterns seen in empirical data about ionization potentials, together with rational scaling laws that can interpolate and extrapolate for situations where no data are available. The results of the investigation of the water molecule include comments, both positive and negative, about technologies involving heavy water, poly water, Brown’s gas, and cold fusion. PMID:22312305

  6. Model for the hyperfine structure of electronically excited KCs molecules

    NASA Astrophysics Data System (ADS)

    Orbán, A.; Vexiau, R.; Krieglsteiner, O.; Nägerl, H.-C.; Dulieu, O.; Crubellier, A.; Bouloufa-Maafa, N.

    2015-09-01

    A model for determining the hyperfine structure of the excited electronic states of diatomic bialkali heteronuclear molecules is formulated from the atomic hyperfine interactions and is applied to the case of bosonic 39KCs and fermionic 40KCs molecules. The hyperfine structure of the potential-energy curves of the states correlated to the K (4 s 2S1 /2) +Cs (6 p 2P1 /2 ,3 /2) dissociation limits is described in terms of different coupling schemes depending on the internuclear distance R . These results provide a step in the calculation of the hyperfine structure of rovibrational levels of these excited molecular states in the perspective of the identification of efficient paths for creating ultracold ground-state KCs molecules.

  7. On the several molecules and nanostructures of water.

    PubMed

    Whitney, Cynthia Kolb

    2012-01-01

    This paper investigates the water molecule from a variety of viewpoints. Water can involve different isotopes of Hydrogen and Oxygen, it can form differently shaped isomer molecules, and, when frozen, it occupies space differently than most other substances do. The tool for conducting the investigation of all this is called 'Algebraic Chemistry'. This tool is a quantitative model for predicting the energy budget for all sorts of changes between different ionization states of atoms that are involved in chemical reactions and in changes of physical state. The model is based on consistent patterns seen in empirical data about ionization potentials, together with rational scaling laws that can interpolate and extrapolate for situations where no data are available. The results of the investigation of the water molecule include comments, both positive and negative, about technologies involving heavy water, poly water, Brown's gas, and cold fusion. PMID:22312305

  8. Cancer Immunotherapy: Selected Targets and Small-Molecule Modulators.

    PubMed

    Weinmann, Hilmar

    2016-03-01

    There is a significant amount of excitement in the scientific community around cancer immunotherapy, as this approach has renewed hope for many cancer patients owing to some recent successes in the clinic. Currently available immuno-oncology therapeutics under clinical development and on the market are mostly biologics (antibodies, proteins, engineered cells, and oncolytic viruses). However, modulation of the immune system with small molecules offers several advantages that may be complementary and potentially synergistic to the use of large biologicals. Therefore, the discovery and development of novel small-molecule modulators is a rapidly growing research area for medicinal chemists working in cancer immunotherapy. This review provides a brief introduction into recent trends related to selected targets and pathways for cancer immunotherapy and their small-molecule pharmacological modulators. PMID:26836578

  9. Infrared spectra of molecules and materials of astrophysical interest

    NASA Technical Reports Server (NTRS)

    Durig, J. R.

    1975-01-01

    The vibrational spectra from 4000 to 33 cm-1 of several modecules which may be present in the atmosphere of the Jovian planets are studied to provide vibrational frequencies which can be used to: (1) determine the composition of the cloud covers of several of the planets; (2) provide structural information under favorable circumstances; (3) provide necessary data from which accurate thermodynamic data can be calculated; and (4) furnish information as to the nature of the potential energy function of the molecules and forces acting within them. Some of the molecules are produced photochemically from methane, ammonia, and hydrogen sulfide which are thought to be constituents of the planets with reducing atmospheres. Some of the compounds polymerize under ultraviolet radiation and drop out of the atmospheres. However, planets with a hot base, like that of Jupiter, may rebuild molecules destroyed photochemically.

  10. Electrochemical Single-Molecule Transistors with Optimized Gate Coupling.

    PubMed

    Osorio, Henrry M; Catarelli, Samantha; Cea, Pilar; Gluyas, Josef B G; Hartl, František; Higgins, Simon J; Leary, Edmund; Low, Paul J; Martín, Santiago; Nichols, Richard J; Tory, Joanne; Ulstrup, Jens; Vezzoli, Andrea; Milan, David C; Zeng, Qiang

    2015-11-18

    Electrochemical gating at the single molecule level of viologen molecular bridges in ionic liquids is examined. Contrary to previous data recorded in aqueous electrolytes, a clear and sharp peak in the single molecule conductance versus electrochemical potential data is obtained in ionic liquids. These data are rationalized in terms of a two-step electrochemical model for charge transport across the redox bridge. In this model the gate coupling in the ionic liquid is found to be fully effective with a modeled gate coupling parameter, ξ, of unity. This compares to a much lower gate coupling parameter of 0.2 for the equivalent aqueous gating system. This study shows that ionic liquids are far more effective media for gating the conductance of single molecules than either solid-state three-terminal platforms created using nanolithography, or aqueous media. PMID:26488257

  11. The synthesis of complex molecules in interstellar clouds

    NASA Technical Reports Server (NTRS)

    Huntress, W. T., Jr.; Mitchell, G. F.

    1979-01-01

    The abundances of polyatomic molecules that may be formed by CH3(+) radiative association reactions in dense interstellar molecular clouds are reevaluated. The formation of a number of complex interstellar molecules via radiative association reactions involving ionic precursors other than CH3(+) is also investigated; these additional precursors include CH3O(+), CH3CO(+), CH5(+), HCO(+), NO(+), H2CN(+), C2H2(+), and NH3(+). The results indicate that the postulated gas-phase ion-molecule radiative association reactions could potentially explain the synthesis of most of the more complex species observed in dense molecular clouds such as Sgr B2. It is concluded, however, that in order to be conclusive, laboratory data are needed to show whether or not these reactions proceed at the required rates at low temperatures.

  12. Hovering and Twirling of Tethered Molecules by Confinement between Surfaces.

    PubMed

    Rios, Laura; Lee, Joonhee; Tallarida, Nicholas; Apkarian, V Ara

    2016-07-01

    Through STM images, we show that azobenzene-terminated alkanethiols hover and twirl when confined between the Ag tip and Au(111) substrate of an STM junction. In contrast with mechanisms of activation used to drive molecular rotors, twirling is induced by the effective elimination of lateral corrugation in the energy landscape when molecules hover by their van der Waals attraction to the approaching tip. While in the stationary state the benzenes of the head group lie flat with an inter-ring separation of 7.5 Å, they stand on-edge as the molecule twirls and their separation contracts to 5.2 Å, close to the value of the free molecule. The captured images of motion allow the characterization of physisorption potentials. PMID:27300256

  13. Stochastic electrotransport selectively enhances the transport of highly electromobile molecules

    PubMed Central

    Kim, Sung-Yon; Cho, Jae Hun; Murray, Evan; Bakh, Naveed; Choi, Heejin; Ohn, Kimberly; Ruelas, Luzdary; Hubbert, Austin; McCue, Meg; Vassallo, Sara L.; Keller, Philipp J.; Chung, Kwanghun

    2015-01-01

    Nondestructive chemical processing of porous samples such as fixed biological tissues typically relies on molecular diffusion. Diffusion into a porous structure is a slow process that significantly delays completion of chemical processing. Here, we present a novel electrokinetic method termed stochastic electrotransport for rapid nondestructive processing of porous samples. This method uses a rotational electric field to selectively disperse highly electromobile molecules throughout a porous sample without displacing the low-electromobility molecules that constitute the sample. Using computational models, we show that stochastic electrotransport can rapidly disperse electromobile molecules in a porous medium. We apply this method to completely clear mouse organs within 1–3 days and to stain them with nuclear dyes, proteins, and antibodies within 1 day. Our results demonstrate the potential of stochastic electrotransport to process large and dense tissue samples that were previously infeasible in time when relying on diffusion. PMID:26578787

  14. How Many Water Molecules Does it Take to Dissociate HCl?

    PubMed

    Vargas-Caamal, Alba; Cabellos, Jose Luis; Ortiz-Chi, Filiberto; Rzepa, Henry S; Restrepo, Albeiro; Merino, Gabriel

    2016-02-18

    The potential energy surfaces of the HCl(H2O)n (n is the number of water molecules) clusters are systematically explored using density functional theory and high-level ab initio computations. On the basis of electronic energies, the number of water molecules needed for HCl dissociation is four as reported by some experimental groups. However, this number is five owing to the inclusion of entropic factors. Wiberg bond indices are calculated and analyzed, and the results provide a quadratic correlation and classification of clusters according to the nondissociated, partially dissociated, and fully dissociated character of the H-Cl bond. Our computations show that if temperature is not controlled during the experiment, the values obtained for the dipole moment (or for any measurable property) are susceptible to change, providing a different picture of the number of water molecules needed for HCl dissociation in a nanoscopic droplet. PMID:26774026

  15. Shape of a water molecule as function of OH separation

    NASA Astrophysics Data System (ADS)

    Gabbay, I.; March, N. H.

    1980-02-01

    For small O-H separation the water molecule becomes linear. The Murrell-Sorbie potential energy surface affords a basis to study the shape of the molecule for larger OH separation. The possible relevance to H 2O outside a metal surface is discussed.

  16. Nanometer Resolution Imaging by SIngle Molecule Switching

    SciTech Connect

    Hu, Dehong; Orr, Galya

    2010-04-02

    The fluorescence intensity of single molecules can change dramatically even under constant laser excitation. The phenomenon is frequently called "blinking" and involves molecules switching between high and low intensity states.[1-3] In additional to spontaneous blinking, the fluorescence of some special fluorophores, such as cyanine dyes and photoactivatable fluorescent proteins, can be switched on and off by choice using a second laser. Recent single-molecule spectroscopy investigations have shed light on mechanisms of single molecule blinking and photoswitching. This ability to controllably switch single molecules led to the invention of a novel fluorescence microscopy with nanometer spatial resolution well beyond the diffraction limit.

  17. Allosteric Small-Molecule Inhibitors of the AKT Kinase

    NASA Astrophysics Data System (ADS)

    Dalafave, D. S.

    This research addresses computational design of small druglike molecules for possible anticancer applications. AKT and SGK are kinases that control important cellular functions. They are highly homologous, having similar activators and targets. Cancers with increased SGK activity may develop resistance to AKT-specific inhibitors. Our goal was to design new molecules that would bind both AKT and SGK, thus preventing the development of drug resistance. Most kinase inhibitors target the kinase ATP-binding site. However, the high similarity in this site among kinases makes it difficult to target specifically. Furthermore, mutations in this site can cause resistance to ATP-competitive kinase inhibitors. We used existing AKT inhibitors as initial templates to design molecules that could potentially bind the allosteric sites of both AKT and SGK. Molecules with no implicit toxicities and optimal drug-like properties were used for docking studies. Binding energies of the stable complexes that the designed molecules formed with AKT and SGK were calculated. Possible applications of the designed putative inhibitors against cancers with overexpressed AKT/SGK is discussed.

  18. Ultracold Long-Range Rydberg Molecules with Complex Multichannel Spectra

    NASA Astrophysics Data System (ADS)

    Eiles, Matthew; Greene, Chris

    2016-05-01

    A generalized class of exotic long-range Rydberg molecules consisting of a multichannel Rydberg atom bound to a distant ground state atom by the Rydberg electron is predicted. These molecules are characterized by the rich physics provided by the strongly perturbed multichannel Rydberg spectra of divalent atoms, in contrast to the regular Rydberg series of the alkali atoms used to form Rydberg molecules to date. These multichannel Rydberg molecules exhibit favorable properties for laser excitation, because states exist where the quantum defect varies strongly with the principal quantum number n. In particular, the nd Rydberg state of calcium becomes nearly degenerate with states of high orbital angular momentum over the range 17 < n < 22 , promoting its admixture into the high l deeply bound ``trilobite'' molecule states and thereby circumventing the usual difficulty posed by electric dipole selection rules. Further novel molecular states are predicted to occur in the low- J states of silicon, which are strongly perturbed due to channel interactions between Rydberg series leading to the spin-orbit split ionization thresholds. These interactions manifest themselves in potential curves exhibiting two distinct length scales, providing novel opportunities for quantum manipulation. Supported in part by the National Science Foundation under Grant No. PHY-1306905.

  19. Manipulation of Costimulatory Molecules by Intracellular Pathogens: Veni, Vidi, Vici!!

    PubMed Central

    Pahari, Susanta; Agrewala, Javed N.

    2012-01-01

    Some of the most successful pathogens of human, such as Mycobacterium tuberculosis (Mtb), HIV, and Leishmania donovani not only establish chronic infections but also remain a grave global threat. These pathogens have developed innovative strategies to evade immune responses such as antigenic shift and drift, interference with antigen processing/presentation, subversion of phagocytosis, induction of immune regulatory pathways, and manipulation of the costimulatory molecules. Costimulatory molecules expressed on the surface of various cells play a decisive role in the initiation and sustenance of immunity. Exploitation of the “code of conduct” of costimulation pathways provides evolutionary incentive to the pathogens and thereby abates the functioning of the immune system. Here we review how Mtb, HIV, Leishmania sp., and other pathogens manipulate costimulatory molecules to establish chronic infection. Impairment by pathogens in the signaling events delivered by costimulatory molecules may be responsible for defective T-cell responses; consequently organisms grow unhindered in the host cells. This review summarizes the convergent devices that pathogens employ to tune and tame the immune system using costimulatory molecules. Studying host-pathogen interaction in context with costimulatory signals may unveil the molecular mechanism that will help in understanding the survival/death of the pathogens. We emphasize that the very same pathways can potentially be exploited to develop immunotherapeutic strategies to eliminate intracellular pathogens. PMID:22719245

  20. Infrared Spectroscopy of Molecules in the Gas Phase

    NASA Astrophysics Data System (ADS)

    Zhang, Keqing

    Fourier transform infrared spectroscopy is applied to the studies of several very different molecular systems. The spectra of the diatomic molecules BF, AlF, and MgF were recorded and analyzed. Dunham coefficients were obtained. The data of two isotopomers, 11BF and 10BF, were used to determine the mass-reduced Dunham coefficients, along with Born-Oppenheimer breakdown constants. Parameterized potential energy functions of BF and AlF were determined by fitting the available data using the solutions of the radial Schrodinger equation. Two vibrational modes of the short-lived and reactive BrCNO molecule were recorded at high resolution. Rotation-vibration transitions of the fundamental bands of both isotopomers 79BrCNO and 81BrCNO were assigned and analyzed. From the rotational constants, it was found that the Br-C bond length in BrCNO anomalously short when a linear geometry was assumed. This may indicate that BrCNO is quasi-linear, simulating the parent HCNO molecule. The emission spectra of the gaseous polycyclic aromatic hydrocarbon (PAH) molecules naphthalene, anthracene, pyrene, and chrysene were recorded in the far-infrared and mid-infrared regions. The assignments of fundamental modes and some combination modes were made. The vibrational bands that lie in the far-infrared are unique for different PAHs and allow discrimination among the four PAH molecules. The far-infrared PAH spectra, therefore, may prove useful in the assignments of unidentified spectral features from astronomical objects.