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Sample records for molecular pattern molecules

  1. Endogenous Damage-Associated Molecular Pattern Molecules at the Crossroads of Inflammation and Cancer1

    PubMed Central

    Srikrishna, Geetha; Freeze, Hudson H

    2009-01-01

    Inflammatory mediators play important roles in the development and progression of cancer. Cellular stress, damage, inflammation, and necrotic cell death cause release of endogenous damage-associated molecular pattern (DAMP) molecules or alarmins, which alert the host of danger by triggering immune responses and activating repair mechanisms through their interaction with pattern recognition receptors. Recent studies show that abnormal persistence of these molecules in chronic inflammation and in tumor microenvironments underlies carcinogenesis and tumor progression, indicating that DAMP molecules and their receptors could provide novel targets for therapy. This review focuses on the role of DAMP molecules high-mobility group box 1 and S100 proteins in inflammation, tumor growth, and early metastatic events. PMID:19568407

  2. The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity.

    PubMed

    Lotze, Michael T; Zeh, Herbert J; Rubartelli, Anna; Sparvero, Louis J; Amoscato, Andrew A; Washburn, Newell R; Devera, Michael E; Liang, Xiaoyan; Tör, Mahmut; Billiar, Timothy

    2007-12-01

    The response to pathogens and damage in plants and animals involves a series of carefully orchestrated, highly evolved, molecular mechanisms resulting in pathogen resistance and wound healing. In metazoans, damage- or pathogen-associated molecular pattern molecules (DAMPs, PAMPs) execute precise intracellular tasks and are also able to exert disparate functions when released into the extracellular space. The emergent consequence for both inflammation and wound healing of the abnormal extracellular persistence of these factors may underlie many clinical disorders. DAMPs/PAMPs are recognized by hereditable receptors including the Toll-like receptors, the NOD1-like receptors and retinoic-acid-inducible gene I-like receptors, as well as the receptor for advanced glycation end products. These host molecules 'sense' not only pathogens but also misfolded/glycated proteins or exposed hydrophobic portions of molecules, activating intracellular cascades that lead to an inflammatory response. Equally important are means to not only respond to these molecules but also to eradicate them. We have speculated that their destruction through oxidative mechanisms normally exerted by myeloid cells, such as neutrophils and eosinophils, or their persistence in the setting of pathologic extracellular reducing environments, maintained by exuberant necrotic cell death and/or oxidoreductases, represent important molecular means enabling chronic inflammatory states. PMID:17979840

  3. Targeting damage-associated molecular pattern molecules (DAMPs) and DAMP receptors in melanoma.

    PubMed

    Boone, Brian A; Lotze, Michael T

    2014-01-01

    Damage-associated molecular pattern molecules (DAMPs) are proteins released from cells under stress due to nutrient deprivation, hypoxia, trauma, or treatment with chemotherapy, among a variety of other causes. When released, DAMPs activate innate immunity, providing a pathway to a systemic inflammatory response in the absence of infection. By regulating inflammation in the tumor microenvironment, promoting angiogenesis, and increasing autophagy with evasion of apoptosis, DAMPs facilitate cancer growth. DAMPs and DAMP receptors have a key role in melanoma pathogenesis. Due to their crucial role in the development of melanoma and chemoresistance, DAMPs represent intriguing targets at a time when novel treatments are desperately needed. PMID:24258998

  4. Cell Death-Associated Molecular-Pattern Molecules: Inflammatory Signaling and Control

    PubMed Central

    Sangiuliano, Beatriz; Pérez, Nancy Marcela; Moreira, Dayson F.; Belizário, José E.

    2014-01-01

    Apoptosis, necroptosis, and pyroptosis are different cellular death programs characterized in organs and tissues as consequence of microbes infection, cell stress, injury, and chemotherapeutics exposure. Dying and death cells release a variety of self-proteins and bioactive chemicals originated from cytosol, nucleus, endoplasmic reticulum, and mitochondria. These endogenous factors are named cell death-associated molecular-pattern (CDAMP), damage-associated molecular-pattern (DAMP) molecules, and alarmins. Some of them cooperate or act as important initial or delayed inflammatory mediators upon binding to diverse membrane and cytosolic receptors coupled to signaling pathways for the activation of the inflammasome platforms and NF-κB multiprotein complexes. Current studies show that the nonprotein thiols and thiol-regulating enzymes as well as highly diffusible prooxidant reactive oxygen and nitrogen species released together in extracellular inflammatory milieu play essential role in controlling pro- and anti-inflammatory activities of CDAMP/DAMP and alarmins. Here, we provide an overview of these emerging concepts and mechanisms of triggering and maintenance of tissue inflammation under massive death of cells. PMID:25140116

  5. Kawasaki Disease-Specific Molecules in the Sera Are Linked to Microbe-Associated Molecular Patterns in the Biofilms

    PubMed Central

    Murata, Kenji; Kanno, Shunsuke; Nishio, Hisanori; Saito, Mitsumasa; Tanaka, Tamami; Yamamura, Kenichiro; Sakai, Yasunari; Takada, Hidetoshi; Miyamoto, Tomofumi; Mizuno, Yumi; Ouchi, Kazunobu; Waki, Kenji; Hara, Toshiro

    2014-01-01

    Background Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The innate immune system is involved in its pathophysiology at the acute phase. We have recently established a novel murine model of KD coronary arteritis by oral administration of a synthetic microbe-associated molecular pattern (MAMP). On the hypothesis that specific MAMPs exist in KD sera, we have searched them to identify KD-specific molecules and to assess the pathogenesis. Methods We performed liquid chromatography-mass spectrometry (LC-MS) analysis of fractionated serum samples from 117 patients with KD and 106 controls. Microbiological and LC-MS evaluation of biofilm samples were also performed. Results KD samples elicited proinflammatory cytokine responses from human coronary artery endothelial cells (HCAECs). By LC-MS analysis of KD serum samples collected at 3 different periods, we detected a variety of KD-specific molecules in the lipophilic fractions that showed distinct m/z and MS/MS fragmentation patterns in each cluster. Serum KD-specific molecules showed m/z and MS/MS fragmentation patterns almost identical to those of MAMPs obtained from the biofilms formed in vitro (common MAMPs from Bacillus cereus, Yersinia pseudotuberculosis and Staphylococcus aureus) at the 1st study period, and from the biofilms formed in vivo (common MAMPs from Bacillus cereus, Bacillus subtilis/Bacillus cereus/Yersinia pseudotuberculosis and Staphylococcus aureus) at the 2nd and 3rd periods. The biofilm extracts from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus aureus also induced proinflammatory cytokines by HCAECs. By the experiments with IgG affinity chromatography, some of these serum KD-specific molecules bound to IgG. Conclusions We herein conclude that serum KD-specific molecules were mostly derived from biofilms and possessed molecular structures common to MAMPs from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus

  6. Damage Associated Molecular Pattern Molecule-Induced microRNAs (DAMPmiRs) in Human Peripheral Blood Mononuclear Cells

    PubMed Central

    Unlu, Sebnem; Tang, Siuwah; Wang, E. na; Martinez, Ivan; Tang, Daolin; Bianchi, Marco E.; Zeh, Herbert J.; Lotze, Michael T.

    2012-01-01

    Endogenous damage associated molecular pattern molecules (DAMPs) released from necrotic, damaged or stressed cells are associated with an inflammatory response. Whether the microRNA (miR) expression signature of this response is different from that of a pathogen associated molecular pattern (PAMP)-stimulated inflammatory response is unknown. We report here that miR-34c and miR-214 are significantly expressed in fresh human peripheral blood mononuclear cells (PBMCs) exposed to DAMP-containing freeze-thaw lysates, or to conditioned media from serum-starved and glucose-deprived cells (p<6×10−4 and p<3.7×10−3), respectively. Interestingly, only miR-34c expression was differentially expressed in PBMCs exposed to freeze-thaw lysates or conditioned media from wildtype High Mobility Group B1 (HMGB1+/+) mouse embryonic fibroblast (MEF) cells, when compared to cultures exposed to lysates or conditioned media from HMGB1−/− MEFs. miR-155 expression in these cultures was negligible, but was significantly expressed in PBMCs stimulated with Lipopolysaccahride (LPS) or most other Toll-like receptor (TLR) ligands, making it the prototypic “PAMPmiR”. Exposure to a damaged human colorectal carcinoma cell line lysate (HCT116) similarly resulted in increased miR-34c and miR-214 levels. When PBMCs were pre-transfected with anti-miR-34c and then exposed to lysate, expression levels of IKKγ mRNA, a putative target of miR-34c, increased, while protein levels of IKKγ in cultures transfected with a pre-miR-34c were abrogated. Levels of miR-34c expression (as well as pro-inflammatory cytokines, IL-1β and TNFα) decreased when PBMC cultures were briefly pre-incubated with the K+ channel (inflammasome) inhibitor, glybenclamide, suggesting that inflammasome activation is upstream of miR-34c expression in response to DAMPs. Our findings demonstrate that a specific microRNA expression signature is associated with the inflammatory response to damaged/injured cells and carries

  7. IgG antibodies from dourine infected horses identify a distinctive Trypanosoma equiperdum antigenic pattern of low molecular weight molecules.

    PubMed

    Luciani, M; Di Pancrazio, C; Di Febo, T; Tittarelli, M; Podaliri Vulpiani, M; Puglielli, M O; Naessens, J; Sacchini, F

    2013-01-15

    Diagnosis and control of dourine is strongly based on serological evidence, but knowledge of the humoral response of horses during infection is limited. In this study we developed a chemiluminescent immunoblotting (cIB) assay to characterise the Trypanosoma equiperdum antigen pattern recognised by IgGs from naturally or experimentally dourine-infected horses and analyse the kinetics of IgG humoral response following the infection. One compounding factor is that sera from uninfected animals often cross-react with T. equiperdum antigens. Development of the cIB assay was based on the hypothesis that serum IgGs from healthy and infected animals recognise different T. equiperdum antigen patterns. We used sera from 8 naturally infected horses which had recovered from Italian outbreaks and 2 experimentally infected mares. In addition, sera from 10 healthy control animals, eight of which were CFT positive but IFA negative for dourine, were collected from disease free regions. Sera were compared by the complement fixation test (CFT), indirect immune fluorescence (IFA) and the cIB assay. cIB analysis revealed that IgGs from infected horses, in contrast to IgGs from healthy horses, specifically recognise a T. equiperdum antigenic profile with low molecular weight bands ranging between 16 and 35 kDa. A time course experiment indicated that IgGs specific for the 16-35 kDa parasite protein fraction appear 17 days post-infection. The cIB assay confirmed all ten infected animals as positive and all controls as negative. This study demonstrated that analysis of IgGs by cIB can provide clear confirmation of trypanosome infection in horses, suggesting that this technique can be applied as a confirmatory serological test for dourine infection. PMID:23218944

  8. Molecular cloning, expression pattern, and phylogenetic analysis of a tetraspanin CD82-like molecule in lamprey Lampetra japonica.

    PubMed

    Zhang, Xiaoping; Song, Xueying; Su, Peng; Gou, Meng; Wang, Hao; Liu, Xin; Li, Qingwei

    2016-03-01

    CD82, a member of the tetraspanins, is originally identified as an accessory molecule in T cell activation, and it participates in the formation of immune synapse both in T cells and antigen-presenting cells of jawed vertebrates. In the present study, a CD82 homologous complementary DNA (cDNA) sequence is identified in the lamprey Lampetra japonica. The open reading frame of this sequence is 801 bp long and encodes a 266-amino acid protein. The multialignment of this sequence with several typical CD82s and CD37s of jawed vertebrates shows that it also possesses their conserved four transmembrane domains and a six-cysteine motif Cys-Cys-Gly…Cys-Ser-Cys…Cys…Cys, which is a characteristic motif of CD82 and CD37 vertebrate tetraspanin sequences. Since it is close to CD82s in sequence similarity, we name it as Lja-CD82-like. From the distribution profile of the conserved motifs of CD82-like, CD82, and CD37 molecules from molluscas to mammals, it seems that the CD82s and CD37s evolved from a common ancestral gene through a gene duplication event to their modern forms by a short insertion or substitution approaches. The phylogenetic analysis indicated that CD82 and CD37 molecules of jawed vertebrates originated from a common ancestral gene which is close to agnathan CD82-like and evolved into two distinct paralogous groups maybe after the divergence of jawed and jawless vertebrates. An expression vector with trigger factor (TF) was constructed to ensure that Lja-CD82-like express in prokaryotic expression host. The expressions of Lja-CD82-like messenger RNA (mRNA) and protein in immune-related tissues of lamprey were detected by real-time quantitative polymerase chain reaction and western blotting. Results showed that the mRNA and the protein levels of Lja-CD82-like were significantly upregulated in lymphocyte-like cells, gills, and supraneural myeloid bodies after stimulation with mixed antigens, respectively. Our data provided a foundation for the further study

  9. Effect of oestradiol and pathogen-associated molecular patterns on class II-mediated antigen presentation and immunomodulatory molecule expression in the mouse female reproductive tract

    PubMed Central

    Ochiel, Daniel O; Rossoll, Richard M; Schaefer, Todd M; Wira, Charles R

    2012-01-01

    Cells of the female reproductive tract (FRT) can present antigen to naive and memory T cells. However, the effects of oestrogen, known to modulate immune responses, on antigen presentation in the FRT remain undefined. In the present study, DO11.10 T-cell antigen receptor transgenic mice specific for the class II MHC-restricted ovalbumin (OVA) 323–339 peptide were used to study the effects of oestradiol and pathogen-associated molecular patterns on antigen presentation in the FRT. We report here that oestradiol inhibited antigen presentation of OVA by uterine epithelial cells, uterine stromal cells and vaginal cells to OVA-specific memory T cells. When ovariectomized animals were treated with oestradiol for 1 or 3 days, antigen presentation was decreased by 20–80%. In contrast, incubation with PAMP increased antigen presentation by epithelial cells (Pam3Cys), stromal cells (peptidoglycan, Pam3Cys) and vaginal cells (Pam3Cys). In contrast, CpG inhibited both stromal and vaginal cell antigen presentation. Analysis of mRNA expression by reverse transcription PCR indicated that oestradiol inhibited CD40, CD80 and class II in the uterus and CD40, CD86 and class II in the vagina. Expression in isolated uterine and vaginal cells paralleled that seen in whole tissues. In contrast, oestradiol increased polymeric immunoglobulin receptor mRNA expression in the uterus and decreased it in the vagina. These results indicate that antigen-presenting cells in the uterus and vagina are responsive to oestradiol, which inhibits antigen presentation and co-stimulatory molecule expression. Further, these findings suggest that antigen-presenting cells in the uterus and vagina respond to selected Toll-like receptor agonists with altered antigen presentation. PMID:22043860

  10. 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.

  11. Bringing Molecules Back into Molecular Evolution

    PubMed Central

    Wilke, Claus O.

    2012-01-01

    Much molecular-evolution research is concerned with sequence analysis. Yet these sequences represent real, three-dimensional molecules with complex structure and function. Here I highlight a growing trend in the field to incorporate molecular structure and function into computational molecular-evolution work. I consider three focus areas: reconstruction and analysis of past evolutionary events, such as phylogenetic inference or methods to infer selection pressures; development of toy models and simulations to identify fundamental principles of molecular evolution; and atom-level, highly realistic computational modeling of molecular structure and function aimed at making predictions about possible future evolutionary events. PMID:22761562

  12. Synthesis of biological molecules on molecular sieves.

    PubMed

    Poncelet, G; Van Assche, A T; Fripiat, J J

    1975-07-01

    Catalytic properties of aluminosilicates may play a role in the synthesis of biological molecules from simple gaseous molecules commonly found in planetary atmospheres. Urea, amino acids and UV absorbing substances have been obtained by heating CO and NH3 with Linde molecular sieves saturated with Ca+2, NH4+ or Fe+3. The yields of amino acids produced have been determined by an amino acid analyzer. The quantity of urea produced largely depends on the nature of the saturating cation. Experiments using 14CO confirm that the amino acids are not due to contaminants adsorbed on the surface of the molecular sieves. PMID:171609

  13. Patterns and conformations in molecularly thin films

    NASA Astrophysics Data System (ADS)

    Basnet, Prem B.

    Molecularly thin films have been a subject of great interest for the last several years because of their large variety of industrial applications ranging from micro-electronics to bio-medicine. Additionally, molecularly thin films can be used as good models for biomembrane and other systems where surfaces are critical. Many different kinds of molecules can make stable films. My research has considered three such molecules: a polymerizable phospholipid, a bent-core molecules, and a polymer. One common theme of these three molecules is chirality. The phospolipid molecules studied here are strongly chiral, which can be due to intrinsically chiral centers on the molecules and also due to chiral conformations. We find that these molecules give rise to chiral patterns. Bent-core molecules are not intrinsically chiral, but individual molecules and groups of molecules can show chiral structures, which can be changed by surface interactions. One major, unconfirmed hypothesis for the polymer conformation at surface is that it forms helices, which would be chiral. Most experiments were carried out at the air/water interface, in what are called Langmuir films. Our major tools for studying these films are Brewster Angle Microscopy (BAM) coupled with the thermodynamic information that can be deduced from surface pressure isotherms. Phospholipids are one of the important constituents of liposomes -- a spherical vesicle com-posed of a bilayer membrane, typically composed of a phospholipid and cholesterol bilayer. The application of liposomes in drug delivery is well-known. Crumpling of vesicles of polymerizable phospholipids has been observed. With BAM, on Langmuir films of such phospholipids, we see novel spiral/target patterns during compression. We have found that both the patterns and the critical pressure at which they formed depend on temperature (below the transition to a i¬‘uid layer). Bent-core liquid crystals, sometimes knows as banana liquid crystals, have drawn

  14. Molecular-beam spectroscopy of interhalogen molecules

    SciTech Connect

    Sherrow, S.A.

    1983-08-01

    A molecular-beam electric-resonance spectrometer employing a supersonic nozzle source has been used to obtain hyperfine spectra of /sup 79/Br/sup 35/Cl. Analyses of these spectra and of microwave spectra published by other authors have yielded new values for the electric dipole moment and for the nuclear quadrupole coupling constants in this molecule. The new constants are significantly different from the currently accepted values. Van der Waals clusters containing chlorine monofluoride have been studied under various expansion conditions by the molecular-beam electric-deflection method. The structural possibilities indicated by the results are discussed, and cluster geometries are proposed.

  15. Rotation and Anisotropic Molecular Orbital Effect in a Single H2TPP Molecule Transistor

    NASA Astrophysics Data System (ADS)

    Sakata, Shuichi; Yoshida, Kenji; Kitagawa, Yuichi; Ishii, Kazuyuki; Hirakawa, Kazuhiko

    2013-12-01

    Electron transport through a single molecule is determined not only by the intrinsic properties of the molecule but also by the configuration of the molecule with respect to the lead electrodes. Here, we show how electron transport through a single H2TPP molecule is modulated by changes in the configuration. The Coulomb stability diagram of a single H2TPP molecule transistor exhibited a few different patterns in different measurement scans. Furthermore, the sample exhibited negative differential resistance, the magnitude of which changed with the pattern in the Coulomb stability diagram. Such behavior can be explained by the rotation of the molecule with anisotropic molecular orbitals in the gap electrodes induced by electrical stress. Moreover, we find that the energy separations between molecular orbitals are also affected by the rotation, confirming that the metal-molecule interface configuration renormalizes the electronic levels in the molecule.

  16. Orientation detection of a single molecule using pupil filter with electrically controllable polarization pattern

    NASA Astrophysics Data System (ADS)

    Hashimoto, Mamoru; Yoshiki, Keisuke; Kurihara, Makoto; Hashimoto, Nobuyuki; Araki, Tsutomu

    2015-12-01

    We have developed a system for measuring the orientation of single molecules using a conventional wide-field fluorescence microscope with a polarization filter consisting of a polarizer and a compact polarization mode converter. The polarization filter electrically controls the pattern of polarization filtering. Since the polarization of the fluorescence from a single molecule highly depends on the angle between the observation direction and the molecular direction, polarization pattern filtering at the pupil plane of the objective lens allows the orientation of a single molecule to be visualized. Using this system, we demonstrated the orientation detection of single molecules.

  17. Molecular cloning and characterisation of a pattern recognition molecule, lipopolysaccharide- and beta-1,3-glucan binding protein (LGBP) from the white shrimp Litopenaeus vannamei.

    PubMed

    Cheng, Winton; Liu, Chun-Hung; Tsai, Chiung-Hui; Chen, Jiann-Chu

    2005-04-01

    A lipopolysaccharide- and beta-1,3-glucan binding protein (LGBP) cDNA was cloned from the haemocyte and hepatopancreas of white shrimp Litopenaeus vannamei using oligonucleotide primers and RT-PCR. Both 3'- and 5'-regions were isolated by rapid amplification of cDNA end RACE method. Analysis of nucleotide sequence revealed that the cDNA clone has an open reading frame of 1101 bp encoding a protein of 367 amino acids including a 17 amino acid signal peptide. The calculated molecular mass of the mature proteins (350 amino acids) is 39.92 kDa with an estimated pI of 4.37. Two putative integrin binding motifs (cell adhesion site), RGD (Arg-Gly-Asp) and a potential recognition motif for beta- (1-->3) linkage of polysaccharides were observed in the LGBP. Sequence comparison showed that LGBP deduced amino acid of L. vannamei has an overall similarity of 95%, 92% and 61% to that of blue shrimp Litopenaeus stylirostris LGBP, tiger shrimp Penaeus monodon BGBP and crayfish Pacifastacus leniusculus LGBP, respectively. Quantitative real-time RT-PCR analysis showed that LGBP transcript in haemocyte of L. vannamei increased in 3- and 6-h post Vibrio alginolyticus injection. PMID:15561560

  18. Single Molecular Spectroscopy: Identification of Individual Fullerene Molecules

    NASA Astrophysics Data System (ADS)

    Tizei, Luiz H. G.; Liu, Zheng; Koshino, Masanori; Iizumi, Yoko; Okazaki, Toshiya; Suenaga, Kazu

    2014-10-01

    We report the molecule-by-molecule spectroscopy of individual fullerenes by means of electron spectroscopy based on scanning transmission electron microscopy. Electron energy-loss fine structure analysis of carbon 1 s absorption spectra is used to discriminate carbon allotropes with known symmetries. C60 and C70 molecules randomly stored inside carbon nanotubes are successfully identified at a single-molecular basis. We show that a single molecule impurity is detectable, allowing the recognition of an unexpected contaminant molecule with a different symmetry. Molecules inside carbon nanotubes thus preserve their intact molecular symmetry. In contrast, molecules anchored at or sandwiched between atomic BN layers show spectral modifications possibly due to a largely degraded structural symmetry. Moreover, by comparing the spectrum from a single C60 molecule and its molecular crystal, we find hints of the influence of solid-state effects on its electronic structure.

  19. Single C59N molecule as a molecular rectifier.

    PubMed

    Zhao, Jin; Zeng, Changgan; Cheng, Xin; Wang, Kedong; Wang, Guanwu; Yang, Jinlong; Hou, J G; Zhu, Qingshi

    2005-07-22

    We report a new kind of experimental realization of a molecular rectifier, which is based on a single azafullerene C59N molecule in a double-barrier tunnel junction via the single electron tunneling effect. An obvious rectifying effect is observed. The positive onset voltage is about 0.5-0.7 V, while the negative onset voltage is about 1.6-1.8 V. Theoretical analyses show that the half-occupied molecular orbital of the C59N molecule and the asymmetric shift of the molecular Fermi level when the molecule is charged are responsible for the molecular rectification. PMID:16090819

  20. Controlling single-molecule junction conductance by molecular interactions

    PubMed Central

    Kitaguchi, Y.; Habuka, S.; Okuyama, H.; Hatta, S.; Aruga, T.; Frederiksen, T.; Paulsson, M.; Ueba, H.

    2015-01-01

    For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single-molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak π-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact to the molecule. The anchoring to the other electrode is kept stable using a chalcogen atom with strong bonding to a Cu(110) substrate. These non-destructive measurements permit us to investigate the variation in single-molecule conductance under different but controlled environmental conditions. Combined with density functional theory calculations, we clarify the role of the electrostatic field in the environmental effect that influences the molecular level alignment. PMID:26135251

  1. Controlling single-molecule junction conductance by molecular interactions.

    PubMed

    Kitaguchi, Y; Habuka, S; Okuyama, H; Hatta, S; Aruga, T; Frederiksen, T; Paulsson, M; Ueba, H

    2015-01-01

    For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single-molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak π-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact to the molecule. The anchoring to the other electrode is kept stable using a chalcogen atom with strong bonding to a Cu(110) substrate. These non-destructive measurements permit us to investigate the variation in single-molecule conductance under different but controlled environmental conditions. Combined with density functional theory calculations, we clarify the role of the electrostatic field in the environmental effect that influences the molecular level alignment. PMID:26135251

  2. Molecular junctions: Single-molecule contacts exposed

    NASA Astrophysics Data System (ADS)

    Nichols, Richard J.; Higgins, Simon J.

    2015-05-01

    Using a scanning tunnelling microscopy-based method it is now possible to get an atomistic-level description of the most probable binding and contact configuration for single-molecule electrical junctions.

  3. Parallel Molecular Dynamics Program for Molecules

    Energy Science and Technology Software Center (ESTSC)

    1995-03-07

    ParBond is a parallel classical molecular dynamics code that models bonded molecular systems, typically of an organic nature. It uses classical force fields for both non-bonded Coulombic and Van der Waals interactions and for 2-, 3-, and 4-body bonded (bond, angle, dihedral, and improper) interactions. It integrates Newton''s equation of motion for the molecular system and evaluates various thermodynamical properties of the system as it progresses.

  4. Molecular machines: Molecules bearing robotic arms

    NASA Astrophysics Data System (ADS)

    Aprahamian, Ivan

    2016-02-01

    Mass production at the nanoscale requires molecular machines that can control, with high fidelity, the spatial orientation of other reactive species. The demonstration of a synthetic system in which a molecular robotic arm can be used to manipulate the position of a chemical cargo is a significant step towards achieving this goal.

  5. Single DNA Molecule Patterning for High-Throughput Epigenetic Mapping

    PubMed Central

    Cerf, Aline; Cipriany, Benjamin R.; Benítez, Jaime J.; Craighead, Harold G.

    2013-01-01

    We present a method for profiling the 5-methyl cytosine distribution on single DNA molecules. Our method combines soft-lithography and molecular elongation to form ordered arrays of more than 250,000 individual DNA molecules immobilized on a solid substrate. The methylation state of the DNA is detected and mapped by binding of fluorescently labeled methyl-CpG binding domain peptides to the elongated dsDNA molecules and imaging of their distribution. The stretched molecules are fixed in their extended configuration by adsorption onto the substrate so analysis can be performed with high spatial resolution and signal averaging. We further prove this technique allows imaging of DNA molecules with different methylation states. PMID:21981444

  6. Molecular electronics with single molecules in solid-state devices.

    PubMed

    Moth-Poulsen, Kasper; Bjørnholm, Thomas

    2009-09-01

    The ultimate aim of molecular electronics is to understand and master single-molecule devices. Based on the latest results on electron transport in single molecules in solid-state devices, we focus here on new insights into the influence of metal electrodes on the energy spectrum of the molecule, and on how the electron transport properties of the molecule depend on the strength of the electronic coupling between it and the electrodes. A variety of phenomena are observed depending on whether this coupling is weak, intermediate or strong. PMID:19734925

  7. Structural understanding of stabilization patterns in engineered bispecific Ig-like antibody molecules

    SciTech Connect

    Jordan, Jacob L.; Arndt, Joseph W.; Hanf, Karl; Li, Guohui; Hall, Janine; Demarest, Stephen; Huang, Flora; Wu, Xiufeng; Miller, Brian; Glaser, Scott; Fernandez, Erik J.; Wang, Deping; Lugovskoy, Alexey

    2010-01-12

    Bispecific immunoglobulin-like antibodies capable of engaging multiple antigens represent a promising new class of therapeutic agents. Engineering of these molecules requires optimization of the molecular properties of one of the domain components. Here, we present a detailed crystallographic and computational characterization of the stabilization patterns in the lymphotoxin-beta receptor (LT{beta}R) binding Fv domain of an anti-LT{beta}R/anti-TNF-related apoptosis inducing ligand receptor-2 (TRAIL-R2) bispecific immunoglobulin-like antibody. We further describe a new hierarchical structure-guided approach toward engineering of antibody-like molecules to enhance their thermal and chemical stability.

  8. A random rotor molecule: Vibrational analysis and molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Li, Yu; Zhang, Rui-Qin; Shi, Xing-Qiang; Lin, Zijing; Van Hove, Michel A.

    2012-12-01

    Molecular structures that permit intramolecular rotational motion have the potential to function as molecular rotors. We have employed density functional theory and vibrational frequency analysis to study the characteristic structure and vibrational behavior of the molecule (4',4″″-(bicyclo[2,2,2]octane-1,4-diyldi-4,1-phenylene)-bis-2,2':6',2″-terpyridine. IR active vibrational modes were found that favor intramolecular rotation. To demonstrate the rotor behavior of the isolated single molecule, ab initio molecular dynamics simulations at various temperatures were carried out. This molecular rotor is expected to be thermally triggered via excitation of specific vibrational modes, which implies randomness in its direction of rotation.

  9. Molecular dynamics of fluids and droplets in patterned nanochannels

    NASA Astrophysics Data System (ADS)

    Cieplak, M.

    2008-07-01

    Molecular dynamics studies of chain molecule fluids in nanochannels reveal new kinds of stationary flows when the walls of the channel are patterned chemically. In the single-fluid case, the patterning is shown to give rise to spatial switching between Poiseuille-like and plug-flow behaviours. In the two-fluid case, such that the two immiscible fluids wet different patches of a chemically patterned channel, the velocity field of the individual components is modulated in a way that is phase shifted relative to the single-fluid case. When the channel is homogeneous and wetting to one fluid component but non-wetting to the other then the resulting coating of the channel walls provides dissipation and thus stabilises flow of the other component. Wettability and geometrical patterning of substrates gives rise to a lotus-like effect in a rolling motion of nanodroplets along the substrate.

  10. Single-Molecule Reaction Chemistry in Patterned Nanowells.

    PubMed

    Bouilly, Delphine; Hon, Jason; Daly, Nathan S; Trocchia, Scott; Vernick, Sefi; Yu, Jaeeun; Warren, Steven; Wu, Ying; Gonzalez, Ruben L; Shepard, Kenneth L; Nuckolls, Colin

    2016-07-13

    A new approach to synthetic chemistry is performed in ultraminiaturized, nanofabricated reaction chambers. Using lithographically defined nanowells, we achieve single-point covalent chemistry on hundreds of individual carbon nanotube transistors, providing robust statistics and unprecedented spatial resolution in adduct position. Each device acts as a sensor to detect, in real-time and through quantized changes in conductance, single-point functionalization of the nanotube as well as consecutive chemical reactions, molecular interactions, and molecular conformational changes occurring on the resulting single-molecule probe. In particular, we use a set of sequential bioconjugation reactions to tether a single-strand of DNA to the device and record its repeated, reversible folding into a G-quadruplex structure. The stable covalent tether allows us to measure the same molecule in different solutions, revealing the characteristic increased stability of the G-quadruplex structure in the presence of potassium ions (K(+)) versus sodium ions (Na(+)). Nanowell-confined reaction chemistry on carbon nanotube devices offers a versatile method to isolate and monitor individual molecules during successive chemical reactions over an extended period of time. PMID:27270004

  11. Ultrafast dynamics in isolated molecules and molecular clusters

    NASA Astrophysics Data System (ADS)

    Hertel, I. V.; Radloff, W.

    2006-06-01

    During the past decade the understanding of photo-induced ultrafast dynamics in molecular systems has improved at an unforeseen speed and a wealth of detailed insight into the fundamental processes has been obtained. This review summarizes our present knowledge on ultrafast dynamics in isolated molecules and molecular clusters evolving after excitation with femtosecond pulses as studied by pump-probe analysis in real time. Experimental tools and methods as well as theoretical models are described which have been developed to glean information on primary, ultrafast processes in photophysics, photochemistry and photobiology. The relevant processes are explained by way of example—from wave packet dynamics in systems with a few atoms all the way to internal conversion via conical intersections in bio-chromophores. A systematic overview on characteristic systems follows, starting with diatomic and including larger organic molecules as well as various types of molecular clusters, such as micro-solvated chromophore molecules. For conciseness the focus is on molecular systems which remain unperturbed by the laser pulses—apart from the excitation and detection processes as such. Thus, only some aspects of controlling and manipulating molecular reactions by shaped and/or very intense laser pulses are discussed briefly for particularly instructive examples, illustrating the perspectives of this prospering field. The material presented in this review comprises some prototypical examples from earlier pioneering work but emphasizes studies from recent years and covers the most important and latest developments until January 2006.

  12. Molecular Rotation Signals: Molecule Chemistry and Particle Physics

    NASA Astrophysics Data System (ADS)

    Grabow, Jens-Uwe

    2015-06-01

    Molecules - large or small - are attractive academic resources, with numerous questions on their chemical behaviour as well as problems in fundamental physics now (or still) waiting to be answered: Targeted by high-resolution spectroscopy, a rotating molecular top can turn into a laboratory for molecule chemistry or a laboratory for particle physics. Once successfully entrained (many species - depending on size and chemical composition - have insufficient vapour pressures or are of transient nature, such that specifically designed pulsed-jet sources are required for their transfer into the gas phase or in-situ generation) into the collision-free environment of a supersonic-jet expansion, each molecular top comes with its own set of challenges, theoretically and experimentally: Multiple internal interactions are causing complicated energy level schemes and the resulting spectra will be rather difficult to predict theoretically. Experimentally, these spectra are difficult to assess and assign. With today's broad-banded chirp microwave techniques, finding and identifying such spectral features have lost their major drawback of being very time consuming for many molecules. For other molecules, the unrivalled resolution and sensitivity of the narrow-banded impulse microwave techniques provide a window to tackle - at the highest precision available to date - fundamental questions in physics, even particle physics - potentially beyond the standard model. Molecular charge distribution, properties of the chemical bond, details on internal dynamics and intermolecular interaction, the (stereo-chemical) molecular structure (including the possibility of their spatial separation) as well as potential evidence for tiny yet significant interactions encode their signature in pure molecular rotation subjected to time-domain microwave spectroscopic techniques. Ongoing exciting technical developments promise rapid progress. We present recent examples from Hannover, new directions, and

  13. Molecular surface analysis by laser ionization of desorbed molecules

    SciTech Connect

    Pellin, M.J.; Lykke, K.R.; Wurz, P.; Parker, D.H.

    1992-01-01

    While elemental analysis of surfaces has progressed dramatically over the past ten years, quantitative molecular surface analysis remains difficult. This is particularly true in the analysis of complex materials such as polymers and rubbers which contain a wide compliment of additives and pigments to enhance their material characteristics. For mass spectrometric analysis the difficulty is two fold. First, desorption of surface molecules must be accompanied with minimal fragmentation and collateral surface damage. Second, the desorbed molecules must be ionized for subsequent mass analysis with high efficiency and without significant cracking. This paper focuses on the second of these problems.

  14. Molecular surface analysis by laser ionization of desorbed molecules

    SciTech Connect

    Pellin, M.J.; Lykke, K.R.; Wurz, P.; Parker, D.H.

    1992-07-01

    While elemental analysis of surfaces has progressed dramatically over the past ten years, quantitative molecular surface analysis remains difficult. This is particularly true in the analysis of complex materials such as polymers and rubbers which contain a wide compliment of additives and pigments to enhance their material characteristics. For mass spectrometric analysis the difficulty is two fold. First, desorption of surface molecules must be accompanied with minimal fragmentation and collateral surface damage. Second, the desorbed molecules must be ionized for subsequent mass analysis with high efficiency and without significant cracking. This paper focuses on the second of these problems.

  15. An extracellular adhesion molecule complex patterns dendritic branching and morphogenesis

    PubMed Central

    Dong, Xintong; Liu, Oliver W.; Howell, Audrey S.; Shen, Kang

    2014-01-01

    Summary Robust dendrite morphogenesis is a critical step in the development of reproducible neural circuits. However, little is known about the extracellular cues that pattern complex dendrite morphologies. In the model nematode C. elegans, the sensory neuron PVD establishes stereotypical, highly-branched dendrite morphology. Here, we report the identification of a tripartite ligand-receptor complex of membrane adhesion molecules that is both necessary and sufficient to instruct spatially restricted growth and branching of PVD dendrites. The ligand complex SAX-7/L1CAM and MNR-1 function at defined locations in the surrounding hypodermal tissue, while DMA-1 acts as the cognate receptor on PVD. Mutations in this complex lead to dramatic defects in the formation, stabilization, and organization of the dendritic arbor. Ectopic expression of SAX-7 and MNR-1 generates a predictable, unnaturally patterned dendritic tree in a DMA-1 dependent manner. Both in vivo and in vitro experiments indicate that all three molecules are needed for interaction. PMID:24120131

  16. Reconstruction of three-dimensional molecular structure from diffraction of laser-aligned molecules.

    PubMed

    Yang, Jie; Makhija, Varun; Kumarappan, Vinod; Centurion, Martin

    2014-07-01

    Diffraction from laser-aligned molecules has been proposed as a method for determining 3-D molecular structures in the gas phase. However, existing structural retrieval algorithms are limited by the imperfect alignment in experiments and the rotational averaging in 1-D alignment. Here, we demonstrate a two-step reconstruction comprising a genetic algorithm that corrects for the imperfect alignment followed by an iterative phase retrieval method in cylindrical coordinates. The algorithm was tested with simulated diffraction patterns. We show that the full 3-D structure of trifluorotoluene, an asymmetric-top molecule, can be reconstructed with atomic resolution. PMID:26798781

  17. Patterning Biomaterials for the Spatiotemporal Delivery of Bioactive Molecules.

    PubMed

    Minardi, Silvia; Taraballi, Francesca; Pandolfi, Laura; Tasciotti, Ennio

    2016-01-01

    The aim of tissue engineering is to promote the repair of functional tissues. For decades, the combined use of biomaterials, growth factors (GFs), and stem cells has been the base of several regeneration strategies. Among these, biomimicry emerged as a robust strategy to efficiently address this clinical challenge. Biomimetic materials, able to recapitulate the composition and architecture of the extracellular matrix, are the materials of choice, for their biocompatibility and higher rate of efficacy. In addition, it has become increasingly clear that restoring the complex biochemical environment of the target tissue is crucial for its regeneration. Toward this aim, the combination of scaffolds and GFs is required. The advent of nanotechnology significantly impacted the field of tissue engineering by providing new ways to reproduce the complex spatial and temporal biochemical patterns of tissues. This review will present the most recent approaches to finely control the spatiotemporal release of bioactive molecules for various tissue engineering applications. PMID:27313997

  18. Patterning Biomaterials for the Spatiotemporal Delivery of Bioactive Molecules

    PubMed Central

    Minardi, Silvia; Taraballi, Francesca; Pandolfi, Laura; Tasciotti, Ennio

    2016-01-01

    The aim of tissue engineering is to promote the repair of functional tissues. For decades, the combined use of biomaterials, growth factors (GFs), and stem cells has been the base of several regeneration strategies. Among these, biomimicry emerged as a robust strategy to efficiently address this clinical challenge. Biomimetic materials, able to recapitulate the composition and architecture of the extracellular matrix, are the materials of choice, for their biocompatibility and higher rate of efficacy. In addition, it has become increasingly clear that restoring the complex biochemical environment of the target tissue is crucial for its regeneration. Toward this aim, the combination of scaffolds and GFs is required. The advent of nanotechnology significantly impacted the field of tissue engineering by providing new ways to reproduce the complex spatial and temporal biochemical patterns of tissues. This review will present the most recent approaches to finely control the spatiotemporal release of bioactive molecules for various tissue engineering applications. PMID:27313997

  19. Molecular Design of Branched and Binary Molecules at Ordered Interfaces

    SciTech Connect

    Kirsten Larson Genson

    2005-12-27

    This study examined five different branched molecular architectures to discern the effect of design on the ability of molecules to form ordered structures at interfaces. Photochromic monodendrons formed kinked packing structures at the air-water interface due to the cross-sectional area mismatch created by varying number of alkyl tails and the hydrophilic polar head group. The lower generations formed orthorhombic unit cell with long range ordering despite the alkyl tails tilted to a large degree. Favorable interactions between liquid crystalline terminal groups and the underlying substrate were observed to compel a flexible carbosilane dendrimer core to form a compressed elliptical conformation which packed stagger within lamellae domains with limited short range ordering. A twelve arm binary star polymer was observed to form two dimensional micelles at the air-water interface attributed to the higher polystyrene block composition. Linear rod-coil molecules formed a multitude of packing structures at the air-water interface due to the varying composition. Tree-like rod-coil molecules demonstrated the ability to form one-dimensional structures at the air-water interface and at the air-solvent interface caused by the preferential ordering of the rigid rod cores. The role of molecular architecture and composition was examined and the influence chemically competing fragments was shown to exert on the packing structure. The amphiphilic balance of the different molecular series exhibited control on the ordering behavior at the air-water interface and within bulk structures. The shell nature and tail type was determined to dictate the preferential ordering structure and molecular reorganization at interfaces with the core nature effect secondary.

  20. Behavior of molecules and molecular ions near a field emitter

    NASA Astrophysics Data System (ADS)

    Gault, Baptiste; Saxey, David W.; Ashton, Michael W.; Sinnott, Susan B.; Chiaramonti, Ann N.; Moody, Michael P.; Schreiber, Daniel K.

    2016-03-01

    The cold emission of particles from surfaces under intense electric fields is a process which underpins a variety of applications including atom probe tomography (APT), an analytical microscopy technique with near-atomic spatial resolution. Increasingly relying on fast laser pulsing to trigger the emission, APT experiments often incorporate the detection of molecular ions emitted from the specimen, in particular from covalently or ionically bonded materials. Notably, it has been proposed that neutral molecules can also be emitted during this process. However, this remains a contentious issue. To investigate the validity of this hypothesis, a careful review of the literature is combined with the development of new methods to treat experimental APT data, the modeling of ion trajectories, and the application of density-functional theory simulations to derive molecular ion energetics. It is shown that the direct thermal emission of neutral molecules is extremely unlikely. However, neutrals can still be formed in the course of an APT experiment by dissociation of metastable molecular ions. This work is a partial contribution of the US Government and therefore is not subject to copyright in the United States.

  1. Apparatus and method of determining molecular weight of large molecules

    DOEpatents

    Fuerstenau, Stephen; Benner, W. Henry; Madden, Norman; Searles, William

    1998-01-01

    A mass spectrometer determines the mass of multiply charged high molecular weight molecules. This spectrometer utilizes an ion detector which is capable of simultaneously measuring the charge z and transit time of a single ion as it passes through the detector. From this transit time, the velocity of the single ion may then be derived, thus providing the mass-to-charge ratio m/z for a single ion which has been accelerated through a known potential. Given z and m/z, the mass m of the single ion can then be calculated. Electrospray ions with masses in excess of 1 MDa and charge numbers greater than 425 e.sup.- are readily detected. The on-axis single ion detection configuration enables a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation.

  2. Apparatus and method of determining molecular weight of large molecules

    DOEpatents

    Fuerstenau, S.; Benner, W.H.; Madden, N.M.; Searles, W.

    1998-06-23

    A mass spectrometer determines the mass of multiply charged high molecular weight molecules. This spectrometer utilizes an ion detector which is capable of simultaneously measuring the charge z and transit time of a single ion as it passes through the detector. From this transit time, the velocity of the single ion may then be derived, thus providing the mass-to-charge ratio m/z for a single ion which has been accelerated through a known potential. Given z and m/z, the mass m of the single ion can then be calculated. Electrospray ions with masses in excess of 1 MDa and charge numbers greater than 425 e{sup {minus}} are readily detected. The on-axis single ion detection configuration enables a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation. 14 figs.

  3. Theoretical investigation of the molecular structure of the isoquercitrin molecule

    NASA Astrophysics Data System (ADS)

    Cornard, J. P.; Boudet, A. C.; Merlin, J. C.

    1999-09-01

    Isoquercitrin is a glycosilated flavonoid that has received a great deal of attention because of its numerous biological effects. We present a theoretical study on isoquercitrin using both empirical (Molecular Mechanics (MM), with MMX force field) and quantum chemical (AM1 semiempirical method) techniques. The most stable structures of the molecule obtained by MM calculations have been used as input data for the semiempirical treatment. The position and orientation of the glucose moiety with regard to the remainder of the molecule have been investigated. The flexibility of isoquercitrin principally lies in rotations around the inter-ring bond and the sugar link. In order to know the structural modifications generated by the substitution by a sugar, geometrical parameters of quercetin (aglycon) and isoquercitrin have been compared. The good accordance between theoretical and experimental electronic spectra permits to confirm the reliability of the structural model.

  4. Localization of molecular orbitals: from fragments to molecule.

    PubMed

    Li, Zhendong; Li, Hongyang; Suo, Bingbing; Liu, Wenjian

    2014-09-16

    Conspectus Localized molecular orbitals (LMO) not only serve as an important bridge between chemical intuition and molecular wave functions but also can be employed to reduce the computational cost of many-body methods for electron correlation and excitation. Therefore, how to localize the usually completely delocalized canonical molecular orbitals (CMO) into confined physical spaces has long been an important topic: It has a long history but still remains active to date. While the known LMOs can be classified into (exact) orthonormal and nonorthogonal, as well as (approximate) absolutely localized MOs, the ways for achieving these can be classified into two categories, a posteriori top-down and a priori bottom-up, depending on whether they invoke the global CMOs (or equivalently the molecular density matrix). While the top-down approaches have to face heavy tasks of minimizing or maximizing a given localization functional typically of many adjacent local extrema, the bottom-up ones have to invoke some tedious procedures for first generating a local basis composed of well-defined occupied and unoccupied subsets and then maintaining or resuming the locality when solving the Hartree-Fock/Kohn-Sham (HF/KS) optimization condition. It is shown here that the good of these kinds of approaches can be combined together to form a very efficient hybrid approach that can generate the desired LMOs for any kind of gapped molecules. Specifically, a top-down localization functional, applied to individual small subsystems only, is minimized to generate an orthonormal local basis composed of functions centered on the preset chemical fragments. The familiar notion for atomic cores, lone pairs, and chemical bonds emerges here automatically. Such a local basis is then employed in the global HF/KS calculation, after which a least action is taken toward the final orthonormal localized molecular orbitals (LMO), both occupied and virtual. This last step is very cheap, implying that, after

  5. Molecular Responses to Small Regulating Molecules against Huanglongbing Disease

    PubMed Central

    Martinelli, Federico; Dolan, David; Fileccia, Veronica; Reagan, Russell L.; Phu, My; Spann, Timothy M.; McCollum, Thomas G.; Dandekar, Abhaya M.

    2016-01-01

    Huanglongbing (HLB; citrus greening) is the most devastating disease of citrus worldwide. No cure is yet available for this disease and infected trees generally decline after several months. Disease management depends on early detection of symptoms and chemical control of insect vectors. In this work, different combinations of organic compounds were tested for the ability to modulate citrus molecular responses to HLB disease beneficially. Three small-molecule regulating compounds were tested: 1) L-arginine, 2) 6-benzyl-adenine combined with gibberellins, and 3) sucrose combined with atrazine. Each treatment contained K-phite mineral solution and was tested at two different concentrations. Two trials were conducted: one in the greenhouse and the other in the orchard. In the greenhouse study, responses of 42 key genes involved in sugar and starch metabolism, hormone-related pathways, biotic stress responses, and secondary metabolism in treated and untreated mature leaves were analyzed. TGA5 was significantly induced by arginine. Benzyladenine and gibberellins enhanced two important genes involved in biotic stress responses: WRKY54 and WRKY59. Sucrose combined with atrazine mainly upregulated key genes involved in carbohydrate metabolism such as sucrose-phosphate synthase, sucrose synthase, starch synthase, and α-amylase. Atrazine also affected expression of some key genes involved in systemic acquired resistance such as EDS1, TGA6, WRKY33, and MYC2. Several treatments upregulated HSP82, which might help protect protein folding and integrity. A subset of key genes was chosen as biomarkers for molecular responses to treatments under field conditions. GPT2 was downregulated by all small-molecule treatments. Arginine-induced genes involved in systemic acquired resistance included PR1, WRKY70, and EDS1. These molecular data encourage long-term application of treatments that combine these regulating molecules in field trials. PMID:27459099

  6. Molecular Responses to Small Regulating Molecules against Huanglongbing Disease.

    PubMed

    Martinelli, Federico; Dolan, David; Fileccia, Veronica; Reagan, Russell L; Phu, My; Spann, Timothy M; McCollum, Thomas G; Dandekar, Abhaya M

    2016-01-01

    Huanglongbing (HLB; citrus greening) is the most devastating disease of citrus worldwide. No cure is yet available for this disease and infected trees generally decline after several months. Disease management depends on early detection of symptoms and chemical control of insect vectors. In this work, different combinations of organic compounds were tested for the ability to modulate citrus molecular responses to HLB disease beneficially. Three small-molecule regulating compounds were tested: 1) L-arginine, 2) 6-benzyl-adenine combined with gibberellins, and 3) sucrose combined with atrazine. Each treatment contained K-phite mineral solution and was tested at two different concentrations. Two trials were conducted: one in the greenhouse and the other in the orchard. In the greenhouse study, responses of 42 key genes involved in sugar and starch metabolism, hormone-related pathways, biotic stress responses, and secondary metabolism in treated and untreated mature leaves were analyzed. TGA5 was significantly induced by arginine. Benzyladenine and gibberellins enhanced two important genes involved in biotic stress responses: WRKY54 and WRKY59. Sucrose combined with atrazine mainly upregulated key genes involved in carbohydrate metabolism such as sucrose-phosphate synthase, sucrose synthase, starch synthase, and α-amylase. Atrazine also affected expression of some key genes involved in systemic acquired resistance such as EDS1, TGA6, WRKY33, and MYC2. Several treatments upregulated HSP82, which might help protect protein folding and integrity. A subset of key genes was chosen as biomarkers for molecular responses to treatments under field conditions. GPT2 was downregulated by all small-molecule treatments. Arginine-induced genes involved in systemic acquired resistance included PR1, WRKY70, and EDS1. These molecular data encourage long-term application of treatments that combine these regulating molecules in field trials. PMID:27459099

  7. Molecular evolution of hemojuvelin and the repulsive guidance molecule family.

    PubMed

    Camus, Laura Marie; Lambert, Lisa A

    2007-07-01

    Repulsive guidance molecules (RGMs) are found in vertebrates and chordates and are involved in embryonic development and iron homeostasis. Members of this family are GPI-linked membrane proteins that contain an N-terminal signal peptide, a C-terminal propeptide, and a conserved RGD motif. Vertebrates are known to possess three paralogues; RGMA and RGMB (sometimes called Dragon) are expressed in the nervous system and are thought to play various roles in neural development. Hemojuvelin (HJV; also called repulsive guidance molecule c, RGMC) is the third member of this family, and mutations in this gene result in a form of juvenile hemochromatosis (type 2A). Phylogenetic analyses of 55 different RGM family sequences from 21 different species support the existence of a novel gene, found only in fish, which we have labeled RGMD. The pattern of conserved residues in each family identifies new candidates for important functional roles, including ligand binding. PMID:17593421

  8. Molecular spectral line surveys and the organic molecules in the interstellar molecular clouds

    NASA Astrophysics Data System (ADS)

    Ohishi, Masatoshi

    2008-10-01

    It is known that more than 140 interstellar and circumstellar molecules have so far been detected, mainly by means of the radio astronomy observations. Many organic molecules are also detected, including alcohols, ketons, ethers, aldehydes, and others, that are distributed from dark clouds and hot cores in the giant molecular clouds. It is believed that most of the organic molecules in space are synthesized through the grain surface reactions, and are evaporated from the grain surface when they are heated up by the UV radiation from adjacent stars. On the other hand the recent claim on the detection of glycine have raised an important issue how difficult it is to confirm secure detection of weak spectra from less abundant organic molecules in the interstellar molecular cloud. I will review recent survey observations of organic molecules in the interstellar molecular clouds, including independent observations of glycine by the 45 m radio telescope in Japan, and will discuss the procedure to securely identify weak spectral lines from organic molecules and the importance of laboratory measurement of organic species.

  9. Large-scale patterning of zwitterionic molecules on a Si(111)-7 × 7 surface.

    PubMed

    El Garah, Mohamed; Makoudi, Younes; Duverger, Eric; Palmino, Frank; Rochefort, Alain; Chérioux, Frédéric

    2011-01-25

    The formation of a large scale pattern on Si(111)-7 × 7 reconstruction is still a challenge. We report herein a new solution to achieve this type of nanostructuration by using of zwitterionic molecules. The formation of a large-scale pattern is successfully obtained due to the perfect match between the molecular geometry and the surface topology and to electrostatic interactions between molecules and surface. The adsorption is described by high-resolution scanning tunneling microscopy (STM) images and supported by density functional theory and STM calculations. PMID:21105746

  10. Single-Molecule Studies of Rotary Molecular Motors

    NASA Astrophysics Data System (ADS)

    Pilizota, Teuta; Sowa, Yoshiyuki; Berry, Richard M.

    Rotary molecular motors are protein complexes that transform chemical or electrochemical energy into mechanical work. There are five known rotary molecular motors in nature; the bacterial flagellar motor, and two motors in each of ATP-synthase and V-ATPase. Rotation of the flagellar motor drives a helical propeller that powers bacterial swimming. The function of the other rotary motors is to couple electrochemical ion gradients to synthesis or hydrolysis of ATP, and rotation is a detail of the coupling mechanism rather than the ultimate purpose of the motors. Much has been learned about the mechanism of the F1 part of ATP-synthase and the flagellar motor by measuring the rotation of single motors with a variety of techniques under a wide range of conditions. This chapter will review the structures of ATP-synthase and the flagellar motor, and what has been learned about their mechanisms using single molecule techniques.

  11. Small-Molecule Hormones: Molecular Mechanisms of Action

    PubMed Central

    Budzińska, Monika

    2013-01-01

    Small-molecule hormones play crucial roles in the development and in the maintenance of an adult mammalian organism. On the molecular level, they regulate a plethora of biological pathways. Part of their actions depends on their transcription-regulating properties, exerted by highly specific nuclear receptors which are hormone-dependent transcription factors. Nuclear hormone receptors interact with coactivators, corepressors, basal transcription factors, and other transcription factors in order to modulate the activity of target genes in a manner that is dependent on tissue, age and developmental and pathophysiological states. The biological effect of this mechanism becomes apparent not earlier than 30–60 minutes after hormonal stimulus. In addition, small-molecule hormones modify the function of the cell by a number of nongenomic mechanisms, involving interaction with proteins localized in the plasma membrane, in the cytoplasm, as well as with proteins localized in other cellular membranes and in nonnuclear cellular compartments. The identity of such proteins is still under investigation; however, it seems that extranuclear fractions of nuclear hormone receptors commonly serve this function. A direct interaction of small-molecule hormones with membrane phospholipids and with mRNA is also postulated. In these mechanisms, the reaction to hormonal stimulus appears within seconds or minutes. PMID:23533406

  12. Molecular dynamics simulation of paracetamol molecules ordering around glycogen

    NASA Astrophysics Data System (ADS)

    Lim, Wilber; Feng, Yuan Ping; Liu, X. Y.

    2005-05-01

    By the use of classical atomistic molecular dynamics simulations, we demonstrate that paracetamol molecules exist in a highly ordered phase in the presence of a glycogen substrate at 317K whereas the paracetamol fluid exists in an isotropic phase in the absence of the glycogen substrate at the same temperature. This result further validates the studies made on polysaccharide regarding its abilities to promote nucleation of paracetamol via liquid preordering. As little is known regarding liquid ordering induced by a polymeric substrate, we seek to explore the ordering mechanism from an energy perspective. This is accomplished using conformation mappings. Our analysis shows that the conformation space accessible to the paracetamol molecule at 317K in the vicinity of glycogen is smaller than the one in the absence of glycogen. An investigation on the orientation of the dipole moments of the glycogen monomers and paracetamol molecules were carried out as well. From the investigations, we show that dipolar interactions play an important role in the ordering process. These studies bear significance to the understanding of the ordering process as well as the promotion and effective control of the nucleation rate.

  13. Discovering structural alerts for mutagenicity using stable emerging molecular patterns.

    PubMed

    Métivier, Jean-Philippe; Lepailleur, Alban; Buzmakov, Aleksey; Poezevara, Guillaume; Crémilleux, Bruno; Kuznetsov, Sergei O; Le Goff, Jérémie; Napoli, Amedeo; Bureau, Ronan; Cuissart, Bertrand

    2015-05-26

    This study is dedicated to the introduction of a novel method that automatically extracts potential structural alerts from a data set of molecules. These triggering structures can be further used for knowledge discovery and classification purposes. Computation of the structural alerts results from an implementation of a sophisticated workflow that integrates a graph mining tool guided by growth rate and stability. The growth rate is a well-established measurement of contrast between classes. Moreover, the extracted patterns correspond to formal concepts; the most robust patterns, named the stable emerging patterns (SEPs), can then be identified thanks to their stability, a new notion originating from the domain of formal concept analysis. All of these elements are explained in the paper from the point of view of computation. The method was applied to a molecular data set on mutagenicity. The experimental results demonstrate its efficiency: it automatically outputs a manageable number of structural patterns that are strongly related to mutagenicity. Moreover, a part of the resulting structures corresponds to already known structural alerts. Finally, an in-depth chemical analysis relying on these structures demonstrates how the method can initiate promising processes of chemical knowledge discovery. PMID:25871768

  14. Polarizable Atomic Multipole-based Molecular Mechanics for Organic Molecules

    PubMed Central

    Ren, Pengyu; Wu, Chuanjie; Ponder, Jay W.

    2011-01-01

    An empirical potential based on permanent atomic multipoles and atomic induced dipoles is reported for alkanes, alcohols, amines, sulfides, aldehydes, carboxylic acids, amides, aromatics and other small organic molecules. Permanent atomic multipole moments through quadrupole moments have been derived from gas phase ab initio molecular orbital calculations. The van der Waals parameters are obtained by fitting to gas phase homodimer QM energies and structures, as well as experimental densities and heats of vaporization of neat liquids. As a validation, the hydrogen bonding energies and structures of gas phase heterodimers with water are evaluated using the resulting potential. For 32 homo- and heterodimers, the association energy agrees with ab initio results to within 0.4 kcal/mol. The RMS deviation of hydrogen bond distance from QM optimized geometry is less than 0.06 Å. In addition, liquid self-diffusion and static dielectric constants computed from molecular dynamics simulation are consistent with experimental values. The force field is also used to compute the solvation free energy of 27 compounds not included in the parameterization process, with a RMS error of 0.69 kcal/mol. The results obtained in this study suggest the AMOEBA force field performs well across different environments and phases. The key algorithms involved in the electrostatic model and a protocol for developing parameters are detailed to facilitate extension to additional molecular systems. PMID:22022236

  15. GAS-PHASE MOLECULAR DYNAMICS: VIBRATIONAL DYNAMICS OF POLYATOMIC MOLECULES

    SciTech Connect

    MUCKERMAN,J.T.

    1999-06-09

    The goal of this research is the understanding of elementary chemical and physical processes important in the combustion of fossil fuels. Interest centers on reactions and properties of short-lived chemical intermediates. High-resolution, high-sensitivity, laser absorption methods are augmented by high-temperature, flow-tube reaction kinetics studies with mass-spectrometric sampling. These experiments provide information on the energy levels, structures and reactivity of molecular free radical species and, in turn, provide new tools for the study of energy flow and chemical bond cleavage in radicals involved in chemical systems. The experimental work is supported by theoretical studies using time-dependent quantum wavepacket calculations, which provide insight into energy flow among the vibrational modes of polyatomic molecules and interference effects in multiple-surface dynamics.

  16. Gas-Phase Molecular Dynamics: Vibrational Dynamics of Polyatomic Molecules

    SciTech Connect

    Muckerman, J.T.

    1999-05-21

    The goal of this research is the understanding of elementary chemical and physical processes important in the combustion of fossil fuels. Interest centers on reactions and properties of short-lived chemical intermediates. High-resolution, high-sensitivity, laser absorption methods are augmented by high- temperature, flow-tube reaction kinetics studies with mass-spectrometic sampling. These experiments provide information on the energy levels, structures and reactivity of molecular free radical species and in turn, provide new tools for the study of energy flow and chemical bond cleavage in the radicals involved in chemical systems. The experimental work is supported by theoretical studies using time-dependent quantum wavepacket calculations, which provide insight into energy flow among the vibrational modes of polyatomic molecules and interference effects in multiple-surface dynamics.

  17. Molecular line parameters for the atmospheric trace molecule spectroscopy experiment

    NASA Technical Reports Server (NTRS)

    Brown, L. R.; Farmer, C. B.; Toth, R. A.; Rinsland, Curtis P.

    1987-01-01

    During its first mission in 1985 onboard Spacelab 3, the ATMOS (atmospheric trace molecule spectroscopy) instrument, a high speed Fourier transform spectrometer, produced a large number of high resolution infrared solar absorption spectra recorded in the occultation mode. The analysis and interpretation of these data in terms of composition, chemistry, and dynamics of the earth's upper atmosphere required good knowledge of the molecular line parameters for those species giving rise to the absorptions in the atmospheric spectra. This paper describes the spectroscopic line parameter database compiled for the ATMOS experiment and referenced in other papers describing ATMOS results. With over 400,000 entries, the linelist catalogs parameters of 46 minor and trace species in the 1-10,000/cm region.

  18. Libraries of Extremely Localized Molecular Orbitals. 1. Model Molecules Approximation and Molecular Orbitals Transferability.

    PubMed

    Meyer, Benjamin; Guillot, Benoît; Ruiz-Lopez, Manuel F; Genoni, Alessandro

    2016-03-01

    Despite more and more remarkable computational ab initio results are nowadays continuously obtained for large macromolecular systems, the development of new linear-scaling techniques is still an open and stimulating field of research in theoretical chemistry. In this family of methods, an important role is occupied by those strategies based on the observation that molecules are generally constituted by recurrent functional units with well-defined intrinsic features. In this context, we propose to exploit the notion of extremely localized molecular orbitals (ELMOs) that, due to their strict localization on small molecular fragments (e.g., atoms, bonds, or functional groups), are in principle transferable from one molecule to another. Accordingly, the construction of orbital libraries to almost instantaneously build up approximate wave functions and electron densities of very large systems becomes conceivable. In this work, the ELMOs transferability is further investigated in detail and, furthermore, suitable rules to construct model molecules for the computation of ELMOs to be stored in future databanks are also defined. The obtained results confirm the reliable transferability of the ELMOs and show that electron densities obtained from the transfer of extremely localized molecular orbitals are very close to the corresponding Hartree-Fock ones. These observations prompt us to construct new ELMOs databases that could represent an alternative/complement to the already popular pseudoatoms databanks both for determining electron densities and for refining crystallographic structures of very large molecules. PMID:26799516

  19. Patterns and processes in microbial biogeography: do molecules and morphologies give the same answers?

    PubMed

    Santoferrara, Luciana F; Grattepanche, Jean-David; Katz, Laura A; McManus, George B

    2016-07-01

    Our knowledge on microbial biogeography depends on the way we define and study diversity. In contrast to most microbes, some protist lineages have conspicuous structures that allow comparisons of diversity concepts and measures-those based on molecules and those based on morphology. We analyzed a group of shell-bearing planktonic ciliates, the tintinnids, in a coast-to-ocean gradient using high-throughput sequencing and microscopy. First, we compared molecular operational taxonomic units (OTUs) and morphospecies in terms of assemblage composition, distribution and relationships with the environment. OTUs revealed potentially novel and rare taxa, while morphospecies showed clearer correlations with environmental factors, and both approaches coincided in supporting a coastal versus oceanic pattern. Second, we explored which processes influence assembly across the environmental gradient examined. Assemblage fluctuations were associated with significant distance-decay and changes in morphospecies size and prey proxies, thus suggesting niche partitioning as a key structuring mechanism. Our conclusion is that molecules and morphologies generally agreed, but they provided complementary data, the first revealing hidden diversity, and the latter making better connections between distribution patterns and ecological processes. This highlights the importance of linking genotypes and phenotypes (using multidisciplinary analyses and/or reliable databases of barcoded species), to understand the diversity, biogeography and ecological roles of microbes. PMID:26849313

  20. ION AND MOLECULE SENSORS USING MOLECULAR RECOGNITION IN LUMINESCENT, CONDUCTIVE POLYMERS

    EPA Science Inventory

    This program integrates three individual, highly interactive projects that will use molecular recognition strategies to develop sensor technology based on luminescent, conductive polymers that contain sites for binding specific molecules or ions in the presence of related molecul...

  1. Application of Machine Learning tools to recognition of molecular patterns in STM images

    NASA Astrophysics Data System (ADS)

    Maksov, Artem; Ziatdinov, Maxim; Fujii, Shintaro; Kiguchi, Manabu; Higashibayashi, Shuhei; Sakurai, Hidehiro; Kalinin, Sergei; Sumpter, Bobby

    The ability to utilize individual molecules and molecular assemblies as data storage elements has motivated scientist for years, concurrent with the continuous effort to shrink a size of data storage devices in microelectronics industry. One of the critical issues in this effort lies in being able to identify individual molecular assembly units (patterns), on a large scale in an automated fashion of complete information extraction. Here we present a novel method of applying machine learning techniques for extraction of positional and rotational information from scanning tunneling microscopy (STM) images of π-bowl sumanene molecules on gold. We use Markov Random Field (MRF) model to decode the polar rotational states for each molecule in a large scale STM image of molecular film. We further develop an algorithm that uses a convolutional Neural Network combined with MRF and input from density functional theory to classify molecules into different azimuthal rotational classes. Our results demonstrate that a molecular film is partitioned into distinctive azimuthal rotational domains consisting typically of 20-30 molecules. In each domain, the ``bowl-down'' molecules are generally surrounded by six nearest neighbor molecules in ``bowl-up'' configuration, and the resultant overall structure form a periodic lattice of rotational and polar states within each domain. Research was supported by the US Department of Energy.

  2. Investigating the correlations among the chemical structures, bioactivity profiles and molecular targets of small molecules

    PubMed Central

    Cheng, Tiejun; Wang, Yanli; Bryant, Stephen H.

    2010-01-01

    Motivation: Most of the previous data mining studies based on the NCI-60 dataset, due to its intrinsic cell-based nature, can hardly provide insights into the molecular targets for screened compounds. On the other hand, the abundant information of the compound–target associations in PubChem can offer extensive experimental evidence of molecular targets for tested compounds. Therefore, by taking advantages of the data from both public repositories, one may investigate the correlations between the bioactivity profiles of small molecules from the NCI-60 dataset (cellular level) and their patterns of interactions with relevant protein targets from PubChem (molecular level) simultaneously. Results: We investigated a set of 37 small molecules by providing links among their bioactivity profiles, protein targets and chemical structures. Hierarchical clustering of compounds was carried out based on their bioactivity profiles. We found that compounds were clustered into groups with similar mode of actions, which strongly correlated with chemical structures. Furthermore, we observed that compounds similar in bioactivity profiles also shared similar patterns of interactions with relevant protein targets, especially when chemical structures were related. The current work presents a new strategy for combining and data mining the NCI-60 dataset and PubChem. This analysis shows that bioactivity profile comparison can provide insights into the mode of actions at the molecular level, thus will facilitate the knowledge-based discovery of novel compounds with desired pharmacological properties. Availability: The bioactivity profiling data and the target annotation information are publicly available in the PubChem BioAssay database (ftp://ftp.ncbi.nlm.nih.gov/pubchem/Bioassay/). Contact: ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20947527

  3. Revisiting molecular ionization: Does a molecule like to share?

    NASA Astrophysics Data System (ADS)

    Madsen, C. B.; Esry, B. D.

    2012-06-01

    The ever-increasing detail obtained in strong-field experiments calls for a deeper understanding of the laser-molecule interaction. For instance, recent measurements reported in PRL 107, 143004 (2011) reveal a limitation in understanding strong-field ionization dynamics in terms of the strong-field approximation. We have addressed the question of how the electron and the nuclei share the energy when H2^+ breaks up in the presence of an intense IR field via the process: H2^++nφ->p+p+e^-. Solving the time-dependent Schr"odinger equation and calculating the ionization probability resolved as a function of the asymptotic electron energy and the nuclear kinetic energy release (KER) allow us to give an answer. The energy sharing is non-trivial and plays an important role in the prediction of, for instance, the KER. We also address the limitations of current understanding of molecular ionization by comparing to models like the strong-field approximation and the Floquet picture. Such benchmarking may be facilitated by XUV+IR pump-probe schemes and carrier-envelope-phase control that allow for time-resolved and spatial probing of the dynamics.

  4. MAMP (microbe-associated molecular pattern) triggered immunity in plants

    PubMed Central

    Newman, Mari-Anne; Sundelin, Thomas; Nielsen, Jon T.; Erbs, Gitte

    2013-01-01

    Plants are sessile organisms that are under constant attack from microbes. They rely on both preformed defenses, and their innate immune system to ward of the microbial pathogens. Preformed defences include for example the cell wall and cuticle, which act as physical barriers to microbial colonization. The plant immune system is composed of surveillance systems that perceive several general microbe elicitors, which allow plants to switch from growth and development into a defense mode, rejecting most potentially harmful microbes. The elicitors are essential structures for pathogen survival and are conserved among pathogens. The conserved microbe-specific molecules, referred to as microbe- or pathogen-associated molecular patterns (MAMPs or PAMPs), are recognized by the plant innate immune systems pattern recognition receptors (PRRs). General elicitors like flagellin (Flg), elongation factor Tu (EF-Tu), peptidoglycan (PGN), lipopolysaccharides (LPS), Ax21 (Activator of XA21-mediated immunity in rice), fungal chitin, and β-glucans from oomycetes are recognized by plant surface localized PRRs. Several of the MAMPs and their corresponding PRRs have, in recent years, been identified. This review focuses on the current knowledge regarding important MAMPs from bacteria, fungi, and oomycetes, their structure, the plant PRRs that recognizes them, and how they induce MAMP-triggered immunity (MTI) in plants. PMID:23720666

  5. Signatures of molecular magnetism in single-molecule transport spectroscopy.

    PubMed

    Jo, Moon-Ho; Grose, Jacob E; Baheti, Kanhayalal; Deshmukh, Mandar M; Sokol, Jennifer J; Rumberger, Evan M; Hendrickson, David N; Long, Jeffrey R; Park, Hongkun; Ralph, D C

    2006-09-01

    We report single-molecule-transistor measurements on devices incorporating magnetic molecules. By studying the electron-tunneling spectrum as a function of magnetic field, we are able to identify signatures of magnetic states and their associated magnetic anisotropy. A comparison of the data to simulations also suggests that sequential electron tunneling may enhance the magnetic relaxation of the magnetic molecule. PMID:16968018

  6. Site-selective patterning of organic luminescent molecules via gas phase deposition.

    PubMed

    Hao, Juanyuan; Lu, Nan; Wu, Qiong; Hu, Wei; Chen, Xiaodong; Zhang, Hongyu; Wu, Ying; Wang, Yue; Chi, Lifeng

    2008-05-20

    In this paper, we present a bottom-up approach to pattern organic luminescent molecules with a feature size down to sub-100 nm over wafer-sized areas. This method is based on the selective gas deposition of organic molecules on self-organized patterned structures, which consist of an organic monolayer with two different phases rather than different materials. The site selectivity is controllable by deposition rate and the pattern features. The reason for the site selectivity may be due to the nucleation and diffusion behaviors of the deposited organic molecules on different monolayer phases. PMID:18370416

  7. Exploration of target molecules for molecular imaging of inflammatory bowel disease

    SciTech Connect

    Higashikawa, Kei; Akada, Naoki; Yagi, Katsuharu; Watanabe, Keiko; Kamino, Shinichiro; Kanayama, Yousuke; Hiromura, Makoto; Enomoto, Shuichi

    2011-07-08

    addition, the alterations of cytokine and cytokine receptor expression levels indicated differences in the expression pattern depending on the pathogenic mechanism or the region of inflammation (e.g., TNF-{alpha}). Our results suggest that these cytokines or cytokine receptors participate in the pathogenesis of IBD and are valuable biomarkers for the detection of the different circumstances underlying inflammation by the molecular imaging method. Finally, the development of an imaging probe for our target molecules is expected to improve our understanding of the inflammatory conditions of IBD.

  8. Molecular 'OR' and 'AND' logic gates integrated in a single molecule

    NASA Astrophysics Data System (ADS)

    Ami, S.; Hliwa, M.; Joachim, C.

    2003-01-01

    Based on the N electrodes elastic scattering quantum chemistry (NESQC) technique, an intramolecular circuit simulator is presented for the design of electronic logic functions integrated inside a single molecule interconnected to the N electrodes. Using molecular rectifier groups, a molecule-OR and a molecule-AND are designed, their current-voltage characteristics calculated and their logic response presented. Both the OR and AND molecules have approximatively the targeted function. The running current of the OR gate, 10 fA, is quite low and the AND gate works only in an output voltage mode. This forbids the design of larger logic functions inside a single molecule with molecular rectifiers.

  9. The long pentraxin PTX3: a paradigm for humoral pattern recognition molecules.

    PubMed

    Mantovani, Alberto; Valentino, Sonia; Gentile, Stefania; Inforzato, Antonio; Bottazzi, Barbara; Garlanda, Cecilia

    2013-05-01

    Pattern recognition molecules (PRMs) are components of the humoral arm of innate immunity; they recognize pathogen-associated molecular patterns (PAMP) and are functional ancestors of antibodies, promoting complement activation, opsonization, and agglutination. In addition, several PRMs have a regulatory function on inflammation. Pentraxins are a family of evolutionarily conserved PRMs characterized by a cyclic multimeric structure. On the basis of structure, pentraxins have been operationally divided into short and long families. C-reactive protein (CRP) and serum amyloid P component are prototypes of the short pentraxin family, while pentraxin 3 (PTX3) is a prototype of the long pentraxins. PTX3 is produced by somatic and immune cells in response to proinflammatory stimuli and Toll-like receptor engagement, and it interacts with several ligands and exerts multifunctional properties. Unlike CRP, PTX3 gene organization and regulation have been conserved in evolution, thus allowing its pathophysiological roles to be evaluated in genetically modified animals. Here we will briefly review the general properties of CRP and PTX3 as prototypes of short and long pentraxins, respectively, emphasizing in particular the functional role of PTX3 as a prototypic PRM with antibody-like properties. PMID:23527487

  10. Elements of the theory of molecular spectra. [multiatomic molecules

    NASA Technical Reports Server (NTRS)

    Gribov, L. A.

    1979-01-01

    The basic aspects of the theory concerning the spectra of multiatomic molecules are presented. The classification of the forms of motions in a molecule, the methods for determining the corresponding Schroudinger levels, the spectral types and the selection rules are discussed in order to identify their presence and state in outer space.

  11. Organic molecules as chemical fossils - The molecular fossil record

    NASA Technical Reports Server (NTRS)

    Eglinton, G.

    1983-01-01

    The study of biochemical clues to the early earth and the origin of life is discussed. The methods used in such investigation are described, including the extraction, fractionation, and analysis of geolipids and the analysis of kerogen. The occurrence of molecular fossils in the geological record is examined, discussing proposed precursor-product relationships and the molecular assessment of deep sea sediments, ancient sediments, and crude petroleums. Alterations in the molecular record due to diagenesis and catagenesis are considered, and the use of microbial lipids as molecular fossils is discussed. The results of searches for molecular fossils in Precambrian sediments are assessed.

  12. Speckle Patterns with Atomic and Molecular de Broglie Waves

    SciTech Connect

    Patton, Forest S.; Deponte, Daniel P.; Kevan, Stephen D.; Elliott, Greg S.

    2006-07-07

    We have developed a nozzle source that delivers a continuous beam of atomic helium or molecular hydrogen having a high degree of transverse coherence and with adequate optical brightness to enable new kinds of experiments. Using this source we have measured single slit diffraction patterns and the first ever speckle-diffraction patterns using atomic and molecular de Broglie waves. Our results suggest fruitful application of coherent matter beams in dynamic scattering and diffractive imaging at short wavelength and with extreme surface sensitivity.

  13. Vibrational symmetry classification and torsional tunneling splitting patterns in G6(EM), G12, and G36(EM) molecules

    NASA Astrophysics Data System (ADS)

    Lattanzi, F.; di Lauro, C.

    It is shown that the torsional splitting patterns in methanol-like molecules, with the excitation of small amplitude vibrational modes in the methyl group, are determined by mechanisms that can be formulated in an almost identical fashion to that for ethane-like molecules. This is achieved by treating ethane-like molecules by the internal axis method (IAM) and methanol-like molecules by the principal axis method (PAM) or rho-axis method (RAM). Using the extended molecular groups G6(EM) or C6v(M) for methanol and G36(EM) for ethane, vibrations perpendicular to the internal rotation axis are conveniently described by modes of higher degeneracy (E for methanol and Gs for ethane) in the absence of coupling of top and frame. Head-tail coupling operators, except the cos-type barrier terms, lower the degeneracy, causing vibrational splittings. Coupled vibrational pairs with torsional splitting patterns that we call 'regular' (pure A1, A2 pairs for methanol and pure E1d, E2d pairs for ethane) or 'inverted' (pure B1, B2 pairs for methanol and pure E1s, E2s pairs for ethane) can be formed as limit cases. Actual splitting patterns occur between the above limits, and are basically determined by torsional Coriolis coupling, which can tune more or less to resonance pairs of uncoupled basis levels linked by specific head-tail coupling operators. The inversion of torsional splitting patterns, observed in perpendicular vibrational modes of the methyl group of methanol, can be predicted by these theoretical considerations. Similar considerations apply to molecules of G12 symmetry.

  14. Single Molecule Switches and Molecular Self-Assembly: Low Temperature STM Investigations and Manipulations

    SciTech Connect

    Iancu, Violeta

    2006-08-01

    This dissertation is devoted to single molecule investigations and manipulations of two porphyrin-based molecules, chlorophyll-a and Co-popphyrin. The molecules are absorbed on metallic substrates and studied at low temperatures using a scanning tunneling microscope. The electronic, structural and mechanical properties of the molecules are investigated in detail with atomic level precision. Chlorophyll-a is the key ingredient in photosynthesis processes while Co-porphyrin is a magnetic molecule that represents the recent emerging field of molecular spintronics. Using the scanning tunneling microscope tip and the substrate as electrodes, and the molecules as active ingredients, single molecule switches made of these two molecules are demonstrated. The first switch, a multiple and reversible mechanical switch, is realized by using chlorophyll-a where the energy transfer of a single tunneling electron is used to rotate a C-C bond of the molecule's tail on a Au(111) surface. Here, the det

  15. Update: affibody molecules for molecular imaging and therapy for cancer.

    PubMed

    Orlova, Anna; Feldwisch, Joachim; Abrahmsén, Lars; Tolmachev, Vladimir

    2007-10-01

    Affibody molecules are scaffold proteins, having a common frame of amino acids determining the overall fold or tertiary structure, but with each member characterized by a unique amino acid composition in an exposed binding surface determining binding specificity and affinity for a certain target. Affibody molecules represent a new class of affinity proteins based on a 58-amino acid residue protein domain, derived from one of the IgG binding domains of staphylococcal protein A. They combine small size ( approximately 6.5 kDa) with high affinity and specificity. Affibody molecules with nanomolar affinities were selected from an initial library (3 x 10(9) members) and, after affinity maturation, picomolar binders were obtained. The small size and simple structure of affibody molecules allow their production by chemical synthesis with homogeneous site-specific incorporation of moieties for further labeling using a wide range of labeling chemistries. The robustness and the refolding properties of affibody molecules make them amenable to labeling conditions that denature most proteins, including incubation at pH 11 at 60 degrees C for up to 60 minutes. Affibody molecules meet the requirements which are key for successful clinical use as imaging agents: high-affinity binding to the chosen target; short plasma half-life time; rapid renal clearance for nonbound drug substance and, high, continuously increasing tumor-to-organ ratios, resulting in high-contrast in vivo images shortly after injection of the diagnostic agent. PMID:17979560

  16. 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.

  17. Chains of quantum dot molecules grown on Si surface pre-patterned by ion-assisted nanoimprint lithography

    SciTech Connect

    Smagina, Zh. V.; Stepina, N. P. Zinovyev, V. A.; Kuchinskaya, P. A.; Novikov, P. L.; Dvurechenskii, A. V.

    2014-10-13

    An original approach based on the combination of nanoimprint lithography and ion irradiation through mask has been developed for fabrication of large-area periodical pattern on Si(100). Using the selective etching of regions amorphized by ion irradiation ordered structures with grooves and ridges were obtained. The shape and depth of the relief were governed by ion energy and by the number of etching stages as well. Laterally ordered chains of Ge quantum dots were fabricated by molecular beam epitaxy of Ge on the pre-patterned Si substrates. For small amount of Ge deposited chains contain separate quantum dot molecules. The increase of deposition amount leads to overlapping of quantum dot molecules with formation of dense homogeneous chains of quantum dots. It was shown that the residual irradiation-induced bulk defects underneath the grooves suppress nucleation of Ge islands at the bottom of grooves. On pre-patterned substrates with whole defect regions, etched quantum dots grow at the bottom of grooves. The observed location of Ge quantum dots is interpreted in terms of local strain-mediated surface chemical potential which controls the sites of islands nucleation. The local chemical potential is affected by additional strain formed by the residual defects. It was shown by molecular dynamics calculations that these defects form the compressive strain at the bottom of grooves.

  18. Reversible gating of smart plasmonic molecular traps using thermoresponsive polymers for single-molecule detection

    PubMed Central

    Zheng, Yuanhui; Soeriyadi, Alexander H.; Rosa, Lorenzo; Ng, Soon Hock; Bach, Udo; Justin Gooding, J.

    2015-01-01

    Single-molecule surface-enhanced Raman spectroscopy (SERS) has attracted increasing interest for chemical and biochemical sensing. Many conventional substrates have a broad distribution of SERS enhancements, which compromise reproducibility and result in slow response times for single-molecule detection. Here we report a smart plasmonic sensor that can reversibly trap a single molecule at hotspots for rapid single-molecule detection. The sensor was fabricated through electrostatic self-assembly of gold nanoparticles onto a gold/silica-coated silicon substrate, producing a high yield of uniformly distributed hotspots on the surface. The hotspots were isolated with a monolayer of a thermoresponsive polymer (poly(N-isopropylacrylamide)), which act as gates for molecular trapping at the hotspots. The sensor shows not only a good SERS reproducibility but also a capability to repetitively trap and release molecules for single-molecular sensing. The single-molecule sensitivity is experimentally verified using SERS spectral blinking and bianalyte methods. PMID:26549539

  19. Reversible gating of smart plasmonic molecular traps using thermoresponsive polymers for single-molecule detection.

    PubMed

    Zheng, Yuanhui; Soeriyadi, Alexander H; Rosa, Lorenzo; Ng, Soon Hock; Bach, Udo; Justin Gooding, J

    2015-01-01

    Single-molecule surface-enhanced Raman spectroscopy (SERS) has attracted increasing interest for chemical and biochemical sensing. Many conventional substrates have a broad distribution of SERS enhancements, which compromise reproducibility and result in slow response times for single-molecule detection. Here we report a smart plasmonic sensor that can reversibly trap a single molecule at hotspots for rapid single-molecule detection. The sensor was fabricated through electrostatic self-assembly of gold nanoparticles onto a gold/silica-coated silicon substrate, producing a high yield of uniformly distributed hotspots on the surface. The hotspots were isolated with a monolayer of a thermoresponsive polymer (poly(N-isopropylacrylamide)), which act as gates for molecular trapping at the hotspots. The sensor shows not only a good SERS reproducibility but also a capability to repetitively trap and release molecules for single-molecular sensing. The single-molecule sensitivity is experimentally verified using SERS spectral blinking and bianalyte methods. PMID:26549539

  20. 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

  1. The Virtual Museum of Minerals and Molecules: Molecular Visualization in a Virtual Hands-On Museum

    ERIC Educational Resources Information Center

    Barak, Phillip; Nater, Edward A.

    2005-01-01

    The Virtual Museum of Minerals and Molecules (VMMM) is a web-based resource presenting interactive, 3-D, research-grade molecular models of more than 150 minerals and molecules of interest to chemical, earth, plant, and environmental sciences. User interactivity with the 3-D display allows models to be rotated, zoomed, and specific regions of…

  2. A Novel Pictorial Approach to Teaching Molecular Motions in Polyatomic Molecules.

    ERIC Educational Resources Information Center

    Verkade, John G.

    1987-01-01

    Describes a procedure for teaching the "generator orbital" (GO) approach of molecular orbital bonding in polyatomic molecules. Explains how the GO can be utilized with students in generating the vibrational, rotational, and translational modes of molecules in a completely pictorial manner. (ML)

  3. Complexity of Danger: The Diverse Nature of Damage-associated Molecular Patterns*

    PubMed Central

    Schaefer, Liliana

    2014-01-01

    In reply to internal or external danger stimuli, the body orchestrates an inflammatory response. The endogenous triggers of this process are the damage-associated molecular patterns (DAMPs). DAMPs represent a heterogeneous group of molecules that draw their origin either from inside the various compartments of the cell or from the extracellular space. Following interaction with pattern recognition receptors in cross-talk with various non-immune receptors, DAMPs determine the downstream signaling outcome of septic and aseptic inflammatory responses. In this review, the diverse nature, structural characteristics, and signaling pathways elicited by DAMPs will be critically evaluated. PMID:25391648

  4. Laser Induced Molecular Spectroscopy of Zn{sub 2} Molecule

    SciTech Connect

    Singh, Subhash C.; Gopal, Ram

    2008-11-14

    Laser produced spectra of zinc molecule have been recorded in the region of 540-670 nm using second harmonics of Nd: YAG laser, computer--controlled TRIAX 320 M monochromator with a reciprocal linear dispersion 2.64 nm/mm fitted with ICCD detector. The spectrum consists of 35 bands, which are classified into D ({sup 1} product {sub u}){yields}A({sup 3} product {sub g}) and C ({sup 1}{sigma}{sub u}{sup +}){yields}A({sup 3} product {sub g}) systems. We have recorded the florescence spectrum of zinc dimer by pumping and probing with the same laser, which proves that produced molecules are stable for more than 0.1 seconds.

  5. Molecular forces for the binding and condensation of DNA molecules.

    PubMed Central

    Cai, Xian-E; Yang, Jie

    2002-01-01

    Atomic force microscopy has been used to investigate the binding between a double-stranded DNA and bilayers of cationic lipids and zwitterionic lipids in low ionic-strength solutions. The binding of a DNA molecule to freshly cleaved mica surface in solution has also been measured. The binding of DNA molecules to cationic lipid bilayers has a minimal strength of approximately 45 pN. On zwitterionic lipid bilayers and mica surface, the minimal binding strength is approximately twice that value. The binding also has a dynamic nature, with only a certain percentage of recorded force curves containing the binding characteristics. Divalent Mg(2+) ions enhance the binding by increasing that percentage without any effect on the binding strength. We have also observed a long-range attraction between DNA molecules and cationic lipid bilayers with a strength much larger than the minimum force and a range well over 50 nm, possibly related to the driving force responsible for the two-dimensional condensation of DNA. PMID:11751322

  6. Small molecule recognition of mephedrone using an anthracene molecular clip.

    PubMed

    Kellett, Kathryn; Broome, J Hugh; Zloh, Mire; Kirton, Stewart B; Fergus, Suzanne; Gerhard, Ute; Stair, Jacqueline L; Wallace, Karl J

    2016-06-14

    An anthracene molecular probe has been synthesised and shown to target mephedrone, a stimulant drug from the cathinone class of new psychoactive substances (NPS). A protocol has been developed to detect mephedrone via the probe using NMR spectroscopy in a simulated street sample containing two of the most common cutting agents, benzocaine and caffeine. PMID:27198990

  7. Selective inner-valence ionization of aligned polyatomic molecules for controlling molecular fragmentation

    NASA Astrophysics Data System (ADS)

    Xie, X.; Doblhoff-Dier, K.; Xu, H.; Roither, S.; Iwasaki, A.; Schöffler, M.; Kartashov, D.; Yamanouchi, K.; Baltuška, A.; Gräfe, S.; Kitzler, M.

    2014-04-01

    We show experimentally and theoretically, using acetylene as an example, that the strong preponderance of ionization from specific molecular orbitals to the alignment of the molecular axis with respect to the laser polarization direction allows implementing a method for controlling fragmentation reactions of polyatomic molecules.

  8. Are Molecular Vibration Patterns of Cell Structural Elements Used for Intracellular Signalling?

    PubMed Central

    Jaross, Werner

    2016-01-01

    Background: To date the manner in which information reaches the nucleus on that part within the three-dimensional structure where specific restorative processes of structural components of the cell are required is unknown. The soluble signalling molecules generated in the course of destructive and restorative processes communicate only as needed. Hypothesis: All molecules show temperature-dependent molecular vibration creating a radiation in the infrared region. Each molecule species has in its turn a specific frequency pattern under given specific conditions. Changes in their structural composition result in modified frequency patterns of the molecules in question. The main structural elements of the cell membrane, of the endoplasmic reticulum, of the Golgi apparatus, and of the different microsomes representing the great variety of polar lipids show characteristic frequency patterns with peaks in the region characterised by low water absorption. These structural elements are very dynamic, mainly caused by the creation of signal molecules and transport containers. By means of the characteristic radiation, the area where repair or substitution services are needed could be identified; this spatial information complements the signalling of the soluble signal molecules. Based on their resonance properties receptors located on the outer leaflet of the nuclear envelope should be able to read typical frequencies and pass them into the nucleus. Clearly this physical signalling must be blocked by the cell membrane to obviate the flow of information into adjacent cells. Conclusion: If the hypothesis can be proved experimentally, it should be possible to identify and verify characteristic infrared frequency patterns. The application of these signal frequencies onto cells would open entirely new possibilities in medicine and all biological disciplines specifically to influence cell growth and metabolism. Similar to this intracellular system, an extracellular signalling system

  9. Research Update: Molecular electronics: The single-molecule switch and transistor

    SciTech Connect

    Sotthewes, Kai; Heimbuch, René Kumar, Avijit; Zandvliet, Harold J. W.; Geskin, Victor

    2014-01-01

    In order to design and realize single-molecule devices it is essential to have a good understanding of the properties of an individual molecule. For electronic applications, the most important property of a molecule is its conductance. Here we show how a single octanethiol molecule can be connected to macroscopic leads and how the transport properties of the molecule can be measured. Based on this knowledge we have realized two single-molecule devices: a molecular switch and a molecular transistor. The switch can be opened and closed at will by carefully adjusting the separation between the electrical contacts and the voltage drop across the contacts. This single-molecular switch operates in a broad temperature range from cryogenic temperatures all the way up to room temperature. Via mechanical gating, i.e., compressing or stretching of the octanethiol molecule, by varying the contact's interspace, we are able to systematically adjust the conductance of the electrode-octanethiol-electrode junction. This two-terminal single-molecule transistor is very robust, but the amplification factor is rather limited.

  10. Dependence of tunneling current through a single molecule of phenylene oligomers on the molecular length.

    PubMed

    Wakamatsu, Satoshi; Fujii, Shintaro; Akiba, Uichi; Fujihira, Masamichi

    2003-01-01

    The electrical properties of single phenylene oligomers were studied in terms of the dependence of the tunneling current on the length of the oligomers using self-assembling techniques and scanning tunneling microscopy (STM). It is important to isolate single molecules in an insulating matrix for the measurement of the conductivity of the single molecule. We demonstrate here a novel self-assembled monolayer (SAM) matrix appropriate for isolation of the single molecules. A bicyclo[2.2.2]octane derivative was used for a SAM matrix, in which the single molecules were inserted at molecular lattice defects. The isolated single molecules of phenylene oligomers inserted in the SAM matrix were observed as protrusions in STM topography using a constant current mode. We measured the topographic heights of the molecular protrusions using STM and estimated the decay constant, beta, of the tunneling current through the single phenylene oligomers using a bilayer tunnel junction model. PMID:12801653

  11. Molecular tips for scanning tunneling microscopy: intermolecular electron tunneling for single-molecule recognition and electronics.

    PubMed

    Nishino, Tomoaki

    2014-01-01

    This paper reviews the development of molecular tips for scanning tunneling microscopy (STM). Molecular tips offer many advantages: first is their ability to perform chemically selective imaging because of chemical interactions between the sample and the molecular tip, thus improving a major drawback of conventional STM. Rational design of the molecular tip allows sophisticated chemical recognition; e.g., chiral recognition and selective visualization of atomic defects in carbon nanotubes. Another advantage is that they provide a unique method to quantify electron transfer between single molecules. Understanding such electron transfer is mandatory for the realization of molecular electronics. PMID:24420248

  12. A comprehensive study of extended tetrathiafulvalene cruciform molecules for molecular electronics: synthesis and electrical transport measurements.

    PubMed

    Parker, Christian R; Leary, Edmund; Frisenda, Riccardo; Wei, Zhongming; Jennum, Karsten S; Glibstrup, Emil; Abrahamsen, Peter Bæch; Santella, Marco; Christensen, Mikkel A; Della Pia, Eduardo Antonio; Li, Tao; Gonzalez, Maria Teresa; Jiang, Xingbin; Morsing, Thorbjørn J; Rubio-Bollinger, Gabino; Laursen, Bo W; Nørgaard, Kasper; van der Zant, Herre; Agrait, Nicolas; Nielsen, Mogens Brøndsted

    2014-11-26

    Cruciform-like molecules with two orthogonally placed π-conjugated systems have in recent years attracted significant interest for their potential use as molecular wires in molecular electronics. Here we present synthetic protocols for a large selection of cruciform molecules based on oligo(phenyleneethynylene) (OPE) and tetrathiafulvalene (TTF) scaffolds, end-capped with acetyl-protected thiolates as electrode anchoring groups. The molecules were subjected to a comprehensive study of their conducting properties as well as their photophysical and electrochemical properties in solution. The complex nature of the molecules and their possible binding in different configurations in junctions called for different techniques of conductance measurements: (1) conducting-probe atomic force microscopy (CP-AFM) measurements on self-assembled monolayers (SAMs), (2) mechanically controlled break-junction (MCBJ) measurements, and (3) scanning tunneling microscopy break-junction (STM-BJ) measurements. The CP-AFM measurements showed structure-property relationships from SAMs of series of OPE3 and OPE5 cruciform molecules; the conductance of the SAM increased with the number of dithiafulvene (DTF) units (0, 1, 2) along the wire, and it increased when substituting two arylethynyl end groups of the OPE3 backbone with two DTF units. The MCBJ and STM-BJ studies on single molecules both showed that DTFs decreased the junction formation probability, but, in contrast, no significant influence on the single-molecule conductance was observed. We suggest that the origins of the difference between SAM and single-molecule measurements lie in the nature of the molecule-electrode interface as well as in effects arising from molecular packing in the SAMs. This comprehensive study shows that for complex molecules care should be taken when directly comparing single-molecule measurements and measurements of SAMs and solid-state devices thereof. PMID:25375316

  13. Molecular assembly of highly symmetric molecules under a hydrogen bond framework controlled by alkyl building blocks: a simple approach to fine-tune nanoscale structures.

    PubMed

    Tanphibal, Pimsai; Tashiro, Kohji; Chirachanchai, Suwabun

    2016-01-14

    To date, molecular assemblies under the contribution of hydrogen bond in combination with weak interactions and their consequent morphologies have been variously reported; however, how the systematic variation of the structure can fine-tune the morphologies has not yet been answered. The present work finds an answer through highly symmetric molecules, i.e. diamine-based benzoxazine dimers. This type of molecule develops unique molecular assemblies with their networks formed by hydrogen bonds at the terminal, while, at the same time, their hydrogen bonded frameworks are further controlled by the hydrophobic segment at the center of the molecule. When this happens, slight differences in hydrophobic alkyl chain lengths (, , and ) bring a significant change to the molecular assemblies, thus resulting in tunable morphologies, i.e. spheres, needles and dendrites. The superimposition between the crystal lattice obtained from X-ray single crystal analysis and the electron diffraction pattern obtained from transmission electron microscopy allows us to identify the molecular alignment from single molecules to self-assembly until the morphologies developed. The present work, for the first time, shows the case of symmetric molecules, where the hydrophobic building block controls the hydrogen bond patterns, leading to the variation of molecular assemblies with tunable morphologies. PMID:26482133

  14. Tracking molecular resonance forms of donor–acceptor push–pull molecules by single-molecule conductance experiments

    PubMed Central

    Lissau, Henriette; Frisenda, Riccardo; Olsen, Stine T.; Jevric, Martyn; Parker, Christian R.; Kadziola, Anders; Hansen, Thorsten; van der Zant, Herre S. J.; Brøndsted Nielsen, Mogens; Mikkelsen, Kurt V.

    2015-01-01

    The ability of molecules to change colour on account of changes in solvent polarity is known as solvatochromism and used spectroscopically to characterize charge-transfer transitions in donor–acceptor molecules. Here we report that donor–acceptor-substituted molecular wires also exhibit distinct properties in single-molecule electronics under the influence of a bias voltage, but in absence of solvent. Two oligo(phenyleneethynylene) wires with donor–acceptor substitution on the central ring (cruciform-like) exhibit remarkably broad conductance peaks measured by the mechanically controlled break-junction technique with gold contacts, in contrast to the sharp peak of simpler molecules. From a theoretical analysis, we explain this by different degrees of charge delocalization and hence cross-conjugation at the central ring. Thus, small variations in the local environment promote the quinoid resonance form (off), the linearly conjugated (on) or any form in between. This shows how the conductance of donor–acceptor cruciforms is tuned by small changes in the environment. PMID:26667583

  15. Paramagnetic molecule induced strong antiferromagnetic exchange coupling on a magnetic tunnel junction based molecular spintronics device.

    PubMed

    Tyagi, Pawan; Baker, Collin; D'Angelo, Christopher

    2015-07-31

    This paper reports our Monte Carlo (MC) studies aiming to explain the experimentally observed paramagnetic molecule induced antiferromagnetic coupling between ferromagnetic (FM) electrodes. Recently developed magnetic tunnel junction based molecular spintronics devices (MTJMSDs) were prepared by chemically bonding the paramagnetic molecules between the FM electrodes along the tunnel junction's perimeter. These MTJMSDs exhibited molecule-induced strong antiferromagnetic coupling. We simulated the 3D atomic model analogous to the MTJMSD and studied the effect of molecule's magnetic couplings with the two FM electrodes. Simulations show that when a molecule established ferromagnetic coupling with one electrode and antiferromagnetic coupling with the other electrode, then theoretical results effectively explained the experimental findings. Our studies suggest that in order to align MTJMSDs' electrodes antiparallel to each other, the exchange coupling strength between a molecule and FM electrodes should be ∼50% of the interatomic exchange coupling for the FM electrodes. PMID:26159362

  16. Dissociation dynamics of ethylene molecules on a Ni cluster using ab initio molecular dynamics simulations.

    PubMed

    Shimamura, K; Shibuta, Y; Ohmura, S; Arifin, R; Shimojo, F

    2016-04-13

    The atomistic mechanism of dissociative adsorption of ethylene molecules on a Ni cluster is investigated by ab initio molecular-dynamics simulations. The activation free energy to dehydrogenate an ethylene molecule on the Ni cluster and the corresponding reaction rate is estimated. A remarkable finding is that the adsorption energy of ethylene molecules on the Ni cluster is considerably larger than the activation free energy, which explains why the actual reaction rate is faster than the value estimated based on only the activation free energy. It is also found from the dynamic simulations that hydrogen molecules and an ethane molecule are formed from the dissociated hydrogen atoms, whereas some exist as single atoms on the surface or in the interior of the Ni cluster. On the other hand, the dissociation of the C-C bonds of ethylene molecules is not observed. On the basis of these simulation results, the nature of the initial stage of carbon nanotube growth is discussed. PMID:26953616

  17. Dissociation dynamics of ethylene molecules on a Ni cluster using ab initio molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Shimamura, K.; Shibuta, Y.; Ohmura, S.; Arifin, R.; Shimojo, F.

    2016-04-01

    The atomistic mechanism of dissociative adsorption of ethylene molecules on a Ni cluster is investigated by ab initio molecular-dynamics simulations. The activation free energy to dehydrogenate an ethylene molecule on the Ni cluster and the corresponding reaction rate is estimated. A remarkable finding is that the adsorption energy of ethylene molecules on the Ni cluster is considerably larger than the activation free energy, which explains why the actual reaction rate is faster than the value estimated based on only the activation free energy. It is also found from the dynamic simulations that hydrogen molecules and an ethane molecule are formed from the dissociated hydrogen atoms, whereas some exist as single atoms on the surface or in the interior of the Ni cluster. On the other hand, the dissociation of the C-C bonds of ethylene molecules is not observed. On the basis of these simulation results, the nature of the initial stage of carbon nanotube growth is discussed.

  18. Molecular dynamics study on condensation/evaporation coefficients of chain molecules at liquid–vapor interface

    SciTech Connect

    Nagayama, Gyoko Takematsu, Masaki; Mizuguchi, Hirotaka; Tsuruta, Takaharu

    2015-07-07

    The structure and thermodynamic properties of the liquid–vapor interface are of fundamental interest for numerous technological implications. For simple molecules, e.g., argon and water, the molecular condensation/evaporation behavior depends strongly on their translational motion and the system temperature. Existing molecular dynamics (MD) results are consistent with the theoretical predictions based on the assumption that the liquid and vapor states in the vicinity of the liquid–vapor interface are isotropic. Additionally, similar molecular condensation/evaporation characteristics have been found for long-chain molecules, e.g., dodecane. It is unclear, however, whether the isotropic assumption is valid and whether the molecular orientation or the chain length of the molecules affects the condensation/evaporation behavior at the liquid–vapor interface. In this study, MD simulations were performed to study the molecular condensation/evaporation behavior of the straight-chain alkanes, i.e., butane, octane, and dodecane, at the liquid–vapor interface, and the effects of the molecular orientation and chain length were investigated in equilibrium systems. The results showed that the condensation/evaporation behavior of chain molecules primarily depends on the molecular translational energy and the surface temperature and is independent of the molecular chain length. Furthermore, the orientation at the liquid–vapor interface was disordered when the surface temperature was sufficiently higher than the triple point and had no significant effect on the molecular condensation/evaporation behavior. The validity of the isotropic assumption was confirmed, and we conclude that the condensation/evaporation coefficients can be predicted by the liquid-to-vapor translational length ratio, even for chain molecules.

  19. Molecular dynamics study on condensation/evaporation coefficients of chain molecules at liquid-vapor interface

    NASA Astrophysics Data System (ADS)

    Nagayama, Gyoko; Takematsu, Masaki; Mizuguchi, Hirotaka; Tsuruta, Takaharu

    2015-07-01

    The structure and thermodynamic properties of the liquid-vapor interface are of fundamental interest for numerous technological implications. For simple molecules, e.g., argon and water, the molecular condensation/evaporation behavior depends strongly on their translational motion and the system temperature. Existing molecular dynamics (MD) results are consistent with the theoretical predictions based on the assumption that the liquid and vapor states in the vicinity of the liquid-vapor interface are isotropic. Additionally, similar molecular condensation/evaporation characteristics have been found for long-chain molecules, e.g., dodecane. It is unclear, however, whether the isotropic assumption is valid and whether the molecular orientation or the chain length of the molecules affects the condensation/evaporation behavior at the liquid-vapor interface. In this study, MD simulations were performed to study the molecular condensation/evaporation behavior of the straight-chain alkanes, i.e., butane, octane, and dodecane, at the liquid-vapor interface, and the effects of the molecular orientation and chain length were investigated in equilibrium systems. The results showed that the condensation/evaporation behavior of chain molecules primarily depends on the molecular translational energy and the surface temperature and is independent of the molecular chain length. Furthermore, the orientation at the liquid-vapor interface was disordered when the surface temperature was sufficiently higher than the triple point and had no significant effect on the molecular condensation/evaporation behavior. The validity of the isotropic assumption was confirmed, and we conclude that the condensation/evaporation coefficients can be predicted by the liquid-to-vapor translational length ratio, even for chain molecules.

  20. Microbes, molecular mimicry and molecules of mood and motivation.

    PubMed

    Morris, J A; Broughton, S J; Wessels, Q

    2016-02-01

    The hypothesis proposed is that functional disorders, such as irritable bowel syndrome, chronic fatigue syndrome and anorexia nervosa are caused by auto-antibodies to neuronal proteins induced by molecular mimicry with microbial antigens. The age incidence of these conditions, the marked female excess, increase with economic and technological advance, precipitation by infection, and the paucity of histological changes are all consistent with the hypothesis. It can be tested directly using human sera to search for cross reaction with brain proteins in model systems such as Drosophila melanogaster. The conditions might be amenable to treatment using pooled immunoglobulin. Identification and elimination from the microbial flora of the bacteria that express the cross reacting antigens should be possible. PMID:26826639

  1. MoFlow: visualizing conformational changes in molecules as molecular flow improves understanding

    PubMed Central

    2015-01-01

    Background Current visualizations of molecular motion use a Timeline-analogous representation that conveys "first the molecule was shaped like this, then like this...". This scheme is orthogonal to the Pathline-like human understanding of motion "this part of the molecule moved from here to here along this path". We present MoFlow, a system for visualizing molecular motion using a Pathline-analogous representation. Results The MoFlow system produces high-quality renderings of molecular motion as atom pathlines, as well as interactive WebGL visualizations, and 3D printable models. In a preliminary user study, MoFlow representations are shown to be superior to canonical representations for conveying molecular motion. Conclusions Pathline-based representations of molecular motion are more easily understood than timeline representations. Pathline representations provide other advantages because they represent motion directly, rather than representing structure with inferred motion. PMID:26361501

  2. New Materials, Methods, and Molecules for Microelectronic and Molecular Electronic Devices

    NASA Astrophysics Data System (ADS)

    Miller, Michael Stephen

    This dissertation reports a variety of new methods and materials for the fabrication of electronic devices. Particular emphasis is placed on low-cost, solution based methods for flexible electronic device fabrication, and new substrates and molecules for molecular electronic tunnel junctions. Chapter 2 reports a low-cost, solution based method for depositing patterned metal circuitry onto a variety of flexible polymer substrates. Microcontact printing an aluminum (III) porphyrin complex activates selected areas of an oxidized polymer substrate to electroless copper metallization. Chapter 3 reports a new transparent conductive electrode for use in optoelectronic devices. A highly conductive, transparent silver nanowire network is embedded at the surface of an optical adhesive, which can be applied to a variety of rigid and flexible polymer substrates. Chapter 4 describes a new approach to the self-assembly of mesoscale components into two-dimensional arrays. Unlike most previously reported self-assembly motifs, this method is completely dry; eliminating solvent makes this method compatible with the assembly of electronic components. Chapter 5 describes a new class of self-assembled monolayer (SAM) on gold formed from dihexadecyldithiophosphinic acid ((C16) 2DTPA) adsorbate molecules. The binding and structure (C16) 2DTPA SAMs is dependent upon the roughness and morphology of the underlying gold substrate. Chapter 6 investigates the influence of chain length on the binding and structure of dialkyl-DTPA SAMs on smooth, template-stripped (TS) gold. Binding of the DTPA head group is independent of the length of the alkyl chain, while the structure of the organic layer has a counter-intuitive dependence: As the length of the alkyl chain increases, these SAMs become more disordered and liquid-like. Chapter 7 describes the fabrication of ultra smooth gold substrates using chemical mechanical polishing (CMP). These substrates are smooth, uniform, and prove to be ideal

  3. Molecular surface point environments for virtual screening and the elucidation of binding patterns (MOLPRINT 3D).

    PubMed

    Bender, Andreas; Mussa, Hamse Y; Gill, Gurprem S; Glen, Robert C

    2004-12-16

    A novel method (MOLPRINT 3D) for virtual screening and the elucidation of ligand-receptor binding patterns is introduced that is based on environments of molecular surface points. The descriptor uses points relative to the molecular coordinates, thus it is translationally and rotationally invariant. Due to its local nature, conformational variations cause only minor changes in the descriptor. If surface point environments are combined with the Tanimoto coefficient and applied to virtual screening, they achieve retrieval rates comparable to that of two-dimensional (2D) fingerprints. The identification of active structures with minimal 2D similarity ("scaffold hopping") is facilitated. In combination with information-gain-based feature selection and a naive Bayesian classifier, information from multiple molecules can be combined and classification performance can be improved. Selected features are consistent with experimentally determined binding patterns. Examples are given for angiotensin-converting enzyme inhibitors, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, and thromboxane A2 antagonists. PMID:15588092

  4. Inflammatory molecules expression pattern for identifying pathogen species in febrile patient serum

    PubMed Central

    LIU, KUAN-TING; LIU, YAO-HUA; LIN, CHUN-YU; KUO, PO-LIN; YEN, MENG-CHI

    2016-01-01

    Inflammatory molecules, such as cytokines and chemokines, have been considered markers for bacterial or viral infection in serum of patients in numerous studies. The aim of the present study was to investigate whether we were able to identify the pathogen species through patterns of inflammatory molecules. A total of 132 patients with elevated body temperature (tympanic temperature, >38.3°C) were recruited for this study. The concentrations of various inflammatory molecules in the patients' serum were evaluated using a cytometric bead array. Higher concentrations of interleukin (IL)-6 and IL-8 were detected in bacterial infection groups (patients with positive and negative blood cultures), as compared with the viral infection group. Viral infection (including influenza and dengue viral infections) was associated with higher concentrations of interferon-γ-inducible protein 10 (IP-10), as compared with the bacterial infection group. In addition, IL-8 levels in the gram-negative bacteria group were higher, as compared with the gram-positive bacteria group. However, IL-8 was insufficient for bacterial species identification. By contrast, dengue virus infection induced the highest serum level of IP-10 among all groups. In conclusion, detection of the patterns of inflammatory molecules may aid the subsequent management and treatment modalities in hospitals, although evaluation of these molecules alone may be insufficient for identifying the pathogen species. PMID:27347055

  5. Conventional, molecular methods and biomarkers molecules in detection of septicemia

    PubMed Central

    Arabestani, Mohammad Reza; Rastiany, Sahar; Kazemi, Sima; Mousavi, Seyed Masoud

    2015-01-01

    Sepsis is a leading cause of morbidity and mortality in hospitalized patients worldwide and based on studies, 30–40% of all cases of severe sepsis and septic shock results from the blood stream infections (BSIs). Identifying of the disease, performing laboratory tests, and consequently treatment are factors that required for optimum management of BSIs. In addition, applying precise and immediate identification of the etiologic agent is a prerequisite for specific antibiotic therapy of pathogen and thereby decreasing mortality rates. The diagnosis of sepsis is difficult because clinical signs of sepsis often overlap with other noninfectious cases of systemic inflammation. BSIs are usually diagnosed by performing a series of techniques such as blood cultures, polymerase chain reaction-based methods, and biomarkers of sepsis. Extremely time-consuming even to take up to several days is a major limitation of conventional methods. In addition, yielding false-negative results due to fastidious and slow-growing microorganisms and also in case of antibiotic pretreated samples are other limitations. In comparison, molecular methods are capable of examining a blood sample obtained from suspicious patient with BSI and gave the all required information to prescribing antimicrobial therapy for detected bacterial or fungal infections immediately. Because of an emergency of sepsis, new methods are being developed. In this review, we discussed about the most important sepsis diagnostic methods and numbered the advantage and disadvantage of the methods in detail. PMID:26261822

  6. Conventional, molecular methods and biomarkers molecules in detection of septicemia.

    PubMed

    Arabestani, Mohammad Reza; Rastiany, Sahar; Kazemi, Sima; Mousavi, Seyed Masoud

    2015-01-01

    Sepsis is a leading cause of morbidity and mortality in hospitalized patients worldwide and based on studies, 30-40% of all cases of severe sepsis and septic shock results from the blood stream infections (BSIs). Identifying of the disease, performing laboratory tests, and consequently treatment are factors that required for optimum management of BSIs. In addition, applying precise and immediate identification of the etiologic agent is a prerequisite for specific antibiotic therapy of pathogen and thereby decreasing mortality rates. The diagnosis of sepsis is difficult because clinical signs of sepsis often overlap with other noninfectious cases of systemic inflammation. BSIs are usually diagnosed by performing a series of techniques such as blood cultures, polymerase chain reaction-based methods, and biomarkers of sepsis. Extremely time-consuming even to take up to several days is a major limitation of conventional methods. In addition, yielding false-negative results due to fastidious and slow-growing microorganisms and also in case of antibiotic pretreated samples are other limitations. In comparison, molecular methods are capable of examining a blood sample obtained from suspicious patient with BSI and gave the all required information to prescribing antimicrobial therapy for detected bacterial or fungal infections immediately. Because of an emergency of sepsis, new methods are being developed. In this review, we discussed about the most important sepsis diagnostic methods and numbered the advantage and disadvantage of the methods in detail. PMID:26261822

  7. How does the molecular linker in dynamic force spectroscopy affect probing molecular interactions at the single-molecule level?

    NASA Astrophysics Data System (ADS)

    Taninaka, Atsushi; Aizawa, Kota; Hanyu, Tatsuya; Hirano, Yuuichi; Takeuchi, Osamu; Shigekawa, Hidemi

    2016-08-01

    Dynamic force spectroscopy (DFS) based on atomic force microscopy, which enables us to obtain information on the interaction potential between molecules such as antigen–antibody complexes at the single-molecule level, is a key technique for advancing molecular science and technology. However, to ensure the reliability of DFS measurement, its basic mechanism must be well understood. We examined the effect of the molecular linker used to fix the target molecule to the atomic force microscope cantilever, i.e., the force direction during measurement, for the first time, which has not been discussed until now despite its importance. The effect on the lifetime and barrier position, which can be obtained by DFS, was found to be ∼10 and ∼50%, respectively, confirming the high potential of DFS.

  8. How does the molecular linker in dynamic force spectroscopy affect probing molecular interactions at the single-molecule level?

    NASA Astrophysics Data System (ADS)

    Taninaka, Atsushi; Aizawa, Kota; Hanyu, Tatsuya; Hirano, Yuuichi; Takeuchi, Osamu; Shigekawa, Hidemi

    2016-08-01

    Dynamic force spectroscopy (DFS) based on atomic force microscopy, which enables us to obtain information on the interaction potential between molecules such as antigen-antibody complexes at the single-molecule level, is a key technique for advancing molecular science and technology. However, to ensure the reliability of DFS measurement, its basic mechanism must be well understood. We examined the effect of the molecular linker used to fix the target molecule to the atomic force microscope cantilever, i.e., the force direction during measurement, for the first time, which has not been discussed until now despite its importance. The effect on the lifetime and barrier position, which can be obtained by DFS, was found to be ˜10 and ˜50%, respectively, confirming the high potential of DFS.

  9. Origins of entropy change for the amphiphilic molecule in micellization: a molecular dynamics study.

    PubMed

    Liu, Guokui; Wei, Yaoyao; Gao, Fengfeng; Yuan, Shiling; Liu, Chengbu

    2016-04-20

    The micellization of amphiphilic molecules is an important phenomenon in the natural world. However, the origin of entropy change during micellization is still unclear. Molecular dynamics simulation was applied to study configurational entropy change of amphiphilic molecules in micellization. The entropy change of polar heads, hydrophobic chains, vibration, translation and rotation are discussed. Analyses provide a clear physical picture of the entropy increase in micellization, and thus foundations for further study. PMID:27056091

  10. Millimeter-Wave Spectroscopic and Collisional Studies of Molecules and Molecular Ions

    NASA Astrophysics Data System (ADS)

    Pearson, John Christoffersen

    1995-01-01

    Molecular spectroscopy in the millimeter- and submillimeter-wave regions is an important tool in molecular physics. Information on molecular motions and interactions is obtained from spectroscopic studies of energy levels and collisions. This information and the data from which it is derived are essential in remote sensing of the atmosphere and the interstellar medium. Remote sensing at submillimeter wavelengths is now possible, making higher frequency and quantum number measurements of known interstellar species like water, propionitrile and ethyl alcohol necessary. Remote sensing improvements have also facilitated the need for spectral data on suspected interstellar molecules like propylene. The desire to extract quantitative information from atmospheric remote sensing has resulted in the need for a better understanding of the molecular interactions that cause pressure broadening. The use of a cold molecular ion to magnify the effects of intermolecular interactions has serious implications for pressure broadening theory. The measurement and analysis of rotational spectra of the asymmetric rotors water and propionitrile and the internal rotors propylene and ethyl alcohol are presented. These investigations provide the data and analysis necessary for astronomical observation. The ethyl alcohol investigation is the first experimental millimeter-wave study of a molecule with an asymmetric internal rotor. This study provides the data necessary for detailed theoretical modeling of this type of problem. A novel new experimental technique for generating and studying molecular ions is presented. The first temperature dependent microwave pressure broadening study of a molecular ion colliding with a neutral molecule, HCO^{+} on H_2 , is presented.

  11. Field-free molecular alignment of asymmetric top molecules using elliptically polarized laser pulses

    NASA Astrophysics Data System (ADS)

    Rouzée, A.; Guérin, S.; Faucher, O.; Lavorel, B.

    2008-04-01

    We show theoretically that a short specific elliptically polarized laser pulse driving an asymmetric top molecule can induce postpulse revivals of three-dimensional (3D) alignment. By choosing the field ellipticity resulting in the best compromise between the alignment of two molecular axes, we demonstrate that efficient 3D alignment can be achieved at low temperature. In the experiment, the field-free alignment of moderately cool ethylene molecules is probed by using a technique based on the optical Kerr effect. Control of 3D field-free alignment opens the door to a large range of applications in chemistry as well as in molecular optics.

  12. Super-Resolution Imaging of Molecular Emission Spectra and Single Molecule Spectral Fluctuations

    PubMed Central

    Mlodzianoski, Michael J.; Curthoys, Nikki M.; Gunewardene, Mudalige S.; Carter, Sean; Hess, Samuel T.

    2016-01-01

    Localization microscopy can image nanoscale cellular details. To address biological questions, the ability to distinguish multiple molecular species simultaneously is invaluable. Here, we present a new version of fluorescence photoactivation localization microscopy (FPALM) which detects the emission spectrum of each localized molecule, and can quantify changes in emission spectrum of individual molecules over time. This information can allow for a dramatic increase in the number of different species simultaneously imaged in a sample, and can create super-resolution maps showing how single molecule emission spectra vary with position and time in a sample. PMID:27002724

  13. Formation of slow molecules in chemical reactions in crossed molecular beams

    NASA Astrophysics Data System (ADS)

    Tscherbul, T. V.; Barinovs, Ğ.; Kłos, J.; Krems, R. V.

    2008-08-01

    We demonstrate that chemical reactions in collisions of molecular beams can generally produce low-velocity molecules in the laboratory-fixed frame. Our analysis shows that collisions of beams may simultaneously yield slow reactant molecules and slow products. The reaction products are formed in selected rovibrational states and scattered in a specific direction, which can be controlled by tuning the kinetic energies of the incident beams and the angle between the beams. Our calculations indicate that chemical reactions of polar alkali-metal dimers are barrierless and we suggest that chemical reactions involving alkali-metal dimers may be particularly suitable for producing slow molecules in crossed beams.

  14. Super-Resolution Imaging of Molecular Emission Spectra and Single Molecule Spectral Fluctuations.

    PubMed

    Mlodzianoski, Michael J; Curthoys, Nikki M; Gunewardene, Mudalige S; Carter, Sean; Hess, Samuel T

    2016-01-01

    Localization microscopy can image nanoscale cellular details. To address biological questions, the ability to distinguish multiple molecular species simultaneously is invaluable. Here, we present a new version of fluorescence photoactivation localization microscopy (FPALM) which detects the emission spectrum of each localized molecule, and can quantify changes in emission spectrum of individual molecules over time. This information can allow for a dramatic increase in the number of different species simultaneously imaged in a sample, and can create super-resolution maps showing how single molecule emission spectra vary with position and time in a sample. PMID:27002724

  15. Paramagnetic molecule induced strong antiferromagnetic exchange coupling on a magnetic tunnel junction based molecular spintronics device

    NASA Astrophysics Data System (ADS)

    Tyagi, Pawan; Baker, Collin; D'Angelo, Christopher

    2015-07-01

    This paper reports our Monte Carlo (MC) studies aiming to explain the experimentally observed paramagnetic molecule induced antiferromagnetic coupling between ferromagnetic (FM) electrodes. Recently developed magnetic tunnel junction based molecular spintronics devices (MTJMSDs) were prepared by chemically bonding the paramagnetic molecules between the FM electrodes along the tunnel junction’s perimeter. These MTJMSDs exhibited molecule-induced strong antiferromagnetic coupling. We simulated the 3D atomic model analogous to the MTJMSD and studied the effect of molecule’s magnetic couplings with the two FM electrodes. Simulations show that when a molecule established ferromagnetic coupling with one electrode and antiferromagnetic coupling with the other electrode, then theoretical results effectively explained the experimental findings. Our studies suggest that in order to align MTJMSDs’ electrodes antiparallel to each other, the exchange coupling strength between a molecule and FM electrodes should be ˜50% of the interatomic exchange coupling for the FM electrodes.

  16. Molecular self-assemblies might discriminate the diffusion of chiral molecules.

    PubMed

    Galstian, Tigran; Allahverdyan, Karen

    2015-06-01

    Biological tissue has many self-aligned anisotropic molecular organizations, which are able to undergo reversible orientational deformations and spatially transfer them. At the same time, the majority of drugs and many biologically important molecules contain chiral centers. It is therefore important to understand the factors affecting the diffusion of chiral molecules in such elastic environments. We experimentally study the diffusion of chiral molecules in a nematic liquid crystal host representing the model of biological tissue. The analogy of Cano's quantization effect is observed (due to the gradient of the chiral dopant) and used to estimate the corresponding diffusion coefficients. It is shown that thanks to the collective orientational correlation of host molecules the diffusion of chiral dopants is noticeably reduced (by a factor of ≈1.6) for the case of rigid alignment of host molecules compared to the case when the same matrix is free to adjust that alignment. PMID:25902722

  17. Carbon Nanotube Biosensors for Space Molecule Detection and Clinical Molecular Diagnostics

    NASA Technical Reports Server (NTRS)

    Han, Jie

    2001-01-01

    Both space molecule detection and clinical molecule diagnostics need to develop ultra sensitive biosensors for detection of less than attomole molecules such as amino acids for DNA. However all the electrode sensor systems including those fabricated from the existing carbon nanotubes, have a background level of nA (nanoAmp). This has limited DNA or other molecule detection to nA level or molecules whose concentration is, much higher than attomole level. A program has been created by NASA and NCI (National Cancer Institute) to exploit the possibility of carbon nanotube based biosensors to solve this problem for both's interest. In this talk, I will present our effort on the evaluation and novel design of carbon nanotubes as electrode biosensors with strategies to minimize background currents while maximizing signal intensity.The fabrication of nanotube electrode arrays, immobilization of molecular probes on nanotube electrodes and in vitro biosensor testing will also be discussed.

  18. Extended orientational correlation study for molecular liquids containing distorted tetrahedral molecules: application to methylene halides.

    PubMed

    Pothoczki, Szilvia; Temleitner, László; Pusztai, László

    2010-04-28

    The method of Rey [Rey, J. Chem. Phys. 126, 164506 (2007)] for describing how molecules orient toward each other in systems with perfect tetrahedral molecules is extended to the case of distorted tetrahedral molecules of c(2v) symmetry by means of introducing 28 subgroups. Additionally, the original analysis developed for perfect tetrahedral molecules, based on six groups, is adapted for molecules with imperfect tetrahedral shape. Deriving orientational correlation functions have been complemented with detailed analyses of dipole-dipole correlations. This way, (up to now) the most complete structure determination can be carried out for such molecular systems. In the present work, these calculations have been applied for particle configurations resulting from reverse Monte Carlo computer modeling. These particle arrangements are fully consistent with structure factors from neutron and x-ray diffraction measurements. Here we present a complex structural study for methylene halide (chloride, bromide, and iodide) molecular liquids, as possibly the best representative examples. It has been found that the most frequent orientations of molecules are of the 2:2 type over the entire distance range in these liquids. Focusing on the short range orientation, neighboring molecules turn toward each other with there "H,Y"-"H,Y" (Y: Cl, Br, I) edges, apart from CH(2)Cl(2) where the H,H-H,Cl arrangement is the most frequent. In general, the structure of methylene chloride appears to be different from the structure of the other two liquids. PMID:20441292

  19. A new graph-based molecular descriptor using the canonical representation of the molecule.

    PubMed

    Hentabli, Hamza; Saeed, Faisal; Abdo, Ammar; Salim, Naomie

    2014-01-01

    Molecular similarity is a pervasive concept in drug design. The basic idea underlying molecular similarity is the similar property principle, which states that structurally similar molecules will exhibit similar physicochemical and biological properties. In this paper, a new graph-based molecular descriptor (GBMD) is introduced. The GBMD is a new method of obtaining a rough description of 2D molecular structure in textual form based on the canonical representations of the molecule outline shape and it allows rigorous structure specification using small and natural grammars. Simulated virtual screening experiments with the MDDR database show clearly the superiority of the graph-based descriptor compared to many standard descriptors (ALOGP, MACCS, EPFP4, CDKFP, PCFP, and SMILE) using the Tanimoto coefficient (TAN) and the basic local alignment search tool (BLAST) when searches were carried. PMID:25140330

  20. Ionizing radiation mediates expression of cell adhesion molecules in distinct histological patterns within the lung.

    PubMed

    Hallahan, D E; Virudachalam, S

    1997-06-01

    Inflammatory cell infiltration of the lung is a predominant histopathological change that occurs during radiation pneumonitis. Emigration of inflammatory cells from the circulation requires the interaction between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. We studied the immunohistochemical pattern of expression of cell adhesion molecules in lungs from mice treated with thoracic irradiation. After X-irradiation, the endothelial leukocyte adhesion molecule 1 (ELAM-1; E-selectin) was primarily expressed in the pulmonary endothelium of larger vessels and minimally in the microvascular endothelium. Conversely, the intercellular adhesion molecule 1 (ICAM-1; CD54) was expressed in the pulmonary capillary endothelium and minimally in the endothelium of larger vessels. Radiation-mediated E-selectin expression was first observed at 6 h, whereas ICAM-1 expression initially increased at 24 h after irradiation. ICAM-1 and E-selectin expression persisted for several days. P-selectin is constitutively expressed in Weibel-Palade bodies in the endothelium, which moved to the vascular lumen within 30 min after irradiation. P-selectin was not detected in the pulmonary endothelium at 6 h after irradiation. The radiation dose required for increased cell adhesion molecule expression within the pulmonary vascular endothelium was 2 Gy, and expression increased in a dose-dependent manner. These data demonstrate that ICAM-1 and E-selectin expression is increased in the pulmonary endothelium following thoracic irradiation. The pattern of expression of E-selectin, P-selectin, and ICAM-1 is distinct from one another. PMID:9187101

  1. Molecular models for the smectic A smectic C phase transition in a system of biaxial molecules

    NASA Astrophysics Data System (ADS)

    Gorkunov, Maxim V.; Osipov, Mikhail A.

    2008-07-01

    A molecular theory of the smectic A-smectic C transition in a system of biaxial molecules is developed in the mean-field approximation. The influence of molecular biaxiality on the transition is considered in detail and it is demonstrated how the biaxial order parameters are induced by the tilt. It is shown that the ordering of biaxial molecules of low symmetry in the smectic C phase is generally described by ten independent orientational order parameters, and there exist three different tilt angles which specify the tilt of three ordering tensors. The order parameters are calculated numerically as functions of temperature for two models of biaxial molecules: molecules with two principal axes and molecules with a pair of off-center transverse dipoles. A substantial difference between the three tilt angles is found, which makes impossible a strict definition of a unique director in the smectic C phase. It is also shown that biaxial interactions may lead to an anomalously weak layer contraction in the smectic C phase. Finally, it is demonstrated that the smectic A-smectic C phase transition may be directly driven by biaxial intermolecular interactions. In this case, the tilt of long molecular axes is not a primary order parameter, and its temperature dependence is very different from convention.

  2. Molecular isomerization and fragmentation of polyatomic molecules controlled by inner-valence recollision-ionization

    NASA Astrophysics Data System (ADS)

    Xie, X.; Doblhoff-Dier, K.; Roither, S.; Schöffler, M.; Kartashov, D.; Xu, H.; Rathje, T.; Paulus, G. G.; Baltuška, A.; Gräfe, S.; Kitzler, M.

    2014-04-01

    Control over various fragmentation reactions of a series of polyatomic molecules (acetylene, ethylene, 1,3-butadiene) by the optical waveform of intense few-cycle laser pulses is demonstrated experimentally. We show both experimentally and theoretically that the responsible mechanism is inelastic ionization from inner-valence molecular orbitals by recolliding electron wave packets.

  3. Ultra high resolution molecular beam cars spectroscopy with application to planetary atmospheric molecules

    NASA Technical Reports Server (NTRS)

    Byer, R. L.

    1982-01-01

    The measurement of high resolution pulsed and continuous wave (CW) coherent anti-Stokes Raman spectroscopy (CARS) measurements in pulsed and steady state supersonic expansions were demonstrated. Pulsed molecular beam sources were characterized, and saturation of a Raman transition and, for the first time, the Raman spectrum of a complex molecular cluster were observed. The observation of CW CARS spectra in a molecular expansion and the effects of transit time broadening is described. Supersonic expansion is established as a viable technique for high resolution Raman spectroscopy of cold molecules with resolutions of 100 MH2.

  4. Field-free molecular orientation of 1Σ and 2Π molecules at high temperature

    NASA Astrophysics Data System (ADS)

    Tehini, R.; Hoque, Md Z.; Faucher, O.; Sugny, D.

    2012-04-01

    We analyze the control of field-free molecular orientation at high temperature by use of a two-color laser bipulse strategy proposed in Zhang [Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.83.043410 83, 043410 (2011)]. A general study shows that there exist two types of linear molecules for which a different mechanism has to be used. For molecules with a large hyperpolarizability, a monochromatic laser pre-pulse is applied before the two-color laser pulse at a time close to the rotational period Tr, while for molecules with a small hyperpolarizability, the optimal delay is found close to Tr/4 or 3Tr/4. We extend this analysis to the case of a 2Π molecule such as NO where a similar control strategy can be derived. These control processes are robust against temperature effects.

  5. Molecular Nanoshearing: An Innovative Approach to Shear off Molecules with AC-Induced Nanoscopic Fluid Flow

    PubMed Central

    Shiddiky, Muhammad J. A.; Vaidyanathan, Ramanathan; Rauf, Sakandar; Tay, Zhikai; Trau, Matt

    2014-01-01

    Early diagnosis of disease requires highly specific measurement of molecular biomarkers from femto to pico-molar concentrations in complex biological (e.g., serum, blood, etc.) samples to provide clinically useful information. While reaching this detection limit is challenging in itself, these samples contain numerous other non-target molecules, most of which have a tendency to adhere to solid surfaces via nonspecific interactions. Herein, we present an entirely new methodology to physically displace nonspecifically bound molecules from solid surfaces by utilizing a newly discovered “tuneable force”, induced by an applied alternating electric field, which occurs within few nanometers of an electrode surface. This methodology thus offers a unique ability to shear-off loosely bound molecules from the solid/liquid interface. Via this approach, we achieved a 5-fold reduction in nonspecific adsorption of non-target protein molecules and a 1000-fold enhancement for the specific capture of HER2 protein in human serum. PMID:24430114

  6. Molecular nanoshearing: an innovative approach to shear off molecules with AC-induced nanoscopic fluid flow.

    PubMed

    Shiddiky, Muhammad J A; Vaidyanathan, Ramanathan; Rauf, Sakandar; Tay, Zhikai; Trau, Matt

    2014-01-01

    Early diagnosis of disease requires highly specific measurement of molecular biomarkers from femto to pico-molar concentrations in complex biological (e.g., serum, blood, etc.) samples to provide clinically useful information. While reaching this detection limit is challenging in itself, these samples contain numerous other non-target molecules, most of which have a tendency to adhere to solid surfaces via nonspecific interactions. Herein, we present an entirely new methodology to physically displace nonspecifically bound molecules from solid surfaces by utilizing a newly discovered "tuneable force", induced by an applied alternating electric field, which occurs within few nanometers of an electrode surface. This methodology thus offers a unique ability to shear-off loosely bound molecules from the solid/liquid interface. Via this approach, we achieved a 5-fold reduction in nonspecific adsorption of non-target protein molecules and a 1000-fold enhancement for the specific capture of HER2 protein in human serum. PMID:24430114

  7. Molecular Nanoshearing: An Innovative Approach to Shear off Molecules with AC-Induced Nanoscopic Fluid Flow

    NASA Astrophysics Data System (ADS)

    Shiddiky, Muhammad J. A.; Vaidyanathan, Ramanathan; Rauf, Sakandar; Tay, Zhikai; Trau, Matt

    2014-01-01

    Early diagnosis of disease requires highly specific measurement of molecular biomarkers from femto to pico-molar concentrations in complex biological (e.g., serum, blood, etc.) samples to provide clinically useful information. While reaching this detection limit is challenging in itself, these samples contain numerous other non-target molecules, most of which have a tendency to adhere to solid surfaces via nonspecific interactions. Herein, we present an entirely new methodology to physically displace nonspecifically bound molecules from solid surfaces by utilizing a newly discovered ``tuneable force'', induced by an applied alternating electric field, which occurs within few nanometers of an electrode surface. This methodology thus offers a unique ability to shear-off loosely bound molecules from the solid/liquid interface. Via this approach, we achieved a 5-fold reduction in nonspecific adsorption of non-target protein molecules and a 1000-fold enhancement for the specific capture of HER2 protein in human serum.

  8. Dynamic molecules: molecular dynamics for everyone. An internet-based access to molecular dynamic simulations: basic concepts.

    PubMed

    Frank, Martin; Gutbrod, Peter; Hassayoun, Chokri; von Der Lieth, Claus-W

    2003-10-01

    Molecular dynamics is a rapidly developing field of science and has become an established tool for studying the dynamic behavior of biomolecules. Although several high quality programs for performing molecular dynamic simulations are freely available, only well-trained scientists are currently able to make use of the broad scientific potential that molecular dynamic simulations offer to gain insight into structural questions at an atomic level. The "Dynamic Molecules" approach is the first internet portal that provides an interactive access to set up, perform and analyze molecular dynamic simulations. It is completely based on standard web technologies and uses only publicly available software. The aim is to open molecular dynamics techniques to a broader range of users including undergraduate students, teachers and scientists outside the bioinformatics field. The time-limiting factors are the availability of free capacity on the computing server to run the simulations and the time required to transport the history file through the internet for the animation mode. The interactive access mode of the portal is acceptable for animations of molecules having up to about 500 atoms. PMID:12908101

  9. Energy-Level Related Nuclear-Spin Effects and Super-Hyperfine Spectral Patterns: how Molecules do Self-Nmr

    NASA Astrophysics Data System (ADS)

    Harter, William; Mitchell, Justin

    2009-06-01

    At several points in his defining works on molecular spectroscopy, Herzberg notes that ``because nuclear moments ldots are so very slight ldots transitions between species ldots are very strictly forbiddenldots '' Herzberg's most recent statement of such selection rules pertained to spherical top spin-species. It has since been shown that spherical top species (as well as those of lower symmetry molecules) converge exponentially with momentum quanta J and K to degenerate level clusters wherein even ``very slight'' nuclear fields and moments cause pervasive resonance and total spin species mixing. Ultra-high resolution spectra of Borde, et .al and Pfister et .al shows how SF_6 and SiF_4 Fluorine nuclear spin levels rearrange from total-spin multiplets to NMR-like patterns as their superfine structure converges. Similar super-hyperfine effects are anticipated for lower symmetry molecules exhibiting converging superfine level-clusters. Examples include PH_3 molecules and asymmetric tops. Following this we consider models that treat nuclear spins as coupled rotors undergoing generalized Hund-case transitions from spin-lab-momentum coupling to various spin-rotor correlations. G. A. Herzberg, Electronic Spectra of Polyatomic Molecules, (Von Norstrand Rheinhold 1966) p. 246. W G. Harter and C. W Patterson, Phys. Rev. A 19, 2277 (1979) W. G. Harter, Phys. Rev. A 24, 192 (1981). Ch. J. Borde, J. Borde, Ch. Breant, Ch. Chardonnet, A. Van Lerberghe, and Ch. Salomon, in Laser Spectroscopy VII, T. W Hensch and Y. R. Shen, eds. (Springer-Verlag, Berlin, 1985). O. Pfister, F. Guernet, G. Charton, Ch. Chardonnet, F. Herlemont, and J. Legrand, J. Opt. Soc. Am. B 10, 1521 (1993). O. Pfister, Ch. Chardonnet, and Ch. J. Bordè, Phys. Rev. Lett. 76, 4516 (1996) S. N. Yurchenko, W. Thiel, S. Patchkovskii, and P. Jensen, Phys. Chem. Chem. Phys.7, 573 (2005)

  10. A scale-bridging modeling approach for anisotropic organic molecules at patterned semiconductor surfaces

    NASA Astrophysics Data System (ADS)

    Kleppmann, Nicola; Klapp, Sabine H. L.

    2015-02-01

    Hybrid systems consisting of organic molecules at inorganic semiconductor surfaces are gaining increasing importance as thin film devices for optoelectronics. The efficiency of such devices strongly depends on the collective behavior of the adsorbed molecules. In the present paper, we propose a novel, coarse-grained model addressing the condensed phases of a representative hybrid system, that is, para-sexiphenyl (6P) at zinc-oxide (ZnO). Within our model, intermolecular interactions are represented via a Gay-Berne potential (describing steric and van-der-Waals interactions) combined with the electrostatic potential between two linear quadrupoles. Similarly, the molecule-substrate interactions include a coupling between a linear molecular quadrupole to the electric field generated by the line charges characterizing ZnO(10-10). To validate our approach, we perform equilibrium Monte Carlo simulations, where the lateral positions are fixed to a 2D lattice, while the rotational degrees of freedom are continuous. We use these simulations to investigate orientational ordering in the condensed state. We reproduce various experimentally observed features such as the alignment of individual molecules with the line charges on the surface, the formation of a standing uniaxial phase with a herringbone structure, as well as the formation of a lying nematic phase.

  11. A scale-bridging modeling approach for anisotropic organic molecules at patterned semiconductor surfaces.

    PubMed

    Kleppmann, Nicola; Klapp, Sabine H L

    2015-02-14

    Hybrid systems consisting of organic molecules at inorganic semiconductor surfaces are gaining increasing importance as thin film devices for optoelectronics. The efficiency of such devices strongly depends on the collective behavior of the adsorbed molecules. In the present paper, we propose a novel, coarse-grained model addressing the condensed phases of a representative hybrid system, that is, para-sexiphenyl (6P) at zinc-oxide (ZnO). Within our model, intermolecular interactions are represented via a Gay-Berne potential (describing steric and van-der-Waals interactions) combined with the electrostatic potential between two linear quadrupoles. Similarly, the molecule-substrate interactions include a coupling between a linear molecular quadrupole to the electric field generated by the line charges characterizing ZnO(10-10). To validate our approach, we perform equilibrium Monte Carlo simulations, where the lateral positions are fixed to a 2D lattice, while the rotational degrees of freedom are continuous. We use these simulations to investigate orientational ordering in the condensed state. We reproduce various experimentally observed features such as the alignment of individual molecules with the line charges on the surface, the formation of a standing uniaxial phase with a herringbone structure, as well as the formation of a lying nematic phase. PMID:25681929

  12. Recognition of damage-associated molecular patterns related to nucleic acids during inflammation and vaccination

    PubMed Central

    Jounai, Nao; Kobiyama, Kouji; Takeshita, Fumihiko; Ishii, Ken J.

    2012-01-01

    All mammalian cells are equipped with large numbers of sensors for protection from various sorts of invaders, who, in turn, are equipped with molecules containing pathogen-associated molecular patterns (PAMPs). Once these sensors recognize non-self antigens containing PAMPs, various physiological responses including inflammation are induced to eliminate the pathogens. However, the host sometimes suffers from chronic infection or continuous injuries, resulting in production of self-molecules containing damage-associated molecular patterns (DAMPs). DAMPs are also responsible for the elimination of pathogens, but promiscuous recognition of DAMPs through sensors against PAMPs has been reported. Accumulation of DAMPs leads to massive inflammation and continuous production of DAMPs; that is, a vicious circle leading to the development of autoimmune disease. From a vaccinological point of view, the accurate recognition of both PAMPs and DAMPs is important for vaccine immunogenicity, because vaccine adjuvants are composed of several PAMPs and/or DAMPs, which are also associated with severe adverse events after vaccination. Here, we review as the roles of PAMPs and DAMPs upon infection with pathogens or inflammation, and the sensors responsible for recognizing them, as well as their relationship with the development of autoimmune disease or the immunogenicity of vaccines. PMID:23316484

  13. Encaged molecules in external electric fields: A molecular "tug-of-war".

    PubMed

    Gurav, Nalini D; Gejji, Shridhar P; Bartolotti, Libero J; Pathak, Rajeev K

    2016-08-21

    Response of polar molecules CH3OH and H2O2 and a non-polar molecule, CO2, as "guests" encapsulated in the dodecahedral water cage (H2O)20 "host," to an external, perturbative electric field is investigated theoretically. We employ the hybrid density-functionals M06-2X and ωB97X-D incorporating the effects of damped dispersion, in conjunction with the maug-cc-pVTZ basis set, amenable for a hydrogen bonding description. While the host cluster (cage) tends to confine the embedded guest molecule through cooperative hydrogen bonding, the applied electric field tends to rupture the cluster-composite by stretching it; these two competitive effects leading to a molecular "tug-of-war." The composite remains stable up to a maximal sustainable threshold electric field, beyond which, concomitant with the vanishing of the HOMO-LUMO gap, the field wins over and the cluster breaks down. The electric-field effects are gauged in terms of the changes in the molecular geometry of the confined species, interaction energy, molecular electrostatic potential surfaces, and frequency shifts of characteristic normal vibrations in the IR regime. Interestingly, beyond the characteristic threshold electric field, the labile, distorted host cluster fragmentizes, and the guest molecule still tethered to a remnant fragment, an effect attributed to the underlying hydrogen-bonded networks. PMID:27544100

  14. Electron transport in asymmetric biphenyl molecular junctions: effects of conformation and molecule-electrode distance

    NASA Astrophysics Data System (ADS)

    Parashar, Sweta; Srivastava, Pankaj; Pattanaik, Manisha; Jain, Sandeep Kumar

    2014-09-01

    On the basis of ab-initio calculations, we predict the effect of conformation and molecule-electrode distance on transport properties of asymmetric molecular junctions for different electrode materials M (M = Au, Ag, Cu, and Pt). The asymmetry in these junctions is created by connecting one end of the biphenyl molecule to conjugated double thiol (model A) and single thiol (model B) groups, while the other end to Cu atom. A variety of phenomena viz. rectification, negative differential resistance (NDR), switching has been observed that can be controlled by tailoring the interface state properties through molecular conformation and molecule-electrode distance for various M. These properties are further analyzed by calculating transmission spectra, molecular orbitals, and orbital energy. It is found that Cu electrode shows significantly enhanced rectifying performance with change in torsion angles, as well as with increase in molecule-electrode distances than Au and Ag electrodes. Moreover, Pt electrode manifests distinctive multifunctional behavior combining switch, diode, and NDR. Thus, the Pt electrode is suggested to be a good potential candidate for a novel multifunctional electronic device. Our findings are compared with available experimental and theoretical results. Supplementary material in the form of one pdf file available from the Journal web page at http://http//dx.doi.org/10.1140/epjb/e2014-50133-2

  15. Molecular replacement with a large number of molecules in the asymmetric unit

    PubMed Central

    Jobichen, Chacko; Swaminathan, Kunchithapadam

    2014-01-01

    The exponential increase in protein structures deposited in the Protein Data Bank (PDB) has resulted in the elucidation of most, if not all, protein folds, thus making molecular replacement (MR) the most frequently used method for structure determination. A survey of the PDB shows that most of the structures determined by molecular replacement contain less than ten molecules in the asymmetric unit and that it is predominantly virus and ribosome structures that contain more than 20 molecules in the asymmetric unit. While the success of the MR method depends on several factors, such as the homology and the size of an input model, it is also a well known fact that this method can become significantly difficult in cases with a large number of molecules in the asymmetric unit, higher crystallographic symmetry and tight packing. In this paper, five representative structures containing 16–18 homomeric molecules in the asymmetric unit and the strategies that have been used to solve these structures are described. The difficulties faced and the lessons learned from these structure-determination efforts will be useful for selected and similar future situations with a large number of molecules in the asymmetric unit. PMID:25195913

  16. Molecular monolayers for attaching electroactive molecules to vertically aligned carbon nanofibers

    NASA Astrophysics Data System (ADS)

    Landis, Elizabeth C.

    Integrating molecular monolayers with nanoscale carbon materials is attractive for a variety of applications including electroanalysis, sensing, and electrocatalysis due to the high stability and high surface area of nanoscale carbon. Vertically aligned carbon nanofibers are particularly interesting because their molecular structure indicates that they may have relatively reactive surfaces compared to other types of nanoscale carbon. This work explores the use of vertically aligned carbon nanofibers as a platform for electrocatalysis. We determined the morphology and binding locations of molecular layers on the nanofiber surface, then describe two methods for covalently binding electroactive molecules to the surface. The electron transfer process through the molecular layers was studied with emphasis on understanding the effects of the molecular linkage between the electroactive molecule and the surface and understanding the role of solvent and electrolyte in the electron transfer process. We determined that the electron transfer mechanism through monolayers on vertically aligned carbon nanofibers is controlled by the morphology of the molecular layers on the surface. Several potential catalysts were attached to the surface to evaluate the carbon nanofibers as scaffolds for electrocatalytic reactions.

  17. Theoretical Study of Donor - Spacer - Acceptor Structure Molecule for Molecular Rectifier

    NASA Astrophysics Data System (ADS)

    Mizuseki, Hiroshi; Kenji, Niimura; Belosludov, Rodion; Farajian, Amir; Kawazoe, Yoshiyuki

    2003-03-01

    Recently, the molecular electronics has attracted strong attention as a ``post-silicone technology'' to establish a future nanoscale electronic devices. To realize this molecular device, unimolecular rectifiering function is one of the most important constituents in nanotechnology [C. Majumder, H. Mizuseki, and Y. Kawazoe, Molecular Scale Rectifier: Theoretical Study, J. Phys. Chem. A, 105 (2001) 9454-9459.]. In the present study, the geometric and electronic structure of alkyl derivative C37H50N4O4 (PNX) molecule, (donor - spacer - acceptor), a leading candidate of molecular rectifying device, has been investigated theoretically using ab initio quantum mechanical calculation. The results suggest that in such donor-acceptor molecular complexes, while the lowest unoccupied orbital concentrates on the acceptor subunit, the highest occupied molecular orbital is localized on the donor subunit. The approximate potential differences for optimized PNX molecule have been estimated at the B3PW91/6-311g++(d,p) level of theory, which achieves quite good agreement with experimentally reported results. This study was performed through Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology of the Japanese Government.

  18. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode.

    PubMed

    Doni, Andrea; Musso, Tiziana; Morone, Diego; Bastone, Antonio; Zambelli, Vanessa; Sironi, Marina; Castagnoli, Carlotta; Cambieri, Irene; Stravalaci, Matteo; Pasqualini, Fabio; Laface, Ilaria; Valentino, Sonia; Tartari, Silvia; Ponzetta, Andrea; Maina, Virginia; Barbieri, Silvia S; Tremoli, Elena; Catapano, Alberico L; Norata, Giuseppe D; Bottazzi, Barbara; Garlanda, Cecilia; Mantovani, Alberto

    2015-06-01

    Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity. PMID:25964372

  19. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode

    PubMed Central

    Doni, Andrea; Musso, Tiziana; Morone, Diego; Bastone, Antonio; Zambelli, Vanessa; Sironi, Marina; Castagnoli, Carlotta; Cambieri, Irene; Stravalaci, Matteo; Pasqualini, Fabio; Laface, Ilaria; Valentino, Sonia; Tartari, Silvia; Ponzetta, Andrea; Maina, Virginia; Barbieri, Silvia S.; Tremoli, Elena; Catapano, Alberico L.; Norata, Giuseppe D.; Bottazzi, Barbara; Garlanda, Cecilia

    2015-01-01

    Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity. PMID:25964372

  20. Carbon Electrode-Molecule Junctions: A Reliable Platform for Molecular Electronics.

    PubMed

    Jia, Chuancheng; Ma, Bangjun; Xin, Na; Guo, Xuefeng

    2015-09-15

    The development of reliable approaches to integrate individual or a small collection of molecules into electrical nanocircuits, often termed "molecular electronics", is currently a research focus because it can not only overcome the increasing difficulties and fundamental limitations of miniaturization of current silicon-based electronic devices, but can also enable us to probe and understand the intrinsic properties of materials at the atomic- and/or molecular-length scale. This development might also lead to direct observation of novel effects and fundamental discovery of physical phenomena that are not accessible by traditional materials or approaches. Therefore, researchers from a variety of backgrounds have been devoting great effort to this objective, which has started to move beyond simple descriptions of charge transport and branch out in different directions, reflecting the interdisciplinarity. This Account exemplifies our ongoing interest and great effort in developing efficient lithographic methodologies capable of creating molecular electronic devices through the combination of top-down micro/nanofabrication with bottom-up molecular assembly. These devices use nanogapped carbon nanomaterials (such as single-walled carbon nanotubes (SWCNTs) and graphene), with a particular focus on graphene, as point contacts formed by electron beam lithography and precise oxygen plasma etching. Through robust amide linkages, functional molecular bridges terminated with diamine moieties are covalently wired into the carboxylic acid-functionalized nanogaps to form stable carbon electrode-molecule junctions with desired functionalities. At the macroscopic level, to improve the contact interface between electrodes and organic semiconductors and lower Schottky barriers, we used SWCNTs and graphene as efficient electrodes to explore the intrinsic properties of organic thin films, and then build functional high-performance organic nanotransistors with ultrahigh responsivities

  1. Microbe Associated Molecular Pattern Signaling in Guard Cells

    PubMed Central

    Ye, Wenxiu; Murata, Yoshiyuki

    2016-01-01

    Stomata, formed by pairs of guard cells in the epidermis of terrestrial plants, regulate gas exchange, thus playing a critical role in plant growth and stress responses. As natural openings, stomata are exploited by microbes as an entry route. Recent studies reveal that plants close stomata upon guard cell perception of molecular signatures from microbes, microbe associated molecular patterns (MAMPs), to prevent microbe invasion. The perception of MAMPs induces signal transduction including recruitment of second messengers, such as Ca2+ and H2O2, phosphorylation events, and change of transporter activity, leading to stomatal movement. In the present review, we summarize recent findings in signaling underlying MAMP-induced stomatal movement by comparing with other signalings. PMID:27200056

  2. Microbe Associated Molecular Pattern Signaling in Guard Cells.

    PubMed

    Ye, Wenxiu; Murata, Yoshiyuki

    2016-01-01

    Stomata, formed by pairs of guard cells in the epidermis of terrestrial plants, regulate gas exchange, thus playing a critical role in plant growth and stress responses. As natural openings, stomata are exploited by microbes as an entry route. Recent studies reveal that plants close stomata upon guard cell perception of molecular signatures from microbes, microbe associated molecular patterns (MAMPs), to prevent microbe invasion. The perception of MAMPs induces signal transduction including recruitment of second messengers, such as Ca(2+) and H2O2, phosphorylation events, and change of transporter activity, leading to stomatal movement. In the present review, we summarize recent findings in signaling underlying MAMP-induced stomatal movement by comparing with other signalings. PMID:27200056

  3. Proposed Molecular Beam Determination of Energy Partition in the Photodissociation of Polyatomic Molecules

    DOE R&D Accomplishments Database

    Zare, P. N.; Herschbach, D. R.

    1964-01-29

    Conventional photochemical experiments give no information about the partitioning of energy between translational recoil and internal excitation of the fragment molecules formed in photodissociation of a polyatomic molecule. In a molecular beam experiment, it becomes possible to determine the energy partition from the form of the laboratory angular distribution of one of the photodissociation products. A general kinematic analysis is worked out in detail, and the uncertainty introduced by the finite angular resolution of the apparatus and the velocity spread in the parent beam is examined. The experimental requirements are evaluated for he photolysis of methyl iodide by the 2537 angstrom Hg line.

  4. Rotational Spectromicroscopy: Imaging the Orbital Interaction between Molecular Hydrogen and an Adsorbed Molecule

    NASA Astrophysics Data System (ADS)

    Li, Shaowei; Yuan, Dingwang; Yu, Arthur; Czap, Gregory; Wu, Ruqian; Ho, W.

    2015-05-01

    A hydrogen molecule can diffuse freely on the surface and be trapped above an adsorbed molecule within the junction of a scanning tunneling microscope. The trapped dihydrogen exhibits the properties of a free rotor. Here we show that the intermolecular interaction between dihydrogen and Mg-porphyrin (MgP) can be visualized by imaging j =0 to 2 rotational excitation of dihydrogen. The interaction leads to a weakened H-H bond and modest electron donation from the dihydrogen to the lowest unoccupied molecular orbital of MgP, a process similarly observed for the interaction between dihydrogen and an adsorbed Au atom.

  5. Rotational Spectromicroscopy: Imaging the Orbital Interaction between Molecular Hydrogen and an Adsorbed Molecule.

    PubMed

    Li, Shaowei; Yuan, Dingwang; Yu, Arthur; Czap, Gregory; Wu, Ruqian; Ho, W

    2015-05-22

    A hydrogen molecule can diffuse freely on the surface and be trapped above an adsorbed molecule within the junction of a scanning tunneling microscope. The trapped dihydrogen exhibits the properties of a free rotor. Here we show that the intermolecular interaction between dihydrogen and Mg-porphyrin (MgP) can be visualized by imaging j=0 to 2 rotational excitation of dihydrogen. The interaction leads to a weakened H-H bond and modest electron donation from the dihydrogen to the lowest unoccupied molecular orbital of MgP, a process similarly observed for the interaction between dihydrogen and an adsorbed Au atom. PMID:26047242

  6. Following the nanostructural molecular orientation guidelines for sulfur versus thiophene units in small molecule photovoltaic cells

    NASA Astrophysics Data System (ADS)

    Kim, Yu Jin; Park, Chan Eon

    2016-03-01

    In bulk heterojunction (BHJ) organic photovoltaics, particularly those using small molecules, electron donor and/or electron acceptor materials form a distributed network in the photoactive layer where critical photo-physical processes occur. Extensive research has recently focused on the importance of sulfur atoms in the small molecules. Little is known about the three-dimensional orientation of these sulfur atom-containing molecules. Herein, we report on our research concerning the heterojunction textures of the crystalline molecular orientation of small compounds having sulfur-containing units in the side chains, specifically, compounds known as DR3TSBDT that contain the alkylthio group and DR3TBDTT that does not. The improved performance of the DR3TBDTT-based devices, particularly in the photocurrent and the fill factor, was attributed to the large population of donor compound crystallites with a favorable face-on orientation along the perpendicular direction. This orientation resulted in efficient charge transport and a reduction in charge recombination. These findings underscore the great potential of small-molecule solar cells and suggest that even higher efficiencies can be achieved through materials development and molecular orientation control.In bulk heterojunction (BHJ) organic photovoltaics, particularly those using small molecules, electron donor and/or electron acceptor materials form a distributed network in the photoactive layer where critical photo-physical processes occur. Extensive research has recently focused on the importance of sulfur atoms in the small molecules. Little is known about the three-dimensional orientation of these sulfur atom-containing molecules. Herein, we report on our research concerning the heterojunction textures of the crystalline molecular orientation of small compounds having sulfur-containing units in the side chains, specifically, compounds known as DR3TSBDT that contain the alkylthio group and DR3TBDTT that does not

  7. Novel Vein Patterns in Arabidopsis Induced by Small Molecules1[OPEN

    PubMed Central

    Cutler, Sean

    2016-01-01

    The critical role of veins in transporting water, nutrients, and signals suggests that some key regulators of vein formation may be genetically redundant and, thus, undetectable by forward genetic screens. To identify such regulators, we screened more than 5000 structurally diverse small molecules for compounds that alter Arabidopsis (Arabidopsis thaliana) leaf vein patterns. Many compound-induced phenotypes were observed, including vein networks with an open reticulum; decreased or increased vein number and thickness; and misaligned, misshapen, or nonpolar vascular cells. Further characterization of several individual active compounds suggests that their targets include hormone cross talk, hormone-dependent transcription, and PIN-FORMED trafficking. PMID:26574596

  8. Fabrication of a highly oriented line structure on an aluminum surface and the nanoscale patterning on the nanoscale structure using highly functional molecules

    SciTech Connect

    Watanabe, Y.; Kato, H.; Takemura, S.; Watanabe, H.; Hayakawa, K.; Kimura, S.; Okumura, D.; Sugiyama, T.; Hiramatsu, T.; Nanba, N.; Nishikawa, O.; Taniguchi, M.

    2009-07-15

    The surface of an Al plate was treated with a combination of chemical and electrochemical processes for fabrication of surface nanoscale structures on Al plates. Chemical treatments by using acetone and pure water under supersonic waves were conducted on an Al surface. Additional electrochemical process in H{sub 2}SO{sub 4} solution created a finer and oriented nanoscale structure on the Al surface. Dynamic force microscopy (DFM) measurement clarified that the nanoscale highly oriented line structure was successfully created on the Al surface. The line distance was estimated approximately 30-40 nm. At the next stage, molecular patterning on the highly oriented line structure by functional molecules such as copper phthalocyanine (CuPc) and fullerene C{sub 60} was also conducted. CuPc or C{sub 60} molecules were deposited on the highly oriented line structure on Al. A toluene droplet containing CuPc molecules was cast on the nanostructured Al plate and was extended on the surface. CuPc or C{sub 60} deposition on the nanostructured Al surface proceeded by evaporation of toluene. DFM and x-ray photoemission spectroscopy measurements demonstrated that a unique molecular pattern was fabricated so that the highly oriented groove channels were filled with the functional molecules.

  9. Proton Fingerprints Portray Molecular Structures: Enhanced Description of the 1H NMR Spectra of Small Molecules

    PubMed Central

    Napolitano, José G.; Lankin, David C.; McAlpine, James B.; Niemitz, Matthias; Korhonen, Samuli-Petrus; Chen, Shao-Nong; Pauli, Guido F.

    2013-01-01

    The characteristic signals observed in NMR spectra encode essential information on the structure of small molecules. However, extracting all of this information from complex signal patterns is not trivial. This report demonstrates how computer-aided spectral analysis enables the complete interpretation of 1D 1H NMR data. The effectiveness of this approach is illustrated with a set of organic molecules, for which replicas of their 1H NMR spectra were generated. The potential impact of this methodology on organic chemistry research is discussed. PMID:24007197

  10. Molecular dynamics of immiscible fluids in chemically patterned nanochannels

    NASA Astrophysics Data System (ADS)

    Cieplak, Marek; Banavar, Jayanth R.

    2008-03-01

    Molecular dynamics simulations of chain molecules are used to elucidate physical phenomena involved in flows of dense immiscible fluids in nanochannels. We first consider a force driven flow in which the channel walls are homogeneous and wetting to one fluid and nonwetting to the other fluid. The coating of the walls by the wetting fluid provides a fluctuating surface that confines the flow of the nonwetting fluid. The resulting dissipation yields stationary Poiseuille-like flows in contrast to the accelerating nature of flow in the absence of the coating. We then consider walls consisting of patches whose wetting preferences to a fluid alternate along the walls. In the resulting flow, the immiscible components exhibit periodic structures in their velocity fields such that the crests are located at the wettability steps in contrast to the behavior of a single fluid for which the crest occurs in the wetting region. We demonstrate that for a single fluid, the modulated velocity field scales with the size of the chain molecules.

  11. Molecular Frame Photoemission: Probe of the Photoionization Dynamics for Molecules in the Gas Phase

    NASA Astrophysics Data System (ADS)

    Dowek, D.; Picard, Y. J.; Billaud, P.; Elkharrat, C.; Houver, J. C.

    2009-04-01

    Molecular frame photoemission is a very sensitive probe of the photoionization (PI) dynamics of molecules. This paper reports a comparative study of non-resonant and resonant photoionization of D2 induced by VUV circularly polarized synchrotron radiation at SOLEIL at the level of the molecular frame photoelectron angular distributions (MFPADs). We use the vector correlation method which combines imaging and time-of-flight resolved electron-ion coincidence techniques, and a generalized formalism for the expression of the I(χ, θe, varphie) MFPADs, where χ is the orientation of the molecular axis with respect to the light quantization axis and (θe, varphie) the electron emission direction in the molecular frame. Selected MFPADs for a molecule aligned parallel or perpendicular to linearly polarized light, or perpendicular to the propagation axis of circularly polarized light, are presented for dissociative photoionization (DPI) of D2 at two photon excitation energies, hν = 19 eV, where direct PI is the only channel opened, and hν = 32.5 eV, i.e. in the region involving resonant excitation of Q1 and Q2 doubly excited state series. We discuss in particular the properties of the circular dichroism characterizing photoemission in the molecular frame for direct and resonant PI. In the latter case, a remarkable behavior is observed which may be attributed to the interference occurring between undistinguishable autoionization decay channels.

  12. Tungsten polyoxometalate molecules as active nodes for dynamic carrier exchange in hybrid molecular/semiconductor capacitors

    SciTech Connect

    Balliou, A.; Douvas, A. M.; Normand, P.; Argitis, P.; Glezos, N.; Tsikritzis, D.; Kennou, S.

    2014-10-14

    In this work we study the utilization of molecular transition metal oxides known as polyoxometalates (POMs), in particular the Keggin structure anions of the formula PW₁₂O₄₀³⁻, as active nodes for potential switching and/or fast writing memory applications. The active molecules are being integrated in hybrid Metal-Insulator/POM molecules-Semiconductor capacitors, which serve as prototypes allowing investigation of critical performance characteristics towards the design of more sophisticated devices. The charging ability as well as the electronic structure of the molecular layer is probed by means of electrical characterization, namely, capacitance-voltage and current-voltage measurements, as well as transient capacitance measurements, C (t), under step voltage polarization. It is argued that the transient current peaks observed are manifestations of dynamic carrier exchange between the gate electrode and specific molecular levels, while the transient C (t) curves under conditions of molecular charging can supply information for the rate of change of the charge that is being trapped and de-trapped within the molecular layer. Structural characterization via surface and cross sectional scanning electron microscopy as well as atomic force microscopy, spectroscopic ellipsometry, UV and Fourier-transform IR spectroscopies, UPS, and XPS contribute to the extraction of accurate electronic structure characteristics and open the path for the design of new devices with on-demand tuning of their interfacial properties via the controlled preparation of the POM layer.

  13. A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

    PubMed Central

    2016-01-01

    Summary This review summarizes part of the author’s research in the area of supramolecular chemistry, beginning with his early life influences and early career efforts in molecular recognition, especially molecular tweezers. Although designed to complex DNA, these hosts proved more applicable to the field of host–guest chemistry. This early experience and interest in intercalation ultimately led to the current efforts to develop small molecule therapeutic agents for myotonic dystrophy using a rational design approach that heavily relies on principles of supramolecular chemistry. How this work was influenced by that of others in the field and the evolution of each area of research is highlighted with selected examples. PMID:26877815

  14. Thermoelectric effect and its dependence on molecular length and sequence in single DNA molecules

    NASA Astrophysics Data System (ADS)

    Li, Yueqi; Xiang, Limin; Palma, Julio L.; Asai, Yoshihiro; Tao, Nongjian

    2016-04-01

    Studying the thermoelectric effect in DNA is important for unravelling charge transport mechanisms and for developing relevant applications of DNA molecules. Here we report a study of the thermoelectric effect in single DNA molecules. By varying the molecular length and sequence, we tune the charge transport in DNA to either a hopping- or tunnelling-dominated regimes. The thermoelectric effect is small and insensitive to the molecular length in the hopping regime. In contrast, the thermoelectric effect is large and sensitive to the length in the tunnelling regime. These findings indicate that one may control the thermoelectric effect in DNA by varying its sequence and length. We describe the experimental results in terms of hopping and tunnelling charge transport models.

  15. Small molecules make big differences: molecular doping effects on electronic and optical properties of phosphorene

    NASA Astrophysics Data System (ADS)

    Jing, Yu; Tang, Qing; He, Peng; Zhou, Zhen; Shen, Panwen

    2015-03-01

    Systematical computations on the density functional theory were performed to investigate the adsorption of three typical organic molecules, tetracyanoquinodimethane (TCNQ), tetracyanoethylene (TCNE) and tetrathiafulvalene (TTF), on the surface of phosphorene monolayers and thicker layers. There exist considerable charge transfer and strong non-covalent interaction between these molecules and phosphorene. In particular, the band gap of phosphorene decreases dramatically due to the molecular modification and can be further tuned by applying an external electric field. Meanwhile, surface molecular modification has proven to be an effective way to enhance the light harvesting of phosphorene in different directions. Our results predict a flexible method toward modulating the electronic and optical properties of phosphorene and shed light on its experimental applications.

  16. Small molecules make big differences: molecular doping effects on electronic and optical properties of phosphorene.

    PubMed

    Jing, Yu; Tang, Qing; He, Peng; Zhou, Zhen; Shen, Panwen

    2015-03-01

    Systematical computations on the density functional theory were performed to investigate the adsorption of three typical organic molecules, tetracyanoquinodimethane (TCNQ), tetracyanoethylene (TCNE) and tetrathiafulvalene (TTF), on the surface of phosphorene monolayers and thicker layers. There exist considerable charge transfer and strong non-covalent interaction between these molecules and phosphorene. In particular, the band gap of phosphorene decreases dramatically due to the molecular modification and can be further tuned by applying an external electric field. Meanwhile, surface molecular modification has proven to be an effective way to enhance the light harvesting of phosphorene in different directions. Our results predict a flexible method toward modulating the electronic and optical properties of phosphorene and shed light on its experimental applications. PMID:25665596

  17. Thermoelectric effect and its dependence on molecular length and sequence in single DNA molecules.

    PubMed

    Li, Yueqi; Xiang, Limin; Palma, Julio L; Asai, Yoshihiro; Tao, Nongjian

    2016-01-01

    Studying the thermoelectric effect in DNA is important for unravelling charge transport mechanisms and for developing relevant applications of DNA molecules. Here we report a study of the thermoelectric effect in single DNA molecules. By varying the molecular length and sequence, we tune the charge transport in DNA to either a hopping- or tunnelling-dominated regimes. The thermoelectric effect is small and insensitive to the molecular length in the hopping regime. In contrast, the thermoelectric effect is large and sensitive to the length in the tunnelling regime. These findings indicate that one may control the thermoelectric effect in DNA by varying its sequence and length. We describe the experimental results in terms of hopping and tunnelling charge transport models. PMID:27079152

  18. Thermoelectric effect and its dependence on molecular length and sequence in single DNA molecules

    PubMed Central

    Li, Yueqi; Xiang, Limin; Palma, Julio L.; Asai, Yoshihiro; Tao, Nongjian

    2016-01-01

    Studying the thermoelectric effect in DNA is important for unravelling charge transport mechanisms and for developing relevant applications of DNA molecules. Here we report a study of the thermoelectric effect in single DNA molecules. By varying the molecular length and sequence, we tune the charge transport in DNA to either a hopping- or tunnelling-dominated regimes. The thermoelectric effect is small and insensitive to the molecular length in the hopping regime. In contrast, the thermoelectric effect is large and sensitive to the length in the tunnelling regime. These findings indicate that one may control the thermoelectric effect in DNA by varying its sequence and length. We describe the experimental results in terms of hopping and tunnelling charge transport models. PMID:27079152

  19. Rotation of water molecules in plastic phase at extreme conditions from first principles molecular dynamics method

    NASA Astrophysics Data System (ADS)

    Tasaka, Tomofumi; Tsumuraya, Kazuo

    2014-03-01

    Water has a variety of polymorphs in wide ranges of temperature and pressure. Ice VII phase transforms to ice X with increased pressure. However the ice VII transforms to a superionic phase at higher temperatures around 2000K and pressure 30GPa in which the protons migrate in the body centered cubic lattice of oxygens. The ice VII transforms into rotator phase (so called plastic phase at lower temperatures around 600K and 5 to 50GPa. The formation of the phase has been confirmed only with the empirical potentials, whereas the experimental confirmation has been postponed until now. The present study elucidates the mechanism of the rotation of the water molecules and the correlation between the molecules during the rotation with the first principles molecular dynamics method. The water molecules rotate around each oxygen atom to conserve the ice VII positions of the protons.

  20. An ab initio molecular dynamics study on hydrogen bonds between water molecules

    NASA Astrophysics Data System (ADS)

    Pan, Zhang; Chen, Jing; Lü, Gang; Geng, Yi-Zhao; Zhang, Hui; Ji, Qing

    2012-04-01

    The quantitative estimation of the total interaction energy of a molecular system containing hydrogen bonds (H bonds) depends largely on how to identify H bonding. The conventional geometric criteria of H bonding are simple and convenient in application, but a certain amount of non-H bonding cases are also identified as H bonding. In order to investigate the wrong identification, we carry out a systematic calculation on the interaction energy of two water molecules at various orientation angles and distances using ab initio molecular dynamics method with the dispersion correction for the Becke-Lee-Yang-Parr (BLYP) functionals. It is shown that, at many orientation angles and distances, the interaction energies of the two water molecules exceed the energy criterion of the H bond, but they are still identified as H-bonded by the conventional "distance-angle" criteria. It is found that in these non-H bonding cases the wrong identification is mainly caused by short-range interaction between the two neighbouring water molecules. We thus propose that, in addition to the conventional distance and angle criteria of H bonding, the distance dHṡṡṡH between the two neighbouring hydrogen atoms of the two water molecules should also be taken as a criterion, and the distance rOṡṡṡH between the hydrogen atom of the H-bond donor molecule and the oxygen atom of the acceptor molecule should be restricted by a lower limit. When dHṡṡṡH and rOṡṡṡH are small (e.g., dHṡṡṡH < 2.0 Å and rOṡṡṡH < 1.62 Å), the repulsion between the two neighbouring atoms increases the total energy of the two water molecules dramatically and apparently weakens the binding of the water dimer. A statistical analysis and comparison of the numbers of the H bonds identified by using different criteria have been conducted on a Car-Parrinello ab initio molecular dynamics simulation with dispersion correction for a system of 64 water molecules at near-ambient temperature. They

  1. Pyrimidinone-Peptoid Hybrid Molecules with Distinct Effects on Molecular Chaperone Function and Cell Proliferation

    PubMed Central

    Wright, Christine M.; Chovatiya, Raj J.; Jameson, Nora E.; Turner, David M.; Zhu, Guangyu; Werner, Stefan; Huryn, Donna M.; Pipas, James M.; Day, Billy W.; Wipf, Peter; Brodsky, Jeffrey L.

    2008-01-01

    The Hsp70 molecular chaperones are ATPases that play critical roles in the pathogenesis of many human diseases, including breast cancer. Hsp70 ATP hydrolysis is relatively weak, but is stimulated by J domain-containing proteins. We identified pyrimidinone-peptoid hybrid molecules that inhibit cell proliferation with greater potency than previously described Hsp70 modulators. In many cases, anti-proliferative activity correlated with inhibition of J domain stimulation of Hsp70. PMID:18164205

  2. Solvation chemical shifts of perylenic antenna molecules from molecular dynamics simulations.

    PubMed

    Özcan, Nergiz; Mareš, Jiří; Sundholm, Dage; Vaara, Juha

    2014-10-28

    Solvation-induced shifts in molecular properties can be realistically simulated by employing a dynamic model with explicit solvent molecules. In this work, (13)C NMR chemical shifts of various candidate antenna molecules for dye-sensitised solar cells have been studied by using density-functional theory calculations both in vacuo and by employing a dynamic solvation model. The solvent effects were investigated using instantaneous molecular dynamics snapshots containing the antenna molecule and surrounding acetonitrile solvent molecules. Such calculations take into account the main mechanisms of solvation-induced chemical shifts. We have analysed the contributions to the solvent shift due to the solvent susceptibility anisotropy, changes in the density of the virtual orbital space and the accessibility of the excited states to the pronouncedly local magnetic hyperfine operator. We present Lorentzian-broadened chemical shift stick spectra in which a comparison of the in vacuo and dynamic-solvation model results is graphically illustrated. The results show that the solvent-accessible atoms at the perimeter of the solute are influenced by the virtual states of the solvent molecules, which are visible to the hyperfine operators of the perimeter nuclei. This enables efficient coupling of the ground state of the solute to the magnetically allowed excited states, resulting in a positive chemical shift contribution of the perimeter nuclei. As a result of solvation, the chemical shift signals of perimeter nuclei are found to be displaced towards larger chemical shift values, whereas the nuclei of the inner region of the solute molecules show the opposite trend. The solvent susceptibility anisotropy is found to cause a small and practically constant contribution. PMID:25222796

  3. A Treasure Trove of Molecules: Uncovering the Molecular Content of Planetary Nebulae

    NASA Astrophysics Data System (ADS)

    Schmidt, Deborah Rose; Ziurys, Lucy M.

    2016-06-01

    We have undertaken a systematic study of the molecular content of planetary nebulae (PNe) using the facilities of the Arizona Radio Observatory (ARO). A search for HCN and HCO+ in seventeen PNe in which CO had previously been detected has been carried out. The J=1→0 and J=3→2 transitions of both molecules were searched for using the ARO 12-M Telescope and ARO Sub-Millimeter Telescope respectively. At least one transition of either molecule was detected in thirteen sources. Assuming a kinetic temperature of 20 K, the abundances of these two molecule, relative to H2, were determined to be f(HCN) ~ 0.1 – 9.1 × 10-7 and f(HCO+) ~ 0.04 – 7.4 × 10-7. The abundances of both species were found to remain relatively constant with nebular age, in contrast to predictions of chemical models. A subset of eleven of these PNe were subsequently searched for the J=1→0 and J=3→2 transitions of CCH and HNC. HNC was detected in ten sources, resulting in HCN/HNC ratios of ~2-6, while CCH has been detected in eight. The most current results for the abundances of both molecules will be reported. The correlation of CCH and C60 will also be presented. Establishing molecular abundances in PNe is vital to our understanding of their environments as well as the nature of their ejecta, which populate the interstellar medium (ISM).

  4. Mechanics and Chemistry: Sinle Molecule Bond Rupture Forces Correlate with Molecular Backbone Structure

    SciTech Connect

    Frei, M.; Hybertsen, M.; Aradhya, S.V.; Koentopp, M.; Venkataraman, L.

    2011-03-02

    We simultaneously measure conductance and force across nanoscale junctions. A new, two-dimensional histogram technique is introduced to statistically extract bond rupture forces from a large data set of individual junction elongation traces. For the case of Au point contacts, we find a rupture force of 1.4 {+-} 0.2 nN, which is in good agreement with previous measurements. We then study systematic trends for single gold metal-molecule-metal junctions for a series of molecules terminated with amine and pyridine linkers. For all molecules studied, single molecule junctions rupture at the Au-N bond. Selective binding of the linker group allows us to correlate the N-Au bond-rupture force to the molecular backbone. We find that the rupture force ranges from 0.8 nN for 4,4' bipyridine to 0.5 nN in 1,4 diaminobenzene. These experimental results are in excellent quantitative agreement with density functional theory based adiabatic molecular junction elongation and rupture calculations.

  5. Photodissociation of laboratory oriented molecules: Revealing molecular frame properties of nonaxial recoil

    SciTech Connect

    Brom, Alrik J. van den; Rakitzis, T. Peter; Janssen, Maurice H.M.

    2004-12-15

    We report the photodissociation of laboratory oriented OCS molecules. A molecular beam of OCS molecules is hexapole state-selected and spatially oriented in the electric field of a velocity map imaging lens. The oriented OCS molecules are dissociated at 230 nm with the linear polarization set at 45 deg. to the orientation direction of the OCS molecules. The CO({nu}=0,J) photofragments are quantum state-selectively ionized by the same 230 nm pulse and the angular distribution is measured using the velocity map imaging technique. The observed CO({nu}=0,J) images are strongly asymmetric and the degree of asymmetry varies with the CO rotational state J. From the observed asymmetry in the laboratory frame we can directly extract the molecular frame angles between the final photofragment recoil velocity and the permanent dipole moment and the transition dipole moment. The data for CO fragments with high rotational excitation reveal that the dissociation dynamics is highly nonaxial, even though conventional wisdom suggests that the nearly limiting {beta} parameter results from fast axial recoil dynamics. From our data we can extract the relative contribution of parallel and perpendicular transitions at 230 nm excitation.

  6. Following the nanostructural molecular orientation guidelines for sulfur versus thiophene units in small molecule photovoltaic cells.

    PubMed

    Kim, Yu Jin; Park, Chan Eon

    2016-03-31

    In bulk heterojunction (BHJ) organic photovoltaics, particularly those using small molecules, electron donor and/or electron acceptor materials form a distributed network in the photoactive layer where critical photo-physical processes occur. Extensive research has recently focused on the importance of sulfur atoms in the small molecules. Little is known about the three-dimensional orientation of these sulfur atom-containing molecules. Herein, we report on our research concerning the heterojunction textures of the crystalline molecular orientation of small compounds having sulfur-containing units in the side chains, specifically, compounds known as that contain the alkylthio group and that does not. The improved performance of the -based devices, particularly in the photocurrent and the fill factor, was attributed to the large population of donor compound crystallites with a favorable face-on orientation along the perpendicular direction. This orientation resulted in efficient charge transport and a reduction in charge recombination. These findings underscore the great potential of small-molecule solar cells and suggest that even higher efficiencies can be achieved through materials development and molecular orientation control. PMID:26987868

  7. Microfluidic parallel patterning and cellular delivery of molecules with a nanofountain probe.

    PubMed

    Kang, Wonmo; McNaughton, Rebecca L; Yavari, Fazel; Minary-Jolandan, Majid; Safi, Asmahan; Espinosa, Horacio D

    2014-02-01

    This brief report describes a novel tool for microfluidic patterning of biomolecules and delivery of molecules into cells. The microdevice is based on integration of nanofountain probe (NFP) chips with packaging that creates a closed system and enables operation in liquid. The packaged NFP can be easily coupled to a micro/nano manipulator or atomic force microscope for precise position and force control. We demonstrate here the functionality of the device for continuous direct-write parallel patterning on a surface in air and in liquid. Because of the small volume of the probes (~3 pL), we can achieve flow rates as low as 1 fL/s and have dispensed liquid drops with submicron to 10 µm diameters in a liquid environment. Furthermore, we demonstrate that this microdevice can be used for delivery of molecules into single cells by transient permeabilization of the cell membrane (i.e., electroporation). The significant advantage of NFP-based electroporation compared with bulk electroporation and other transfection techniques is that it allows for precise and targeted delivery while minimizing stress to the cell. We discuss the ongoing development of the tool toward automated operation and its potential as a multifunctional device for microarray applications and time-dependent single-cell studies. PMID:23897012

  8. The Functional Basis of Wing Patterning in Heliconius Butterflies: The Molecules Behind Mimicry

    PubMed Central

    Kronforst, Marcus R.; Papa, Riccardo

    2015-01-01

    Wing-pattern mimicry in butterflies has provided an important example of adaptation since Charles Darwin and Alfred Russell Wallace proposed evolution by natural selection >150 years ago. The neotropical butterfly genus Heliconius played a central role in the development of mimicry theory and has since been studied extensively in the context of ecology and population biology, behavior, and mimicry genetics. Heliconius species are notable for their diverse color patterns, and previous crossing experiments revealed that much of this variation is controlled by a small number of large-effect, Mendelian switch loci. Recent comparative analyses have shown that the same switch loci control wing-pattern diversity throughout the genus, and a number of these have now been positionally cloned. Using a combination of comparative genetic mapping, association tests, and gene expression analyses, variation in red wing patterning throughout Heliconius has been traced back to the action of the transcription factor optix. Similarly, the signaling ligand WntA has been shown to control variation in melanin patterning across Heliconius and other butterflies. Our understanding of the molecular basis of Heliconius mimicry is now providing important insights into a variety of additional evolutionary phenomena, including the origin of supergenes, the interplay between constraint and evolvability, the genetic basis of convergence, the potential for introgression to facilitate adaptation, the mechanisms of hybrid speciation in animals, and the process of ecological speciation. PMID:25953905

  9. The functional basis of wing patterning in Heliconius butterflies: the molecules behind mimicry.

    PubMed

    Kronforst, Marcus R; Papa, Riccardo

    2015-05-01

    Wing-pattern mimicry in butterflies has provided an important example of adaptation since Charles Darwin and Alfred Russell Wallace proposed evolution by natural selection >150 years ago. The neotropical butterfly genus Heliconius played a central role in the development of mimicry theory and has since been studied extensively in the context of ecology and population biology, behavior, and mimicry genetics. Heliconius species are notable for their diverse color patterns, and previous crossing experiments revealed that much of this variation is controlled by a small number of large-effect, Mendelian switch loci. Recent comparative analyses have shown that the same switch loci control wing-pattern diversity throughout the genus, and a number of these have now been positionally cloned. Using a combination of comparative genetic mapping, association tests, and gene expression analyses, variation in red wing patterning throughout Heliconius has been traced back to the action of the transcription factor optix. Similarly, the signaling ligand WntA has been shown to control variation in melanin patterning across Heliconius and other butterflies. Our understanding of the molecular basis of Heliconius mimicry is now providing important insights into a variety of additional evolutionary phenomena, including the origin of supergenes, the interplay between constraint and evolvability, the genetic basis of convergence, the potential for introgression to facilitate adaptation, the mechanisms of hybrid speciation in animals, and the process of ecological speciation. PMID:25953905

  10. Single-molecule study of molecular mobility in the cytoplasm of Escherichia coli

    NASA Astrophysics Data System (ADS)

    Lill, Yoriko; Kaserer, Wallace A.; Newton, Salete M.; Lill, Markus; Klebba, Phillip E.; Ritchie, Ken

    2012-08-01

    The cytoplasm of bacterial cells is filled with individual molecules and molecular complexes that rely on diffusion to bring them together for interaction. The mobility of molecules in the cytoplasm has been characterized by several techniques mainly using fluorescent probes and ensemble methods. In order to probe the microenvrionment inside the cytoplasm as viewed by an individual molecule, we have studied single green fluorescent proteins (GFPs) diffusing in the cytoplasm of Escherichia coli cells at observation at rates ranging from 60 to 1000 Hz. Over long times the diffusion shows confinement due to the geometry of the cells themselves. A simulation in model cells using the actual distribution of cell sizes found in the experiments describes accurately the experimental results as well as reveals a short time diffusion coefficient that agrees well with that determined by ensemble methods. Higher short time diffusion coefficients can be obtained by filling the simulated cell with small spheres modeling cytoplasmic molecules and, depending on the density of particles included in the modeled cytoplasm, can approach the diffusion coefficient of GFPs found in water. Thus, single-molecule tracking combined with analysis using simple simulation of Brownian motion is able to reveal the main contributors to the GFP mobility in the cytoplasm of E. coli.

  11. Single-molecule study of molecular mobility in the cytoplasm of Escherichia coli.

    PubMed

    Lill, Yoriko; Kaserer, Wallace A; Newton, Salete M; Lill, Markus; Klebba, Phillip E; Ritchie, Ken

    2012-08-01

    The cytoplasm of bacterial cells is filled with individual molecules and molecular complexes that rely on diffusion to bring them together for interaction. The mobility of molecules in the cytoplasm has been characterized by several techniques mainly using fluorescent probes and ensemble methods. In order to probe the microenvrionment inside the cytoplasm as viewed by an individual molecule, we have studied single green fluorescent proteins (GFPs) diffusing in the cytoplasm of Escherichia coli cells at observation at rates ranging from 60 to 1000 Hz. Over long times the diffusion shows confinement due to the geometry of the cells themselves. A simulation in model cells using the actual distribution of cell sizes found in the experiments describes accurately the experimental results as well as reveals a short time diffusion coefficient that agrees well with that determined by ensemble methods. Higher short time diffusion coefficients can be obtained by filling the simulated cell with small spheres modeling cytoplasmic molecules and, depending on the density of particles included in the modeled cytoplasm, can approach the diffusion coefficient of GFPs found in water. Thus, single-molecule tracking combined with analysis using simple simulation of Brownian motion is able to reveal the main contributors to the GFP mobility in the cytoplasm of E. coli. PMID:23005785

  12. Hydroxyl and water molecule orientations in trypsin: Comparison to molecular dynamics structures

    SciTech Connect

    McDowell, R.S.; Kossiakoff, A.A.

    1994-12-31

    A comparison is presented of experimentally observed hydroxyl and water hydrogens in trypsin determined from neutron density maps with the results of a 140ps molecular dynamics (MD) simulation. Experimental determination of hydrogen and deuterium atom positions in molecules as large as proteins is a unique capability of neutron diffraction. The comparison addresses the degree to which a standard force-field approach can adequately describe the local electrostatic and van der Waals forces that determine the orientations of these hydrogens. Neutron densities, derived from 2.1{Angstrom} D{sub 2}O-H{sub 2}O difference Fourier maps, provide a database of 27 well-ordered hydroxyl hydrogens. Most of the simulated hydroxyl orientations are within a standard deviation of the experimentally-observed positions, including several examples in which both the simulation and the neutron density indicate that a hydroxyl group is shifted from a {open_quote}standard{close_quote} rotamer. For the most highly ordered water molecules, the hydrogen distributions calculated from the trajectory were in good agreement with neutron density; simulated water molecules that displayed multiple hydrogen bonding networks had correspondingly broadened neutron density profiles. This comparison was facilitated by development of a method to construct a pseudo 2{Angstrom} density map based on the hydrogen atom distributions from the simulation. The degree of disorder of internal water molecules is shown to result primarily from the electrostatic environment surrounding that water molecule as opposed to the cavity size available to the molecule. A method is presented for comparing the discrete observations sampled in a dynamics trajectory with the time- averaged data obtained from X-ray or neutron diffraction studies. This method is particularly useful for statically-disordered water molecules, in which the average location assigned from a trajectory may represent a site of relatively low occupancy.

  13. Allele-Specific Behavior of Molecular Networks: Understanding Small-Molecule Drug Response in Yeast

    PubMed Central

    Li, Chunquan; Hao, Dapeng; Zhang, Shaojun; Zhou, Meng; Su, Fei; Chen, Xi; Zhi, Hui; Li, Xia

    2013-01-01

    The study of systems genetics is changing the way the genetic and molecular basis of phenotypic variation, such as disease susceptibility and drug response, is being analyzed. Moreover, systems genetics aids in the translation of insights from systems biology into genetics. The use of systems genetics enables greater attention to be focused on the potential impact of genetic perturbations on the molecular states of networks that in turn affects complex traits. In this study, we developed models to detect allele-specific perturbations on interactions, in which a genetic locus with alternative alleles exerted a differing influence on an interaction. We utilized the models to investigate the dynamic behavior of an integrated molecular network undergoing genetic perturbations in yeast. Our results revealed the complexity of regulatory relationships between genetic loci and networks, in which different genetic loci perturb specific network modules. In addition, significant within-module functional coherence was found. We then used the network perturbation model to elucidate the underlying molecular mechanisms of individual differences in response to 100 diverse small molecule drugs. As a result, we identified sub-networks in the integrated network that responded to variations in DNA associated with response to diverse compounds and were significantly enriched for known drug targets. Literature mining results provided strong independent evidence for the effectiveness of these genetic perturbing networks in the elucidation of small-molecule responses in yeast. PMID:23308257

  14. Superstructures and Electronic Properties of Manganese-Phthalocyanine Molecules on Au(110) from Submonolayer Coverage to Ultrathin Molecular Films.

    PubMed

    Topyła, M; Néel, N; Kröger, J

    2016-07-12

    The adsorption of manganese-phthalocyanine molecules on Au(110) was investigated using a low-temperature scanning tunneling microscope. A rich variety of commensurate superstructures was observed upon increasing the molecule coverage from submonolayers to ultrathin films. All structures were associated with reconstructions of the Au(110) substrate. Molecules adsorbed in the second molecular layer exhibited negative differential conductance occurring symmetrically around zero bias voltage. A double-barrier tunneling model rationalized this observation in terms of a peaked molecular resonance at the Fermi energy together with a voltage drop across the molecular film. PMID:27322189

  15. Multiscale Molecular Simulation of Solution Processing of SMDPPEH: PCBM Small-Molecule Organic Solar Cells.

    PubMed

    Lee, Cheng-Kuang; Pao, Chun-Wei

    2016-08-17

    Solution-processed small-molecule organic solar cells are a promising renewable energy source because of their low production cost, mechanical flexibility, and light weight relative to their pure inorganic counterparts. In this work, we developed a coarse-grained (CG) Gay-Berne ellipsoid molecular simulation model based on atomistic trajectories from all-atom molecular dynamics simulations of smaller system sizes to systematically study the nanomorphology of the SMDPPEH/PCBM/solvent ternary blend during solution processing, including the blade-coating process by applying external shear to the solution. With the significantly reduced overall system degrees of freedom and computational acceleration from GPU, we were able to go well beyond the limitation of conventional all-atom molecular simulations with a system size on the order of hundreds of nanometers with mesoscale molecular detail. Our simulations indicate that, similar to polymer solar cells, the optimal blending ratio in small-molecule organic solar cells must provide the highest specific interfacial area for efficient exciton dissociation, while retaining balanced hole/electron transport pathway percolation. We also reveal that blade-coating processes have a significant impact on nanomorphology. For given donor/acceptor blending ratios, applying an external shear force can effectively promote donor/acceptor phase segregation and stacking in the SMDPPEH domains. The present study demonstrated the capability of an ellipsoid-based coarse-grained model for studying the nanomorphology evolution of small-molecule organic solar cells during solution processing/blade-coating and provided links between fabrication protocols and device nanomorphologies. PMID:27435212

  16. Symmetry of extremely floppy molecules: Molecular states beyond rotation-vibration separation.

    PubMed

    Schmiedt, Hanno; Schlemmer, Stephan; Jensen, Per

    2015-10-21

    Traditionally, molecules are theoretically described as near-static structures rotating in space. Vibrational motion causing small structural deformations induces a perturbative treatment of the rotation-vibration interaction, which fails in highly fluxional molecules, where all vibrational motions have amplitudes comparable in size to the linear dimensions of the molecule. An example is protonated methane (CH5(+)) [P. Kumar and D. Marx, Phys. Chem. Chem. Phys. 8, 573 (2006); Z. Jin et al., J. Phys. Chem. A 110, 1569 (2006); and A. S. Petit et al., J. Phys. Chem. A 118, 7206 (2014)]. For these molecules, customary theory fails to simulate reliably even the low-energy spectrum [T. Oka, Science 347, 1313-1314 (2015) and O. Asvany et al., Science 347, 1346-1349 (2015)]. Within the traditional view of rotation and vibration being near-separable, rotational and vibrational wavefunctions can be symmetry classified separately in the molecular symmetry (MS) group [P. Bunker and P. Jensen, Molecular Symmetry and Spectroscopy, NRC Monograph Publishing Program (NRC Research Press, 2006)]. In this article, we discuss a fundamental group theoretical approach to the problem of determining the symmetries of molecular rotation-vibration states. We will show that all MS groups discussed so far are isomorphic to subgroups of the special orthogonal group in three dimensions SO(3). This leads to a group theoretical foundation of the technique of equivalent rotations [H. Longuet-Higgins, Mol. Phys. 6, 445 (1963)]. The group G240 (the MS group of protonated methane) represents, to the best of our knowledge, the first example of a MS group which is not isomorphic to a subgroup of SO(3) (nor of O(3) or of SU(2)). Because of this, a separate symmetry classification of vibrational and rotational wavefunctions becomes impossible in this MS group, consistent with the fact that a decoupling of vibrational and rotational motion is impossible. We discuss here the consequences of this. In

  17. Symmetry of extremely floppy molecules: Molecular states beyond rotation-vibration separation

    NASA Astrophysics Data System (ADS)

    Schmiedt, Hanno; Schlemmer, Stephan; Jensen, Per

    2015-10-01

    Traditionally, molecules are theoretically described as near-static structures rotating in space. Vibrational motion causing small structural deformations induces a perturbative treatment of the rotation-vibration interaction, which fails in highly fluxional molecules, where all vibrational motions have amplitudes comparable in size to the linear dimensions of the molecule. An example is protonated methane (CH 5+ ) [P. Kumar and D. Marx, Phys. Chem. Chem. Phys. 8, 573 (2006); Z. Jin et al., J. Phys. Chem. A 110, 1569 (2006); and A. S. Petit et al., J. Phys. Chem. A 118, 7206 (2014)]. For these molecules, customary theory fails to simulate reliably even the low-energy spectrum [T. Oka, Science 347, 1313-1314 (2015) and O. Asvany et al., Science 347, 1346-1349 (2015)]. Within the traditional view of rotation and vibration being near-separable, rotational and vibrational wavefunctions can be symmetry classified separately in the molecular symmetry (MS) group [P. Bunker and P. Jensen, Molecular Symmetry and Spectroscopy, NRC Monograph Publishing Program (NRC Research Press, 2006)]. In this article, we discuss a fundamental group theoretical approach to the problem of determining the symmetries of molecular rotation-vibration states. We will show that all MS groups discussed so far are isomorphic to subgroups of the special orthogonal group in three dimensions SO(3). This leads to a group theoretical foundation of the technique of equivalent rotations [H. Longuet-Higgins, Mol. Phys. 6, 445 (1963)]. The group G240 (the MS group of protonated methane) represents, to the best of our knowledge, the first example of a MS group which is not isomorphic to a subgroup of SO(3) (nor of O(3) or of SU(2)). Because of this, a separate symmetry classification of vibrational and rotational wavefunctions becomes impossible in this MS group, consistent with the fact that a decoupling of vibrational and rotational motion is impossible. We discuss here the consequences of this. In

  18. The atom in a molecule: Implications for molecular structure and properties

    NASA Astrophysics Data System (ADS)

    Langhoff, Peter; Mills, Jeffrey; Boatz, Jerry

    2016-05-01

    The apparent impossibility of meaningful assignments of indistinguishable electrons to particular atomic nuclei in a molecule seemingly precludes quantum-mechanical definition of fragment atomic Hamiltonian operators. Structural symmetry, conformations, and isomers, as well as the electronic energies and properties of constituent atoms are accordingly perceived as ill defined. Here we provide assignments of electrons to atoms in molecules and define their energies and properties. A separable Hilbert space in the form of orthonormal (Eisenschitz-London) outer-products of atomic eigenstates facilitates assignments of electrons to particular atomic nuclei and also provides support for totally antisymmetric solutions of the Schrödinger equation. Self-adjoint atomic operators within a molecule are shown to have Hermitian matrix representatives and physically significant expectation values in molecular eigenstates. Nuanced descriptions of molecular structures and properties emerge naturally from this representation in the absence of additional subjective conditions, including the interplay between atomic promotion and interaction energies, atomic hybridization and charge apportionment, and atomic-state entanglements upon dissociation, attributes revealed by illustrative calculations. Work support in part by Grants from AFRL, NRC, ASEE, NSF.

  19. Vibrational spectra and molecular dynamics of hydrogen peroxide molecules at quartz/water interfaces

    NASA Astrophysics Data System (ADS)

    Lv, Ye-qing; Zheng, Shi-li; Wang, Shao-na; Yan, Wen-yi; Zhang, Yi; Du, Hao

    2016-06-01

    The influence of H2O2 on the water vibration at quartz interface was examined using sum-frequency generation (SFG) spectroscopy, and the effect of H2O2 concentration has been systematically studied. Further, the number density and radical distribution of water molecules, H2O2 molecules, and quartz surface silanol groups were calculated using molecular dynamics (MD) simulation to provide molecular level interpretation for the SFG spectra. It is concluded from this study that the hydrogen peroxide molecules prefers to donate H-bonds to the in-plane silanol groups rather than accepting H-bonds from out-of-plane silanol groups, as evidenced by the strengthening of the peak located at 3400 cm-1 assigned to "liquid-like" hydrogen-bonding network. The SFG results have been supported by the MD calculation results, which demonstrate that the relative intensity of the peak located at 3400 cm-1 to that of located at 3200 cm-1 increases monotonously with the increase in the number of hydrogen peroxide in the first hydration shell of silanol.

  20. How, when, and where in pattern formation: Spying on embryonic development one molecule at a time

    NASA Astrophysics Data System (ADS)

    Garcia, Hernan

    An abiding mystery in the study of living matter is how a single cell develops into a multicellular organism. As this cell divides, its progeny read the program encoded on their DNA and adopt different fates becoming familiar cell types such as those found in muscle, liver and our brains. We now know that the decisions that cells make during development are not so much based on which genes to express, but rather on when, where and how to express them. Despite advances in determining the identities of the molecules that mediate these decisions we are still incapable of predicting how simple physical parameters such as the number, position and affinity of binding sites for these molecules on the DNA determine developmental fates. Using the fruit fly, one of the classic model systems for embryonic development, I will show how a combination of new technologies, quantitative experiments, and statistical mechanics is providing new insights about cellular decision making during development. In particular, I will describe how the specification of macroscopic body parts in an organism is linked to the non-equilibrium molecular-scale processes inside single cells. The goal of this interdisciplinary research is to produce a predictive understanding of developmental programs which will enable the rational control of biological size, shape and function.

  1. Distance-dependent patterns of molecular divergences in Tuatara mitogenomes.

    PubMed

    Subramanian, Sankar; Mohandesan, Elmira; Millar, Craig D; Lambert, David M

    2015-01-01

    Population genetic models predict that populations that are geographically close to each other are expected to be genetically more similar to each other compared to those that are widely separate. However the patterns of relationships between geographic distance and molecular divergences at neutral and constrained regions of the genome are unclear. We attempted to clarify this relationship by sequencing complete mitochondrial genomes of the relic species Tuatara (Sphenodon punctatus) from ten offshore islands of New Zealand. We observed a positive relationship that showed a proportional increase in the neutral diversity at synonymous sites (dS), with increasing geographical distance. In contrast we showed that diversity at evolutionarily constrained sites (dC) was elevated in the case of comparisons involving closely located populations. Conversely diversity was reduced in the case of comparisons between distantly located populations. These patterns were confirmed by a significant negative relationship between the ratio of dC/dS and geographic distance. The observed high dC/dS could be explained by the abundance of deleterious mutations in comparisons involving closely located populations, due to the recent population divergence times. Since distantly related populations were separated over long periods of time, deleterious mutations might have been removed by purifying selection. PMID:25731894

  2. Molecular tailoring approach for geometry optimization of large molecules: Energy evaluation and parallelization strategies

    NASA Astrophysics Data System (ADS)

    Ganesh, V.; Dongare, Rameshwar K.; Balanarayan, P.; Gadre, Shridhar R.

    2006-09-01

    A linear-scaling scheme for estimating the electronic energy, gradients, and Hessian of a large molecule at ab initio level of theory based on fragment set cardinality is presented. With this proposition, a general, cardinality-guided molecular tailoring approach (CG-MTA) for ab initio geometry optimization of large molecules is implemented. The method employs energy gradients extracted from fragment wave functions, enabling computations otherwise impractical on PC hardware. Further, the method is readily amenable to large scale coarse-grain parallelization with minimal communication among nodes, resulting in a near-linear speedup. CG-MTA is applied for density-functional-theory-based geometry optimization of a variety of molecules including α-tocopherol, taxol, γ-cyclodextrin, and two conformations of polyglycine. In the tests performed, energy and gradient estimates obtained from CG-MTA during optimization runs show an excellent agreement with those obtained from actual computation. Accuracy of the Hessian obtained employing CG-MTA provides good hope for the application of Hessian-based geometry optimization to large molecules.

  3. Molecular dynamics simulations on aqueous two-phase systems - Single PEG-molecules in solution

    PubMed Central

    2012-01-01

    Background Molecular Dynamics (MD) simulations are a promising tool to generate molecular understanding of processes related to the purification of proteins. Polyethylene glycols (PEG) of various length are commonly used in the production and purification of proteins. The molecular mechanisms behind PEG driven precipitation, aqueous two-phase formation or the effects of PEGylation are however still poorly understood. Results In this paper, we ran MD simulations of single PEG molecules of variable length in explicitly simulated water. The resulting structures are in good agreement with experimentally determined 3D structures of PEG. The increase in surface hydrophobicity of PEG of longer chain length could be explained on an atomic scale. PEG-water interactions as well as aqueous two-phase formation in the presence of PO4 were found to be correlated to PEG surface hydrophobicity. Conclusions We were able to show that the taken MD simulation approach is capable of generating both structural data as well as molecule descriptors in agreement with experimental data. Thus, we are confident of having a good in silico representation of PEG. PMID:22873343

  4. Higher Molecular Mass Organic Matter Molecules Compete with Orthophosphate for Adsorption to Iron (Oxy)hydroxide.

    PubMed

    Chassé, Alexander W; Ohno, Tsutomu

    2016-07-19

    The competition between orthophosphate and water-extractable organic matter (WEOM) for adsorption to iron (oxy)hydroxide mineral surfaces is an important factor in determining the plant bioavailability of P in soils. Chemical force spectroscopy was used to determine the binding force between orthophosphate and iron (oxy)hydroxide that was coated onto atomic force microscopy (AFM) tips and adsorbed with WEOM. The force measurements were conducted at pH 4.65 and 0.02 M ionic strength which are representative of typical acid soil solutions. The chemical composition of the WEOM was determined by ultrahigh resolution electrospray ionization Fourier transform ion cyclotron mass spectrometry. The results indicate a correlation between aromatic WEOM molecules that are greater than 600 Da and the reduced binding force of orthophosphate to WEOM-adsorbed iron (oxy)hydroxide AFM tips suggesting that the molecular mass of aromatic WEOM molecules plays a critical role in regulating the WEOM-P interactions with surface functional groups of minerals. Based on the results of this study, we show the importance of obtaining a detailed, molecular-scale understanding of soil processes that can help develop better management strategies to reduce waste of limited P resources and adverse environmental impacts. Specifically, soil amendments with greater content of high molecular mass aromatic components may positively affect dissolved P use efficiency in soils by maintaining P in soil solution. PMID:27362894

  5. Exceptional Single-Molecule Transport Properties of Ladder-Type Heteroacene Molecular Wires.

    PubMed

    Cai, Zhengxu; Lo, Wai-Yip; Zheng, Tianyue; Li, Lianwei; Zhang, Na; Hu, Yubing; Yu, Luping

    2016-08-24

    A series of ladder-type fused heteroacenes consisting of thiophenes and benzothiophenes were synthesized and functionalized with thiol groups for single-molecule electrical measurements via a scanning tunneling microscopy break-junction method. It was found that this molecular wire system possesses exceptional charge transport properties with weak length dependence. The tunneling decay constant β was estimated to be 0.088 and 0.047 Å(-1) under 0.1 and 0.5 bias, respectively, which is one of the lowest β values among other non-metal-containing molecular wires, indicating that a planar ladder structure favors charge transport. Transition voltage spectroscopy showed that the energy barrier decreases as the length of the molecule increases. The general trend of the energy offsets derived from the transition voltage via the Newns-Anderson model agrees well with that of the Fermi/HOMO energy level difference. Nonequilibrium Green's function/density functional theory was used to further investigate the transport process in these molecular wires. PMID:27488536

  6. Affinity flow fractionation of cells via transient interactions with asymmetric molecular patterns

    NASA Astrophysics Data System (ADS)

    Bose, Suman; Singh, Rishi; Hanewich-Hollatz, Mikhail; Shen, Chong; Lee, Chia-Hua; Dorfman, David M.; Karp, Jeffrey M.; Karnik, Rohit

    2013-07-01

    Flow fractionation of cells using physical fields to achieve lateral displacement finds wide applications, but its extension to surface molecule-specific separation requires labeling. Here we demonstrate affinity flow fractionation (AFF) where weak, short-range interactions with asymmetric molecular patterns laterally displace cells in a continuous, label-free process. We show that AFF can directly draw neutrophils out of a continuously flowing stream of blood with an unprecedented 400,000-fold depletion of red blood cells, with the sorted cells being highly viable, unactivated, and functionally intact. The lack of background erythrocytes enabled the use of AFF for direct enumeration of neutrophils by a downstream detector, which could distinguish the activation state of neutrophils in blood. The compatibility of AFF with capillary microfluidics and its ability to directly separate cells with high purity and minimal sample preparation will facilitate the design of simple and portable devices for point-of-care diagnostics and quick, cost-effective laboratory analysis.

  7. Bond orientation properties in lipid molecules of membranes: molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Rabinovich, Alexander L.; Lyubartsev, Alexander P.

    2014-05-01

    Atomistic molecular dynamics simulations have been carried out for 16 different fully hydrated phosphatidylcholine lipid bilayers, having 16 or 18 carbon atoms in fully saturated sn - 1 chain and from 18 to 22 carbon atoms in sn - 2 chain with different degree of unsaturation, with the purpose to investigate the effect of unsaturation on physical properties of lipid bilayers. Special attention has been paid to profiles of C-C and C-H bond order parameters of lipid molecules and the orientational fluctuations of these bond vectors. It was shown that the study of anisotropy degree of bond orientations probability distributions allows distinguishing extended regions with different types of angular fluctuations of bonds in a membrane formed by lipid molecules with unsaturated chains.

  8. Small Molecule Activators of the Heat Shock Response: Chemical Properties, Molecular Targets, and Therapeutic Promise

    PubMed Central

    West, James D.; Wang, Yanyu; Morano, Kevin A.

    2012-01-01

    All cells have developed various mechanisms to respond and adapt to a variety of environmental challenges, including stresses that damage cellular proteins. One such response, the heat shock response (HSR), leads to the transcriptional activation of a family of molecular chaperone proteins that promote proper folding or clearance of damaged proteins within the cytosol. In addition to its role in protection against acute insults, the HSR also regulates lifespan and protects against protein misfolding that is associated with degenerative diseases of aging. As a result, identifying pharmacological regulators of the HSR has become an active area of research in recent years. Here, we review progress made in identifying small molecule activators of the HSR, what cellular targets these compounds interact with to drive response activation, and how such molecules may ultimately be employed to delay or reverse protein misfolding events that contribute to a number of diseases. PMID:22799889

  9. Nanotubule and Tour Molecule Based Molecular Electronics: Suggestion for a Hybrid Approach

    NASA Technical Reports Server (NTRS)

    Srivastava, Deepak; Saini, Subhash (Technical Monitor)

    1998-01-01

    Recent experimental and theoretical attempts and results indicate two distinct broad pathways towards future molecular electronic devices and architectures. The first is the approach via Tour type ladder molecules and their junctions which can be fabricated with solution phase chemical approaches. Second are fullerenes or nanotubules and their junctions which may have better conductance, switching and amplifying characteristics but can not be made through well controlled and defined chemical means. A hybrid approach combining the two pathways to take advantage of the characteristics of both is suggested. Dimension and scale of such devices would be somewhere in between isolated molecule and nanotubule based devices but it maybe possible to use self-assembly towards larger functional and logicalunits.

  10. Carbon-based molecular devices: Fano effects controlled by the molecule length and the gate voltage.

    PubMed

    Yang, X F; Kuang, Y W; Liu, Y S; Zhang, D B; Shao, Z G; Yu, H L; Hong, X K; Feng, J F; Chen, X S; Wang, X F

    2016-08-25

    Fano effect is an important quantum phenomenon in mesoscopic systems, which arises from an interference between the localized state and the extended state. Here we observe an obvious Fano effect near the Fermi level in an all-carbon molecular device consisting of an acene molecule sandwiched between two zigzag graphene nanoribbon (ZGNR) electrodes. By increasing the length of the molecule, an extended state gradually evolves into a localized state. With the aid of the nearby extended state, a Fano effect is achieved. Using a gate voltage, we can easily tune the Fano effect induced by the single-transmission channel. When the spin degree of freedom is involved, the all-carbon device can show a half-metallic property with positive or negative 100% spin polarization at the Fermi level under the gate voltage; meanwhile the spin thermoelectric effect can also be enhanced. PMID:27528438

  11. Molecular dynamics simulations for the study of optical properties in conjugated semiconducting molecules

    NASA Astrophysics Data System (ADS)

    Wildman, Jack; Denis, Jean-Christophe; Repiščák, Peter; Paterson, Martin J.; Galbraith, Ian

    Conformational disorder of conjugated polymers strongly influences their optical and electronic properties. Molecular Dynamics (MD) simulations can provide a quantitative understanding of these effects. Given the ever-expanding range of molecules with potential for device applications, it is critical to systematically establish accurate MD parameters for such simulations. We present an experimentally verified, general and optimised procedure, based on a computationally inexpensive methodology for generating the required MD parameters for conjugated molecules. By combining a large sample (~1000) of MD generated conformations with DFT calculations for the resulting electronic states we can explore the influence of conformational disorder on the optical properties. Using this scheme, we determine the effect of conformational variation on both linear and two-photon absorption spectra in a number of different conjugated semiconducting oligomers. Our results indicate that, while there exists significant inhomogeneous broadening in the linear absorption, there is only a weak conformational influence on the two-photon absorption spectrum.

  12. A virus-like molecule in the early stage of encoded molecular evolution

    NASA Astrophysics Data System (ADS)

    Nemoto, Naoto; Yanagawa, Hiroshi; Husimi, Yuzuru

    1996-10-01

    The recent advances of the evolutionary molecular engineering revealed the effectiveness of bonding strategy for assignment of the phenotype to its genotype, which non-enveloped viruses such as simple bacteriophages adopt. On the other hand, cellular organisms adopt another kind of the strategy, namely the compartmentalzation of both genotype and phenotype molecules in a single compartment enclosed with a cell membrane. The simplest strategy is that adopted by ribozymes in the RNA world. A single molecule carries both genotype and its phenotype. Based on the definition of “virus”-type and “cell”-type of the assignment strategy, we propose a virus-early/cell-late model of the history of life.

  13. Molecular length dictates the nature of charge carriers in single-molecule junctions of oxidized oligothiophenes.

    PubMed

    Dell, Emma J; Capozzi, Brian; Xia, Jianlong; Venkataraman, Latha; Campos, Luis M

    2015-03-01

    To develop advanced materials for electronic devices, it is of utmost importance to design organic building blocks with tunable functionality and to study their properties at the molecular level. For organic electronic and photovoltaic applications, the ability to vary the nature of charge carriers and so create either electron donors or acceptors is critical. Here we demonstrate that charge carriers in single-molecule junctions can be tuned within a family of molecules that contain electron-deficient thiophene-1,1-dioxide (TDO) building blocks. Oligomers of TDO were designed to increase electron affinity and maintain delocalized frontier orbitals while significantly decreasing the transport gap. Through thermopower measurements we show that the dominant charge carriers change from holes to electrons as the number of TDO units is increased. This results in a unique system in which the charge carrier depends on the backbone length, and provides a new means to tune p- and n-type transport in organic materials. PMID:25698329

  14. A molecular dynamics study on slow ion interactions with the polycyclic aromatic hydrocarbon molecule anthracene

    SciTech Connect

    Postma, J.; Hoekstra, R.; Schlathölter, T.; Tielens, A. G. G. M.

    2014-03-01

    Atomic collisions with polycyclic aromatic hydrocarbon (PAH) molecules are astrophysically particularly relevant for collision energies of less than 1 keV. In this regime, the interaction dynamics are dominated by elastic interactions. We have employed a molecular dynamics simulation based on analytical interaction potentials to model the interaction of low energy hydrogen and helium projectiles with isolated anthracene (C{sub 14}H{sub 10}) molecules. This approach allows for a very detailed investigation of the elastic interaction dynamics on an event by event basis. From the simulation data the threshold projectile kinetic energies above which direct C atom knock out sets in were determined. Anthracene differential energy transfer cross sections and total (dissociation) cross sections were computed for a wide range of projectile kinetic energies. The obtained results are interpreted in the context of PAH destruction in astrophysical environments.

  15. High-resolution single-molecule recognition imaging of the molecular details of ricin-aptamer interaction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The molecular details of DNA aptamer-ricin interactions were investigated. The toxic protein ricin molecules were immobilized on Au(111) surface using N-hydroxysuccinimide (NHS) ester to specifically react with lysine residues located on the ricin B chains. A single ricin molecule was visualized in ...

  16. Anomalous water molecules and mechanistic effects of water nanotube clusters confined to molecular porous crystals.

    PubMed

    Tadokoro, Makoto; Ohhara, Takashi; Ohhata, Yuhki; Suda, Takaaki; Miyasato, Yuji; Yamada, Takeshi; Kikuchi, Tatsuya; Tanaka, Ichiro; Kurihara, Kazuo; Oguni, Masaharu; Nakasuji, Kazuhiro; Yamamuro, Osamu; Ryota, Kuroki

    2010-02-18

    The movement of water molecules in the limited space present within nanoscale regions, which is different from the molecular motion of bulk water, is significantly affected by strong interfacial interactions with the surrounding outer walls. Hence, most of the water molecules that are confined to nanochannel spaces having widths less than ca. 2 nm can generally be classified together as "structural water". Since the motions of such water molecules are limited by interfacial interactions with the outer wall, the nature of structural water, which is strongly influenced by the interactions, will have different characteristics from normal water. For our investigations on the characteristics of structural water, we have developed a nanoporous crystal with a diameter of ca. 1.6 nm; it was constructed from 1-D hydrophilic channels by self-organization of the designed molecules. A tubelike three-layered water cluster, called a water nanotube (WNT), is formed in each internal channel space and is regulated by H-bonds with the outer wall. The WNT undergoes a glass transition (T(g) = 107 K) and behaves as a liquid; it freezes at 234 K and changes into an icelike nanotube cluster. In this study, the structure of the WNT is investigated through neutron structure analysis, and it is observed to stabilize by a mechanistic anchor effect of structural water. Furthermore, from neutron-scattering experiments, it is seen that a few water molecules around the center of the WNT move approximately with the same diffusion constant as those in bulk water; however, the residence time and average jump length are longer, despite the restrictions imposed by the H-bonding with structural water. The behavior of mobile water within a WNT is investigated; this can be used to elucidate the mechanism for the effect of structural water on vital functions on the cell surface. PMID:20102158

  17. Retrieving transient conformational molecular structure information from inner-shell photoionization of laser-aligned molecules

    DOE PAGESBeta

    Wang, Xu; Le, Anh -Thu; Yu, Chao; Lucchese, R. R.; Lin, C. D.

    2016-03-30

    We discuss a scheme to retrieve transient conformational molecular structure information using photoelectron angular distributions (PADs) that have averaged over partial alignments of isolated molecules. The photoelectron is pulled out from a localized inner-shell molecular orbital by an X-ray photon. We show that a transient change in the atomic positions from their equilibrium will lead to a sensitive change in the alignment-averaged PADs, which can be measured and used to retrieve the former. Exploiting the experimental convenience of changing the photon polarization direction, we show that it is advantageous to use PADs obtained from multiple photon polarization directions. Lastly, amore » simple single-scattering model is proposed and benchmarked to describe the photoionization process and to do the retrieval using a multiple-parameter fitting method.« less

  18. Retrieving transient conformational molecular structure information from inner-shell photoionization of laser-aligned molecules

    NASA Astrophysics Data System (ADS)

    Wang, Xu; Le, Anh-Thu; Yu, Chao; Lucchese, R. R.; Lin, C. D.

    2016-03-01

    We discuss a scheme to retrieve transient conformational molecular structure information using photoelectron angular distributions (PADs) that have averaged over partial alignments of isolated molecules. The photoelectron is pulled out from a localized inner-shell molecular orbital by an X-ray photon. We show that a transient change in the atomic positions from their equilibrium will lead to a sensitive change in the alignment-averaged PADs, which can be measured and used to retrieve the former. Exploiting the experimental convenience of changing the photon polarization direction, we show that it is advantageous to use PADs obtained from multiple photon polarization directions. A simple single-scattering model is proposed and benchmarked to describe the photoionization process and to do the retrieval using a multiple-parameter fitting method.

  19. Retrieving transient conformational molecular structure information from inner-shell photoionization of laser-aligned molecules

    PubMed Central

    Wang, Xu; Le, Anh-Thu; Yu, Chao; Lucchese, R. R.; Lin, C. D.

    2016-01-01

    We discuss a scheme to retrieve transient conformational molecular structure information using photoelectron angular distributions (PADs) that have averaged over partial alignments of isolated molecules. The photoelectron is pulled out from a localized inner-shell molecular orbital by an X-ray photon. We show that a transient change in the atomic positions from their equilibrium will lead to a sensitive change in the alignment-averaged PADs, which can be measured and used to retrieve the former. Exploiting the experimental convenience of changing the photon polarization direction, we show that it is advantageous to use PADs obtained from multiple photon polarization directions. A simple single-scattering model is proposed and benchmarked to describe the photoionization process and to do the retrieval using a multiple-parameter fitting method. PMID:27025410

  20. On the separability of the extended molecule: Constructing the best localized molecular orbitals for an organic molecule bridging two model electrodes

    SciTech Connect

    Moreira, Rodrigo A.; Melo, Celso P. de

    2014-09-28

    Based on a quantum chemical valence formalism that allows the rigorous construction of best-localized molecular orbitals on specific parts of an extended system, we examined the separability of individual components of model systems relevant to the description of electron transport in molecular devices. We started by examining how to construct the maximally localized electronic density at the tip of a realistic model of a gold electrode. By varying the number of gold atoms included in the local region where to project the total electronic density, we quantitatively assess how many molecular orbitals are entirely localized in that region. We then considered a 1,4-benzene-di-thiol molecule connected to two model gold electrodes and examined how to localize the electronic density of the total system in the extended molecule, a fractional entity comprising the organic molecule plus an increasing number of the closest metal atoms. We were able to identify in a rigorous manner the existence of three physically different electronic populations, each one corresponding to a distinct set of molecular orbitals. First, there are those entirely localized in the extended molecule, then there is a second group of those completely distributed in the gold atoms external to that region, and, finally, there are those delocalized over the entire system. This latter group can be associated to the shared electronic population between the extended molecule and the rest of the system. We suggest that the treatment here presented could be useful in the theoretical analysis of the electronic transport in nanodevices whenever the use of localized molecular states are required by the physics of the specific problem, such as in cases of weak coupling and super-exchange limits.

  1. LC-MS with electron ionization of cold molecules in supersonic molecular beams

    NASA Astrophysics Data System (ADS)

    Granot, Ori; Amirav, Aviv

    2005-06-01

    A new approach is described for the combination of electron ionization and LC-MS based on sample ionization as vibrationally cold molecules in a supersonic molecular beam (Cold EI). Cold EI of sample compounds in liquid solutions (methanol, acetonitrile, water, etc.) is achieved through spray formation, followed by soft thermal vaporization of the sample particles prior to their supersonic expansion and direct electron ionization of the sample compounds while they are contained in a supersonic molecular beam (SMB). Cold EI mass spectra were demonstrated to combine an enhanced molecular ion and improved mass spectral information (in comparison with standard EI), plus all the library searchable fragments. Cold EI enables the ionization of a broad range of compounds, including the full range of non-polar samples. Four orders of magnitude linear dynamic range is demonstrated and a detection limit of 2 pg was achieved for a 774 amu compound in single ion monitoring mode at m/z = 774. The method and apparatus are under continuous development and we feel that it can excel particularly in the analysis of unknown samples, while enabling fast LC-MS analysis through automated mass spectral deconvolution of coeluting LC peaks. In addition, the same MS system can also serve as an advanced GC-MS with supersonic molecular beams.

  2. On Achieving Experimental Accuracy from Molecular Dynamics Simulations of Flexible Molecules: Aqueous Glycerol

    PubMed Central

    Yongye, Austin B.; Foley, B. Lachele; Woods, Robert J.

    2014-01-01

    The rotational isomeric states (RIS) of glycerol at infinite dilution have been characterized in the aqueous phase via a 1 μs conventional molecular dynamics (MD) simulation, a 40 ns enhanced sampling replica exchange molecular dynamics (REMD) simulation, and a reevaluation of the experimental NMR data. The MD and REMD simulations employed the GLYCAM06/AMBER force field with explicit treatment of solvation. The shorter time scale of the REMD sampling method gave rise to RIS and theoretical scalar 3JHH coupling constants that were comparable to those from the much longer traditional MD simulation. The 3JHH coupling constants computed from the MD methods were in excellent agreement with those observed experimentally. Despite the agreement between the computed and the experimental J-values, there were variations between the rotamer populations computed directly from the MD data and those derived from the experimental NMR data. The experimentally derived populations were determined utilizing limiting J-values from an analysis of NMR data from substituted ethane molecules and may not be completely appropriate for application in more complex molecules, such as glycerol. Here, new limiting J-values have been derived via a combined MD and quantum mechanical approach and were used to decompose the experimental 3JHH coupling constants into population distributions for the glycerol RIS. PMID:18311953

  3. First principles investigations of vinazene molecule and molecular crystal: a prospective candidate for organic photovoltaic applications.

    PubMed

    Mohamad, Mazmira; Ahmed, Rashid; Shaari, Amirudin; Goumri-Said, Souraya

    2015-02-01

    Escalating demand for sustainable energy resources, because of the rapid exhaustion of conventional energy resources as well as to maintain the environmental level of carbon dioxide (CO2) to avoid its adverse effect on the climate, has led to the exploitation of photovoltaic technology manifold more than ever. In this regard organic materials have attracted great attention on account of demonstrating their potential to harvest solar energy at an affordable rate for photovoltaic technology. 2-vinyl-4,5-dicyanoimidazole (vinazene) is considered as a suitable material over the fullerenes for photovoltaic applications because of its particular chemical and physical nature. In the present study, DFT approaches are employed to provide an exposition of optoelectronic properties of vinazene molecule and molecular crystal. To gain insight into its properties, different forms of exchange correlation energy functional/potential such as LDA, GGA, BLYP, and BL3YP are used. Calculated electronic structure of vinazene molecule has been displayed via HOMO-LUMO isosurfaces, whereas electronic structure of the vinazene molecular crystal, via electronic band structure, is presented. The calculated electronic and optical properties were analyzed and compared as well. Our results endorse vinazene as a suitable material for organic photovoltaic applications. PMID:25631921

  4. The peptide-receptive transition state of MHC-1 molecules: Insight from structure and molecular dynamics

    SciTech Connect

    Robinson H.; Mage, M.; Dolan, M.; Wang, R.; Boyd, L.; Revilleza, M.; Natarajan, K.; Myers, N.; Hansen, T.; Margulies, D.

    2012-05-01

    MHC class I (MHC-I) proteins of the adaptive immune system require antigenic peptides for maintenance of mature conformation and immune function via specific recognition by MHC-I-restricted CD8(+) T lymphocytes. New MHC-I molecules in the endoplasmic reticulum are held by chaperones in a peptide-receptive (PR) transition state pending release by tightly binding peptides. In this study, we show, by crystallographic, docking, and molecular dynamics methods, dramatic movement of a hinged unit containing a conserved 3(10) helix that flips from an exposed 'open' position in the PR transition state to a 'closed' position with buried hydrophobic side chains in the peptide-loaded mature molecule. Crystallography of hinged unit residues 46-53 of murine H-2L(d) MHC-I H chain, complexed with mAb 64-3-7, demonstrates solvent exposure of these residues in the PR conformation. Docking and molecular dynamics predict how this segment moves to help form the A and B pockets crucial for the tight peptide binding needed for stability of the mature peptide-loaded conformation, chaperone dissociation, and Ag presentation.

  5. Probing Solvation Dynamics around Aromatic and Biological Molecules at the Single-Molecular Level.

    PubMed

    Dopfer, Otto; Fujii, Masaaki

    2016-05-11

    Solvation processes play a crucial role in chemical reactions and biomolecular recognition phenomena. Although solvation dynamics of interfacial or biological water has been studied extensively in aqueous solution, the results are generally averaged over several solvation layers and the motion of individual solvent molecules is difficult to capture. This review describes the development and application of a new experimental approach, namely, picosecond time-resolved pump-probe infrared spectroscopy of size- and isomer-selected aromatic clusters, in which for the first time the dynamics of a single individual solvent molecule can be followed in real time. The intermolecular isomerization reaction is triggered by resonant photoionization (pump), and infrared photodissociation (probe) at variable delay generates the spectroscopic signature of salient properties of the reaction, including rates, yields, pathways, branching ratios of competing reactions, existence of reaction intermediates, occurrence of back reactions, and time scales of energy relaxation processes. It is shown that this relevant information can reliably be decoded from the experimental spectra by sophisticated molecular dynamics simulations. This review covers a description of the experimental strategies and spectroscopic methods along with all applications to date, which range from aromatic clusters with nonpolar solvent molecules to aromatic monohydrated biomolecules. PMID:27054835

  6. Molecular design of non-linear optical properties and synthesis of organic molecules

    SciTech Connect

    Clark, R.D.; Tan, L.; Martinez, A.; Romero, E.; Ballard, J.; Penn, B.; Moore, C.; Cardelino, B.; Sanghadasa, M.

    1995-06-01

    Non-linear optical properties of organic molecules are of interest because of their possible use in telecommunications and optical computers. Prediction of these properties prior to synthesis is of importance in order to save synthesis time. The second-order polarizabilities of a series of compounds have been predicted based on a finite-field approach using a modified version of the MOPAC program together with the HYPER program developed by Cardelino and Moore. These predictions have then been compared with EFISH measurements made on selected compounds. The EFISH results were adjusted to account for dispersion and solvent effects. As expected, with nitroanilines, the amino group and the aromatic ring of the molecular must be coplanar in order to give a good correlation. The theoretical technique is currently being used to design and identify candidate molecules that should have high second-order polarizability values. Synthesis and measurements of selected candidate molecules are being undertaken; crystal growth and thin film work will follow as appropriate.

  7. The immunoproteasome controls the availability of the cardioprotective pattern recognition molecule Pentraxin3.

    PubMed

    Paeschke, Anna; Possehl, Anna; Klingel, Karin; Voss, Martin; Voss, Karolin; Kespohl, Meike; Sauter, Martina; Overkleeft, Hermen S; Althof, Nadine; Garlanda, Cecilia; Voigt, Antje

    2016-03-01

    Cardiomyocyte death as a result of viral infection is an excellent model for dissecting the inflammatory stress response that occurs in heart tissue. We reported earlier that a specific proteasome isoform, the immunoproteasome, prevents exacerbation of coxsackievirus B3 (CVB3)-induced myocardial destruction and preserves cell vitality in heart tissue inflammation. Following the aim to decipher molecular targets of immunoproteasome-dependent proteolysis, we investigated the function and regulation of the soluble PRR Pentraxin3 (PTX3). We show that the ablation of PTX3 in mice aggravated CVB3-triggered inflammatory injury of heart tissue, without having any significant effect on viral titers. Thus, there might be a role of PTX3 in preventing damage-associated molecular pattern-induced cell death. We found that the catalytic activity of the immunoproteasome subunit LMP7 regulates the timely availability of factors controlling PTX3 production. We report on immunoproteasome-dependent alteration of ERK1/2 and p38MAPKs, which were both found to be involved in PTX3 expression control. Our finding of a cardioprotective function of immunoproteasome-dependent PTX3 expression revealed a crucial mechanism of the stress-induced damage response in myocardial inflammation. In addition to antigen presentation and cytokine production, proteolysis by the immunoproteasome can also regulate the innate immune response during viral infection. PMID:26578407

  8. Molecular resonant dissociation of surface-adsorbed molecules by plasmonic nanoscissors

    NASA Astrophysics Data System (ADS)

    Zhang, Zhenglong; Sheng, Shaoxiang; Zheng, Hairong; Xu, Hongxing; Sun, Mengtao

    2014-04-01

    The ability to break individual bonds or specific modes in chemical reactions is an ardently sought goal by chemists and physicists. While photochemistry based methodologies are very successful in controlling e.g. photocatalysis, photosynthesis and the degradation of plastic, it is hard to break individual molecular bonds for those molecules adsorbed on the surface because of the weak light-absorption in molecules and the redistribution of the resulting vibrational energy both inside the molecule and to its surrounding environment. Here we show how to overcome these obstacles with a plasmonic hot-electron mediated process and demonstrate a new method that allows the sensitive control of resonant dissociation of surface-adsorbed molecules by `plasmonic' scissors. To that end, we used a high-vacuum tip-enhanced Raman spectroscopy (HV-TERS) setup to dissociate resonantly excited NC2H6 fragments from Malachite green. The surface plasmons (SPs) excited at the sharp metal tip not only enhance the local electric field to harvest the light incident from the laser, but crucially supply `hot electrons' whose energy can be transferred to individual bonds. These processes are resonant Raman, which result in some active chemical bonds and then weaken these bonds, followed by dumping in lots of indiscriminant energy and breaking the weakest bond. The method allows for sensitive control of both the rate and probability of dissociation through their dependence on the density of hot electrons, which can be manipulated by tuning the laser intensity or tunneling current/bias voltage in the HV-TERS setup, respectively. The concepts of plasmonic scissors open up new versatile avenues for the deep understanding of in situ surface-catalyzed chemistry.The ability to break individual bonds or specific modes in chemical reactions is an ardently sought goal by chemists and physicists. While photochemistry based methodologies are very successful in controlling e.g. photocatalysis

  9. Body-fixed relativistic molecular Hamiltonian and its application to nuclear spin-rotation tensor: Linear molecules

    NASA Astrophysics Data System (ADS)

    Xiao, Yunlong; Liu, Wenjian

    2013-07-01

    The relativistic molecular Hamiltonian written in the body-fixed frame of reference is the basis for high-precision calculations of spectroscopic parameters involving nuclear vibrations and/or rotations. Such a Hamiltonian that describes electrons fully relativistically and nuclei quasi-relativistically is just developed for semi-rigid nonlinear molecules [Y. Xiao and W. Liu, J. Chem. Phys. 138, 134104 (2013)], 10.1063/1.4797496. Yet, the formulation should somewhat be revised for linear molecules thanks to some unusual features arising from the redundancy of the rotation around the molecular axis. Nonetheless, the resulting isomorphic Hamiltonian is rather similar to that for nonlinear molecules. Consequently, the relativistic formulation of nuclear spin-rotation (NSR) tensor for linear molecules is very much the same as that for nonlinear molecules. So is the relativistic mapping between experimental NSR and NMR.

  10. Nanofibers for drug delivery – incorporation and release of model molecules, influence of molecular weight and polymer structure

    PubMed Central

    Hrib, Jakub; Hobzova, Radka; Hampejsova, Zuzana; Bosakova, Zuzana; Munzarova, Marcela; Michalek, Jiri

    2015-01-01

    Summary Nanofibers were prepared from polycaprolactone, polylactide and polyvinyl alcohol using NanospiderTM technology. Polyethylene glycols with molecular weights of 2 000, 6 000, 10 000 and 20 000 g/mol, which can be used to moderate the release profile of incorporated pharmacologically active compounds, served as model molecules. They were terminated by aromatic isocyanate and incorporated into the nanofibers. The release of these molecules into an aqueous environment was investigated. The influences of the molecular length and chemical composition of the nanofibers on the release rate and the amount of released polyethylene glycols were evaluated. Longer molecules released faster, as evidenced by a significantly higher amount of released molecules after 72 hours. However, the influence of the chemical composition of nanofibers was even more distinct – the highest amount of polyethylene glycol molecules released from polyvinyl alcohol nanofibers, the lowest amount from polylactide nanofibers. PMID:26665065

  11. Invariance of molecular charge transport upon changes of extended molecule size and several related issues.

    PubMed

    Bâldea, Ioan

    2016-01-01

    As a sanity test for the theoretical method employed, studies on (steady-state) charge transport through molecular devices usually confine themselves to check whether the method in question satisfies the charge conservation. Another important test of the theory's correctness is to check that the computed current does not depend on the choice of the central region (also referred to as the "extended molecule"). This work addresses this issue and demonstrates that the relevant transport and transport-related properties are indeed invariant upon changing the size of the extended molecule, when the embedded molecule can be described within a general single-particle picture (namely, a second-quantized Hamiltonian bilinear in the creation and annihilation operators). It is also demonstrates that the invariance of nonequilibrium properties is exhibited by the exact results but not by those computed approximately within ubiquitous wide- and flat-band limits (WBL and FBL, respectively). To exemplify the limitations of the latter, the phenomenon of negative differential resistance (NDR) is considered. It is shown that the exactly computed current may exhibit a substantial NDR, while the NDR effect is absent or drastically suppressed within the WBL and FBL approximations. The analysis done in conjunction with the WBLs and FBLs reveals why general studies on nonequilibrium properties require a more elaborate theoretical than studies on linear response properties (e.g., ohmic conductance and thermopower) at zero temperature. Furthermore, examples are presented that demonstrate that treating parts of electrodes adjacent to the embedded molecule and the remaining semi-infinite electrodes at different levels of theory (which is exactly what most NEGF-DFT approaches do) is a procedure that yields spurious structures in nonlinear ranges of current-voltage curves. PMID:27335734

  12. Ultrafast molecular dynamics of liquid aromatic molecules and the mixtures with CCl4

    NASA Astrophysics Data System (ADS)

    Shirota, Hideaki

    2005-01-01

    The ultrafast molecular dynamics of liquid aromatic molecules, benzene, toluene, ethylbenzene, cumene, and 1,3-diphenylpropane, and the mixtures with CCl4 have been investigated by means of femtosecond optical heterodyne-detected Raman-induced Kerr effect spectroscopy. The picosecond Kerr transients of benzene, toluene, ethylbenzene, and cumene and the mixtures with CCl4 show a biexponential feature. 1,3-Diphenylpropane and the mixtures with CCl4 show triexponential picosecond Kerr transients. The slow relaxation time constants of the aromatic molecules and the mixtures with CCl4 are qualitatively described by the Stoke-Einstein-Debye hydrodynamic model. The ultrafast dynamics have been discussed based on the Kerr spectra in the frequency range of 0-800 cm-1 obtained by the Fourier transform analysis of the Kerr transients. The line shapes of the low-frequency intermolecular spectra located at 0-180 cm-1 frequency range have been analyzed by two Brownian oscillators (˜11 cm-1 and ˜45 cm-1 peaks) and an antisymmetric Gaussian function (˜65 cm-1 peak). The spectrum shape of 1,3-diphenylpropane is quite different from the spectrum shapes of the other aromatic molecules for the low magnitude of the low-frequency mode of 1,3-diphenylpropane and/or an intramolecular vibration. Although the concentration dependences of the low- and intermediate-frequency intermolecular modes (Brownian oscillators) do not show a significant trend, the width of high-frequency intermolecular mode (antisymmetric Gaussian) becomes narrower with the higher CCl4 concentration for all the aromatics mixtures with CCl4. The result indicates that the inhomogeneity of the intermolecular vibrational mode in aromatics/CCl4 mixtures is decreasing with the lower concentration of aromatics. The intramolecular vibrational modes of the aromatic molecules observed in the Kerr spectra are also shown with the calculation results based on the density functional theory.

  13. Dressed-bound-state molecular strong-field approximation: Application to above-threshold ionization of heteronuclear diatomic molecules

    SciTech Connect

    Hasovic, E.; Busuladzic, M.; Becker, W.; Milosevic, D. B.

    2011-12-15

    The molecular strong-field approximation (MSFA), which includes dressing of the molecular bound state, is introduced and applied to above-threshold ionization of heteronuclear diatomic molecules. Expressions for the laser-induced molecular dipole and polarizability as functions of the laser parameters (intensity and frequency) and molecular parameters [molecular orientation, dipole, and parallel and perpendicular polarizabilities of the highest occupied molecular orbital (HOMO)] are presented. Our previous MSFA theory, which incorporates the rescattering effects, is generalized from homonuclear to heteronuclear diatomic molecules. Angle- and energy-resolved high-order above-threshold ionization spectra of oriented heteronuclear diatomic molecules, exemplified by the carbon monoxide (CO) molecule, exhibit pronounced minima, which can be related to the shape of their HOMO-electron-density distribution. For the CO molecule we have found an analytical condition for the positions of these minima. We have also shown that the effect of the dressing of the HOMO is twofold: (i) the laser-induced Stark shift decreases the ionization yield and (ii) the laser-induced time-dependent dipole and polarizability change the oscillatory structure of the spectra.

  14. The Role of Molecular Dipole Orientation in Single-Molecule Fluorescence Microscopy and Implications for Super-Resolution Imaging

    PubMed Central

    Backlund, Mikael P.; Lew, Matthew D.; Backer, Adam S.; Sahl, Steffen J.

    2014-01-01

    Numerous methods for determining the orientation of single-molecule transition dipole moments from microscopic images of the molecular fluorescence have been developed in recent years. At the same time, techniques that rely on nanometer-level accuracy in the determination of molecular position, such as single-molecule super-resolution imaging, have proven immensely successful in their ability to access unprecedented levels of detail and resolution previously hidden by the optical diffraction limit. However, the level of accuracy in the determination of position is threatened by insufficient treatment of molecular orientation. Here we review a number of methods for measuring molecular orientation using fluorescence microscopy, focusing on approaches that are most compatible with position estimation and single-molecule super-resolution imaging. We highlight recent methods based on quadrated pupil imaging and on double-helix point spread function microscopy and apply them to the study of fluorophore mobility on immunolabeled microtubules. PMID:24382708

  15. Structure of the F-spondin Domain of Mindin an Integrin Ligand and Pattern Recognition Molecule

    SciTech Connect

    Y Li; C Cao; W Jia; L Yu; M Mo; Q Wang; Y Huang; J Lim; M Ishihara; et. al.

    2011-12-31

    Mindin (spondin-2) is an extracellular matrix protein of unknown structure that is required for efficient T-cell priming by dendritic cells. Additionally, mindin functions as a pattern recognition molecule for initiating innate immune responses. These dual functions are mediated by interactions with integrins and microbial pathogens, respectively. Mindin comprises an N-terminal F-spondin (FS) domain and C-terminal thrombospondin type 1 repeat (TSR). We determined the structure of the FS domain at 1.8-A resolution. The structure revealed an eight-stranded antiparallel beta-sandwich motif resembling that of membrane-targeting C2 domains, including a bound calcium ion. We demonstrated that the FS domain mediates integrin binding and identified the binding site by mutagenesis. The mindin FS domain therefore represents a new integrin ligand. We further showed that mindin recognizes lipopolysaccharide (LPS) through its TSR domain, and obtained evidence that C-mannosylation of the TSR influences LPS binding. Through these dual interactions, the FS and TSR domains of mindin promote activation of both adaptive and innate immune responses.

  16. Structure of the F-spondin domain of mindin, an integrin ligand and pattern recognition molecule

    PubMed Central

    Li, Yili; Cao, Chunzhang; Jia, Wei; Yu, Lily; Mo, Min; Wang, Qian; Huang, Yuping; Lim, Jae-Min; Ishihara, Mayumi; Wells, Lance; Azadi, Parastoo; Robinson, Howard; He, You-Wen; Zhang, Li; Mariuzza, Roy A

    2009-01-01

    Mindin (spondin-2) is an extracellular matrix protein of unknown structure that is required for efficient T-cell priming by dendritic cells. Additionally, mindin functions as a pattern recognition molecule for initiating innate immune responses. These dual functions are mediated by interactions with integrins and microbial pathogens, respectively. Mindin comprises an N-terminal F-spondin (FS) domain and C-terminal thrombospondin type 1 repeat (TSR). We determined the structure of the FS domain at 1.8-Å resolution. The structure revealed an eight-stranded antiparallel β-sandwich motif resembling that of membrane-targeting C2 domains, including a bound calcium ion. We demonstrated that the FS domain mediates integrin binding and identified the binding site by mutagenesis. The mindin FS domain therefore represents a new integrin ligand. We further showed that mindin recognizes lipopolysaccharide (LPS) through its TSR domain, and obtained evidence that C-mannosylation of the TSR influences LPS binding. Through these dual interactions, the FS and TSR domains of mindin promote activation of both adaptive and innate immune responses. PMID:19153605

  17. Collision dynamics of methyl radicals and highly vibrationally excited molecules using crossed molecular beams

    SciTech Connect

    Chu, P.M.Y.

    1991-10-01

    The vibrational to translational (V{yields}T) energy transfer in collisions between large highly vibrationally excited polyatomics and rare gases was investigated by time-of-flight techniques. Two different methods, UV excitation followed by intemal conversion and infrared multiphoton excitation (IRMPE), were used to form vibrationally excited molecular beams of hexafluorobenzene and sulfur hexafluoride, respectively. The product translational energy was found to be independent of the vibrational excitation. These results indicate that the probability distribution function for V{yields}T energy transfer is peaked at zero. The collisional relaxation of large polyatomic molecules with rare gases most likely occurs through a rotationally mediated process. Photodissociation of nitrobenzene in a molecular beam was studied at 266 nm. Two primary dissociation channels were identified including simple bond rupture to produce nitrogen dioxide and phenyl radical and isomerization to form nitric oxide and phenoxy radical. The time-of-flight spectra indicate that simple bond rupture and isomerization occurs via two different mechanisms. Secondary dissociation of the phenoxy radicals to carbon monoxide and cyclopentadienyl radicals was observed as well as secondary photodissociation of phenyl radical to give H atom and benzyne. A supersonic methyl radical beam source is developed. The beam source configuration and conditions were optimized for CH{sub 3} production from the thermal decomposition of azomethane. Elastic scattering of methyl radical and neon was used to differentiate between the methyl radicals and the residual azomethane in the molecular beam.

  18. Modeling corrosion inhibition efficacy of small organic molecules as non-toxic chromate alternatives using comparative molecular surface analysis (CoMSA).

    PubMed

    Fernandez, Michael; Breedon, Michael; Cole, Ivan S; Barnard, Amanda S

    2016-10-01

    Traditionally many structural alloys are protected by primer coatings loaded with corrosion inhibiting additives. Strontium Chromate (or other chromates) have been shown to be extremely effectively inhibitors, and find extensive use in protective primer formulations. Unfortunately, hexavalent chromium which imbues these coatings with their corrosion inhibiting properties is also highly toxic, and their use is being increasingly restricted by legislation. In this work we explore a novel tridimensional Quantitative-Structure Property Relationship (3D-QSPR) approach, comparative molecular surface analysis (CoMSA), which was developed to recognize "high-performing" corrosion inhibitor candidates from the distributions of electronegativity, polarizability and van der Waals volume on the molecular surfaces of 28 small organic molecules. Multivariate statistical analysis identified five prototypes molecules, which are capable of explaining 71% of the variance within the inhibitor data set; whilst a further five molecules were also identified as archetypes, describing 75% of data variance. All active corrosion inhibitors, at a 80% threshold, were successfully recognized by the CoMSA model with adequate specificity and precision higher than 70% and 60%, respectively. The model was also capable of identifying structural patterns, that revealed reasonable starting points for where structural changes may augment corrosion inhibition efficacy. The presented methodology can be applied to other functional molecules and extended to cover structure-activity studies in a diverse range of areas such as drug design and novel material discovery. PMID:27362530

  19. A 160-kilobit molecular electronic memory patterned at 1011 bits per square centimetre

    NASA Astrophysics Data System (ADS)

    Green, Jonathan E.; Wook Choi, Jang; Boukai, Akram; Bunimovich, Yuri; Johnston-Halperin, Ezekiel; Deionno, Erica; Luo, Yi; Sheriff, Bonnie A.; Xu, Ke; Shik Shin, Young; Tseng, Hsian-Rong; Stoddart, J. Fraser; Heath, James R.

    2007-01-01

    The primary metric for gauging progress in the various semiconductor integrated circuit technologies is the spacing, or pitch, between the most closely spaced wires within a dynamic random access memory (DRAM) circuit. Modern DRAM circuits have 140nm pitch wires and a memory cell size of 0.0408μm2. Improving integrated circuit technology will require that these dimensions decrease over time. However, at present a large fraction of the patterning and materials requirements that we expect to need for the construction of new integrated circuit technologies in 2013 have `no known solution'. Promising ingredients for advances in integrated circuit technology are nanowires, molecular electronics and defect-tolerant architectures, as demonstrated by reports of single devices and small circuits. Methods of extending these approaches to large-scale, high-density circuitry are largely undeveloped. Here we describe a 160,000-bit molecular electronic memory circuit, fabricated at a density of 1011bitscm-2 (pitch 33nm memory cell size 0.0011μm2), that is, roughly analogous to the dimensions of a DRAM circuit projected to be available by 2020. A monolayer of bistable, [2]rotaxane molecules served as the data storage elements. Although the circuit has large numbers of defects, those defects could be readily identified through electronic testing and isolated using software coding. The working bits were then configured to form a fully functional random access memory circuit for storing and retrieving information.

  20. Therapeutic Opportunities in Damage-Associated Molecular Pattern-Driven Metabolic Diseases

    PubMed Central

    Garcia-Martinez, Irma; Shaker, Mohamed E.

    2015-01-01

    Abstract Significance: Sterile inflammation is a common finding present in various metabolic disorders. This type of inflammation is mediated by damage-associated molecular patterns (DAMPs) that are released upon cellular injury to activate pattern recognition receptors on innate immune cells and amplify organ damage. Recent Advances: In the last decade, DAMPs, such as high-mobility group protein B1, nucleic acids (DNA, RNA), adenosine triphosphate, and other metabolites, were found to contribute to the inflammatory response in diabetes, gout, obesity, steatohepatitis, and atherosclerosis. Varied receptors, including Toll-like receptors (TLRs), the purinergic P2X7 receptors, and nucleotide-binding domain, and leucine-rich repeat protein 3 (NLRP3)-inflammasome sense DAMPs and DAMP-like molecules and release the proinflammatory cytokines, interleukin (IL)-1β and IL-18. Critical Issues: Available therapeutic approaches that interfered with the signaling of TLRs, P2X7, NLRP3-inflammasome, and IL-1β showed encouraging results in metabolic diseases, which will be also highlighted in this review. Future Directions: It is important to understand the origination of DAMPs and how they contribute to the inflammatory response in metabolic disorders to develop selective and efficient therapeutics for intervention. Antioxid. Redox Signal. 23, 1305–1315. PMID:26055926

  1. Patterned graphone—a novel template for molecular packing

    NASA Astrophysics Data System (ADS)

    Reddy, C. D.; Zhang, Y. W.; Shenoy, V. B.

    2012-04-01

    Precise positioning and packing of nanoscale building blocks is essential for the fabrication of many nanoelectro-mechanical devices. Carrying out such manipulations at the nanoscale still remains a challenge. Here we propose the use of graphone domain arrays embedded in a graphene sheet as a template to precisely position and pack molecules. Our atomistic simulations show that a graphone domain is able to adopt well-defined three-dimensional geometries, which in turn create ‘energy wells’ to trap molecules by means of physisorption. Using the C60 molecule as a model block, the stable trapping conditions are identified. The present work presents a novel route to position and pack molecules for nanoengineering applications.

  2. Molecular Formula Identification Using Isotope Pattern Analysis and Calculation of Fragmentation Trees

    PubMed Central

    Dührkop, Kai; Hufsky, Franziska; Böcker, Sebastian

    2014-01-01

    We present the results of a fully automated de novo approach for identification of molecular formulas in the CASMI 2013 contest. Only results for Category 1 (molecular formula identification) were submitted. Our approach combines isotope pattern analysis and fragmentation pattern analysis and is completely independent from any (spectral and structural) database. We correctly identified the molecular formula for ten out of twelve challenges, being the best automated method competing in this category. PMID:26819880

  3. Two-dimensional model of resonant electron collisions with diatomic molecules and molecular cations

    NASA Astrophysics Data System (ADS)

    Vana, Martin; Hvizdos, David; Houfek, Karel; Curik, Roman; Greene, Chris H.; Rescigno, Thomas N.; McCurdy, C. William

    2016-05-01

    A simple model for resonant collisions of electrons with diatomic molecules with one electronic and one nuclear degree of freedom (2D model) which was solved numerically exactly within the time-independent approach was used to probe the local complex potential approximation and nonlocal approximation to nuclear dynamics of these collisions. This model was reformulated in the time-dependent picture and extended to model also electron collisions with molecular cations, especially with H2+.This model enables an assessment of approximate methods, such as the boomerang model or the frame transformation theory. We will present both time-dependent and time-independent results and show how we can use the model to extract deeper insight into the dynamics of the resonant collisions.

  4. 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

  5. Fungal innate immunity induced by bacterial microbe-associated molecular patterns (MAMPs)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants and animals detect bacterial presence through Microbe-Associated Molecular Patterns (MAMPs) which induce an innate immune response. The field of fungal-bacterial interaction at the molecular level is still in its infancy and very little is known about fungal molecular responses to bacteria, a...

  6. Invariance of molecular charge transport upon changes of extended molecule size and several related issues

    PubMed Central

    2016-01-01

    Summary As a sanity test for the theoretical method employed, studies on (steady-state) charge transport through molecular devices usually confine themselves to check whether the method in question satisfies the charge conservation. Another important test of the theory’s correctness is to check that the computed current does not depend on the choice of the central region (also referred to as the “extended molecule”). This work addresses this issue and demonstrates that the relevant transport and transport-related properties are indeed invariant upon changing the size of the extended molecule, when the embedded molecule can be described within a general single-particle picture (namely, a second-quantized Hamiltonian bilinear in the creation and annihilation operators). It is also demonstrates that the invariance of nonequilibrium properties is exhibited by the exact results but not by those computed approximately within ubiquitous wide- and flat-band limits (WBL and FBL, respectively). To exemplify the limitations of the latter, the phenomenon of negative differential resistance (NDR) is considered. It is shown that the exactly computed current may exhibit a substantial NDR, while the NDR effect is absent or drastically suppressed within the WBL and FBL approximations. The analysis done in conjunction with the WBLs and FBLs reveals why general studies on nonequilibrium properties require a more elaborate theoretical than studies on linear response properties (e.g., ohmic conductance and thermopower) at zero temperature. Furthermore, examples are presented that demonstrate that treating parts of electrodes adjacent to the embedded molecule and the remaining semi-infinite electrodes at different levels of theory (which is exactly what most NEGF-DFT approaches do) is a procedure that yields spurious structures in nonlinear ranges of current–voltage curves. PMID:27335734

  7. Kinetic modeling of molecular motors: pause model and parameter determination from single-molecule experiments

    NASA Astrophysics Data System (ADS)

    Morin, José A.; Ibarra, Borja; Cao, Francisco J.

    2016-05-01

    Single-molecule manipulation experiments of molecular motors provide essential information about the rate and conformational changes of the steps of the reaction located along the manipulation coordinate. This information is not always sufficient to define a particular kinetic cycle. Recent single-molecule experiments with optical tweezers showed that the DNA unwinding activity of a Phi29 DNA polymerase mutant presents a complex pause behavior, which includes short and long pauses. Here we show that different kinetic models, considering different connections between the active and the pause states, can explain the experimental pause behavior. Both the two independent pause model and the two connected pause model are able to describe the pause behavior of a mutated Phi29 DNA polymerase observed in an optical tweezers single-molecule experiment. For the two independent pause model all parameters are fixed by the observed data, while for the more general two connected pause model there is a range of values of the parameters compatible with the observed data (which can be expressed in terms of two of the rates and their force dependencies). This general model includes models with indirect entry and exit to the long-pause state, and also models with cycling in both directions. Additionally, assuming that detailed balance is verified, which forbids cycling, this reduces the ranges of the values of the parameters (which can then be expressed in terms of one rate and its force dependency). The resulting model interpolates between the independent pause model and the indirect entry and exit to the long-pause state model

  8. A modular molecular framework for utility in small-molecule solution-processed organic photovoltaic devices

    SciTech Connect

    Welch, Gregory C.; Perez, Louis A.; Hoven, Corey V.; Zhang, Yuan; Dang, Xuan-Dung; Sharenko, Alexander; Toney, Michael F.; Kramer, Edward J.; Nguyen, Thuc-Quyen; Bazan, Guillermo C.

    2011-07-22

    We report on the design, synthesis and characterization of light harvesting small molecules for use in solution-processed small molecule bulk heterojunction (SM-BHJ) solar cell devices. These molecular materials are based upon an acceptor/donor/acceptor (A/D/A) core with donor endcapping units. Utilization of a dithieno(3,2-b;2',3'-d)silole (DTS) donor and pyridal[2,1,3]thiadiazole (PT) acceptor leads to strong charge transfer characteristics, resulting in broad optical absorption spectra extending well beyond 700 nm. SM-BHJ solar cell devices fabricated with the specific example 5,5'-bis{7-(4-(5-hexylthiophen-2-yl)thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-c]pyridine}-3,3'-di-2-ethylhexylsilylene-2,2'-bithiophene (6) as the donor and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) as the acceptor component showed short circuit currents above -10 mA cm-2 and power conversion efficiencies (PCEs) over 3%. Thermal processing is a critical factor in obtaining favorable active layer morphologies and high PCE values. A combination of UV-visible spectroscopy, conductive and photo-conductive atomic force microscopies, dynamic secondary mass ion spectrometry (DSIMS), and grazing incident wide angle X-ray scattering (GIWAXS) experiments were carried out to characterize how thermal treatment influences the active layer structure and organization.

  9. Interpretation of atomic motion in flexible molecules: Accelerating molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Omelyan, Igor; Kovalenko, Andriy

    2012-02-01

    We propose a new approach to split up the velocities of atoms of flexible molecules into translational, rotational, and vibrational components. As a result, the kinetic energy of the system can easily be expressed in terms of only three parts related to the above components. This is distinct from the standard Eckart method, where the cumbersome Coriolis contribution to the kinetic energy appears additionally. The absence of such a contribution within the proposed approach allows us to readily extend the microcanonical multiple-time-step dynamics of flexible molecules to the canonical-isokinetic Nosé-Hoover chain ensemble by explicitly integrating the translational, orientational, and vibrational motion. The previous extensions dealt exclusively with translational degrees of freedom of separate atoms, leading to a limitation on the size of the outer time step of 100 femtoseconds. We show on molecular dynamics simulations of the flexible TIP3P water model that the new canonical-isokinetic formulation gives a possibility to significantly overcome this limitation. In particular, huge outer time steps of order from a few hundred femtoseconds up to several picoseconds can now be employed to study conformational properties without loss of accuracy.

  10. Predicting Molecular Targets for Small-Molecule Drugs with a Ligand-Based Interaction Fingerprint Approach.

    PubMed

    Cao, Ran; Wang, Yanli

    2016-06-20

    The computational prediction of molecular targets for small-molecule drugs remains a great challenge. Herein we describe a ligand-based interaction fingerprint (LIFt) approach for target prediction. Together with physics-based docking and sampling methods, we assessed the performance systematically by modeling the polypharmacology of 12 kinase inhibitors in three stages. First, we examined the capacity of this approach to differentiate true targets from false targets with the promiscuous binder staurosporine, based on native complex structures. Second, we performed large-scale profiling of kinase selectivity on the clinical drug sunitinib by means of computational simulation. Third, we extended the study beyond kinases by modeling the cross-inhibition of bromodomain-containing protein 4 (BRD4) for 10 well-established kinase inhibitors. On this basis, we made prospective predictions by exploring new kinase targets for the anticancer drug candidate TN-16, originally known as a colchicine site binder and microtubule disruptor. As a result, p38α was highlighted from a panel of 187 different kinases. Encouragingly, our prediction was validated by an in vitro kinase assay, which showed TN-16 as a low-micromolar p38α inhibitor. Collectively, our results suggest the promise of the LIFt approach in predicting potential targets for small-molecule drugs. PMID:26222196

  11. Encaged molecules in external electric fields: a molecular `tug-of-war'

    NASA Astrophysics Data System (ADS)

    Pathak, Rajeev; Gurav, Nalini; Gejji, Shridhar; Bartolotti, Libero

    We investigate applying ab initio theoretical methods, the molecules Hydrogen peroxide, H2O2, and Methanol, CH3OH, encaged in hydrogen-bonded water ``buckyballs'' (H2O)20 , subjected to an externally applied electric field. While the water-cage (host) tends to confine the guest-molecule, the external electric field tends to stretch it along with its labile hydrogen-bonded host, resulting into a molecular `tug-of-war'. We appraise these two competing effects in terms of the extent of `screening' of the host by the cage and compare the response of the composite system in the form of the consequent structural mutations, redistributions in the electron density and the electrostatic potential leading to emergence and suppression of the covalent O-H characteristic frequency shifts in the infra-red vibrational spectrum. This study brings forth the cooperative effect of hydrogen-bonding up to a maximally sustainable threshold electric field, beyond which fragmentation of the water cage occurs. Partial support from The Center for Development in Advanced Computing (C-DAC) in terms of Computer time on the PARAM Supercomputing facility at Pune, MH, India, is gratefully acknowledged.

  12. High-efficiency molecular counting in solution: Single-molecule detection in electrodynamically focused microdroplet streams

    SciTech Connect

    Lermer, N.; Barnes, M.D.; Kung, C.Y.; Whitten, W.B.; Ramsey, J.M.

    1997-06-01

    We report fluorescence detection of individual rhodamine 6G molecules using a linear quadrupole to focus streams of microdroplets through the waist of a counterpropagating cw Ar{sup +} laser. Since the terminal velocity scales as the square of the droplet diameter, the droplet-laser interaction time was `tunable` between 5 and 200 ms by using water samples spiked with a small, variable (2-5% v/v) amount of glycerol. Fluorescence bursts from droplets containing single molecules were clearly distinguished from the blanks in real time with an average signal-to-noise ratio of about 10, limited primarily by photobleaching and droplet size fluctuations (<1%). The volume throughput rates associated with this approach (approx. 10 pL/s) are roughly 10{sup 3} higher than those associated with particle levitation techniques, with minimal sacrifice in sensitivity. Total molecular detection efficiencies of about 80% (at >99% confidence) were obtained for 100 and 15 fM rhodamine 6G solutions, in good agreement with detailed theoretical calculations and statistical limitations. 39 refs., 7 figs., 1 tab.

  13. Exploring Molecular Complexity with ALMA: Deuterated complex organic molecules in Sgr B2

    NASA Astrophysics Data System (ADS)

    Belloche, A.; Müller, H. S. P.; Garrod, R. T.; Menten, K. M.

    2016-05-01

    Apart from the case of methanol, little is known about deuterium fractionation of complex organic molecules in the interstellar medium, especially in high mass star forming regions. We take advantage of the EMoCA spectral line survey to search for deuterated complex organic molecules toward the hot molecular core Sgr B2(N2). We report the secure detection of CH2DCN with a deuteration level of 0.4% and tentative detections of CH2DOH, CH2DCH2CN, CH3CHDCN, and DC3N with levels in the range 0.05-0.12%. Except for methyl cyanide, the measured deuteration levels lie at least a factor of four below the predictions of current astrochemical models. They are also lower than in Orion KL by a factor of a few up to a factor ten. These discrepancies and differences may be due to the higher temperatures that prevail in the Galactic Center region compared to nearby clouds, or they may result from a lower overall abundance of deuterium itself in the Galactic Center region by up to a factor ten.

  14. Single molecule molecular inversion probes for targeted, high-accuracy detection of low-frequency variation

    PubMed Central

    Hiatt, Joseph B.; Pritchard, Colin C.; Salipante, Stephen J.; O'Roak, Brian J.; Shendure, Jay

    2013-01-01

    The detection and quantification of genetic heterogeneity in populations of cells is fundamentally important to diverse fields, ranging from microbial evolution to human cancer genetics. However, despite the cost and throughput advances associated with massively parallel sequencing, it remains challenging to reliably detect mutations that are present at a low relative abundance in a given DNA sample. Here we describe smMIP, an assay that combines single molecule tagging with multiplex targeted capture to enable practical and highly sensitive detection of low-frequency or subclonal variation. To demonstrate the potential of the method, we simultaneously resequenced 33 clinically informative cancer genes in eight cell line and 45 clinical cancer samples. Single molecule tagging facilitated extremely accurate consensus calling, with an estimated per-base error rate of 8.4 × 10−6 in cell lines and 2.6 × 10−5 in clinical specimens. False-positive mutations in the single molecule consensus base-calls exhibited patterns predominantly consistent with DNA damage, including 8-oxo-guanine and spontaneous deamination of cytosine. Based on mixing experiments with cell line samples, sensitivity for mutations above 1% frequency was 83% with no false positives. At clinically informative sites, we identified seven low-frequency point mutations (0.2%–4.7%), including BRAF p.V600E (melanoma, 0.2% alternate allele frequency), KRAS p.G12V (lung, 0.6%), JAK2 p.V617F (melanoma, colon, two lung, 0.3%–1.4%), and NRAS p.Q61R (colon, 4.7%). We anticipate that smMIP will be broadly adoptable as a practical and effective method for accurately detecting low-frequency mutations in both research and clinical settings. PMID:23382536

  15. The molecular chaperone calnexin facilitates folding and assembly of class I histocompatibility molecules.

    PubMed Central

    Vassilakos, A; Cohen-Doyle, M F; Peterson, P A; Jackson, M R; Williams, D B

    1996-01-01

    Calnexin, a membrane protein of the endoplasmic reticulum, is generally thought to function as a molecular chaperone, based on indirect or correlative evidence. To examine calnexin's functions more directly, we reconstituted the assembly of class I histocompatibility molecules in the absence or presence of calnexin in Drosophila melanogaster cells. Calnexin enhanced the assembly of class I heavy chains with beta 2-microglobulin as much as 5-fold. The improved assembly appeared largely due to more efficient folding of heavy chains, as evidenced by increased reactivity with a conformation-sensitive monoclonal antibody and by a reduction in the level of aggregates. Similar findings were obtained in mouse or human cells when the interaction of calnexin with class I heavy chains was prevented by treatment with the oligosaccharide processing inhibitor castanospermine. The ability of calnexin to facilitate castanospermine. The ability of calnexin to facilitate heavy chain folding and to prevent the formation of aggregates provides compelling evidence that calnexin functions as a bona fide molecular chaperone. Images PMID:8612572

  16. Molecular dynamics simulation studies of hyperbranched polyglycerols and their encapsulation behaviors of small drug molecules.

    PubMed

    Yu, Chunyang; Ma, Li; Li, Ke; Li, Shanlong; Liu, Yannan; Zhou, Yongfeng; Yan, Deyue

    2016-08-10

    Hyperbranched polyglycerol (HPG) is one of the most important hyperbranched polymers (HBPs) due to its interesting properties and applications. Herein, the conformation of HPGs depending on the degree of polymerization (DP) and the degree of branching (DB) is investigated explicitly by molecular dynamics simulations. This study shows that the radius of gyration (Rg) scales as Rg ∼ DP(1/3), which is in close agreement with the result of the SANS experiment. For HPGs with the same DP, the radius of gyration, asphericities and solvent accessible surface area all monotonically decrease with the increase of DB; while for HPGs with the same DB, the molecular anisotropy decreases with the increase of DP. The radial density investigation discloses that the cavities are randomly distributed in the interior of the HPG core to support the "dendritic box effect", which can be used to encapsulate the guest molecules. Interestingly, the terminal groups of HPGs with a high Wiener index (WI) are more favorable to fold back into the interiors than those with the low WI when in water. For the hyperbranched multi-arm copolymer with a HPG core and many polyethylene glycol (PEG) arms, drug encapsulation studies show that the PEG caps can not only effectively prevent tamoxifen from leaving the HPG core, but also encapsulate tamoxifen inside the PEG chains. These simulation results have provided more details for understanding the structure-property relationships of HPGs in water. PMID:27465863

  17. A titanosilicate molecular sieve with adjustable pores for size-selective adsorption of molecules.

    PubMed

    Kuznicki, S M; Bell, V A; Nair, S; Hillhouse, H W; Jacubinas, R M; Braunbarth, C M; Toby, B H; Tsapatsis, M

    2001-08-16

    Zeolites and related crystalline microporous oxides-tetrahedrally coordinated atoms covalently linked into a porous framework-are of interest for applications ranging from catalysis to adsorption and ion-exchange. In some of these materials (such as zeolite rho) adsorbates, ion-exchange, and dehydration and cation relocation can induce strong framework deformations. Similar framework flexibility has to date not been seen in mixed octahedral/tetrahedral microporous framework materials, a newer and rapidly expanding class of molecular sieves. Here we show that the framework of the titanium silicate ETS-4, the first member of this class of materials, can be systematically contracted through dehydration at elevated temperatures to 'tune' the effective size of the pores giving access to the interior of the crystal. We show that this so-called 'molecular gate' effect can be used to tailor the adsorption properties of the materials to give size-selective adsorbents suitable for commercially important separations of gas mixtures of molecules with similar size in the 4.0 to 3.0 A range, such as that of N2/CH4, Ar/O2 and N2/O2. PMID:11507636

  18. Planar Microdevices Enhance Transport of Large Molecular Weight Molecules Across Retinal Pigment Epithelial Cells

    PubMed Central

    Wade, Jennifer S.; Desai, Tejal A.

    2014-01-01

    Large molecular weight drug delivery to the posterior eye is challenging due to cellular barriers that hinder drug transport. Understanding how to enhance transport across the retinal barrier is important for the design of new drug delivery systems. A novel mechanism to enhance drug transport is the use of geometric properties, which has not been extensively explored in the retina. Planar SU-8/ Poly(ethyleneglycol)dimethacrylate microdevices were constructed using photolithography to deliver FITC dextran across an in vitro retinal model. The model consists of retinal pigment epithelial (RPE) cells grown to confluence on transwell inserts, which provides an environment to investigate the influence of geometry on paracellular and transcellular delivery of encapsulated large molecules. Planar microdevices enhanced transport of large molecular weight dextrans across different models of RPE in a size dependent fashion. Increased drug permeation across the RPE was observed with the addition of microdevices as compared to a traditional bolus of FITC dextran. This phenomena was initiated by a non-toxic interaction between the microdevices and the retinal tight junction proteins. Suggesting that increased drug transport occurs via a paracellular pathway. These experiments provide evidence to support the future use of planar unidirectional microdevices for delivery of biologics in ocular applications. PMID:24789225

  19. Molecular quantum spintronics: supramolecular spin valves based on single-molecule magnets and carbon nanotubes.

    PubMed

    Urdampilleta, Matias; Nguyen, Ngoc-Viet; Cleuziou, Jean-Pierre; Klyatskaya, Svetlana; Ruben, Mario; Wernsdorfer, Wolfgang

    2011-01-01

    We built new hybrid devices consisting of chemical vapor deposition (CVD) grown carbon nanotube (CNT) transistors, decorated with TbPc(2) (Pc = phthalocyanine) rare-earth based single-molecule magnets (SMMs). The drafting was achieved by tailoring supramolecular π-π interactions between CNTs and SMMs. The magnetoresistance hysteresis loop measurements revealed steep steps, which we can relate to the magnetization reversal of individual SMMs. Indeed, we established that the electronic transport properties of these devices depend strongly on the relative magnetization orientations of the grafted SMMs. The SMMs are playing the role of localized spin polarizer and analyzer on the CNT electronic conducting channel. As a result, we measured magneto-resistance ratios up to several hundred percent. We used this spin valve effect to confirm the strong uniaxial anisotropy and the superparamagnetic blocking temperature (T(B) ~ 1 K) of isolated TbPc(2) SMMs. For the first time, the strength of exchange interaction between the different SMMs of the molecular spin valve geometry could be determined. Our results introduce a new design for operable molecular spintronic devices using the quantum effects of individual SMMs. PMID:22072910

  20. Room-temperature repositioning of individual C60 molecules at Cu steps: Operation of a molecular counting device

    NASA Astrophysics Data System (ADS)

    Cuberes, M. T.; Schlittler, R. R.; Gimzewski, J. K.

    1996-11-01

    C60 molecules absorbed on a monoatomic Cu step have been reversibly repositioned at room temperature with the tip of a scanning tunneling microscope by performing controlled displacements along the step direction. We demonstrate the feasibility of building an abacus on the nanometer scale using single molecules as ``counters,'' Cu monoatomic steps as ``rods'' that constrain the molecular motion to one dimension, and the scanning tunneling microscope as an ``actuator'' for counting operations.

  1. Trapping cold molecules and atoms: Simultaneous magnetic deceleration and trapping of cold molecular Oxygen with Lithium atoms

    NASA Astrophysics Data System (ADS)

    Akerman, Nitzan; Karpov, Michael; Segev, Yair; Bibelink, Natan; Narevicius, Julia; Narevicius, Edvardas

    2016-05-01

    Cooling molecules to the ultra-cold regime remains a major challenge in the growing field of cold molecules. The molecular internal degrees of freedom complicate the effort of direct application of laser cooling. An alternative and general path towards ultra-cold molecules relies on sympathetic cooling via collisions with laser-cooled atoms. Here, we demonstrate the first step towards application of sympathetic cooling by co-trapping of molecular Oxygen with Lithium atoms in a magnetic trap at a temperature of 300 mK. Our experiment begins with a pulsed supersonic beam which is a general source for cold high-flux atomic and molecular beams. Although the supersonic expansion efficiently cools the beam to temperatures below 1K, it also accelerates the beam to high mean velocities. We decelerate a beam of O2 in a moving magnetic trap decelerator from 375 m/s to a stop. We entrained the molecular beam with Li atoms by laser ablation prior to deceleration. The deceleration ends with loading the molecules and atoms into a static quadrupole trap, which is generated by two permanent magnets. We estimate 109 trapped molecules with background limited lifetime of 0.6 Sec. Our achievement enables application of laser cooling on the Li atoms in order to sympathetically cool the O2.

  2. A molecular symmetry analysis of the electronic states and transition dipole moments for molecules with two torsional degrees of freedom

    SciTech Connect

    Obaid, R.; Leibscher, M.

    2015-02-14

    We present a molecular symmetry analysis of electronic states and transition dipole moments for molecules which undergo large amplitude intramolecular torsions. The method is based on the correlation between the point group of the molecule at highly symmetric configurations and the molecular symmetry group. As an example, we determine the global irreducible representations of the electronic states and transition dipole moments for the quinodimethane derivative 2-[4-(cyclopenta-2,4-dien-1-ylidene)cyclohexa-2,5-dien-1-ylidene]-2H-1, 3-dioxole for which two torsional degrees of freedom can be activated upon photo-excitation and construct the resulting symmetry adapted transition dipole functions.

  3. Reconstruction of two-dimensional molecular structure with laser-induced electron diffraction from laser-aligned polyatomic molecules

    DOE PAGESBeta

    Yu, Chao; Wei, Hui; Wang, Xu; Le, Anh -Thu; Lu, Ruifeng; Lin, C. D.

    2015-10-27

    Imaging the transient process of molecules has been a basic way to investigate photochemical reactions and dynamics. Based on laser-induced electron diffraction and partial one-dimensional molecular alignment, here we provide two effective methods for reconstructing two-dimensional structure of polyatomic molecules. We demonstrate that electron diffraction images in both scattering angles and broadband energy can be utilized to retrieve complementary structure information, including positions of light atoms. Lastly, with picometre spatial resolution and the inherent femtosecond temporal resolution of lasers, laser-induced electron diffraction method offers significant opportunities for probing atomic motion in a large molecule in a typical pump-probe measurement.

  4. Reconstruction of two-dimensional molecular structure with laser-induced electron diffraction from laser-aligned polyatomic molecules

    PubMed Central

    Yu, Chao; Wei, Hui; Wang, Xu; Le, Anh-Thu; Lu, Ruifeng; Lin, C. D.

    2015-01-01

    Imaging the transient process of molecules has been a basic way to investigate photochemical reactions and dynamics. Based on laser-induced electron diffraction and partial one-dimensional molecular alignment, here we provide two effective methods for reconstructing two-dimensional structure of polyatomic molecules. We demonstrate that electron diffraction images in both scattering angles and broadband energy can be utilized to retrieve complementary structure information, including positions of light atoms. With picometre spatial resolution and the inherent femtosecond temporal resolution of lasers, laser-induced electron diffraction method offers significant opportunities for probing atomic motion in a large molecule in a typical pump-probe measurement. PMID:26503116

  5. On the widths of Stokes lines in Raman scattering from molecules adsorbed at metal surfaces and in molecular conduction junctions

    NASA Astrophysics Data System (ADS)

    Gao, Yi; Galperin, Michael; Nitzan, Abraham

    2016-06-01

    Within a generic model we analyze the Stokes linewidth in surface enhanced Raman scattering (SERS) from molecules embedded as bridges in molecular junctions. We identify four main contributions to the off-resonant Stokes signal and show that under zero voltage bias (a situation pertaining also to standard SERS experiments) and at low bias junctions only one of these contributions is pronounced. The linewidth of this component is determined by the molecular vibrational relaxation rate, which is dominated by interactions with the essentially bosonic thermal environment when the relevant molecular electronic energy is far from the metal(s) Fermi energy(ies). It increases when the molecular electronic level is close to the metal Fermi level so that an additional vibrational relaxation channel due to electron-hole (eh) exciton in the molecule opens. Other contributions to the Raman signal, of considerably broader linewidths, can become important at larger junction bias.

  6. Evolution of complex organic molecules in hot molecular cores. Synthetic spectra at (sub-)mm wavebands

    NASA Astrophysics Data System (ADS)

    Choudhury, R.; Schilke, P.; Stéphan, G.; Bergin, E.; Möller, T.; Schmiedeke, A.; Zernickel, A.

    2015-03-01

    Context. Hot molecular cores (HMCs) are intermediate stages of high-mass star formation and are also known for their rich chemical reservoirs and emission line spectra at (sub-)mm wavebands. Complex organic molecules (COMs) such as methanol (CH3OH), ethanol (C2H5OH), dimethyl ether (CH3OCH3), and methyl formate (HCOOCH3) produce most of these observed lines. The observed spectral feature of HMCs such as total number of emission lines and associated line intensities are also found to vary with evolutionary stages. Aims: We aim to investigate the spectral evolution of these COMs to explore the initial evolutionary stages of high-mass star formation including HMCs. Methods: We developed various 3D models for HMCs guided by the evolutionary scenarios proposed by recent empirical and modeling studies. We then investigated the spatio-temporal variation of temperature and molecular abundances in HMCs by consistently coupling gas-grain chemical evolution with radiative transfer calculations. We explored the effects of varying physical conditions on molecular abundances including density distribution and luminosity evolution of the central protostar(s) among other parameters. Finally, we simulated the synthetic spectra for these models at different evolutionary timescales to compare with observations. Results: Temperature has a profound effect on the formation of COMs through the depletion and diffusion on grain surface to desorption and further gas-phase processing. The time-dependent temperature structure of the hot core models provides a realistic framework for investigating the spatial variation of ice mantle evaporation as a function of evolutionary timescales. We find that a slightly higher value (15 K) than the canonical dark cloud temperature (10 K) provides a more productive environment for COM formation on grain surface. With increasing protostellar luminosity, the water ice evaporation font (~100 K) expands and the spatial distribution of gas phase abundances of

  7. Targeted Polymeric Nanoparticles for Brain Delivery of High Molecular Weight Molecules in Lysosomal Storage Disorders

    PubMed Central

    Belletti, Daniela; D’Avanzo, Francesca; Pederzoli, Francesca; Ruozi, Barbara; Marin, Oriano; Vandelli, Maria Angela; Forni, Flavio; Scarpa, Maurizio; Tomanin, Rosella; Tosi, Giovanni

    2016-01-01

    Lysosomal Storage Disorders (LSDs) are a group of metabolic syndromes, each one due to the deficit of one lysosomal enzyme. Many LSDs affect most of the organ systems and overall about 75% of the patients present neurological impairment. Enzyme Replacement Therapy, although determining some systemic clinical improvements, is ineffective on the CNS disease, due to enzymes' inability to cross the blood-brain barrier (BBB). With the aim to deliver the therapeutic enzymes across the BBB, we here assayed biodegradable and biocompatible PLGA-nanoparticles (NPs) in two murine models for LSDs, Mucopolysaccharidosis type I and II (MPS I and MPS II). PLGA-NPs were modified with a 7-aminoacid glycopeptide (g7), yet demonstrated to be able to deliver low molecular weight (MW) molecules across the BBB in rodents. We specifically investigated, for the first time, the g7-NPs ability to transfer a model drug (FITC-albumin) with a high MW, comparable to the enzymes to be delivered for LSDs brain therapy. In vivo experiments, conducted on wild-type mice and knockout mouse models for MPS I and II, also included a whole series of control injections to obtain a broad preliminary view of the procedure efficiency. Results clearly showed efficient BBB crossing of albumin in all injected mice, underlying the ability of NPs to deliver high MW molecules to the brain. These results encourage successful experiments with enzyme-loaded g7-NPs to deliver sufficient amounts of the drug to the brain district on LSDs, where exerting a corrective effect on the pathological phenotype. PMID:27228099

  8. Molecular dynamics study of structure H clathrate hydrates of methane and large guest molecules.

    PubMed

    Susilo, Robin; Alavi, Saman; Ripmeester, John A; Englezos, Peter

    2008-05-21

    Methane storage in structure H (sH) clathrate hydrates is attractive due to the relatively higher stability of sH as compared to structure I methane hydrate. The additional stability is gained without losing a significant amount of gas storage density as happens in the case of structure II (sII) methane clathrate. Our previous work has showed that the selection of a specific large molecule guest substance (LMGS) as the sH hydrate former is critical in obtaining the optimum conditions for crystallization kinetics, hydrate stability, and methane content. In this work, molecular dynamics simulations are employed to provide further insight regarding the dependence of methane occupancy on the type of the LMGS and pressure. Moreover, the preference of methane molecules to occupy the small (5(12)) or medium (4(3)5(6)6(3)) cages and the minimum cage occupancy required to maintain sH clathrate mechanical stability are examined. We found that thermodynamically, methane occupancy depends on pressure but not on the nature of the LMGS. The experimentally observed differences in methane occupancy for different LMGS may be attributed to the differences in crystallization kinetics and/or the nonequilibrium conditions during the formation. It is also predicted that full methane occupancies in both small and medium clathrate cages are preferred at higher pressures but these cages are not fully occupied at lower pressures. It was found that both small and medium cages are equally favored for occupancy by methane guests and at the same methane content, the system suffers a free energy penalty if only one type of cage is occupied. The simulations confirm the instability of the hydrate when the small and medium cages are empty. Hydrate decomposition was observed when less than 40% of the small and medium cages are occupied. PMID:18500878

  9. Molecular dynamics study of structure H clathrate hydrates of methane and large guest molecules

    NASA Astrophysics Data System (ADS)

    Susilo, Robin; Alavi, Saman; Ripmeester, John A.; Englezos, Peter

    2008-05-01

    Methane storage in structure H (sH) clathrate hydrates is attractive due to the relatively higher stability of sH as compared to structure I methane hydrate. The additional stability is gained without losing a significant amount of gas storage density as happens in the case of structure II (sII) methane clathrate. Our previous work has showed that the selection of a specific large molecule guest substance (LMGS) as the sH hydrate former is critical in obtaining the optimum conditions for crystallization kinetics, hydrate stability, and methane content. In this work, molecular dynamics simulations are employed to provide further insight regarding the dependence of methane occupancy on the type of the LMGS and pressure. Moreover, the preference of methane molecules to occupy the small (512) or medium (435663) cages and the minimum cage occupancy required to maintain sH clathrate mechanical stability are examined. We found that thermodynamically, methane occupancy depends on pressure but not on the nature of the LMGS. The experimentally observed differences in methane occupancy for different LMGS may be attributed to the differences in crystallization kinetics and/or the nonequilibrium conditions during the formation. It is also predicted that full methane occupancies in both small and medium clathrate cages are preferred at higher pressures but these cages are not fully occupied at lower pressures. It was found that both small and medium cages are equally favored for occupancy by methane guests and at the same methane content, the system suffers a free energy penalty if only one type of cage is occupied. The simulations confirm the instability of the hydrate when the small and medium cages are empty. Hydrate decomposition was observed when less than 40% of the small and medium cages are occupied.

  10. Stochastic switching in gene networks can occur by a single-molecule event or many molecular steps.

    PubMed

    Choi, Paul J; Xie, X Sunney; Shakhnovich, Eugene I

    2010-02-12

    Due to regulatory feedback, biological networks can exist stably in multiple states, leading to heterogeneous phenotypes among genetically identical cells. Random fluctuations in protein numbers, tuned by specific molecular mechanisms, have been hypothesized to drive transitions between these different states. We develop a minimal theoretical framework to analyze the limits of switching in terms of simple experimental parameters. Our model identifies and distinguishes between two distinct molecular mechanisms for generating stochastic switches. In one class of switches, the stochasticity of a single-molecule event, a specific and rare molecular reaction, directly controls the macroscopic change in a cell's state. In the second class, no individual molecular event is significant, and stochasticity arises from the propagation of biochemical noise through many molecular pathways and steps. As an example, we explore switches based on protein-DNA binding fluctuations and predict relations between transcription factor kinetics, absolute switching rate, robustness, and efficiency that differentiate between switching by single-molecule events or many molecular steps. Finally, we apply our methods to recent experimental data on switching in Escherichia coli lactose metabolism, providing quantitative interpretations of a single-molecule switching mechanism. PMID:19931280

  11. In situ patterning of organic molecules in aqueous solutions using an inverted electron-beam lithography system

    NASA Astrophysics Data System (ADS)

    Miyazako, Hiroki; Ishihara, Kazuhiko; Mabuchi, Kunihiko; Hoshino, Takayuki

    2016-06-01

    A method for in situ controlling the detachment and deposition of organic molecules such as sugars and biocompatible polymers in aqueous solutions by electron-beam (EB) scan is proposed and evaluated. It was demonstrated that EB irradiation could detach 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers from a silicon nitride membrane. Moreover, organic molecules such as cationic polymers and sugars could be deposited on the membrane by EB irradiation. Spatial distributions of scattered electrons were numerically simulated, and acceleration voltage dependences of the detachment and deposition phenomena were experimentally measured. The simulations and experimental results suggest that the detachment of MPC polymers is mainly due to electrical effects of primary electrons, and that the deposition of organic molecules is mainly due to chemical reactions induced by primary electrons. In view of these findings, the proposed method can be applied to in situ and nanoscale patterning such as the fabrication of cell scaffolds.

  12. Liquid-helium temperature long-path infrared spectroscopy of molecular clusters and supercooled molecules

    NASA Astrophysics Data System (ADS)

    Bauerecker, Sigurd; Taraschewski, Michael; Weitkamp, Claus; Cammenga, Heiko K.

    2001-10-01

    Collisional cooling and supersonic jet expansion both allow us to perform infrared spectroscopy of supercooled molecules and atomic and molecular clusters. Collisional cooling has the advantage of higher sensitivity per molecule and enables working in thermal equilibrium. A new powerful method of collisional cooling is presented in this article. It is based on a cooling cell with integrated temperature-invariant White optics and pulsed or continuous sample-gas inlet. The system can be cooled with liquid nitrogen or liquid helium and operated at gas pressures between <10-5 and 13 bar. Temperatures range from 4.2 to 400 K and can be adjusted to an accuracy of ±0.2 K over most of the useable range. A three-zone heating design allows homogeneous or inhomogeneous temperature distributions. Optical path lengths can be selected up to values of 20 m for Fourier transform infrared (FTIR) and 40 m for laser operation. The cell axis is vertical, so optical windows are at room temperature. Diffusive trapping shields and low-power electric heating keep the mirrors free from perturbing deposits. The cell can be operated in a dynamic buffer-gas flow-cooling mode. A comprehensive review of existing collisional cooling cells is given. The formation of CO clusters from the gas phase was investigated using FTIR spectroscopy. For the isotope mixture consisting of 13C16O,13C18O, and 12C16O, a conspicuous change in the main spectroscopic structure of the clusters was observed between 20 and 5 K. The cluster bandwidth of the main isotope 13C16O triples. This behavior could be interpreted as a change from the crystalline to the amorphous state or as a decrease in size to smaller clusters with relatively larger surfaces. To our knowledge, this is the first IR investigation of molecular clusters obtained by collisional cooling in this temperature range. For CO2 the change from the monomer to crystalline clusters was investigated. The observed spectra vary considerably with temperature

  13. Biomimicry issues: the quest for sensing molecules at the origin of life using molecularly imprinter polymer

    NASA Astrophysics Data System (ADS)

    Carbonnier, Benjamin; Chehimi, Mohamed M.; Bakas, Idriss; Salmi, Zakaria; Mazerie, Isabelle; Floner, Didier; Geneste, Florence; Guerrouache, Mohamed

    The use of real time sensing analysis is becoming very popular in many applications and research areas such as, environment and agriculture for in situ monitoring of contaminants and food safety analysis, fundamental biology for studying for example protein-membrane interactions or drug discovery, health research for clinical diagnosis.[1] More recently, chip technology involving antibody-based detection system has been envisioned to search for life outside the Earth with a specific focus on Mars. [2] Sensors using such natural receptors are usually costly and suffer from the unstability of the surface-immobilized receptors. In this respect, the use of synthetic receptors appears as a very promising approach. Molecularly imprinting is undoubtedly one of the most promising approaches for designing biomimetic materials. In this respect, sensing microdevices based on molecularly imprinted polymers (MIPs) have attracted a great deal of interest over the recent years given their ability to recognize specifically and selectively molecules, proteins and even microorganisms, with excellent detection limits. MIPs can be prepared as powders, colloids and ultrathin films. The latter option is particularly interesting because it limits diffusion of the analytes to the artificial receptor sites within the sensing layers [3] and facilitates the making of nanostructured MIP grafts [4]. In addition, MIP sensing ultrathin layers are amenable to the detection of the analytes with varied transducing methods among which electrochemistry, a simple, versatile and easy to implement technique is very appealing to detect analytes concentrations in the picomolar or sub-picomolar range [5]. In this contribution, the important parameters in obtaining molecularly imprinted polymer layers grafted on gold working electrodes and exhibiting high sensitivity towards acid and base molecules are addressed. Square wave voltammetry is demonstrated to be a very powerful electroanalytical while the limit

  14. Limited-projection-angle hybrid fluorescence molecular tomography of multiple molecules.

    PubMed

    Radrich, Karin; Mohajerani, Pouyan; Bussemer, Johanna; Schwaiger, Markus; Beer, Ambros J; Ntziachristos, Vasilis

    2014-04-01

    An advantage of fluorescence methods over other imaging modalities is the ability to concurrently resolve multiple moieties using fluorochromes emitting at different spectral regions. Simultaneous imaging of spectrally separated agents is helpful in interrogating multiple functions or establishing internal controls for accurate measurements. Herein, we investigated multimoiety imaging in the context of a limited-projection-angle hybrid fluorescence molecular tomography (FMT), and x-ray computed tomography implementation and the further registration with positron emission tomography (PET) data. Multichannel FMT systems may image fluorescent probes of varying distribution patterns. Therefore, it is possible that different channels may require different use of priors and regularization parameters. We examined the performance of automatically estimating regularization factors implementing priors, using data-driven regularization specific for limited-projection-angle schemes. We were particularly interested in identifying the implementation variations between hybrid-FMT channels due to probe distribution variation. For this reason, initial validation of the data-driven algorithm on a phantom was followed by imaging different agent distributions in animals, assuming superficial and deep seated activity. We further demonstrate the benefits of combining hybrid FMT with PET to gain multiple readings on the molecular composition of disease. PMID:24770661

  15. Pattern Speeds of BIMA SONG Galaxies with Molecule-dominated Interstellar Mediums Using the Tremaine-Weinberg Method

    NASA Astrophysics Data System (ADS)

    Rand, Richard J.; Wallin, John F.

    2004-10-01

    We apply the Tremaine-Weinberg method of pattern speed determination to data cubes of CO emission in six spiral galaxies from the BIMA Survey of Nearby Galaxies, each with an interstellar medium dominated by molecular gas. We compare derived pattern speeds with estimates based on other methods, usually involving the identification of a predicted behavior at one or more resonances of the pattern(s). In two cases (NGC 1068 and NGC 4736), we find evidence for a central bar pattern speed that is greater than that of the surrounding spiral and roughly consistent with previous estimates. However, the spiral pattern speed in both cases is much larger than previous determinations. For the barred spirals NGC 3627 and NGC 4321, the method is insensitive to the bar pattern speed (the bar in each is nearly parallel to the major axis; in this case the method will not work), but for the former galaxy the spiral pattern speed found agrees with previous estimates of the bar pattern speed, suggesting that these two structures are part of a single pattern. For the latter, the spiral pattern speed found is in agreement with several previous determinations. For the flocculent spiral NGC 4414 and the ``Evil Eye'' galaxy NGC 4826, the method does not support the presence of a large-scale coherent pattern. We also apply the method to a simulated barred galaxy in order to demonstrate its validity and to understand its sensitivity to various observational parameters. In addition, we study the results of applying the method to a simulated, clumpy axisymmetric disk with no wave present. The Tremaine & Weinberg method in this case may falsely indicate a well-defined pattern.

  16. PDMS-Glass bonding using grafted polymeric adhesive - Alternative process flow for compatibility with patterned biological molecules

    PubMed Central

    Beh, Cyrus Weijie; Zhou, Weizhuang

    2013-01-01

    We report a novel modification of silicone elastomer, polydimethylsiloxane (PDMS) with a polymer graft that allows interfacial bonding between elastomer and glass substrate to be performed without exposure of said substrate to harsh treatment conditions like oxygen plasma. Organic molecules can thus be patterned within microfluidic channels and still remain functional post-bonding. In addition, after polymer grafting the PDMS can be stored in a desiccator for at least 40 days, and activated upon exposure to acidic buffer for bonding. The bonded devices remain fully bonded in excess of 80 psi driving pressure, with no signs of compromise to the bond integrity. Finally, we demonstrate the compatibility of our method with biological molecules using a proof-of-concept DNA sensing device, in which fluorescently-labelled DNA targets are successfully captured by a patterned probe in a device sealed using our method, while the pattern on a plasma-treated device was completely destroyed. Therefore, this method provides a much-needed alternative bonding process for incorporation of biological molecules in microfluidic devices. PMID:22858861

  17. Molecular-scale quantitative charge density measurement of biological molecule by frequency modulation atomic force microscopy in aqueous solutions

    NASA Astrophysics Data System (ADS)

    Umeda, Kenichi; Kobayashi, Kei; Oyabu, Noriaki; Matsushige, Kazumi; Yamada, Hirofumi

    2015-07-01

    Surface charge distributions on biological molecules in aqueous solutions are essential for the interactions between biomolecules, such as DNA condensation, antibody-antigen interactions, and enzyme reactions. There has been a significant demand for a molecular-scale charge density measurement technique for better understanding such interactions. In this paper, we present the local electric double layer (EDL) force measurements on DNA molecules in aqueous solutions using frequency modulation atomic force microscopy (FM-AFM) with a three-dimensional force mapping technique. The EDL forces measured in a 100 mM KCl solution well agreed with the theoretical EDL forces calculated using reasonable parameters, suggesting that FM-AFM can be used for molecular-scale quantitative charge density measurements on biological molecules especially in a highly concentrated electrolyte.

  18. Molecular-Counting-Free and Electrochemiluminescent Single-Molecule Immunoassay with Dual-Stabilizers-Capped CdSe Nanocrystals as Labels.

    PubMed

    Zhang, Xin; Zhang, Bin; Miao, Wujian; Zou, Guizheng

    2016-05-17

    Biorelated single-molecule detection (SMD) has been achieved typically by imaging the redox fluorescent labels and then determining each label one by one. Herein, we demonstrated that the capping agents (i.e., mercaptopropionic acid and sodium hexametaphosphate) can facilitate the electrochemical involved hole (or electron) injecting process and improve the stability of the dual-stabilizers-capped CdSe nanocrystals (NCs), so that the CdSe NCs could be electrochemically and repeatedly inspired to excited states by giving off electrochemiluminescence (ECL) in a cyclic pattern. With the CdSe NCs as ECL label and carcinoembryonic antigen (CEA) as target molecule, a convenient single-molecule immunoassay was proposed by simply detecting the ECL intensity of the dual-stabilizers-capped CdSe NCs in a sandwich-typed immune complex. The limit of detection is 0.10 fg/mL at S/N = 3, which corresponds to about 6-8 CEA molecules in 20 μL of serum sample. Importantly, the ECL spectra of both CdSe NCs and its conjugate with probe antigen in the immune complex were almost identical to the photoluminescence spectrum of bare CdSe NCs, indicating that all emissions were originated from the same excited species. The molecular-counting-free and ECL-based SMD might be a promising alternative to the fluorescent SMD. PMID:27118637

  19. Plant immunity triggered by engineered in vivo release of oligogalacturonides, damage-associated molecular patterns.

    PubMed

    Benedetti, Manuel; Pontiggia, Daniela; Raggi, Sara; Cheng, Zhenyu; Scaloni, Flavio; Ferrari, Simone; Ausubel, Frederick M; Cervone, Felice; De Lorenzo, Giulia

    2015-04-28

    Oligogalacturonides (OGs) are fragments of pectin that activate plant innate immunity by functioning as damage-associated molecular patterns (DAMPs). We set out to test the hypothesis that OGs are generated in planta by partial inhibition of pathogen-encoded polygalacturonases (PGs). A gene encoding a fungal PG was fused with a gene encoding a plant polygalacturonase-inhibiting protein (PGIP) and expressed in transgenic Arabidopsis plants. We show that expression of the PGIP-PG chimera results in the in vivo production of OGs that can be detected by mass spectrometric analysis. Transgenic plants expressing the chimera under control of a pathogen-inducible promoter are more resistant to the phytopathogens Botrytis cinerea, Pectobacterium carotovorum, and Pseudomonas syringae. These data provide strong evidence for the hypothesis that OGs released in vivo act as a DAMP signal to trigger plant immunity and suggest that controlled release of these molecules upon infection may be a valuable tool to protect plants against infectious diseases. On the other hand, elevated levels of expression of the chimera cause the accumulation of salicylic acid, reduced growth, and eventually lead to plant death, consistent with the current notion that trade-off occurs between growth and defense. PMID:25870275

  20. Plant immunity triggered by engineered in vivo release of oligogalacturonides, damage-associated molecular patterns

    PubMed Central

    Benedetti, Manuel; Pontiggia, Daniela; Raggi, Sara; Cheng, Zhenyu; Scaloni, Flavio; Ferrari, Simone; Ausubel, Frederick M.; Cervone, Felice; De Lorenzo, Giulia

    2015-01-01

    Oligogalacturonides (OGs) are fragments of pectin that activate plant innate immunity by functioning as damage-associated molecular patterns (DAMPs). We set out to test the hypothesis that OGs are generated in planta by partial inhibition of pathogen-encoded polygalacturonases (PGs). A gene encoding a fungal PG was fused with a gene encoding a plant polygalacturonase-inhibiting protein (PGIP) and expressed in transgenic Arabidopsis plants. We show that expression of the PGIP–PG chimera results in the in vivo production of OGs that can be detected by mass spectrometric analysis. Transgenic plants expressing the chimera under control of a pathogen-inducible promoter are more resistant to the phytopathogens Botrytis cinerea, Pectobacterium carotovorum, and Pseudomonas syringae. These data provide strong evidence for the hypothesis that OGs released in vivo act as a DAMP signal to trigger plant immunity and suggest that controlled release of these molecules upon infection may be a valuable tool to protect plants against infectious diseases. On the other hand, elevated levels of expression of the chimera cause the accumulation of salicylic acid, reduced growth, and eventually lead to plant death, consistent with the current notion that trade-off occurs between growth and defense. PMID:25870275

  1. Angle-Resolved High-Order Above-Threshold Ionization of a Molecule: Sensitive Tool for Molecular Characterization

    SciTech Connect

    Busuladzic, M.; Gazibegovic-Busuladzic, A.; Milosevic, D. B.; Becker, W.

    2008-05-23

    The strong-field approximation for ionization of diatomic molecules by an intense laser field is generalized to include rescattering of the ionized electron off the various centers of its molecular parent ion. The resulting spectrum and its interference structure strongly depend on the symmetry of the ground state molecular orbital. For N{sub 2}, if the laser polarization is perpendicular to the molecular axis, we observe a distinct minimum in the emission spectrum, which survives focal averaging and allows determination of, e.g., the internuclear separation. In contrast, for O{sub 2}, rescattering is absent in the same situation.

  2. Non-equilibrium all-atom molecular dynamics simulations of free and tethered DNA molecules in nanochannel shear flows

    NASA Astrophysics Data System (ADS)

    Wang, Guan M.; Sandberg, William C.

    2007-04-01

    In order to gain insight into the mechanical and dynamical behaviour of free and tethered short chains of ss/ds DNA molecules in flow, and in parallel to investigate the properties of long chain molecules in flow fields, we have developed a series of quantum and molecular methods to extend the well developed equilibrium software CHARMM to handle non-equilibrium dynamics. These methods have been applied to cases of DNA molecules in shear flows in nanochannels. Biomolecules, both free and wall-tethered, have been simulated in the all-atom style in solvent-filled nanochannels. The new methods were demonstrated by carrying out NEMD simulations of free single-stranded DNA (ssDNA) molecules of 21 bases as well as double-stranded DNA (dsDNA) molecules of 21 base pairs tethered on gold surfaces in an ionic water shear flow. The tethering of the linker molecule (6-mercapto-1-hexanol) to perfect Au(111) surfaces was parametrized based on density functional theory (DFT) calculations. Force field parameters were incorporated into the CHARMM database. Gold surfaces are simulated in a Lennard-Jones style model that was fitted to the Morse potential model of bulk gold. The bonding force of attachment of the DNA molecules to the gold substrate linker molecule was computed to be up to a few nN when the DNA molecules are fully stretched at high shear rates. For the first time, we calculated the relaxation time of DNA molecules in picoseconds (ps) and the hydrodynamic force up to a few nanoNewtons (nN) per base pair in a nanochannel flow. The velocity profiles in the solvent due to the presence of the tethered DNA molecules were found to be nonlinear only at high shear flow rates. Free ssDNA molecules in a shear flow were observed to behave differently from each other depending upon their initial orientation in the flow field. Both free and tethered DNA molecules are clearly observed to be stretching, rotating and relaxing. Methods developed in this initial work can be incorporated

  3. Designing High-Affinity Peptides for Organic Molecules by Explicit Solvent Molecular Dynamics.

    PubMed

    Gladich, Ivan; Rodriguez, Alex; Hong Enriquez, Rolando P; Guida, Filomena; Berti, Federico; Laio, Alessandro

    2015-10-15

    Short peptides offer a cheap alternative to antibodies for developing sensing units in devices for concentration measurement. We here describe a computational procedure that allows designing peptides capable of binding with high affinity a target organic molecule in aqueous or nonstandard solvent environments. The algorithm is based on a stochastic search in the space of the possible sequences of the peptide, and exploits finite temperature molecular dynamics simulations in explicit solvent to check if a proposed mutation improves the binding affinity or not. The procedure automatically produces peptides which form thermally stable complexes with the target. The estimated binding free energy reaches the 13 kcal/mol for Irinotecan anticancer drug, the target considered in this work. These peptides are by construction solvent specific; namely, they recognize the target only in the solvent in which they have been designed. This feature of the algorithm calls for applications in devices in which the peptide-based sensor is required to work in denaturants or under extreme conditions of pressure and temperature. PMID:26398715

  4. 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.

  5. 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.

  6. Pattern Formations in Polymer-Molecular Motor Networks

    NASA Astrophysics Data System (ADS)

    Smith, David; Humphrey, David; Duggan, Cynthia; Käs, Josef

    2001-03-01

    In previous studies with the microtubule-kinesin system, organized patterns such as asters and rotating vortices have been seen (Nedelec et al, Nature 1997), which were of a dynamic nature and dependent on active motors. A similar system was constructed using actin and myosin, which displays similar patterns, however, with drastically different dynamics. These patterns arise independent of the initial amount of immediate use energy (in the form of ATP), assembling only upon the near exhaustion of available ATP. Further studies have clearly shown that in fact these patterns are not dependent upon the motor activity of the myosin but its propensity to serve as a cross-linking element in an actin network, with the motor activity serving to prevent the arising of order in the system. We believe the dynamic differences inherent between the two polymer-motor systems studied lies primarily in the structural nature of the motor complexes, with the kinesin complex ordering the system by pushing multiple filaments in a parallel direction, and the myosin complexes disordering the system by pushing filaments in an antiparallel manner.

  7. Ion and molecule sensors using molecular recognition in luminescent, conductive polymers. FY 1997 year-end progress report

    SciTech Connect

    Wasielewski, M.R.

    1997-01-01

    'The purpose of this project is to use molecular recognition strategies to develop sensor technology based on luminescent, conductive polymers that contain sites for binding specific molecules or ions in the presence of related molecules or ions. Selective binding of a particular molecule or ion of interest to these polymers will result in a large change in their luminescence and/or conductivity, which can be used to both qualitatively and quantitatively sense the presence of the bound molecules or ions. The main thrusts and accomplishments in the first year of this project involve developing polymer syntheses that yield conjugated polymers to which a wide variety of ligands for metal ion binding can be readily incorporated.'

  8. Continuously Adjustable, Molecular-Sieving “Gate” on 5A Zeolite for Distinguishing Small Organic Molecules by Size

    PubMed Central

    Song, Zhuonan; Huang, Yi; Xu, Weiwei L.; Wang, Lei; Bao, Yu; Li, Shiguang; Yu, Miao

    2015-01-01

    Zeolites/molecular sieves with uniform, molecular-sized pores are important for many adsorption-based separation processes. Pore size gaps, however, exist in the current zeolite family. This leads to a great challenge of separating molecules with size differences at ~0.01 nm level. Here, we report a novel concept, pore misalignment, to form a continuously adjustable, molecular-sieving “gate” at the 5A zeolite pore entrance without sacrificing the internal capacity. Misalignment of the micropores of the alumina coating with the 5A zeolite pores was related with and facilely adjusted by the coating thickness. For the first time, organic molecules with sub-0.01 nm size differences were effectively distinguished via appropriate misalignment. This novel concept may have great potential to fill the pore size gaps of the zeolite family and realize size-selective adsorption separation. PMID:26358480

  9. Mosaic cellular patterning in the nose: Adhesion molecules give their two scents.

    PubMed

    Beaudoin, Gerard M J

    2016-02-29

    The sense of smell is mediated by the olfactory epithelium, which is composed of a mosaic pattern of olfactory sensory cells surrounded by supporting cells. In this issue, Katsunuma et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201509020) show that the differential expression of nectins and cadherins establishes this pattern. PMID:26929448

  10. Practical Approaches for Mining Frequent Patterns in Molecular Datasets.

    PubMed

    Naulaerts, Stefan; Moens, Sandy; Engelen, Kristof; Berghe, Wim Vanden; Goethals, Bart; Laukens, Kris; Meysman, Pieter

    2016-01-01

    Pattern detection is an inherent task in the analysis and interpretation of complex and continuously accumulating biological data. Numerous itemset mining algorithms have been developed in the last decade to efficiently detect specific pattern classes in data. Although many of these have proven their value for addressing bioinformatics problems, several factors still slow down promising algorithms from gaining popularity in the life science community. Many of these issues stem from the low user-friendliness of these tools and the complexity of their output, which is often large, static, and consequently hard to interpret. Here, we apply three software implementations on common bioinformatics problems and illustrate some of the advantages and disadvantages of each, as well as inherent pitfalls of biological data mining. Frequent itemset mining exists in many different flavors, and users should decide their software choice based on their research question, programming proficiency, and added value of extra features. PMID:27168722

  11. Practical Approaches for Mining Frequent Patterns in Molecular Datasets

    PubMed Central

    Naulaerts, Stefan; Moens, Sandy; Engelen, Kristof; Berghe, Wim Vanden; Goethals, Bart; Laukens, Kris; Meysman, Pieter

    2016-01-01

    Pattern detection is an inherent task in the analysis and interpretation of complex and continuously accumulating biological data. Numerous itemset mining algorithms have been developed in the last decade to efficiently detect specific pattern classes in data. Although many of these have proven their value for addressing bioinformatics problems, several factors still slow down promising algorithms from gaining popularity in the life science community. Many of these issues stem from the low user-friendliness of these tools and the complexity of their output, which is often large, static, and consequently hard to interpret. Here, we apply three software implementations on common bioinformatics problems and illustrate some of the advantages and disadvantages of each, as well as inherent pitfalls of biological data mining. Frequent itemset mining exists in many different flavors, and users should decide their software choice based on their research question, programming proficiency, and added value of extra features. PMID:27168722

  12. Opening the way to molecular cycloaddition of large molecules on supported silicene

    NASA Astrophysics Data System (ADS)

    Stephan, Régis; Hanf, Marie-Christine; Sonnet, Philippe

    2015-10-01

    Within density functional theory, the adsorption of the H2Pc molecule on the (3 × 3) silicene/(4 × 4) Ag(111) surface has been investigated. We observe an electronic redistribution in the central macrocycle of the H2Pc molecule and the formation of two Si - N covalent bonds between the molecule and the silicene, in agreement with a cycloaddition reaction. However, while on SiC(0001)(3 × 3) or Si ( 111 ) ( √{ 3 } × √{ 3 } ) R 30 °-boron, the H2Pc molecule remains planar, and the H2Pc molecule takes a butterfly conformation on the silicene/Ag substrate due to an electrostatic or a polarization repulsion between the molecule and the silicene. Our study opens a way to the experimental adsorption of large organic molecules on supported silicene.

  13. Turing Patterning Using Gene Circuits with Gas-Induced Degradation of Quorum Sensing Molecules

    PubMed Central

    Hasty, Jeff; Tsimring, Lev

    2016-01-01

    The Turing instability was proposed more than six decades ago as a mechanism leading to spatial patterning, but it has yet to be exploited in a synthetic biology setting. Here we characterize the Turing instability in a specific gene circuit that can be implemented in vitro or in populations of clonal cells producing short-range activator N-Acyl homoserine lactone (AHL) and long-range inhibitor hydrogen peroxide (H2O2) gas. Slowing the production rate of the AHL-degrading enzyme, AiiA, generates stable fixed states, limit cycle oscillations and Turing patterns. Further tuning of signaling parameters determines local robustness and controls the range of unstable wavenumbers in the patterning regime. These findings provide a roadmap for optimizing spatial patterns of gene expression based on familiar quorum and gas sensitive E. coli promoters. The circuit design and predictions may be useful for (re)programming spatial dynamics in synthetic and natural gene expression systems. PMID:27148743

  14. Molecular Characterisation of Small Molecule Agonists Effect on the Human Glucagon Like Peptide-1 Receptor Internalisation

    PubMed Central

    Thompson, Aiysha; Stephens, Jeffrey W.; Bain, Stephen C.

    2016-01-01

    The glucagon-like peptide receptor (GLP-1R), which is a G-protein coupled receptor (GPCR), signals through both Gαs and Gαq coupled pathways and ERK phosphorylation to stimulate insulin secretion. The aim of this study was to determine molecular details of the effect of small molecule agonists, compounds 2 and B, on GLP-1R mediated cAMP production, intracellular Ca2+ accumulation, ERK phosphorylation and its internalisation. In human GLP-1R (hGLP-1R) expressing cells, compounds 2 and B induced cAMP production but caused no intracellular Ca2+ accumulation, ERK phosphorylation or hGLP-1R internalisation. GLP-1 antagonists Ex(9–39) and JANT-4 and the orthosteric binding site mutation (V36A) in hGLP-1R failed to inhibit compounds 2 and B induced cAMP production, confirming that their binding site distinct from the GLP-1 binding site on GLP-1R. However, K334A mutation of hGLP-1R, which affects Gαs coupling, inhibited GLP-1 as well as compounds 2 and B induced cAMP production, indicating that GLP-1, compounds 2 and B binding induce similar conformational changes in the GLP-1R for Gαs coupling. Additionally, compound 2 or B binding to the hGLP-1R had significantly reduced GLP-1 induced intracellular Ca2+ accumulation, ERK phosphorylation and hGLP-1R internalisation. This study illustrates pharmacology of differential activation of GLP-1R by GLP-1 and compounds 2 and B. PMID:27100083

  15. Hunting complex differential gene interaction patterns across molecular contexts

    PubMed Central

    Song, Mingzhou; Zhang, Yang; Katzaroff, Alexia J.; Edgar, Bruce A.; Buttitta, Laura

    2014-01-01

    Heterogeneity in genetic networks across different signaling molecular contexts can suggest molecular regulatory mechanisms. Here we describe a comparative chi-square analysis (CPχ2) method, considerably more flexible and effective than other alternatives, to screen large gene expression data sets for conserved and differential interactions. CPχ2 decomposes interactions across conditions to assess homogeneity and heterogeneity. Theoretically, we prove an asymptotic chi-square null distribution for the interaction heterogeneity statistic. Empirically, on synthetic yeast cell cycle data, CPχ2 achieved much higher statistical power in detecting differential networks than alternative approaches. We applied CPχ2 to Drosophila melanogaster wing gene expression arrays collected under normal conditions, and conditions with overexpressed E2F and Cabut, two transcription factor complexes that promote ectopic cell cycling. The resulting differential networks suggest a mechanism by which E2F and Cabut regulate distinct gene interactions, while still sharing a small core network. Thus, CPχ2 is sensitive in detecting network rewiring, useful in comparing related biological systems. PMID:24482443

  16. Patterning of polypyrrole using a fluoropolymer as an adsorption-protecting molecule

    NASA Astrophysics Data System (ADS)

    Kwon, Sunil; Ha, Jong-Wook; Noh, Jiwhan; Lee, Sang-Yup

    2010-10-01

    Patterning of the conducting polymer polypyrrole (PPy) was achieved using perfluoropolyether (PFPE) as a mask material. The fluoropolymer PFPE has both hydrophobic and oleophobic properties that allowed the generation of passivated patterns against PPy deposition. We exploited these properties to achieve the selective micropattern deposition of PPy, by simple chemical oxidation in an aqueous solution. Using a microcontact printing method, circle patterns with exposed carboxyl groups were prepared, while other region was protected by PFPE. Chemical oxidation of PPy on the patterned substrate resulted in selective deposition of PPy onto only the carboxylate-terminated regions, with little deposition on the PFPE layer. Cross-sectional analysis of the pattern revealed that the PFPE layer would form a hole-like structure around the carboxylate-terminated surfaces, with PPy deposition only in the holes. The PFPE layer had little influence on surface smoothness, compared to other self-assembled monolayers. These results suggest that PFPE can be used as a protective material for the surface modification and patterning of various materials.

  17. Monitoring patterned enzymatic polymerization on DNA origami at single-molecule level

    NASA Astrophysics Data System (ADS)

    Okholm, A. H.; Aslan, H.; Besenbacher, F.; Dong, M.; Kjems, J.

    2015-06-01

    DNA origami has been used to orchestrate reactions with nano-precision using a variety of biomolecules. Here, the dynamics of albumin-assisted, localized single-molecule DNA polymerization by terminal deoxynucleotidyl transferase on a 2D DNA origami are monitored using AFM in liquid. Direct visualization of the surface activity revealed the mechanics of growth.DNA origami has been used to orchestrate reactions with nano-precision using a variety of biomolecules. Here, the dynamics of albumin-assisted, localized single-molecule DNA polymerization by terminal deoxynucleotidyl transferase on a 2D DNA origami are monitored using AFM in liquid. Direct visualization of the surface activity revealed the mechanics of growth. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01945a

  18. Molecular Ions and Other Exotic Molecules in Space: A Coordinated Astronomical, Laboratory, and Theoretical Study

    NASA Astrophysics Data System (ADS)

    McCarthy, Michael

    This proposal request funds to continue a laboratory program in close coordination with radio astronomical observations dedicated to the study of highly reactive molecular ions, radicals, and metastable isomers that are thought to be key intermediates in rich interstellar and circumstellar sources. Determining the carriers of strong unidentified lines, such as U617.6 which has recently been observed with the Herschel space satellite, is the type of problem in laboratory astrophysics that our group is particularly adept at, and will be also emphasized in the upcoming grant period. Most new molecular species will be detected using microwave cavity rotational spectroscopy, followed either by microwave/millimeter-wave double resonance or millimeter/THz absorption to better characterize the rotational spectra in bands where Herschel and SOFIA operate. Using this combined approach, the rotational spectra of a number of ions of astronomical interest such as the cis- and trans isomers of HOSO+, H2NCO+, HNCOH+, H2CCHCNH+, C3N-, and NCO- have recently been detected in our laboratory, as have metastable isomers or derivatives of isocyanic acid, HNCO. As a result of this work, HOCN, HSCN, TiO2, and several molecular anions have been identified for the first time in space in the span of only a few years. Emphasis in the upcoming grant period will be placed on the detection of diatomic and small polyatomic ions such as SiH+, SiN-, CN+, NCS-, etc., other prototypical ions, including protonated benzene C6H7+, and silicon- and phosphorus-bearing species of astronomical interest. On the assumption that U617.6 is the fundamental b-type transition of a small polyatomic molecule, systematic searches for species of the form XOH, where X is likely either an atom or diatomic, will be given high priority because slightly bent species with this functional group (e.g., NNOH+, SiOH, etc.) possess an A rotational constants of about the right magnitude. Instrumental refinement will also be

  19. Electronic transport in biphenyl single-molecule junctions with carbon nanotubes electrodes: The role of molecular conformation and chirality

    SciTech Connect

    Brito Silva, C. A. Jr.; Granhen, E. R.; Silva, S. J. S. da; Leal, J. F. P.; Del Nero, J.; Pinheiro, F. A.

    2010-08-15

    We investigate, by means of ab initio calculations, electronic transport in molecular junctions composed of a biphenyl molecule attached to metallic carbon nanotubes. We find that the conductance is proportional to cos{sup 2} {theta}, with {theta} the angle between phenyl rings, when the Fermi level of the contacts lies within the frontier molecular orbitals energy gap. This result, which agrees with experiments in biphenyl junctions with nonorganic contacts, suggests that the cos{sup 2} {theta} law has a more general applicability, irrespective of the nature of the electrodes. We calculate the geometrical degree of chirality of the junction, which only depends on the atomic positions, and demonstrate that it is not only proportional to cos{sup 2} {theta} but also is strongly correlated with the current through the system. These results indicate that molecular conformation plays the preponderant role in determining transport properties of biphenyl-carbon nanotubes molecular junctions.

  20. Patterning and characterization of surfaces with organic and biological molecules by the scanning electrochemical microscope.

    PubMed

    Turyan, I; Matsue, T; Mandler, D

    2000-08-01

    A novel approach for micropatterning of surfaces with organic and biological microstructures using the scanning electrochemical microscope (SECM) is described. The approach is based on the introduction of the spatial resolution by local deposition of gold particles followed by monolayer formation and functionalization. Specifically, gold patterns were deposited locally on silicon wafers with the SECM as a result of the controlled anodic dissolution of a gold microelectrode. The gold patterns were further used as microsubstrates for assembling cystamine monolayers to which either fluoresceine isothiocyanate (FIT) or glucose oxidase (GOD) were covalently attached. Characterization of the organic monolayers, as well as the biological activity of the enzyme patterns, was carried out by fluorescence microscopy and the SECM, respectively. PMID:10952523

  1. Molecular model of biaxial ordering in nematic liquid crystals composed of flat molecules with four mesogenic groups

    NASA Astrophysics Data System (ADS)

    Gorkunov, M. V.; Osipov, M. A.; Kocot, A.; Vij, J. K.

    2010-06-01

    Relative stability of uniaxial and biaxial nematic phases is analyzed in a model nematic liquid crystal composed of flat molecules of C2h symmetry with four mesogenic groups rigidly linked to the same center. The generalized effective quadrupole mean-field potential is proposed and its constants are evaluated numerically for the pair intermolecular potential based on Gay-Berne interaction between mesogenic groups. The dependencies of the constants on molecular shape parameters are systematically analyzed. Order parameters of the uniaxial and biaxial nematic phases are evaluated by direct minimization of the free energy at different temperatures. The corresponding phase diagrams are obtained enabling one to study the effects of molecular model parameters on the stability regions of uniaxial and biaxial phases. The results are used to clarify the nature of experimentally observed biaxial ordering in nematic liquid crystals composed of tetrapode molecules with the same symmetry.

  2. Molecular orientation effect on the differential cross sections for the electron-impact double ionization of oriented water molecules

    SciTech Connect

    Champion, C.; Dal Cappello, C.; Oubaziz, D.; Aouchiche, H.; Popov, Yu. V.

    2010-03-15

    Double ionization of isolated water molecules fixed in space is here investigated in a theoretical approach based on the first Born approximation. Secondary electron angular distributions are reported for particular (e,3e) kinematical conditions and compared in terms of shape and magnitude. Strong dependence of the fivefold differential cross sections on the molecular target orientation is clearly observed in (e,3-1e) as well as (e,3e) channels. Furthermore, for the major part of the kinematics considered, we identified the different mechanisms involved in the double ionization of water molecule, namely, the direct shake-off process as well as the two-step1 process. They are both discussed and analyzed with respect to the molecular target orientation.

  3. Molecular model of biaxial ordering in nematic liquid crystals composed of flat molecules with four mesogenic groups.

    PubMed

    Gorkunov, M V; Osipov, M A; Kocot, A; Vij, J K

    2010-06-01

    Relative stability of uniaxial and biaxial nematic phases is analyzed in a model nematic liquid crystal composed of flat molecules of C2h symmetry with four mesogenic groups rigidly linked to the same center. The generalized effective quadrupole mean-field potential is proposed and its constants are evaluated numerically for the pair intermolecular potential based on Gay-Berne interaction between mesogenic groups. The dependencies of the constants on molecular shape parameters are systematically analyzed. Order parameters of the uniaxial and biaxial nematic phases are evaluated by direct minimization of the free energy at different temperatures. The corresponding phase diagrams are obtained enabling one to study the effects of molecular model parameters on the stability regions of uniaxial and biaxial phases. The results are used to clarify the nature of experimentally observed biaxial ordering in nematic liquid crystals composed of tetrapode molecules with the same symmetry. PMID:20866427

  4. Single molecular recognition force spectroscopy study of a DNA aptamer with the target epithelial cell adhesion molecule.

    PubMed

    Wang, Nan; Liu, Huiqing; Hao, Jinhui; Bai, Xiaojing; Li, Huiyan; Zhang, Zhe; Wang, Hongda; Tang, Jilin

    2015-09-21

    The epithelial cell adhesion molecule (EpCAM) is a tumor-specific antigen for malignancies of the epithelialis lineage. In this study the interaction between the DNA-based EpCAM aptamer (SYL3C) and EpCAM was explored using single molecular recognition force spectroscopy (SMFS). The capability of aptamer SYL3C to recognize the EpCAM protein and the kinetic parameters were investigated. PMID:26229987

  5. Pick-up, transport and release of a molecular cargo using a small-molecule robotic arm

    NASA Astrophysics Data System (ADS)

    Kassem, Salma; Lee, Alan T. L.; Leigh, David A.; Markevicius, Augustinas; Solà, Jordi

    2016-02-01

    Modern-day factory assembly lines often feature robots that pick up, reposition and connect components in a programmed manner. The idea of manipulating molecular fragments in a similar way has to date only been explored using biological building blocks (specifically DNA). Here, we report on a wholly artificial small-molecule robotic arm capable of selectively transporting a molecular cargo in either direction between two spatially distinct, chemically similar, sites on a molecular platform. The arm picks up/releases a 3-mercaptopropanehydrazide cargo by formation/breakage of a disulfide bond, while dynamic hydrazone chemistry controls the cargo binding to the platform. Transport is controlled by selectively inducing conformational and configurational changes within an embedded hydrazone rotary switch that steers the robotic arm. In a three-stage operation, 79-85% of 3-mercaptopropanehydrazide molecules are transported in either (chosen) direction between the two platform sites, without the cargo at any time fully dissociating from the machine nor exchanging with other molecules in the bulk.

  6. Susceptibility Patterns and Molecular Identification of Trichosporon Species

    PubMed Central

    Rodriguez-Tudela, Juan L.; Diaz-Guerra, Teresa M.; Mellado, Emilia; Cano, Virginia; Tapia, Cecilia; Perkins, Alexander; Gomez-Lopez, Alicia; Rodero, Laura; Cuenca-Estrella, Manuel

    2005-01-01

    The physiological patterns, the sequence polymorphisms of the internal transcriber spacer (ITS), and intergenic spacer regions (IGS) of the rRNA genes and the antifungal susceptibility profile were evaluated for their ability to identify Trichosporon spp. and their specificity for the identification of 49 clinical isolates of Trichosporon spp. Morphological and biochemical methodologies were unable to differentiate among the Trichosporon species. ITS sequencing was also unable to differentiate several species. However, IGS1 sequencing unambiguously identified all Trichosporon isolates. Following the results of DNA-based identification, Trichosporon asahii was the species most frequently isolated from deep sites (15 of 25 strains; 60%). In the main, other Trichosporon species were recovered from cutaneous samples. The majority of T. asahii, T. faecale, and T. coremiiforme clinical isolates exhibited resistance in vitro to amphotericin B, with geometric mean (GM) MICs >4 μg/ml. The other species of Trichosporon did not show high MICs of amphotericin B, and GM MICs were <1 μg/ml. Azole agents were active in vitro against the majority of clinical strains. The most potent compound in vitro was voriconazole, with a GM MIC ≤0.14 μg/ml. The sequencing of IGS correctly identified Trichosporon isolates; however, this technique is not available in many clinical laboratories, and strains should be dispatched to reference centers where these complex methods are available. Therefore, it seems to be more practical to perform antifungal susceptibility testing of all isolates belonging to Trichosporon spp., since correct identification could take several weeks, delaying the indication of an antifungal agent which exhibits activity against the infectious strain. PMID:16189076

  7. De novo design of drug-like molecules by a fragment-based molecular evolutionary approach.

    PubMed

    Kawai, Kentaro; Nagata, Naoya; Takahashi, Yoshimasa

    2014-01-27

    This paper describes a similarity-driven simple evolutionary approach to producing candidate molecules of new drugs. The aim of the method is to explore the candidates that are structurally similar to the reference molecule and yet somewhat different in not only peripheral chains but also their scaffolds. The method employs a known active molecule of our interest as a reference molecule which is used to navigate a huge chemical space. The reference molecule is also used to obtain seed fragments. An initial set of individual structures is prepared with the seed fragments and additional fragments using several connection rules. The fragment library is preferably prepared from a collection of known molecules related to the target of the reference molecule. Every fragment of the library can be used for fragment-based mutation. All the fragments are categorized into three classes; rings, linkers, and side chains. New individuals are produced by the crossover and the fragment-based mutation with the fragment library. Computer experiments with our own fragment library prepared from GPCR SARfari verified the feasibility of our approach to drug discovery. PMID:24372539

  8. Molecular entrapment of small molecules within the interior of horse spleen ferritin.

    PubMed

    Webb, B; Frame, J; Zhao, Z; Lee, M L; Watt, G D

    1994-02-15

    A procedure for trapping small molecules inside the interior of horse spleen ferritin (HoSF) and methods for characterizing HoSF and its small entrapped molecules are described. HoSF is first dissociated into subunits by adjustment to pH 2 in the presence of the small molecules to be trapped. The pH of the dissociated HoSF is then increased to 7 at which time the dissociated subunits reassemble reforming the 24-mer HoSF, thereby trapping solvent within its interior. HoSF is then separated from unbound molecules by dialysis, ultrafiltration, and/or ammonium sulfate precipitation. Sephadex G-25 and DEAE chromatographic methods were also used to separate HoSF from unbound small molecules. Capillary electrophoresis (CE) was used to demonstrate the association of small molecules with HoSF after the pH-induced unfolding-refolding process. The pH indicator neutral red was clearly associated with HoSF and presumed trapped within the ferritin interior. Acid/base titrations suggested that the trapped indicator had a different pKa than the free indicator, a result which indicates that the ferritin interior is different than the external solution. The utility of using trapped molecules for gaining information on ferritin function is proposed and discussed. PMID:8117106

  9. Atomic Spectral Methods for Ab Initio Molecular Electronic Energy Surfaces: Transitioning From Small-Molecule to Biomolecular-Suitable Approaches.

    PubMed

    Mills, Jeffrey D; Ben-Nun, Michal; Rollin, Kyle; Bromley, Michael W J; Li, Jiabo; Hinde, Robert J; Winstead, Carl L; Sheehy, Jeffrey A; Boatz, Jerry A; Langhoff, Peter W

    2016-08-25

    Continuing attention has addressed incorportation of the electronically dynamical attributes of biomolecules in the largely static first-generation molecular-mechanical force fields commonly employed in molecular-dynamics simulations. We describe here a universal quantum-mechanical approach to calculations of the electronic energy surfaces of both small molecules and large aggregates on a common basis which can include such electronic attributes, and which also seems well-suited to adaptation in ab initio molecular-dynamics applications. In contrast to the more familiar orbital-product-based methodologies employed in traditional small-molecule computational quantum chemistry, the present approach is based on an "ex-post-facto" method in which Hamiltonian matrices are evaluated prior to wave function antisymmetrization, implemented here in the support of a Hilbert space of orthonormal products of many-electron atomic spectral eigenstates familiar from the van der Waals theory of long-range interactions. The general theory in its various forms incorporates the early semiempirical atoms- and diatomics-in-molecules approaches of Moffitt, Ellison, Tully, Kuntz, and others in a comprehensive mathematical setting, and generalizes the developments of Eisenschitz, London, Claverie, and others addressing electron permutation symmetry adaptation issues, completing these early attempts to treat van der Waals and chemical forces on a common basis. Exact expressions are obtained for molecular Hamiltonian matrices and for associated energy eigenvalues as sums of separate atomic and interaction-energy terms, similar in this respect to the forms of classical force fields. The latter representation is seen to also provide a long-missing general definition of the energies of individual atoms and of their interactions within molecules and matter free from subjective additional constraints. A computer code suite is described for calculations of the many-electron atomic eigenspectra and

  10. Laser slowing of CaF molecules to near the capture velocity of a molecular MOT

    NASA Astrophysics Data System (ADS)

    Hemmerling, Boerge; Chae, Eunmi; Ravi, Aakash; Anderegg, Loic; Drayna, Garrett K.; Hutzler, Nicholas R.; Collopy, Alejandra L.; Ye, Jun; Ketterle, Wolfgang; Doyle, John M.

    2016-09-01

    Laser slowing of CaF molecules down to the capture velocity of a magneto-optical trap for molecules is achieved. Starting from a two-stage buffer gas beam source, we apply frequency-broadened ‘white-light’ slowing and observe approximately 6× {10}4 CaF molecules in a single pulse with velocities 10 ± 4 m s‑1. CaF is a candidate for collisional studies in the mK regime. This work represents a significant step towards magneto-optical trapping of CaF.

  11. The dynamics of some metal-organic and organic molecules in water solution studied by molecular mechanical and molecular dynamical methods

    NASA Astrophysics Data System (ADS)

    Broo, Anders

    1993-07-01

    A force field is developed to reproduce geometries and vibration spectra of rutheniumhexaamine(III) and rutheniumhexamine(II) complexes. The force constants for ruthenium were then used in molecular dynamics simulation of a Ru 2+ ion, a Ru 3+ ion and Ru(NH 3) 5-pyrazine 2+ in water solution. Simulations of pyrazine and 1,3-dimethyluracile in water solution were also performed. A comparison of different ways of how to include solvation effects in quantum chemical calculations is discussed using the results from the simulations. The MD simulations show that the solvent surrounding a small charged ion, such as a Ru 2+ ion, have a pronounced shell structure and the first layer of solvent molecules is stable during a 61 ps simulation. For a metal-organic molecule as Ru(NH 3) 5-pyrazine the solvent shows shell structure, but the water molecules are exchanged frequently. In the relatively charge-symmetric pyrazine the solvent is not polarized around the molecule. In a molecule like 1,3-dimethyluracile, which is non-symmetric in the charge distribution, the water is strongly polarized.

  12. 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.

  13. Global molecular identification from graphs. Neutral and ionized main-group diatomic molecules.

    PubMed

    James, Bryan; Caviness, Ken; Geach, Jonathan; Walters, Chris; Hefferlin, Ray

    2002-01-01

    Diophantine equations and inequalities are presented for main-group closed-shell diatomic molecules. Specifying various bond types (covalent, dative, ionic, van der Waals) and multiplicities, it becomes possible to identify all possible molecules. While many of the identified species are probably unstable under normal conditions, they are interesting and present a challenge for computational or experimental analysis. Ionized molecules with net charges of -1, 1, and 2 are also identified. The analysis applies to molecules with atoms from periods 2 and 3 but can be generalized by substituting isovalent atoms. When closed-shell neutral diatomics are positioned in the chemical space (with axes enumerating the numbers of valence electrons of the free atoms), it is seen that they lie on a few parallel isoelectronic series. PMID:11855960

  14. Molecular Combing of Single DNA Molecules on the 10 Megabase Scale

    PubMed Central

    Kaykov, Atanas; Taillefumier, Thibaud; Bensimon, Aaron; Nurse, Paul

    2016-01-01

    DNA combing allows the investigation of DNA replication on genomic single DNA molecules, but the lengths that can be analysed have been restricted to molecules of 200–500 kb. We have improved the DNA combing procedure so that DNA molecules can be analysed up to the length of entire chromosomes in fission yeast and up to 12 Mb fragments in human cells. Combing multi-Mb-scale DNA molecules revealed previously undetected origin clusters in fission yeast and shows that in human cells replication origins fire stochastically forming clusters of fired origins with an average size of 370 kb. We estimate that a single human cell forms around 3200 clusters at mid S-phase and fires approximately 100,000 origins to complete genome duplication. The procedure presented here will be adaptable to other organisms and experimental conditions. PMID:26781994

  15. The Distribution of Complex Organic Molecules in the Orion KL Molecular Core

    NASA Technical Reports Server (NTRS)

    Kuan, Yi-Jehng; Hsu, Yu-Sen; Charnley, Steven B.; Wang, Kuo-Song

    2011-01-01

    We conducted high angular-resolution observations toward the massive star-forming region Orion KL at 1.3 mm using the Submillimeter Array (SMA). Spectral emission from twelve complex organic molecules was simultaneously imaged. We discuss the distinct chemical characteristics among four sub- regions in Orion KL by comparing the spatial distributions and fractional abundances of these complex molecules. These observations will allow us to test and constrain chemical models of interstellar organic synthesis.

  16. Amine-linked single-molecule circuits: systematic trends across molecular families.

    PubMed

    Hybertsen, Mark S; Venkataraman, Latha; Klare, Jennifer E; Whalley, Adam C; Steigerwald, Michael L; Nuckolls, Colin

    2008-09-17

    A comprehensive review is presented of single-molecule junction conductance measurements across families of molecules measured while breaking a gold point contact in a solution of molecules with amine end groups. A theoretical framework unifies the picture for the amine-gold link bonding and the tunnel coupling through the junction using density functional theory based calculations. The reproducible electrical characteristics and utility for many molecules is shown to result from the selective binding between the gold electrodes and amine link groups through a donor-acceptor bond to undercoordinated gold atoms. While the bond energy is modest, the maximum force sustained by the junction is comparable to, but less than, that required to break gold point contacts. The calculated tunnel coupling provides conductance trends for all 41 molecule measurements presented here, as well as insight into the variability of conductance due to the conformational changes within molecules with torsional degrees of freedom. The calculated trends agree to within a factor of 2 with the measured values for conductance ranging from 10(-7)G(0) to 10(-2)G(0), where G(0) is the quantum of conductance (2e(2)/h). PMID:21694422

  17. Differential adhesiveness between blood and marrow leukemic cells having similar pattern of VLA adhesion molecule expression.

    PubMed

    Thomas, X; Anglaret, B; Bailly, M; Maritaz, O; Magaud, J P; Archimbaud, E

    1998-10-01

    Functional adhesion of blood and marrow leukemic cells from 14 acute myeloid leukemia patients presenting with hyperleukocytosis was evaluated by performing cytoadhesion assays on purified (extracellular matrix proteins) and non-purified supports (MRC5 fibroblastic cell line). Results, in 30-min chromium release assay, show a mean +/- S.D. adhesion to fibronectin, collagen, and laminin respectively of 30 +/- 17%, 20 +/- 13%, 25 +/- 17% for blood leukemic cells and 18 +/- 11%, 11 +/- 10%, 11 +/- 8% for marrow leukemic cells. These differences between blood and marrow cells were statistically significant (respectively P = 0.005, P = 0.01 and P = 0.002), while no difference was noted regarding adhesion to non-purified supports. The higher adhesion of blood blast cells to purified supports was observed regardless of CD34 expression. No significant difference was observed in the expression of cell surface VLA-molecules (CD29, CD49b, CD49d, CD49e, CD49f) between blood and marrow blast cells. The addition of GM-CSF or G-CSF induced increased adhesion of marrow blasts and decreased adhesion of blood blasts leading to a loss of the difference between blood and marrow cells. In a 60-min chromium release assay, marrow blasts adhered even more than blood leukemic cells to fibronectin. In contrast, marrow blasts from 'aleukemic' acute myeloid leukemia patients did not show any modification regarding their adhesion to extracellular matrix proteins when co-cultured with growth factors. PMID:9766756

  18. Patterning a hydrogen-bonded molecular monolayer with a hand-controlled scanning probe microscope.

    PubMed

    Green, Matthew F B; Esat, Taner; Wagner, Christian; Leinen, Philipp; Grötsch, Alexander; Tautz, F Stefan; Temirov, Ruslan

    2014-01-01

    One of the paramount goals in nanotechnology is molecular-scale functional design, which includes arranging molecules into complex structures at will. The first steps towards this goal were made through the invention of the scanning probe microscope (SPM), which put single-atom and single-molecule manipulation into practice for the first time. Extending the controlled manipulation to larger molecules is expected to multiply the potential of engineered nanostructures. Here we report an enhancement of the SPM technique that makes the manipulation of large molecular adsorbates much more effective. By using a commercial motion tracking system, we couple the movements of an operator's hand to the sub-angstrom precise positioning of an SPM tip. Literally moving the tip by hand we write a nanoscale structure in a monolayer of large molecules, thereby showing that our method allows for the successful execution of complex manipulation protocols even when the potential energy surface that governs the interaction behaviour of the manipulated nanoscale object(s) is largely unknown. PMID:25383304

  19. Patterning a hydrogen-bonded molecular monolayer with a hand-controlled scanning probe microscope

    PubMed Central

    Green, Matthew F B; Esat, Taner; Wagner, Christian; Leinen, Philipp; Grötsch, Alexander; Tautz, F Stefan

    2014-01-01

    Summary One of the paramount goals in nanotechnology is molecular-scale functional design, which includes arranging molecules into complex structures at will. The first steps towards this goal were made through the invention of the scanning probe microscope (SPM), which put single-atom and single-molecule manipulation into practice for the first time. Extending the controlled manipulation to larger molecules is expected to multiply the potential of engineered nanostructures. Here we report an enhancement of the SPM technique that makes the manipulation of large molecular adsorbates much more effective. By using a commercial motion tracking system, we couple the movements of an operator's hand to the sub-angstrom precise positioning of an SPM tip. Literally moving the tip by hand we write a nanoscale structure in a monolayer of large molecules, thereby showing that our method allows for the successful execution of complex manipulation protocols even when the potential energy surface that governs the interaction behaviour of the manipulated nanoscale object(s) is largely unknown. PMID:25383304

  20. Movies of molecular motions and reactions: the single-molecule, real-time transmission electron microscope imaging technique.

    PubMed

    Nakamura, Eiichi

    2013-01-01

    "The truth is, the Science of Nature has been already too long made only a work of the Brain and the Fancy: It is now high time that it should return to the plainness and soundness of Observations on material and obvious things," proudly declared Robert Hooke in his highly successful picture book of microscopic and telescopic images, "Micrographia" in 1665. Hooke's statement has remained true in chemistry, where a considerable work of the brain and the fancy is still necessary. Single-molecule, real-time transmission electron microscope (SMRT-TEM) imaging at an atomic resolution now allows us to learn about molecules simply by watching movies of them. Like any dream come true, the new analytical technique challenged the old common sense of the communities, and offers new research opportunities that are unavailable by conventional methods. With its capacity to visualize the motions and the reactions of individual molecules and molecular clusters, the SMRT-TEM technique will become an indispensable tool in molecular science and the engineering of natural and synthetic substances, as well as in science education. PMID:23280645

  1. Molecular and developmental contributions to divergent pigment patterns in marine and freshwater sticklebacks

    PubMed Central

    Greenwood, Anna K.; Cech, Jennifer N.; Peichel, Catherine L.

    2012-01-01

    SUMMARY Pigment pattern variation across species or populations offers a tractable framework in which to investigate the evolution of development. Juvenile threespine sticklebacks (Gasterosteus aculeatus) from marine and freshwater environments exhibit divergent pigment patterns that are associated with ecological differences. Juvenile marine sticklebacks have a silvery appearance, whereas sticklebacks from freshwater environments exhibit a pattern of vertical bars. We investigated both the developmental and molecular basis of this population-level variation in pigment pattern. Time course imaging during the transition from larval to juvenile stages revealed differences between marine and freshwater fish in spatial patterns of chromatophore differentiation as well as in pigment amount and dispersal. In freshwater fish, melanophores appear primarily within dark bars whereas iridophores appear within light bars. By contrast, in marine fish, these chromatophores are interspersed across the flank. In addition to spatially segregated chromatophore differentiation, pigment amount and dispersal within melanophores varies spatially across the flank of freshwater, but not marine fish. To gain insight into the molecular pathways that underlie the differences in pigment pattern development, we evaluated differential gene expression in the flanks of developing fish using high throughput cDNA sequencing (RNA-seq) and quantitative PCR. We identified several genes that were differentially expressed across dark and light bars of freshwater fish, and between freshwater and marine fish. Together, these experiments begin to shed light on the process of pigment pattern evolution in sticklebacks. PMID:22765206

  2. Excitation of Ultracold Molecules to ``TRILOBITE-LIKE" Long-Range Molecular Rydberg States

    NASA Astrophysics Data System (ADS)

    Bellos, M. A.; Carollo, R.; Banerjee, J.; Eyler, E. E.; Gould, P. L.; Stwalley, W. C.

    2013-06-01

    A class of long-range Rydberg molecules, sometimes called ``trilobite states", occurs when a ground-state atom is embedded in the electronic cloud of a Rydberg atom. The bond between the Rydberg atom and the ground-state atom originates from the low-energy scattering of the Rydberg electron from the ground-state atom. We produce trilobite-like states of ultracold Rb_2 at low principal quantum numbers and at internuclear separations less than 40 bohr. We populate these states through single-photon ultraviolet transitions starting from molecules in high-lying vibrational levels of the lowest triplet state. This demonstrates that long-range Rydberg molecules can also be excited through bound-bound transitions, in addition to previous studies that used free-bound transitions. We also discuss the advantages of a bound-bound pathway. C. H. Greene, A. S. Dickinson, and H. R. Sadeghpour, Phys. Rev. Lett. 85, 2458 (2000).

  3. Molecular spectroscopy for producing ultracold ground-state NaRb molecules

    NASA Astrophysics Data System (ADS)

    Wang, Dajun; Guo, Mingyang; Zhu, Bing; Lu, Bo; Ye, Xin; Wang, Fudong; Vexiau, Romain; Bouloufa-Maafa, Nadia; Quéméner, Goulven; Dulieu, Olivier

    2016-05-01

    Recently, we have successfully created an ultracold sample of absolute ground-state NaRb molecules by two-photon Raman transfer of weakly bound Feshbach molecules. Here we will present the detailed spectroscopic investigations on both the excited and the rovibrational ground states for finding the two-photon path. For the excited state, we focus on the A1Σ+ /b3 Π singlet and triplet admixture. We discovered an anomalously strong coupling between the Ω =0+ and 0- components which renders efficient population transfer possible. In the ground state, the pure nuclear hyperfine levels have been clearly resolved, which allows us to create molecules in the absolute ground state directly with Raman transfer. This work is jointly supported by Agence Nationale de la Recherche (#ANR-13- IS04-0004-01) and Hong Kong Research Grant Council (#A-CUHK403/13) through the COPOMOL project.

  4. LARGE SCALE EVALUATION OF A PATTERN RECOGNITION/EXPERT SYSTEM FOR MASS SPECTRAL MOLECULAR WEIGHT ESTIMATION

    EPA Science Inventory

    A fast, personal-computer based method of estimating molecular weights of organic compounds from low resolution mass I spectra has been thoroughly evaluated. he method is based on a rule-based pattern,recognition/expert system approach which uses empirical linear corrections whic...

  5. Molecular locks and keys: the role of small molecules in phytohormone research

    PubMed Central

    Fonseca, Sandra; Rosado, Abel; Vaughan-Hirsch, John; Bishopp, Anthony; Chini, Andrea

    2014-01-01

    Plant adaptation, growth and development rely on the integration of many environmental and endogenous signals that collectively determine the overall plant phenotypic plasticity. Plant signaling molecules, also known as phytohormones, are fundamental to this process. These molecules act at low concentrations and regulate multiple aspects of plant fitness and development via complex signaling networks. By its nature, phytohormone research lies at the interface between chemistry and biology. Classically, the scientific community has always used synthetic phytohormones and analogs to study hormone functions and responses. However, recent advances in synthetic and combinational chemistry, have allowed a new field, plant chemical biology, to emerge and this has provided a powerful tool with which to study phytohormone function. Plant chemical biology is helping to address some of the most enduring questions in phytohormone research such as: Are there still undiscovered plant hormones? How can we identify novel signaling molecules? How can plants activate specific hormone responses in a tissue-specific manner? How can we modulate hormone responses in one developmental context without inducing detrimental effects on other processes? The chemical genomics approaches rely on the identification of small molecules modulating different biological processes and have recently identified active forms of plant hormones and molecules regulating many aspects of hormone synthesis, transport and response. We envision that the field of chemical genomics will continue to provide novel molecules able to elucidate specific aspects of hormone-mediated mechanisms. In addition, compounds blocking specific responses could uncover how complex biological responses are regulated. As we gain information about such compounds we can design small alterations to the chemical structure to further alter specificity, enhance affinity or modulate the activity of these compounds. PMID:25566283

  6. Direct observation of molecularly-aligned molecules in the second physisorbed layer-CO/Ag(110)

    SciTech Connect

    Lee, J.-G.; Hong, S.-H.; Ahner, J.; Zhao, X.; Chen, L.; Johnson, J.K.; Yates, J.T., Jr.

    2006-01-25

    We report the direct observation of oriented second-layer physisorbed molecules on a single crystal surface by electron stimulated desorption. Experiments and simulations show that the orientation of the second-layer physisorbed CO molecules on Ag(110) is the result of both electrostatic and dispersion forces from the underlying chemisorbed CO and Ag atoms. At 25 K, the physisorbed C-O bond is tilted and azimuthally oriented with the C-O bond axis inclined in an azimuthal plane at 45° to the principal Ag( 110) azimuthal crystallographic directions. The O atom in CO is directed outward, giving an O+ beam at 43° to the normal.

  7. The non-covalent nature of the molecular structure of the benzene molecule.

    PubMed

    Cardozo, Thiago Messias; Fantuzzi, Felipe; Nascimento, Marco Antonio Chaer

    2014-06-14

    The benzene molecule is one of the most emblematic systems in chemistry, with its structural features being present in numerous different compounds. We have carried out an analysis of the influence of quantum mechanical interference on the geometric features of the benzene molecule, showing that many of the characteristics of its equilibrium geometry are a consequence of non-covalent contributions to the energy. This result implies that quasi-classical reasoning should be sufficient to predict the defining aspects of the benzene structure such as its planarity and equivalence of its bond lengths. PMID:24779029

  8. Calculation of the fourth-rank molecular hypermagnetizability of some small molecules.

    PubMed

    Pagola, G I; Caputo, M C; Ferraro, M B; Lazzeretti, P

    2004-05-22

    A computational scheme has been developed within the framework of Rayleigh-Schrödinger perturbation theory to evaluate nonlinear interaction energy contributions for a molecule in the presence of an external spatially uniform, time-independent magnetic field. Terms connected with the fourth power of the perturbing field, representing the fourth-rank hypermagnetizabilities of five small molecules, have been evaluated at the coupled Hartree-Fock level of accuracy within the conventional common-origin approach. Gaugeless basis sets of increasing size and flexibility have been employed in a numerical test, adopting two different coordinate systems to estimate the degree of convergence of theoretical tensor components. PMID:15267967

  9. Calculation of the fourth-rank molecular hypermagnetizability of some small molecules

    NASA Astrophysics Data System (ADS)

    Pagola, G. I.; Caputo, M. C.; Ferraro, M. B.; Lazzeretti, P.

    2004-05-01

    A computational scheme has been developed within the framework of Rayleigh-Schrödinger perturbation theory to evaluate nonlinear interaction energy contributions for a molecule in the presence of an external spatially uniform, time-independent magnetic field. Terms connected with the fourth power of the perturbing field, representing the fourth-rank hypermagnetizabilities of five small molecules, have been evaluated at the coupled Hartree-Fock level of accuracy within the conventional common-origin approach. Gaugeless basis sets of increasing size and flexibility have been employed in a numerical test, adopting two different coordinate systems to estimate the degree of convergence of theoretical tensor components.

  10. Array formatting of the heat-transfer method (HTM) for the detection of small organic molecules by molecularly imprinted polymers.

    PubMed

    Wackers, Gideon; Vandenryt, Thijs; Cornelis, Peter; Kellens, Evelien; Thoelen, Ronald; De Ceuninck, Ward; Losada-Pérez, Patricia; van Grinsven, Bart; Peeters, Marloes; Wagner, Patrick

    2014-01-01

    In this work we present the first steps towards a molecularly imprinted polymer (MIP)-based biomimetic sensor array for the detection of small organic molecules via the heat-transfer method (HTM). HTM relies on the change in thermal resistance upon binding of the target molecule to the MIP-type receptor. A flow-through sensor cell was developed, which is segmented into four quadrants with a volume of 2.5 μL each, allowing four measurements to be done simultaneously on a single substrate. Verification measurements were conducted, in which all quadrants received a uniform treatment and all four channels exhibited a similar response. Subsequently, measurements were performed in quadrants, which were functionalized with different MIP particles. Each of these quadrants was exposed to the same buffer solution, spiked with different molecules, according to the MIP under analysis. With the flow cell design we could discriminate between similar small organic molecules and observed no significant cross-selectivity. Therefore, the MIP array sensor platform with HTM as a readout technique, has the potential to become a low-cost analysis tool for bioanalytical applications. PMID:24955945

  11. Alignment of liquid crystals using a molecular layer with patterned molecular density.

    PubMed

    Son, Jong-Ho; Zin, Wang-Cheol; Takezoe, Hideo; Song, Jang-Kun

    2012-11-27

    The surface of self-constructed molecular density modulation (SDM) exhibits a wide range of liquid crystal alignment capabilities including planar, tilted, and homeotropic alignments, disclination-free uniform and heterogeneous alignments, and even spatially varying alignments through the single non-contact process. Alignment defects are eliminated by temporary lowering the frictional energy barrier via the open-boundary elastic stabilization (OES) treatment. PMID:22945601

  12. The Frontier of Molecular Spintronics Based on Multiple-Decker Phthalocyaninato Tb(III) Single-Molecule Magnets.

    PubMed

    Katoh, Keiichi; Komeda, Tadahiro; Yamashita, Masahiro

    2016-04-01

    Ever since the first example of a double-decker complex (SnPc2) was discovered in 1936, MPc2 complexes with π systems and chemical and physical stabilities have been used as components in molecular electronic devices. More recently, in 2003, TbPc2 complexes were shown to be single-molecule magnets (SMMs), and researchers have utilized their quantum tunneling of the magnetization (QTM) and magnetic relaxation behavior in spintronic devices. Herein, recent developments in Ln(III)-Pc-based multiple-decker SMMs on surfaces for molecular spintronic devices are presented. In this account, we discuss how dinuclear Tb(III)-Pc multiple-decker complexes can be used to elucidate the relationship between magnetic dipole interactions and SMM properties, because these complexes contain two TbPc2 units in one molecule and their intramolecular Tb(III)-Tb(III) distances can be controlled by changing the number of stacks. Next, we focus on the switching of the Kondo signal of Tb(III)-Pc-based multiple-decker SMMs that are adsorbed onto surfaces, their characterization using STM and STS, and the relationship between the molecular structure, the electronic structure, and the Kondo resonance of Tb(III)-Pc multiple-decker complexes. PMID:26991524

  13. Molecular Dynamics Simulations on Parallel Computers: a Study of Polar Versus Nonpolar Media Effects in Small Molecule Solvation.

    NASA Astrophysics Data System (ADS)

    Debolt, Stephen Edward

    Solvent effects were studied and described via molecular dynamics (MD) and free energy perturbation (FEP) simulations using the molecular mechanics program AMBER. The following specific topics were explored:. Polar solvents cause a blue shift of the rm nto pi^* transition band of simple alkyl carbonyl compounds. The ground- versus excited-state solvation effects responsible for the observed solvatochromism are described in terms of the molecular level details of solute-solvent interactions in several modeled solvents spanning the range from polar to nonpolar, including water, methanol, and carbon tetrachloride. The structure and dynamics of octanol media were studied to explore the question: "why is octanol/water media such a good biophase analog?". The formation of linear and cyclic polymers of hydrogen-bonded solvent molecules, micelle-like clusters, and the effects of saturating waters are described. Two small drug-sized molecules, benzene and phenol, were solvated in water-saturated octanol. The solute-solvent structure and dynamics were analysed. The difference in their partitioning free energies was calculated. MD and FEP calculations were adapted for parallel computation, increasing their "speed" or the time span accessible by a simulation. The non-cyclic polyether ionophore salinomycin was studied in methanol solvent via parallel FEP. The path of binding and release for a potassium ion was investigated by calculating the potential of mean force along the "exit vector".

  14. 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.

  15. Extended molecular Ornstein-Zernike integral equation for fully anisotropic solute molecules: Formulation in a rectangular coordinate system

    NASA Astrophysics Data System (ADS)

    Ishizuka, Ryosuke; Yoshida, Norio

    2013-08-01

    An extended molecular Ornstein-Zernike (XMOZ) integral equation is formulated to calculate the spatial distribution of solvent around a solute of arbitrary shape and solid surfaces. The conventional MOZ theory employs spherical harmonic expansion technique to treat the molecular orientation of components of solution. Although the MOZ formalism is fully exact analytically, the truncation of the spherical harmonic expansion requires at a finite order for numerical calculation and causes the significant error for complex molecules. The XMOZ integral equation is the natural extension of the conventional MOZ theory to a rectangular coordinate system, which is free from the truncation of spherical harmonic expansion with respect to solute orientation. In order to show its applicability, we applied the XMOZ theory to several systems using the hypernetted-chain (HNC) and Kovalenko-Hirata approximations. The quality of results obtained within our theory is discussed by comparison with values from the conventional MOZ theory, molecular dynamics simulation, and three-dimensional reference interaction site model theory. The spatial distributions of water around the complex of non-charged sphere and dumbbell were calculated. Using this system, the approximation level of the XMOZ and other methods are discussed. To assess our theory, we also computed the excess chemical potentials for three realistic molecules (water, methane, and alanine dipeptide). We obtained the qualitatively reasonable results by using the XMOZ/HNC theory. The XMOZ theory covers a wide variety of applications in solution chemistry as a useful tool to calculate solvation thermodynamics.

  16. Extended molecular Ornstein-Zernike integral equation for fully anisotropic solute molecules: formulation in a rectangular coordinate system.

    PubMed

    Ishizuka, Ryosuke; Yoshida, Norio

    2013-08-28

    An extended molecular Ornstein-Zernike (XMOZ) integral equation is formulated to calculate the spatial distribution of solvent around a solute of arbitrary shape and solid surfaces. The conventional MOZ theory employs spherical harmonic expansion technique to treat the molecular orientation of components of solution. Although the MOZ formalism is fully exact analytically, the truncation of the spherical harmonic expansion requires at a finite order for numerical calculation and causes the significant error for complex molecules. The XMOZ integral equation is the natural extension of the conventional MOZ theory to a rectangular coordinate system, which is free from the truncation of spherical harmonic expansion with respect to solute orientation. In order to show its applicability, we applied the XMOZ theory to several systems using the hypernetted-chain (HNC) and Kovalenko-Hirata approximations. The quality of results obtained within our theory is discussed by comparison with values from the conventional MOZ theory, molecular dynamics simulation, and three-dimensional reference interaction site model theory. The spatial distributions of water around the complex of non-charged sphere and dumbbell were calculated. Using this system, the approximation level of the XMOZ and other methods are discussed. To assess our theory, we also computed the excess chemical potentials for three realistic molecules (water, methane, and alanine dipeptide). We obtained the qualitatively reasonable results by using the XMOZ/HNC theory. The XMOZ theory covers a wide variety of applications in solution chemistry as a useful tool to calculate solvation thermodynamics. PMID:24006986

  17. A probe molecule composed of seventeen percent of total diffracting matter gives correct solutions in molecular replacement.

    PubMed

    Oh, B H

    1995-03-01

    It is often found in the crystallization of enzyme-inhibitor complexes that an inhibitor causes crystal packing which is different to that of native protein. This is the case for crystals of human non-pancreatic secreted phospholipase A(2) (124 residues) containing six molecules in the asymmetric unit when the protein is complexed with a potential acylamino analogue of a phospholid. The hexameric structure was determined by molecular replacement using the structure of monomeric native protein as a probe. As an extension to the experiment, it was tested whether a backbone polypeptide composed of 17% of a known monomeric structure could find its correct position on a target molecule in molecular replacement. A probe model composed of the backbone atoms of the N-terminal 77 residues of lysine-, arginine-, ornithine-binding protein (LAO, a total of 238 residues) liganded with lysine correctly finds its position on LAO liganded with histidine which crystallizes as a monomer in the asymmetric unit. The results indicate that as little as 17% of total diffracting matter can be used in molecular replacement to solve crystal structures or to obtain phase information which can be combined with phases obtained by the isomorphous-replacement method. PMID:15299314

  18. Binding site identification and role of permanent water molecule of PIM-3 kinase: A molecular dynamics study.

    PubMed

    Ul-Haq, Zaheer; Gul, Sana; Usmani, Saman; Wadood, Abdul; Khan, Waqasuddin

    2015-11-01

    The kinome is a protein kinase complement of the human genome, categorized as serine/threonine and tyrosine kinases. These kinases catalyze phosphorylation reaction by using ATP as phosphoryl donor. Proviral Integration Site for Moloney Murine Leukemia Virus (PIM) kinase encodes serine/threonine protein kinases that recognized as proto-oncogene, responsible for rapid growth of cancerous cells. It is implicated in cell survival and function via cell cycle progression and its metabolism. PIM-3, sub-member of PIM kinases is a proto-oncogene, its overexpression inhibits apoptosis, and results in progression of hepatocellular carcinoma. PIM-3 is considered as a promising drug target but attempts to develop its specific inhibitors is slowed down due to the lack of 3D structure by any experimental technique. In silico techniques generally facilitate scientist to explore hidden structural features in order to improve drug discovery. In the present study, homology modeling, molecular docking and MD simulation techniques were utilized to explore the structure and dynamics of PIM-3 kinase. Induction of water molecules during molecular docking simulation explored differences in the hinge region between PIM-1 and PIM-3 kinases that may be responsible for specificity. Furthermore, role of water molecules in the active site was also explored via radial distribution function (RDF) after a 10 ns molecular dynamics (MD) simulations. Generated RDF plots exhibited the importance of water for inhibitor binding through their bridging capability that links the ligand with binding site residues. PMID:26529487

  19. Boiling Points of the Family of Small Molecules CHwFxClyBrz: How Are They Related to Molecular Mass?

    NASA Astrophysics Data System (ADS)

    Laing, Michael

    2001-11-01

    A plot of boiling point versus molecular mass for the family of tetrahedral molecular compounds CHw Fx Cly Brz is not linear, but yields a two-dimensional array with the data for molecules of similar formulae lying on straight lines. A plot of boiling point versus molar refraction (polarizability) of the compounds gives three near-parallel straight lines. The highest is for the family of compounds CH2XY; the lowest is for the all-halogen compounds CFxCyBrz; the compounds CHXxYyZz and CH3X lie intermediate. The boiling points of the compounds containing hydrogen are enhanced relative to what their molecular refraction suggests (excepting CH4). Boiling point is related to the macroscopic properties of refractive index and density of the liquid and to the molecular properties of molar refraction and dipole moment. These are connected by the molecular mass, which, with the density, determines the molar volume and thus the polarizability.

    See Letter re: this article.

    See Second Letter re: this article.

  20. 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

  1. Self-assembly and separation of nematic colloids through photo-patterned molecular orientation

    NASA Astrophysics Data System (ADS)

    Peng, Chenhui; Guo, Yubing; Conklin, Christopher; Viñals, Jorge; Shiyanovskii, Sergij; Wei, Qi-Huo; Lavrentovich, Oleg; Oleg D. Lavrentovich Team; Jorge Viñals Collaboration

    Design and control of particles self-assembly is an important theme in colloidal science. Dispersions of colloids in a nematic liquid crystal (LC) show a diversity of self-assembled structures guided by long-range interactions. Here we describe a versatile approach to control colloidal structures through surface-patterned molecular orientation and dynamic processes of LC-enabled electrokinetics (LCEK). In presence of the electric field, the surface-imprinted pattern of molecular orientation triggers LCEK flows which transport the colloidal aggregates to specified locations. The aggregation is directed by the director gradients. Colloids that differ in surface anchoring or shape are guided into different areas of the cell, thus being sorted. The dynamic approach to control colloidal systems through LCEK in cells with patterned director field opens the opportunities in the microfluidic and lab on a chip applications. This work was supported by NSF grants DMR-1507637 , DMS-1434185 and CMMI-1436565.

  2. Peripheral Neural Detection of Danger–Associated and Pathogen–Associated Molecular Patterns

    PubMed Central

    Kazymov, Vitaly; Marina, Nephtali; Singer, Mervyn; Gourine, Alexander V.

    2013-01-01

    Objective: Bidirectional links between the nervous and immune systems modulate inflammation. The cellular mechanisms underlying the detection of danger-associated molecular patterns and pathogen-associated molecular patterns by the nervous system are not well understood. We hypothesized that the carotid body, a tissue of neural crest origin, detect pathogen associated molecular patterns and danger associated molecular patterns via an inflammasome-dependent mechanism similar to that described in immune cells. Design: Randomized, controlled laboratory investigation. Setting: University laboratory. Subjects: C57Bl/6J mice; juvenile Sprague-Dawley rats, primary human neutrophils. Interventions: Rat carotid body chemosensitive cells, and human neutrophils, were treated with TLR agonists to activate inflammasome-dependent pathways. In mice, systemic inflammation was induced by the pathogen associated molecular pattern zymosan (intraperitoneal injection; 500 mg/kg). Isolated carotid body/carotid sinus nerve preparations were used to assess peripheral chemoafferent activity. Ventilation was measured by whole-body plethysmography. Measurements and Main Results: Chemosensitive carotid body glomus cells exhibited toll-like receptor (TLR-2 and TLR-4), NLRP1, and NLRP3 inflammasome immunoreactivities. Zymosan increased NLRP3 inflammasome and interleukin-1β expression in glomus cells (p < 0.01). Human neutrophils demonstrated similar LPS-induced changes in inflammasome expression. Carotid body glomus cells also expressed IL-1 receptor and responded to application of IL-1β with increases in intracellular [Ca2+]. Four hours after injection of zymosan carotid sinus nerve chemoafferent discharge assessed in vitro (i.e., in the absence of acidosis/circulating inflammatory mediators) was increased five-fold (p < 0.001). Accordingly, zymosan-induced systemic inflammation was accompanied by enhanced respiratory activity. Conclusions: In carotid body chemosensitive glomus cells

  3. Efficient new ribozyme mimics: direct mapping of molecular design principles from small molecules to macromolecular, biomimetic catalysts

    PubMed Central

    Putnam, William C.; Daniher, Andrew T.; Trawick, Bobby N.; Bashkin, James K.

    2001-01-01

    Dramatic improvements in ribozyme mimics have been achieved by employing the principles of small molecule catalysis to the design of macromolecular, biomimetic reagents. Ribozyme mimics derived from the ligand 2,9-dimethylphenanthroline (neocuproine) show at least 30-fold improvements in efficiency at sequence-specific RNA cleavage when compared with analogous o-phenanthroline- and terpyridine-derived reagents. The suppression of hydroxide-bridged dimers and the greater activation of coordinated water by Cu(II) neocuproine (compared with the o-phananthroline and terpyridine complexes) better allow Cu(II) to reach its catalytic potential as a biomimetic RNA cleavage agent. This work demonstrates the direct mapping of molecular design principles from small-molecule cleavage to macromolecular cleavage events, generating enhanced biomimetic, sequence-specific RNA cleavage agents. PMID:11353090

  4. Tonal Interface to MacroMolecules (TIMMol): A Textual and Tonal Tool for Molecular Visualization

    ERIC Educational Resources Information Center

    Cordes, Timothy J.; Carlson, C. Britt; Forest, Katrina T.

    2008-01-01

    We developed the three-dimensional visualization software, Tonal Interface to MacroMolecules or TIMMol, for studying atomic coordinates of protein structures. Key features include audio tones indicating x, y, z location, identification of the cursor location in one-dimensional and three-dimensional space, textual output that can be easily linked…

  5. Large-area ordered Ge-Si compound quantum dot molecules on dot-patterned Si (001) substrates

    NASA Astrophysics Data System (ADS)

    Lei, Hui; Zhou, Tong; Wang, Shuguang; Fan, Yongliang; Zhong, Zhenyang

    2014-08-01

    We report on the formation of large-area ordered Ge-Si compound quantum dot molecules (CQDMs) in a combination of nanosphere lithography and self-assembly. Truncated-pyramid-like Si dots with {11n} facets are readily formed, which are spatially ordered in a large area with controlled period and size. Each Si dot induces four self-assembled Ge-rich dots at its base edges that can be fourfold symmetric along <110> directions. A model based on surface chemical potential accounts well for these phenomena. Our results disclose the critical effect of surface curvature on the diffusion and the aggregation of Ge adatoms and shed new light on the unique features and the inherent mechanism of self-assembled QDs on patterned substrates. Such a configuration of one Si QD surrounded by fourfold symmetric Ge-rich QDs can be seen as a CQDM with unique features, which will have potential applications in novel devices.

  6. Between molecules and experience: role of early patterns of coordinated activity for the development of cortical maps and sensory abilities.

    PubMed

    Hanganu-Opatz, Ileana L

    2010-09-01

    Sensory systems processing information from the environment rely on precisely formed and refined neuronal networks that build maps of sensory receptor epithelia at different subcortical and cortical levels. These sensory maps share similar principles of function and emerge according to developmental processes common in visual, somatosensory and auditory systems. Whereas molecular cues set the coarse organization of cortico-subcortical topography, its refinement is known to succeed under the influence of experience-dependent electrical activity during critical periods. However, coordinated patterns of activity synchronize the cortico-subcortical networks long before the meaningful impact of environmental inputs on sensory maps. Recent studies elucidated the cellular and network mechanisms underlying the generation of these early patterns of activity and highlighted their similarities across species. Moreover, the experience-independent activity appears to act as a functional template for the maturation of sensory networks and cortico-subcortical maps. A major goal for future research will be to analyze how this early activity interacts with the molecular cues and to determine whether it is permissive or rather supporting for the establishment of sensory topography. PMID:20381527

  7. Templating effects in molecular growth of blended films for efficient small-molecule photovoltaics.

    PubMed

    Wang, Zhiping; Miyadera, Tetsuhiko; Yamanari, Toshihiro; Yoshida, Yuji

    2014-05-14

    A strategy to control the molecular growth of coevaporated zinc phthalocyanine (ZnPc) and fullerene (C60) blended films for efficient organic photovoltaic (OPV) cells was demonstrated. Introduction of a 2,5-bis(4-biphenylyl)-bithiophene (BP2T) film or a ZnPc film on BP2T as nanostructured templates not only results in phase-separated domains in blended films with clear interpenetrating networks but also improves the crystallinity of ZnPc domains, both of which enhance photocurrent generation and charge carrier transport. Such morphology is strongly associated with the molecular growth of the templating layers. Roughness and adhesion of the templating layers are of great importance for the molecular growth of the blended films and in turn for cell characteristics. By carefully regulating the molecular growth of the blended films, the power conversion efficiency was improved by 125%, from 1.85 to 4.15% under 1 sun. PMID:24712371

  8. Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids

    DOE PAGESBeta

    Aradi, Bálint; Niklasson, Anders M. N.; Frauenheim, Thomas

    2015-06-26

    A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born–Oppenheimer molecular dynamics. Furthermore, for systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can also be applied to a broad range of problems in materialsmore » science, chemistry, and biology.« less

  9. Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids

    SciTech Connect

    Aradi, Bálint; Niklasson, Anders M. N.; Frauenheim, Thomas

    2015-06-26

    A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born–Oppenheimer molecular dynamics. Furthermore, for systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can also be applied to a broad range of problems in materials science, chemistry, and biology.

  10. 'Molecules and monkeys': George Gaylord Simpson and the challenge of molecular evolution.

    PubMed

    Aronson, Jay D

    2002-01-01

    In this paper, I analyze George Gaylord Simpson's response to the molecularization of evolutionary biology from his unique perspective as a paleontologist. I do so by exploring his views on early attempts to reconstruct phylogenetic relationships among primates using molecular data. Particular attention is paid to Simpson's role in the evolutionary synthesis of the 1930s and 1940s, as well as his concerns about the rise of molecular biology as a powerful discipline and world-view in the 1960s. I argue that Simpson's belief in the supremacy of natural selection as the primary driving force of evolution, as well as his view that biology was a historical science that seeks ultimate causes and highlights contingency, prevented him from acknowledging that the study of molecular evolution was an inherently valuable part of the life sciences. PMID:15045833

  11. Design and development of a field-deployable single-molecule detector (SMD) for the analysis of molecular markers†

    PubMed Central

    Emory, Jason M.; Peng, Zhiyong; Young, Brandon; Hupert, Mateusz L.; Rousselet, Arnold; Patterson, Donald; Ellison, Brad; Soper, Steven A.

    2012-01-01

    Single-molecule detection (SMD) has demonstrated some attractive benefits for many types of biomolecular analyses including enhanced processing speed by eliminating processing steps, elimination of ensemble averaging and single-molecule sensitivity. However, it's wide spread use has been hampered by the complex instrumentation required for its implementation when using fluorescence as the readout modality. We report herein a simple and compact fluorescence single-molecule instrument that is straightforward to operate and consisted of fiber optics directly coupled to a microfluidic device. The integrated fiber optics served as waveguides to deliver the laser excitation light to the sample and collecting the resulting emission, simplifying the optical requirements associated with traditional SMD instruments by eliminating the need for optical alignment and simplification of the optical train. Additionally, the use of a vertical cavity surface emitting laser and a single photon avalanche diode serving as the excitation source and photon transducer, respectively, as well as a field programmable gate array (FPGA) integrated into the processing electronics assisted in reducing the instrument footprint. This small footprint SMD platform was tested using fluorescent microspheres and single AlexaFluor 660 molecules to determine the optimal operating parameters and system performance. As a demonstration of the utility of this instrument for biomolecular analyses, molecular beacons (MBs) were designed to probe bacterial cells for the gene encoding Gram-positive species. The ability to monitor biomarkers using this simple and portable instrument will have a number of important applications, such as strain-specific detection of pathogenic bacteria or the molecular diagnosis of diseases requiring rapid turn-around-times directly at the point-of-use. PMID:22005669

  12. Water-inducing molecular self-assembly of amphiphilic molecules into nanofibers

    SciTech Connect

    Zhang, Weiguang; Zhao, Pusu; Song, Jie

    2011-12-15

    Graphical abstract: TPDP nanofibers with smooth surfaces can be obtained by reprecipitation method using ethanol as good solvent and water as poor solvent. In the self-assembly process, during the water adding to the amphiphilic molecules' saturated solution, the amphiphilic molecules firstly assembled into needle-like small rods. With an increase in the self-assembled time, a large number of the nanofibers are produced. The assembly behavior was revealed in the course of direct in situ monitoring of its growth with optical microscopy. Highlights: Black-Right-Pointing-Pointer 2,3,6,7-Tetramethoxy-9,10-di(4-pyridyl)-9,10-dihydroanthracen (TPDP) was synthesized. Black-Right-Pointing-Pointer TPDP nanofibers can be obtained by reprecipitation method. Black-Right-Pointing-Pointer The assembly behavior was revealed in situ monitoring with optical microscopy. -- Abstract: We present investigations on the microcosmic self-assembly process of new synthesized amphiphilic TPDP molecules. It can be seen that pure TPDP nanofibers with smooth surfaces can be obtained by reprecipitation method using ethanol as good solvent and water as poor solvent. In the self-assembly process, during the water adding to the amphiphilic molecules' saturated solution, the amphiphilic molecules firstly assembled into needle-like small rods. With an increase in the self-assembled time, a large number of the nanofibers are produced. The assembly behavior was revealed in the course of direct in situ monitoring of its growth with optical microscopy. Field emission scanning electron microscopy was adopted to characterize the morphologies of the products.

  13. Musical molecules: the molecular junction as an active component in audio distortion circuits

    NASA Astrophysics Data System (ADS)

    Bergren, Adam Johan; Zeer-Wanklyn, Lucas; Semple, Mitchell; Pekas, Nikola; Szeto, Bryan; McCreery, Richard L.

    2016-03-01

    Molecular junctions that have a non-linear current-voltage characteristic consistent with quantum mechanical tunneling are demonstrated as analog audio clipping elements in overdrive circuits widely used in electronic music, particularly with electric guitars. The performance of large-area molecular junctions fabricated at the wafer level is compared to currently standard semiconductor diode clippers, showing a difference in the sound character. The harmonic distributions resulting from the use of traditional and molecular clipping elements are reported and discussed, and differences in performance are noted that result from the underlying physics that controls the electronic properties of each clipping component. In addition, the ability to tune the sound using the molecular junction is demonstrated. Finally, the hybrid circuit is compared to an overdriven tube amplifier, which has been the standard reference electric guitar clipped tone for over 60 years. In order to investigate the feasibility of manufacturing molecular junctions for use in commercial applications, devices are fabricated using a low-density format at the wafer level, where 38 dies per wafer, each containing two molecular junctions, are made with exceptional non-shorted yield (99.4%, representing 718 out of 722 tested devices) without requiring clean room facilities.

  14. Musical molecules: the molecular junction as an active component in audio distortion circuits.

    PubMed

    Bergren, Adam Johan; Zeer-Wanklyn, Lucas; Semple, Mitchell; Pekas, Nikola; Szeto, Bryan; McCreery, Richard L

    2016-03-01

    Molecular junctions that have a non-linear current-voltage characteristic consistent with quantum mechanical tunneling are demonstrated as analog audio clipping elements in overdrive circuits widely used in electronic music, particularly with electric guitars. The performance of large-area molecular junctions fabricated at the wafer level is compared to currently standard semiconductor diode clippers, showing a difference in the sound character. The harmonic distributions resulting from the use of traditional and molecular clipping elements are reported and discussed, and differences in performance are noted that result from the underlying physics that controls the electronic properties of each clipping component. In addition, the ability to tune the sound using the molecular junction is demonstrated. Finally, the hybrid circuit is compared to an overdriven tube amplifier, which has been the standard reference electric guitar clipped tone for over 60 years. In order to investigate the feasibility of manufacturing molecular junctions for use in commercial applications, devices are fabricated using a low-density format at the wafer level, where 38 dies per wafer, each containing two molecular junctions, are made with exceptional non-shorted yield (99.4%, representing 718 out of 722 tested devices) without requiring clean room facilities. PMID:26871885

  15. H{sub 2} MOLECULAR CLUSTERS WITH EMBEDDED MOLECULES AND ATOMS AS THE SOURCE OF THE DIFFUSE INTERSTELLAR BANDS

    SciTech Connect

    Bernstein, L. S.; Clark, F. O.; Lynch, D. K. E-mail: dave@thulescientific.com

    2013-05-01

    We suggest that the diffuse interstellar bands (DIBs) arise from absorption lines of electronic transitions in molecular clusters primarily composed of a single molecule, atom, or ion ({sup s}eed{sup )}, embedded in a single-layer shell of H{sub 2} molecules. Less abundant variants of the cluster, including two seed molecules and/or a two-layer shell of H{sub 2} molecules, may also occur. The lines are broadened, blended, and wavelength-shifted by interactions between the seed and surrounding H{sub 2} shell. We refer to these clusters as contaminated H{sub 2} clusters (CHCs). We show that CHC spectroscopy matches the diversity of observed DIB spectral profiles and provides good fits to several DIB profiles based on a rotational temperature of 10 K. CHCs arise from {approx}centimeter-sized, dirty H{sub 2} ice balls, called contaminated H{sub 2} ice macro-particles (CHIMPs), formed in cold, dense, giant molecular clouds (GMCs), and later released into the interstellar medium (ISM) upon GMC disruption. Attractive interactions, arising from Van der Waals and ion-induced dipole potentials, between the seeds and H{sub 2} molecules enable CHIMPs to attain centimeter-sized dimensions. When an ultraviolet (UV) photon is absorbed in the outer layer of a CHIMP, it heats the icy matrix and expels CHCs into the ISM. While CHCs are quickly destroyed by absorbing UV photons, they are replenished by the slowly eroding CHIMPs. Since CHCs require UV photons for their release, they are most abundant at, but not limited to, the edges of UV-opaque molecular clouds, consistent with the observed, preferred location of DIBs. An inherent property of CHCs, which can be characterized as nanometer size, spinning, dipolar dust grains, is that they emit in the radio-frequency region. We also show that the CHCs offer a natural explanation for the anomalous microwave emission feature in the {approx}10-100 GHz spectral region.

  16. Molecular analogs of the hemihelix: A computational study of chain molecules containing left- and right-handed helices

    NASA Astrophysics Data System (ADS)

    Pichierri, Fabio

    2014-08-01

    Using density functional theory (DFT) we design two novel chain molecules containing a left-handed (thia)helicene unit connected to a right-handed (thia)helicene unit via a phosphoroussbnd phosphorous (Psbnd P) bond. These chains represent the molecular analogs of the novel hemihelix structure recently discovered by a group of Harvard University scientists. The HOMO and LUMO levels of the heterochiral chains, termed hemihelicenes, are localized on the left- and right-handed blocks, respectively. In contrast, the frontier orbitals of the chains containing homochiral (thia)helicenes connected by a Psbnd P bond are delocalized all over the chain.

  17. Sialyllactose in Viral Membrane Gangliosides Is a Novel Molecular Recognition Pattern for Mature Dendritic Cell Capture of HIV-1

    PubMed Central

    Contreras, F.-Xabier; Rodriguez-Plata, Maria T.; Glass, Bärbel; Erkizia, Itziar; Prado, Julia G.; Casas, Josefina; Fabriàs, Gemma; Kräusslich, Hans-Georg; Martinez-Picado, Javier

    2012-01-01

    HIV-1 is internalized into mature dendritic cells (mDCs) via an as yet undefined mechanism with subsequent transfer of stored, infectious virus to CD4+ T lymphocytes. Thus, HIV-1 subverts a DC antigen capture mechanism to promote viral spread. Here, we show that gangliosides in the HIV-1 membrane are the key molecules for mDC uptake. HIV-1 virus-like particles and liposomes mimicking the HIV-1 lipid composition were shown to use a common internalization pathway and the same trafficking route within mDCs. Hence, these results demonstrate that gangliosides can act as viral attachment factors, in addition to their well known function as cellular receptors for certain viruses. Furthermore, the sialyllactose molecule present in specific gangliosides was identified as the determinant moiety for mDC HIV-1 uptake. Thus, sialyllactose represents a novel molecular recognition pattern for mDC capture, and may be crucial both for antigen presentation leading to immunity against pathogens and for succumbing to subversion by HIV-1. PMID:22545022

  18. CERAMIDE AND SPHINGOSINE-1-PHOSPHATE ACT AS PHOTODYNAMIC THERAPY-ELICITED DAMAGE-ASSOCIATED MOLECULAR PATTERNS: CELL SURFACE EXPOSURE

    PubMed Central

    Korbelik, Mladen; Banáth, Judit; Sun, Jinghai; Canals, Daniel; Hannun, Yusuf A.; Separovic, Duska

    2014-01-01

    Molecules that appear on the surface of tumor cells after their therapy treatment may have important roles either as damage-associated molecular patterns (DAMPs) or signals for phagocytes influencing the disposal of these cells. Treatment of SCCVII and CAL27 cells, models of mouse and human squamous cell carcinoma respectively, by photodynamic therapy (PDT) resulted in the presentation of ceramide and sphingosine-1-phposphate (S1P) on the cell surface. This was documented by anti-ceramide and anti-S1P antibody staining followed by flow cytometry. The exposure of these key sphingolipid molecules on PDT-treated tumor cells was PDT dose-dependent and it varied in intensity with different photosensitizers used for PDT. The above results, together with the finding that both ceramide and S1P can activate NFκB signaling in macrophages co-incubated with PDT-treated tumor cells, establish that these two sphingolipids can act as DAMPs stimulating inflammatory/immune reactions critical for tumor therapy response. PMID:24713544

  19. Sulphur-bearing molecules in diffuse molecular clouds: new results from SOFIA/GREAT and the IRAM 30 m telescope

    NASA Astrophysics Data System (ADS)

    Neufeld, D. A.; Godard, B.; Gerin, M.; Pineau des Forêts, G.; Bernier, C.; Falgarone, E.; Graf, U. U.; Güsten, R.; Herbst, E.; Lesaffre, P.; Schilke, P.; Sonnentrucker, P.; Wiesemeyer, H.

    2015-05-01

    We have observed five sulphur-bearing molecules in foreground diffuse molecular clouds lying along the sight-lines to five bright continuum sources. We have used the GREAT instrument on SOFIA to observe the SH 1383 GHz 2Π3/2 J = 5/2 ← 3/2 lambda doublet toward the star-forming regions W31C, G29.96-0.02, G34.3+0.1, W49N and W51, detecting foreground absorption towards all five sources; and the EMIR receivers on the IRAM 30 m telescope at Pico Veleta to detect the H2S 110-101 (169 GHz), CS J = 2-1 (98 GHz) and SO 32-21 (99 GHz) transitions. Upper limits on the H3S+10-00 (293 GHz) transition were also obtained at the IRAM 30 m. In nine foreground absorption components detected towards these sources, the inferred column densities of the four detected molecules showed relatively constant ratios, with N(SH) /N(H2S) in the range 1.1-3.0, N(CS) /N(H2S) in the range 0.32-0.61, and N(SO) /N(H2S) in the range 0.08-0.30. The column densities of the sulphur-bearing molecules are very well correlated amongst themselves, moderately well correlated with CH (a surrogate tracer for H2), and poorly correlated with atomic hydrogen. The observed SH/H2 ratios - in the range 5 to 26 × 10-9 - indicate that SH (and other sulphur-bearing molecules) account for ≪ 1% of the gas-phase sulphur nuclei. The observed abundances of sulphur-bearing molecules, however, greatly exceed those predicted by standard models of cold diffuse molecular clouds, providing further evidence for the enhancement of endothermic reaction rates by elevated temperatures or ion-neutral drift. We have considered the observed abundance ratios in the context of shock and turbulent dissipation region (TDR) models. Using the TDR model, we find that the turbulent energy available at large scale in the diffuse ISM is sufficient to explain the observed column densities of SH and CS. Standard shock and TDR models, however, fail to reproduce the column densities of H2S and SO by a factor of about 10; more elaborate shock

  20. Interaction between water molecules and zinc sulfide nanoparticles studied by temperature-programmed desorption and molecular dynamics simulations.

    PubMed

    Zhang, Hengzhong; Rustad, James R; Banfield, Jillian F

    2007-06-14

    We have investigated the bonding of water molecules to the surfaces of ZnS nanoparticles (approximately 2-3 nm sphalerite) using temperature-programmed desorption (TPD). The activation energy for water desorption was derived as a function of the surface coverage through kinetic modeling of the experimental TPD curves. The binding energy of water equals the activation energy of desorption if it is assumed that the activation energy for adsorption is nearly zero. Molecular dynamics (MD) simulations of water adsorption on 3 and 5 nm sphalerite nanoparticles provided insights into the adsorption process and water binding at the atomic level. Water binds with the ZnS nanoparticle surface mainly via formation of Zn-O bonds. As compared with bulk ZnS crystals, ZnS nanoparticles can adsorb more water molecules per unit surface area due to the greatly increased curvature, which increases the distance between adjacent adsorbed molecules. Results from both TPD and MD show that the water binding energy increases with decreasing the water surface coverage. We attribute the increase in binding energy with decreasing surface water coverage to the increasing degree of surface under-coordination as removal of water molecules proceeds. MD also suggests that the water binding energy increases with decreasing particle size due to the further distance and hence lower interaction between adsorbed water molecules on highly curved smaller particle surfaces. Results also show that the binding energy, and thus the strength of interaction of water, is highest in isolated nanoparticles, lower in nanoparticle aggregates, and lowest in bulk crystals. Given that water binding is driven by surface energy reduction, we attribute the decreased binding energy for aggregated as compared to isolated particles to the decrease in surface energy that occurs as the result of inter-particle interactions. PMID:17518448

  1. 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.

  2. Molecular and functional characterization of granulin-like molecules of insects.

    PubMed

    Hanington, Patrick C; Brennan, Lesley J; Belosevic, Miodrag; Andrew Keddie, B

    2008-05-01

    Granulins are a group of highly conserved growth factors that have been described from a variety of organisms spanning the metazoa. Here, we report on the identification of two partial transcripts encoding granulin-like molecules from Aa23 embryonic cells of Aedes albopictus and primary haemocytes from Manduca sexta. Both these partial transcripts had the characteristic 12-cysteine motif that is a hallmark of the granulin family and they represent the first granulin mRNA transcripts identified from insects. Moreover, we demonstrate that the recombinant granulin molecule that we originally cloned in the goldfish, induced proliferation of both Aa23 embryonic cells and primary haemocytes. Interestingly, this proliferative effect was upregulated in the presence of the intracellular symbiotic bacterium Wolbachia pipientis. Thus, granulin appears to be a highly conserved growth factor not only in lower vertebrates but also invertebrates. PMID:18405836

  3. Phospholipid Membrane Protection by Sugar Molecules during Dehydration-Insights into Molecular Mechanisms Using Scattering Techniques

    SciTech Connect

    Garvey, Christopher J.; Lenné, Thomas; Koster, Karen L.; Kent, Ben; Bryant, Gary

    2014-09-24

    Scattering techniques have played a key role in our understanding of the structure and function of phospholipid membranes. These techniques have been applied widely to study how different molecules (e.g., cholesterol) can affect phospholipid membrane structure. However, there has been much less attention paid to the effects of molecules that remain in the aqueous phase. One important example is the role played by small solutes, particularly sugars, in protecting phospholipid membranes during drying or slow freezing. In this paper, we present new results and a general methodology, which illustrate how contrast variation small angle neutron scattering (SANS) and synchrotron-based X-ray scattering (small angle (SAXS) and wide angle (WAXS)) can be used to quantitatively understand the interactions between solutes and phospholipids. Specifically, we show the assignment of lipid phases with synchrotron SAXS and explain how SANS reveals the exclusion of sugars from the aqueous region in the particular example of hexagonal II phases formed by phospholipids.

  4. Small molecule interaction with lipid bilayers: a molecular dynamics study of chlorhexidine.

    PubMed

    Van Oosten, Brad; Marquardt, Drew; Komljenović, Ivana; Bradshaw, Jeremy P; Sternin, Edward; Harroun, Thad A

    2014-03-01

    Chlorhexidine (CHX) is an effective anti-bacterial agent whose mode of action is thought to be the disruption of the cell membrane. We tested the capability of the Slipids all atom force fields using data from neutron scattering and NMR experiments on the drug chlorhexidine in a 1,2-dimyrisoyl-3-sn-phosphatidylcholine (DMPC) membrane. Since it is not known what the charge of the CHX molecule is inside an apolar environment, a neutral, as well as a +1 and +2 charge model for the molecule were created and tested at several concentrations. This study shows that the location of CHX is minorly dependent on concentration, and dominantly reliant on the charge. The effect of adding CHX to DMPC is a thinning of the membrane, thus increasing the area per lipid. PMID:24440582

  5. Modeling Stochastic Kinetics of Molecular Machines at Multiple Levels: From Molecules to Modules

    PubMed Central

    Chowdhury, Debashish

    2013-01-01

    A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here. PMID:23746505

  6. Spectroscopic [FT-IR and FT-Raman] and molecular modeling (MM) study of benzene sulfonamide molecule using quantum chemical calculations

    NASA Astrophysics Data System (ADS)

    Vinod, K. S.; Periandy, S.; Govindarajan, M.

    2016-07-01

    The spectroscopic and molecular modeling (MM) study includes, FT-IR, FT-Raman and 13C NMR and 1H NMR spectra of the Benzene sulfonamide were recorded for the analysis. The observed experimental and theoretical frequencies (IR and Raman) were assigned according to their distinctive region. The present study of this title molecule have been carried out by hybrid computational calculations of HF and DFT (B3LYP) methods with 6-311+G(d,p) and 6-311++G(d,p) basis sets and the corresponding results are tabulated. The structural modifications of the compound due to the substitutions of NH2 and SO2 were investigated. The minimum energy conformers of the compound were studied using conformational analysis. The alternations of the vibrational pattern of the base structure related to the substitutions were analyzed. The thermodynamic parameters (such as zero-point vibrational energy, thermal energy, specific heat capacity, rotational constants, entropy, and dipole moment) of Benzene sulfonamide have been calculated. The donor acceptor interactions of the compound and the corresponding UV transitions are found out using NBO analysis. The NMR spectra were simulated by using the gauge independent atomic orbital (GIAO) method with B3LYP methods and the 6-311++G(d,p) basis set and their spectra were simulated and the chemical shifts related to TMS were compared. A quantum computational study on the electronic and optical properties absorption wavelengths, excitation energy, dipole moment and frontier molecular orbital energies, were performed by HF and DFT methods. The energy gap of the present compound was calculated related to HOMO and LUMO energies which confirm the occurring of charge transformation between the base and ligand group. Besides frontier molecular orbitals (FMO), molecular electrostatic potential (MEP) was performed. The thermodynamic properties (heat capacity, entropy, and enthalpy) of the title compound at different temperatures were calculated in gas phase and

  7. Molecular Dynamics Simulation Study of Permeation of Molecules through Skin Lipid Bilayer.

    PubMed

    Gupta, Rakesh; Sridhar, D B; Rai, Beena

    2016-09-01

    Stratum Corneum (SC), the outermost layer of skin, is mainly responsible for skin's barrier function. The complex lipid matrix of SC determines these barrier properties. In this study, the lipid matrix is modeled as an equimolar mixture of ceramide (CER), cholesterol (CHOL), and free fatty acid (FFA). The permeation of water, oxygen, ethanol, acetic acid, urea, butanol, benzene, dimethyl sulfoxide (DMSO), toluene, phenol, styrene, and ethylbenzene across this layer is studied using a constrained MD simulations technique. Several long constrained simulations are performed at a skin temperature of 310 K under NPT conditions. The free energy profiles and diffusion coefficients along the bilayer normal have been calculated for each molecule. Permeability coefficients are also calculated and compared with experimental data. The main resistance for the permeation of hydrophilic and hydrophobic permeants has been found to be in the interior of the lipid bilayer and near the lipid-water interface, respectively. The obtained permeability is found to be a few orders of magnitude higher than experimental values for hydrophilic molecules while for hydrophobic molecules more discrepancy was observed. Overall, the qualitative ranking is consistent with the experiments. PMID:27518707

  8. Fundamental Molecular Mechanism for the Cellular Uptake of Guanidinium-Rich Molecules

    PubMed Central

    2015-01-01

    Guanidinium-rich molecules, such as cell-penetrating peptides, efficiently enter living cells in a non-endocytic energy-independent manner and transport a wide range of cargos, including drugs and biomarkers. The mechanism by which these highly cationic molecules efficiently cross the hydrophobic barrier imposed by the plasma membrane remains a fundamental open question. Here, a combination of computational results and in vitro and live-cell experimental evidence reveals an efficient energy-independent translocation mechanism for arginine-rich molecules. This mechanism unveils the essential role of guanidinium groups and two universal cell components: fatty acids and the cell membrane pH gradient. Deprotonated fatty acids in contact with the cell exterior interact with guanidinium groups, leading to a transient membrane channel that facilitates the transport of arginine-rich peptides toward the cell interior. On the cytosolic side, the fatty acids become protonated, releasing the peptides and resealing the channel. This fundamental mechanism appears to be universal across cells from different species and kingdoms. PMID:25405895

  9. Fundamental molecular mechanism for the cellular uptake of guanidinium-rich molecules.

    PubMed

    Herce, Henry D; Garcia, Angel E; Cardoso, M Cristina

    2014-12-17

    Guanidinium-rich molecules, such as cell-penetrating peptides, efficiently enter living cells in a non-endocytic energy-independent manner and transport a wide range of cargos, including drugs and biomarkers. The mechanism by which these highly cationic molecules efficiently cross the hydrophobic barrier imposed by the plasma membrane remains a fundamental open question. Here, a combination of computational results and in vitro and live-cell experimental evidence reveals an efficient energy-independent translocation mechanism for arginine-rich molecules. This mechanism unveils the essential role of guanidinium groups and two universal cell components: fatty acids and the cell membrane pH gradient. Deprotonated fatty acids in contact with the cell exterior interact with guanidinium groups, leading to a transient membrane channel that facilitates the transport of arginine-rich peptides toward the cell interior. On the cytosolic side, the fatty acids become protonated, releasing the peptides and resealing the channel. This fundamental mechanism appears to be universal across cells from different species and kingdoms. PMID:25405895

  10. Multicomponent redox catalysts for reduction of large biological molecules using molecular hydrogen as the reductant

    SciTech Connect

    Chao, S.; Simon, R.A.; Mallouk, T.E.; Wrighton, M.S.

    1988-03-30

    One-electron reduction of the large biological molecules horse heart cytochrome c, sperm whale myoglobin, and horseradish peroxidase using H/sub 2/ as the reductant can be catalyzed by two-component, high surface area heterogeneous catalysts. The catalysts can be prepared by first functionalizing high surface area SiO/sub 2/ with a polycationic polymer into which is dispersed MCl/sub 4//sup 2 -/ (M = Pd, Pt). Reduction with H/sub 2/ yields elemental Pd or Pt dispersed in the polymer. The particles are finally functionalized with a redox polymer derived from hydrolysis of Si(OR)/sub 3/ groups of an N,N'-dialkyl-4,4'-bipyridinium- or from a cobalticenium-based monomer. The two components of the heterogeneous catalysts are the buried noble metal capable of activating the H/sub 2/ and the redox polymer, which can equilibrate both with the noble metal and with the large biological molecule. Reduction of the large biological molecules in aqueous solution can be effected at room temperature and 1 atm H/sub 2/ using the catalysts under conditions where the biological materials would not be reducible with H/sub 2/ alone or when the noble metal alone would be used as the catalyst.

  11. Initiating Molecular Growth in the Interstellar Medium via Dimeric Complexes of Observed Ions and Molecules

    NASA Technical Reports Server (NTRS)

    Bera, Partha P.; Head-Gordon, Martin; Lee, Timothy J.

    2011-01-01

    A feasible initiation step for particle growth in the interstellar medium (ISM) is simulated by means of ab quantum chemistry methods. The systems studied are dimer ions formed by pairing nitrogen containing small molecules known to exist in the ISM with ions of unsaturated hydrocarbons or vice versa. Complexation energies, structures of ensuing complexes and electronic excitation spectra of the encounter complexes are estimated using various quantum chemistry methods. Moller-Plesset perturbation theory (MP2, Z-averaged perturbation theory (ZAP2), coupled cluster singles and doubles with perturbative triples corrections (CCSD(T)), and density functional theory (DFT) methods (B3LYP) were employed along with the correlation consistent cc-pVTZ and aug-cc-pVTZ basis sets. Two types of complexes are predicted. One type of complex has electrostatic binding with moderate (7-20 kcal per mol) binding energies, that are nonetheless significantly stronger than typical van der Waals interactions between molecules of this size. The other type of complex develops strong covalent bonds between the fragments. Cyclic isomers of the nitrogen containing complexes are produced very easily by ion-molecule reactions. Some of these complexes show intense ultraviolet visible spectra for electronic transitions with large oscillator strengths at the B3LYP, omegaB97, and equations of motion coupled cluster (EOM-CCSD) levels. The open shell nitrogen containing carbonaceous complexes especially exhibit a large oscillator strength electronic transition in the visible region of the electromagnetic spectrum.

  12. Healthy dietary patterns and risk of breast cancer by molecular subtype.

    PubMed

    Hirko, Kelly A; Willett, Walter C; Hankinson, Susan E; Rosner, Bernard A; Beck, Andrew H; Tamimi, Rulla M; Eliassen, A Heather

    2016-02-01

    We examined associations between dietary quality indices and breast cancer risk by molecular subtype among 100,643 women in the prospective Nurses' Health Study (NHS) cohort, followed from 1984 to 2006. Dietary quality scores for the Alternative Healthy Eating Index (AHEI), alternate Mediterranean diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) dietary patterns were calculated from semi-quantitative food frequency questionnaires collected every 2-4 years. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor status from immunostained tumor microarrays in combination with histologic grade. Cox proportional hazards models, adjusted for age and breast cancer risk factors, were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Competing risk analyses were used to assess heterogeneity by subtype. We did not observe any significant associations between the AHEI or aMED dietary patterns and risk of breast cancer by molecular subtype. However, a significantly reduced risk of HER2-type breast cancer was observed among women in 5th versus 1st quintile of the DASH dietary pattern [n = 134 cases, Q5 vs. Q1 HR (95 % CI) = 0.44 (0.25-0.77)], and the inverse trend across quintiles was significant (p trend = 0.02). We did not observe any heterogeneity in associations between AHEI (p het = 0.25), aMED (p het = 0.71), and DASH (p het = 0.12) dietary patterns and breast cancer by subtype. Adherence to the AHEI, aMED, and DASH dietary patterns was not strongly associated with breast cancer molecular subtypes. PMID:26872903

  13. A recombinant horseshoe crab plasma lectin recognizes specific pathogen-associated molecular patterns of bacteria through rhamnose.

    PubMed

    Ng, Sim-Kun; Huang, Yu-Tsyr; Lee, Yuan-Chuan; Low, Ee-Ling; Chiu, Cheng-Hsun; Chen, Shiu-Ling; Mao, Liang-Chi; Chang, Margaret Dah-Tsyr

    2014-01-01

    Horseshoe crab is an ancient marine arthropod that, in the absence of a vertebrate-like immune system, relies solely on innate immune responses by defense molecules found in hemolymph plasma and granular hemocytes for host defense. A plasma lectin isolated from the hemolymph of Taiwanese Tachypleus tridentatus recognizes bacteria and lipopolysaccharides (LPSs), yet its structure and mechanism of action remain unclear, largely because of limited availability of horseshoe crabs and the lack of a heterogeneous expression system. In this study, we have successfully expressed and purified a soluble and functional recombinant horseshoe crab plasma lectin (rHPL) in an Escherichia coli system. Interestingly, rHPL bound not only to bacteria and LPSs like the native HPL but also to selective medically important pathogens isolated from clinical specimens, such as Gram-negative Pseudomonas aeruginosa and Klebsiella pneumoniae and Gram-positive Streptococcus pneumoniae serotypes. The binding was demonstrated to occur through a specific molecular interaction with rhamnose in pathogen-associated molecular patterns (PAMPs) on the bacterial surface. Additionally, rHPL inhibited the growth of P. aeruginosa PAO1 in a concentration-dependent manner. The results suggest that a specific protein-glycan interaction between rHPL and rhamnosyl residue may further facilitate development of novel diagnostic and therapeutic strategies for microbial pathogens. PMID:25541995

  14. A Recombinant Horseshoe Crab Plasma Lectin Recognizes Specific Pathogen-Associated Molecular Patterns of Bacteria through Rhamnose

    PubMed Central

    Ng, Sim-Kun; Huang, Yu-Tsyr; Lee, Yuan-Chuan; Low, Ee-Ling; Chiu, Cheng-Hsun; Chen, Shiu-Ling; Mao, Liang-Chi; Chang, Margaret Dah-Tsyr

    2014-01-01

    Horseshoe crab is an ancient marine arthropod that, in the absence of a vertebrate-like immune system, relies solely on innate immune responses by defense molecules found in hemolymph plasma and granular hemocytes for host defense. A plasma lectin isolated from the hemolymph of Taiwanese Tachypleus tridentatus recognizes bacteria and lipopolysaccharides (LPSs), yet its structure and mechanism of action remain unclear, largely because of limited availability of horseshoe crabs and the lack of a heterogeneous expression system. In this study, we have successfully expressed and purified a soluble and functional recombinant horseshoe crab plasma lectin (rHPL) in an Escherichia coli system. Interestingly, rHPL bound not only to bacteria and LPSs like the native HPL but also to selective medically important pathogens isolated from clinical specimens, such as Gram-negative Pseudomonas aeruginosa and Klebsiella pneumoniae and Gram-positive Streptococcus pneumoniae serotypes. The binding was demonstrated to occur through a specific molecular interaction with rhamnose in pathogen-associated molecular patterns (PAMPs) on the bacterial surface. Additionally, rHPL inhibited the growth of P. aeruginosa PAO1 in a concentration-dependent manner. The results suggest that a specific protein-glycan interaction between rHPL and rhamnosyl residue may further facilitate development of novel diagnostic and therapeutic strategies for microbial pathogens. PMID:25541995

  15. Meet the Molecules in Chocolate: Informal Opportunities for Building Thematic Molecular Models with Children

    ERIC Educational Resources Information Center

    Amey, Jennifer R.; Fletcher, Matthew D.; Fletcher, Rachael V.; Jones, Alison; Roberts, Erica W.; Roberts, Ieuan O.

    2008-01-01

    We describe the development and use of a molecular model building activity with a chocolate theme, suitable for a public presentation of chemistry through interaction with visitors to science festivals and museums, and as a special classroom activity during science weeks, and so forth. (Contains 3 figures.)

  16. Molecular entomology: analyzing tiny molecules to answer big questions about disease vectors and their biology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The entomologists at the Arthropod-Borne Animal Diseases Research Unit at USDA-Agricultural Research Service are tasked with protecting the nation’s livestock from domestic, foreign and emerging vector-borne diseases. To accomplish this task, a vast array of molecular techniques are being used in pr...

  17. Red Fluorescent Line Emission from Hydrogen Molecules in Diffuse Molecular Clouds

    NASA Technical Reports Server (NTRS)

    Neufeld, David A.; Spaans, Marco

    1996-01-01

    We have modeled the fluorescent pumping of electronic and vibrational emissions of molecular hydrogen (H2) within diffuse molecular clouds that are illuminated by ultraviolet continuum radiation. Fluorescent line intensities are predicted for transitions at ultraviolet, infrared, and red visible wavelengths as functions of the gas density, the visual extinction through the cloud, and the intensity of the incident UV continuum radiation. The observed intensity in each fluorescent transition is roughly proportional to the integrated rate of H2 photodissociation along the line of sight. Although the most luminous fluorescent emissions detectable from ground-based observatories lie at near-infrared wavelengths, we argue that the lower sky brightness at visible wavelengths makes the red fluorescent transitions a particularly sensitive probe. Fabry-Perot spectrographs of the type that have been designed to observe very faint diffuse Ha emissions are soon expected to yield sensitivities that will be adequate to detect H2 vibrational emissions from molecular clouds that are exposed to ultraviolet radiation no stronger than the mean radiation field within the Galaxy. Observations of red H2 fluorescent emission together with cospatial 21 cm H I observations could serve as a valuable probe of the gas density in diffuse molecular clouds.

  18. Mechanical Operation and Intersubunit Coordination of Ring-Shaped Molecular Motors: Insights from Single-Molecule Studies

    PubMed Central

    Liu, Shixin; Chistol, Gheorghe; Bustamante, Carlos

    2014-01-01

    Ring NTPases represent a large and diverse group of proteins that couple their nucleotide hydrolysis activity to a mechanical task involving force generation and some type of transport process in the cell. Because of their shape, these enzymes often operate as gates that separate distinct cellular compartments to control and regulate the passage of chemical species across them. In this manner, ions and small molecules are moved across membranes, biopolymer substrates are segregated between cells or moved into confined spaces, double-stranded nucleic acids are separated into single strands to provide access to the genetic information, and polypeptides are unfolded and processed for recycling. Here we review the recent advances in the characterization of these motors using single-molecule manipulation and detection approaches. We describe the various mechanisms by which ring motors convert chemical energy to mechanical force or torque and coordinate the activities of individual subunits that constitute the ring. We also examine how single-molecule studies have contributed to a better understanding of the structural elements involved in motor-substrate interaction, mechanochemical coupling, and intersubunit coordination. Finally, we discuss how these molecular motors tailor their operation—often through regulation by other cofactors—to suit their unique biological functions. PMID:24806916

  19. Development of small molecule non-peptide formyl peptide receptor (FPR) ligands and molecular modeling of their recognition.

    PubMed

    Schepetkin, I A; Khlebnikov, A I; Giovannoni, M P; Kirpotina, L N; Cilibrizzi, A; Quinn, M T

    2014-01-01

    Formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCRs) expressed on a variety of cell types. These receptors play an important role in the regulation of inflammatory reactions and sensing cellular damage. They have also been implicated in the pathogenesis of various diseases, including neurodegenerative diseases, cataract formation, and atherogenesis. Thus, FPR ligands, both agonists and antagonists, may represent novel therapeutics for modulating host defense and innate immunity. A variety of molecules have been identified as receptor subtype-selective and mixed FPR agonists with potential therapeutic value during last decade. This review describes our efforts along with recent advances in the identification, optimization, biological evaluation, and structure-activity relationship (SAR) analysis of small molecule non-peptide FPR agonists and antagonists, including chiral molecules. Questions regarding the interaction at the molecular level of benzimidazoles, pyrazolones, pyridazin-3(2H)-ones, N-phenylureas and other derivatives with FPR1 and FPR2 are discussed. Application of computational models for virtual screening and design of FPR ligands is also considered. PMID:24350845

  20. Long-range molecular states dissociating to the three or four lowest asymptotes for the ten heteronuclear diatomic alkali molecules

    NASA Astrophysics Data System (ADS)

    Bussery, Béatrice; Achkar, Yamina; Aubert-Frécon, Monique

    1987-09-01

    Long-range energy matrix elements have been calculated in the multipolar expansion approximation for all the molecular states dissociating to the three or four lowest asymptotes for the molecules LiNa, LiK, LiRb, LiCs, NaK, NaRb, NaCs, KRb, KCs and RbCs using the semi-empirical perturbative model we proposed recently. Two different assumptions have been investigated: including or excluding the spin-orbit effects within each atom. Full numerical results are presented for NaK and LiCs which have been chosen as examples. For the ten molecules in the non-interacting assumption the long-range coefficients C6 and C8 have been found for each state when neglecting atomic spin-orbit effects while the fitted value C*6 and C*8 are presented for each state when including atomic spin-orbit effects. When considering the interacting states, those dissociating to ns + n's and to ns + 5d(Cs) are seen to be slightly perturbed while the states dissociating to ns + n'p and to np + n's are significantly perturbed. The wavefunctions for the interacting 3Σ +, 3Π, 0 +, 0 -, 1, 2 states for the molecules NaK and LiCs are presented for various internuclear distances.

  1. Crossed molecular beams study of O({sup 1}D) reactions with H{sub 2} molecules

    SciTech Connect

    Miau, T.T.

    1995-05-01

    Reaction dynamics of O({sup 1}D) atoms with H{sub 2} molecules was reinvestigated using the crossed molecular beams technique with pulsed beams. The O({sup 1}D) beam was generated by photodissociating O{sub 3} molecules at 248 nm. Time-of-flight spectra and the laboratory angular distribution of the OH products were measured. The derived OH product center-of-mass flux-velocity contour diagram shows more backward scattered intensity with respect to the O({sup 1}D) beam. In contrast to previous studies which show that the insertion mechanism is the dominant process, our results indicate that the contribution from the collinear approach of the O({sup 1}D) atom to the H{sub 2} molecule on the first excited state potential energy surface is significant and the energy barrier for the collinear approach is therefore minimal. Despite the increased time resolution in this experiment, no vibrational structure in the OH product time-of-flight spectra was resolved. This is in agreement with LIF studies, which have shown that the rotational distributions of the OH products in all vibrational states are broad and highly inverted.

  2. Anisotropic time-resolved solution X-ray scattering patterns from explicit-solvent molecular dynamics

    NASA Astrophysics Data System (ADS)

    Brinkmann, Levin U. L.; Hub, Jochen S.

    2015-09-01

    Time-resolved wide-angle X-ray scattering (TR-WAXS) is an emerging experimental technique used to track chemical reactions and conformational transitions of proteins in real time. Thanks to increased time resolution of the method, anisotropic TR-WAXS patterns were recently reported, which contain more structural information than isotropic patterns. So far, however, no method has been available to compute anisotropic WAXS patterns of biomolecules, thus limiting the structural interpretation. Here, we present a method to compute anisotropic TR-WAXS patterns from molecular dynamics simulations. The calculations accurately account for scattering of the hydration layer and for thermal fluctuations. For many photo-excitable proteins, given a low intensity of the excitation laser, the anisotropic pattern is described by two independent components: (i) an isotropic component, corresponding to common isotropic WAXS experiments and (ii) an anisotropic component depending on the orientation of the excitation dipole of the solute. We present a set of relations for the calculation of these two components from experimental scattering patterns. Notably, the isotropic component is not obtained by a uniform azimuthal average on the detector. The calculations are illustrated and validated by computing anisotropic WAXS patterns of a spheroidal protein model and of photoactive yellow protein. Effects due to saturated excitation at high intensities of the excitation laser are discussed, including opportunities to extract additional structural information by modulating the laser intensity.

  3. Anisotropic time-resolved solution X-ray scattering patterns from explicit-solvent molecular dynamics.

    PubMed

    Brinkmann, Levin U L; Hub, Jochen S

    2015-09-14

    Time-resolved wide-angle X-ray scattering (TR-WAXS) is an emerging experimental technique used to track chemical reactions and conformational transitions of proteins in real time. Thanks to increased time resolution of the method, anisotropic TR-WAXS patterns were recently reported, which contain more structural information than isotropic patterns. So far, however, no method has been available to compute anisotropic WAXS patterns of biomolecules, thus limiting the structural interpretation. Here, we present a method to compute anisotropic TR-WAXS patterns from molecular dynamics simulations. The calculations accurately account for scattering of the hydration layer and for thermal fluctuations. For many photo-excitable proteins, given a low intensity of the excitation laser, the anisotropic pattern is described by two independent components: (i) an isotropic component, corresponding to common isotropic WAXS experiments and (ii) an anisotropic component depending on the orientation of the excitation dipole of the solute. We present a set of relations for the calculation of these two components from experimental scattering patterns. Notably, the isotropic component is not obtained by a uniform azimuthal average on the detector. The calculations are illustrated and validated by computing anisotropic WAXS patterns of a spheroidal protein model and of photoactive yellow protein. Effects due to saturated excitation at high intensities of the excitation laser are discussed, including opportunities to extract additional structural information by modulating the laser intensity. PMID:26374019

  4. Proton Donor/acceptor Propensities of Ammonia: Rotational Studies of its Molecular Complexes with Organic Molecules

    NASA Astrophysics Data System (ADS)

    Giuliano, Barbara M.; Maris, Assimo; Melandri, Sonia; Favero, Laura B.; Evangelisti, Luca; Caminati, Walther

    2009-06-01

    We studied the rotational spectra of the adducts of ammonia with several organic molecules, namely tert-butanol, glycidol, ethyl alcohol, anisol and 1,4-difluorobenzene. The adducts with glycidol and ethanol have been observed for both conformers of the substrate molecule. Based on the rotational and ^{14}N quadrupole coupling constants of the various complexes, we found a considerably different behaviour of ammonia, with respect to water, in its proton donor/acceptor double role. In the interaction with the three alcohol molecules, NH_{3} acts as a proton acceptor and the OH groups as a proton donor. However, in the case of glycidol-NH_{3}, a secundary N-H\\cdotsO interaction occurrs between ammonia and the ether oxygen. This interaction generates a sizable V_{3} barrier to the internal rotation of the NH_{3} moiety, while NH_{3} undergoes a free rotation in tert-butanol-NH_{3} and in ethanol-NH_{3}. As to the anisole-NH_{3} and 1,4-difluorobenzene-NH_{3} complexes, the NH_{3} group explicits its double proton donor/acceptor role, although through two weak (C_{Me}-H\\cdotsN and N-H\\cdotsπ) H-bonds. There is, however, an important difference between the two complexes, because in the first one NH_{3} lies out of the aromatic plane, while in the second one it is in the plane of the aromatic ring. B. M. Giuliano, M. C. Castrovilli, A. Maris, S. Melandri, W. Caminati and E. A. Cohen, Chem.Phys.Lett., 2008, 463, 330 B. M. Giuliano, S. Melandri, A. Maris, L. B. Favero and W. Caminati, Angew.Chem.Int.Ed., 2009, 48, 1102

  5. Nanopore Analysis of Nucleic Acids: Single-Molecule Studies of Molecular Dynamics, Structure, and Base Sequence

    NASA Astrophysics Data System (ADS)

    Olasagasti, Felix; Deamer, David W.

    Nucleic acids are linear polynucleotides in which each base is covalently linked to a pentose sugar and a phosphate group carrying a negative charge. If a pore having roughly the crosssectional diameter of a single-stranded nucleic acid is embedded in a thin membrane and a voltage of 100 mV or more is applied, individual nucleic acids in solution can be captured by the electrical field in the pore and translocated through by single-molecule electrophoresis. The dimensions of the pore cannot accommodate anything larger than a single strand, so each base in the molecule passes through the pore in strict linear sequence. The nucleic acid strand occupies a large fraction of the pore's volume during translocation and therefore produces a transient blockade of the ionic current created by the applied voltage. If it could be demonstrated that each nucleotide in the polymer produced a characteristic modulation of the ionic current during its passage through the nanopore, the sequence of current modulations would reflect the sequence of bases in the polymer. According to this basic concept, nanopores are analogous to a Coulter counter that detects nanoscopic molecules rather than microscopic [1,2]. However, the advantage of nanopores is that individual macromolecules can be characterized because different chemical and physical properties affect their passage through the pore. Because macromolecules can be captured in the pore as well as translocated, the nanopore can be used to detect individual functional complexes that form between a nucleic acid and an enzyme. No other technique has this capability.

  6. Molecular mimicry of substrate oxygen atoms by water molecules in the beta-amylase active site.

    PubMed

    Pujadas, G; Palau, J

    2001-08-01

    Soybean beta-amylase (EC 3.2.1.2) has been crystallized both free and complexed with a variety of ligands. Four water molecules in the free-enzyme catalytic cleft form a multihydrogen-bond network with eight strategic residues involved in enzyme-ligand hydrogen bonds. We show here that the positions of these four water molecules are coincident with the positions of four potential oxygen atoms of the ligands within the complex. Some of these waters are displaced from the active site when the ligands bind to the enzyme. How many are displaced depends on the shape of the ligand. This means that when one of the four positions is not occupied by a ligand oxygen atom, the corresponding water remains. We studied the functional/structural role of these four waters and conclude that their presence means that the conformation of the eight side chains is fixed in all situations (free or complexed enzyme) and preserved from unwanted or forbidden conformational changes that could hamper the catalytic mechanism. The water structure at the active pocket of beta-amylase is therefore essential for providing the ligand recognition process with plasticity. It does not affect the protein active-site geometry and preserves the overall hydrogen-bonding network, irrespective of which ligand is bound to the enzyme. We also investigated whether other enzymes showed a similar role for water. Finally, we discuss the potential use of these results for predicting whether water molecules can mimic ligand atoms in the active center. PMID:11468361

  7. The RCSB PDB “Molecule of the Month”: Inspiring a Molecular View of Biology

    PubMed Central

    Goodsell, David S.; Dutta, Shuchismita; Zardecki, Christine; Voigt, Maria; Berman, Helen M.; Burley, Stephen K.

    2015-01-01

    The Research Collaboratory for Structural Bioinformatics (RCSB) Molecule of the Month series provides a curated introduction to the 3-D biomolecular structures available in the Protein Data Bank archive and the tools that are available at the RCSB website for accessing and exploring them. A variety of educational materials, such as articles, videos, posters, hands-on activities, lesson plans, and curricula, build on this series for use in a variety of educational settings as a general introduction to key topics, such as enzyme action, protein synthesis, and viruses. The series and associated educational materials are freely available at www.rcsb.org. PMID:25942442

  8. The RCSB PDB "Molecule of the Month": Inspiring a Molecular View of Biology.

    PubMed

    Goodsell, David S; Dutta, Shuchismita; Zardecki, Christine; Voigt, Maria; Berman, Helen M; Burley, Stephen K

    2015-05-01

    The Research Collaboratory for Structural Bioinformatics (RCSB) Molecule of the Month series provides a curated introduction to the 3-D biomolecular structures available in the Protein Data Bank archive and the tools that are available at the RCSB website for accessing and exploring them. A variety of educational materials, such as articles, videos, posters, hands-on activities, lesson plans, and curricula, build on this series for use in a variety of educational settings as a general introduction to key topics, such as enzyme action, protein synthesis, and viruses. The series and associated educational materials are freely available at www.rcsb.org. PMID:25942442

  9. Molecular Probing of the HPV-16 E6 Protein Alpha Helix Binding Groove with Small Molecule Inhibitors

    PubMed Central

    Rietz, Anne; Petrov, Dino P.; Bartolowits, Matthew; DeSmet, Marsha; Davisson, V. Jo; Androphy, Elliot J.

    2016-01-01

    The human papillomavirus (HPV) HPV E6 protein has emerged as a central oncoprotein in HPV-associated cancers in which sustained expression is required for tumor progression. A majority of the E6 protein interactions within the human proteome use an alpha-helix groove interface for binding. The UBE3A/E6AP HECT domain ubiquitin ligase binds E6 at this helix-groove interface. This enables formation of a trimeric complex with p53, resulting in destruction of this tumor suppressor. While recent x-ray crystal structures are useful, examples of small molecule probes that can modulate protein interactions at this interface are limited. To develop insights useful for potential structure-based design of ligands for HPV E6, a series of 2,6-disubstituted benzopyranones were prepared and tested as competitive antagonists of E6-E6AP helix-groove interactions. These small molecule probes were used in both binding and functional assays to evaluate recognition features of the E6 protein. Evidence for an ionic functional group interaction within the helix groove was implicated by the structure-activity among the highest affinity ligands. The molecular topographies of these protein-ligand interactions were evaluated by comparing the binding and activities of single amino acid E6 mutants with the results of molecular dynamic simulations. A group of arginine residues that form a rim-cap over the E6 helix groove offer compensatory roles in binding and recognition of the small molecule probes. The flexibility and impact on the overall helix-groove shape dictated by these residues offer new insights for structure-based targeting of HPV E6. PMID:26915086

  10. Molecular Probing of the HPV-16 E6 Protein Alpha Helix Binding Groove with Small Molecule Inhibitors.

    PubMed

    Rietz, Anne; Petrov, Dino P; Bartolowits, Matthew; DeSmet, Marsha; Davisson, V Jo; Androphy, Elliot J

    2016-01-01

    The human papillomavirus (HPV) HPV E6 protein has emerged as a central oncoprotein in HPV-associated cancers in which sustained expression is required for tumor progression. A majority of the E6 protein interactions within the human proteome use an alpha-helix groove interface for binding. The UBE3A/E6AP HECT domain ubiquitin ligase binds E6 at this helix-groove interface. This enables formation of a trimeric complex with p53, resulting in destruction of this tumor suppressor. While recent x-ray crystal structures are useful, examples of small molecule probes that can modulate protein interactions at this interface are limited. To develop insights useful for potential structure-based design of ligands for HPV E6, a series of 2,6-disubstituted benzopyranones were prepared and tested as competitive antagonists of E6-E6AP helix-groove interactions. These small molecule probes were used in both binding and functional assays to evaluate recognition features of the E6 protein. Evidence for an ionic functional group interaction within the helix groove was implicated by the structure-activity among the highest affinity ligands. The molecular topographies of these protein-ligand interactions were evaluated by comparing the binding and activities of single amino acid E6 mutants with the results of molecular dynamic simulations. A group of arginine residues that form a rim-cap over the E6 helix groove offer compensatory roles in binding and recognition of the small molecule probes. The flexibility and impact on the overall helix-groove shape dictated by these residues offer new insights for structure-based targeting of HPV E6. PMID:26915086

  11. Orbital tomography: Molecular band maps, momentum maps and the imaging of real space orbitals of adsorbed molecules

    PubMed Central

    Offenbacher, Hannes; Lüftner, Daniel; Ules, Thomas; Reinisch, Eva Maria; Koller, Georg; Puschnig, Peter; Ramsey, Michael G.

    2015-01-01

    The frontier orbitals of molecules are the prime determinants of their chemical, optical and electronic properties. Arguably, the most direct method of addressing the (filled) frontier orbitals is ultra-violet photoemission spectroscopy (UPS). Although UPS is a mature technique from the early 1970s on, the angular distribution of the photoemitted electrons was thought to be too complex to be analysed quantitatively. Recently angle resolved UPS (ARUPS) work on conjugated molecules both, in ordered thick films and chemisorbed monolayers, has shown that the angular (momentum) distribution of the photocurrent from orbital emissions can be simply understood. The approach, based on the assumption of a plane wave final state is becoming known as orbital tomography. Here we will demonstrate, with selected examples of pentacene (5A) and sexiphenyl (6P), the potential of orbital tomography. First it will be shown how the full angular distribution of the photocurrent (momentum map) from a specific orbital is related to the real space orbital by a Fourier transform. Examples of the reconstruction of 5A orbitals will be given and the procedure for recovering the lost phase information will be outlined. We then move to examples of sexiphenyl where we interrogate the original band maps of thick sexiphenyl in the light of our understanding of orbital tomography that has developed since then. With comparison to theoretical simulations of the molecular band maps, the molecular conformation and orientation will be concluded. New results for the sexiphenyl monolayer on Al(1 1 0) will then be presented. From the band maps it will be concluded that the molecule is planarised and adopts a tilted geometry. Finally the momentum maps down to HOMO-11 will be analysed and real space orbitals reconstructed. PMID:26752804

  12. Movement of Ng2 molecules confined in a C60 cage: An ab initio molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Khatua, Munmun; Pan, Sudip; Chattaraj, Pratim K.

    2014-08-01

    An ab initio molecular dynamics study on Ng2@C60 (Ng = Hesbnd Kr) systems is performed to analyze the movement of Ng2 molecules inside a C60 cage. Within 500 fs time window, the He2 undergoes precession encompassing translation, vibration and rotation readily whereas other Ng2 molecules show usual vibration but the degrees of translation and rotation decrease with an increase in size of the Ng atoms. Increase in interaction between the Ng centers and cage carbons and an increased distortion of cage in moving from He to Kr seem to be responsible for this. During the movement, the Ng2 units behave as single entity. To check the kinetic stability of these systems through ab initio molecular dynamics study since they are thermodynamically unstable. Frenking et al. [40] argued about the free precession of the Ng2 units inside the cage on the basis of the very small energy differences between differently oriented Ng2 units. We need to check whether these Ng2 units really precess inside the C60 cage at room temperature and if yes then by what extent, up to 500 fs time scale. To check whether these weakly interacting He2 and Ne2 systems can be termed as molecules we would like to analyze the Ngsbnd Ng bond distance values at different time steps. In order to check the applicability of maximum hardness principle and minimum electrophilicity principle during time evolution of these endohedrally trapped systems the variation of hardness and electrophilicity with time during simulation and their correlation with the change in energy of the systems are studied.

  13. Molecular understanding of atmospheric particle formation from sulfuric acid and large oxidized organic molecules

    PubMed Central

    Schobesberger, Siegfried; Junninen, Heikki; Bianchi, Federico; Lönn, Gustaf; Ehn, Mikael; Lehtipalo, Katrianne; Dommen, Josef; Ehrhart, Sebastian; Ortega, Ismael K.; Franchin, Alessandro; Nieminen, Tuomo; Riccobono, Francesco; Hutterli, Manuel; Duplissy, Jonathan; Almeida, João; Amorim, Antonio; Breitenlechner, Martin; Downard, Andrew J.; Dunne, Eimear M.; Flagan, Richard C.; Kajos, Maija; Keskinen, Helmi; Kirkby, Jasper; Kupc, Agnieszka; Kürten, Andreas; Kurtén, Theo; Laaksonen, Ari; Mathot, Serge; Onnela, Antti; Praplan, Arnaud P.; Rondo, Linda; Santos, Filipe D.; Schallhart, Simon; Schnitzhofer, Ralf; Sipilä, Mikko; Tomé, António; Tsagkogeorgas, Georgios; Vehkamäki, Hanna; Wimmer, Daniela; Baltensperger, Urs; Carslaw, Kenneth S.; Curtius, Joachim; Hansel, Armin; Petäjä, Tuukka; Kulmala, Markku; Donahue, Neil M.; Worsnop, Douglas R.

    2013-01-01

    Atmospheric aerosols formed by nucleation of vapors affect radiative forcing and therefore climate. However, the underlying mechanisms of nucleation remain unclear, particularly the involvement of organic compounds. Here, we present high-resolution mass spectra of ion clusters observed during new particle formation experiments performed at the Cosmics Leaving Outdoor Droplets chamber at the European Organization for Nuclear Research. The experiments involved sulfuric acid vapor and different stabilizing species, including ammonia and dimethylamine, as well as oxidation products of pinanediol, a surrogate for organic vapors formed from monoterpenes. A striking resemblance is revealed between the mass spectra from the chamber experiments with oxidized organics and ambient data obtained during new particle formation events at the Hyytiälä boreal forest research station. We observe that large oxidized organic compounds, arising from the oxidation of monoterpenes, cluster directly with single sulfuric acid molecules and then form growing clusters of one to three sulfuric acid molecules plus one to four oxidized organics. Most of these organic compounds retain 10 carbon atoms, and some of them are remarkably highly oxidized (oxygen-to-carbon ratios up to 1.2). The average degree of oxygenation of the organic compounds decreases while the clusters are growing. Our measurements therefore connect oxidized organics directly, and in detail, with the very first steps of new particle formation and their growth between 1 and 2 nm in a controlled environment. Thus, they confirm that oxidized organics are involved in both the formation and growth of particles under ambient conditions. PMID:24101502

  14. Molecular understanding of atmospheric particle formation from sulfuric acid and large oxidized organic molecules.

    PubMed

    Schobesberger, Siegfried; Junninen, Heikki; Bianchi, Federico; Lönn, Gustaf; Ehn, Mikael; Lehtipalo, Katrianne; Dommen, Josef; Ehrhart, Sebastian; Ortega, Ismael K; Franchin, Alessandro; Nieminen, Tuomo; Riccobono, Francesco; Hutterli, Manuel; Duplissy, Jonathan; Almeida, João; Amorim, Antonio; Breitenlechner, Martin; Downard, Andrew J; Dunne, Eimear M; Flagan, Richard C; Kajos, Maija; Keskinen, Helmi; Kirkby, Jasper; Kupc, Agnieszka; Kürten, Andreas; Kurtén, Theo; Laaksonen, Ari; Mathot, Serge; Onnela, Antti; Praplan, Arnaud P; Rondo, Linda; Santos, Filipe D; Schallhart, Simon; Schnitzhofer, Ralf; Sipilä, Mikko; Tomé, António; Tsagkogeorgas, Georgios; Vehkamäki, Hanna; Wimmer, Daniela; Baltensperger, Urs; Carslaw, Kenneth S; Curtius, Joachim; Hansel, Armin; Petäjä, Tuukka; Kulmala, Markku; Donahue, Neil M; Worsnop, Douglas R

    2013-10-22

    Atmospheric aerosols formed by nucleation of vapors affect radiative forcing and therefore climate. However, the underlying mechanisms of nucleation remain unclear, particularly the involvement of organic compounds. Here, we present high-resolution mass spectra of ion clusters observed during new particle formation experiments performed at the Cosmics Leaving Outdoor Droplets chamber at the European Organization for Nuclear Research. The experiments involved sulfuric acid vapor and different stabilizing species, including ammonia and dimethylamine, as well as oxidation products of pinanediol, a surrogate for organic vapors formed from monoterpenes. A striking resemblance is revealed between the mass spectra from the chamber experiments with oxidized organics and ambient data obtained during new particle formation events at the Hyytiälä boreal forest research station. We observe that large oxidized organic compounds, arising from the oxidation of monoterpenes, cluster directly with single sulfuric acid molecules and then form growing clusters of one to three sulfuric acid molecules plus one to four oxidized organics. Most of these organic compounds retain 10 carbon atoms, and some of them are remarkably highly oxidized (oxygen-to-carbon ratios up to 1.2). The average degree of oxygenation of the organic compounds decreases while the clusters are growing. Our measurements therefore connect oxidized organics directly, and in detail, with the very first steps of new particle formation and their growth between 1 and 2 nm in a controlled environment. Thus, they confirm that oxidized organics are involved in both the formation and growth of particles under ambient conditions. PMID:24101502

  15. Selective IR multiphoton dissociation of molecules in a pulsed gas-dynamically cooled molecular flow interacting with a solid surface as an alternative to low-energy methods of molecular laser isotope separation

    NASA Astrophysics Data System (ADS)

    Makarov, G. N.; Petin, A. N.

    2016-03-01

    We report the results of studies on the isotope-selective infrared multiphoton dissociation (IR MFD) of SF6 and CF3I molecules in a pulsed, gas-dynamically cooled molecular flow interacting with a solid surface. The productivity of this method in the conditions of a specific experiment (by the example of SF6 molecules) is evaluated. A number of low-energy methods of molecular laser isotope separation based on the use of infrared lasers for selective excitation of molecules are analysed and their productivity is estimated. The methods are compared with those of selective dissociation of molecules in the flow interacting with a surface. The advantages of this method compared to the low-energy methods of molecular laser isotope separation and the IR MPD method in the unperturbed jets and flows are shown. It is concluded that this method could be a promising alternative to the low-energy methods of molecular laser isotope separation.

  16. Single ionization of hydrogen molecules by fast protons as a function of the molecular alignment

    SciTech Connect

    Johnson, Nora G.; Mello, R. N.; Lundy, Michael E.; Kapplinger, J.; Wells, E.; Parke, Eli; Carnes, K. D.; Ben-Itzhak, I.

    2005-11-15

    Relative cross sections for the 4 MeV H{sup +}+D{sub 2} ({sup 1}{sigma}{sub g}{sup +}){yields}H{sup +}+D{sub 2}{sup +}(1s{sigma})+e{sup -} ionization process were measured as a function of the molecular alignment during the interaction. The angle between the molecular axis and the projectile was obtained by using a momentum imagining technique and isolating the events in which the D{sub 2}{sup +}(1s{sigma}) ions are excited to the vibrational continuum and subsequently dissociate. While anisotropic cross sections have been observed in the past for a number of collision processes involving both target electrons, the one electron process investigated here is isotropic within our experimental uncertainties.

  17. Dust around AFGL 2688, molecular shielding, and the production of carbon chain molecules

    NASA Technical Reports Server (NTRS)

    Jura, M.; Kroto, H.

    1990-01-01

    The molecular, IR, and optical maps of the evolved carbon star AFGL 2688 (the 'Egg' Nebula) are all consistent with a model of a bipolar outflow of approximately 0.0001 solar masses/yr that stopped as this object evolved beyond the asymptotic giant branch about 200 years ago. In order to explain the extended HC7N emission around this star, it is proposed that carbon grains are collisionally fragmented as they supersonically steam through the circumstellar envelope.

  18. Size and number of DNA molecules from Chinese hamster ovary cells determined by molecular autoradiography

    SciTech Connect

    Todd, M.B.

    1980-06-01

    A new method for visualization of separable subunits of DNA is described. Autoradiography of tritium-labeled DNA from one or a few nuclei, lysed with detergent, moderate salt, and proteases, and gently deposited on a filter, allows determination of subunit molecular weight, size distribution, number per nucleus, and organization. The shape of the size distribution of CHO subunit images is similar to that of CHO mitotic chromosomes, and the numbers of subunits per nucleus supports a model of eight subunits per chromosome.

  19. Universal scaling behavior of molecular electronic stopping cross section for protons colliding with small molecules and nucleobases

    NASA Astrophysics Data System (ADS)

    Trujillo-López, L. N.; Martínez-Flores, C.; Cabrera-Trujillo, R.

    2013-10-01

    The electronic stopping cross section and mean excitation energy for molecules and 5 nucleobases have been calculated within the first Born approximation in terms of an orbital decomposition to take into account the molecular structure. The harmonic oscillator (HO) description of the stopping cross section together with a Floating Spherical Gaussian Orbital (FSGO) model is implemented to account for the chemical composition of the target. This approach allows us to use bonds, cores, and lone pairs as HO basis to describe the ground state molecular structure. In the HO model, the orbital angular frequency is the only parameter that connects naturally with the mean excitation energy. As a result, we obtain a simple expression for the equivalent mean excitation energy in terms of the orbital radius parameter, as well as an analytical expression of the stopping cross section. For gas phase molecular targets, we provide HO based orbital mean excitation energies to describe any molecule containing C, N, O, H, and P atoms. We present results for protons colliding with H2, N2, O2, H2O, CO2, propylene (C3H6), methane (CH4), ethylene (C2H4) and the nucleobases - guanine (C5H5N5O), cytosine (C4H5N2O2), thymine (C5H6N2O2), adenine (C5H5N5) and uracil (C4H4N2O2). The results for the stopping cross section are compared with available experimental and theoretical data showing good to excellent agreement in the region of validity of the model. The HO approach allows us to obtain a universal stopping cross section formula to describe a universal scaling behavior for the energy loss process. The universal scaled curve is confirmed by the experimental data.

  20. Exploring molecular complexity with ALMA (EMoCA): Deuterated complex organic molecules in Sagittarius B2(N2)

    NASA Astrophysics Data System (ADS)

    Belloche, A.; Müller, H. S. P.; Garrod, R. T.; Menten, K. M.

    2016-03-01

    Context. Deuteration is a powerful tracer of the history of the cold prestellar phase in star-forming regions. Apart from methanol, little is known about deuterium fractionation of complex organic molecules in the interstellar medium, especially in regions forming high-mass stars. Aims: Our goal is to detect deuterated complex organic molecules toward the high mass star-forming region Sagittarius B2 (Sgr B2) and derive the level of deuteration for these molecules. Methods: We use a complete 3-mm spectral line survey performed with the Atacama Large Millimeter/submillimeter Array (ALMA) to search for deuterated complex organic molecules toward the hot molecular core Sgr B2(N2). We constructed population diagrams and integrated intensity maps to fit rotational temperatures and emission sizes for each molecule. Column densities are derived by modeling the full spectrum under the assumption of local thermodynamic equilibrium. We compare the results to predictions of two astrochemical models that treat the deuteration process. Results: We report the detection of CH2DCN toward Sgr B2(N2) with a deuteration level of 0.4%, and tentative detections of CH2DOH, CH2DCH2CN, the chiral molecule CH3CHDCN, and DC3N with levels in the range 0.05%-0.12%. A stringent deuteration upper limit is obtained for CH3OD (<0.07%). Upper limits in the range 0.5-1.8% are derived for the three deuterated isotopologues of vinyl cyanide, the four deuterated species of ethanol, and CH2DOCHO. Ethyl cyanide is less deuterated than methyl cyanide by at least a factor five. The [CH2DOH]/[CH3OD] abundance ratio is higher than 1.8. It may still be consistent with the value obtained in Orion KL. Except for methyl cyanide, the measured deuteration levels lie at least a factor four below the predictions of current astrochemical models. The deuteration levels in Sgr B2(N2) are also lower than in Orion KL by a factor of a few up to a factor ten. Conclusions: The discrepancy between the deuteration levels of

  1. Relationship between molecular structure, concentration and odor qualities of oxygenated aliphatic molecules.

    PubMed

    Laing, D G; Legha, P K; Jinks, A L; Hutchinson, I

    2003-01-01

    Increasing the concentration of an odorant increases the number of receptor cells and glomeruli in the olfactory bulb that are stimulated, and it is commonly acknowledged that these represent increased numbers of receptor types. Currently, it is not known whether a receptor type is associated with a unique quality and a unique molecular feature of an odorant, or its activation is used by the brain in a combinatorial manner with other activated receptor types to produce a characteristic quality. The present study investigated the proposal that a molecular feature common to several aliphatic odorants and known to be the key feature required to stimulate the same mitral cells in the olfactory bulb results in a quality that is common to the odorants. Since the common structural feature may activate a specific receptor type possibly at a similar concentration, the qualities of the odorants were determined at seven concentrations where the lowest and highest concentrations were the detection threshold (DT) and 729DT of each subject. A list of 146 descriptors was used by 15 subjects to describe the qualities of each odorant at each concentration. The results indicate that each of the five odorants was characterized by different qualities and the qualities of four of the odorants changed with changes in concentration. Importantly, no quality common to each of the odorants that had the same molecular feature could be identified and it is proposed that identification of the odorants occurs via a combinatorial mechanism involving several types of receptors. PMID:12502524

  2. From molecule to man: integrating molecular biology with whole organ physiology in studying respiratory disease.

    PubMed

    Königshoff, Melanie; Uhl, Franziska; Gosens, Reinoud

    2011-10-01

    Chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are all characterized by structural changes of the airways and/or lungs that limit airflow and/or gas exchange. Currently, there is no therapy available that adequately targets the structural remodeling of the airways and lungs in these diseases. This underscores the great need for insight into the mechanisms that underpin the development of airway remodeling, fibrosis and emphysema in these diseases, in order to identify suitable drug targets. It is increasingly evident that structural cell-cell communication within the lung is central to the development of remodeling, indicating that a more integrative approach should be considered when studying molecular and cellular mechanisms of remodeling. Therefore, there is a great need to study molecular and cellular physiological and pathophysiological mechanisms in as much detail as possible, but with as little as possible loss of the physiological context. Here, we will review the use of models such as cellular co-culture, tissue culture, and lung slice culture, in which cell-cell communication and tissue architecture are better preserved or mimicked than in cell culture, and zoom in on the usefulness of molecular and cellular biological tools in these complex model systems to read out or control signaling and gene/protein regulation. PMID:21356323

  3. Biomolecular Crowding Arising from Small Molecules, Molecular Constraints, Surface Packing, and Nano-Confinement

    PubMed Central

    Hilaire, Mary Rose; Abaskharon, Rachel M.; Gai, Feng

    2015-01-01

    The effect of macromolecular crowding on the structure, dynamics, and reactivity of biomolecules is well-established and the relevant research has been extensively reviewed. Herein, we focus our discussion on crowding effects arising from small co-solvent molecules and densely packed surface conditions. In addition, we highlight recent efforts that capitalize on the excluded volume effect for various tailored biochemical and biophysical applications. Specifically, we discuss how a targeted increase in local mass density can be exploited to gain insight into the folding dynamics of the protein of interest and how confinement via reverse micelles can be used to study a range of biophysical questions, from protein hydration dynamics to amyloid formation. PMID:26266732

  4. Influence of molecular structure on anisotropic photoinduced decomposition of polyimide molecules

    NASA Astrophysics Data System (ADS)

    Usami, Kiyoaki; Sakamoto, Kenji; Ushioda, Sukekatsu

    2001-05-01

    We have investigated the anisotropic decomposition of polyimide molecules induced by irradiation of linearly polarized ultraviolet light (LPUVL). Three polyimides were examined: poly [4,4'-oxydiphenylene-pyromellitimide], poly [4,4'-oxydiphenylene-1,2,3,4-butanetetracarboximide] and poly [4,4'-oxydiphenylene-1,2,3,4-cyclobutanetetracarboximide] (CBDA-ODA). Anisotropic decomposition was monitored by measuring the polarized infrared absorption spectra of ˜10 nm thick films as a function of LPUVL exposure. Among the three polyimides, CBDA-ODA showed the largest anisotropy of decomposition in the initial stage of LPUVL exposure. This result suggests that CBDA-ODA is a suitable polyimide material for photoinduced liquid crystal alignment based on photodecomposition reactions. The details of the LPUVL exposure dependence of the film anisotropy are discussed.

  5. Structural flexibility of the sulfur mustard molecule at finite temperature from Car-Parrinello molecular dynamics simulations.

    PubMed

    Lach, Joanna; Goclon, Jakub; Rodziewicz, Pawel

    2016-04-01

    Sulfur mustard (SM) is one of the most dangerous chemical compounds used against humans, mostly at war conditions but also in terrorist attacks. Even though the sulfur mustard has been synthesized over a hundred years ago, some of its molecular properties are not yet resolved. We investigate the structural flexibility of the SM molecule in the gas phase by Car-Parrinello molecular dynamics simulations. Thorough conformation analysis of 81 different SM configurations using density functional theory is performed to analyze the behavior of the system at finite temperature. The conformational diversity is analyzed with respect to the formation of intramolecular blue-shifting CH⋯S and CH⋯Cl hydrogen bonds. Molecular dynamics simulations indicate that all structural rearrangements between SM local minima are realized either in direct or non-direct way, including the intermediate structure in the last case. We study the lifetime of the SM conformers and perform the population analysis. Additionally, we provide the anharmonic dynamical finite temperature IR spectrum from the Fourier Transform of the dipole moment autocorrelation function to mimic the missing experimental IR spectrum. PMID:26774981

  6. Guided cell patterning on gold-silicon dioxide substrates by surface molecular engineering.

    PubMed

    Veiseh, Mandana; Wickes, Bronwyn T; Castner, David G; Zhang, Miqin

    2004-07-01

    We report an effective approach to patterning cells on gold-silicon dioxide substrates with high precision, selectivity, stability, and reproducibility. This technique is based on photolithography and surface molecular engineering and requires no cell positioning or delivery devices, thus significantly reducing the potential damage to cells. The cell patterning was achieved by activating the gold regions of the substrate with functionalized thiols that covalently bind proteins onto the gold regions to guide subsequent cell adhesion while passivating the silicon dioxide background with polyethylene glycol to resist cell adhesion. Fourier transform infrared reflectance spectroscopy verified the successful immobilization of proteins on gold surfaces. Protein patterns were visualized by tagging proteins with Rhodamine fluorescent probes. Time-of-flight secondary ion mass spectrometry was used to characterize the chemistry of both the cell-adhesive and cell-resistant regions of surfaces after each key chemical reaction occurring during the molecular surface engineering. The ability of the engineered surfaces to guide cell adhesion was illustrated by differential interference contrast (DIC) reflectance microscopy. The cell patterning technique introduced in this study is compatible with micro- and photo-electronics, and may have many medical, environmental, and defense applications. PMID:14980426

  7. Small molecule interactions with lipid bilayers: a molecular dynamics study of chlorhexidine

    NASA Astrophysics Data System (ADS)

    van Oosten, Brad; Marquardt, Drew; Sternin, Edward; Harroun, Thad

    2013-03-01

    Chlorhexidine presents an interesting modelling challenge with a hydrophobic hexane connecting two biguanides (arginine analogues) and two aromatic rings. We conducted molecular dynamic simulations using the GROMACS simulation software to reproduce the experimental environment of chlorhexidine in a 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC) bilayer to produce atomic-level information. We constructed an all-atom force field of chlorhexidine from the CHARMM36 force field using well established parameters of certain amino acids. Partial charges were treated differently, which were calculated using GAUSSIAN software. We will compare and contrast the results of our model to that of our neutron scattering experiments previously done in our lab.

  8. Molecular patterns of X chromosome-linked color vision genes among 134 men of European ancestry.

    PubMed

    Drummond-Borg, M; Deeb, S S; Motulsky, A G

    1989-02-01

    We used Southern blot hybridization to study X chromosome-linked color vision genes encoding the apoproteins of red and green visual pigments in 134 unselected Caucasian men. One hundred and thirteen individuals (84.3%) had a normal arrangement of their color vision pigment genes. All had one red pigment gene; the number of green pigment genes ranged from one to five with a mode of two. The frequency of molecular genotypes indicative of normal color vision (84.3%) was significantly lower than had been observed in previous studies of color vision phenotypes. Color vision defects can be due to deletions of red or green pigment genes or due to formation of hybrid genes comprising portions of both red and green pigment genes [Nathans, J., Piantanida, T.P., Eddy, R.L., Shows, T.B., Jr., & Hogness, D.S. (1986) Science 232, 203-210]. Characteristic anomalous patterns were seen in 15 (11.2%) individuals: 7 (5.2%) had patterns characteristic of deuteranomaly (mild defect in green color perception), 2 (1.5%) had patterns characteristic of deuteranopia (severe defect in green color perception), and 6 (4.5%) had protan patterns (the red perception defects protanomaly and protanopia cannot be differentiated by current molecular methods). Previously undescribed hybrid gene patterns consisting of both green and red pigment gene fragments in addition to normal red and green genes were observed in another 6 individuals (4.5%). Only 2 of these patterns were considered as deuteranomalous. Thus, DNA testing detected anomalous color vision pigment genes at a higher frequency than expected from phenotypic color vision tests. Some color vision gene arrays associated with hybrid genes are likely to mediate normal color vision. PMID:2915991

  9. Molecular Dynamics of 8-oxoguanine Lesioned B-DNA Molecule — Structure and Energy Analysis

    NASA Astrophysics Data System (ADS)

    Pinak, M.; O'Neill, P.; Fujimoto, H.; Nemoto, T.

    2004-04-01

    The molecular dynamics (MD) simulation of DNA mutagenic oxidative lesion — 7,8-dihydro-8-oxoguanine (8-oxoG), complexed with the repair enzyme — human oxoguanine glycosylase 1 (hOGG1) was performed for 1 nanosecond (ns) in order to describe the dynamical process of DNA-enzyme complex formation. After 900 picoseconds of MD the lesioned DNA and enzyme formed a complex that lasted until the end of the simulation at 1 ns. The amino group of arginine 324 was located close to the phosphodiester bond of nucleotide with 8-oxoG enabling chemical reactions between amino acid and lesion. Phosphodiester bond at C5' of 8-oxoG was displaced to the position close to the amino group of arginine 324. In the background simulation of the identical molecular system with the native DNA, neither the complex nor the water mediated hydrogen bond network were observed. The electrostatic energy is supposed to be significant factor causing the disruption of DNA base stacking in DNA duplex and may also to serve as a signal toward the repair enzyme informing on the presence of the lesion.

  10. Conserved molecular mechanisms underlying the effects of small molecule xenobiotic chemotherapeutics on cells

    PubMed Central

    SARIN, HEMANT

    2016-01-01

    For proper determination of the apoptotic potential of chemoxenobiotics in synergism, it is important to understand the modes, levels and character of interactions of chemoxenobiotics with cells in the context of predicted conserved biophysical properties. Chemoxenobiotic structures are studied with respect to atom distribution over molecular space, the predicted overall octanol-to-water partition coefficient (Log OWPC; unitless) and molecular size viz a viz van der Waals diameter (vdWD). The Log OWPC-to-vdWD (nm−1) parameter is determined, and where applicable, hydrophilic interacting moiety/core-to-vdWD (nm−1) and lipophilic incorporating hydrophobic moiety/core-to-vdWD (nm−1) parameters of their part-structures are determined. The cellular and sub-cellular level interactions of the spectrum of xenobiotic chemotherapies have been characterized, for which a classification system has been developed based on predicted conserved biophysical properties with respect to the mode of chemotherapeutic effect. The findings of this study are applicable towards improving the effectiveness of existing combination chemotherapy regimens and the predictive accuracy of personalized cancer treatment algorithms as well as towards the selection of appropriate novel xenobiotics with the potential to be potent chemotherapeutics for dendrimer nanoparticle-based effective transvascular delivery. PMID:26998284

  11. Mechanism of Mcl-1 Conformational Regulation Upon Small Molecule Binding Revealed by Molecular Dynamic Simulation.

    PubMed

    Wang, Anhui; Song, Ting; Wang, Ziqian; Liu, Yubo; Fan, Yudan; Zhang, Yahui; Zhang, Zhichao

    2016-04-01

    Inhibition of interactions between Mcl-1 and proapoptotic proteins is considered to be a therapeutic strategy to induce apoptosis in cancer cells. Here, we adopted molecular dynamics simulation with molecular mechanics-Poisson Boltzmann/surface area method (MM-PB/SA) to study the inhibition mechanism of three Mcl-1 inhibitors, compounds 1, 2 and 3. Analysis of energy components shows that the better binding free energy of compound 3 than compounds 1 and 2 is attributable to the van der Waals energy (ΔEvdw ) and non-polar solvation energy (ΔGnp ) upon binding. In addition to the excellent agreement with previous experimentally determined affinities, our simulation results further show a bend of helix 4 on Mcl-1 upon compound 3 binding, which is driven by hydrophobic interaction with residue Val(253) , leading to a narrowed BH3-binding groove to impede Puma(BH) (3) binding. The computational result is consistent with our competitive isothermal titration calorimetry (ITC) assays, which shows that the competitive ability of compound 3 toward Mcl-1/Puma(BH) (3) complex is improved beyond its direct binding affinity toward Mcl-1 itself, and compound 3 exhibits much more efficiency to compete with Puma(BH) (3) than compound 2. Our study provides a new strategy to improve inhibitory activity on Mcl-1 based on the conformational dynamic change. PMID:26518611

  12. Molecular phylogeny of the phylum Gastrotricha: new data brings together molecules and morphology.

    PubMed

    Paps, Jordi; Riutort, Marta

    2012-04-01

    Gastrotricha is a species-rich phylum of microscopical animals that contains two main orders, Chaetonotida and Macrodasyida. Gastrotrichs are important members of the aquatic environment and significant players in the study of animal evolution. In spite of their ecological and evolutionary importance, their internal relationships are not yet well understood. We have produced new sequences for the 18S rDNA gene to improve both the quality and quantity of taxon sampling for the gastrotrichs. Our phylogeny recovers the monophyly of the two main Gastrotricha clades, in contrast to recent studies with similar sampling, but in agreement with morphology based analyses. However, our topology is not able to resolve the first branches of the macrodasyidans or settle the position of the puzzling Neodasys, a controversial genus classified as a chaetonotidan on morphological grounds but placed within macrodasyidans by molecular studies. This analysis is the most exhaustive molecular phylogeny of the phylum to date, and significantly increases our knowledge of gastrotrich evolution. PMID:22198640

  13. Adsorption of Hydrogen Molecules on Carbon Nanotubes Using Quantum Chemistry and Molecular Dynamics.

    PubMed

    Faginas-Lago, N; Yeni, D; Huarte, F; Wang, Y; Alcamí, M; Martin, F

    2016-08-18

    Physisorption and storage of molecular hydrogen on single-walled carbon nanotube (SWCNT) of various diameters and chiralities are studied by means of classical molecular dynamics (MD) simulations and a force field validated using DFT-D2 and CCSD(T) calculations. A nonrigid carbon nanotube model is implemented with stretching (C-C) and valence angle potentials (C-C-C) formulated as Morse and Harmonic cosine potentials, respectively. Our results evidence that the standard Lennard-Jones potential fails to describe the H2-H2 binding energies. Therefore, our simulations make use of a potential that contains two-body term with parameters obtained from fitting CCSD(T)/CBS binding energies. From our MD simulations, we have analyzed the interaction energies, radial distribution functions, gravimetric densities (% wt), and the distances of the adsorbed H2 layers to the three zigzag type of nanotubes (5,0), (10,0), and (15,0) at 100 and 300 K. PMID:27467122

  14. Monte Carlo simulations of ferroelectric crystal growth and molecular electronic structure of atoms and molecules

    NASA Astrophysics Data System (ADS)

    Suewattana, Malliga

    In this thesis, we explore two stochastic techniques to study properties of materials in realistic systems. Specifically, the kinetic Monte Carlo (KMC) method is utilized to study the crystal growth process of ferroelectric materials and the quantum Monte Carlo (QMC) approach is used to investigate the ground state properties of atoms and molecules. In the growth simulations, we study the growth rates and chemical ordering of ferroelectric alloys using an electrostatic model with long-range Coulomb interactions. Crystal growth is characterized by thermodynamic processes involving adsorption and evaporation, with solid-on-solid restrictions and excluding diffusion. A KMC algorithm is formulated to simulate this model efficiently in the presence of long-range interactions. The growth process is simulated as a function of temperature, chemical composition, and substrate orientation. We carried out the simulations on two heterovalent binaries, those of the NaCl and the Ba(Mg1/3Nb2/3))O3(BMN) structures. Compared to the simple rocksalt ordered structures, ordered BMN grows only at very low temperatures and only under finely tuned conditions. For materials with tetravalent compositions, such as (1-x)Ba(Mg 1/3Nb2/3))O3 + x BaZrO3 (BMN-BZ), the model does not incorporate tetravalent ions at low-temperature, exhibiting a phase-separated ground state instead. At higher temperatures, tetravalent ions can be incorporated, but the resulting crystals show no chemical ordering in the absence of diffusive mechanisms. In the second part of the thesis, we present results from an auxiliary field quantum Monte Carlo (AFQMC) study of ground state properties, in particular dissociation and ionization energy, of second-row atoms and molecules. The method projects the many-body ground state from a trial wavefunction by random walks in the space of Slater determinants. The Hubbard-Stratonovich transformation is employed to decouple the Coulomb interaction between electrons. A trial wave

  15. Studies of Molecular Lasers, Atmospheric Molecules and Imaging in the Millimeter/submillimeter Spectral Region.

    NASA Astrophysics Data System (ADS)

    Crownover, Richard L.

    The millimeter/submillimeter portion of the electromagnetic spectrum is able to address fundamental questions in astronomy, cosmology, atmospheric science, molecular physics, quantum electronics, plasma physics, and other fields. Also, this spectral region has transmission characteristics which make it desirable for communications within the atmosphere and potentially for imaging. In order to demonstrate that detector technology in this region is sufficiently mature to permit the construction of reliable quasi-optical devices using off the shelf components, we have generated passive images using a broadband detector cooled to 0.35 K with a commercially produced ^3He refrigerator. We have shown the possibility of an extremely simple, highly sensitive, passive imaging system which operates in an attractive spectral region and is capable of upscaling to provide practical spatial resolution and real time operation over useful ranges. International public concern about acid rain, ozone depletion, and urban smog has spurred intense study of atmospheric chemistry. Spectra of two minor atmospheric constituents (HNO_3, ^ {16}O^{18}O) have been studied in the laboratory to assist with remote monitoring of atmospheric dynamics, modelling of atmospheric chemistry, and selection of communication frequencies which have some immunity to atmospheric perturbations. The nitric acid observations have allowed us to determine effective rotational constants for the first five vibrational states (nu_0, nu_9 , nu_7, nu _6, nu_8) and assign transitions in the perturbed nu_5 state. In addition, the concentration of ^{16}O^{18 }O in interstellar molecular clouds has been identified as a key discriminator between competing models of stellar formation; the measurements presented here will assist astronomers attempting to determine the abundance of this species in molecular clouds and proto-stars. We have recorded and analyzed the spectra of two important lasing species (^{12} CH_3F, ^{12 }CH_2

  16. Folding and assembly of the large molecular machine Hsp90 studied in single-molecule experiments

    PubMed Central

    Jahn, Markus; Buchner, Johannes; Hugel, Thorsten; Rief, Matthias

    2016-01-01

    Folding of small proteins often occurs in a two-state manner and is well understood both experimentally and theoretically. However, many proteins are much larger and often populate misfolded states, complicating their folding process significantly. Here we study the complete folding and assembly process of the 1,418 amino acid, dimeric chaperone Hsp90 using single-molecule optical tweezers. Although the isolated C-terminal domain shows two-state folding, we find that the isolated N-terminal as well as the middle domain populate ensembles of fast-forming, misfolded states. These intradomain misfolds slow down folding by an order of magnitude. Modeling folding as a competition between productive and misfolding pathways allows us to fully describe the folding kinetics. Beyond intradomain misfolding, folding of the full-length protein is further slowed by the formation of interdomain misfolds, suggesting that with growing chain lengths, such misfolds will dominate folding kinetics. Interestingly, we find that small stretching forces applied to the chain can accelerate folding by preventing the formation of cross-domain misfolding intermediates by leading the protein along productive pathways to the native state. The same effect is achieved by cotranslational folding at the ribosome in vivo. PMID:26787848

  17. SI-BEARING MOLECULES TOWARD IRC+10216: ALMA UNVEILS THE MOLECULAR ENVELOPE OF CWLEO

    PubMed Central

    Prieto, L. Velilla; Cernicharo, J.; Quintana–Lacaci, G.; Agúndez, M.; Castro–Carrizo, A.; Fonfŕia, J. P.; Marcelino, N.; Zúñiga, J.; Requena, A.; Bastida, A.; Lique, F.; Guélin, M.

    2015-01-01

    We report the detection of SiS rotational lines in high-vibrational states as well as SiO and SiC2 lines in their ground vibrational state toward IRC+10216 during the Atacama Large Millimeter Array Cycle 0. The spatial distribution of these molecules shows compact emission for SiS and a more extended emission for SiO and SiC2, and also proves the existence of an increase in the SiC2 emission at the outer shells of the circumstellar envelope. We analyze the excitation conditions of the vibrationally excited SiS using the population diagram technique, and we use a large velocity gradient model to compare with the observations. We found moderate discrepancies between the observations and the models that could be explained if SiS lines detected are optically thick. Additionally, the line profiles of the detected rotational lines in the high energy vibrational states show a decreasing linewidth with increasing energy levels. This may be evidence that these lines could be excited only in the inner shells, i.e., the densest and hottest, of the circumstellar envelope of IRC+10216. PMID:26688711

  18. The Synthesis of Organic Molecules of Intrinsic Microporosity Designed to Frustrate Efficient Molecular Packing

    PubMed Central

    Taylor, Rupert G. D.; Bezzu, C. Grazia; Carta, Mariolino; Msayib, Kadhum J.; Walker, Jonathan; Short, Rhys; Kariuki, Benson M.

    2016-01-01

    Abstract Efficient reactions between fluorine‐functionalised biphenyl and terphenyl derivatives with catechol‐functionalised terminal groups provide a route to large, discrete organic molecules of intrinsic microporosity (OMIMs) that provide porous solids solely by their inefficient packing. By altering the size and substituent bulk of the terminal groups, a number of soluble compounds with apparent BET surface areas in excess of 600 m2 g−1 are produced. The efficiency of OMIM structural units for generating microporosity is in the order: propellane>triptycene>hexaphenylbenzene>spirobifluorene>naphthyl=phenyl. The introduction of bulky hydrocarbon substituents significantly enhances microporosity by further reducing packing efficiency. These results are consistent with findings from previously reported packing simulation studies. The introduction of methyl groups at the bridgehead position of triptycene units reduces intrinsic microporosity. This is presumably due to their internal position within the OMIM structure so that they occupy space, but unlike peripheral substituents they do not contribute to the generation of free volume by inefficient packing. PMID:26751824

  19. Molecular dynamics simulation of dextran extension by constant force in single molecule AFM.

    PubMed

    Neelov, Igor M; Adolf, David B; McLeish, Tom C B; Paci, Emanuele

    2006-11-15

    The extension of 1-6 polysaccharides has been studied in a series of recent single molecule AFM experiments. For dextran, a key finding was the existence of a plateau in the force-extension curve at forces between 700 and 1000 pN. We studied the extension of the dextran 10-mer under constant force using atomistic simulation with various force fields. All the force fields reproduce the experimental plateau on the force-extension curve. With AMBER94 and AMBER-GLYCAM04 force fields the plateau can be explained by a transition of the glucopyranose rings in the dextran monomers from the chair ((4)C(1)) to the inverted chair ((1)C(4)) conformation while other processes occur at smaller (rotation around C5-C6 bond) or higher (chairs to boat transitions) forces. The CHARMM force field provides a different picture which associates the occurrence of the plateau to chair-boat transitions of the glucopyranose rings. PMID:16950842

  20. Si-bearing Molecules Toward IRC+10216: ALMA Unveils the Molecular Envelope of CWLeo

    NASA Astrophysics Data System (ADS)

    Velilla Prieto, L.; Cernicharo, J.; Quintana-Lacaci, G.; Agúndez, M.; Castro-Carrizo, A.; Fonfría, J. P.; Marcelino, N.; Zúñiga, J.; Requena, A.; Bastida, A.; Lique, F.; Guélin, M.

    2015-06-01

    We report the detection of SiS rotational lines in high-vibrational states as well as SiO and SiC2 lines in their ground vibrational state toward IRC+10216 during the Atacama Large Millimeter Array Cycle 0. The spatial distribution of these molecules shows compact emission for SiS and a more extended emission for SiO and SiC2 and also proves the existence of an increase in the SiC2 emission at the outer shells of the circumstellar envelope (CSE). We analyze the excitation conditions of the vibrationally excited SiS using the population diagram technique, and we use a large velocity gradient model to compare with the observations. We found moderate discrepancies between the observations and the models that could be explained if SiS lines detected are optically thick. Additionally, the line profiles of the detected rotational lines in the high-energy vibrational states show a decreasing linewidth with increasing energy levels. This may be evidence that these lines could be excited only in the inner shells, i.e., the densest and hottest, of the CSE of IRC+10216.

  1. Tonal interface to MacroMolecules (TIMMol): A textual and tonal tool for molecular visualization.

    PubMed

    Cordes, Timothy J; Carlson, C Britt; Forest, Katrina T

    2008-05-01

    We developed the three-dimensional visualization software, Tonal Interface to MacroMolecules or TIMMol, for studying atomic coordinates of protein structures. Key features include audio tones indicating x, y, z location, identification of the cursor location in one-dimensional and three-dimensional space, textual output that can be easily linked to speech or Braille output, and the ability to scroll along the main chain backbone of a protein structure. This program was initially designed for visually impaired users, and it already has shown its effectiveness in helping a blind researcher study X-ray crystal structure data. Subsequently, TIMMol has been enhanced with a graphical display to act as a bridge to ease communication between sighted and visually impaired users as well as to serve users with spatial visualization difficulties. We performed a pilot study to assess the efficacy of the program in conveying three-dimensional information about proteins with and without graphical output to a general scientific audience. Attitudes regarding using TIMMol were assessed using Rasmol, a common visualization package, for comparison. With the use of text and tones exclusively, a majority of users were able to identify specific secondary structure elements, three-dimensional relationships among atoms, and atoms coordinating a ligand. In addition, a majority of users saw benefits in using TIMMol and would recommend it to those having difficulty with standard tools. PMID:21591192

  2. Recognizing molecular patterns by machine learning: an agnostic structural definition of the hydrogen bond.

    PubMed

    Gasparotto, Piero; Ceriotti, Michele

    2014-11-01

    The concept of chemical bonding can ultimately be seen as a rationalization of the recurring structural patterns observed in molecules and solids. Chemical intuition is nothing but the ability to recognize and predict such patterns, and how they transform into one another. Here, we discuss how to use a computer to identify atomic patterns automatically, so as to provide an algorithmic definition of a bond based solely on structural information. We concentrate in particular on hydrogen bonding--a central concept to our understanding of the physical chemistry of water, biological systems, and many technologically important materials. Since the hydrogen bond is a somewhat fuzzy entity that covers a broad range of energies and distances, many different criteria have been proposed and used over the years, based either on sophisticate electronic structure calculations followed by an energy decomposition analysis, or on somewhat arbitrary choices of a range of structural parameters that is deemed to correspond to a hydrogen-bonded configuration. We introduce here a definition that is univocal, unbiased, and adaptive, based on our machine-learning analysis of an atomistic simulation. The strategy we propose could be easily adapted to similar scenarios, where one has to recognize or classify structural patterns in a material or chemical compound. PMID:25381505

  3. Recognizing molecular patterns by machine learning: An agnostic structural definition of the hydrogen bond

    NASA Astrophysics Data System (ADS)

    Gasparotto, Piero; Ceriotti, Michele

    2014-11-01

    The concept of chemical bonding can ultimately be seen as a rationalization of the recurring structural patterns observed in molecules and solids. Chemical intuition is nothing but the ability to recognize and predict such patterns, and how they transform into one another. Here, we discuss how to use a computer to identify atomic patterns automatically, so as to provide an algorithmic definition of a bond based solely on structural information. We concentrate in particular on hydrogen bonding - a central concept to our understanding of the physical chemistry of water, biological systems, and many technologically important materials. Since the hydrogen bond is a somewhat fuzzy entity that covers a broad range of energies and distances, many different criteria have been proposed and used over the years, based either on sophisticate electronic structure calculations followed by an energy decomposition analysis, or on somewhat arbitrary choices of a range of structural parameters that is deemed to correspond to a hydrogen-bonded configuration. We introduce here a definition that is univocal, unbiased, and adaptive, based on our machine-learning analysis of an atomistic simulation. The strategy we propose could be easily adapted to similar scenarios, where one has to recognize or classify structural patterns in a material or chemical compound.

  4. Recognizing molecular patterns by machine learning: An agnostic structural definition of the hydrogen bond

    SciTech Connect

    Gasparotto, Piero; Ceriotti, Michele

    2014-11-07

    The concept of chemical bonding can ultimately be seen as a rationalization of the recurring structural patterns observed in molecules and solids. Chemical intuition is nothing but the ability to recognize and predict such patterns, and how they transform into one another. Here, we discuss how to use a computer to identify atomic patterns automatically, so as to provide an algorithmic definition of a bond based solely on structural information. We concentrate in particular on hydrogen bonding – a central concept to our understanding of the physical chemistry of water, biological systems, and many technologically important materials. Since the hydrogen bond is a somewhat fuzzy entity that covers a broad range of energies and distances, many different criteria have been proposed and used over the years, based either on sophisticate electronic structure calculations followed by an energy decomposition analysis, or on somewhat arbitrary choices of a range of structural parameters that is deemed to correspond to a hydrogen-bonded configuration. We introduce here a definition that is univocal, unbiased, and adaptive, based on our machine-learning analysis of an atomistic simulation. The strategy we propose could be easily adapted to similar scenarios, where one has to recognize or classify structural patterns in a material or chemical compound.

  5. Organic molecules in the atmosphere of Jupiter. [low molecular weight hydrocarbons

    NASA Technical Reports Server (NTRS)

    Ponnamperuma, C. A.

    1978-01-01

    Organic synthesis in the primitive solar system was simulated by Fischer Tropsch type experiments. Particular attention was given to the formation of lower molecular weight hydrocarbons. In a gas flow experiment, a gas mixture of H2 and CO was introduced into a heated reaction tube at a constant flow rate and passed through a catalyst (powdered Canyon Diablo). The products that emerged were directly analyzed by gas chromatography. The results of 21 runs under various gas mixing rations, reaction temperatures, and gas-catalyst contact times showed the predominance of the saturated hydrocarbon formation at C sub 4 and C sub 5 over the unsaturated ones. Saturate/unsaturate ratios were mostly less than 0.4 and none showed over 0.7.

  6. UCLA's Molecular Screening Shared Resource: enhancing small molecule discovery with functional genomics and new technology.

    PubMed

    Damoiseaux, Robert

    2014-05-01

    The Molecular Screening Shared Resource (MSSR) offers a comprehensive range of leading-edge high throughput screening (HTS) services including drug discovery, chemical and functional genomics, and novel methods for nano and environmental toxicology. The MSSR is an open access environment with investigators from UCLA as well as from the entire globe. Industrial clients are equally welcome as are non-profit entities. The MSSR is a fee-for-service entity and does not retain intellectual property. In conjunction with the Center for Environmental Implications of Nanotechnology, the MSSR is unique in its dedicated and ongoing efforts towards high throughput toxicity testing of nanomaterials. In addition, the MSSR engages in technology development eliminating bottlenecks from the HTS workflow and enabling novel assays and readouts currently not available. PMID:24661210

  7. Features in the electronic structure and photoemission spectra of organic molecular semiconductors: The molecules of metal-phthalocyanines and PTCDA

    NASA Astrophysics Data System (ADS)

    Tikhonov, E. V.; Uspenskii, Yu. A.; Khokhlov, D. R.

    2013-09-01

    The role of many-electron effects in the formation of electronic quasiparticle spectra in organic molecular semiconductors (OMS) is analyzed. Many-body perturbation theory, ab initio calculations of metal phthalocyanines and PTCDA molecules, and experimental photoemission spectra are applied to this analysis. It is shown that density functional theory (DFT) poorly reproduces the electronic spectra of OMS. The use of a hybrid functional method (HFM) provides precise reproduction of both valence and conducting bands, while the HOMO-LUMO gap remains underestimated. The correct gap width is obtained in both DFT and HFM, when it is calculated through ionization and affinity energies. It is shown that such an approach gives a formula for gap correction due to electron correlations, which is close to an expression derived from the GW approximation.

  8. Spatiotemporal patterns enhanced by intra- and inter-molecular fluctuations in arrays of allosterically regulated enzymes

    NASA Astrophysics Data System (ADS)

    Togashi, Yuichi; Casagrande, Vanessa

    2015-03-01

    Enzymatic reactions often involve slow conformational changes, with reaction cycles that sometimes require milliseconds or seconds to complete. The dynamics are strongly affected by fluctuations at the nanoscale. However, such enzymes often occur in small numbers in a cell; hence, the fluctuations caused by finite numbers of molecules should also be substantial. Because of these factors, the behavior of the system is likely to deviate from that of classical reaction-diffusion equations, in which immediate reaction events are assumed to occur without memory and between a huge number of molecules. In this work, we model each enzyme as a unit represented by a phase variable to investigate the effects of fluctuations in arrays of enzymes. Using an analysis based on partial differential equations and stochastic simulations, we show that fluctuations arising from internal states of enzymes (intramolecular fluctuations) and those arising from the stochastic nature of interactions between molecules (intermolecular fluctuations) have distinctive effects on spatiotemporal patterns; the former generally disturb synchronization at high frequencies, whereas the latter can enhance synchronization. The balance of the two types of fluctuations may determine the spatiotemporal behavior of biochemical processes.

  9. Symbolic computation engines and molecular modeling templates: Maple-assisted point group analysis of the vibrational activity of molecules

    NASA Astrophysics Data System (ADS)

    Vail, Benjamin; Aris, Damian; Scarlete, Mihai

    The present study proposes an algorithm for point-group analysis (PGA) of the vibrational activity of molecules, adapted for the efficient utilization of the linear packages incorporated into currently available symbolic computation engines (SCE), such as Maple, Mathcad, or Mathematica. By the creation of this algorithm, we have addressed the need for a numerically friendly environment, outside the "locked" procedures within molecular modeling packages, which will preserve its flexibility, transparency, and maneuverability, regardless of the complexity of the calculation. The format of the character tables of the point groups significant to chemical species has been adapted to ensure automatic numerization, and consistent input of the alphanumeric data from the existent character tables into the SCE templates designed to perform the PGA. The two proposed templates address two complementary objectives: (i) a totally transparent and interactive file has been designed to allow access to all intermediate results at all levels of the procedure for easy implementation of potential additional modules of special interest 1-5, and (ii) for fast output and routine calculations of the IR/Raman vibrational activity of molecules based on their point groups, a totally automatic file with a highly simplified input interface has been designed. The numerical interface conveniently replaces the usual graphic user interface that is common to most commercial molecular modeling software packages, requiring minimum input determination. The structure for both templates is based on the use of the digitized forms for the character tables, for the symmetry operations, and for symmetry elements, all saved in dedicated libraries uploaded to the numerical database of the SCE.

  10. Constant pH Molecular Dynamics Reveals pH-Modulated Binding of Two Small-Molecule BACE1 Inhibitors.

    PubMed

    Ellis, Christopher R; Tsai, Cheng-Chieh; Hou, Xinjun; Shen, Jana

    2016-03-17

    Targeting β-secretase (BACE1) with small-molecule inhibitors offers a promising route for treatment of Alzheimer's disease. However, the intricate pH dependence of BACE1 function and inhibitor efficacy has posed major challenges for structure-based drug design. Here we investigate two structurally similar BACE1 inhibitors that have dramatically different inhibitory activity using continuous constant pH molecular dynamics (CpHMD). At high pH, both inhibitors are stably bound to BACE1; however, within the enzyme active pH range, only the iminopyrimidinone-based inhibitor remains bound, while the aminothiazine-based inhibitor becomes partially dissociated following the loss of hydrogen bonding with the active site and change of the 10s loop conformation. The drastically lower activity of the second inhibitor is due to the protonation of a catalytic aspartate and the lack of a propyne tail. This work demonstrates that CpHMD can be used for screening pH-dependent binding profiles of small-molecule inhibitors, providing a new tool for structure-based drug design and optimization. PMID:26905811

  11. Magnetic interaction between a radical spin and a single-molecule magnet in a molecular spin-valve.

    PubMed

    Urdampilleta, Matias; Klayatskaya, Svetlana; Ruben, Mario; Wernsdorfer, Wolfgang

    2015-04-28

    Molecular spintronics using single molecule magnets (SMMs) is a fast growing field of nanoscience that proposes to manipulate the magnetic and quantum information stored in these molecules. Herein we report evidence of a strong magnetic coupling between a metallic ion and a radical spin in one of the most extensively studied SMMs: the bis(phtalocyaninato)terbium(III) complex (TbPc2). For that we use an original multiterminal device comprising a carbon nanotube laterally coupled to the SMMs. The current through the device, sensitive to magnetic interactions, is used to probe the magnetization of a single Tb ion. Combining this electronic read-out with the transverse field technique has allowed us to measure the interaction between the terbium ion, its nuclear spin, and a single electron located on the phtalocyanine ligands. We show that the coupling between the Tb and this radical is strong enough to give extra resonances in the hysteresis loop that are not observed in the anionic form of the complex. The experimental results are then modeled by diagonalization of a three-spins Hamiltonian. This strong coupling offers perspectives for implementing nuclear and electron spin resonance techniques to perform basic quantum operations in TbPc2. PMID:25858088

  12. Molecular magnetic resonance imaging of acute vascular cell adhesion molecule-1 expression in a mouse model of cerebral ischemia.

    PubMed

    Hoyte, Lisa C; Brooks, Keith J; Nagel, Simon; Akhtar, Asim; Chen, Ruoli; Mardiguian, Sylvie; McAteer, Martina A; Anthony, Daniel C; Choudhury, Robin P; Buchan, Alastair M; Sibson, Nicola R

    2010-06-01

    The pathogenesis of stroke is multifactorial, and inflammation is thought to have a critical function in lesion progression at early time points. Detection of inflammatory processes associated with cerebral ischemia would be greatly beneficial in both designing individual therapeutic strategies and monitoring outcome. We have recently developed a new approach to imaging components of the inflammatory response, namely endovascular adhesion molecule expression on the brain endothelium. In this study, we show specific imaging of vascular cell adhesion molecule (VCAM)-1 expression in a mouse model of middle cerebral artery occlusion (MCAO), and a reduction in this inflammatory response, associated with improved behavioral outcome, as a result of preconditioning. The spatial extent of VCAM-1 expression is considerably greater than the detectable lesion using diffusion-weighted imaging (25% versus 3% total brain volume), which is generally taken to reflect the core of the lesion at early time points. Thus, VCAM-1 imaging seems to reveal both core and penumbral regions, and our data implicate VCAM-1 upregulation and associated inflammatory processes in the progression of penumbral tissue to infarction. Our findings indicate that such molecular magnetic resonance imaging (MRI) approaches could be important clinical tools for patient evaluation, acute monitoring of therapy, and design of specific treatment strategies. PMID:20087364

  13. Structure formation during the crystallization induction period of a short chain-molecule system: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Takeuchi, Hisao

    1998-10-01

    A molecular dynamics simulation has been performed for a short chain-molecule system to study structure formation during the crystallization induction period. A model simulating n-alkane having 20 methylene units was used for the short-chain molecule. A model system containing either 250 or 2000 chains was quenched from a high temperature, and the structure formation was examined at constant temperature and pressure. The model system containing 250 chains eventually forms an ordered phase after the induction period, during which macroscopic quantities, such as volume, remain almost constant. In spite of these small changes in the macroscopic quantities, development of local parallel order is significant during the induction period. We also found that the development of local parallel order causes density fluctuations which appear as a weak small-angle peak in the structure factor. A characteristic length scale corresponding to the density fluctuations becomes larger as time elapses in the induction period. These features are qualitatively in accord with recent experimental findings on a different polymer system [M. Imai et al., Phys. Rev. B 52, 12 696 (1995)].

  14. Fast and General Method To Predict the Physicochemical Properties of Druglike Molecules Using the Integral Equation Theory of Molecular Liquids.

    PubMed

    Palmer, David S; Mišin, Maksim; Fedorov, Maxim V; Llinas, Antonio

    2015-09-01

    We report a method to predict physicochemical properties of druglike molecules using a classical statistical mechanics based solvent model combined with machine learning. The RISM-MOL-INF method introduced here provides an accurate technique to characterize solvation and desolvation processes based on solute-solvent correlation functions computed by the 1D reference interaction site model of the integral equation theory of molecular liquids. These functions can be obtained in a matter of minutes for most small organic and druglike molecules using existing software (RISM-MOL) (Sergiievskyi, V. P.; Hackbusch, W.; Fedorov, M. V. J. Comput. Chem. 2011, 32, 1982-1992). Predictions of caco-2 cell permeability and hydration free energy obtained using the RISM-MOL-INF method are shown to be more accurate than the state-of-the-art tools for benchmark data sets. Due to the importance of solvation and desolvation effects in biological systems, it is anticipated that the RISM-MOL-INF approach will find many applications in biophysical and biomedical property prediction. PMID:26212723

  15. 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

  16. Molecular bioelectricity: how endogenous voltage potentials control cell behavior and instruct pattern regulation in vivo

    PubMed Central

    Levin, Michael

    2014-01-01

    In addition to biochemical gradients and transcriptional networks, cell behavior is regulated by endogenous bioelectrical cues originating in the activity of ion channels and pumps, operating in a wide variety of cell types. Instructive signals mediated by changes in resting potential control proliferation, differentiation, cell shape, and apoptosis of stem, progenitor, and somatic cells. Of importance, however, cells are regulated not only by their own Vmem but also by the Vmem of their neighbors, forming networks via electrical synapses known as gap junctions. Spatiotemporal changes in Vmem distribution among nonneural somatic tissues regulate pattern formation and serve as signals that trigger limb regeneration, induce eye formation, set polarity of whole-body anatomical axes, and orchestrate craniofacial patterning. New tools for tracking and functionally altering Vmem gradients in vivo have identified novel roles for bioelectrical signaling and revealed the molecular pathways by which Vmem changes are transduced into cascades of downstream gene expression. Because channels and gap junctions are gated posttranslationally, bioelectrical networks have their own characteristic dynamics that do not reduce to molecular profiling of channel expression (although they couple functionally to transcriptional networks). The recent data provide an exciting opportunity to crack the bioelectric code, and learn to program cellular activity at the level of organs, not only cell types. The understanding of how patterning information is encoded in bioelectrical networks, which may require concepts from computational neuroscience, will have transformative implications for embryogenesis, regeneration, cancer, and synthetic bioengineering. PMID:25425556

  17. Patterns of cryptic host specificity in duck lice based on molecular data.

    PubMed

    Escalante, G C; Sweet, A D; McCracken, K G; Gustafsson, D R; Wilson, R E; Johnson, K P

    2016-06-01

    Documenting patterns of host specificity in parasites relies on the adequate definition of parasite species. In many cases, parasites have simplified morphology, making species delimitation based on traditional morphological characters difficult. Molecular data can help in assessing whether widespread parasites harbour cryptic species and, alternatively, in guiding further taxonomic revision in cases in which there is morphological variation. The duck louse genus Anaticola (Phthiraptera: Philopteridae), based on current taxonomy, contains both host-specific and widespread species. Mitochondrial and nuclear DNA sequences of samples from this genus were used to document patterns of host specificity. The comparison of these patterns with morphological variations in Anaticola revealed a general correspondence between the groups identified by DNA sequences and morphology, respectively. These results suggest that a more thorough taxonomic review of this genus is needed. In general, the groups identified on the basis of molecular data were associated with particular groups of waterfowl (e.g. dabbling ducks, sea ducks, geese) or specific biogeographic regions (e.g. North America, South America, Australia, Eurasia). PMID:26753998

  18. Liquid crystal polymer networks: preparation, properties, and applications of films with patterned molecular alignment.

    PubMed

    Liu, Danqing; Broer, Dirk J

    2014-11-18

    Monolithically ordered liquid crystal polymer networks are formed by the photoinitiated polymerization of multifunctional liquid crystal monomers. This paper describes the relevant principles and methods, the basic structure-property relationships in terms of mesogenic properties of the monomers, and the mechanical and optical properties of the polymers. Strategies are discussed to control the molecular orientation by various means and in all three dimensions. The versatility of the process is demonstrated by two examples of films with a patterned molecular order. It is shown that patterned retarders can be made by a two-step polymerization process which is successfully employed in a transflective display principle. A transflective display is a liquid crystal display that operates in both a reflective mode using ambient light and a transmissive mode with light coming from a backlight system. Furthermore, a method is discussed to create a patterned film in a single polymerization process. This film has alternating planar chiral nematic areas next to perpendicularly oriented (so-called homeotropic) areas. When applied as a coating to a substrate, the film changes its surface texture. During exposure to UV light, it switches from a flat to a corrugated state. PMID:24707811

  19. Molecular Framework of a Regulatory Circuit Initiating Two-Dimensional Spatial Patterning of Stomatal Lineage

    PubMed Central

    Rychel, Amanda L.; Garrick, Jacqueline M.; Kawaguchi, Masayoshi; Peterson, Kylee M.; Torii, Keiko U.

    2015-01-01

    Stomata, valves on the plant epidermis, are critical for plant growth and survival, and the presence of stomata impacts the global water and carbon cycle. Although transcription factors and cell-cell signaling components regulating stomatal development have been identified, it remains unclear as to how their regulatory interactions are translated into two-dimensional patterns of stomatal initial cells. Using molecular genetics, imaging, and mathematical simulation, we report a regulatory circuit that initiates the stomatal cell-lineage. The circuit includes a positive feedback loop constituting self-activation of SCREAMs that requires SPEECHLESS. This transcription factor module directly binds to the promoters and activates a secreted signal, EPIDERMAL PATTERNING FACTOR2, and the receptor modifier TOO MANY MOUTHS, while the receptor ERECTA lies outside of this module. This in turn inhibits SPCH, and hence SCRMs, thus constituting a negative feedback loop. Our mathematical model accurately predicts all known stomatal phenotypes with the inclusion of two additional components to the circuit: an EPF2-independent negative-feedback loop and a signal that lies outside of the SPCH•SCRM module. Our work reveals the intricate molecular framework governing self-organizing two-dimensional patterning in the plant epidermis. PMID:26203655

  20. Second virial coefficient of rod-shaped molecules and molecular dynamics simulations of the isotropic phase

    NASA Astrophysics Data System (ADS)

    Heyes, D. M.; Turner, P.; English, R. J.; Williams, R.; Brańka, A. C.

    2015-04-01

    The second virial coefficient, B2 is computed of linear rigid rods composed of m equally spaced sites interacting with sites on other rods via the hard-sphere or Weeks-Chandler-Andersen (WCA) pair potentials. The dependence of B2 on a wide range of separation distance between the sites L and m for both types of potential is computed. Molecular dynamics simulations were carried out of the thermodynamic, static, and percolation properties of the WCA rigid rods in the isotropic phase as a function of rod number density ρ . Simple scaling relationships are discovered between thermodynamic and other static properties as a function of ρ and m , which extend well into the semidilute density range. The percolation threshold distance (PTD) between the centers of mass of the rods complies well with a mean-field random orientation approximation from low density well into the semidilute regime. The corresponding site-site PTD proved more problematic to represent by simple functions, but at high rod density, scales better with the number of sites density rather than the rod number density.

  1. Oxidation of nickel surfaces through the energetic impacts of oxygen molecules: Reactive molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Amiri, Negar; Behnejad, Hassan

    2016-04-01

    Molecular dynamics approach accompanied by reactive force field is used to study the characteristics of the oxide growth process on Ni(100) and Ni(111) surfaces at the temperatures of 300, 600, and 900 K and 5 eV as the energy of the O2 impacts. The exposure of Ni surfaces to the high-energy O2 impacts indicates that the primary oxide nuclei can be formed on any impact site. The results of kinetic studies clarify that the oxide growth kinetics cannot be accurately explained with the island growth model and increasing the surface temperature raises failure of the model. Under the present conditions, the growth kinetics is found to obey a Langmuir growth model. Increasing the surface temperature from 300 to 900 K results in ˜18.75% and ˜23% more oxygen consumption by (100) and (111) surfaces of Ni, respectively. The structure of nickel oxide (NiO) film formed after 200 successive O2 impacts per surface super-cell is investigated utilizing radial distribution functions and oxygen density profiles. These calculations demonstrate that the structure of the formed NiO film is amorphous. Moreover, the charge profiles in Ni/NiO system are illustrated and discussed.

  2. Tunable spin filter and molecular hybridization in a quantum dot molecule

    NASA Astrophysics Data System (ADS)

    Mireles, F.; Ulloa, S. E.

    2005-03-01

    Spin filtering using few electron semiconductor quantum dots formed in two-dimensional electron gas systems has attracted much recent attention in spintronics. Spin filtering has been achieved in a quantum dot via universal conductance fluctuations and electron magnetic focusing [1]. A bipolar spin filter (SF) has been realized recently using a semiconductor quantum dot which can operate practically as a perfect SF, provided there is a large enough Zeeman splitting [2]. In this work we present calculations showing that the tunable (molecular) hybridization between two quantum dots with few electrons and connected ``in parallel,'' produces a singlet-triplet transition in the ground state which can be used as a robust bipolar SF in both the linear and non-linear regimes of transport. The bipolar SF is found to be fully tunable by only electrical gating at low temperatures. We show that a singlet-triplet transition in the energy spectrum gives rise to the natural spin selectivity in the odd-to-even electron number transition in Coulomb blockade experiments. The competition between the Zeeman, Coulomb, and tunneling energies is studied in detail to determine the optimal conditions to achieve the singlet-triplet transition, so that it becomes broadly useful as a bipolar SF. [1] J. A. Folk et al., Science 299, 679 (2003). [2] R. Hanson et al., cond-mat/0311414 (2003). *Supported by DGAPA-UNAM project 1N114403, CONACYT, projects J40521F and 143673F, and NSF-IMC.

  3. Oxidation of nickel surfaces through the energetic impacts of oxygen molecules: Reactive molecular dynamics simulations.

    PubMed

    Amiri, Negar; Behnejad, Hassan

    2016-04-14

    Molecular dynamics approach accompanied by reactive force field is used to study the characteristics of the oxide growth process on Ni(100) and Ni(111) surfaces at the temperatures of 300, 600, and 900 K and 5 eV as the energy of the O2 impacts. The exposure of Ni surfaces to the high-energy O2 impacts indicates that the primary oxide nuclei can be formed on any impact site. The results of kinetic studies clarify that the oxide growth kinetics cannot be accurately explained with the island growth model and increasing the surface temperature raises failure of the model. Under the present conditions, the growth kinetics is found to obey a Langmuir growth model. Increasing the surface temperature from 300 to 900 K results in ∼18.75% and ∼23% more oxygen consumption by (100) and (111) surfaces of Ni, respectively. The structure of nickel oxide (NiO) film formed after 200 successive O2 impacts per surface super-cell is investigated utilizing radial distribution functions and oxygen density profiles. These calculations demonstrate that the structure of the formed NiO film is amorphous. Moreover, the charge profiles in Ni/NiO system are illustrated and discussed. PMID:27083743

  4. A Molecular Dynamics Study on the Confinement of Carbon Dioxide Molecules in Carbon Nanotubes

    NASA Astrophysics Data System (ADS)

    Lazor, Meagan; Rende, Deniz; Baysal, Nihat; Ozisik, Rahmi

    2012-02-01

    The influence of atmospheric carbon dioxide (CO2) concentration on global warming is considered as one of the primary environmental issues of the past two decades. The main source of CO2 emission is human activity, such as the use of fossil fuels in transportation and industrial plants. Following the release of Kyoto Protocol in 1997, effective ways of controlling CO2 emissions received much attention. As a result, various materials such as activated carbon, zeolites, and carbon nanotubes (CNTs) were investigated for their CO2 adsorbing properties. CNTs were reported to have CO2 adsorption capability twice that of activated carbon, hence they received the most attention. In the current study, single walled carbon nanotubes (SWNTs) were used as one dimensional nanoporous materials and their CO2 adsorption capacity was analyzed with Molecular Dynamics simulations. Results indicated that SWNTs are excellent CO2 adsorbers and their effectiveness increase at low CO2 concentrations. In addition, we showed that by varying temperature, CO2 can be removed from the SWNTs, providing a simple method to reuse SWNTs.

  5. Predicting Adsorption Affinities of Small Molecules on Carbon Nanotubes Using Molecular Dynamics Simulation.

    PubMed

    Comer, Jeffrey; Chen, Ran; Poblete, Horacio; Vergara-Jaque, Ariela; Riviere, Jim E

    2015-12-22

    Computational techniques have the potential to accelerate the design and optimization of nanomaterials for applications such as drug delivery and contaminant removal; however, the success of such techniques requires reliable models of nanomaterial surfaces as well as accurate descriptions of their interactions with relevant solutes. In the present work, we evaluate the ability of selected models of naked and hydroxylated carbon nanotubes to predict adsorption equilibrium constants for about 30 small aromatic compounds with a variety of functional groups. The equilibrium constants determined using molecular dynamics coupled with free-energy calculation techniques are directly compared to those derived from experimental measurements. The calculations are highly predictive of the relative adsorption affinities of the compounds, with excellent correlation (r ≥ 0.9) between calculated and measured values of the logarithm of the adsorption equilibrium constant. Moreover, the agreement in absolute terms is also reasonable, with average errors of less than one decade. We also explore possible effects of surface loading, although we demonstrate that they are negligible for the experimental conditions considered. Given the degree of reliability demonstrated, we move on to employing the in silico techniques in the design of nanomaterials, using the optimization of adsorption affinity for the herbacide atrazine as an example. Our simulations suggest that, compared to other modifications of graphenic carbon, polyvinylpyrrolidone conjugation gives the highest affinity for atrazine-substantially greater than that of graphenic carbon alone-and may be useful as a nanomaterial for delivery or sequestration of atrazine. PMID:26506132

  6. Reconstitution of biologically active 50S ribosomal subunits with artificial 5S RNA molecules carrying disturbances in the base pairing within the molecular stalk.

    PubMed Central

    Raué, H A; Lorenz, S; Erdmann, V A; Planta, R J

    1981-01-01

    Bacillus stearothermophilus 50S ribosomal subunits were reconstituted in vitro using artificial 5S RNA molecules constructed by combining parts of major and minor type (Raué et al. (1976) Europ. J. Biochem. 68, 169-176) B. licheniformis 5S RNA. The artificial 5S RNA molecules carry defined disturbances (A.C juxtapositions and extra G.U pairs) in the base pairing between the 5'- and 3'-terminal sequences of the molecule (the molecular stalk region). The biological activity of the reconstituted subunits was determined in an E. coli cell-free system programmed with poly-U. The results show that conservation of the base pairing within the molecular stalk is not required for biological activity of 5S RNA. Disturbances of the base pairing within this region do reduce the rate of reconstitution, however. Normal base pairing in the molecular stalk is thus required to ensure efficient ribosome assembly. PMID:6164987

  7. Molecular printing

    PubMed Central

    Braunschweig, Adam B.; Huo, Fengwei; Mirkin, Chad A.

    2014-01-01

    Molecular printing techniques, which involve the direct transfer of molecules to a substrate with submicrometre resolution, have been extensively developed over the past decade and have enabled many applications. Arrays of features on this scale have been used to direct materials assembly, in nanoelectronics, and as tools for genetic analysis and disease detection. The past decade has witnessed the maturation of molecular printing led by two synergistic technologies: dip-pen nanolithography and soft lithography. Both are characterized by material and substrate flexibility, but dip-pen nanolithography has unlimited pattern design whereas soft lithography has limited pattern flexibility but is low in cost and has high throughput. Advances in DPN tip arrays and inking methods have increased the throughput and enabled applications such as multiplexed arrays. A new approach to molecular printing, polymer-pen lithography, achieves low-cost, high-throughput and pattern flexibility. This Perspective discusses the evolution and future directions of molecular printing. PMID:21378889

  8. Modelling rotations, vibrations, and rovibrational couplings in astructural molecules - a case study based on the H+5 molecular ion

    NASA Astrophysics Data System (ADS)

    Sarka, János; Fábri, Csaba; Szidarovszky, Tamás; Császár, Attila G.; Lin, Zhou; McCoy, Anne B.

    2015-07-01

    One-dimensional (1D) and two-dimensional (2D) models are investigated, which help to understand the unusual rovibrational energy-level structure of the astronomically relevant and chemically interesting astructural molecular ion H+5. Due to the very low hindering barrier characterising the 1D torsion-only vibrational model of H+5, this model yields strongly divergent energy levels. The results obtained using a realistic model for the torsion potential, including the computed (near) degeneracies, can be rationalised in terms of the model with no barrier. Coupling of the torsional motion with a single rotational degree of freedom is also investigated in detail. It is shown how the embedding-dependent rovibrational models yield energy levels that can be rationalised via the 2D vibrational model containing two independent torsions. Insight into the complex rovibrational energy level structure of the models and of H+5 is gained via variational nuclear motion and diffusion Monte Carlo computations and by the analysis of the wavefunctions they provide. The modelling results describing the transition from the zero barrier limit to the large barrier limit should prove to be useful for the important class of molecules and molecular ions that contain two weakly coupled internal rotors.

  9. Combined fragment molecular orbital cluster in molecule approach to massively parallel electron correlation calculations for large systems.

    PubMed

    Findlater, Alexander D; Zahariev, Federico; Gordon, Mark S

    2015-04-16

    The local correlation "cluster-in-molecule" (CIM) method is combined with the fragment molecular orbital (FMO) method, providing a flexible, massively parallel, and near-linear scaling approach to the calculation of electron correlation energies for large molecular systems. Although the computational scaling of the CIM algorithm is already formally linear, previous knowledge of the Hartree-Fock (HF) reference wave function and subsequent localized orbitals is required; therefore, extending the CIM method to arbitrarily large systems requires the aid of low-scaling/linear-scaling approaches to HF and orbital localization. Through fragmentation, the combined FMO-CIM method linearizes the scaling, with respect to system size, of the HF reference and orbital localization calculations, achieving near-linear scaling at both the reference and electron correlation levels. For the 20-residue alanine α helix, the preliminary implementation of the FMO-CIM method captures 99.6% of the MP2 correlation energy, requiring 21% of the MP2 wall time. The new method is also applied to solvated adamantine to illustrate the multilevel capability of the FMO-CIM method. PMID:25794346

  10. Mixed-metal molecular complexes: Single-molecule nanomagnets and bioinorganic models of the water oxidizing complex of photosystem II

    NASA Astrophysics Data System (ADS)

    Mishra, Abhudaya

    2006-12-01

    The current burgeoning research in high nuclearity manganese-containing carboxylate clusters is primarily due to their relevance in areas as diverse as magnetic materials and bioinorganic chemistry. In the former, the ability of single molecules to retain, below a critical temperature (T B), their magnetization vector, resulting in the observation of bulk magnetization in the absence of a field and without long-range ordering of the spins, has termed such molecules as Single-Molecule Magnets (SMMs), or molecular nanomagnets. These molecules display superparamagnet like slow magnetization relaxation arising from the combination of a large molecular spin, S, and a large and negative magnetoanisotropy, D. Traditionally, these nanomagnets have been Mn containing species. An out of the box approach towards synthesizing SMMs is engineering mixed-metal Mn-containing compounds. An attractive choice towards this end is the use of Lanthanides (Ln), which possess both a high spin, S, and a large D. A family of related MnIII8Ce IV SMMs has been synthesized. However, the Ce ion of these complexes is diamagnetic (CeIV). Thus, further investigation has led to the isolation of a family of MnIII11Ln III4 complexes in which all but the Ln = Eu complex function as single-molecule nanomagnets. The mixed-metal synthetic effort has been extended to include actinides with the successful isolation of a Mn IV10ThIV6 complex, albeit this homovalent complex is not a SMM. In the bioinorganic research, the Water Oxidizing Complex (WOC) in Photosystem II (PS II) catalyzes the oxidation of H2O to O2 in green plants, algae and cyanobacteria. Recent crystal structures of the WOC confirm it to be a Mn4CaOx cluster with primarily carboxylate ligation. To date, various multinuclear Mn complexes have been synthesized as putative models of the WOC. On the contrary, there have been no synthetic MnCa(Sr) mixed-metal complexes. Thus, in this bioinorganic modeling research of the WOC, various synthetic

  11. Novel strategy for biofilm inhibition by using small molecules targeting molecular chaperone DnaK.

    PubMed

    Arita-Morioka, Ken-ichi; Yamanaka, Kunitoshi; Mizunoe, Yoshimitsu; Ogura, Teru; Sugimoto, Shinya

    2015-01-01

    Biofilms are complex communities of microorganisms that attach to surfaces and are embedded in a self-produced extracellular matrix. Since these cells acquire increased tolerance against antimicrobial agents and host immune systems, biofilm-associated infectious diseases tend to become chronic. We show here that the molecular chaperone DnaK is important for biofilm formation and that chemical inhibition of DnaK cellular functions is effective in preventing biofilm development. Genetic, microbial, and microscopic analyses revealed that deletion of the dnaK gene markedly reduced the production of the extracellular functional amyloid curli, which contributes to the robustness of Escherichia coli biofilms. We tested the ability of DnaK inhibitors myricetin (Myr), telmisartan, pancuronium bromide, and zafirlukast to prevent biofilm formation of E. coli. Only Myr, a flavonol widely distributed in plants, inhibited biofilm formation in a concentration-dependent manner (50% inhibitory concentration [IC50] = 46.2 μM); however, it did not affect growth. Transmission electron microscopy demonstrated that Myr inhibited the production of curli. Phenotypic analyses of thermosensitivity, cell division, intracellular level of RNA polymerase sigma factor RpoH, and vulnerability to vancomycin revealed that Myr altered the phenotype of E. coli wild-type cells to make them resemble those of the isogenic dnaK deletion mutant, indicating that Myr inhibits cellular functions of DnaK. These findings provide insights into the significance of DnaK in curli-dependent biofilm formation and indicate that DnaK is an ideal target for antibiofilm drugs. PMID:25403660

  12. Novel Strategy for Biofilm Inhibition by Using Small Molecules Targeting Molecular Chaperone DnaK

    PubMed Central

    Arita-Morioka, Ken-ichi; Yamanaka, Kunitoshi; Mizunoe, Yoshimitsu; Ogura, Teru

    2014-01-01

    Biofilms are complex communities of microorganisms that attach to surfaces and are embedded in a self-produced extracellular matrix. Since these cells acquire increased tolerance against antimicrobial agents and host immune systems, biofilm-associated infectious diseases tend to become chronic. We show here that the molecular chaperone DnaK is important for biofilm formation and that chemical inhibition of DnaK cellular functions is effective in preventing biofilm development. Genetic, microbial, and microscopic analyses revealed that deletion of the dnaK gene markedly reduced the production of the extracellular functional amyloid curli, which contributes to the robustness of Escherichia coli biofilms. We tested the ability of DnaK inhibitors myricetin (Myr), telmisartan, pancuronium bromide, and zafirlukast to prevent biofilm formation of E. coli. Only Myr, a flavonol widely distributed in plants, inhibited biofilm formation in a concentration-dependent manner (50% inhibitory concentration [IC50] = 46.2 μM); however, it did not affect growth. Transmission electron microscopy demonstrated that Myr inhibited the production of curli. Phenotypic analyses of thermosensitivity, cell division, intracellular level of RNA polymerase sigma factor RpoH, and vulnerability to vancomycin revealed that Myr altered the phenotype of E. coli wild-type cells to make them resemble those of the isogenic dnaK deletion mutant, indicating that Myr inhibits cellular functions of DnaK. These findings provide insights into the significance of DnaK in curli-dependent biofilm formation and indicate that DnaK is an ideal target for antibiofilm drugs. PMID:25403660

  13. Collectin liver 1 and collectin kidney 1 and other complement-associated pattern recognition molecules in systemic lupus erythematosus.

    PubMed

    Troldborg, A; Thiel, S; Jensen, L; Hansen, S; Laska, M J; Deleuran, B; Jensenius, J C; Stengaard-Pedersen, K

    2015-11-01

    The objective of this study was to explore the involvement of collectin liver 1 (CL-L1) and collectin kidney 1 (CL-K1) and other pattern recognition molecules (PRMs) of the lectin pathway of the complement system in a cross-sectional cohort of systemic lupus erythematosus (SLE) patients. Concentrations in plasma of CL-L1, CL-K1, mannan-binding lectin (MBL), M-ficolin, H-ficolin and L-ficolin were determined in 58 patients with SLE and 65 healthy controls using time-resolved immunoflourometric assays. The SLE patients' demographic, diagnostic, clinical and biochemical data and collection of plasma samples were performed prospectively during 4 months. CL-L1, CL-K1 and M-ficolin plasma concentrations were lower in SLE patients than healthy controls (P-values < 0.001, 0.033 and < 0.001, respectively). H-ficolin concentration was higher in SLE patients (P < 0.0001). CL-L1 and CL-K1 plasma concentrations in the individuals correlated in both patients and controls. Patients with low complement component 3 (C3) demonstrated a negative correlation between C3 and CL-L1 and CL-K1 (P = 0.022 and 0.031, respectively). Patients positive for anti-dsDNA antibodies had lower levels of MBL in plasma than patients negative for anti-dsDNA antibodies (P = 0.02). In a cross-sectional cohort of SLE patients, we found differences in the plasma concentrations of CL-L1, CL-K1, M-ficolin and H-ficolin compared to a group of healthy controls. Alterations in plasma concentrations of the PRMs of the lectin pathway in SLE patients and associations to key elements of the disease support the hypothesis that the lectin pathway plays a role in the pathogenesis of SLE. PMID:26154564

  14. Fungal Innate Immunity Induced by Bacterial Microbe-Associated Molecular Patterns (MAMPs)

    PubMed Central

    Ipcho, Simon; Sundelin, Thomas; Erbs, Gitte; Kistler, H. Corby; Newman, Mari-Anne; Olsson, Stefan

    2016-01-01

    Plants and animals detect bacterial presence through Microbe-Associated Molecular Patterns (MAMPs) which induce an innate immune response. The field of fungal–bacterial interaction at the molecular level is still in its infancy and little is known about MAMPs and their detection by fungi. Exposing Fusarium graminearum to bacterial MAMPs led to increased fungal membrane hyperpolarization, a putative defense response, and a range of transcriptional responses. The fungus reacted with a different transcript profile to each of the three tested MAMPs, although a core set of genes related to energy generation, transport, amino acid production, secondary metabolism, and especially iron uptake were detected for all three. Half of the genes related to iron uptake were predicted MirA type transporters that potentially take up bacterial siderophores. These quick responses can be viewed as a preparation for further interactions with beneficial or pathogenic bacteria, and constitute a fungal innate immune response with similarities to those of plants and animals. PMID:27172188

  15. Fungal Innate Immunity Induced by Bacterial Microbe-Associated Molecular Patterns (MAMPs).

    PubMed

    Ipcho, Simon; Sundelin, Thomas; Erbs, Gitte; Kistler, H Corby; Newman, Mari-Anne; Olsson, Stefan

    2016-01-01

    Plants and animals detect bacterial presence through Microbe-Associated Molecular Patterns (MAMPs) which induce an innate immune response. The field of fungal-bacterial interaction at the molecular level is still in its infancy and little is known about MAMPs and their detection by fungi. Exposing Fusarium graminearum to bacterial MAMPs led to increased fungal membrane hyperpolarization, a putative defense response, and a range of transcriptional responses. The fungus reacted with a different transcript profile to each of the three tested MAMPs, although a core set of genes related to energy generation, transport, amino acid production, secondary metabolism, and especially iron uptake were detected for all three. Half of the genes related to iron uptake were predicted MirA type transporters that potentially take up bacterial siderophores. These quick responses can be viewed as a preparation for further interactions with beneficial or pathogenic bacteria, and constitute a fungal innate immune response with similarities to those of plants and animals. PMID:27172188

  16. The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma

    PubMed Central

    Ronchetti, D; Todoerti, K; Tuana, G; Agnelli, L; Mosca, L; Lionetti, M; Fabris, S; Colapietro, P; Miozzo, M; Ferrarini, M; Tassone, P; Neri, A

    2012-01-01

    Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may have a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM) by profiling purified malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCLs) and 4 normal controls. Overall, a global sno/scaRNAs downregulation was found in MMs and, even more, in sPCLs compared with normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the translocation/cyclin D4 (TC4) MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by an imprinting center at 15q11, which, however, resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information to the bio-molecular complexity of plasma cell dyscrasias. PMID:23178508

  17. A molecular dynamics study of phobic/philic nano-patterning on pool boiling heat transfer

    NASA Astrophysics Data System (ADS)

    Diaz, Ricardo; Guo, Zhixiong

    2016-07-01

    Molecular dynamics (MD) simulations were employed to investigate the pool boiling heat transfer of a liquid argon thin film on a flat, horizontal copper wall structured with vertical nanoscale pillars. The efficacy of phobic/philic nano-patterning for enhancing boiling heat transfer was scrutinized. Both nucleate and explosive boiling modes were considered. An error analysis demonstrated that the typical 2.5σ cutoff in MD simulations could under-predict heat flux by about 8.7 %, and 6σ cutoff was chosen here in order to maintain high accuracy. A new coordination number criterion was also introduced to better quantify evaporation characteristics. Results indicate that the argon-phobic/philic patterning tends to either have no effect, or decrease overall boiling heat flux, while the argon-philic nano-pillar/argon-philic wall shows the best heat transfer performance.

  18. Molecular basis of natural variation and environmental control of trichome patterning.

    PubMed

    Hauser, Marie-Theres

    2014-01-01

    Trichomes are differentiated epidermal cells on above ground organs of nearly all land plants. They play important protective roles as structural defenses upon biotic attacks such as herbivory, oviposition and fungal infections, and against abiotic stressors such as drought, heat, freezing, excess of light, and UV radiation. The pattern and density of trichomes is highly variable within natural population suggesting tradeoffs between traits positively affecting fitness such as resistance and the costs of trichome production. The spatial distribution of trichomes is regulated through a combination of endogenous developmental programs and external signals. This review summarizes the current understanding on the molecular basis of the natural variation and the role of phytohormones and environmental stimuli on trichome patterning. PMID:25071803

  19. Intramolecular vibrations and noise effects on pattern formation in a molecular helix.

    PubMed

    Fouda, H P Ekobena; Tabi, C B; Mohamadou, A; Kofané, T C

    2011-09-21

    Modulational instability in a biexciton molecular chain is addressed. We show that the model can be reduced to a set of three coupled equations: two nonlinear Schrödinger equations and a Boussinesq equation. The linear stability analysis of continuous wave solutions of the coupled systems is performed and the growth rate of instability is found numerically. Simulations of the full discrete systems reveal some behaviors of modulational instability, since wave patterns are observed for the excitons and the phonon spectrum. We also take the effect of thermal fluctuations into account and we numerically study both the stability and the instability of the plane waves under 300 K. The plane wave is found to be stable under modulation, but displays a gradual increase of the wave amplitudes. Under modulation, the same behaviors are observed and wave patterns are found to resist thermal fluctuations, which is in agreement with earlier research on localized structure stability under thermal noise. PMID:21878712

  20. 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.

  1. Gate-induced switching and negative differential resistance in a single-molecule transistor: emergence of fixed and shifting states with molecular length.

    PubMed

    Farajian, A A; Belosludov, R V; Mizuseki, H; Kawazoe, Y; Hashizume, T; Yakobson, B I

    2007-07-14

    The quantum transport of a gated polythiophene nanodevice is analyzed using density functional theory and nonequilibrium Green's function approach. For this typical molecular field effect transistor, we prove the existence of two main features of electronic components, i.e., negative differential resistance and good switching. Ab initio based explanations of these features are provided by distinguishing fixed and shifting conducting states, which are shown to arise from the interface and functional molecule, respectively. The results show that proper functional molecules can be used in conjunction with metallic electrodes to achieve basic electronics functionality at molecular length scales. PMID:17640145

  2. Tuning of EAG K+ channel inactivation: Molecular determinants of amplification by mutations and a small molecule

    PubMed Central

    Garg, Vivek; Sachse, Frank B.

    2012-01-01

    Ether-à-go-go (EAG) and EAG-related gene (ERG) K+ channels are close homologues but differ markedly in their gating properties. ERG1 channels are characterized by rapid and extensive C-type inactivation, whereas mammalian EAG1 channels were previously considered noninactivating. Here, we show that human EAG1 channels exhibit an intrinsic voltage-dependent slow inactivation that is markedly enhanced in rate and extent by 1–10 µM 3-nitro-N-(4-phenoxyphenyl) benzamide, or ICA105574 (ICA). This compound was previously reported to have the opposite effect on ERG1 channels, causing an increase in current magnitude by inhibition of C-type inactivation. The voltage dependence of 2 µM ICA-induced inhibition of EAG1 current was half-maximal at −73 mV, 62 mV negative to the half-point for channel activation. This finding suggests that current inhibition by the drug is mediated by enhanced inactivation and not open-channel block, where the voltage half-points for current inhibition and channel activation are predicted to overlap, as we demonstrate for clofilium and astemizole. The mutation Y464A in the S6 segment also induced inactivation of EAG1, with a time course and voltage dependence similar to that caused by 2 µM ICA. Several Markov models were investigated to describe gating effects induced by multiple concentrations of the drug and the Y464A mutation. Models with the smallest fit error required both closed- and open-state inactivation. Unlike typical C-type inactivation, the rate of Y464A- and ICA-induced inactivation was not decreased by external tetraethylammonium or elevated [K+]e. EAG1 channel inactivation introduced by Y464A was prevented by additional mutation of a nearby residue located in the S5 segment (F359A) or pore helix (L434A), suggesting a tripartite molecular model where interactions between single residues in S5, S6, and the pore helix modulate inactivation of EAG1 channels. PMID:22930803

  3. Tuning of EAG K(+) channel inactivation: molecular determinants of amplification by mutations and a small molecule.

    PubMed

    Garg, Vivek; Sachse, Frank B; Sanguinetti, Michael C

    2012-09-01

    Ether-à-go-go (EAG) and EAG-related gene (ERG) K(+) channels are close homologues but differ markedly in their gating properties. ERG1 channels are characterized by rapid and extensive C-type inactivation, whereas mammalian EAG1 channels were previously considered noninactivating. Here, we show that human EAG1 channels exhibit an intrinsic voltage-dependent slow inactivation that is markedly enhanced in rate and extent by 1-10 µM 3-nitro-N-(4-phenoxyphenyl) benzamide, or ICA105574 (ICA). This compound was previously reported to have the opposite effect on ERG1 channels, causing an increase in current magnitude by inhibition of C-type inactivation. The voltage dependence of 2 µM ICA-induced inhibition of EAG1 current was half-maximal at -73 mV, 62 mV negative to the half-point for channel activation. This finding suggests that current inhibition by the drug is mediated by enhanced inactivation and not open-channel block, where the voltage half-points for current inhibition and channel activation are predicted to overlap, as we demonstrate for clofilium and astemizole. The mutation Y464A in the S6 segment also induced inactivation of EAG1, with a time course and voltage dependence similar to that caused by 2 µM ICA. Several Markov models were investigated to describe gating effects induced by multiple concentrations of the drug and the Y464A mutation. Models with the smallest fit error required both closed- and open-state inactivation. Unlike typical C-type inactivation, the rate of Y464A- and ICA-induced inactivation was not decreased by external tetraethylammonium or elevated [K(+)](e). EAG1 channel inactivation introduced by Y464A was prevented by additional mutation of a nearby residue located in the S5 segment (F359A) or pore helix (L434A), suggesting a tripartite molecular model where interactions between single residues in S5, S6, and the pore helix modulate inactivation of EAG1 channels. PMID:22930803

  4. Prototropic tautomerism of 4-Methyl 1,2,4-Triazole-3-Thione molecule in solvent water medium: DFT and Car-Parrinello molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Dutta, Bipan; De, Rina; Chowdhury, Joydeep

    2015-12-01

    The ground state prototropic tautomerism of 4-Methyl 1,2,4-Triazole-3-Thione molecule in solvent water medium has been investigated with the aid of DFT and Car-Parrinello molecular dynamics (CPMD) simulation studies. The CPMD simulations envisage the possibility of proton transfer reactions of the molecule through the solvent water medium. Probable proton transfer pathways have been predicted from the DFT calculations which are substantiated by the natural bond orbital analyses. The evolution and breaking of the concerned bonds of the molecule for different proton transfer reaction pathways are also estimated.

  5. Liquid crystals with patterned molecular orientation as an electrolytic active medium.

    PubMed

    Peng, Chenhui; Guo, Yubing; Conklin, Christopher; Viñals, Jorge; Shiyanovskii, Sergij V; Wei, Qi-Huo; Lavrentovich, Oleg D

    2015-11-01

    Transport of fluids and particles at the microscale is an important theme in both fundamental and applied science. One of the most successful approaches is to use an electric field, which requires the system to carry or induce electric charges. We describe a versatile approach to generate electrokinetic flows by using a liquid crystal (LC) with surface-patterned molecular orientation as an electrolyte. The surface patterning is produced by photoalignment. In the presence of an electric field, the spatially varying orientation induces space charges that trigger flows of the LC. The active patterned LC electrolyte converts the electric energy into the LC flows and transport of embedded particles of any type (fluid, solid, gaseous) along a predesigned trajectory, posing no limitation on the electric nature (charge, polarizability) of these particles and interfaces. The patterned LC electrolyte exhibits a quadratic field dependence of the flow velocities; it induces persistent vortices of controllable rotation speed and direction that are quintessential for micro- and nanoscale mixing applications. PMID:26651712

  6. Liquid crystals with patterned molecular orientation as an electrolytic active medium

    NASA Astrophysics Data System (ADS)

    Peng, Chenhui; Guo, Yubing; Conklin, Christopher; Viñals, Jorge; Shiyanovskii, Sergij V.; Wei, Qi-Huo; Lavrentovich, Oleg D.

    2015-11-01

    Transport of fluids and particles at the microscale is an important theme in both fundamental and applied science. One of the most successful approaches is to use an electric field, which requires the system to carry or induce electric charges. We describe a versatile approach to generate electrokinetic flows by using a liquid crystal (LC) with surface-patterned molecular orientation as an electrolyte. The surface patterning is produced by photoalignment. In the presence of an electric field, the spatially varying orientation induces space charges that trigger flows of the LC. The active patterned LC electrolyte converts the electric energy into the LC flows and transport of embedded particles of any type (fluid, solid, gaseous) along a predesigned trajectory, posing no limitation on the electric nature (charge, polarizability) of these particles and interfaces. The patterned LC electrolyte exhibits a quadratic field dependence of the flow velocities; it induces persistent vortices of controllable rotation speed and direction that are quintessential for micro- and nanoscale mixing applications.

  7. Liquid self-diffusion of H2O and DMF molecules in Co-MOF-74: molecular dynamics simulations and dielectric spectroscopy studies.

    PubMed

    Bermúdez-García, J M; Vicent-Luna, J M; Yáñez-Vilar, S; Hamad, S; Sánchez-Andújar, M; Castro-García, S; Calero, S; Señarís-Rodríguez, M A

    2016-07-20

    In this work we use molecular dynamics simulations to study the diffusion of N,N-dimethylformamide (DMF) and H2O as a function of temperature within the well-known metal-organic framework Co2(dobdc)·[G] (G = 2DMF·1H2O), also known as Co-MOF-74. The molecular dynamics simulations show that the diffusivity of guest molecules, which is almost negligible at low temperatures (T < 200 K), increases in the range of 200 < T (K) < 400 up to 3 and 4 orders of magnitude for DMF and H2O, respectively. This molecular diffusion can be easily detected by dielectric spectroscopy as it gives rise to extrinsic interfacial polarization effects that result in an apparent "colossal" dielectric constant at room temperature, εr' ∼ 42 000 (T = 300 K, ν = 10 Hz). Furthermore, the measured dielectric constant exhibits a thermal dependence similar to that of the diffusion coefficient, revealing the parallelism of the dielectric response and the molecular diffusion as a function of temperature. These results highlight: (a) the great utility of the fast and non-destructive dielectric and impedance spectroscopy techniques for the study and detection of the molecular transport of small polar molecules within porous metal-organic frameworks and related materials; (b) the peculiarity and uniqueness of MOF materials with "medium" size nanopores containing guest molecules as they are solid materials in which the guest molecules display a liquid state-like behaviour close to room temperature; and PMID:27353249

  8. Intracellular patterns of sialophorin expression define a new molecular classification of breast cancer and represent new targets for therapy

    PubMed Central

    Fu, Q; Cash, S E; Andersen, J J; Kennedy, C R; Madadi, A R; Raghavendra, M; Dietrich, L L; Agger, W A; Shelley, C S

    2014-01-01

    Background: Sialophorin is a transmembrane sialoglycoprotein. Normally, the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signalling, apoptosis, migration and proliferation. Methods: Normal breast tissue and primary breast tumours were analysed by immunohistochemistry for sialophorin expression. The sialophorin-positive breast cancer cell line MCF7 was engineered to stably express either non-targeted or sialophorin-targeted small interfering RNA (siRNA). Assays were then performed in vitro to assess apoptosis, intracellular adhesion, transendothelial migration and cytotoxicity. An orthotopic mouse model assayed ability to produce tumours in vivo. Results: Normal breast epithelial cells exhibit expression of the N-terminal domain of sialophorin in the cytoplasm but not the nucleus. The majority of these normal cells are also negative for expression of the C-terminal domain. In contrast, malignant breast epithelial cells exhibit N-terminal expression both in the cytoplasm and nucleus and the majority express the C-terminus in the nucleus. Using differential patterns of intracellular expression of the N and C termini of sialophorin, we define six subtypes of breast cancer that are independent of histological and receptor status classification. Targeting sialophorin with siRNA resulted in the MCF7 breast cancer cell line exhibiting increased homotypic adhesion, decreased transendothelial migration, increased susceptibility to apoptosis, increased vulnerability to lysis by natural killer cells and decreased ability to produce tumours in mice. Conclusion: Our results indicate that intracellular patterns of sialophorin expression define a new molecular classification of breast cancer and that sialophorin represents a novel therapeutic target. PMID:24281005

  9. Application of pattern recognition in molecular spectroscopy: Automatic line search in high-resolution spectra

    NASA Astrophysics Data System (ADS)

    Bykov, A. D.; Pshenichnikov, A. M.; Sinitsa, L. N.; Shcherbakov, A. P.

    2004-07-01

    An expert system has been developed for the initial analysis of a recorded spectrum, namely, for the line search and the determination of line positions and intensities. The expert system is based on pattern recognition algorithms. Object recognition learning allows the system to achieve the needed flexibility and automatically detect groups of overlapping lines, whose profiles should be fit together. Gauss, Lorentz, and Voigt profiles are used as model profiles to which spectral lines are fit. The expert system was applied to processing of the Fourier transform spectrum of the D2O molecule in the region 3200-4200 cm-1, and it detected 4670 lines in the spectrum, which consisted of 439000 dots. No one experimentally observed line exceeding the noise level was missed.

  10. Nuclear Architecture and Patterns of Molecular Evolution Are Correlated in the Ciliate Chilodonella uncinata.

    PubMed

    Maurer-Alcalá, Xyrus X; Katz, Laura A

    2016-01-01

    The relationship between nuclear architecture and patterns of molecular evolution in lineages across the eukaryotic tree of life is not well understood, partly because molecular evolution is traditionally explored as changes in base pairs along a linear sequence without considering the context of nuclear position of chromosomes. The ciliate Chilodonella uncinata is an ideal system to address the relationship between nuclear architecture and patterns of molecular evolution as the somatic macronucleus of this ciliate is composed of a peripheral DNA-rich area (orthomere) and a DNA-poor central region (paramere) to form a "heteromeric" macronucleus. Moreover, because the somatic chromosomes of C. uncinata are highly processed into "gene-sized" chromosomes (i.e., nanochromosomes), we can assess fine-scale relationships between location and sequence evolution. By combining fluorescence microscopy and analyses of transcriptome data from C. uncinata, we find that highly expressed genes have the greatest codon usage bias and are enriched in DNA-poor regions. In contrast, genes with less biased sequences tend to be concentrated in DNA abundant areas, at least during vegetative growth. Our analyses are consistent with recent work in plants and animals where nuclear architecture plays a role in gene expression. At the same time, the unusual localization of nanochromosomes suggests that the highly structured nucleus in C. uncinata may create a "gene bank" that facilitates rapid changes in expression of genes required only in specific life history stages. By using "nonmodel" organisms like C. uncinata, we can explore the universality of eukaryotic features while also providing examples of novel properties (i.e., the presence of a gene bank) that build from these features. PMID:27189988

  11. Nuclear Architecture and Patterns of Molecular Evolution Are Correlated in the Ciliate Chilodonella uncinata

    PubMed Central

    Maurer-Alcalá, Xyrus X.; Katz, Laura A.

    2016-01-01

    The relationship between nuclear architecture and patterns of molecular evolution in lineages across the eukaryotic tree of life is not well understood, partly because molecular evolution is traditionally explored as changes in base pairs along a linear sequence without considering the context of nuclear position of chromosomes. The ciliate Chilodonella uncinata is an ideal system to address the relationship between nuclear architecture and patterns of molecular evolution as the somatic macronucleus of this ciliate is composed of a peripheral DNA-rich area (orthomere) and a DNA-poor central region (paramere) to form a “heteromeric” macronucleus. Moreover, because the somatic chromosomes of C. uncinata are highly processed into “gene-sized” chromosomes (i.e., nanochromosomes), we can assess fine-scale relationships between location and sequence evolution. By combining fluorescence microscopy and analyses of transcriptome data from C. uncinata, we find that highly expressed genes have the greatest codon usage bias and are enriched in DNA-poor regions. In contrast, genes with less biased sequences tend to be concentrated in DNA abundant areas, at least during vegetative growth. Our analyses are consistent with recent work in plants and animals where nuclear architecture plays a role in gene expression. At the same time, the unusual localization of nanochromosomes suggests that the highly structured nucleus in C. uncinata may create a “gene bank” that facilitates rapid changes in expression of genes required only in specific life history stages. By using “nonmodel” organisms like C. uncinata, we can explore the universality of eukaryotic features while also providing examples of novel properties (i.e., the presence of a gene bank) that build from these features. PMID:27189988

  12. SPARCoC: A New Framework for Molecular Pattern Discovery and Cancer Gene Identification

    PubMed Central

    Ma, Shiqian; Johnson, Daniel; Ashby, Cody; Xiong, Donghai; Cramer, Carole L.; Moore, Jason H.; Zhang, Shuzhong; Huang, Xiuzhen

    2015-01-01

    It is challenging to cluster cancer patients of a certain histopathological type into molecular subtypes of clinical importance and identify gene signatures directly relevant to the subtypes. Current clustering approaches have inherent limitations, which prevent them from gauging the subtle heterogeneity of the molecular subtypes. In this paper we present a new framework: SPARCoC (Sparse-CoClust), which is based on a novel Common-background and Sparse-foreground Decomposition (CSD) model and the Maximum Block Improvement (MBI) co-clustering technique. SPARCoC has clear advantages compared with widely-used alternative approaches: hierarchical clustering (Hclust) and nonnegative matrix factorization (NMF). We apply SPARCoC to the study of lung adenocarcinoma (ADCA), an extremely heterogeneous histological type, and a significant challenge for molecular subtyping. For testing and verification, we use high quality gene expression profiling data of lung ADCA patients, and identify prognostic gene signatures which could cluster patients into subgroups that are significantly different in their overall survival (with p-values < 0.05). Our results are only based on gene expression profiling data analysis, without incorporating any other feature selection or clinical information; we are able to replicate our findings with completely independent datasets. SPARCoC is broadly applicable to large-scale genomic data to empower pattern discovery and cancer gene identification. PMID:25768286

  13. Phage display identification of functional binding peptides against 4-acetamidophenol (Paracetamol): an exemplified approach to target low molecular weight organic molecules.

    PubMed

    Smith, Mathew W; Smith, Jonathan W; Harris, Charlotte; Brancale, Andrea; Allender, Christopher J; Gumbleton, Mark

    2007-06-22

    Peptide-phage display has been widely used to explore protein-protein interactions, however, despite the potential range of applications the use of this technology to identify peptides that bind low molecular weight organic molecules has not been explored. In this current study, we identified a phage clone (PARA-061) displaying the cyclic 7-mer peptide sequence N' AC-NPNNLSH-CGGGS C' that binds the low molecular weight organic molecule 4-acetamidophenol (4-AAP; paracetamol). To avoid occupancy of key functional groups on the target 4-AAP molecule our panning strategy was directed against insoluble complexes of 4-AAP rather than against the target linked to a stationary support or bearing an affinity tag. To augment the panning procedure we deleted phage that also bound the 4-AAP isomers, 2-AAP and 3-AAP. The identified PARA-061 peptide-phage clone displayed functional binding properties against 4-AAP in solution, able in a peptide sequence-dependant manner to prevent the in vitro hepatotoxicity of 4-AAP and reduce ( approximately 20%) the permeability of 4-AAP across a semi-permeable membrane. Molecular dynamic simulations generated a stable binding conformation between the PARA-061 peptide sequence and 4-AAP. In conclusion, we show that a phage display library can be used to identify peptide sequence-specific clones able to modulate the functional binding of a low molecular weight organic molecule. Such peptides may be expected to find utility in the next generation of hybrid polymer-based biosensing devices. PMID:17482566

  14. Atomic-Scale Molecular Dynamics Simulations of DNA-Polycation Complexes: Two Distinct Binding Patterns.

    PubMed

    Kondinskaia, Diana A; Kostritskii, Andrei Yu; Nesterenko, Alexey M; Antipina, Alexandra Yu; Gurtovenko, Andrey A

    2016-07-14

    Synthetic cationic polymers represent a promising class of delivery vectors for gene therapy. Here, we employ atomistic molecular dynamics simulations to gain insight into the structure and properties of complexes of DNA with four linear polycations: polyethylenimine (PEI), poly-l-lysine (PLL), polyvinylamine (PVA), and polyallylamine (PAA). These polycations differ in their polymer geometries, protonation states, and hydrophobicities of their backbone chains. Overall, our results demonstrate for the first time the existence of two distinct patterns of binding of DNA with polycations. For PEI, PLL, and PAA, the complex is stabilized by the electrostatic attraction between protonated amine groups of the polycation and phosphate groups of DNA. In contrast, PVA demonstrates an alternative binding pattern as it gets embedded into the DNA major groove. It is likely that both the polymer topology and affinity of the backbone chain of PVA to the DNA groove are responsible for such behavior. The differences in binding patterns can have important biomedical implications: embedding PVA into a DNA groove makes it less sensitive to changes in the aqueous environment (pH level, ionic strength, etc.) and could therefore hinder the intracellular release of genetic material from a delivery vector, leading to lower transfection activity. PMID:27280954

  15. Rapid screening for citrus canker resistance employing pathogen-associated molecular pattern-triggered immunity responses

    PubMed Central

    Pitino, Marco; Armstrong, Cheryl M; Duan, Yongping

    2015-01-01

    Citrus canker, caused by the bacterial pathogen Xanthomonas citri ssp. citri (Xcc), has been attributed to millions of dollars in loss or damage to commercial citrus crops in subtropical production areas of the world. Since identification of resistant plants is one of the most effective methods of disease management, the ability to screen for resistant seedlings plays a key role in the production of a long-term solution to canker. Here, an inverse correlation between reactive oxygen species (ROS) production by the plant and the ability of Xcc to grow and form lesions on infected plants is reported. Based on this information, a novel screening method that can rapidly identify citrus seedlings that are less susceptible to early infection by Xcc was devised by measuring ROS accumulation triggered by a 22-amino acid sequence of the conserved N-terminal part of flagellin (flg22) from X. citri ssp. citri (Xcc-flg22). In addition to limiting disease symptoms, ROS production was also correlated with the expression of basal defense-related genes such as the pattern recognition receptors LRR8 and FLS2, the leucine-rich repeat receptor-like protein RLP12, and the defense-related gene PR1, indicating an important role for pathogen-associated molecular pattern-triggered immunity (PTI) in determining resistance to citrus canker. Moreover, the differential expression patterns observed amongst the citrus seedlings demonstrated the existence of genetic variations in the PTI response among citrus species/varieties. PMID:26504581

  16. Molecular and structural characterization of dissolved organic matter from the deep ocean by FTICR-MS, including hydrophilic nitrogenous organic molecules

    USGS Publications Warehouse

    Reemtsma, T.; These, A.; Linscheid, M.; Leenheer, J.; Spitzy, A.

    2008-01-01

    Dissolved organic matter isolated from the deep Atlantic Ocean and fractionated into a so-called hydrophobic (HPO) fraction and a very hydrophilic (HPI) fraction was analyzed for the first time by Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) to resolve the molecular species, to determine their exact masses, and to calculate their molecular formulas. The elemental composition of about 300 molecules was identified. Those in the HPO fraction (14C age of 5100 year) are very similar to much younger freshwater fulvic acids, but less aromatic and more oxygenated molecules are more frequent. This trend continues toward the HPI fraction and may indicate biotic and abiotic aging processes that this material experienced since its primary production thousands of years ago. In the HPI fraction series of nitrogenous molecules containing one, two, or three nitrogens were identified by FTICR-MS. Product ion spectra of the nitrogenous molecules suggest that the nitrogen atoms in these molecules are included in the (alicyclic) backbone of these molecules, possibly in reduced form. These mass spectrometric data suggest that a large set of stable fulvic acids is ubiquitous in all aquatic compartments. Although sources may differ, their actual composition and structure appears to be quite similar and largely independent from their source, because they are the remainder of intensive oxidative degradation processes. ?? 2008 American Chemical Society.

  17. Activation of coherent lattice phonon following ultrafast molecular spin-state photo-switching: A molecule-to-lattice energy transfer

    PubMed Central

    Marino, A.; Cammarata, M.; Matar, S. F.; Létard, J.-F.; Chastanet, G.; Chollet, M.; Glownia, J. M.; Lemke, H. T.; Collet, E.

    2015-01-01

    We combine ultrafast optical spectroscopy with femtosecond X-ray absorption to study the photo-switching dynamics of the [Fe(PM-AzA)2(NCS)2] spin-crossover molecular solid. The light-induced excited spin-state trapping process switches the molecules from low spin to high spin (HS) states on the sub-picosecond timescale. The change of the electronic state (<50 fs) induces a structural reorganization of the molecule within 160 fs. This transformation is accompanied by coherent molecular vibrations in the HS potential and especially a rapidly damped Fe-ligand breathing mode. The time-resolved studies evidence a delayed activation of coherent optical phonons of the lattice surrounding the photoexcited molecules. PMID:26798836

  18. Activation of coherent lattice phonon following ultrafast molecular spin-state photo-switching: A molecule-to-lattice energy transfer.

    PubMed

    Marino, A; Cammarata, M; Matar, S F; Létard, J-F; Chastanet, G; Chollet, M; Glownia, J M; Lemke, H T; Collet, E

    2016-03-01

    We combine ultrafast optical spectroscopy with femtosecond X-ray absorption to study the photo-switching dynamics of the [Fe(PM-AzA)2(NCS)2] spin-crossover molecular solid. The light-induced excited spin-state trapping process switches the molecules from low spin to high spin (HS) states on the sub-picosecond timescale. The change of the electronic state (<50 fs) induces a structural reorganization of the molecule within 160 fs. This transformation is accompanied by coherent molecular vibrations in the HS potential and especially a rapidly damped Fe-ligand breathing mode. The time-resolved studies evidence a delayed activation of coherent optical phonons of the lattice surrounding the photoexcited molecules. PMID:26798836

  19. Nitric Oxide-Enhanced Molecular Imaging of Atheroma using Vascular Cellular Adhesion Molecule-1 Targeted Echogenic Immunoliposomes

    PubMed Central

    Kim, Hyunggun; Kee, Patrick H.; Rim, Yonghoon; Moody, Melanie R.; Klegerman, Melvin E.; Vela, Deborah; Huang, Shao-Ling; McPherson, David D.; Laing, Susan T.

    2015-01-01

    This study aimed to demonstrate whether pretreatment with nitric-oxide loaded echogenic liposomes (NO-ELIP) plus ultrasound can improve highlighting by molecularly targeted [anti-vascular cell adhesion molecule-1 (VCAM-1)] ELIP of atheroma components. Atherosclerotic animals were treated with anti-VCAM-1 ELIP or immunoglobulin (IgG)-ELIP. Each group was randomized to receive pretreatment with standard ELIP plus ultrasound, NO-ELIP without ultrasound, or NO-ELIP plus ultrasound. Intravascular ultrasound highlighting data of the same arterial segments were collected before and after treatment. Pretreatment with NO-ELIP plus ultrasound demonstrated a significant increase in acoustic enhancement by anti-VCAM-1 ELIP (21.3 ± 1.5% for gray scale value, 53.9 ± 3.1% for radiofrequency data; p<0.001 vs. IgG-ELIP, p<0.05 vs. pretreatment with standard ELIP plus ultrasound or NO-ELIP without ultrasound). NO-ELIP plus ultrasound can improve highlighting of atheroma by anti-VCAM-1 ELIP. This NO pretreatment strategy may be useful for optimizing contrast agent delivery to the vascular wall for both diagnostic and therapeutic applications. PMID:25819469

  20. Nitric Oxide-Enhanced Molecular Imaging of Atheroma using Vascular Cellular Adhesion Molecule 1-Targeted Echogenic Immunoliposomes.

    PubMed

    Kim, Hyunggun; Kee, Patrick H; Rim, Yonghoon; Moody, Melanie R; Klegerman, Melvin E; Vela, Deborah; Huang, Shao-Ling; McPherson, David D; Laing, Susan T

    2015-06-01

    The aim of this study was to determine whether pre-treatment with nitric oxide-loaded echogenic liposomes (NO-ELIP) plus ultrasound can improve highlighting by molecularly targeted (anti-vascular cell adhesion molecule 1 [VCAM-1]) ELIP of atheroma components. Atherosclerotic animals were treated with anti-VCAM-1-ELIP or immunoglobulin (IgG)-ELIP. Each group was selected at random to receive pre-treatment with standard ELIP plus ultrasound, NO-ELIP without ultrasound and NO-ELIP plus ultrasound. Intravascular ultrasound highlighting data for the same arterial segments were collected before and after treatment. Pre-treatment with NO-ELIP plus ultrasound resulted in a significant increase in acoustic enhancement by anti-VCAM-1-ELIP (21.3 ± 1.5% for gray-scale value, 53.9 ± 3.1% for radiofrequency data; p < 0.001 vs. IgG-ELIP, p < 0.05 vs. pre-treatment with standard ELIP plus ultrasound or NO-ELIP without ultrasound). NO-ELIP plus ultrasound can improve highlighting of atheroma by anti-VCAM-1 ELIP. This NO pre-treatment strategy may be useful in optimizing contrast agent delivery to the vascular wall for both diagnostic and therapeutic applications. PMID:25819469

  1. Theoretical study of quantum molecular reaction dynamics and of the effects of intense laser radiation on a diatomic molecule

    SciTech Connect

    Dardi, P.S.

    1984-11-01

    Within the very broad field of molecular dynamics, we have concentrated on two simple yet important systems. The systems are simple enough so that they are adequately described with a single Born-Oppenheimer potential energy surface and that the dynamics can be calculated accurately. They are important because they give insight into solving more complicated systems. First we discuss H + H/sub 2/ reactive scattering. We present an exact formalism for atom-diatom reactive scattering which avoids the problem of finding a coordinate system appropriate for both reactants and products. We present computational results for collinear H + H/sub 2/ reactive scattering which agree very well with previous calculations. We also present a coupled channel distorted wave Born approximation for atom-diatom reactive scattering which we show is a first order approximation to our exact formalism. We present coupled channel DWBA results for three dimensional H + H/sub 2/ reactive scattering. The second system is an isolated HF molecule in an intense laser field. Using classical trajectories and quantum dynamics, we look at energy absorbed and transition probabilities as a function of the laser pulse time and also averaged over the pulse time. Calculations are performed for both rotating and nonrotating HF. We examine one and two photon absorption about the fundamental frequency, multiphoton absorption, and overtone absorption. 127 references, 31 figures, 12 tables.

  2. Structure and energetics of model amphiphilic molecules at the water liquid-vapor interface - A molecular dynamics study

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew; Benjamin, Ilan

    1993-01-01

    A molecular dynamics study of adsorption of p-n-pentylphenol at infinite dilution at the water liquid-vapor interface is reported. The calculated free energy of adsorption is -8.8 +/- 0.7 kcal/mol, in good agreement with the experimental value of -7.3 kcal/mol. The transition between the interfacial region and the bulk solution is sharp and well-defined by energetic, conformational, and orientational criteria. At the water surface, the phenol head group is mostly immersed in aqueous solvent. The most frequent orientation of the hydrocarbon tail is parallel to the interface, due to dispersion interactions with the water surface. This arrangement of the phenol ring and the alkyl chain requires that the chain exhibits a kink. As the polar head group is being moved into the solvent, the chain length increases and the tail becomes increasingly aligned toward the surface normal, such that the nonpolar part of the molecule exposed to water is minimized. The same effect was achieved when phenol was replaced by a more polar head group, phenolate.

  3. Molecular Order in Buried Layers of TbPc2 Single-Molecule Magnets Detected by Torque Magnetometry.

    PubMed

    Perfetti, Mauro; Serri, Michele; Poggini, Lorenzo; Mannini, Matteo; Rovai, Donella; Sainctavit, Philippe; Heutz, Sandrine; Sessoli, Roberta

    2016-08-01

    Cantilever torque magnetometry is used to elucidate the orientation of magnetic molecules in thin films. The technique allows depth-resolved investigations by intercalating a layer of anisotropic magnetic molecules in a film of its isotropic analogues. The proof-of-concept is here demonstrated with the single-molecule magnet TbPc2 evidencing also an exceptional long-range templating effect on substrates coated by the organic molecule perylene-3,4,9,10-tetracarboxylic dianhydride. PMID:27232580

  4. Phases, line tension and pattern formation in molecularly thin films at the air-water interface

    NASA Astrophysics Data System (ADS)

    Mandal, Pritam

    A Langmuir film, which is a molecularly thin insoluble film on a liquid substrate, is one practical realization of a quasi-two dimensional matter. The major advantages of this system for the study of phase separation and phase co-existence are (a) it allows accurate control of the components and molecular area of the film and (b) it can be studied by various methods that require very flat films. Phase separation in molecularly thin films plays an important role in a range of systems from biomembranes to biosensors. For example, phase-separated lipid nano-domains in biomembranes are thought to play crucial roles in membrane function. I use Brewster Angel Microscopy (BAM) coupled with Fluorescence Microscopy (FM) and static Light Scattering Microscopy (LSM) to image phases and patterns within Langmuir films. The three microscopic techniques --- BAM, FM and LSM --- are complimentary to each other, providing distinct sets of information. They allow direct comparison with literature results in lipid systems. I have quantitatively validated the use of detailed hydrodynamic simulations to determine line tension in monolayers. Line tension decreases as temperature rises. This decrease gives us information on the entropy associated with the line, and thus about line structure. I carefully consider the thermodynamics of line energy and entropy to make this connection. In the longer run, LSM will be exploited to give us further information about line structure. I have also extended the technique by testing it on domains within the curved surface of a bilayer vesicle. I also note that in the same way that the presence of surface-active agents, known as surfactants, affects surface energy, the addiction of line active agents alters the inter-phase line energy. Thus my results set to stage to systematically study the influence of line active agents ---'linactants' --- on the inter-phase line energy. Hierarchal self-assembled chiral patterns were observed as a function of

  5. Comparison of the Singer method and the constraints method for molecular dynamics with linear molecules on the vector computer CYBER 205

    NASA Astrophysics Data System (ADS)

    Hoheisel, C.; Vogelsang, R.; Schoen, M.

    1987-01-01

    The vectorization of FORTRAN programmes for the computation of the forces in molecular dynamics (MD) calculations are described. For systems containing linear molecules, two equivalent MD methods can be used: the Singer method and the constraints method. The FORTRAN vector code is presented and discussed for both methods. A comparison of computational times on the CYBER 205 is presented. For the two-centre Lennard-Jones potential, the constraints algorithm becomes increasingly less efficient than the Singer algorithm when executed on the CYBER 205. The reason for this is the difference in the neighbour-list which is made for the centre of each molecule in the Singer method and for each site in the molecule in the constraints method. Both programmes run about a factor of 15 faster on the Cyber 205 than on the conventional computer Cyber 175, for 108 or 256 linear molecules.

  6. Imaging of isolated molecules with ultrafast electron pulses.

    PubMed

    Hensley, Christopher J; Yang, Jie; Centurion, Martin

    2012-09-28

    Imaging isolated molecules in three dimensions with atomic resolution is important for elucidating complex molecular structures and intermediate states in molecular dynamics. This goal has so far remained elusive due to the random orientation of molecules in the gas phase. We show that three-dimensional structural information can be retrieved from multiple electron diffraction patterns of aligned molecules. The molecules are aligned impulsively with a femtosecond laser pulse and probed with a femtosecond electron pulse two picoseconds later, when the degree of alignment reaches a maximum. PMID:23030087

  7. Multielectron effects in high harmonic generation in N2 and benzene: Simulation using a non-adiabatic quantum molecular dynamics approach for laser-molecule interactions

    NASA Astrophysics Data System (ADS)

    Dundas, Daniel

    2012-05-01

    A mixed quantum-classical approach is introduced which allows the dynamical response of molecules driven far from equilibrium to be modeled. This method is applied to the interaction of molecules with intense, short-duration laser pulses. The electronic response of the molecule is described using time-dependent density functional theory (TDDFT) and the resulting Kohn-Sham equations are solved numerically using finite difference techniques in conjunction with local and global adaptations of an underlying grid in curvilinear coordinates. Using this approach, simulations can be carried out for a wide range of molecules and both all-electron and pseudopotential calculations are possible. The approach is applied to the study of high harmonic generation in N2 and benzene using linearly polarized laser pulses and, to the best of our knowledge, the results for benzene represent the first TDDFT calculations of high harmonic generation in benzene using linearly polarized laser pulses. For N2 an enhancement of the cut-off harmonics is observed whenever the laser polarization is aligned perpendicular to the molecular axis. This enhancement is attributed to the symmetry properties of the Kohn-Sham orbital that responds predominantly to the pulse. In benzene we predict that a suppression in the cut-off harmonics occurs whenever the laser polarization is aligned parallel to the molecular plane. We attribute this suppression to the symmetry-induced response of the highest-occupied molecular orbital.

  8. Evolutionary animation: how do molecular phylogenies compare to Mayr's reconstruction of speciation patterns in the sea?

    PubMed

    Palumbi, Stephen R; Lessios, H A

    2005-05-01

    Ernst Mayr used the geography of closely related species in various stages of increasing divergence to "animate" the process of geographic, or allopatric, speciation. This approach was applied to a wide set of taxa, and a seminal paper by Mayr used it to explore speciation patterns in tropical sea urchins. Since then, taxonomic information in several of these genera has been augmented by detailed molecular phylogenies. We compare Mayr's animation with the phylogenies of eight sea urchin genera placed by Mayr into four speciation groups. True to Mayr's predictions, early-stage genera have on average lower species divergence and more polytypic species than genera in later stages. For six of these genera, we also have information about the evolution of the gamete recognition protein bindin, which is critical to reproductive isolation. These comparisons show that later-stage genera with many sympatric species tend to be those with rapid bindin evolution. By contrast, early-stage genera with few sympatric species are not necessarily earlier in the divergence process; they happen to be those with slow rates of bindin evolution. These results show that the rate of speciation in sea urchins does not only depend on the steady accumulation of genome divergence over time, but also on the rate of evolution of gamete recognition proteins. The animation method used by Mayr is generally supported by molecular phylogenies. However, the existence of multiple rates in the acquisition of reproductive isolation complicates placement of different genera in an evolutionary series. PMID:15851681

  9. Molecular Phylogeny of Echiuran Worms (Phylum: Annelida) Reveals Evolutionary Pattern of Feeding Mode and Sexual Dimorphism

    PubMed Central

    Goto, Ryutaro; Okamoto, Tomoko; Ishikawa, Hiroshi; Hamamura, Yoichi; Kato, Makoto

    2013-01-01

    The Echiura, or spoon worms, are a group of marine worms, most of which live in burrows in soft sediments. This annelid-like animal group was once considered as a separate phylum because of the absence of segmentation, although recent molecular analyses have placed it within the annelids. In this study, we elucidate the interfamily relationships of echiuran worms and their evolutionary pattern of feeding mode and sexual dimorphism, by performing molecular phylogenetic analyses using four genes (18S, 28S, H3, and COI) of representatives of all extant echiuran families. Our results suggest that Echiura is monophyletic and comprises two unexpected groups: [Echiuridae+Urechidae+Thalassematidae] and [Bonelliidae+Ikedidae]. This grouping agrees with the presence/absence of marked sexual dimorphism involving dwarf males and the paired/non-paired configuration of the gonoducts (genital sacs). Furthermore, the data supports the sister group relationship of Echiuridae and Urechidae. These two families share the character of having anal chaetae rings around the posterior trunk as a synapomorphy. The analyses also suggest that deposit feeding is a basal feeding mode in echiurans and that filter feeding originated once in the common ancestor of Urechidae. Overall, our results contradict the currently accepted order-level classification, especially in that Echiuroinea is polyphyletic, and provide novel insights into the evolution of echiuran worms. PMID:23457618

  10. [Tuberculosis in Europe and Poland--new molecular families and new resistance patterns].

    PubMed

    Augustynowicz-Kopeć, Ewa; Zwolska, Zofia

    2008-01-01

    At present despite methods of fast recognition of the disease and efficient antituberculosis drugs not only we cannot contain the epidemic but we can see an increase in new cases of tuberculosis including its drug resistant variety. Causes of aggravation of the situation are varied and ought to be examined separately in case of any particular region. One of the major ones are bad programmes of fighting against the disease or their inadequate realization, ignoring a problem of tuberculosis in developed countries, lack of money for treatment in developing countries and coincidence with HIV virus. Among the mentioned factors the phenomenon of drug resistance is considered one of most important reasons of expansion of tuberculosis in the modern world. In epidemiological investigations it is important to determine, apart from drug resistance patterns, what molecular families strains belong to. This allows us to track their transmission routes. Genotyping has given us knowledge of the threats connected with transmission of the infection and made it possible to identify a risk factor which is the cause of MDR (multidrug-resistant), XDR (extensively drug-resistant tuberculosis) strains dissemination as well as strains representing new molecular families. Results of some analyses proved to be surprising. For instance high proportion of genetically similar strains has been shown in countries of low incidence. It proves higher than expected transmission in societies of high economic standard. Analyses of DNA of mycobacteria led to distinguishing several genetic families among which M. tuberculosis Beijing is one of most important. PMID:18536233

  11. The detection method for small molecules coupled with a molecularly imprinted polymer/quantum dot chip using a home-built optical system.

    PubMed

    Liu, Yixi; Wang, Yong; Liu, Le; He, Yonghong; He, Qinghua; Ji, Yanhong

    2016-07-01

    A method to detect small molecules with a molecularly imprinted polymer/quantum dot (MIP-QD) chip using a home-built optical fluidic system was first proposed in this study. Ractopamine (RAC) was used as the model molecule to demonstrate its feasibility. The sensing of the target molecule is based on the quenching amount of the quantum dots. The method is facile, cost-saving, easy for miniaturization and avoids the cumbersome steps that are needed to get the fluorescent quenching curve using a spectrofluorometer. Most importantly, more details and accurate response time can be obtained by use of this method. The experimental results show that the prepared chips with low cost are highly selective and the home-built detection system allows the fast binding kinetics. The recorded quenching process was used to study the kinetic uptake of RAC onto the MIP-QD chip and the specificity towards RAC. The system can further be utilized to study the effect of the solvent, pH and temperature on the selectivity of the prepared MIP. The methodology could be extended to other similar studies with different molecules. Graphical abstract Schematic illustration of the molecularly imprinted polymer/quantum dot chip capturing the target molecule. PMID:27235159

  12. Analysis of molecular expression patterns and integration with other knowledge bases using probabilistic Bayesian network models

    SciTech Connect

    Moler, Edward J.; Mian, I.S.

    2000-03-01

    How can molecular expression experiments be interpreted with greater than ten to the fourth measurements per chip? How can one get the most quantitative information possible from the experimental data with good confidence? These are important questions whose solutions require an interdisciplinary combination of molecular and cellular biology, computer science, statistics, and complex systems analysis. The explosion of data from microarray techniques present the problem of interpreting the experiments. The availability of large-scale knowledge bases provide the opportunity to maximize the information extracted from these experiments. We have developed new methods of discovering biological function, metabolic pathways, and regulatory networks from these data and knowledge bases. These techniques are applicable to analyses for biomedical engineering, clinical, and fundamental cell and molecular biology studies. Our approach uses probabilistic, computational methods that give quantitative interpretations of data in a biological context. We have selected Bayesian statistical models with graphical network representations as a framework for our methods. As a first step, we use a nave Bayesian classifier to identify statistically significant patterns in gene expression data. We have developed methods which allow us to (a) characterize which genes or experiments distinguish each class from the others, (b) cross-index the resulting classes with other databases to assess biological meaning of the classes, and (c) display a gross overview of cellular dynamics. We have developed a number of visualization tools to convey the results. We report here our methods of classification and our first attempts at integrating the data and other knowledge bases together with new visualization tools. We demonstrate the utility of these methods and tools by analysis of a series of yeast cDNA microarray data and to a set of cancerous/normal sample data from colon cancer patients. We discuss

  13. The toll of the gridiron: damage-associated molecular patterns and hypertension in American football.

    PubMed

    McCarthy, Cameron G; Webb, R Clinton

    2016-01-01

    American football has unequivocally been linked to elevations in blood pressure and hypertension, especially in linemen. However, the mechanisms of this increase cannot be attributed solely to increased body weight and associated cardiometabolic risk factors (e.g.,dyslipidemia or hyperglycemia). Therefore, understanding the etiology of football-associated hypertension is essential for improving the quality of life in this mostly young population, as well as for lowering the potential for chronic disease in the future. We propose that inflammatogenic damage-associated molecular patterns (DAMPs) released into the circulation from football-induced musculoskeletal trauma activate pattern-recognition receptors of the innate immune system-specifically, high mobility group box 1 protein (HMGB1) and mitochondrial (mt)DNA which activate Toll-like receptor (TLR)4 and -9, respectively. Previously, we observed that circulating levels of these 2 DAMPs are increased in hypertension, and activation of TLR4 and -9 causes endothelial dysfunction and hypertension. Therefore, our novel hypothesis is that musculoskeletal injury from repeated hits in football players, particularly in linemen, leads to elevated circulating HMGB1 and mtDNA to activate TLRs on endothelial cells leading to impaired endothelium-dependent vasodilation, increased vascular tone, and hypertension. PMID:26316270

  14. COPD disease severity and innate immune response to pathogen-associated molecular patterns

    PubMed Central

    Fan, Vincent S; Gharib, Sina A; Martin, Thomas R; Wurfel, Mark M

    2016-01-01

    The airways of COPD patients are often colonized with bacteria leading to increased airway inflammation. This study sought to determine whether systemic cytokine responses to microbial pathogen-associated molecular patterns (PAMPs) are increased among subjects with severe COPD. In an observational cross-sectional study of COPD subjects, PAMP-induced cytokine responses were measured in whole blood ex vivo. We used PAMPs derived from microbial products recognized by toll-like receptors 1, 2, 4, 5, 6, 7, and 8. Patterns of cytokine response to PAMPs were assessed using hierarchical clustering. One-sided Student’s t-tests were used to compare PAMP-induced cytokine levels in blood from patients with and without severe COPD, and for subjects with and without chronic bronchitis. Of 28 male patients, 12 had moderate COPD (FEV1 50%–80%) and 16 severe COPD (FEV1 <50%); 27 participants provided data on self-reported chronic bronchitis, of which 15 endorsed chronic bronchitis symptoms and 12 did not. Cytokine responses to PAMPs in severe COPD were generally lower than in subjects with milder COPD. This finding was particularly strong for PAMP-induced interleukin (IL)-10, granulocyte colony stimulating factor, and IL-1β. Subjects with chronic bronchitis showed higher PAMP-induced IL-1RA responses to most of the PAMPs evaluated. COPD patients with more severe disease demonstrated a diminished cytokine response to PAMPs, suggesting that chronic colonization with bacteria may dampen the systemic innate immune response. PMID:27019597

  15. Molecular dynamics of single-particle impacts predicts phase diagrams for large scale pattern formation.

    PubMed

    Norris, Scott A; Samela, Juha; Bukonte, Laura; Backman, Marie; Djurabekova, Flyura; Nordlund, Kai; Madi, Charbel S; Brenner, Michael P; Aziz, Michael J

    2011-01-01

    Energetic particle irradiation can cause surface ultra-smoothening, self-organized nanoscale pattern formation or degradation of the structural integrity of nuclear reactor components. A fundamental understanding of the mechanisms governing the selection among these outcomes has been elusive. Here we predict the mechanism governing the transition from pattern formation to flatness using only parameter-free molecular dynamics simulations of single-ion impacts as input into a multiscale analysis, obtaining good agreement with experiment. Our results overturn the paradigm attributing these phenomena to the removal of target atoms via sputter erosion: the mechanism dominating both stability and instability is the impact-induced redistribution of target atoms that are not sputtered away, with erosive effects being essentially irrelevant. We discuss the potential implications for the formation of a mysterious nanoscale topography, leading to surface degradation, of tungsten plasma-facing fusion reactor walls. Consideration of impact-induced redistribution processes may lead to a new design criterion for stability under irradiation. PMID:21505432

  16. Molecular Analysis of Geographic Patterns of Eukaryotic Diversity in Antarctic Soils

    PubMed Central

    Lawley, Blair; Ripley, Sarah; Bridge, Paul; Convey, Peter

    2004-01-01

    We describe the application of molecular biological techniques to estimate eukaryotic diversity (primarily fungi, algae, and protists) in Antarctic soils across a latitudinal and environmental gradient between approximately 60 and 87°S. The data were used to (i) test the hypothesis that diversity would decrease with increasing southerly latitude and environmental severity, as is generally claimed for “higher” faunal and plant groups, and (ii) investigate the level of endemicity displayed in different taxonomic groups. Only limited support was obtained for a systematic decrease in diversity with latitude, and then only at the level of a gross comparison between maritime (Antarctic Peninsula/Scotia Arc) and continental Antarctic sites. While the most southerly continental Antarctic site was three to four times less diverse than all maritime sites, there was no evidence for a trend of decreasing diversity across the entire range of the maritime Antarctic (60 to 72°S). Rather, we found the reverse pattern, with highest diversity at sites on Alexander Island (ca. 72°S), at the southern limit of the maritime Antarctic. The very limited overlap found between the eukaryotic biota of the different study sites, combined with their generally low relatedness to existing sequence databases, indicates a high level of Antarctic site isolation and possibly endemicity, a pattern not consistent with similar studies on other continents. PMID:15466539

  17. Molecular insights into the origin of the Hox-TALE patterning system

    PubMed Central

    Hudry, Bruno; Thomas-Chollier, Morgane; Volovik, Yael; Duffraisse, Marilyne; Dard, Amélie; Frank, Dale; Technau, Ulrich; Merabet, Samir

    2014-01-01

    Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior–posterior axis. Hox proteins exert their function by interaction with TALE transcription factors. Hox and TALE members are also present in some but not all non-bilaterian phyla, raising the question of how Hox–TALE interactions evolved to provide positional information. By using proteins from unicellular and multicellular lineages, we showed that these networks emerged from an ancestral generic motif present in Hox and other related protein families. Interestingly, Hox-TALE networks experienced additional and extensive molecular innovations that were likely crucial for differentiating Hox functions along body plans. Together our results highlight how homeobox gene families evolved during eukaryote evolution to eventually constitute a major patterning system in Eumetazoans. DOI: http://dx.doi.org/10.7554/eLife.01939.001 PMID:24642410

  18. The relation between recombination rate and patterns of molecular evolution and variation in Drosophila melanogaster.

    PubMed

    Campos, José L; Halligan, Daniel L; Haddrill, Penelope R; Charlesworth, Brian

    2014-04-01

    Genetic recombination associated with sexual reproduction increases the efficiency of natural selection by reducing the strength of Hill-Robertson interference. Such interference can be caused either by selective sweeps of positively selected alleles or by background selection (BGS) against deleterious mutations. Its consequences can be studied by comparing patterns of molecular evolution and variation in genomic regions with different rates of crossing over. We carried out a comprehensive study of the benefits of recombination in Drosophila melanogaster, both by contrasting five independent genomic regions that lack crossing over with the rest of the genome and by comparing regions with different rates of crossing over, using data on DNA sequence polymorphisms from an African population that is geographically close to the putatively ancestral population for the species, and on sequence divergence from a related species. We observed reductions in sequence diversity in noncrossover (NC) regions that are inconsistent with the effects of hard selective sweeps in the absence of recombination. Overall, the observed patterns suggest that the recombination rate experienced by a gene is positively related to an increase in the efficiency of both positive and purifying selection. The results are consistent with a BGS model with interference among selected sites in NC regions, and joint effects of BGS, selective sweeps, and a past population expansion on variability in regions of the genome that experience crossing over. In such crossover regions, the X chromosome exhibits a higher rate of adaptive protein sequence evolution than the autosomes, implying a Faster-X effect. PMID:24489114

  19. COPD disease severity and innate immune response to pathogen-associated molecular patterns.

    PubMed

    Fan, Vincent S; Gharib, Sina A; Martin, Thomas R; Wurfel, Mark M

    2016-01-01

    The airways of COPD patients are often colonized with bacteria leading to increased airway inflammation. This study sought to determine whether systemic cytokine responses to microbial pathogen-associated molecular patterns (PAMPs) are increased among subjects with severe COPD. In an observational cross-sectional study of COPD subjects, PAMP-induced cytokine responses were measured in whole blood ex vivo. We used PAMPs derived from microbial products recognized by toll-like receptors 1, 2, 4, 5, 6, 7, and 8. Patterns of cytokine response to PAMPs were assessed using hierarchical clustering. One-sided Student's t-tests were used to compare PAMP-induced cytokine levels in blood from patients with and without severe COPD, and for subjects with and without chronic bronchitis. Of 28 male patients, 12 had moderate COPD (FEV1 50%-80%) and 16 severe COPD (FEV1 <50%); 27 participants provided data on self-reported chronic bronchitis, of which 15 endorsed chronic bronchitis symptoms and 12 did not. Cytokine responses to PAMPs in severe COPD were generally lower than in subjects with milder COPD. This finding was particularly strong for PAMP-induced interleukin (IL)-10, granulocyte colony stimulating factor, and IL-1β. Subjects with chronic bronchitis showed higher PAMP-induced IL-1RA responses to most of the PAMPs evaluated. COPD patients with more severe disease demonstrated a diminished cytokine response to PAMPs, suggesting that chronic colonization with bacteria may dampen the systemic innate immune response. PMID:27019597

  20. Pathogen associated molecular pattern (PAMP)-triggered immunity is compromised under C-limited growth.

    PubMed

    Park, Hyeong Cheol; Lee, Shinyoung; Park, Bokyung; Choi, Wonkyun; Kim, Chanmin; Lee, Sanghun; Chung, Woo Sik; Lee, Sang Yeol; Sabir, Jamal; Bressan, Ray A; Bohnert, Hans J; Mengiste, Tesfaye; Yun, Dae-Jin

    2015-01-31

    In the interaction between plants and pathogens, carbon (C) resources provide energy and C skeletons to maintain, among many functions, the plant immune system. However, variations in C availability on pathogen associated molecular pattern (PAMP) triggered immunity (PTI) have not been systematically examined. Here, three types of starch mutants with enhanced susceptibility to Pseudomonas syringae pv. tomato DC3000 hrcC were examined for PTI. In a dark period-dependent manner, the mutants showed compromised induction of a PTI marker, and callose accumulation in response to the bacterial PAMP flagellin, flg22. In combination with weakened PTI responses in wild type by inhibition of the TCA cycle, the experiments determined the necessity of C-derived energy in establishing PTI. Global gene expression analyses identified flg22 responsive genes displaying C supply-dependent patterns. Nutrient recycling-related genes were regulated similarly by C-limitation and flg22, indicating re-arrangements of expression programs to redirect resources that establish or strengthen PTI. Ethylene and NAC transcription factors appear to play roles in these processes. Under C-limitation, PTI appears compromised based on suppression of genes required for continued biosynthetic capacity and defenses through flg22. Our results provide a foundation for the intuitive perception of the interplay between plant nutrition status and pathogen defense. PMID:25387755

  1. Vigilant keratinocytes trigger pathogen-associated molecular pattern signaling in response to streptococcal M1 protein.

    PubMed

    Persson, Sandra T; Wilk, Laura; Mörgelin, Matthias; Herwald, Heiko

    2015-12-01

    The human skin exerts many functions in order to maintain its barrier integrity and protect the host from invading microorganisms. One such pathogen is Streptococcus pyogenes, which can cause a variety of superficial skin wounds that may eventually progress into invasive deep soft tissue infections. Here we show that keratinocytes recognize soluble M1 protein, a streptococcal virulence factor, as a pathogen-associated molecular pattern to release alarming inflammatory responses. We found that this interaction initiates an inflammatory intracellular signaling cascade involving the activation of the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal protein kinase and the subsequent induction and mobilization of the transcription factors NF-κB and AP-1. We also determined the imprint of the inflammatory mediators released, such as interleukin-8 (IL-8), growth-related oncogene alpha, migration inhibitory factor, extracellular matrix metalloproteinase inducer, IL-1α, IL-1 receptor a, and ST2, in response to streptococcal M1 protein. The expression of IL-8 is dependent on Toll-like receptor 2 activity and subsequent activation of the mitogen-activated protein kinases ERK and p38. Notably, this signaling seems to be distinct for IL-8 release, and it is not shared with the other inflammatory mediators. We conclude that keratinocytes participate in a proinflammatory manner in streptococcal pattern recognition and that expression of the chemoattractant IL-8 by keratinocytes constitutes an important protective mechanism against streptococcal M1 protein. PMID:26416902

  2. Morphologic and molecular evaluation of Chlamydia trachomatis growth in human endocervix reveals distinct growth patterns

    PubMed Central

    Lewis, Maria E.; Belland, Robert J.; AbdelRahman, Yasser M.; Beatty, Wandy L.; Aiyar, Ashok A.; Zea, Arnold H.; Greene, Sheila J.; Marrero, Luis; Buckner, Lyndsey R.; Tate, David J.; McGowin, Chris L.; Kozlowski, Pamela A.; O'Brien, Michelle; Lillis, Rebecca A.; Martin, David H.; Quayle, Alison J.

    2014-01-01

    In vitro models of Chlamydia trachomatis growth have long been studied to predict growth in vivo. Alternative or persistent growth modes in vitro have been shown to occur under the influence of numerous stressors but have not been studied in vivo. Here, we report the development of methods for sampling human infections from the endocervix in a manner that permits a multifaceted analysis of the bacteria, host and the endocervical environment. Our approach permits evaluating total bacterial load, transcriptional patterns, morphology by immunofluorescence and electron microscopy, and levels of cytokines and nutrients in the infection microenvironment. By applying this approach to two pilot patients with disparate infections, we have determined that their contrasting growth patterns correlate with strikingly distinct transcriptional biomarkers, and are associated with differences in local levels of IFNγ. Our multifaceted approach will be useful to dissect infections in the human host and be useful in identifying patients at risk for chronic disease. Importantly, the molecular and morphological analyses described here indicate that persistent growth forms can be isolated from the human endocervix when the infection microenvironment resembles the in vitro model of IFNγ-induced persistence. PMID:24959423

  3. Vigilant Keratinocytes Trigger Pathogen-Associated Molecular Pattern Signaling in Response to Streptococcal M1 Protein

    PubMed Central

    Wilk, Laura; Mörgelin, Matthias; Herwald, Heiko

    2015-01-01

    The human skin exerts many functions in order to maintain its barrier integrity and protect the host from invading microorganisms. One such pathogen is Streptococcus pyogenes, which can cause a variety of superficial skin wounds that may eventually progress into invasive deep soft tissue infections. Here we show that keratinocytes recognize soluble M1 protein, a streptococcal virulence factor, as a pathogen-associated molecular pattern to release alarming inflammatory responses. We found that this interaction initiates an inflammatory intracellular signaling cascade involving the activation of the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal protein kinase and the subsequent induction and mobilization of the transcription factors NF-κB and AP-1. We also determined the imprint of the inflammatory mediators released, such as interleukin-8 (IL-8), growth-related oncogene alpha, migration inhibitory factor, extracellular matrix metalloproteinase inducer, IL-1α, IL-1 receptor a, and ST2, in response to streptococcal M1 protein. The expression of IL-8 is dependent on Toll-like receptor 2 activity and subsequent activation of the mitogen-activated protein kinases ERK and p38. Notably, this signaling seems to be distinct for IL-8 release, and it is not shared with the other inflammatory mediators. We conclude that keratinocytes participate in a proinflammatory manner in streptococcal pattern recognition and that expression of the chemoattractant IL-8 by keratinocytes constitutes an important protective mechanism against streptococcal M1 protein. PMID:26416902

  4. Contribution of damage-associated molecular patterns to transfusion-related acute lung injury in cardiac surgery

    PubMed Central

    Müller, Marcella C.A.; Tuinman, Pieter R.; Vlaar, Alexander P.; Tuip, Anita M.; Maijoor, Kelly; Achouiti, Achmed; van t Veer, Cornelis; Vroom, Margreeth B.; Juffermans, Nicole P.

    2014-01-01

    Background The incidence of transfusion-related acute lung injury (TRALI) in cardiac surgery patients is high and this condition contributes to an adverse outcome. Damage-associated molecular pattern (DAMP) molecules, HMGB1 and S100A12, are thought to mediate inflammatory changes in acute respiratory distress syndrome. We aimed to determine whether DAMP are involved in the pathogenesis of TRALI in cardiac surgery patients. Materials and methods This was a secondary analysis of a prospective observational trial in cardiac surgery patients admitted to the Intensive Care Unit of a university hospital in the Netherlands. Fourteen TRALI cases were randomly matched with 32 transfused and non-transfused controls. Pulmonary levels of HMGB1, S100A12 and inflammatory cytokines (interleukins-1β, -6, and -8 and tumour necrosis factor-α) were determined when TRALI evolved. In addition, systemic and pulmonary levels of soluble receptor for advanced glycation end products (sRAGE) were determined. Results HMGB1 expression and levels of sRAGE in TRALI patients did not differ from those in controls. There was a trend towards higher S100A12 levels in TRALI patients compared to the controls. Furthermore, S100A12 levels were associated with increased levels of markers of pulmonary inflammation, prolonged cardiopulmonary bypass, hypoxemia and duration of mechanical ventilation. Conclusion No evidence was found that HMGB1 and sRAGE contribute to the development of TRALI. S100A12 is associated with duration of cardiopulmonary bypass, pulmonary inflammation, hypoxia and prolonged mechanical ventilation and may contribute to acute lung injury in cardiac surgery patients. PMID:24887223

  5. Delta-like 1 homolog in Capra hircus: molecular characteristics, expression pattern and phylogeny.

    PubMed

    Hu, Jiangtao; Zhao, Wei; Zhan, Siyuan; Xiao, Ping; Zhou, Jingxuan; Wang, Linjie; Li, Li; Zhang, Hongping; Niu, Lili; Zhong, Tao

    2016-06-01

    To research the molecular characteristics, expression pattern and phylogeny of the Delta-like 1 homolog gene (Dlk1) in goats. Dlk1 transcripts were identified in the Jianyang Da'er goats by reverse-transcription polymerase chain reaction (RT-PCR). Phylogenetic trees were constructed by Bayesian inference and neighbor-joining methods. Quantitative real-time PCR (qPCR), western blotting and in situ hybridization were performed to analyze the expression pattern of Dlk1. Five alternatively transcripts were identified in different tissues and designated as Dlk1-AS1, 2, 3, 4 and 5. Compared with the normal transcript Dlk1-AS1, Dlk1-AS4 and Dlk1-AS5 retained the identical open reading frame (ORF) and encoded proteins with truncated epidermal-growth-factor like repeats of 121 and 83 amino acids, respectively. Using the Bayesian inference method, the consensus phylogenetic tree indicated that caprine Dlk1 had a closer relationship with bovine Dlk1 than with Dlk1 from pigs, humans and mice. qPCR revealed high expression levels of Dlk1 in the kidney (P < 0.01). However, mRNA and protein levels presented an inconsistent correlation, possibly because of post-transcriptional regulation. RNA in situ hybridization indicated that Dlk1 mRNA was localized in the interlobular bile duct and alongside the hepatocyte nuclei, in the epithelial cells of proximal and distal convoluted tubules and in the connective region between the mesothelium and myocardium in the heart. The Dlk1 gene in goats produces alternatively spliced transcripts, with specific expression and cellular localization patterns. These findings would lay the foundation for further study. PMID:27108112

  6. Intensity enhancement and selective detection of proximate solvent molecules by molecular near-field effect in resonance hyper-Raman scattering

    NASA Astrophysics Data System (ADS)

    Shimada, Rintaro; Kano, Hideaki; Hamaguchi, Hiro-o.

    2008-07-01

    A new molecular phenomenon associated with resonance hyper-Raman (HR) scattering in solution has been discovered. Resonance HR spectra of all-trans-β-carotene and all-trans-lycopene in various solvents exhibited several extra bands that were not assignable to the solute but were unequivocally assigned to the solvents. Neat solvents did not show detectable HR signals under the same experimental conditions. Similar experiments with all-trans-retinal did not exhibit such enhancement either. All-trans-β-carotene and all-trans-lycopene have thus been shown to induce enhanced HR scattering of solvent molecules through a novel molecular effect that is not associated with all-trans-retinal. We call this new effect the "molecular near-field effect." In order to explain this newly found effect, an extended vibronic theory of resonance HR scattering is developed where the vibronic interaction including the proximate solvent molecule (intermolecular vibronic coupling) is explicitly introduced in the solute hyperpolarizability tensor. The potential of "molecular near-field HR spectroscopy," which selectively detects molecules existing in the close vicinity of a HR probe in complex chemical or biological systems, is discussed.

  7. Nanopolaritonics with a continuum of molecules: simulations of molecular-induced selectivity in plasmonics transport through a continuous Y-shape.

    PubMed

    Neuhauser, Daniel

    2011-11-28

    Using the recent NF (near-field) formulation for electrodynamics on the nanoscale, we simulate transport in a Y-shape gold nanostructure in the presence of 2-level molecules. NF is shown to be easily integrated with the Liouville equation, producing a simple and efficient nanopolaritons (plasmons-excitons) solver, with a large time step. Two cases are considered: coating of the gold structure with molecular layers thinner than the structure, and filling space with aligned molecules. In both cases significant effects on the radiation transport are obtained even for low molecular densities. At low densities the effects are primarily an overall reduction of the plasmonics peak, but at higher densities there is a significant selectivity control by the molecules. A redshift is predicted, especially for the space-filling case. The combined nanopolariton shows qualitative hybridization, and the spectral peaks separate with increasing coupling, i.e., with increasing molecular densities. The results open the way to "control of light by light," i.e., controlling plasmonic light transport by inducing a change in the direction of the guiding molecular dipoles through radiation or other means. PMID:22128933

  8. Use of Mo/ller-Plesset perturbation theory in molecular calculations: Spectroscopic constants of first row diatomic molecules

    SciTech Connect

    Dunning, T.H. , Jr.; Peterson, K.A.

    1998-03-01

    The convergence of Mo/ller{endash}Plesset perturbation expansions (MP2{endash}MP4/MP5) for the spectroscopic constants of a selected set of diatomic molecules (BH, CH, HF, N{sub 2}, CO, and F{sub 2}) has been investigated. It was found that the second-order perturbation contributions to the spectroscopic constants are strongly dependent on basis set, more so for HF and CO than for BH. The MP5 contributions for HF were essentially zero for the cc-pVDZ basis set, but increased significantly with basis set illustrating the difficulty of using small basis sets as benchmarks for correlated calculations. The convergence behavior of the {ital exact} Mo/ller{endash}Plesset perturbation expansions were investigated using estimates of the {ital complete basis set limits} obtained using large correlation consistent basis sets. For BH and CH, the perturbation expansions of the spectroscopic constants converge monotonically toward the experimental values, while for HF, N{sub 2}, CO, and F{sub 2}, the expansions oscillate about the experimental values. The perturbation expansions are, in general, only slowly converging and, for HF, N{sub 2}, CO, and F{sub 2}, appear to be far from convergence at MP4. In fact, for HF, N{sub 2}, and CO, the errors in the calculated spectroscopic constants for the MP4 method are {ital larger} than those for the MP2 method (the only exception is D{sub e}). The current study, combined with other recent studies, raises serious doubts about the use of Mo/ller{endash}Plesset perturbation theory to describe electron correlation effects in atomic and molecular calculations. {copyright} {ital 1998 American Institute of Physics.}

  9. Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis

    PubMed Central

    Ramaswamy, Vijay; Remke, Marc; Bouffet, Eric; Faria, Claudia C.; Perreault, Sebastien; Cho, Yoon-Jae; Shih, David J.; Luu, Betty; Dubuc, Adrian M.; Northcott, Paul A.; Schüller, Ulrich; Gururangan, Sridharan; McLendon, Roger; Bigner, Darell; Fouladi, Maryam; Ligon, Keith L.; Pomeroy, Scott L.; Dunn, Sandra; Triscott, Joanna; Jabado, Nada; Fontebasso, Adam; Jones, David T. W.; Kool, Marcel; Karajannis, Matthias A.; Gardner, Sharon L.; Zagzag, David; Nunes, Sofia; Pimentel, José; Mora, Jaume; Lipp, Eric; Walter, Andrew W.; Ryzhova, Marina; Zheludkova, Olga; Kumirova, Ella; Alshami, Jad; Croul, Sidney E.; Rutka, James T.; Hawkins, Cynthia; Tabori, Uri; Codispoti, Kari-Elise T.; Packer, Roger J.; Pfister, Stefan M.; Korshunov, Andrey; Taylor, Michael D.

    2014-01-01

    Background Recurrent medulloblastoma is a daunting therapeutic challenge as it is almost universally fatal. Recent studies confirmed that medulloblastoma comprises four distinct subgroups. We sought to delineate subgroup specific differences in medulloblastoma recurrence patterns. Methods We retrospectively identified a discovery cohort of all recurrent medulloblastomas at the Hospital for Sick Children between 1994-2012, and performed molecular subgrouping on FFPE tissues using a nanoString-based assay. The anatomical site of recurrence (local tumour bed or leptomeningeal metastasis), time to recurrence and survival post-recurrence were determined in a subgroup specific fashion. Subgroup specific recurrence patterns were confirmed in two independent, non-overlapping FFPE validation cohorts. Where possible molecular subgrouping was performed on tissue obtained from both the initial surgery and at recurrence. Results A screening cohort of 30 recurrent medulloblastomas was assembled; nine with local recurrences, and 21 metastatic. When re-analysed in a subgroup specific manner, local recurrences were more frequent in SHH tumours (8/9, 88%) and metastatic recurrences were more common in Group 3 and 4 (17/20 [85%] with one WNT, p=0.0014, local vs metastatic recurrence, SHH vs Group 3 vs Group 4). The subgroup specific location of recurrence was confirmed in a multicenter validation cohort (p=0·0013 for local vs metastatic recurrence SHH vs Group 3 vs Group 4, n=77), and a second independent validation cohort comprising 96 recurrences (p<0·0001 for local vs metastatic recurrence SHH vs Group 3 vs Group 4, n=96). Treatment with craniospinal irradiation at diagnosis was not significantly associated with the anatomical pattern of recurrence. Survival post recurrence was significantly longer in Group 4 patients (p=0·013) as confirmed in a multicenter validation cohort (p=0·0075). Strikingly, subgroup affiliation remained stable at recurrence in all 34 cases with

  10. Multiscale modeling of cellular epigenetic states: stochasticity in molecular networks, chromatin folding in cell nuclei, and tissue pattern formation of cells

    PubMed Central

    Liang, Jie; Cao, Youfang; Gürsoy, Gamze; Naveed, Hammad; Terebus, Anna; Zhao, Jieling

    2016-01-01

    Genome sequences provide the overall genetic blueprint of cells, but cells possessing the same genome can exhibit diverse phenotypes. There is a multitude of mechanisms controlling cellular epigenetic states and that dictate the behavior of cells. Among these, networks of interacting molecules, often under stochastic control, depending on the specific wirings of molecular components and the physiological conditions, can have a different landscape of cellular states. In addition, chromosome folding in three-dimensional space provides another important control mechanism for selective activation and repression of gene expression. Fully differentiated cells with different properties grow, divide, and interact through mechanical forces and communicate through signal transduction, resulting in the formation of complex tissue patterns. Developing quantitative models to study these multi-scale phenomena and to identify opportunities for improving human health requires development of theoretical models, algorithms, and computational tools. Here we review recent progress made in these important directions. PMID:27480462

  11. Toll-like receptors: cellular signal transducers for exogenous molecular patterns causing immune responses.

    PubMed

    Kirschning, C J; Bauer, S

    2001-09-01

    Innate immunity initiates protection of the host organism against invasion and subsequent multiplication of microbes by specific recognition. Germ line-encoded receptors have been identified for microbial products such as mannan, lipopeptide, peptidoglycan (PGN), lipoteichoic acid (LTA), lipopolysaccharide (LPS), and CpG-DNA. The Drosophila Toll protein has been shown to be involved in innate immune response of the adult fruitfly. Members of the family of Toll-like receptors (TLRs) in vertebrates have been implicated as pattern recognition receptors (PRRs). Ten TLRs are known and six of these have been demonstrated to mediate cellular activation by distinct microbial products. TLR4 has been implicated as activator of adaptive immunity, and analysis of systemic LPS responses in mice led to the identification of LPS-resistant strains instrumental in its identification as a transmembrane LPS signal transducer. Structural similarities between TLRs and receptor molecules involved in immune responses such as CD14 and the IL-1 receptors (IL-1Rs), as well as functional analysis qualified TLR2 as candidate receptor for LPS and other microbial products. Targeted disruption of the TLR9 gene in mice led to identification of TLR9 as CpG-DNA signal transducer. Involvement of TLR5 in cell activation by bacterial flagellin has been demonstrated. Further understanding of recognition and cellular signaling activated through the ancient host defense system represented by Toll will eventually lead to means for its therapeutic modulation. PMID:11680785

  12. Diverse redox-active molecules bearing O-, S-, or Se-terminated tethers for attachment to silicon in studies of molecular information storage.

    PubMed

    Balakumar, Arumugham; Lysenko, Andrey B; Carcel, Carole; Malinovskii, Vladimir L; Gryko, Daniel T; Schweikart, Karl-Heinz; Loewe, Robert S; Yasseri, Amir A; Liu, Zhiming; Bocian, David F; Lindsey, Jonathan S

    2004-03-01

    A molecular approach to information storage employs redox-active molecules tethered to an electroactive surface. Attachment of the molecules to electroactive surfaces requires control over the nature of the tether (linker and surface attachment group). We have synthesized a collection of redox-active molecules bearing different linkers and surface anchor groups in free or protected form (hydroxy, mercapto, S-acetylthio, and Se-acetylseleno) for attachment to surfaces such as silicon, germanium, and gold. The molecules exhibit a number of cationic oxidation states, including one (ferrocene), two [zinc(II)porphyrin], three [cobalt(II)porphyrin], or four (lanthanide triple-decker sandwich compound). Electrochemical studies of monolayers of a variety of the redox-active molecules attached to Si(100) electrodes indicate that molecules exhibit a regular mode of attachment (via a Si-X bond, X = O, S, or Se), relatively homogeneous surface organization, and robust reversible electrochemical behavior. The acetyl protecting group undergoes cleavage during the surface deposition process, enabling attachment to silicon via thio or seleno groups without handling free thiols or selenols. PMID:14986994

  13. Investigation of multi-state charge-storage properties of redox-active organic molecules in silicon-molecular hybrid devices for DRAM and Flash applications

    NASA Astrophysics Data System (ADS)

    Gowda, Srivardhan Shivappa

    Molecular electronics has recently spawned a considerable amount of interest with several molecules possessing charge-conduction and charge-storage properties proposed for use in electronic devices. Hybrid silicon-molecular technology has the promise of augmenting the current silicon technology and provide for a transitional path to future molecule-only technology. The focus of this dissertation work has been on developing a class of hybrid silicon-molecular electronic devices for DRAM and Flash memory applications utilizing redox-active molecules. This work exploits the ability of molecules to store charges with single-electron precision at room temperature. The hybrid devices are fabricated by forming self-assembled monolayers of redox-active molecules on Si and oxide (SiO2 and HfO2) surfaces via formation of covalent linkages. The molecules possess discrete quantum states from which electrons can tunnel to the Si substrate at discrete applied voltages (oxidation process, cell write), leaving behind a positively charged layer of molecules. The reduction (erase) process, which is the process of electrons tunneling back from Si to the molecules, neutralizes the positively charged molecular monolayer. Hybrid silicon-molecular capacitor test structures were electrically characterized with an electrolyte gate using cyclic voltammetry (CyV) and impedance spectroscopy (CV) techniques. The redox voltages, kinetics (write/erase speeds) and charge-retention characteristics were found to be strongly dependent on the Si doping type and densities, and ambient light. It was also determined that the redox energy states in the molecules communicate with the valence band of the Si substrate. This allows tuning of write and read states by modulating minority carriers in n- and p-Si substrates. Ultra-thin dielectric tunnel barriers (SiO2, HfO2) were placed between the molecules and the Si substrate to augment charge-retention for Flash memory applications. The redox response was

  14. 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.

  15. Patterns of integration of DNA microinjected into cultured mammalian cells: evidence for homologous recombination between injected plasmid DNA molecules.

    PubMed Central

    Folger, K R; Wong, E A; Wahl, G; Capecchi, M R

    1982-01-01

    We examined the fate of DNA microinjected into nuclei of cultured mammalian cells. The sequence composition and the physical form of the vector carrying the selectable gene affected the efficiency of DNA-mediated transformation. Introduction of sequences near the simian virus 40 origin of DNA replication or in the long terminal repeat of avian sarcoma provirus into a recombinant plasmid containing the herpes simplex virus thymidine kinase gene. (pBR322/HSV-tk) enhanced the frequency of transformation of LMtk- and RAT-2tk- cells to the TK+ phenotype 20- to 40-fold. In cells receiving injections of only a few plasmid DNA molecules, the transformation frequency was 40-fold higher after injection of linear molecules than after injection of supercoiled molecules. By controlling the number of gene copies injected into a recipient cell, we could obtain transformants containing a single copy or as many as 50 to 100 copies of the selectable gene. Multiple copies of the transforming gene were not scattered throughout the host genome but were integrated as a concatemer at one or a very few sites in the host chromosome. Independent transformants contained the donated genes in different chromosomes. The orientation of the gene copies within the concatemer was not random; rather, the copies were organized as tandem head-to-tail arrays. By analyzing transformants obtained by coinjecting two vectors which were identical except that in one a portion of the vector was inverted, we were able to conclude that the head-to-tail concatemers were generated predominantly by homologous recombination. Surprisingly, these head-to-tail concatemers were found in transformants obtained by injecting either supercoiled or linear plasmid DNA. Even though we demonstrated that cultured mammalian cells contain the enzymes for ligating two DNA molecules very efficiently irrespective of the sequences or topology at their ends, we found that even linear plasmid DNA was recruited into the concatemer by

  16. Short communication: Single molecule, real-time sequencing technology revealed species- and strain-specific methylation patterns of 2 Lactobacillus strains.

    PubMed

    Zhang, Wenyi; Sun, Zhihong; Menghe, Bilige; Zhang, Heping

    2015-05-01

    Pacific Biosciences' (Menlo Park, CA) single molecule, real-time sequencing technology was reported to have some advantages in generating finished genomes and characterizing the epigenome of bacteria. In the present study, this technology was used to sequence 2 Lactobacillus strains, Lactobacillus casei Zhang and Lactobacillus plantarum P-8. Previously, the former bacterium was sequenced by an Applied Biosystems 3730 DNA analyzer (Grand Island, NY), whereas the latter one was analyzed with Roche 454 (Indianapolis, IN) and Illumina sequencing technologies (San Diego, CA). The results showed that single molecule, real-time sequencing resulted in high-quality, finished genomes for both strains. Interestingly, epigenome analysis indicates the presence of 1 active N(6)-methyladenine methyltransferase in L. casei Zhang, but none in L. plantarum P-8. Our study revealed for the first time a completely different methylation pattern in 2 Lactobacillus strains. PMID:25747834

  17. Ship in a breakable bottle: fluoride-induced release of an organic molecule from a Pr(iii)-linked molecular cage.

    PubMed

    Lee, Juhoon; Waggoner, Nolan W; Polanco, Luis; You, Ga Rim; Lynch, Vincent M; Kim, Sung Kuk; Humphrey, Simon M; Sessler, Jonathan L

    2016-06-30

    A 3-dimensional networked molecular cage, , has been synthesized. This macrocycle-based framework was prepared from a solvothermal reaction involving a flexible organic building block, calix[4]pyrrole dibenzoic acid (H2), and Pr(NO3)3·6H2O. A unique feature of is that it retains free calix[4]pyrrole molecules in the framework pores. Treatment with a fluoride anion source serves to destroy the network and allows release of the organic guest. The net result is a 'molecular ship' in a 'breakable bottle'. PMID:27273123

  18. Patterns of integration of DNA microinjected into cultured mammalian cells: Evidence for homologous recombination between injected plasmid DNA molecules

    SciTech Connect

    Folger, K.R.; Wong, E.A.; Wahl, G.; Capecchi, M.R.

    1982-11-01

    The authors examined the fate of DNA microinjected into nuclei of cultured mammalian cells. The sequence composition and the physical form of the vector carrying the selectable gene affected the efficiency of DNA-mediated transformation. Introduction of sequences near the simian virus 40 origin of DNA replication or in the long terminal repeat of avian sarcoma provirus into a recombinant plasmid containing the herpes simplex virus thymidine kinase gene (pBR322/HSV-tk) enhanced the frequency of transformation of LMtk/sup -/ and RAT-2tk/sup -/ cells to the TK/sup +/ phenotype 20- to 40-fold. In cells receiving injections of only a few plasmid DNA molecules, the transformation frequency was 40-fold higher after injection of linear molecules than after injection of supercoiled molecules. By controlling the number of gene copies injected into a recipient cell, we could obtain transformants containing a single copy or as many as 50 to 100 copies of the selectable gene. By analyzing transformants obtained by coinjecting two vectors which were identical except that in one a portion of the vector was inverted, the authors were able to conclude that the head-to-tail concatemers were generated predominantly by homologous recombination. Surprisingly, these head-to-tail concatemers were found in transformants obtained by injecting either supercoiled or linear plasmid DNA.

  19. Identification of a small molecule inhibitor of serine 276 phosphorylation of the p65 subunit of NF-κB using in silico molecular docking

    PubMed Central

    Law, Mary; Corsino, Patrick; Parker, Nicole Teoh; Law, Brian K.

    2009-01-01

    NF-κB is activated in many types of cancer. Phosphorylation of p65 at serine 276 is required for the expression of a subset of NF-κB regulated genes, including vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8). Thus, inhibition of serine 276 phosphorylation may prevent metastasis and angiogenesis in certain tumor types. Using in silico molecular docking, small molecules that are predicted to bind to a structural pocket near serine 276 were identified. One compound, NSC-127102, hinders serine 276 phosphorylation and the expression of IL-8 and VCAM-1. Small molecules such as NSC-127102 may be optimized for the future treatment of cancer. PMID:19910110

  20. Positron-attachment to small molecules: Vibrational enhancement of positron affinities with configuration interaction level of multi-component molecular orbital approach

    SciTech Connect

    Tachikawa, Masanori

    2015-12-31

    To theoretically demonstrate the binding of a positron to small polarized molecules, we have calculated the vibrational averaged positron affinity (PA) values along the local vibrational contribution with the configuration interaction level of multi-component molecular orbital method. This method can take the electron-positron correlation contribution into account through single electronic - single positronic excitation configurations. The PA values are enhanced by including the local vibrational contribution from vertical PA values due to the anharmonicity of the potential.