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Sample records for molecular pattern molecules

  1. 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

  2. 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

  3. Exploring the folding pattern of a polymer chain in a single crystal by combining single-molecule force spectroscopy and steered molecular dynamics simulations.

    PubMed

    Song, Yu; Feng, Wei; Liu, Kai; Yang, Peng; Zhang, Wenke; Zhang, Xi

    2013-03-26

    Understanding the folding pattern of a single polymer chain within its single crystal will shed light on the mechanism of crystallization. Here, we use the combined techniques of atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) and steered molecular dynamics (SMD) simulations to study the folding pattern of a polyethylene oxide (PEO) chain in its single crystal. Our results show that the folding pattern of a PEO chain in the crystal formed in dilute solution follows the adjacent re-entry folding model. While in the crystal obtained from the melt, the nonadjacent folding with large and irregular loops contributes to big force fluctuations in the force-extension curves. The method established here can offer a novel strategy to directly unravel the chain-folding pattern of polymer single crystals at single-molecule level.

  4. 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

  5. Molecular spintronics using single-molecule magnets.

    PubMed

    Bogani, Lapo; Wernsdorfer, Wolfgang

    2008-03-01

    A revolution in electronics is in view, with the contemporary evolution of the two novel disciplines of spintronics and molecular electronics. A fundamental link between these two fields can be established using molecular magnetic materials and, in particular, single-molecule magnets. Here, we review the first progress in the resulting field, molecular spintronics, which will enable the manipulation of spin and charges in electronic devices containing one or more molecules. We discuss the advantages over more conventional materials, and the potential applications in information storage and processing. We also outline current challenges in the field, and propose convenient schemes to overcome them.

  6. 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

  7. 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.

  8. 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

  9. Tiling patterns from ABC star molecules: 3-colored foams?

    PubMed

    Kirkensgaard, Jacob J K; Pedersen, Martin C; Hyde, Stephen T

    2014-10-01

    We present coarse-grained simulations of the self-assembly of 3-armed ABC star polyphiles. In systems of star polyphiles with two arms of equal length the simulations corroborate and expand previous findings from related miktoarm star terpolymer systems on the formation of patterns containing columnar domains whose sections are 2D planar tilings. However, the systematic variation of face topologies as the length of the third (unequal) arm is varied differs from earlier findings regarding the compositional dependence. We explore 2D 3-colored foams to establish the optimal patterns based on interfacial energy alone. A generic construction algorithm is described that accounts for all observed 2D tiling patterns and suggests other patterns likely to be found beyond the range of the simulations reported here. Patterns resulting from this algorithm are relaxed using Surface Evolver calculations to form 2D foams with minimal interfacial length as a function of composition. This allows us to estimate the interfacial enthalpic contributions to the free energy of related star molecular assemblies assuming strong segregation. We compare the resulting phase sequence with a number of theoretical results from particle-based simulations and field theory, allowing us to tease out relative enthalpic and entropic contributions as a function of the chain lengths making up the star molecules. Our results indicate that a richer polymorphism is to be expected in systems not dominated by chain entropy. Further, analysis of corresponding planar tiling patterns suggests that related two-periodic columnar structures are unlikely hypothetical phases in 4-arm star polyphile melts in the absence of sufficient arm configurational freedom for minor domains to form lens-shaped di-gons, which require higher molecular weight polymeric arms. Finally, we discuss the possibility of forming a complex tiling pattern that is a quasi-crystalline approximant for 3-arm star polyphiles with unequal arm

  10. Assembling molecular electronic junctions one molecule at a time.

    PubMed

    Bonifas, Andrew P; McCreery, Richard L

    2011-11-01

    Diffusion of metal atoms onto a molecular monolayer attached to a conducting surface permits electronic contact to the molecules with minimal heat transfer or structural disturbance. Surface-mediated metal deposition (SDMD) involves contact between "cold" diffusing metal atoms and molecules, due to shielding of the molecules from direct exposure to metal vapor. Measurement of the current through the molecular layer during metal diffusion permits observation of molecular conductance for junctions containing as few as one molecule. Discrete conductance steps were observed for 1-10 molecules within a monolayer during a single deposition run, corresponding to "recruitment" of additional molecules as the contact area between the diffusing Au layer and molecules increases. For alkane monolayers, the molecular conductance measured with SDMD exhibited an exponential dependence on molecular length with a decay constant (β) of 0.90 per CH(2) group, comparable to that observed by other techniques. Molecular conductance values were determined for three azobenzene molecules, and correlated with the offset between the molecular HOMO and the contact Fermi level, as expected for hole-mediated tunneling. Current-voltage curves were obtained during metal deposition showed no change in shape for junctions containing 1, 2, and 10 molecules, implying minimal intermolecular interactions as single molecule devices transitioned into several molecules devices. SDMD represents a "soft" metal deposition method capable of providing single molecule conductance values, then providing quantitative comparisons to molecular junctions containing 10(6) to 10(10) molecules.

  11. Large Molecule Structures by Broadband Fourier Transform Molecular Rotational Spectroscopy

    NASA Astrophysics Data System (ADS)

    Evangelisti, Luca; Seifert, Nathan A.; Spada, Lorenzo; Pate, Brooks

    2016-06-01

    Fourier transform molecular rotational resonance spectroscopy (FT-MRR) using pulsed jet molecular beam sources is a high-resolution spectroscopy technique that can be used for chiral analysis of molecules with multiple chiral centers. The sensitivity of the molecular rotational spectrum pattern to small changes in the three dimensional structure makes it possible to identify diastereomers without prior chemical separation. For larger molecules, there is the additional challenge that different conformations of each diastereomer may be present and these need to be differentiated from the diastereomers in the spectral analysis. Broadband rotational spectra of several larger molecules have been measured using a chirped-pulse FT-MRR spectrometer. Measurements of nootkatone (C15H22O), cedrol (C15H26O), ambroxide (C16H28O) and sclareolide (C16H26O2) are presented. These spectra are measured with high sensitivity (signal-to-noise ratio near 1,000:1) and permit structure determination of the most populated isomers using isotopic analysis of the 13C and 18O isotopologues in natural abundance. The accuracy of quantum chemistry calculations to identify diastereomers and conformers and to predict the dipole moment properties needed for three wave mixing measurements is examined.

  12. Adaptive reorganization of 2D molecular nanoporous network induced by coadsorbed guest molecule.

    PubMed

    Zheng, Qing-Na; Wang, Lei; Zhong, Yu-Wu; Liu, Xuan-He; Chen, Ting; Yan, Hui-Juan; Wang, Dong; Yao, Jian-Nian; Wan, Li-Jun

    2014-03-25

    The ordered array of nanovoids in nanoporous networks, such as honeycomb, Kagome, and square, provides a molecular template for the accommodation of "guest molecules". Compared with the commonly studied guest molecules featuring high symmetry evenly incorporated into the template, guest molecules featuring lower symmetry are rare to report. Herein, we report the formation of a distinct patterned superlattice of guest molecules by selective trapping of guest molecules into the honeycomb network of trimesic acid (TMA). Two distinct surface patterns have been achieved by the guest inclusion induced adaptive reconstruction of a 2D molecular nanoporous network. The honeycomb networks can synergetically tune the arrangement upon inclusion of the guest molecules with different core size but similar peripherals groups, resulting in a trihexagonal Kagome or triangular patterns.

  13. 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

  14. Controlling single-molecule junction conductance by molecular interactions

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

    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.

  15. Parallel Molecular Dynamics Program for Molecules

    SciTech Connect

    Plimpton, Steve

    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.

  16. 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.

  17. Probing molecular choreography through single-molecule biochemistry.

    PubMed

    van Oijen, Antoine M; Dixon, Nicholas E

    2015-12-01

    Single-molecule approaches are having a dramatic impact on views of how proteins work. The ability to observe molecular properties at the single-molecule level allows characterization of subpopulations and acquisition of detailed kinetic information that would otherwise be hidden in the averaging over an ensemble of molecules. In this Perspective, we discuss how such approaches have successfully been applied to in vitro-reconstituted systems of increasing complexity.

  18. Single rotating molecule-machines: nanovehicles and molecular motors.

    PubMed

    Rapenne, Gwénaël; Joachim, Christian

    2014-01-01

    In the last decade many molecular machines with controlled molecular motions have been synthesized. In the present review chapter we will present and discuss our contribution to the field, in particular through some examples of rotating molecular machines that have been designed, synthesized, and studied in our group. After starting by explaining why it is so important to study such machines as single molecules, we will focus on two families of molecular machines, nanovehicles and molecular motors. The first members of the nanovehicle family are molecules with two triptycenes as wheels: the axle and the wheelbarrow. Then come the four-wheel nanocars. Since triptycene wheels are not very mobile on metallic surfaces, alternative wheels with a bowl-shape structure have also been synthesized and studied on surfaces. The molecular motors are built around ruthenium organometallic centers and have a piano-stool geometry with peripheric ferrocenyl groups.

  19. Single rotating molecule-machines: nanovehicles and molecular motors.

    PubMed

    Rapenne, Gwénaël; Joachim, Christian

    2014-01-01

    In the last decade many molecular machines with controlled molecular motions have been synthesized. In the present review chapter we will present and discuss our contribution to the field, in particular through some examples of rotating molecular machines that have been designed, synthesized, and studied in our group. After starting by explaining why it is so important to study such machines as single molecules, we will focus on two families of molecular machines, nanovehicles and molecular motors. The first members of the nanovehicle family are molecules with two triptycenes as wheels: the axle and the wheelbarrow. Then come the four-wheel nanocars. Since triptycene wheels are not very mobile on metallic surfaces, alternative wheels with a bowl-shape structure have also been synthesized and studied on surfaces. The molecular motors are built around ruthenium organometallic centers and have a piano-stool geometry with peripheric ferrocenyl groups. PMID:24563010

  20. Mitochondrial damage-associated molecular patterns and vascular function†

    PubMed Central

    Wenceslau, Camilla Ferreira; McCarthy, Cameron G.; Szasz, Theodora; Spitler, Kathryn; Goulopoulou, Styliani; Webb, R. Clinton

    2014-01-01

    Immune system activation occurs not only due to foreign stimuli, but also due to endogenous molecules. As such, endogenous molecules that are released into the circulation due to cell death and/or injury alarm the immune system that something has disturbed homeostasis and a response is needed. Collectively, these molecules are known as damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs (mtDAMPs) are potent immunological activators due to the bacterial ancestry of mitochondria. Mitochondrial DAMPs are recognized by specific pattern recognition receptors of the innate immune system, some of which are expressed in the cardiovascular system. Cell death leads to release of mtDAMPs that may induce vascular changes by mechanisms that are currently not well understood. This review will focus on recently published evidence linking mtDAMPs and immune system activation to vascular dysfunction and cardiovascular disease. PMID:24569027

  1. Identifying molecular signatures in metal-molecule-metal junctions.

    PubMed

    Tsutsui, Makusu; Taniguchi, Masateru; Shoji, Kohei; Yokota, Kazumichi; Kawai, Tomoji

    2009-10-01

    Single molecule identification in metal-molecule-metal junctions provides an ultimate probe that opens a new avenue for revolutionary advances in demonstrating single molecule device functions. Inelastic electron tunneling spectroscopy (IETS) is an ultra-sensitive method for probing vibrational characteristics of molecules with atomic resolution. State-of-the-art experiments on the inelastic transport in self-assembled monolayers of organic molecules have demonstrated the utility of the IETS technique to derive structural information concerning molecular conformations and contact configurations. Here we report the vibrational fingerprint of an individual pi-conjugated molecule sandwiched between gold nanoelectrodes. Our strategy combines analyses of single molecule conductance and vibrational spectra exploiting the nanofabricated mechanically-controllable break junction. We performed IETS measurements on 1,4-benzenedithiol and 2,5-dimercapto-1,3,4-thiadiazole to examine chemical discrimination at the single-molecule level. We found distinct IET spectra unique to the test molecules that agreed excellently with the Raman and theoretical spectra in the fingerprint region, and thereby succeeded in electrical identification of single molecule junctions.

  2. Identifying molecular signatures in metal-molecule-metal junctions

    NASA Astrophysics Data System (ADS)

    Tsutsui, Makusu; Taniguchi, Masateru; Shoji, Kohei; Yokota, Kazumichi; Kawai, Tomoji

    2009-09-01

    Single molecule identification in metal-molecule-metal junctions provides an ultimate probe that opens a new avenue for revolutionary advances in demonstrating single molecule device functions. Inelastic electron tunneling spectroscopy (IETS) is an ultra-sensitive method for probing vibrational characteristics of molecules with atomic resolution. State-of-the-art experiments on the inelastic transport in self-assembled monolayers of organic molecules have demonstrated the utility of the IETS technique to derive structural information concerning molecular conformations and contact configurations. Here we report the vibrational fingerprint of an individual π-conjugated molecule sandwiched between gold nanoelectrodes. Our strategy combines analyses of single molecule conductance and vibrational spectra exploiting the nanofabricated mechanically-controllable break junction. We performed IETS measurements on 1,4-benzenedithiol and 2,5-dimercapto-1,3,4-thiadiazole to examine chemical discrimination at the single-molecule level. We found distinct IET spectra unique to the test molecules that agreed excellently with the Raman and theoretical spectra in the fingerprint region, and thereby succeeded in electrical identification of single molecule junctions.

  3. Deciphering Complexity in Molecular Biophysics with Single-Molecule Resolution.

    PubMed

    Deniz, Ashok A

    2016-01-29

    The structural features and dynamics of biological macromolecules underlie the molecular biology and correct functioning of cells. However, heterogeneity and other complexity of these molecules and their interactions often lead to loss of important information in traditional biophysical experiments. Single-molecule methods have dramatically altered the conceptual thinking and experimental tests available for such studies, leveraging their ability to avoid ensemble averaging. Here, I discuss briefly the rise of fluorescence single-molecule methods over the past two decades, a few key applications, and end with a view to challenges and future prospects. PMID:26707199

  4. Tailoring Ferromagnet-Molecule Interfaces: Towards Molecular Spintronics

    NASA Astrophysics Data System (ADS)

    Raman, Karthik V.; Atodiresei, Nicolae; Moodera, Jagadeesh S.

    2014-09-01

    Understanding the interaction of organic molecules adsorbed on magnetic surfaces has shown considerable progress in recent years. The creation of hybridized interface between carbon-based aromatic molecule and the magnetic surface is observed to give rise to new interface states with unique electronic and magnetic character. This study has opened up a molecular-design initiative to tailor the spin dependent electronic and magnetic functionalities of the hybrid interface. The purpose of this article is to provide a fundamental understanding of the spin-chemistry and spin-physics associated with the formation of such ferromagnet-molecule hybrid interfaces. We also discuss the recent progress in this field using state-of-the-art experiments and theoretical calculations with focus on the magnetic properties of the molecule and the magnetic surface. The study reveals several interesting interface phenomena: formation of induced molecular moment and exchange coupling with the magnetic surface, and molecular spin-filters. It also demonstrates significant changes in the magnetic anisotropy and inter-atomic magnetic exchange coupling of the magnetic surface. These studies open the possibilities of exploring new molecular functionalities toward further research in the subfield of interface-assisted molecular spintronics.

  5. 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.

  6. 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.

  7. Effects of fixed pattern noise on single molecule localization microscopy.

    PubMed

    Long, F; Zeng, S Q; Huang, Z L

    2014-10-21

    The newly developed scientific complementary metal oxide semiconductor (sCMOS) cameras are capable of realizing fast single molecule localization microscopy without sacrificing field-of-view, benefiting from their readout speed which is significantly higher than that of conventional charge-coupled device (CCD) cameras. However, the poor image uniformity (suffered from fixed pattern noise, FPN) is a major obstruction for widespread use of sCMOS cameras in single molecule localization microscopy. Here we present a quantitative investigation on the effects of FPN on single molecule localization microscopy via localization precision and localization bias. We found that FPN leads to almost no effect on localization precision, but introduces a certain amount of localization bias. However, for a commercial Hamamatsu Flash 4.0 sCMOS camera, such localization bias is usually <2 nm and thus can be neglected for most localization microscopy experiments. This study addresses the FPN concern which worries researchers, and thus will promote the application of sCMOS cameras in single molecule localization microscopy.

  8. Photocleavable linker for the patterning of bioactive molecules

    NASA Astrophysics Data System (ADS)

    Wegner, Seraphine V.; Sentürk, Oya I.; Spatz, Joachim P.

    2015-12-01

    Herein, we report the use of a versatile photocleavable nitrobenzyl linker to micropattern a wide variety of bioactive molecules and photorelease them on demand. On one end, the linker has an NHS group that can be coupled with any amine, such as peptides, proteins or amine-linkers, and on the other end an alkyne for convenient attachment to materials with an azide functional group. This linker was conjugated with NTA-amine or the cell adhesion peptide cRGD to enable straightforward patterning of His6-tagged proteins or cells, respectively, on PEGylated glass surfaces. This approach provides a practical way to control the presentation of a wide variety of bioactive molecules with high spatial and temporal resolution. The extent of photocleavage can also be controlled to tune the biomolecule density and degree of cell attachment to the surface.

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

    PubMed

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

    2013-10-10

    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 Caenorhabditis 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, whereas 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

  10. Studies of the Pattern Recognition Molecule H-ficolin

    PubMed Central

    Zacho, Rikke M.; Jensen, Lisbeth; Terp, Randi; Jensenius, Jens C.; Thiel, Steffen

    2012-01-01

    Ficolins are pattern recognition molecules of the innate immune system. H-ficolin is found in plasma associated with mannan-binding lectin-associated serine proteases (MASPs). When H-ficolin binds to microorganisms the MASPs are activated, which in turn activate the complement system. H-ficolin is the most abundant ficolin in humans, yet its ligand binding characteristics and biological role remain obscure. We examined the binding of H-ficolin to Aerococcus viridans as well as to a more defined artificial target, i.e. acetylated bovine serum albumin. A strict dependence for calcium ions and inhibition at high NaCl concentration was found. The binding to acetylated bovine serum albumin was inhibited by acetylsalicylic acid and sodium acetate as well as by N-acetylated glucosamine and galactosamine (GlcNAc and GalNAc) and glycine (GlyNAc). The binding to A. viridans was sensitive to the same compounds, but, importantly, higher concentrations were needed for inhibition. N-Acetylated cysteine was also inhibitory, but this inhibition was parallel with reduction in the oligomerization of H-ficolin and thus represents structural changes of the molecule. Based on our findings, we developed a procedure for the purification of H-ficolin from serum, involving PEG precipitation, affinity chromatography on Sepharose derivatized with acetylated serum albumin, ion exchange chromatography, and gel permeation chromatography. The purified H-ficolin was observed to elute at 700 kDa, similar to what we find for H-ficolin in whole serum. MASP-2 was co-purified with H-ficolin, and the purified H-ficolin·MASP-2 complex could activate complement as measured by cleavage of complement factor C4. This study extends our knowledge of the specificity of this pattern recognition molecule, and the purified product will enable further studies. PMID:22238349

  11. Single Molecule Spectroscopy Illuminating the Molecular Dynamics of Life

    NASA Astrophysics Data System (ADS)

    Webb, Watt W.

    This chapter summarizes a series of new single-molecule spectroscopy investigations in the life sciences at Cornell University that began with our invention of Fluorescence Correlation Spectroscopy (FCS) about 1970. Our invention of FCS became my first focus on the "Molecular Dynamics of Life." It motivated my transition from research on quantum fluctuations and transport in condensed matter physics including superconductivity and in the molecular dynamics of coherent fluctuations and nano-transport in inanimate physical and chemical systems subject to the nonlinear dynamics of continuous phase transitions. These interdisciplinary transitions exemplify the productivity of such interdisciplinary interactions in science.

  12. Signal transduction molecule patterns indicating potential glioblastoma therapy approaches

    PubMed Central

    Cruceru, Maria Linda; Enciu, Ana-Maria; Popa, Adrian Claudiu; Albulescu, Radu; Neagu, Monica; Tanase, Cristiana Pistol; Constantinescu, Stefan N

    2013-01-01

    Purpose The expression of an array of signaling molecules, along with the assessment of real-time cell proliferation, has been performed in U87 glioma cell line and in patients’ glioblastoma established cell cultures in order to provide a better understanding of cellular and molecular events involved in glioblastoma pathogenesis. Experimental therapy was performed using a phosphatidylinositol-3′-kinase (PI3K) inhibitor. Patients and methods xMAP technology was employed to assess expression levels of several signal transduction molecules and real-time xCELLigence platform for cell behavior. Results PI3K inhibition induced the most significant effects on global signaling pathways in patient-derived cell cultures, especially on members of the mitogen-activated protein-kinase family, P70S6 serine-threonine kinase, and cAMP response element-binding protein expression and further prevented tumor cell proliferation. Conclusion The PI3K pathway might be a prime target for glioblastoma treatment. PMID:24348050

  13. 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.

  14. 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

  15. 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

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

    SciTech Connect

    Genson, Kirsten Larson

    2005-01-01

    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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. Nanometric molecular separation measurements by single molecule photobleaching.

    PubMed

    Webb, Stephen E D; Hirsch, Michael; Needham, Sarah R; Coles, Benjamin C; Scherer, Kathrin M; Roberts, Selene K; Zanetti-Domingues, Laura C; Tynan, Christopher J; Martin-Fernandez, Marisa L; Rolfe, Daniel J

    2015-10-15

    Although considerable progress has been made in imaging distances in cells below the diffraction limit using FRET and super-resolution microscopy, methods for determining the separation of macromolecules in the 10-50 nm range have been elusive. We have developed fluorophore localisation imaging with photobleaching (FLImP), based on the quantised bleaching of individual protein-bound dye molecules, to quantitate the molecular separations in oligomers and nanoscale clusters. We demonstrate the benefits of using our method in studying the nanometric organisation of the epidermal growth factor receptor in cells.

  5. Maskless RGB color patterning of vacuum-deposited small molecule OLED displays by diffusion of luminescent dopant molecules.

    PubMed

    Kajiyama, Yoshitaka; Kajiyama, Koichi; Aziz, Hany

    2015-06-29

    A maskless RGB color patterning technique based on diffusion of luminescent dopant molecules is proposed here for vacuum-deposited small molecule OLED displays. The proposed maskless color patterning technique enables us to overcome challenging issues in OLED display manufacturing arising from shadow mask limitations. This approach utilizes selective diffusion of luminescent dopant molecules from a donor substrate to an acceptor substrate. Results show that sufficiently high doping levels can be achieved through this technique and that devices with performance similar to those produced by standard co-deposition can be easily produced. Red, green and blue OLEDs are successfully fabricated side by side on one substrate using this technique.

  6. Molecular patterning of the mammalian dentition.

    PubMed

    Lan, Yu; Jia, Shihai; Jiang, Rulang

    2014-01-01

    Four conserved signaling pathways, including the bone morphogenetic proteins (Bmp), fibroblast growth factors (Fgf), sonic hedgehog (Shh), and wingless-related (Wnt) pathways, are each repeatedly used throughout tooth development. Inactivation of any of these resulted in early tooth developmental arrest in mice. The mutations identified thus far in human patients with tooth agenesis also affect these pathways. Recent studies show that these signaling pathways interact through positive and negative feedback loops to regulate not only morphogenesis of individual teeth but also tooth number, shape, and spatial pattern. Increased activity of each of the Fgf, Shh, and canonical Wnt signaling pathways revitalizes development of the physiologically arrested mouse diastemal tooth germs whereas constitutive activation of canonical Wnt signaling in the dental epithelium is able to induce supernumerary tooth formation even in the absence of Msx1 and Pax9, two transcription factors required for normal tooth development beyond the early bud stage. Bmp4 and Msx1 act in a positive feedback loop to drive sequential tooth formation whereas the Osr2 transcription factor restricts Msx1-mediated expansion of the mesenchymal odontogenic field along both the buccolingual and anteroposterior axes to pattern mouse molar teeth in a single row. Moreover, the ectodermal-specific ectodysplasin (EDA) signaling pathway controls tooth number and tooth shape through regulation of Fgf20 expression in the dental epithelium, whereas Shh suppresses Wnt signaling through a negative feedback loop to regulate spatial patterning of teeth. In this article, we attempt to integrate these exciting findings in the understanding of the molecular networks regulating tooth development and patterning.

  7. A molecular tuning fork in single-molecule mechanochemical sensing.

    PubMed

    Mandal, Shankar; Koirala, Deepak; Selvam, Sangeetha; Ghimire, Chiran; Mao, Hanbin

    2015-06-22

    The separate arrangement of target recognition and signal transduction in conventional biosensors often compromises the real-time response and can introduce additional noise. To address these issues, we combined analyte recognition and signal reporting by mechanochemical coupling in a single-molecule DNA template. We incorporated a DNA hairpin as a mechanophore in the template, which, under a specific force, undergoes stochastic transitions between folded and unfolded hairpin structures (mechanoescence). Reminiscent of a tuning fork that vibrates at a fixed frequency, the device was classified as a molecular tuning fork (MTF). By monitoring the lifetime of the folded and unfolded hairpins with equal populations, we were able to differentiate between the mono- and bivalent binding modes during individual antibody-antigen binding events. We anticipate these mechanospectroscopic concepts and methods will be instrumental for the development of novel bioanalyses.

  8. Patterning small-molecule biocapture surfaces: microcontact insertion printing vs. photolithography.

    PubMed

    Shuster, M J; Vaish, A; Cao, H H; Guttentag, A I; McManigle, J E; Gibb, A L; Martinez-Rivera, M; Martinez, M M; Nezarati, R M; Hinds, J M; Liao, W-S; Weiss, P S; Andrews, A M

    2011-10-14

    Chemical patterns prepared by self-assembly, combined with soft lithography or photolithography, are directly compared. Pattern fidelity can be controlled in both cases but patterning at the low densities necessary for small-molecule probe capture of large biomolecule targets is better accomplished using microcontact insertion printing (μCIP). Surfaces patterned by μCIP are used to capture biomolecule binding partners for the small molecules dopamine and biotin.

  9. Simple molecular model for the binding of antibiotic molecules to bacterial ion channels

    NASA Astrophysics Data System (ADS)

    Mafé, Salvador; Ramírez, Patricio; Alcaraz, Antonio

    2003-10-01

    A molecular model aimed at explaining recent experimental data by Nestorovich et al. [Proc. Natl. Acad. Sci. USA 99, 9789 (2002)] on the interaction of ampicillin molecules with the constriction zone in a channel of the general bacterial porin, OmpF (outer membrane protein F), is presented. The model extends T. L. Hill's theory for intermolecular interactions in a pair of binding sites [J. Am. Chem. Soc. 78, 3330 (1956)] by incorporating two binding ions and two pairs of interacting sites. The results provide new physical insights on the role of the complementary pattern of the charge distributions in the ampicillin molecule and the narrowest part of the channel pore. Charge matching of interacting sites facilitates drug binding. The dependence of the number of ampicillin binding events per second with the solution pH and salt concentration is explained qualitatively using a reduced number of fundamental concepts.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. Complete Photo-Induced Breakup of the H2 Molecule as a Probe of Molecular Electron Correlation

    NASA Astrophysics Data System (ADS)

    Vanroose, Wim; Martín, Fernando; Rescigno, Thomas N.; McCurdy, C. William

    2005-12-01

    Despite decades of progress in quantum mechanics, electron correlation effects are still only partially understood. Experiments in which both electrons are ejected from an oriented hydrogen molecule by absorption of a single photon have recently demonstrated a puzzling phenomenon: The ejection pattern of the electrons depends sensitively on the bond distance between the two nuclei as they vibrate in their ground state. Here, we report a complete numerical solution of the Schrödinger equation for the double photoionization of H2. The results suggest that the distribution of photoelectrons emitted from aligned molecules reflects electron correlation effects that are purely molecular in origin.

  15. Complete Photo-Induced Breakup of the H2 Molecule as a Probe ofMolecular Electron Correlation

    SciTech Connect

    Vanroose, Wim; Martin, Fernando; Rescigno, Thomas N.; McCurdy, C.William

    2005-11-17

    Despite decades of progress in quantum mechanics, electron correlation effects are still only partially understood. Experiments in which both electrons are ejected from an oriented hydrogen molecule by absorption of a single photon have recently demonstrated a puzzling phenomenon: The ejection pattern of the electrons depends sensitively on the bond distance between the two nuclei as they vibrate in their ground state. Here we report a complete numerical solution of the Schrodinger equation for the double photoionization of H2. The results suggest that the distribution of photoelectrons emitted from aligned molecules reflects electron correlation effects that are purely molecular in origin.

  16. Direct patterning of rhodamine 6G molecules on mica by dip-pen nanolithography [rapid communication

    NASA Astrophysics Data System (ADS)

    Zhou, Hualan; Li, Zhuang; Wu, Aiguo; Wei, Gang; Liu, Zhiguo

    2004-09-01

    Dip-pen nanolithography (DPN) has been developed to pattern monolayer film of various molecules on suitable substrate through the controlled movement of ink-coated atomic force microscopy (AFM) tip, which makes DPN a potentially powerful tool for making the functional nanoscale devices. In this paper, the direct patterning of rhodamine 6G on mica by dip-pen nanolithography was demonstrated. R6G features patterned on the mica was successfully achieved with different tip movement which can be programmed by Nanoscript™ language. From the AFM image of R6G patterns, we know that R6G molecule is flatly binding to the mica surface through electrostatic interaction, thus stable R6G nanostructures could be formed on mica. The influence of translation speed and contact time on DPN was discussed. The method can be extended to direct patterning of many other organic molecules, and should open many opportunities for miniaturized optical device and site-specific biological staining.

  17. 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.

  18. Laboratory astrophysics and molecular astronomy of pure carbon molecules.

    PubMed

    Bernath, P F

    1995-03-01

    The pure carbon molecules Cn are currently of great experimental and theoretical interest. Our work in this area begins with detection of the SiC molecule, which is isovalent with C2. New infrared electronic transitions of C2 and C3 were discovered by emission spectroscopy of hydrocarbon dicharges. The C3 and C5 molecules were found by infrared vibration-rotation spectroscopy of the prototypical obscured carbon star, IRC+10216. C7 and C9 were searched for in the same source, but not found. The laboratory infrared emission spectrum of C60 was recorded to aid in a search for C60 in extraterrestrial sources.

  19. Time-Resolved Molecular Frame Dynamics of Fixed-in-Space CS2 Molecules

    SciTech Connect

    Bisgaard, Christer; Clarkin, Owen; Wu, Guorong; Lee, Anthony; Gessner, Oliver; Hayden, Carl; Stolow, Albert

    2009-04-02

    Random orientation of molecules within a sample leads to blurred observationsof chemical reactions studied from the laboratory perspective. Methodsdeveloped for the dynamic imaging of molecular structures and processesstruggle with this, as measurements are optimally made in the molecular frame.Here we uselaser alignment to transiently fix CS2 molecules in space longenough to elucidate, in the molecular reference frame, details of ultrafast electronic vibrationaldynamics during a photochemical reaction. These three-dimensional photoelectron imaging results, combined with ongoing efforts in molecular alignment and orientation, presage a wide range of insights obtainable fromtime-resolved studies in the molecular frame.

  20. 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

  1. 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

  2. Molecular imprinted polymer-coated optical fiber sensor for the identification of low molecular weight molecules.

    PubMed

    Lépinay, Sandrine; Ianoul, Anatoli; Albert, Jacques

    2014-10-01

    A biomimetic optical probe for detecting low molecular weight molecules (maltol, 3-hydroxy-2-methyl-4H-pyran-4-one, molecular weight of 126.11 g/mol), was designed, fabricated, and characterized. The sensor couples a molecular imprinted polymer (MIP) and the Bragg grating refractometry technology into an optical fiber. The probe is fabricated first by inscribing tilted grating planes in the core of the fiber, and then by photopolymerization to immobilize a maltol imprinted MIP on the fiber cladding surface over the Bragg grating. The sensor response to the presence of maltol in different media is obtained by spectral interrogation of the fiber transmission signal. The results showed that the limit of detection of the sensor reached 1 ng/mL in pure water with a sensitivity of 6.3 × 10(8)pm/M. The selectivity of the sensor against other compounds and its reusability were also studied experimentally. Finally, the unambiguous detection of concentrations as little as 10nM of maltol in complex media (real food samples) by the MIP-coated tilted fiber Bragg grating sensor was demonstrated.

  3. 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.

  4. 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.

  5. Electrostatic Spin Crossover in a Molecular Junction of a Single-Molecule Magnet Fe2

    NASA Astrophysics Data System (ADS)

    Hao, Hua; Zheng, Xiaohong; Song, Lingling; Wang, Ruining; Zeng, Zhi

    2012-01-01

    Spin crossover by means of an electric bias is investigated by spin-polarized density-functional theory calculations combined with the Keldysh nonequilibrium Green’s technique in a molecular junction, where an individual single-molecule magnet Fe2(acpybutO)(O2CMe)(NCS)2 is sandwiched between two infinite Au(100) nanoelectrodes. Our study demonstrates that the spin crossover, based on the Stark effect, is achieved in this molecular junction under an electric bias but not in the isolated molecule under external electric fields. The main reason is that the polarizability of the molecular junction has an opposite sign to that of the isolated molecule, and thus from the Stark effect the condition for the spin crossover in the molecular junction is contrary to that in the isolated molecule.

  6. 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

  7. 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

  8. 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…

  9. 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.

  10. 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

  11. Photochromic molecules as building blocks for molecular electronics.

    PubMed

    Peter, Belser

    2010-01-01

    Energy and electron transfer processes can be easily induced by a photonic excitation of a donor metal complex ([Ru(bpy)3]2), which is connected via a wire-type molecular fragment to an acceptor metal complex ([Os(bpy)3]2+). The rate constant for the transfer process can be determined by emission measurements of the two connected metal complexes. The system can be modified by incorporation of a switching unit or an interrupter into the wire, influencing the transfer process. Such a molecular device corresponds to an interrupter, mimic the same function applied in molecular electronics. We have used organic switches, which show photochromic properties. By irradiation with light of different wavelengths, the switch changes its functionality by a photochemical reaction from an OFF- to an ON-state and vice versa. The ON- respectively OFF-state is manifested by a color change but also in different conductivity properties for energy and electron transfer processes. Therefore, the mentioned molecular device can work as a simple interrupter, controlling the rate of the transfer processes.

  12. PALM--a pattern language for molecular biology.

    PubMed

    Helgesen, C; Sibbald, P R

    1993-01-01

    This paper presents a new pattern language, PALM, for describing patterns in molecular biology sequences. The language is intended for representing knowledge about such patterns in a declarative, clear and concise way. It is also shown that its expressive power enables the definition of any regular or context free language, and also higher languages in the Chomsky hierarchy by parameter attachment, variables and procedural attachment. It is also possible to define approximate patterns. The language is rigorously defined, and several examples of its use and expressive power are given. PMID:7584333

  13. 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.

  14. High-order harmonic spectroscopy for molecular imaging of polyatomic molecules.

    PubMed

    Negro, M; Devetta, M; Faccialá, D; De Silvestri, S; Vozzi, C; Stagira, S

    2014-01-01

    High-order harmonic generation is a powerful and sensitive tool for probing atomic and molecular structures, combining in the same measurement an unprecedented attosecond temporal resolution with a high spatial resolution of the order of an angstrom. Imaging of the outermost molecular orbital by high-order harmonic generation has been limited for a long time to very simple molecules, like nitrogen. Recently we demonstrated a technique that overcame several of the issues that have prevented the extension of molecular orbital tomography to more complex species, showing that molecular imaging can be applied to a triatomic molecule like carbon dioxide. Here we report on the application of such a technique to nitrous oxide (N(2)O) and acetylene (C(2)H(2)). This result represents a first step towards the imaging of fragile compounds, a category which includes most of the fundamental biological molecules.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

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

    PubMed

    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.

  3. 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

  4. 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

  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. Syntheses of molecularly imprinted polymers: Molecular recognition of cyproheptadine using original print molecules and azatadine as dummy templates.

    PubMed

    Feás, X; Seijas, J A; Vázquez-Tato, M P; Regal, P; Cepeda, A; Fente, C

    2009-01-12

    The use of custom-made polymeric materials with high selectivities as target molecules in solid-phase extraction (SPE), known as molecularly imprinted solid-phase extraction (MISPE), is becoming an increasingly important sample preparation technique. However, the potential risk of leakage of the imprinting molecules during the desorption phase has limited application. The use of a mimicking template, called a dummy molecular imprinting polymer (DMIP), that bears the structure of a related molecule and acts as a putative imprinting molecule may provide a useful solution to this problem. In the current study, cyproheptadine (CPH) and azatadine (AZA) were used as templates in the development of an MIP and DMIP for acrylic acid and methacrylic acid monomers. Our results indicate that DMIPs have equal recognition of CPH, avoiding the problem of leakage of original template during the desorption phase relative to MIPs synthesized in presence of the print molecule CPH. Examination of the surface structure of the two polymer products by SEM shows appreciable differences in structural morphology and function of the monomers employed. These results are well supplemented by data obtained for swelling ratios and solvent uptake. Molecular modelling of CPH and AZA suggests that both substrates are similar in shape and volume.

  7. Single molecule switches and molecular self-assembly: Low temperature STM investigations and manipulations

    NASA Astrophysics Data System (ADS)

    Iancu, Violeta

    This dissertation is devoted to single molecule investigations and manipulations of two porphyrin-based molecules, chlorophyll-a and Co-porphyrin. The molecules are adsorbed 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 detailed underlying switching mechanisms are uncovered from the statistical analyses conducted over 1200 switching events together with the support of geometrically relaxed parametric calculations. The second switch, a spintronic switch, uses Co-porphyrin conformational changes to tune the spin-electron interaction between the Co atom and Cu(111) electrons. A change in the molecular conformation, from saddle to planar, leads to enhanced spin-electron coupling strength, and consequently, elevated Kondo temperatures. Self-assembly process is exploited for both the molecules and the analyses reveal important information regarding the layer growth and the electronic differences that appear due to the modified molecule-substrate environment.

  8. Immunopathological roles of cytokines, chemokines, signaling molecules, and pattern-recognition receptors in systemic lupus erythematosus.

    PubMed

    Yu, Shui-Lian; Kuan, Woon-Pang; Wong, Chun-Kwok; Li, Edmund K; Tam, Lai-Shan

    2012-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology affecting more than one million individuals each year. It is characterized by B- and T-cell hyperactivity and by defects in the clearance of apoptotic cells and immune complexes. Understanding the complex process involved and the interaction between various cytokines, chemokines, signaling molecules, and pattern-recognition receptors (PRRs) in the immune pathways will provide valuable information on the development of novel therapeutic targets for treating SLE. In this paper, we review the immunopathological roles of novel cytokines, chemokines, signaling molecules, PRRs, and their interactions in immunoregulatory networks and suggest how their disturbances may implicate pathological conditions in SLE.

  9. 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.

  10. 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.

  11. Non-linear molecular pattern classification using molecular beacons with multiple targets.

    PubMed

    Lee, In-Hee; Lee, Seung Hwan; Park, Tai Hyun; Zhang, Byoung-Tak

    2013-12-01

    In vitro pattern classification has been highlighted as an important future application of DNA computing. Previous work has demonstrated the feasibility of linear classifiers using DNA-based molecular computing. However, complex tasks require non-linear classification capability. Here we design a molecular beacon that can interact with multiple targets and experimentally shows that its fluorescent signals form a complex radial-basis function, enabling it to be used as a building block for non-linear molecular classification in vitro. The proposed method was successfully applied to solving artificial and real-world classification problems: XOR and microRNA expression patterns.

  12. 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.

  13. 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

  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. Molecular level studies on binding modes of labeling molecules with polyalanine peptides

    NASA Astrophysics Data System (ADS)

    Mao, Xiaobo; Wang, Chenxuan; Ma, Xiaojing; Zhang, Min; Liu, Lei; Zhang, Lan; Niu, Lin; Zeng, Qindao; Yang, Yanlian; Wang, Chen

    2011-04-01

    In this work, the binding modes of typical labeling molecules (thioflavin T (ThT), Congo red (CR) and copper(ii) phthalocyanine tetrasulfonic acid tetrasodium salt (PcCu(SO3Na)4)) on pentaalanine, which is a model peptide segment of amyloidpeptides, have been resolved at the molecular level by using scanning tunneling microscopy (STM). In the STM images, ThT molecules are predominantly adsorbed parallel to the peptide strands and two binding modes could be identified. It was found that ThT molecules are preferentially binding on top of the peptide strand, and the mode of intercalated between neighboring peptides also exists. The parallel binding mode of CR molecules can be observed with pentaalaninepeptides. Besides the binding modes of labeling molecules, the CR and PcCu(SO3Na)4 display different adsorption affinity with the pentaalaninepeptides. The results could be beneficial for obtaining molecular level insight of the interactions between labeling molecules and peptides.In this work, the binding modes of typical labeling molecules (thioflavin T (ThT), Congo red (CR) and copper(ii) phthalocyanine tetrasulfonic acid tetrasodium salt (PcCu(SO3Na)4)) on pentaalanine, which is a model peptide segment of amyloidpeptides, have been resolved at the molecular level by using scanning tunneling microscopy (STM). In the STM images, ThT molecules are predominantly adsorbed parallel to the peptide strands and two binding modes could be identified. It was found that ThT molecules are preferentially binding on top of the peptide strand, and the mode of intercalated between neighboring peptides also exists. The parallel binding mode of CR molecules can be observed with pentaalaninepeptides. Besides the binding modes of labeling molecules, the CR and PcCu(SO3Na)4 display different adsorption affinity with the pentaalaninepeptides. The results could be beneficial for obtaining molecular level insight of the interactions between labeling molecules and peptides. Electronic

  16. A comparative study on the molecular descriptors for predicting drug-likeness of small molecules

    PubMed Central

    Mishra, Hrishikesh; Singh, Nitya; Lahiri, Tapobrata; Misra, Krishna

    2009-01-01

    Screening of “ drug-like” molecule from the molecular database produced through high throughput techniques and their large repositories requires robust classification. In our work, a set of heuristically chosen nine molecular descriptors including four from Lipinski's rule, were used as classification parameter for screening “drug-like” molecules. The robustness of classification was compared with four fundamental descriptors of Lipinski. Back propagation neural network based classifier was applied on a database of 60000 molecules for classification of, “ drug-like” and “non drug-like” molecules. Classification result using nine descriptors showed high classification accuracy of 96.1% in comparison to that using four Lipinski's descriptors which yielded an accuracy of 82.48%. Also a significant decrease of false positives resulted while using nine descriptors causing a sharp 18% increase of specificity of classification. From this study it appeared that Lipinski's descriptors which mainly deal with pharmacokinetic properties of molecules form the basis for identification of “drug-like” molecules that can be substantially improved by adding more descriptors representing pharmaco­dynamics properties of molecules. PMID:19707563

  17. Monitoring molecular beacon DNA probe hybridization at the single-molecule level.

    PubMed

    Yao, Gang; Fang, Xiaohong; Yokota, Hiroaki; Yanagida, Toshio; Tan, Weihong

    2003-11-21

    We have monitored the reaction dynamics of the DNA hybridization process on a liquid/solid interface at the single-molecule level by using a hairpin-type molecular beacon DNA probe. Fluorescence images of single DNA probes were recorded by using total internal reflection fluorescence microscopy. The fluorescence signal of single DNA probes during the hybridization to individual complementary DNA probes was monitored over time. Among 400 molecular beacon DNA probes that we tracked, 349 molecular beacons (87.5 %) were hybridized quickly and showed an abrupt fluorescence increase, while 51 probes (12.5 %) reacted slowly, resulting in a gradual fluorescence increase. This ratio stayed about the same when varying the concentrations of cDNA in MB hybridization on the liquid/surface interface. Statistical data of the 51 single-molecule hybridization images showed that there was a multistep hybridization process. Our results also showed that photostability for the dye molecules associated with the double-stranded hybrids was better than that for those with the single-stranded molecular beacon DNA probes. Our results demonstrate the ability to obtain a better understanding of DNA hybridization processes using single-molecule techniques, which will improve biosensor and biochip development where surface-immobilized molecular beacon DNA probes provide unique advantages in signal transduction.

  18. A New Graph-Based Molecular Descriptor Using the Canonical Representation of the Molecule

    PubMed Central

    Hentabli, Hamza; 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

  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. Application of DNQ-based microlithography to patterning bioactive molecules and cells

    NASA Astrophysics Data System (ADS)

    Nicolau, Dan V.; Taguchi, Takahisa; Taniguchi, Hiroshi; Yoshikawa, Susumu; Dusa, Mircea V.

    1996-06-01

    Photochemically induced surface functionality manipulation of Diazo-Naphto-Quinone/novolak polymeric films was used for controlling the specificity of the attachment and growth of neuronal cells and biologically active molecules (proteins and peptides) patterning. Different microlithographic techniques (standard positive tone, negative tone image reversal based on catalyzed decarboxylation, positive tone of image reversal resist, and surface imaging based on silylation), controlling the surface hydrophobicity and surface concentration of carboxylic groups, were assessed in the view of the suitability as microlithographic techniques for patterning biologically active molecules and cells. It was found that DNQ-based materials and techniques can be easily transferred in bio-microlithography, which is the building of laterally ordered architectures with biological structural elements.

  1. Nano-fabrication of molecular electronic junctions by targeted modification of metal-molecule bonds

    NASA Astrophysics Data System (ADS)

    Jafri, S. Hassan M.; Löfås, Henrik; Blom, Tobias; Wallner, Andreas; Grigoriev, Anton; Ahuja, Rajeev; Ottosson, Henrik; Leifer, Klaus

    2015-09-01

    Reproducibility, stability and the coupling between electrical and molecular properties are central challenges in the field of molecular electronics. The field not only needs devices that fulfill these criteria but they also need to be up-scalable to application size. In this work, few-molecule based electronics devices with reproducible electrical characteristics are demonstrated. Our previously reported 5 nm gold nanoparticles (AuNP) coated with ω-triphenylmethyl (trityl) protected 1,8-octanedithiol molecules are trapped in between sub-20 nm gap spacing gold nanoelectrodes forming AuNP-molecule network. When the trityl groups are removed, reproducible devices and stable Au-thiol junctions are established on both ends of the alkane segment. The resistance of more than 50 devices is reduced by orders of magnitude as well as a reduction of the spread in the resistance histogram is observed. By density functional theory calculations the orders of magnitude decrease in resistance can be explained and supported by TEM observations thus indicating that the resistance changes and strongly improved resistance spread are related to the establishment of reproducible and stable metal-molecule bonds. The same experimental sequence is carried out using 1,6-hexanedithiol functionalized AuNPs. The average resistances as a function of molecular length, demonstrated herein, are comparable to the one found in single molecule devices.

  2. Nano-fabrication of molecular electronic junctions by targeted modification of metal-molecule bonds.

    PubMed

    Jafri, S Hassan M; Löfås, Henrik; Blom, Tobias; Wallner, Andreas; Grigoriev, Anton; Ahuja, Rajeev; Ottosson, Henrik; Leifer, Klaus

    2015-01-01

    Reproducibility, stability and the coupling between electrical and molecular properties are central challenges in the field of molecular electronics. The field not only needs devices that fulfill these criteria but they also need to be up-scalable to application size. In this work, few-molecule based electronics devices with reproducible electrical characteristics are demonstrated. Our previously reported 5 nm gold nanoparticles (AuNP) coated with ω-triphenylmethyl (trityl) protected 1,8-octanedithiol molecules are trapped in between sub-20 nm gap spacing gold nanoelectrodes forming AuNP-molecule network. When the trityl groups are removed, reproducible devices and stable Au-thiol junctions are established on both ends of the alkane segment. The resistance of more than 50 devices is reduced by orders of magnitude as well as a reduction of the spread in the resistance histogram is observed. By density functional theory calculations the orders of magnitude decrease in resistance can be explained and supported by TEM observations thus indicating that the resistance changes and strongly improved resistance spread are related to the establishment of reproducible and stable metal-molecule bonds. The same experimental sequence is carried out using 1,6-hexanedithiol functionalized AuNPs. The average resistances as a function of molecular length, demonstrated herein, are comparable to the one found in single molecule devices.

  3. Evolution of the gyrB gene and the molecular phylogeny of Enterobacteriaceae: a model molecule for molecular systematic studies.

    PubMed

    Dauga, Catherine

    2002-03-01

    Phylogenetic trees showing the evolutionary relatedness of Enterobacteriaceae based upon gyrB and 16S rRNA genes were compared. Congruence among trees of these molecules indicates that the genomes of these species are not completely mosaic and that molecular systematic studies can be carried out. Phylogenetic trees based on gyrB sequences appeared to be more reliable at determining relationships among Serratia species than trees based on 16S rRNA gene sequences. gyrB sequences from Serratia species formed a monophyletic group validated by significant bootstrap values. Serratia fonticola had the most deeply branching gyrB sequence in the Serratia monophyletic group, which was consistent with its atypical phenotypic characteristics. Klebsiella and Enterobacter genera seemed to be polyphyletic, but the branching patterns of gyrB and 16S rRNA gene trees were not congruent. Enterobacter aerogenes was grouped with Klebsiella pneumoniae on the gyrB phylogenetic tree, which supports that this species could be transferred to the Klebsiella genus. Unfortunately, 16S rRNA and gyrB phylogenetic trees gave conflicting evolutionary relationships for Citrobacter freundii because of its unusual gyrB evolutionary process. gyrB lateral gene transfer was suspected for Hafnia alvei. Saturation of gyrB genes was observed by the pairwise comparison of Proteus spp., Providencia alcalifaciens and Morganella morganii sequences. Depending on their level of variability, 16S rRNA gene sequences were useful for describing phylogenetic relationships between distantly related Enterobacteriaceae, whereas gyrB sequence comparison was useful for inferring intra- and some intergeneric relationships.

  4. Rotational viscosity of fluids composed of linear molecules: An equilibrium molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Moore, R. J. D.; Hansen, J. S.; Todd, B. D.

    2008-06-01

    In this paper, we investigate the rotational viscosity for a chlorine fluid and for a fluid composed of small linear molecules by using equilibrium molecular dynamics simulations. The rotational viscosity is calculated over a large range of state points. It is found that the rotational viscosity is almost independent of temperature in the range studied here but exhibits a power-law dependency on density. The rotational viscosity also shows a power-law relationship with the molecular length, and the ratio between the shear and rotational viscosities approaches 0.5 for the longest molecule studied here. By changing the number of atoms or united atomic units per molecule and by keeping the molecule length fixed, we show that fluids composed of molecules which have a rodlike shape have a lower rotational viscosity. We argue that this phenomenon is due to the reduction in intermolecular connectivity, which leads to larger fluctuations around the values possessed by the fluid on average. The conclusions here can be extended to fluids composed of uniaxial molecules of arbitrary length.

  5. Single-molecule chemical reaction reveals molecular reaction kinetics and dynamics.

    PubMed

    Zhang, Yuwei; Song, Ping; Fu, Qiang; Ruan, Mingbo; Xu, Weilin

    2014-06-25

    Understanding the microscopic elementary process of chemical reactions, especially in condensed phase, is highly desirable for improvement of efficiencies in industrial chemical processes. Here we show an approach to gaining new insights into elementary reactions in condensed phase by combining quantum chemical calculations with a single-molecule analysis. Elementary chemical reactions in liquid-phase, revealed from quantum chemical calculations, are studied by tracking the fluorescence of single dye molecules undergoing a reversible redox process. Statistical analyses of single-molecule trajectories reveal molecular reaction kinetics and dynamics of elementary reactions. The reactivity dynamic fluctuations of single molecules are evidenced and probably arise from either or both of the low-frequency approach of the molecule to the internal surface of the SiO2 nanosphere or the molecule diffusion-induced memory effect. This new approach could be applied to other chemical reactions in liquid phase to gain more insight into their molecular reaction kinetics and the dynamics of elementary steps.

  6. Tris-thiourea tripodal-based molecules as chloride transmembrane transporters: insights from molecular dynamics simulations.

    PubMed

    Marques, Igor; Colaço, Ana R; Costa, Paulo J; Busschaert, Nathalie; Gale, Philip A; Félix, Vítor

    2014-05-28

    The interaction of six tripodal synthetic chloride transmembrane transporters with a POPC bilayer was investigated by means of molecular dynamics simulations using the general Amber force field (GAFF) for the transporters and the LIPID11 force field for phospholipids. These transporters are structurally simple molecules, based on the tris(2-aminoethyl)amine scaffold, containing three thiourea binding units coupled with three n-butyl (1), phenyl (2), fluorophenyl (3), pentafluorophenyl (4), trifluoromethylphenyl (5), or bis(trifluoromethyl)phenyl (6) substituents. The passive diffusion of 1-6⊃ Cl(-) was evaluated with the complexes initially positioned either in the water phase or inside the bilayer. In the first scenario the chloride is released in the water solution before the synthetic molecules achieve the water-lipid interface and permeate the membrane. In the latter one, only when the chloride complex reaches the interface is the anion released to the water phase, with the transporter losing the initial ggg tripodal shape. Independently of the transporter used in the membrane system, the bilayer structure is preserved and the synthetic molecules interact with the POPC molecules at the phosphate headgroup level, via N-H···O hydrogen bonds. Overall, the molecular dynamics simulations' results indicate that the small tripodal molecules in this series have a low impact on the bilayer and are able to diffuse with chloride inside the lipid environment. Indeed, these are essential conditions for these molecules to promote the transmembrane transport as anion carriers, in agreement with experimental efflux data. PMID:24663079

  7. 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.

  8. 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

    2014-01-16

    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.

  9. 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.

  10. Molecular Threading: Mechanical Extraction, Stretching and Placement of DNA Molecules from a Liquid-Air Interface

    PubMed Central

    Kemmish, Kent; Hamalainen, Mark; Bowell, Charlotte; Bleloch, Andrew; Klejwa, Nathan; Lehrach, Wolfgang; Schatz, Ken; Stark, Heather; Marblestone, Adam; Church, George; Own, Christopher S.; Andregg, William

    2013-01-01

    We present “molecular threading”, a surface independent tip-based method for stretching and depositing single and double-stranded DNA molecules. DNA is stretched into air at a liquid-air interface, and can be subsequently deposited onto a dry substrate isolated from solution. The design of an apparatus used for molecular threading is presented, and fluorescence and electron microscopies are used to characterize the angular distribution, straightness, and reproducibility of stretched DNA deposited in arrays onto elastomeric surfaces and thin membranes. Molecular threading demonstrates high straightness and uniformity over length scales from nanometers to micrometers, and represents an alternative to existing DNA deposition and linearization methods. These results point towards scalable and high-throughput precision manipulation of single-molecule polymers. PMID:23935923

  11. Interaction between encapsulated excited organic molecules and free nitroxides: communication across a molecular wall.

    PubMed

    Porel, Mintu; Jockusch, Steffen; Ottaviani, M Francesca; Turro, N J; Ramamurthy, V

    2011-09-01

    Communication between two molecules, one confined and excited (triplet or singlet) and one free and paramagnetic, has been explored through quenching of fluorescence and/or phosphorescence by nitroxides as paramagnetic radical species. Quenching of excited states by nitroxides has been investigated in solution, and the mechanism is speculated to involve charge transfer and/or exchange processes, both of which require close orbital interaction between excited molecule and quencher. We show in this report that such a quenching, which involves electron-electron spin communication, can occur even when there is a molecular wall between the two. The excited state molecule is confined within an organic capsule made up of two molecules of a deep cavity cavitand, octa acid, that exists in the anionic form in basic aqueous solution. The nitroxide is kept free in aqueous solution. (1)H NMR and EPR experiments were carried out to ascertain the location of the two molecules. The distance between the excited molecule and the paramagnetic quencher was manipulated by the use of cationic, anionic, and neutral nitroxide and also by selectively including the cationic nitroxide within the cavity of cucurbituril. Results presented here highlight the role of the lifetime of the encounter complex in electron-electron spin communication when the direct orbital overlap between the two molecules is prevented by the intermediary wall. PMID:21749113

  12. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    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.

  14. 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

  15. Heterogeneity of Synovial Molecular Patterns in Patients with Arthritis

    PubMed Central

    Lauwerys, Bernard R.; Hernández-Lobato, Daniel; Gramme, Pierre; Ducreux, Julie; Dessy, Adrien; Focant, Isabelle; Ambroise, Jérôme; Bearzatto, Bertrand; Nzeusseu Toukap, Adrien; Van den Eynde, Benoît J.; Elewaut, Dirk; Gala, Jean-Luc; Durez, Patrick; Houssiau, Frédéric A.; Helleputte, Thibault; Dupont, Pierre

    2015-01-01

    Objectives Early diagnosis of rheumatoid arthritis (RA) is an unmet medical need in the field of rheumatology. Previously, we performed high-density transcriptomic studies on synovial biopsies from patients with arthritis, and found that synovial gene expression profiles were significantly different according to the underlying disorder. Here, we wanted to further explore the consistency of the gene expression signals in synovial biopsies of patients with arthritis, using low-density platforms. Methods Low-density assays (cDNA microarray and microfluidics qPCR) were designed, based on the results of the high-density microarray data. Knee synovial biopsies were obtained from patients with RA, spondyloarthropathies (SA) or osteoarthritis (OA) (n = 39), and also from patients with initial undifferentiated arthritis (UA) (n = 49). Results According to high-density microarray data, several molecular pathways are differentially expressed in patients with RA, SA and OA: T and B cell activation, chromatin remodelling, RAS GTPase activation and extracellular matrix regulation. Strikingly, disease activity (DAS28-CRP) has a significant influence on gene expression patterns in RA samples. Using the low-density assays, samples from patients with OA are easily discriminated from RA and SA samples. However, overlapping molecular patterns are found, in particular between RA and SA biopsies. Therefore, prediction of the clinical diagnosis based on gene expression data results in a diagnostic accuracy of 56.8%, which is increased up to 98.6% by the addition of specific clinical symptoms in the prediction algorithm. Similar observations are made in initial UA samples, in which overlapping molecular patterns also impact the accuracy of the diagnostic algorithm. When clinical symptoms are added, the diagnostic accuracy is strongly improved. Conclusions Gene expression signatures are overall different in patients with OA, RA and SA, but overlapping molecular signatures are found in

  16. 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

  17. 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

  18. 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

  19. 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.

  20. An aptazyme-based molecular device that converts a small-molecule input into an RNA output.

    PubMed

    Ayukawa, Shotaro; Sakai, Yoko; Kiga, Daisuke

    2012-08-01

    We describe the construction of an aptazyme-based molecular device that converts, through a cascade of reactions, a small-molecule input into output RNA strands. This device is applicable as an interface between a small molecule and a molecular system that accepts only nucleic acid input.

  1. Site-Selection in Single-Molecule Junction for Highly Reproducible Molecular Electronics.

    PubMed

    Kaneko, Satoshi; Murai, Daigo; Marqués-González, Santiago; Nakamura, Hisao; Komoto, Yuki; Fujii, Shintaro; Nishino, Tomoaki; Ikeda, Katsuyoshi; Tsukagoshi, Kazuhito; Kiguchi, Manabu

    2016-02-01

    Adsorption sites of molecules critically determine the electric/photonic properties and the stability of heterogeneous molecule-metal interfaces. Then, selectivity of adsorption site is essential for development of the fields including organic electronics, catalysis, and biology. However, due to current technical limitations, site-selectivity, i.e., precise determination of the molecular adsorption site, remains a major challenge because of difficulty in precise selection of meaningful one among the sites. We have succeeded the single site-selection at a single-molecule junction by performing newly developed hybrid technique: simultaneous characterization of surface enhanced Raman scattering (SERS) and current-voltage (I-V) measurements. The I-V response of 1,4-benzenedithiol junctions reveals the existence of three metastable states arising from different adsorption sites. Notably, correlated SERS measurements show selectivity toward one of the adsorption sites: "bridge sites". This site-selectivity represents an essential step toward the reliable integration of individual molecules on metallic surfaces. Furthermore, the hybrid spectro-electric technique reveals the dependence of the SERS intensity on the strength of the molecule-metal interaction, showing the interdependence between the optical and electronic properties in single-molecule junctions.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. Molecular physics. Production of trilobite Rydberg molecule dimers with kilo-Debye permanent electric dipole moments.

    PubMed

    Booth, D; Rittenhouse, S T; Yang, J; Sadeghpour, H R; Shaffer, J P

    2015-04-01

    Permanent electric dipole moments are important for understanding symmetry breaking in molecular physics, control of chemical reactions, and realization of strongly correlated many-body quantum systems. However, large molecular permanent electric dipole moments are challenging to realize experimentally. We report the observation of ultralong-range Rydberg molecules with bond lengths of ~100 nanometers and kilo-Debye permanent electric dipole moments that form when an ultracold ground-state cesium (Cs) atom becomes bound within the electronic cloud of an extended Cs electronic orbit. The electronic character of this hybrid class of "trilobite" molecules is dominated by degenerate Rydberg manifolds, making them difficult to produce by conventional photoassociation. We used detailed coupled-channel calculations to reproduce their properties quantitatively. Our findings may lead to progress in ultracold chemistry and strongly correlated many-body physics.

  8. Correlating Molecular Structures with Transport Dynamics in High-Efficiency Small-Molecule Organic Photovoltaics.

    PubMed

    Peng, Jiajun; Chen, Yani; Wu, Xiaohan; Zhang, Qian; Kan, Bin; Chen, Xiaoqing; Chen, Yongsheng; Huang, Jia; Liang, Ziqi

    2015-06-24

    Efficient charge transport is a key step toward high efficiency in small-molecule organic photovoltaics. Here we applied time-of-flight and organic field-effect transistor to complementarily study the influences of molecular structure, trap states, and molecular orientation on charge transport of small-molecule DRCN7T (D1) and its analogue DERHD7T (D2). It is revealed that, despite the subtle difference of the chemical structures, D1 exhibits higher charge mobility, the absence of shallow traps, and better photosensitivity than D2. Moreover, charge transport is favored in the out-of-plane structure within D1-based organic solar cells, while D2 prefers in-plane charge transport.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. Correlating Molecular Structures with Transport Dynamics in High-Efficiency Small-Molecule Organic Photovoltaics.

    PubMed

    Peng, Jiajun; Chen, Yani; Wu, Xiaohan; Zhang, Qian; Kan, Bin; Chen, Xiaoqing; Chen, Yongsheng; Huang, Jia; Liang, Ziqi

    2015-06-24

    Efficient charge transport is a key step toward high efficiency in small-molecule organic photovoltaics. Here we applied time-of-flight and organic field-effect transistor to complementarily study the influences of molecular structure, trap states, and molecular orientation on charge transport of small-molecule DRCN7T (D1) and its analogue DERHD7T (D2). It is revealed that, despite the subtle difference of the chemical structures, D1 exhibits higher charge mobility, the absence of shallow traps, and better photosensitivity than D2. Moreover, charge transport is favored in the out-of-plane structure within D1-based organic solar cells, while D2 prefers in-plane charge transport. PMID:26066398

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. Femtosecond observation of benzyne intermediates in a molecular beam: Bergman rearrangement in the isolated molecule.

    PubMed

    Diau, E W; Casanova, J; Roberts, J D; Zewail, A H

    2000-02-15

    In this communication, we report our femtosecond real-time observation of the dynamics for the three didehydrobenzene molecules (p-, m-, and o-benzyne) generated from 1,4-, 1,3-, and 1, 2-dibromobenzene, respectively, in a molecular beam, by using femtosecond time-resolved mass spectrometry. The time required for the first and the second C-Br bond breakage is less than 100 fs; the benzyne molecules are produced within 100 fs and then decay with a lifetime of 400 ps or more. Density functional theory and high-level ab initio calculations are also reported herein to elucidate the energetics along the reaction path. We discuss the dynamics and possible reaction mechanisms for the disappearance of benzyne intermediates. Our effort focuses on the isolated molecule dynamics of the three isomers on the femtosecond time scale.

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

    PubMed

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

    2012-04-28

    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 d(H···H) between the two neighbouring hydrogen atoms of the two water molecules should also be taken as a criterion, and the distance r(O···H) 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 d(H···H) and r(O···H) are small (e.g., d(H···H) < 2.0 Å and r(O···H) < 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 show that

  1. 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

  2. Detecting differential patterns of interaction in molecular pathways

    PubMed Central

    Yajima, Masanao; Telesca, Donatello; Ji, Yuan; Müller, Peter

    2015-01-01

    We consider statistical inference for potentially heterogeneous patterns of association characterizing the expression of bio-molecular pathways across different biologic conditions. We discuss a modeling approach based on Gaussian-directed acyclic graphs and provide computational and methodological details needed for posterior inference. Our application finds motivation in reverse phase protein array data from a study on acute myeloid leukemia, where interest centers on contrasting refractory versus relapsed patients. We illustrate the proposed method through both synthetic and case study data. PMID:25519431

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

    PubMed

    Kim, Yu Jin; Park, Chan Eon

    2016-04-14

    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.

  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. Molecular release from patterned nanoporous gold thin films

    NASA Astrophysics Data System (ADS)

    Kurtulus, Ozge; Daggumati, Pallavi; Seker, Erkin

    2014-05-01

    Nanostructured materials have shown significant potential for biomedical applications that require high loading capacity and controlled release of drugs. Nanoporous gold (np-Au), produced by an alloy corrosion process, is a promising novel material that benefits from compatibility with microfabrication, tunable pore morphology, electrical conductivity, well-established gold-thiol conjugate chemistry, and biocompatibility. While np-Au's non-biological applications are abundant, its performance in the biomedical field is nascent. In this work, we employ a combination of techniques including nanoporous thin film synthesis, quantitative electron microscopy, fluorospectrometry, and electrochemical surface characterization to study loading capacity and molecular release kinetics as a function of film properties and discuss underlying mechanisms. The sub-micron-thick sputter-coated nanoporous gold films provide small-molecule loading capacities up to 1.12 μg cm-2 and molecular release half-lives between 3.6 hours to 12.8 hours. A systematic set of studies reveals that effective surface area of the np-Au thin films on glass substrates plays the largest role in determining loading capacity. The release kinetics on the other hand depends on a complex interplay of micro- and nano-scale morphological features.Nanostructured materials have shown significant potential for biomedical applications that require high loading capacity and controlled release of drugs. Nanoporous gold (np-Au), produced by an alloy corrosion process, is a promising novel material that benefits from compatibility with microfabrication, tunable pore morphology, electrical conductivity, well-established gold-thiol conjugate chemistry, and biocompatibility. While np-Au's non-biological applications are abundant, its performance in the biomedical field is nascent. In this work, we employ a combination of techniques including nanoporous thin film synthesis, quantitative electron microscopy

  7. Distribution patterns of small-molecule ligands in the protein universe and implications for origin of life and drug discovery

    PubMed Central

    Ji, Hong-Fang; Kong, De-Xin; Shen, Liang; Chen, Ling-Ling; Ma, Bin-Guang; Zhang, Hong-Yu

    2007-01-01

    Background Extant life depends greatly on the binding of small molecules (such as ligands) with macromolecules (such as proteins), and one ligand can bind multiple proteins. However, little is known about the global patterns of ligand-protein mapping. Results By examining 2,186 well-defined small-molecule ligands and thousands of protein domains derived from a database of druggable binding sites, we show that a few ligands bind tens of protein domains or folds, whereas most ligands bind only one, which indicates that ligand-protein mapping follows a power law. Through assigning the protein-binding orders (early or late) for bio-ligands, we demonstrate that the preferential attachment principle still holds for the power-law relation between ligands and proteins. We also found that polar molecular surface area, H-bond acceptor counts, H-bond donor counts and partition coefficient are potential factors to discriminate ligands from ordinary molecules and to differentiate super ligands (shared by three or more folds) from others. Conclusion These findings have significant implications for evolution and drug discovery. First, the chronology of ligand-protein binding can be inferred by the power-law feature of ligand-protein mapping. Some nucleotide-containing ligands, such as ATP, ADP, GDP, NAD, FAD, dihydro-nicotinamide-adenine-dinucleotide phosphate (NDP), nicotinamide-adenine-dinucleotide phosphate (NAP), flavin mononucleotide (FMN) and AMP, are found to be the earliest cofactors bound to proteins, agreeing with the current understanding of evolutionary history. Second, the finding that about 30% of ligands are shared by two or more domains will help with drug discovery, such as in finding new functions from old drugs, developing promiscuous drugs and depending more on natural products. PMID:17727706

  8. 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

  9. 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

  10. 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.

  11. Manipulating the motion of large molecules: Information from the molecular frame

    NASA Astrophysics Data System (ADS)

    Küpper, Jochen

    2011-05-01

    Large molecules have complex potential-energy surfaces with many local minima. They exhibit multiple stereoisomers, even at the low temperatures (~1 K) in a molecular beam, with rich intra- and intermolecular dynamics. Over the last years, we have developed methods to manipulate the motion of large, complex molecules and to select their quantum states. We have exploited this state-selectivity, for example, to spatially separate individual structural isomers of complex molecules and to demonstrate unprecedented degrees of laser alignment and mixed-field orientation of these molecules. Such clean, well-defined samples strongly benefit, or simply allow, novel experiments on the dynamics of complex molecules, for instance, femtosecond pump-probe measurements, X-ray or electron diffraction of molecular ensembles (including diffraction-from-within experiments), or tomographic reconstructions of molecular orbitals. These samples could also be very advantageous for metrology applications, such as, for example, matter-wave interferometry or the search for electroweak interactions in chiral molecules. Moreover, they provide an extreme level of control for stereo-dynamically controlled reaction dynamics. We have recently exploited these state-selected and oriented samples to measure photoelectron angular distributions in the molecular frame (MFPADs) from non-resonant femtosecond-laser photoionization and using the X-ray Free-Electron-Laser LCLS. We have also investigated X-ray diffraction imaging and, using ion momentum imaging, the induced radiation damage of these samples using the LCLS. This work was carried out within a collaboration for which J. Küpper, H. Chapman, and D. Rolles are spokespersons. The collaboration consists of CFEL (DESY, MPG, University Hamburg), Fritz-Haber-Institute Berlin, MPI Nuclear Physics Heidelberg, MPG Semi-conductor Lab, Aarhus University, FOM AMOLF Amsterdam, Lund University, MPI Medical Research Heidelberg, TU Berlin, Max Born Institute

  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. Beyond Tissue Injury—Damage-Associated Molecular Patterns, Toll-Like Receptors, and Inflammasomes Also Drive Regeneration and Fibrosis

    PubMed Central

    2014-01-01

    Tissue injury initiates an inflammatory response through the actions of immunostimulatory molecules referred to as damage-associated molecular patterns (DAMPs). DAMPs encompass a group of heterogenous molecules, including intracellular molecules released during cell necrosis and molecules involved in extracellular matrix remodeling such as hyaluronan, biglycan, and fibronectin. Kidney-specific DAMPs include crystals and uromodulin released by renal tubular damage. DAMPs trigger innate immunity by activating Toll-like receptors, purinergic receptors, or the NLRP3 inflammasome. However, recent evidence revealed that DAMPs also trigger re-epithelialization upon kidney injury and contribute to epithelial-mesenchymal transition and, potentially, to myofibroblast differentiation and proliferation. Thus, these discoveries suggest that DAMPs drive not only immune injury but also kidney regeneration and renal scarring. Here, we review the data from these studies and discuss the increasingly complex connection between DAMPs and kidney diseases. PMID:24762401

  14. Exploring the aqueous vertical ionization of organic molecules by molecular simulation and liquid microjet photoelectron spectroscopy.

    PubMed

    Tentscher, Peter R; Seidel, Robert; Winter, Bernd; Guerard, Jennifer J; Arey, J Samuel

    2015-01-01

    To study the influence of aqueous solvent on the electronic energy levels of dissolved organic molecules, we conducted liquid microjet photoelectron spectroscopy (PES) measurements of the aqueous vertical ionization energies (VIEaq) of aniline (7.49 eV), veratrole alcohol (7.68 eV), and imidazole (8.51 eV). We also reanalyzed previously reported experimental PES data for phenol, phenolate, thymidine, and protonated imidazolium cation. We then simulated PE spectra by means of QM/MM molecular dynamics and EOM-IP-CCSD calculations with effective fragment potentials, used to describe the aqueous vertical ionization energies for six molecules, including aniline, phenol, veratrole alcohol, imidazole, methoxybenzene, and dimethylsulfide. Experimental and computational data enable us to decompose the VIEaq into elementary processes. For neutral compounds, the shift in VIE upon solvation, ΔVIEaq, was found to range from ≈-0.5 to -0.91 eV. The ΔVIEaq was further explained in terms of the influence of deforming the gas phase solute into its solution phase conformation, the influence of solute hydrogen-bond donor and acceptor interactions with proximate solvent molecules, and the polarization of about 3000 outerlying solvent molecules. Among the neutral compounds, variability in ΔVIEaq appeared largely controlled by differences in solute-solvent hydrogen-bonding interactions. Detailed computational analysis of the flexible molecule veratrole alcohol reveals that the VIE is strongly dependent on molecular conformation in both gas and aqueous phases. Finally, aqueous reorganization energies of the oxidation half-cell ionization reaction were determined from experimental data or estimated from simulation for the six compounds aniline, phenol, phenolate, veratrole alcohol, dimethylsulfide, and methoxybenzene, revealing a surprising constancy of 2.06 to 2.35 eV. PMID:25516011

  15. The Correlation of Physical Properties of Organic Molecules with Computed Molecular Surface Areas

    NASA Astrophysics Data System (ADS)

    Mebane, Robert C.; Schanley, Shannon A.; Rybolt, Thomas R.; Bruce, Chrystal D.

    1999-05-01

    Considerable interest has been shown in the calculation of molecular surface areas because molecular behavior is influenced by the outer surface of molecules. The objective of this paper is to show that a student's understanding of molecular properties can be enhanced with the study of molecular surface areas obtained from readily available molecular modeling software. We develop correlations using molecular surface areas (A), or solvent-accessible surface areas (S), for various organic compounds and a variety of physical properties that are sensitive to intermolecular forces of attraction. For n-alkanes, heat of vaporization (DHvap) and the ratio of critical temperature to the square root of critical pressure (Tc/Pc0.5) give linear relationships with A. A linear correlation is also observed between the logarithm of molal aqueous solubility (ln Sol) and the S of ketones and ethyl esters. Distinct curves are obtained when the boiling points of n-alkanes and alcohols are plotted versus their respective solvent-accessible surface areas. The alcohol curve tends to converge with the n-alkane curve with increasing surface area, demonstrating the increasing hydrocarbon contribution to the boiling point of alcohols.

  16. Patterned domains of supported phospholipid bilayer using microcontact printing of Pll-g-PEG molecules.

    PubMed

    Chalmeau, Jerome; le Grimellec, Christian; Sternick, John; Vieu, Christophe

    2012-01-01

    In this work, we propose a reliable microcontact printing (μCP) process for generating Patterned Supported Phospholipids Bilayer (P-SPB) confined by Poly-L-(lysine)-grafted-polyethylene(glycol) (Pll-g-PEG) molecular barriers. The efficiency of Pll-g-PEG for inhibiting the fusion process of incubated liposome was first analyzed by Quartz Micro Balance (QCM) measurements. The quality and stability of Pll-g-PEG patterns were then both verified by fluorescence microscopy and Atomic Force Microscopy (AFM) in liquid media. The micro domains of P-SPB produced were stable in liquid environment during several weeks and also during AFM imaging. This exceptional stability is a clear improvement compared to previous studies involving proteins as confinement barriers.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Molecular spectroscopy for ground-state transfer of ultracold RbCs molecules.

    PubMed

    Debatin, Markus; Takekoshi, Tetsu; Rameshan, Raffael; Reichsöllner, Lukas; Ferlaino, Francesca; Grimm, Rudolf; Vexiau, Romain; Bouloufa, Nadia; Dulieu, Olivier; Nägerl, Hanns-Christoph

    2011-11-14

    We perform one- and two-photon high resolution spectroscopy on ultracold samples of RbCs Feshbach molecules with the aim to identify a suitable route for efficient ground-state transfer in the quantum-gas regime to produce quantum gases of dipolar RbCs ground-state molecules. One-photon loss spectroscopy allows us to probe deeply bound rovibrational levels of the mixed excited (A(1)Σ(+)-b(3)Π)0(+) molecular states. Two-photon dark state spectroscopy connects the initial Feshbach state to the rovibronic ground state. We determine the binding energy of the lowest rovibrational level |v'' = 0, J'' = 0> of the X(1)Σ(+) ground state to be D = 3811.5755(16) cm(-1), a 300-fold improvement in accuracy with respect to previous data. We are now in the position to perform stimulated two-photon Raman transfer to the rovibronic ground state. PMID:21853182

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. [DAMPs (damage-associated molecular patterns) and inflammation].

    PubMed

    Ooboshi, Hiroaki; Shichita, Takashi

    2016-04-01

    Post-ischemic inflammation is re-appraised as an important player in the progression of ischemic stroke. Activation of inflammatory cells via Toll-like receptor 2 (TLR2) and TLR4 is caused by several damage-associated molecular patterns (DAMPs), including high mobility group box-1 (HMGB-1) and heat shock proteins. We have recently found that peroxiredoxin (Prx) is one of the strong DAMPs and activates infiltrating macrophages in brain ischemia. We have also found that interleukin-23 (IL-23) from the activated macrophages stimulates γδT cells which release IL-17, thereby causing the delayed expansion of infarct lesions. Further investigation of the innate immune response would lead to development of novel stroke treatment with a broad therapeutic time window. PMID:27333742

  12. Localization of molecules with restricted patterns of expression in morphogenesis: an immunohistochemical approach.

    PubMed

    Thibodeau, A; Duchaine, J; Simard, J L; Vincent, M

    1989-06-01

    In a search for molecules with restricted patterns of expression during development, monoclonal antibodies were raised against different transitory structures of the chick embryo. Mice were immunized with cell suspensions from lightly homogenized embryonic tissues explanted from morphogenetically active regions. A convenient immunohistochemical assay was used to screen the hybridoma supernatants on a large scale. It relied on the use of poly(ethylene glycol) as embedding medium. Its water miscibility allowed, in a one-step incubation with antibody-containing supernatants, the dewaxing and rehydration of the tissue sections as well as antibody binding. We report here the usefulness of this approach in selecting monoclonals with unique patterns of immunoreactivity. In this study, cephalic neural crest cells in early or late phase of migration, together with their surrounding tissues, were used as immunogens. The monoclonal antibodies obtained have been classified into regional, cell-lineage, cell-cycle or extracellular material-associated markers. The information provided by the direct visualization of the immunoreactivity of the various monoclonal antibodies on tissue sections, as early as the first round of screening, allows rapid determination of the subsequent strategy to be followed for further characterization of the individual markers.

  13. 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 ...

  14. 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

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

    PubMed

    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

  16. 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

  17. Single molecule vibrationally mediated chemistry. Towards state-specific strategies for molecular handling

    NASA Astrophysics Data System (ADS)

    Pascual, J. I.

    2005-08-01

    Tunnelling electrons may scatter inelastically with an adsorbate, releasing part of their energy through the excitation of molecular vibrations. The resolution of inelastic processes with a low temperature scanning tunnelling microscope (STM) provides a valuable tool to chemically characterize single adsorbates and their adsorption mechanisms. Here, we present a molecular scale picture of single molecule vibrational chemistry, as resolved by STM. To understand the way a reaction proceed it is needed knowledge about both the excitation and damping of a molecular vibration. The excitation is mediated by the specific coupling between electronic molecular resonances present at the Fermi level and vibrational states of the adsorbate. Thus, the two-dimensional mapping of the inelastic signal with an STM provides the spatial distribution of the adsorbate electronic states (near the Fermi level) which are predominantly coupled to the particular vibrational mode observed. The damping of the vibration follows a competition between different mechanisms, mediated via the creation of electron-hole pairs or via anharmonic coupling between vibrational states. This latter case give rise to effective energy transfer mechanisms which eventually may focus vibrational energy in a specific reaction coordinate. In this single-molecule work-bench, STM provides alternative tools to understand reactivity in the limit of low excitation rate, which demonstrate the existence of state-specific excitation strategies which may lead to selectivity in the product of a reaction. The author acknowledges his co-workers in the work presented here, H. Conrad, N. Lorente, H.-P. Rust, and Z. Song, as well as collaborations with J. Gómez Herrero, J.J. Jackiw, D. Sánchez-Portal and P.S. Weiss.

  18. Direct observation of molecular orbitals in an individual single-molecule magnet Mn12 on Bi(111).

    PubMed

    Sun, Kai; Park, Kyungwha; Xie, Jiale; Luo, Jiyong; Yuan, Hongkuan; Xiong, Zuhong; Wang, Junzhong; Xue, Qikun

    2013-08-27

    Single-molecule nanomagnets have unique quantum properties, and their potential applications require characterization and accessibility of individual single-molecule magnets on various substrates. We develop a gentle tip-deposition method to bring individual prototype single-molecule magnets, manganese-12-acetate (Mn12) molecules, onto the semimetallic Bi(111) surface without linker molecules, using low-temperature scanning tunneling microscopy. We are able to identify both the almost flat-lying and side-lying orientations of Mn12 molecules at 4.5 K. Energy-resolved spectroscopic mapping enables the first observation of several molecular orbitals of individual Mn12 molecules in real space, which is consistent with density functional theory calculations. Both experimental and theoretical results suggest that an energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the almost flat-lying Mn12 is only 40% of such a gap for an isolated (free) Mn12 molecule, which is caused by charge transfer from the metallic surface states of Bi to the Mn12. Despite the reduction of this gap, STM images show that the local lattices of Bi(111) covered with Mn12 remain essentially intact, indicating that Mn12-Bi interactions are not strong. Our findings open an avenue to address directly the local structural and electronic properties of individual single-molecule magnets on solid substrates.

  19. 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.

  20. 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.

  1. Extracellular matrix molecules exhibit unique expression pattern in the climbing fiber-generating precerebellar nucleus, the inferior olive.

    PubMed

    Kecskes, S; Gaál, B; Rácz, É; Birinyi, A; Hunyadi, A; Matesz, C

    2015-01-22

    Extracellular matrix (ECM) accumulates around different neuronal compartments of the central nervous system (CNS) or appears in diffuse reticular form throughout the neuropil. In the adult CNS, the perineuronal net (PNN) surrounds the perikarya and dendrites of various neuron types, whereas the axonal coats are aggregations of ECM around the individual synapses, and the nodal ECM is localized at the nodes of Ranvier. Previous studies in our laboratory demonstrated on rats that the heterogeneous distribution and molecular composition of ECM is associated with the variable cytoarchitecture and hodological organization of the vestibular nuclei and may also be related to their specific functions in gaze and posture control as well as in the compensatory mechanisms following vestibular lesion. Here, we investigated the ECM expression pattern in the climbing fiber-generating inferior olive (IO), which is functionally related to the vestibular nuclei. By using histochemical and immunohistochemical methods, the most characteristic finding was the lack of PNNs, presumably due to the absence of synapses on the perikarya and proximal dendrites of IO neurons. On the other hand, the darkly stained dots or ring-like structures in the neuropil might represent the periaxonal coats around the axon terminals of olivary synaptic glomeruli. We have observed positive ECM reaction for the hyaluronan, tenascin-R, hyaluronan and proteoglycan link protein 1 (HAPLN1) and various chondroitin sulfate proteoglycans. The staining intensity and distribution of ECM molecules revealed a number of differences between the functionally different subnuclei of IO. We hypothesized that the different molecular composition and intensity differences of ECM reaction is associated with different control mechanisms of gaze and posture control executed by the visuomotor-vestibular, somatosensory and integrative subnuclei of the IO.

  2. 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.

  3. Electron capture from a hydrogen molecule at a fixed orientation of the molecular axis

    NASA Astrophysics Data System (ADS)

    Deb, N. C.; Jain, A.; McGuire, J. H.

    1988-10-01

    Electron capture in fast-proton-H2 collisions has been reexamined in the Brinkman-Kramers approximation. The interference, first noted by T. F. Tuan and E. Gerjuoy [Phys. Rev. 117, 756 (1960)], between two capture amplitudes associated with two centers in the molecule is found to be more pronounced at fixed orientations of the molecular axis as compared to the results obtained by averaging over all orientations. This interference effect varies significantly with the orientations of the molecule. For example, in a certain angular range the number of oscillations in the differential cross sections (DCS) is maximum at θρ=90°, φρ=0°, where θρ and φρ are the polar and azimuthal angles, respectively, of the molecular axis with respect to the incident-beam direction. The number of oscillations of the DCS decreases (i) as impact energy decreases at a fixed value of orientation and (ii) as the orientation changes from the perpendicular position (θρ=90°, φρ=0°) to other orientations for a fixed proton energy. This interference effect has not yet been observed experimentally.

  4. A molecular-beacon-based screen for small molecule inhibitors of miRNA maturation.

    PubMed

    Bose, Debojit; Jayaraj, Gopal Gunanathan; Kumar, Santosh; Maiti, Souvik

    2013-05-17

    miRNAs are small non-coding RNAs that regulate about 60% of mammalian genes by modulating their transcript levels. Network scale studies of miRNA-mediated regulatory circuits demonstrate the central importance of this class of small RNA in the maintenance of biological robustness. More recently, several reports have described the deregulation of numerous miRNA to be causally associated with many diseases, including cancer. These studies have highlighted the potential for development of therapeutic modalities against miRNA. Previous screening protocols, for small molecules targeting miRNA function, are either costly or technically too complex to be applied in a high-throughput manner in standard chemical laboratories. We describe a simple in vitro screening method using a DNA-based molecular beacon that overcomes the limitations associated with earlier screens. We used this method to identify inhibitors of miR-27a function from a library of 14 aminoglycosides as a pilot study. Inhibitory molecules identified were further scrutinized to identify the validity of screen. With this proof of concept we illustrate the utility of a scalable molecular-beacon-based screening strategy for miRNA inhibitors.

  5. 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.

  6. Native molecular state of adeno-associated viral vectors revealed by single-molecule sequencing.

    PubMed

    Kapranov, Philipp; Chen, Lingxia; Dederich, Debra; Dong, Biao; He, Jie; Steinmann, Kathleen E; Moore, Andrea R; Thompson, John F; Milos, Patrice M; Xiao, Weidong

    2012-01-01

    The single-stranded genome of adeno-associated viral (AAV) vectors is one of the key factors leading to slow-rising but long-term transgene expression kinetics. Previous molecular studies have established what is now considered a textbook molecular model of AAV genomes with two copies of inverted tandem repeats at either end. In this study, we profiled hundreds of thousands of individual molecules of AAV vector DNA directly isolated from capsids, using single-molecule sequencing (SMS), which avoids any intermediary steps such as plasmid cloning. The sequence profile at 3' ends of both the regular and oversized vector did show the presence of an inverted terminal repeat (ITR), which provided direct confirmation that AAV vector packaging initiates from its 3' end. Furthermore, the vector 5'-terminus profile showed inconsistent termination for oversized vectors. Such incomplete vectors would not be expected to undergo canonical synthesis of the second strand of their genomic DNA and thus could function only via annealing of complementary strands of DNA. Furthermore, low levels of contaminating plasmid DNA were also detected. SMS may become a valuable tool during the development phase of vectors that are candidates for clinical use and for facilitating/accelerating studies on vector biology. PMID:21875357

  7. Molecular ions and protonated molecules observed in the atmospheric solids analysis probe analysis of steroids.

    PubMed

    Ray, Andrew D; Hammond, Janet; Major, Hilary

    2010-01-01

    Atmospheric pressure chemical ionisation (APCI) has often been used to ionise steroids in mass spectrometry, usually when interfaced to high-performance liquid chromatography (HPLC). However, in positive ion mode, a dehydrated protonated molecule is often observed with a loss of structural information. The recently introduced technique of atmospheric solids analysis probe (ASAP) has the advantage that the sample can be analysed directly and does not need to be interfaced to HPLC. Existing ionisation sources such as direct analysis in real time (DART) and desorption electrospray ionisation (DESI) have shown the advantage of direct analysis techniques in a variety of applications. ASAP can be performed on commercial atmospheric pressure ionisation (API) mass spectrometers with only simple modifications to API sources. The samples are vaporised by hot nitrogen gas from the electrospray desolvation heater and ionised by a corona discharge. A range of commercially available steroids were analysed by ASAP to investigate the mechanism of ionisation. ASAP analysis of steroids generally results in the formation of the parent molecular ion as either the radical cation M+* or the protonated molecule MH+. The formation of the protonated molecule is a result of proton transfer from ionised water clusters in the source. However, if the source is dry, then formation of the radical cation is the primary ionisation mechanism.

  8. 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

  9. Small-molecule G-quadruplex interactions: Systematic exploration of conformational space using multiple molecular dynamics.

    PubMed

    Husby, Jarmila; Todd, Alan K; Platts, James A; Neidle, Stephen

    2013-12-01

    G-quadruplexes are higher-order four-stranded structures formed from repetitive guanine-containing tracts in nucleic acids. They comprise a core of stacked guanine-quartets linked by loops of length and sequence that vary with the context in which the quadruplex sequence occurs. Such sequences can be found in a number of genomic environments; at the telomeric ends of eukaryotic chromosomes, in promoter regions, in untranslated sequences and in open reading frames. Quadruplex formation can inhibit telomere maintenance, transcription and translation, especially when enhanced by quadruplex-binding small molecules, and quadruplex targeting is currently of considerable interest. The available experimental structural data shows that quadruplexes can have high conformational flexibility, especially in loop regions, which has hampered attempts to use high-throughput docking to find quadruplex-binding small-molecules with new scaffolds or to optimize existing ones with structure-based design methods. An approach to overcome the challenge of quadruplex conformational flexibility is presented here, which uses a combined multiple molecular dynamics and sampling approach. Two test small molecules have been used, RHPS4 and pyridostatin, which themselves have contrasting degrees of conformational flexibility.

  10. Patterning nanostructured, synthetic, polymeric receptors by simultaneous projection photolithography, nanomolding, and molecular imprinting.

    PubMed

    Linares, Ana V; Falcimaigne-Cordin, Aude; Gheber, Levi A; Haupt, Karsten

    2011-08-22

    Microscope projection photolithography is combined with nanomolding and molecular imprinting for the fast microfabrication of molecularly imprinted polymer (MIP) arrays in the form of micrometric islands of nanofilaments. Dot diameters from 70-90 μm are easily obtained using a 10× objective and a photomask carrying the desired pattern. The dots are composed of parallel nanofilaments of a high aspect ratio, 150 nm in diameter and several micrometers in length, which are obtained through a nanomolding procedure on porous alumina. The arrays are molecularly imprinted with the small molecule fluorescein or with the protein myoglobin. The fluorescein MIP arrays are able to specifically recognize their target, as demonstrated by fluorescence microscopy. A four-fold increase in binding capacity and imprinting factor (IF = 13) is obtained compared to non-nanostructured porous dots. Imprinting of the nanofilament arrays with the protein myoglobin as the template is also possible and allows for a high imprinting factor of 4.3. Such nanostructured microarrays of synthetic receptors obtained by projection photolithography have great potential in biosensor and biochip development.

  11. Molecular features determining different partitioning patterns of papain and bromelain in aqueous two-phase systems.

    PubMed

    Rocha, Maria Victoria; Nerli, Bibiana Beatriz

    2013-10-01

    The partitioning patterns of papain (PAP) and bromelain (BR), two well-known cysteine-proteases, in polyethyleneglycol/sodium citrate aqueous two-phase systems (ATPSs) were determined. Polyethyleneglycols of different molecular weight (600, 1000, 2000, 4600 and 8000) were assayed. Thermodynamic characterization of partitioning process, spectroscopy measurements and computational calculations of protein surface properties were also carried out in order to explain their differential partitioning behavior. PAP was observed to be displaced to the salt-enriched phase in all the assayed systems with partition coefficients (KpPAP) values between 0.2 and 0.9, while BR exhibited a high affinity for the polymer phase in systems formed by PEGs of low molecular weight (600 and 1000) with partition coefficients (KpBR) values close to 3. KpBR values resulted higher than KpPAP in all the cases. This difference could be assigned neither to the charge nor to the size of the partitioned biomolecules since PAP and BR possess similar molecular weight (23,000) and isoelectric point (9.60). The presence of highly exposed tryptophans and positively charged residues (Lys, Arg and His) in BR molecule would be responsible for a charge transfer interaction between PEG and the protein and, therefore, the uneven distribution of BR in these systems.

  12. Molecular Spectroscopy in Space: Discovering New Molecules from Line Surveys and Laboratory Spectroscopy

    NASA Astrophysics Data System (ADS)

    Cernicharo, Jose

    2016-06-01

    The increasing sensitivity offered by the new generation of radio astronomical receivers and radio telescopes (single dishes and radio interferometers) has provided an enormous impact in our capacity to study the molecular content of interstellar and circumstellar clouds. Astronomers face now the challenging problem of interpreting the thousands of lines detected in hot cores which arise from isotopologues and vibrationally excited states of most known molecules. Although all strong features have been already assigned to abundant species, many of the lines still pending to be assigned could arise from very abundant molecular species having low dipole moment and/or very large partition functions. The only way to address this problem in astrophysics is through a close collaboration between astrophysicists and laboratory spectroscopists. In this talk I am going to present the results obtained over the last 10 years in interpreting the line surveys of Orion gathered with the 30m IRAM radio telescope and with ALMA. The most recent molecule found in this cloud is methyl isocyanate, CH3NCO, for which near 400 lines have been found in Oriona in the 80-280 GHz domain. This molecule has an abundance only a factor 5-20 below that of the well-known species HNCO and CH3CN. The molecule has been also found towards the giant cloud SgrB2b in the galactic center. Finally, I will present the case of the submillimeter spectrum of the carbon-rich evolved star IRC+10216 in which we have recently found Si2C with an abundance similar to SiC2. Our recent ALMA observations in a narrow band of 20 GHz around 265 GHz show near 200 features corresponding to the J=3-2 transition of hot HCN (vibrational levels up to 11000 cm-1). In addition to HCN lines, a forest of several hundreds of U lines dominates the spectrum. Most of these lines arise from molecules that condensate very quickly into dust grainsc. aJ. Cernicharo, Z.Kisiel, B.Tercero, et al., A&A 587, L4 (2016). bD.T. Halfen, V

  13. 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

  14. Developer molecular size dependence of pattern formation of polymer type electron beam resists with various molecular weights

    NASA Astrophysics Data System (ADS)

    Takayama, Tomohiro; Asada, Hironori; Kishimura, Yukiko; Ochiai, Shunsuke; Hoshino, Ryoichi; Kawata, Atsushi

    2016-05-01

    The sensitivity and the resolution are affected by not only the nature of the resist such as a chemical structure and a molecular weight but also the developing process such as a developer molecular size. Exposure characteristics of positive-tone polymer resists having various molecular weights (Mw's) ranging from 60 k to 500 k are investigated using different ester solvents as a developer. The line-and-space (L/S) patterns are exposed by the electron beam writing system with an acceleration voltage of 50 kV and the samples are developed by amyl acetate, hexyl acetate and heptyl acetate. The pattern shape becomes better and the surface of the resist also becomes smoother with increasing developer molecular size, though the exposure dose required for the formation of the L/S pattern increases. The dose margin of pattern formation is also wider in all the resists having the different molecular weights. The dissolution in the unexposed portions of the 60k-Mw resist for heptyl acetate is reduced significantly compared with those for amyl acetate and hexyl acetate. The improvement of the pattern shape and the increasing of dose margin are remarkable in the low molecular weight resist. The 3σ of line width roughness tends to be smaller in the higher molecular weight resist and with the larger molecular size developer. Exposure experiment of the 35 nm pitch pattern using the 500k-Mw resist developed at the room temperature is presented.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Catalytic and molecular beacons for amplified detection of metal ions and organic molecules with high sensitivity.

    PubMed

    Zhang, Xiao-Bing; Wang, Zidong; Xing, Hang; Xiang, Yu; Lu, Yi

    2010-06-15

    The catalytic beacon has emerged as a general platform for sensing metal ions and organic molecules. However, few reports have taken advantage of the true potential of catalytic beacons in signal amplification through multiple enzymatic turnovers, as existing designs require either equal concentrations of substrate and DNAzyme or an excess of DNAzyme in order to maintain efficient quenching, eliminating the excess of substrate necessary for multiple turnovers. On the basis of the large difference in the melting temperatures between the intramolecular molecular beacon stem and intermolecular products of identical sequences, we here report a general strategy of catalytic and molecular beacon (CAMB) that combines the advantages of the molecular beacon for highly efficient quenching with the catalytic beacon for amplified sensing through enzymatic turnovers. Such a CAMB design allows detection of metal ions such as Pb(2+) with a high sensitivity (LOD = 600 pM). Furthermore, the aptamer sequence has been introduced into DNAzyme to use the modified CAMB for amplified sensing of adenosine with similar high sensitivity. These results together demonstrate that CAMB provides a general platform for amplified detection of a wide range of targets.

  20. 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.

  1. 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.

  2. 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

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

    PubMed Central

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

    2016-01-01

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

  4. 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.

  5. Operation mechanism of rotary molecular motor F1 probed by single-molecule techniques

    NASA Astrophysics Data System (ADS)

    Iino, Ryota

    2013-03-01

    F1 is a rotary motor protein. Three catalytic β - subunitsinthestator 33ring are torque generators, and rotate the rotor γ-subunit by sequential and cooperative conformational changes coupled with adenosine triphosphate (ATP) hydrolysis reaction. F1 shows remarkable performances such as rotation rate faster than 10,000 rpm, high reversibility and efficiency in chemo-mechanical energy conversion. I will introduce basic characteristics of F1 revealed by single-molecule imaging and manipulation techniques based on optical microscopy and high-speed atomic force microscopy. I will also discuss the possible operation mechanism behind the F1, along with structurally-related hexameric ATPases, also mentioning the possibility of generating hybrid molecular motors.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. Ultraviolet Pretreatment of Titanium Dioxide and Tin-Doped Indium Oxide Surfaces as a Promoter of the Adsorption of Organic Molecules in Dry Deposition Processes: Light Patterning of Organic Nanowires.

    PubMed

    Oulad-Zian, Youssef; Sanchez-Valencia, Juan R; Parra-Barranco, Julian; Hamad, Said; Espinos, Juan P; Barranco, Angel; Ferrer, Javier; Coll, Mariona; Borras, Ana

    2015-08-01

    In this article we present the preactivation of TiO2 and ITO by UV irradiation under ambient conditions as a tool to enhance the incorporation of organic molecules on these oxides by evaporation at low pressures. The deposition of π-stacked molecules on TiO2 and ITO at controlled substrate temperature and in the presence of Ar is thoroughly followed by SEM, UV-vis, XRD, RBS, and photoluminescence spectroscopy, and the effect is exploited for the patterning formation of small-molecule organic nanowires (ONWs). X-ray photoelectron spectroscopy (XPS) in situ experiments and molecular dynamics simulations add critical information to fully elucidate the mechanism behind the increase in the number of adsorption centers for the organic molecules. Finally, the formation of hybrid organic/inorganic semiconductors is also explored as a result of the controlled vacuum sublimation of organic molecules on the open thin film microstructure of mesoporous TiO2.

  12. Ultraviolet Pretreatment of Titanium Dioxide and Tin-Doped Indium Oxide Surfaces as a Promoter of the Adsorption of Organic Molecules in Dry Deposition Processes: Light Patterning of Organic Nanowires.

    PubMed

    Oulad-Zian, Youssef; Sanchez-Valencia, Juan R; Parra-Barranco, Julian; Hamad, Said; Espinos, Juan P; Barranco, Angel; Ferrer, Javier; Coll, Mariona; Borras, Ana

    2015-08-01

    In this article we present the preactivation of TiO2 and ITO by UV irradiation under ambient conditions as a tool to enhance the incorporation of organic molecules on these oxides by evaporation at low pressures. The deposition of π-stacked molecules on TiO2 and ITO at controlled substrate temperature and in the presence of Ar is thoroughly followed by SEM, UV-vis, XRD, RBS, and photoluminescence spectroscopy, and the effect is exploited for the patterning formation of small-molecule organic nanowires (ONWs). X-ray photoelectron spectroscopy (XPS) in situ experiments and molecular dynamics simulations add critical information to fully elucidate the mechanism behind the increase in the number of adsorption centers for the organic molecules. Finally, the formation of hybrid organic/inorganic semiconductors is also explored as a result of the controlled vacuum sublimation of organic molecules on the open thin film microstructure of mesoporous TiO2. PMID:26168350

  13. Nontypable Haemophilus influenzae Displays a Prevalent Surface Structure Molecular Pattern in Clinical Isolates

    PubMed Central

    Mauro, Silvia; Hood, Derek W.; Viadas, Cristina; Calatayud, Laura; Morey, Pau; Servin, Alain; Liñares, Josefina; Oliver, Antonio; Bengoechea, José Antonio; Garmendia, Junkal

    2011-01-01

    Non-typable Haemophilus influenzae (NTHi) is a Gram negative pathogen that causes acute respiratory infections and is associated with the progression of chronic respiratory diseases. Previous studies have established the existence of a remarkable genetic variability among NTHi strains. In this study we show that, in spite of a high level of genetic heterogeneity, NTHi clinical isolates display a prevalent molecular feature, which could confer fitness during infectious processes. A total of 111 non-isogenic NTHi strains from an identical number of patients, isolated in two distinct geographical locations in the same period of time, were used to analyse nine genes encoding bacterial surface molecules, and revealed the existence of one highly prevalent molecular pattern (lgtF+, lic2A+, lic1D+, lic3A+, lic3B+, siaA−, lic2C+, ompP5+, oapA+) displayed by 94.6% of isolates. Such a genetic profile was associated with a higher bacterial resistance to serum mediated killing and enhanced adherence to human respiratory epithelial cells. PMID:21698169

  14. 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

  15. 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

  16. 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

  17. Small-molecule inhibitors of cathepsin L incorporating functionalized ring-fused molecular frameworks.

    PubMed

    Song, Jiangli; Jones, Lindsay M; Chavarria, Gustavo E; Charlton-Sevcik, Amanda K; Jantz, Adam; Johansen, Audra; Bayeh, Liela; Soeung, Victoria; Snyder, Lindsey K; Lade, Shawn D; Chaplin, David J; Trawick, Mary Lynn; Pinney, Kevin G

    2013-05-01

    Cathepsin L is a cysteine protease that is upregulated in a variety of malignant tumors and plays a significant role in cancer cell invasion and migration. It is an attractive target for the development of small-molecule inhibitors, which may prove beneficial as treatment agents to limit or arrest cancer metastasis. We have previously identified a structurally diverse series of thiosemicarbazone-based inhibitors that incorporate the benzophenone and thiochromanone molecular scaffolds. Herein we report an important extension of this work designed to explore fused aryl-alkyl ring molecular systems that feature nitrogen atom incorporation (dihydroquinoline-based) and carbon atom exclusivity (tetrahydronaphthalene-based). In addition, analogues that contain oxygen (chromanone-based), sulfur (thiochroman-based), sulfoxide, and sulfone functionalization have been prepared in order to further investigate the structure-activity relationship aspects associated with these compounds and their ability to inhibit cathepsins L and B. From this small-library of 30 compounds, five were found to be strongly inhibitory (IC50 <500 nM) against cathepsin L with the most active compound (7-bromodihydroquinoline thiosemicarbazone 48) demonstrating an IC50=164 nM. All of the compounds evaluated were inactive (IC50 >10,000 nM) as inhibitors of cathepsin B, thus establishing a high degree (>20-fold) of selectivity (cathepsin L vs. cathepsin B) for the most active cathepsin L inhibitors in this series.

  18. 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.

  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. 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. 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.

  2. 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...

  3. 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.

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

    NASA Astrophysics Data System (ADS)

    Obaid, R.; Leibscher, M.

    2015-02-01

    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.

  5. 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.

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

    SciTech Connect

    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.

  7. Molecular dynamics study on evaporation and reflection of monatomic molecules to construct kinetic boundary condition in vapor-liquid equilibria

    NASA Astrophysics Data System (ADS)

    Kobayashi, Kazumichi; Hori, Kazumasa; Kon, Misaki; Sasaki, Kiyofumi; Watanabe, Masao

    2016-09-01

    Using molecular dynamics simulations, the present study investigates the precise characteristics of evaporating and reflecting monatomic molecules (argon) composing a kinetic boundary condition (KBC) in a vapor-liquid equilibria. We counted the evaporating and reflecting molecules utilizing two boundaries (vapor and liquid boundaries) proposed by the previous studies (Meland et al. in Phys Fluids 16:223-243, 2004; Gu et al. in Fluid Phase Equilib 297:77-89, 2010). In the present study, we improved the method using the two boundaries incorporating the concept of the spontaneously evaporating molecular mass flux. The present method allows us to count the evaporating and reflecting molecules easily, to investigate the detail motion of the evaporating and reflecting molecules, and also to evaluate the velocity distribution function of the KBC at the vapor-liquid interface, appropriately. From the results, we confirm that the evaporating and reflecting molecules in the normal direction to the interface have slightly faster and significantly slower average velocities than that of the Maxwell distribution at the liquid temperature, respectively. Also, the stall time of the reflecting molecules at the interphase that is the region in the vicinity of the vapor-liquid interface is much shorter than those of the evaporating molecules. Furthermore, we discuss our method for constructing the KBC that incorporates condensation and evaporation coefficients. Based on these results, we suggest that the proposed method is appropriate for investigating KBC in various nonequilibrium states or multi-component systems.

  8. 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.

  9. 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

  10. 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

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

    PubMed

    Salvalaio, Marika; Rigon, Laura; 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.

  12. Assembling Gold Nanoparticle Patterns for Molecular Electronics Applications

    NASA Astrophysics Data System (ADS)

    Parodi, M. T.; Ricci, D.; Rocchia, W.; Sbrana, F.; di Zitti, E.

    2000-12-01

    A physical system where nanometer sized gold particles are embedded within an ultrathin organic film has been built by exploiting the self-ordering properties of Langmuir-Blodgett films. Dipalmitoyl-Phosphatidyl-Ethanolamine (DPPE) molecules, functionalised with gold atomic clusters, have been mixed in various proportions with cadmium arachidate and alkanes, and hence deposited onto a substrate. The conformational properties of films obtained onto mica and glass substrates have been investigated by means of atomic force microscopy and scanning electron microscopy. This study reveals many interesting features, most prominent among them the possibility to have phase-separated regions of DPPE-nanogold and organic molecules.

  13. 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

  14. 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.

  15. 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

  16. Low molecular weight molecules of oyster nacre induce mineralization of the MC3T3-E1 cells.

    PubMed

    Rousseau, Marthe; Boulzaguet, Hélène; Biagianti, Julie; Duplat, Denis; Milet, Christian; Lopez, Evelyne; Bédouet, Laurent

    2008-05-01

    The nacre layer from the pearl oyster shell is considered as a promising osteoinductive biomaterial. Nacre contains one or more signal molecules capable of stimulating bone formation. The identity and the mode of action of these molecules on the osteoblast differentiation were analyzed. Water-soluble molecules from nacre were fractionated according to dialysis, solvent extraction, and reversed-phase HPLC. The activity of a fraction composed of low molecular weight molecules in the mineralization of the MC3T3-E1 extracellular matrix was investigated. Mineralization of the preosteoblast cells was monitored according to alizarin red staining, Raman spectroscopy, scanning electron microscopy, and quantitative RT-PCR. Molecules isolated from nacre, ranging from 50 to 235 Da, induced a red alizarin staining of the preosteoblasts extracellular matrix after 16 days of culture. Raman spectroscopy demonstrated the presence of hydroxyapatite (HA) in samples treated with these molecules. Scanning electron microscopy pictures showed at the surface of the treated cells the occurrence of clusters of spherical particles resembling to HA. The treatment of cells with nacre molecules accelerated expression of collagen I and increased the mRNA expression of Runx2 and osteopontin. This study indicated that the nacre molecules efficient in bone cell differentiation are certainly different from proteins, and could be useful for in vivo bone repair.

  17. Correlation between molecular recoil and molecular orientation in collisions of symmetric top molecules with hot hydrogen atoms

    NASA Astrophysics Data System (ADS)

    Ni, C. K.; Flynn, G. W.

    1992-05-01

    Nascent Doppler profiles are measured for hot H-atom—molecule collisions in numerous rotational sublevels of two symmetric tops. Linewidths for CDF 3 molecules due to hot H-atom collisions increase with the quantum number K. In contrast, linewidths for CD 3F molecules due to hot H-atom collisions decrease with the quantum number K. A simple model is proposed to explain the K dependent linewidths.

  18. 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.

  19. PDMS-glass bonding using grafted polymeric adhesive--alternative process flow for compatibility with patterned biological molecules.

    PubMed

    Beh, Cyrus Weijie; Zhou, Weizhuang; Wang, Tza-Huei

    2012-10-21

    We report a novel modification of silicone elastomer polydimethylsiloxane (PDMS) with a polymer graft that allows interfacial bonding between an elastomer and glass substrate to be performed without exposure of the substrate to harsh treatment conditions, such as 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.

  20. 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

  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. A Simple Molecular Orbital Treatment of the Barrier to Internal Rotation in the Ethane Molecule

    NASA Astrophysics Data System (ADS)

    Smith, Derek W.

    1998-07-01

    The origin of the barrier to internal rotation in the ethane molecule is explored in terms of elementary molecular orbital (MO) considerations. Emphasis is placed on the antibonding effect, i.e. the result that an antibonding MO is more destabilized than its bonding counterpart is stabilized, relative to the parent atomic orbitals (AOs). It is shown that, in the case of two equivalent AOs, this effect is approximately proportional to the square of the overlap integral. By constructing the ethane Mos from those of two methyl fragments, it is shown that the most important orbital energy changes consequent upon rotation about the C-C bond can be expressed in terms of the antibonding effect arising from the filled twofold-degenerate p-bonding and -antibonding MOs. This can be reduced to the dependence on the rotation angle of the vicinal H-H overlap integrals, which are calculated explicitly, showing that the antibonding effect is minimised in the staggered conformation. A letter from Lawrence J. Sacks in our April 2000 issue addresses the above.

  3. 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

  4. Real-space imaging of molecular structure and chemical bonding by single-molecule inelastic tunneling probe.

    PubMed

    Chiang, Chi-lun; Xu, Chen; Han, Zhumin; Ho, W

    2014-05-23

    The arrangement of atoms and bonds in a molecule influences its physical and chemical properties. The scanning tunneling microscope can provide electronic and vibrational signatures of single molecules. However, these signatures do not relate simply to the molecular structure and bonding. We constructed an inelastic tunneling probe based on the scanning tunneling microscope to sense the local potential energy landscape of an adsorbed molecule with a carbon monoxide (CO)-terminated tip. The skeletal structure and bonding of the molecule are revealed from imaging the spatial variations of a CO vibration as the CO-terminated tip probes the core of the interactions between adjacent atoms. An application of the inelastic tunneling probe reveals the sharing of hydrogen atoms among multiple centers in intramolecular and extramolecular bonding.

  5. Specific features of propagation of femtosecond laser pulses through a molecular gaseous medium under conditions of efficient alignment of molecules

    SciTech Connect

    Gulyaev, A V; Tikhonova, O V

    2013-07-31

    The propagation of femtosecond laser pulses in a molecular gaseous medium is studied with the rotational dynamics of molecules under the action of these pulses taken into account. Based on the simultaneous numerical solution of the wave equation describing the laser pulse evolution and the Schroedinger equation that determines the quantum state evolution of the medium molecules, the rotational dynamics of molecules in the laser field and the laser pulse evolution are analysed with their mutual influence taken into account. Efficient dynamic alignment of molecules along the direction of laser radiation polarisation is observed, which causes variation in the spatiotemporal pulse profile, as well as significant broadening and deformation of its spectrum in the course of propagation through the medium. The physical mechanisms of the observed phenomena are analysed by using the approximate analytical solution of the problem, derived for the case of preliminary excitation of the medium by a pump pulse (the pump-probe scheme). (nonlinear optical phenomena)

  6. 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.'

  7. Continuously adjustable, molecular-sieving “gate” on 5A zeolite for distinguishing small organic molecules by size

    DOE PAGESBeta

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

    2015-09-11

    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 weremore » effectively distinguished via appropriate misalignment. Lastly, this novel concept may have great potential to fill the pore size gaps of the zeolite family and realize size-selective adsorption separation.« less

  8. Continuously adjustable, molecular-sieving “gate” on 5A zeolite for distinguishing small organic molecules by size

    SciTech Connect

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

    2015-09-11

    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. Lastly, this novel concept may have great potential to fill the pore size gaps of the zeolite family and realize size-selective adsorption separation.

  9. 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

  10. Different cytokeratin and neuronal cell adhesion molecule staining patterns in focal nodular hyperplasia and hepatic adenoma and their significance

    PubMed Central

    Iyer, Anita; Robert, Marie E.; Bifulco, Carlo B.; Salem, Ronald R.; Jain, Dhanpat

    2013-01-01

    Summary Differentiating focal nodular hyperplasia from hepatic adenoma can be challenging. Cytokeratin 7, neuronal cell adhesion molecule, and cytokeratin 19 are differentially expressed in hepatocytes, biliary epithelium, and possibly hepatic progenitor/stem cells. CD34 is known to have altered expression patterns in the hepatic endothelium in conditions associated with abnormal perfusion and in hepatocellular carcinoma. The purpose of this study was to examine the expression pattern of these markers in focal nodular hyperplasia and hepatic adenoma and assess their diagnostic use. Ten resection specimens each of hepatic adenoma and focal nodular hyperplasia (including a case of telangiectatic focal nodular hyperplasia) were selected for the study. Immunohistochemical analysis was performed using antibodies against cytokeratin 7, cytokeratin 19, neuronal cell adhesion molecule, and CD34 on formalin-fixed, paraffin-embedded sections from each case. The staining patterns and intensity for each marker were analyzed. In hepatic adenoma, the cytokeratin 7 stain revealed strong positivity in hepatocytes in patches, with a gradual decrease in the staining intensity as the cells differentiated towards mature hepatocytes. Although bile ducts were typically absent in hepatic adenoma, occasional ductules could be identified with cytokeratin 7 stain. In focal nodular hyperplasia, cytokeratin 7 showed strong staining of the biliary epithelium within the fibrous septa and staining of the peripheral hepatocytes of most lobules that was focal and weaker than hepatic adenoma. Cytokeratin 19 and neuronal cell adhesion molecule showed patchy and moderate staining in the biliary epithelium of the ductules in focal nodular hyperplasia. While in the hepatic adenoma, cytokeratin 19 showed only rare positivity in occasional cells within ductules, and neuronal cell adhesion molecule marked occasional isolated cells in the lesion. CD34 showed staining of sinusoids in the inflow areas

  11. A purification method for a molecular complex in which a scaffold molecule is fully loaded with heterogeneous molecules.

    PubMed

    Ohuchi, Shoji J; Sagawa, Fumihiko; Ohno, Hirohisa; Inoue, Tan

    2015-01-01

    An affinity resin-based pull-down method is convenient for the purification of biochemical materials. However, its use is difficult for the isolation of a molecular complex fully loaded with multiple components from a reaction mixture containing the starting materials and intermediate products. To overcome this problem, we have developed a new purification procedure that depends on sequential elimination of the residues. In practice, two affinity resins were used for purifying a triangular-shaped RNP (RNA-protein complex) consisting of three ribosomal proteins (L7Ae) bound to an RNA scaffold. First, a resin with immobilized L7Ae protein captured the incomplete RNP complexes and the free RNA scaffold. Next, another resin with an immobilized chemically modified RNA of a derivative of Box C/D motif, the binding partner of L7Ae, was used to capture free protein. The complete triangular RNP was successfully purified from the mixture by these two steps. Obviously, the purified triangular RNP displaying three protein-binding peptides exhibited an improved performance when compared with the unrefined product. Conceptually, this purification procedure should be applicable for the purification of a variety of complexes consisting of multiple components other than RNP.

  12. 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

  13. 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.

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

    PubMed

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

    2015-10-21

    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)R30°-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.

  15. [Participation of damage-associated molecular patterns in conventional treatment of cancer].

    PubMed

    Rojo-León, Verónica; Aguilar-Cázares, Dolores; Prado-García, Heriberto; Carlos-Reyes, Angeles; López-González, José Sullivan

    2012-01-01

    Cells of the innate immune system are involved in discriminating between the innocuous cell death (apoptosis) which occurs in tissues during homeostasis, and the cell death associated to tissue damage (necrosis). Recently, a new variant of apoptosis termed immunogenic apoptosis has been described. In cancer, this type of cell death has acquired great relevance. In vitro and in vivo experimental models support that radiotherapy and some chemotherapeutic drugs induce the immunogenic apoptosis of malignant cells. Dying cells express at cytoplasmic membrane or release several nuclear or intracytoplasmic molecules termed "danger signals" or damage associated molecular patterns (DAMPs). DAMPs alert the organism and play a role inducing an efficient anti-tumor immune response. In this review, the importance of cell death by immunogenic apoptosis, the cytotoxic drugs that induce this type of cell death, the biologic role of some DAMPs and their participation in the activation of the antitumor immune response, in particular in the phagocytic cell, are indicated. The goal of this information should impact in improving the participation of the immune system in the recognition and efficient elimination of the residual tumor cells and to overcome the evasion mechanisms of tumor cells. This knowledge should lead to a better control of the growth of tumors with a concomitant reduction in the tumor recurrence. Also, an increase in the survival of the cancer patients or probably their definitive cure could be reached in the future.

  16. Adenovirus-mediated gene transfer of pathogen-associated molecular patterns for cancer immunotherapy.

    PubMed

    Tosch, C; Geist, M; Ledoux, C; Ziller-Remi, C; Paul, S; Erbs, P; Corvaia, N; Von Hoegen, P; Balloul, J-M; Haegel, H

    2009-04-01

    The delivery of stimulatory signals to dendritic cells (DCs) in the tumor microenvironment could be an effective means to break tumor-induced tolerance. The work presented here evaluates the immunostimulatory properties of pathogen-associated molecular patterns (PAMPs), microbial molecules which bind Toll-like receptors and deliver activating signals to immune cells, when expressed in tumor cells using adenoviral (Ad) vectors. In vitro, transduction of A549 tumor cells with Ad vectors expressing either flagellin from Listeria monocytogenes or P40 protein from Klebsiella pneumoniae induced the maturation of human monocyte-derived DCs in co-cultures. In mixed lymphocyte reactions (MLRs), Ad-flagellin and Ad-P40 transduction of tumor cells stimulated lymphocyte proliferation and the secretion of IFN-gamma. In vivo, these vectors were used either as stand-alone immunoadjuvants injected intratumorally or as vaccine adjuvants combined with a tumor antigen-expressing vector. When Ad-PAMPs were administered intratumorally to mice bearing subcutaneous syngeneic B16F0-CAR (cocksackie-adenovirus receptor) melanomas, tumor progression was transiently inhibited by Ad-P40. In a therapeutic vaccine setting, the combination of Ad-MUC1 and Ad-PAMP vectors injected subcutaneously delayed the growth of implanted RenCa-MUC1 tumors and improved tumor rejection when compared with vaccination with Ad-MUC1 alone. These results suggest that Ad-PAMPs could be effective immunoadjuvants for cancer immunotherapy. PMID:18949016

  17. 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.

  18. 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

  19. Molecular spintronics based on single-molecule magnets composed of multiple-decker phthalocyaninato terbium(III) complex.

    PubMed

    Katoh, Keiichi; Isshiki, Hironari; Komeda, Tadahiro; Yamashita, Masahiro

    2012-06-01

    Unlike electronics, which is based on the freedom of the charge of an electron whose memory is volatile, spintronics is based on the freedom of the charge, spin, and orbital of an electron whose memory is non-volatile. Although in most GMR, TMR, and CMR systems, bulk or classical magnets that are composed of transition metals are used, this Focus Review considers the growing use of single-molecule magnets (SMMs) that are composed of multinuclear metal complexes and nanosized magnets, which exhibit slow magnetic-relaxation processes and quantum tunneling. Molecular spintronics, which combines spintronics and molecular electronics, is an emerging field of research. Using molecules is advantageous because their electronic and magnetic properties can be manipulated under specific conditions. Herein, recent developments in [LnPc]-based multiple-decker SMMs on surfaces for molecular spintronic devices are presented. First, we discuss the strategies for preparing single-molecular-memory devices by using SMMs. Next, we focus on the switching of the Kondo signal of [LnPc]-based multiple-decker SMMs that are adsorbed onto surfaces, their characterization by using STM and STS, and the relationship between the molecular structure, the electronic structure, and the Kondo resonance of [TbPc(2)]. Finally, the field-effect-transistor (FET) properties of surface-adsorbed [LnPc(2)] and [Ln(2)Pc(3)] cast films are reported, which is the first step towards controlling SMMs through their spins for applications in single-molecular memory and spintronics devices.

  20. Dynamical behavior of one-dimensional water molecule chains in zeolites: Nanosecond time-scale molecular dynamics simulations of bikitaite

    NASA Astrophysics Data System (ADS)

    Demontis, Pierfranco; Stara, Giovanna; Suffritti, Giuseppe B.

    2004-05-01

    Nanosecond scale molecular dynamics simulations of the behavior of the one-dimensional water molecule chains adsorbed in the parallel nanochannels of bikitaite, a rare lithium containing zeolite, were performed at different temperatures and for the fully and partially hydrated material. New empirical potential functions have been developed for representing lithium-water interactions. The structure and the vibrational spectrum of bikitaite were in agreement both with experimental data and Car-Parrinello molecular dynamics results. Classical molecular dynamics simulations were extended to the nanosecond time scale in order to study the flip motion of water molecules around the hydrogen bonds connecting adjacent molecules in the chains, which has been observed by NMR experiments, and the dehydration mechanism at high temperature. Computed relaxation times of the flip motion follow the Arrhenius behavior found experimentally, but the activation energy of the simulated system is slightly underestimated. Based on the results of the simulations, it may be suggested that the dehydration proceeds by a defect-driven stepwise diffusion. The diffusive mechanism appears as a single-file motion: the molecules never pass one another, even at temperatures as high as about 1000 K, nor can they switch between different channels. However, the mean square displacement (MSD) of the molecules, computed with respect to the center of mass of the simulated system, shows an irregular trend from which the single-file diffusion cannot be clearly evidenced. If the MSDs are evaluated with respect to the center of mass of the molecules hosted in each channel, the expected dependence on the square root of time finally appears.

  1. 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.

  2. 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

  3. Metallacryptate single-molecule magnets: effect of lower molecular symmetry on blocking temperature.

    PubMed

    Zaleski, Curtis M; Depperman, Ezra C; Dendrinou-Samara, Catherine; Alexiou, Maria; Kampf, Jeff W; Kessissoglou, Dimitris P; Kirk, Martin L; Pecoraro, Vincent L

    2005-09-21

    The structural characterization of complexes [Mn(II)4Mn(III)22(pdol)12(OCH3)12(O)16(N3)6] (1) and [Mn(II)4Mn(III)22(pdol)12(OCH3)12(O)16(OH)2(H3O)(OCH3)3].ClO4.5CH3OH (2), where pdol(2-) is di-2-pyridyl methanediol, reveals that each has a metallacryptand shell that encapsulates a manganese oxide core. Variable-temperature direct current magnetic susceptibility measurements on 2 indicate a paramagnetic ground state that results from an overall antiferromagnetic interaction in the cluster, with chiT values decreasing from 300 K (51.2 cm3 K mol(-1)) to 2 K (19.8 cm3 K mol(-1)). Variable-temperature alternating current magnetic susceptibility measurements imply that both 1 and 2 behave as single-molecule magnets. Fitting the frequency-dependent out-of-phase magnetic susceptibility to the Arrhenius equation yields an effective energy barrier, Ueff, to magnetization relaxation of 16.5 +/- 0.7 K (11.5 +/- 0.5 cm(-1)) for 1 and 36.2 +/- 2.0 K (25.1 +/- 1.4 cm(-1)) for 2. The larger value for 2 is in agreement with the lower molecular symmetry, larger magnetoanisotropy, and higher ground spin state of 2 compared to those of 1. This observation suggests a new strategy for increasing the blocking temperatures in high-nuclearity manganese clusters.

  4. 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

  5. Lipoteichoic acid is an important microbe-associated molecular pattern of Lactobacillus rhamnosus GG

    PubMed Central

    2012-01-01

    Background Probiotic bacteria are increasingly used as immunomodulatory agents. Yet detailed molecular knowledge on the immunomodulatory molecules of these bacteria is lagging behind. Lipoteichoic acid (LTA) is considered a major microbe-associated molecular pattern (MAMP) of Gram-positive bacteria. However, many details and quantitative data on its immune signalling capacity are still unknown, especially in beneficial bacteria. Recently, we have demonstrated that a dltD mutant of the model probiotic Lactobacillus rhamnosus GG (LGG), having modified LTA molecules, has an enhanced probiotic efficacy in a DSS-induced colitis model as compared to wild-type. Results In this study, the importance of D-alanylated and acylated LTA for the pro-inflammatory activity of LGG was studied in vitro. Purified native LTA of LGG wild-type exhibited a concentration-dependent activation of NF-κB signalling in HEK293T cells after interaction with TLR2/6, but not with TLR2 alone. Chemical deacylation of LTA interfered with the TLR2/6 interaction, while a moderate effect was observed with chemical dealanylation. Similarly, the dltD mutant of LGG exhibited a significantly reduced capacity to activate TLR2/6-dependent NF-κB signalling in a HEK293T reporter cell line compared to wild-type. In addition, the dltD mutant of LGG showed a reduced induction of mRNA of the chemokine IL-8 in the Caco-2 epithelial cell line compared to wild-type. Experiments with highly purified LTA of LGG confirmed that LTA is a crucial factor for IL-8 mRNA induction in Caco-2 epithelial cells. Chemical dealanylation and deacylation reduced IL-8 mRNA expression. Conclusions Taken together, our results indicate that LTA of LGG is a crucial MAMP with pro-inflammatory activities such as IL-8 induction in intestinal epithelial cells and NF-κB induction in HEK293T cells via TLR2/6 interaction. The lipid chains of LGG LTA are needed for these activities, while also the D-alanine substituents are important, especially

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. Comparison of DNA hydration patterns obtained using two distinct computational methods, molecular dynamics simulation and three-dimensional reference interaction site model theory.

    PubMed

    Yonetani, Yoshiteru; Maruyama, Yutaka; Hirata, Fumio; Kono, Hidetoshi

    2008-05-14

    Because proteins and DNA interact with each other and with various small molecules in the presence of water molecules, we cannot ignore their hydration when discussing their structural and energetic properties. Although high-resolution crystal structure analyses have given us a view of tightly bound water molecules on their surface, the structural data are still insufficient to capture the detailed configurations of water molecules around the surface of these biomolecules. Thanks to the invention of various computational algorithms, computer simulations can now provide an atomic view of hydration. Here, we describe the apparent patterns of DNA hydration calculated by using two different computational methods: Molecular dynamics (MD) simulation and three-dimensional reference interaction site model (3D-RISM) theory. Both methods are promising for obtaining hydration properties, but until now there have been no thorough comparisons of the calculated three-dimensional distributions of hydrating water. This rigorous comparison showed that MD and 3D-RISM provide essentially similar hydration patterns when there is sufficient sampling time for MD and a sufficient number of conformations to describe molecular flexibility for 3D-RISM. This suggests that these two computational methods can be used to complement one another when evaluating the reliability of the calculated hydration patterns. PMID:18532849

  12. Comparison of DNA hydration patterns obtained using two distinct computational methods, molecular dynamics simulation and three-dimensional reference interaction site model theory

    NASA Astrophysics Data System (ADS)

    Yonetani, Yoshiteru; Maruyama, Yutaka; Hirata, Fumio; Kono, Hidetoshi

    2008-05-01

    Because proteins and DNA interact with each other and with various small molecules in the presence of water molecules, we cannot ignore their hydration when discussing their structural and energetic properties. Although high-resolution crystal structure analyses have given us a view of tightly bound water molecules on their surface, the structural data are still insufficient to capture the detailed configurations of water molecules around the surface of these biomolecules. Thanks to the invention of various computational algorithms, computer simulations can now provide an atomic view of hydration. Here, we describe the apparent patterns of DNA hydration calculated by using two different computational methods: Molecular dynamics (MD) simulation and three-dimensional reference interaction site model (3D-RISM) theory. Both methods are promising for obtaining hydration properties, but until now there have been no thorough comparisons of the calculated three-dimensional distributions of hydrating water. This rigorous comparison showed that MD and 3D-RISM provide essentially similar hydration patterns when there is sufficient sampling time for MD and a sufficient number of conformations to describe molecular flexibility for 3D-RISM. This suggests that these two computational methods can be used to complement one another when evaluating the reliability of the calculated hydration patterns.

  13. 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.

  14. 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.

  15. A third-generation density-functional-theory-based method for calculating canonical molecular orbitals of large molecules.

    PubMed

    Hirano, Toshiyuki; Sato, Fumitoshi

    2014-07-28

    We used grid-free modified Cholesky decomposition (CD) to develop a density-functional-theory (DFT)-based method for calculating the canonical molecular orbitals (CMOs) of large molecules. Our method can be used to calculate standard CMOs, analytically compute exchange-correlation terms, and maximise the capacity of next-generation supercomputers. Cholesky vectors were first analytically downscaled using low-rank pivoted CD and CD with adaptive metric (CDAM). The obtained Cholesky vectors were distributed and stored on each computer node in a parallel computer, and the Coulomb, Fock exchange, and pure exchange-correlation terms were calculated by multiplying the Cholesky vectors without evaluating molecular integrals in self-consistent field iterations. Our method enables DFT and massively distributed memory parallel computers to be used in order to very efficiently calculate the CMOs of large molecules. PMID:24622472

  16. 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.

  17. A third-generation density-functional-theory-based method for calculating canonical molecular orbitals of large molecules.

    PubMed

    Hirano, Toshiyuki; Sato, Fumitoshi

    2014-07-28

    We used grid-free modified Cholesky decomposition (CD) to develop a density-functional-theory (DFT)-based method for calculating the canonical molecular orbitals (CMOs) of large molecules. Our method can be used to calculate standard CMOs, analytically compute exchange-correlation terms, and maximise the capacity of next-generation supercomputers. Cholesky vectors were first analytically downscaled using low-rank pivoted CD and CD with adaptive metric (CDAM). The obtained Cholesky vectors were distributed and stored on each computer node in a parallel computer, and the Coulomb, Fock exchange, and pure exchange-correlation terms were calculated by multiplying the Cholesky vectors without evaluating molecular integrals in self-consistent field iterations. Our method enables DFT and massively distributed memory parallel computers to be used in order to very efficiently calculate the CMOs of large molecules.

  18. 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.

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

    PubMed

    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.

  20. 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.

  1. 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

  2. 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

  3. The molecular transport and intercalation of guest molecules into hydrogen-bonded metal-organic frameworks (HMOFs)

    NASA Astrophysics Data System (ADS)

    Hogan, Greg Anthony

    The process of molecular transport and intercalation has been widely studied for many years, resulting in the discovery of molecular frameworks that are capable of hosting guest molecules or ions. Layered and porous metal-organic frameworks (MOFs) have been found to have applications in the field of catalysis, storage, separations, and ion-exchange. More recently, molecular components with peripheral hydrogen-bonding moieties have been used to affect the synthesis of hydrogen-bonded metal-organic frameworks (HMOFs) as an alternative to MOFs, which are interconnected via coordinate-covalent bonds. While MOFs are perhaps stronger materials, HMOFs have the advantage of being easily modifiable and more flexible. Because HMOFs have not been extensively studied for their ability to host molecules, and because their ability to withstand guest loss and guest exchange is essentially unknown, here we report the synthesis and molecular transport properties of both close-packed and porous HMOFs. Layered materials can mimic the behavior of naturally occurring clays, where guest molecules are absorbed and the layer will expand to accommodate the entering guest molecule. We have created a clay mimic composed of a metal pyridine-dicarboxylates and ammonium counterions (a layered HMOF), which is suitable for studying the ability of such materials to absorb guest molecules. We can control the distance of the interlayer region, as well as the chemical nature (hydrophobic or hydrophilic) by varying the organic amine. The metal complex contains axial water ligands that are replaceable, and such ligand exchange has precedence in coordination polymer (MOF) systems, and has been termed "coordinative intercalation". Using the synthesized layered material we examined the process of intercalation, having chosen a variety of guest molecules ranging from alkyl to aryl molecules, each of which have substituents varying in size, shape and electronics. The first set of guest molecules are non

  4. 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.

  5. 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.

  6. [Interactions of DNA bases with individual water molecules. Molecular mechanics and quantum mechanics computation results vs. experimental data].

    PubMed

    Gonzalez, E; Lino, J; Deriabina, A; Herrera, J N F; Poltev, V I

    2013-01-01

    To elucidate details of the DNA-water interactions we performed the calculations and systemaitic search for minima of interaction energy of the systems consisting of one of DNA bases and one or two water molecules. The results of calculations using two force fields of molecular mechanics (MM) and correlated ab initio method MP2/6-31G(d, p) of quantum mechanics (QM) have been compared with one another and with experimental data. The calculations demonstrated a qualitative agreement between geometry characteristics of the most of local energy minima obtained via different methods. The deepest minima revealed by MM and QM methods correspond to water molecule position between two neighbor hydrophilic centers of the base and to the formation by water molecule of hydrogen bonds with them. Nevertheless, the relative depth of some minima and peculiarities of mutual water-base positions in' these minima depend on the method used. The analysis revealed insignificance of some differences in the results of calculations performed via different methods and the importance of other ones for the description of DNA hydration. The calculations via MM methods enable us to reproduce quantitatively all the experimental data on the enthalpies of complex formation of single water molecule with the set of mono-, di-, and trimethylated bases, as well as on water molecule locations near base hydrophilic atoms in the crystals of DNA duplex fragments, while some of these data cannot be rationalized by QM calculations.

  7. Virus-based surface patterning of biological molecules, probes, and inorganic materials.

    PubMed

    Ahn, Suji; Jeon, Seongho; Kwak, Eun-A; Kim, Jong-Man; Jaworski, Justyn

    2014-10-01

    An essential requirement for continued technological advancement in many areas of biology, physics, chemistry, and materials science is the growing need to generate custom patterned materials. Building from recent achievements in the site-specific modification of virus for covalent surface tethering, we show in this work that stable 2D virus patterns can be generated in custom geometries over large area glass surfaces to yield templates of biological, biochemical, and inorganic materials in high density. As a nanomaterial building block, filamentous viruses have been extensively used in recent years to produce materials with interesting properties, owing to their ease of genetic and chemical modification. By utilizing un-natural amino acids generated at specific locations on the filamentous fd bacteriophage protein coat, surface immobilization is carried out on APTES patterned glass resulting in precise geometries of covalently linked virus material. This technique facilitated the surface display of a high density of virus that were labeled with biomolecules, fluorescent probes, and gold nanoparticles, thereby opening the possibility of integrating virus as functional components for surface engineering.

  8. 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

  9. 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.

  10. Imaging molecular structure through femtosecond photoelectron diffraction on aligned and oriented gas-phase molecules.

    PubMed

    Boll, Rebecca; Rouzée, Arnaud; Adolph, Marcus; Anielski, Denis; Aquila, Andrew; Bari, Sadia; Bomme, Cédric; Bostedt, Christoph; Bozek, John D; Chapman, Henry N; Christensen, Lauge; Coffee, Ryan; Coppola, Niccola; De, Sankar; Decleva, Piero; Epp, Sascha W; Erk, Benjamin; Filsinger, Frank; Foucar, Lutz; Gorkhover, Tais; Gumprecht, Lars; Hömke, André; Holmegaard, Lotte; Johnsson, Per; Kienitz, Jens S; Kierspel, Thomas; Krasniqi, Faton; Kühnel, Kai-Uwe; Maurer, Jochen; Messerschmidt, Marc; Moshammer, Robert; Müller, Nele L M; Rudek, Benedikt; Savelyev, Evgeny; Schlichting, Ilme; Schmidt, Carlo; Scholz, Frank; Schorb, Sebastian; Schulz, Joachim; Seltmann, Jörn; Stener, Mauro; Stern, Stephan; Techert, Simone; Thøgersen, Jan; Trippel, Sebastian; Viefhaus, Jens; Vrakking, Marc; Stapelfeldt, Henrik; Küpper, Jochen; Ullrich, Joachim; Rudenko, Artem; Rolles, Daniel

    2014-01-01

    This paper gives an account of our progress towards performing femtosecond time-resolved photoelectron diffraction on gas-phase molecules in a pump-probe setup combining optical lasers and an X-ray free-electron laser. We present results of two experiments aimed at measuring photoelectron angular distributions of laser-aligned 1-ethynyl-4-fluorobenzene (C(8)H(5)F) and dissociating, laser-aligned 1,4-dibromobenzene (C(6)H(4)Br(2)) molecules and discuss them in the larger context of photoelectron diffraction on gas-phase molecules. We also show how the strong nanosecond laser pulse used for adiabatically laser-aligning the molecules influences the measured electron and ion spectra and angular distributions, and discuss how this may affect the outcome of future time-resolved photoelectron diffraction experiments.

  11. 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.

  12. Extracting physics of life at the molecular level: A review of single-molecule data analyses.

    PubMed

    Colomb, Warren; Sarkar, Susanta K

    2015-06-01

    Studying individual biomolecules at the single-molecule level has proved very insightful recently. Single-molecule experiments allow us to probe both the equilibrium and nonequilibrium properties as well as make quantitative connections with ensemble experiments and equilibrium thermodynamics. However, it is important to be careful about the analysis of single-molecule data because of the noise present and the lack of theoretical framework for processes far away from equilibrium. Biomolecular motion, whether it is free in solution, on a substrate, or under force, involves thermal fluctuations in varying degrees, which makes the motion noisy. In addition, the noise from the experimental setup makes it even more complex. The details of biologically relevant interactions, conformational dynamics, and activities are hidden in the noisy single-molecule data. As such, extracting biological insights from noisy data is still an active area of research. In this review, we will focus on analyzing both fluorescence-based and force-based single-molecule experiments and gaining biological insights at the single-molecule level. Inherently nonequilibrium nature of biological processes will be highlighted. Simulated trajectories of biomolecular diffusion will be used to compare and validate various analysis techniques.

  13. Molecular evolutionary genetics of isozymes: pattern, theory, and application.

    PubMed

    Nevo, E

    1990-01-01

    Isozyme studies at the population genetics-ecology interface conducted at the Institute of Evolution, University of Haifa, during 15 years, 1974-1989, are reviewed in terms of the evidence, theoretical, and practical implications. These studies involve numerous individuals, populations, species, and higher taxa in nature of plants, animals, and humans tested for variation at 15 to 50 primary isozyme loci. The isozyme studies have been conducted mainly in individuals sampled in natural populations at the local, regional, and global levels. Two of the species studied were wild cereals, the progenitors of wheat and barley in the Near East Fertile Crescent. These studies have been complemented by laboratory controlled a priori experimentation of inorganic and organic pollution biology. The human genetics laboratory compared isozyme structure of Jewish and non-Jewish populations. Our results indicate that: (i) isozyme diversity in nature in abundant, at least partly adaptive, and is oriented and maintained primarily by ecological factors. (ii) Natural selection in action is highlighted by stresses involving among others thermal, chemical, and climatic factors. (iii) Speciation can occur with little change in isozyme diversity. (iv) Jews from diverse countries, and in spite of 2,000 years of Diaspora, retain in the frequencies of some isozymes their Near Eastern origins. (v) Wild cereals harbor rich genetic resources exploitable in breeding either directly as adaptive structures, or indirectly as genetic markers for genotypic production of elite agronomic traits. (vi) Isozymes have been utilized as genetic monitors of marine pollution thereby contributing to environmental quality and conservation. (vii) Isozymes can substantially contribute to conservation biology. (viii) Isozymes have been successfully utilized in constructing molecular phylogenies and in revealing new sibling species. (ix) Future theoretical and practical directions of isozyme studies at the protein

  14. Radiation-induced meningioma: a distinct molecular genetic pattern?

    PubMed

    Shoshan, Y; Chernova, O; Juen, S S; Somerville, R P; Israel, Z; Barnett, G H; Cowell, J K

    2000-07-01

    Radiation-induced meningiomas arise after low-dose irradiation treatment of certain medical conditions and are recognized as clinically separate from sporadic meningioma. These tumors are often aggressive or malignant, they are likely to be multiple, and they have a high recurrence rate following treatment compared with sporadic meningiomas. To understand the molecular mechanism by which radiation-induced meningioma (RIM) arise, we compared genetic changes in 7 RIM and 8 sporadic meningioma (SM) samples. The presence of mutations in the 17 exons of the neurofibromatosis type 2 (NF2) gene, which has been shown to be inactivated in sporadic meningiomas, was analyzed in RIM and SM using single-strand conformation polymorphism (SSCP) and DNA sequencing. In contrast to SM, which showed NF2 mutations in 50% of specimens, no mutations were found in RIM. In addition, Western blot analysis of schwannomin/merlin protein, the NF2 gene product, demonstrated protein levels comparable to normal brain in 4/4 RIM tumor samples analyzed. Loss of heterozygosity (LOH) of genomic regions, which were reported for SM, was also analyzed in all cases of RIM using 22 polymorphic DNA markers. Allele losses were found on chromosomes 1p (4/7), 9p (2/7), 19q (2/7), 22q (2/7), and 18q (1/7). From these observations we conclude that unlike sporadic meningiomas, NF2 gene inactivation and chromosome 22q deletions are far less frequent in RIM, and their role in meningioma development following low dose irradiation is less significant. Other chromosomal lesions, especially loss of 1p, possibly induced by irradiation, may be more important in the development of these tumors. PMID:10901233

  15. Molecular evolutionary genetics of isozymes: pattern, theory, and application.

    PubMed

    Nevo, E

    1990-01-01

    Isozyme studies at the population genetics-ecology interface conducted at the Institute of Evolution, University of Haifa, during 15 years, 1974-1989, are reviewed in terms of the evidence, theoretical, and practical implications. These studies involve numerous individuals, populations, species, and higher taxa in nature of plants, animals, and humans tested for variation at 15 to 50 primary isozyme loci. The isozyme studies have been conducted mainly in individuals sampled in natural populations at the local, regional, and global levels. Two of the species studied were wild cereals, the progenitors of wheat and barley in the Near East Fertile Crescent. These studies have been complemented by laboratory controlled a priori experimentation of inorganic and organic pollution biology. The human genetics laboratory compared isozyme structure of Jewish and non-Jewish populations. Our results indicate that: (i) isozyme diversity in nature in abundant, at least partly adaptive, and is oriented and maintained primarily by ecological factors. (ii) Natural selection in action is highlighted by stresses involving among others thermal, chemical, and climatic factors. (iii) Speciation can occur with little change in isozyme diversity. (iv) Jews from diverse countries, and in spite of 2,000 years of Diaspora, retain in the frequencies of some isozymes their Near Eastern origins. (v) Wild cereals harbor rich genetic resources exploitable in breeding either directly as adaptive structures, or indirectly as genetic markers for genotypic production of elite agronomic traits. (vi) Isozymes have been utilized as genetic monitors of marine pollution thereby contributing to environmental quality and conservation. (vii) Isozymes can substantially contribute to conservation biology. (viii) Isozymes have been successfully utilized in constructing molecular phylogenies and in revealing new sibling species. (ix) Future theoretical and practical directions of isozyme studies at the protein

  16. Soluble Collectin-12 (CL-12) Is a Pattern Recognition Molecule Initiating Complement Activation via the Alternative Pathway.

    PubMed

    Ma, Ying Jie; Hein, Estrid; Munthe-Fog, Lea; Skjoedt, Mikkel-Ole; Bayarri-Olmos, Rafael; Romani, Luigina; Garred, Peter

    2015-10-01

    Soluble defense collagens including the collectins play important roles in innate immunity. Recently, a new member of the collectin family named collectin-12 (CL-12 or CL-P1) has been identified. CL-12 is highly expressed in umbilical cord vascular endothelial cells as a transmembrane receptor and may recognize certain bacteria and fungi, leading to opsonophagocytosis. However, based on its structural and functional similarities with soluble collectins, we hypothesized the existence of a fluid-phase analog of CL-12 released from cells, which may function as a soluble pattern-recognition molecule. Using recombinant CL-12 full length or CL-12 extracellular domain, we determined the occurrence of soluble CL-12 shed from in vitro cultured cells. Western blot showed that soluble recombinant CL-12 migrated with a band corresponding to ∼ 120 kDa under reducing conditions, whereas under nonreducing conditions it presented multimeric assembly forms. Immunoprecipitation and Western blot analysis of human umbilical cord plasma enabled identification of a natural soluble form of CL-12 having an electrophoretic mobility pattern close to that of shed soluble recombinant CL-12. Soluble CL-12 could recognize Aspergillus fumigatus partially through the carbohydrate-recognition domain in a Ca(2+)-independent manner. This led to activation of the alternative pathway of complement exclusively via association with properdin on A. fumigatus as validated by detection of C3b deposition and formation of the terminal complement complex. These results demonstrate the existence of CL-12 in a soluble form and indicate a novel mechanism by which the alternative pathway of complement may be triggered directly by a soluble pattern-recognition molecule.

  17. Different patterns of soluble adhesion molecules in systemic and cutaneous lupus erythematosus.

    PubMed

    Nyberg, F; Acevedo, F; Stephansson, E

    1997-10-01

    Circulating isoforms of cellular adhesion molecules (CAMs) have been described recently, and elevated levels of certain sCAMs have been reported in various inflammatory diseases such as systemic lupus erythematosus (SLE). There are previously no reports on sCAMs in cutaneous LE. Sera from 61 patients with LE: systemic (SLE: n=24), chronic cutaneous (discoid LE, DLE: n= 19) or subacute cutaneous (SCLE: n=8), chronic biologically false positive (CBFP) reactors for syphilis (n= 10) and 32 controls were examined for sICAM-1, sVCAM-1 and sE-Selectin with specific ELISA kits. Protocol forms were reviewed. We found significantly elevated levels of sE-Selectin in patients with DLE and widespread cutaneous symptoms, and a correlation between active cutaneous disease as well as polymorphous light eruption (PLE) and elevated levels of sE-Selectin. In contrast, patients with systemic LE did not have elevated levels of sE-Selectin, but in concordance with earlier reports, sICAM-1 and sVCAM-1 levels were elevated compared to controls in SLE, as well as in SCLE patients, which has not been reported previously. Since activated endothelial cells are the only source for E-Selectin, the elevated sE-Selectin level in patients with widespread and active cutaneous disease suggests a more important role for endothelial cells in the pathogenesis of cutaneous LE than previously assumed.

  18. 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

  19. 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

  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.

  1. 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.

  2. Unique expression patterns of cell fate molecules delineate sequential stages of dentate gyrus development.

    PubMed

    Pleasure, S J; Collins, A E; Lowenstein, D H

    2000-08-15

    The dentate gyrus of the hippocampus is uniquely organized with a displaced proliferative zone that continues to generate dentate granule cells throughout life. We have analyzed the expression of Notch receptors, Notch ligands, and basic helix-loop-helix (bHLH) genes during dentate gyrus development to determine whether the need to maintain a pool of undifferentiated precursors is reflected in the patterns of expression of these genes. Many of these genes are expressed diffusely throughout the cortical neuroepithelium at embryonic days 16 and 17 in the rat, just preceding the migration of newly born granule cells and dentate precursor cells into the dentate anlage. However, at this time, Mash1, Math3, and Id3 expression are all concentrated in the area that specifically gives rise to granule cells and dentate precursor cells. Two days later, at the time of migration of the first granule cells and dentate precursor cells, cells expressing Mash1 are seen in the migratory route from the subventricular zone to the developing dentate gyrus. Newly born granule cells expressing NeuroD are also present in this migratory pathway. In the first postnatal week, precursor cells expressing Mash1 reside in the dentate hilus, and by the third postnatal week they have largely taken up their final position in the subgranular zone along the hilar side of the dentate granule cell layer. After terminal differentiation, granule cells born in the hilus or the subgranular zone begin to express NeuroD followed by NeuroD2. This study establishes that the expression patterns of bHLH mRNAs evolve during the formation of the dentate gyrus, and the precursor cells resident in the mature dentate gyrus share features with precursor cells found in development. Thus, many of the same mechanisms that are known to regulate cell fate and precursor pool size in other brain regions are likely to be operative in the dentate gyrus at all stages of development.

  3. 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

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

    PubMed

    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.

  5. 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.

  6. 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

    2014-06-20

    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.

  7. Array Formatting of the Heat-Transfer Method (HTM) for the Detection of Small Organic Molecules by Molecularly Imprinted Polymers

    PubMed Central

    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

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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…

  13. [Strategy of molecular design of drugs: the unification of macro-properties and micro-structures of a molecule].

    PubMed

    Guo, Zong-Ru

    2008-03-01

    The interaction of a drug with the organism involves both the disposition of a drug by the organism and the action of a drug on the organism. The disposition of various exogenous substances, including drugs, complies with general rules. The underlying physical and chemical changes to different drugs in view of time and space, i. e. pharmacokinetics, share common characteristics, that is the tout ensemble of a molecule and its macroscopic properties convey direct effect on the pharmacokinetic behavior as the tendency and consequence of biological evolution. The action of a drug on the organism, on the other hand, implicates the physico-chemical binding of a drug molecule to the target protein, which induces pharmacological and toxicological effects. The biological reactions, no matter beneficial or adverse, are all specific and individual manifestation of the drug molecule and determined by the interactive binding between definitive atoms or groups of the drug molecule and the macromolecular target in three-dimension. Such critical atoms, groups, or fragments responsible for the interaction reflect the microscopic structures of drug molecules and are called pharmacophore. In this context, a drug molecule is presumed as an assembly of macroscopic property and microscopic structure, with the macroscopic properties determining the absorption, distribution, metabolism and elimination of drugs and the microscopic structure coining pharmacological action. The knowledge of the internal relationship between macroscopy/microscopy and PK/PD conduces to comprehension of drug action and guides molecular drug design, because this conception facilitates the identification of structural features necessary for biological response, and the determination of factors modulating the physico-chemical and pharmacokinetic properties. The factors determining macro-properties include molecular weight, solubility, charge, lipophilicity (partition), and polar surface area, etc., which are

  14. [Strategy of molecular design of drugs: the unification of macro-properties and micro-structures of a molecule].

    PubMed

    Guo, Zong-Ru

    2008-03-01

    The interaction of a drug with the organism involves both the disposition of a drug by the organism and the action of a drug on the organism. The disposition of various exogenous substances, including drugs, complies with general rules. The underlying physical and chemical changes to different drugs in view of time and space, i. e. pharmacokinetics, share common characteristics, that is the tout ensemble of a molecule and its macroscopic properties convey direct effect on the pharmacokinetic behavior as the tendency and consequence of biological evolution. The action of a drug on the organism, on the other hand, implicates the physico-chemical binding of a drug molecule to the target protein, which induces pharmacological and toxicological effects. The biological reactions, no matter beneficial or adverse, are all specific and individual manifestation of the drug molecule and determined by the interactive binding between definitive atoms or groups of the drug molecule and the macromolecular target in three-dimension. Such critical atoms, groups, or fragments responsible for the interaction reflect the microscopic structures of drug molecules and are called pharmacophore. In this context, a drug molecule is presumed as an assembly of macroscopic property and microscopic structure, with the macroscopic properties determining the absorption, distribution, metabolism and elimination of drugs and the microscopic structure coining pharmacological action. The knowledge of the internal relationship between macroscopy/microscopy and PK/PD conduces to comprehension of drug action and guides molecular drug design, because this conception facilitates the identification of structural features necessary for biological response, and the determination of factors modulating the physico-chemical and pharmacokinetic properties. The factors determining macro-properties include molecular weight, solubility, charge, lipophilicity (partition), and polar surface area, etc., which are

  15. Efficient new ribozyme mimics: direct mapping of molecular design principles from small molecules to macromolecular, biomimetic catalysts.

    PubMed

    Putnam, W C; Daniher, A T; Trawick, B N; Bashkin, J K

    2001-05-15

    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-phenanthroline 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Large-area ordered Ge-Si compound quantum dot molecules on dot-patterned Si (001) substrates.

    PubMed

    Lei, Hui; Zhou, Tong; Wang, Shuguang; Fan, Yongliang; Zhong, Zhenyang

    2014-08-29

    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. PMID:25078348

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. ATOMIC AND MOLECULAR PHYSICS: Lie Algebraic Approach to Energy Transfer for Collinear Collision of Two Anharmonic Diatomic Molecules

    NASA Astrophysics Data System (ADS)

    Wang, Xiao-Yan; Wang, Peng-Cheng; Qiu, Jian-Feng; Wang, Jin-Xi; Hou, Li-Xia; Xie, Jin-Dong Ding, Shi-Liang

    2010-02-01

    An anharmonic oscillator algebra model is used to study the collinear collisions of two diatomic molecules. The transition probability for vibration-vibration energy transfer is presented. For an application of the method, we talk about the collision of N2+CO, N2+O2, and N2+N2. Through long time averaging, the transition probability changes to the function of total energy of the system. Comparing the results with the quantum results, we can see that the dynamical Lie algebraic method is useful for describing the anharmonic diatomic molecular collision.

  8. 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

  9. Molecular dynamics study of the structures and dynamics of the iodine molecules confined in AlPO(4)-11 crystals.

    PubMed

    Hu, J M; Zhai, J P; Wu, F M; Tang, Z K

    2010-12-16

    Structural and dynamical properties of iodine molecules incorporated in one-dimensional elliptic channels of AlPO(4)-11 (AEL) crystals were studied by means of molecular dynamics (MD) simulations. It was found that the iodine molecules in the AEL channels are restricted in the (101) planes with only two favorite orientations: lying along the channels and standing along the major axes of the ellipses, which are well consistent with the experimental observations. In addition, the iodine structures are largely dependent on the loading level: with the increase of loading, the iodine specimens change their structures accordingly from isolated molecules as in the gas phase to single molecular chains and molecular ribbon sheets. The molecular ribbon sheets are composed of equally distributed and parallel molecules as in the iodine crystals. The simulation results show that the standing iodine molecules in the AEL channels are well restricted due to both the appropriate size of ellipses and their alternation throughout the channels. They can diffuse along the channels only after overcoming the rotational barriers to become lying molecules, which indicate that the iodine molecules in the ribbon sheets can keep the configurations without rotational and translational motion. The confined iodine molecules with such structures and properties may be used to improve the accuracy of the frequency standards.

  10. 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

  11. Molecular overlap in the regulation of SK channels by small molecules and phosphoinositides

    PubMed Central

    Zhang, Miao; Meng, Xuan-Yu; Zhang, Ji-fang; Cui, Meng; Logothetis, Diomedes E.

    2015-01-01

    Phosphatidylinositol 4,5-bisphosphate (PIP2) directly interacts with the small-conductance Ca2+-activated K+ 2-a (SK2-a) channel/calmodulin complex, serving as a critical element in the regulation of channel activity. We report that changes of protein conformation in close proximity to the PIP2 binding site induced by a small-molecule SK channel modulator, NS309, can effectively enhance the interaction between the protein and PIP2 to potentiate channel activity. This novel modulation of PIP2 sensitivity by small-molecule drugs is likely not to be limited in its application to SK channels, representing an intriguing strategy to develop drugs controlling the activity of the large number of PIP2-dependent proteins. PMID:26366439

  12. 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.

  13. 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

  14. 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

  15. Modeling stochastic kinetics of molecular machines at multiple levels: from molecules to modules.

    PubMed

    Chowdhury, Debashish

    2013-06-01

    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.

  16. Molecular Mechanics of Single Protein Molecules Measured with the Atomic Force Microscope

    NASA Astrophysics Data System (ADS)

    Hansma, Paul K.

    2000-03-01

    After a short history of AFM development in our lab, including recent developments with small cantilevers, this talk will focus on 1) pulling single protein molecules to explore the forces involved in unfolding and 2) watching single protein molecules in action to learn how they function mechanically. 1) Pulling experiments on proteins used as marine adhesives in abalone shells and other biological composite materials reveal modules bound together by sacrificial bonds that are weaker than the backbone bonds in the polypeptide chain.1 These self-healing modules provide effective energy absorption and appear to be a real key to understanding the impressive fracture resistance of biological composite materials. For example, the abalone shell is 3000 times more fracture resistant than a single crystal of calcium carbonate, despite the fact that 97% of the mass of the shell is crystalline calcium carbonate. 2) It is becoming possible, again with AFMs, to learn how some enzymes, nature's nanomachines, do their exquisite materials synthesis and processing. The talk will focus on the chaperonin system of GroEL and GroES that processes incorrectly folded proteins and assists them in refolding correctly. It is becoming possible not only to see single molecule events such as the association and disassociation of the GroEL-Gro-ES complex, but also to measure potential energy functions for the molecules in various conformational states. These new measurements, together with detailed structural measurements from other techniques, give new clues about how these proteins use the energy of ATP to do their work. Since the AFMs of today are very far from fundamental limits, this is only the beginning. 1. B. L. Smith, T. E. Schaffer, M. Viani, J. B. Thompson, N. A. Frederick, J. Kindt, A. Belcher, G. D. Stucky, D. E. Morse and P. K. Hansma, Nature 399, 761 (1999)

  17. ATOMIC AND MOLECULAR PHYSICS: A Time-Dependent Wavepacket Method for Photodissociation Dynamics of Triatomic Molecule

    NASA Astrophysics Data System (ADS)

    Mohammad Noh, Daud; Gabriel, Balint-Kurti G.

    2009-07-01

    We report a time-dependent quantum wavepacket theory employed to interpret the photoabsorption spectrum of the N2O molecule in terms of the nuclear motion on the upper 21A‧ and 11A″ potential energy surfaces. The N2-O bond breaks upon excitation leading to dissociation. The total angular momentum is treated correctly taking into account the vector property of the electric field of the exciting radiation.

  18. 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

  19. 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.

  20. 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.

  1. Molecular characterization of a new begomovirus infecting Sida cordifolia and its associated satellite DNA molecules.

    PubMed

    Guo, Xiaojian; Zhou, Xueping

    2006-12-01

    Two virus isolates Hn57 and Hn60 were obtained from Sida cordifolia showing mild upward leaf-curling symptoms in Hainan province of China. Comparison of partial sequences of DNA-A like molecule confirmed the existence of a single type of begomovirus. The complete nucleotide sequence of DNA-A of Hn57 was determined to be 2757 nucleotides, with a genomic organization typical of begomoviruses. Complete sequence comparison with other reported begomoviruses revealed that Hn57 DNA-A has the highest sequence identity (71.0%) with that of Tobacco leaf curl Yunnan virus. Consequently, Hn57 was considered to be a new begomovirus species, for which the name Sida leaf curl virus (SiLCV) is proposed. In addition to DNA-A molecule, two additional circular single-stranded satellite DNA molecules corresponding to DNAbeta and DNA1 were found to be associated with SiLCV isolates. Both DNAbeta and DNA1 were approximately half the size of their cognate genomic DNA. Sequence analysis shows that DNAbeta of Hn57 and Hn60 share 93.8% nucleotide sequence identity, and they have the highest sequence identity (58.5%) with DNAbeta associated with Ageratum leaf curl disease (AJ316027). The nucleotide sequence identity between DNA1 of Hn57 and that of Hn60 was 83.8%, they share 58.2-79.3% nucleotide sequence identities in comparison with other previously reported DNAl.

  2. Investigating the molecular and aggregated states of a drug molecule rutaecarpine using spectroscopy, microscopy, crystallography and computational studies.

    PubMed

    Dandpat, Shiba Sundar; Sarkar, Moloy

    2015-06-01

    The photophysical properties of a potential drug molecule rutaecarpine have been investigated in molecular as well as aggregated states. All systems have been characterized by various spectroscopic, microscopic and dynamic light scattering (DLS) techniques. The investigation has been carried out by keeping the fact in mind that hydrophobic organic molecules have a strong tendency to form aggregates in aqueous solution. A blue shift in the absorption spectrum of rutaecarpine has been observed for aggregates (compared to molecular solution) indicating the formation of H-type aggregates. The intermolecular interactions responsible for such aggregation have been further investigated through crystallographic and computational studies. It has been observed that π-π stacking interactions among the monomer units play an important role in the formation of H-type aggregates. Quantum mechanical calculations also substantiate the blue shift in the absorption that has been observed for aggregates. In the present case, enhanced emission for aggregates as compared to the molecular solution of rutaecarpine has also been observed. The observed enhanced emission upon aggregation is attributed to the decrease of the non-radiative rate constant (knr) upon aggregation. The effect of a surface active ionic liquid (SAIL), 1-dodecyl-3-methylimidazolium bromide ([C12mim]Br), on the aggregation of rutaecarpine has been investigated. Interestingly, in addition to the decrease in the particle size, a change in the morphology of the aggregates has also been observed with gradual addition of [C12mim]Br to the colloidal solution of rutaecarpine. The present study demonstrates that a SAIL can effectively be used as a medium for dissociation of colloidal aggregates and encapsulation of molecular species, which in turn would be helpful in influencing the drug activity. PMID:25948504

  3. 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.

  4. RNA:DNA hybrids are a novel molecular pattern sensed by TLR9

    PubMed Central

    Rigby, Rachel E; Webb, Lauren M; Mackenzie, Karen J; Li, Yue; Leitch, Andrea; Reijns, Martin A M; Lundie, Rachel J; Revuelta, Ailsa; Davidson, Donald J; Diebold, Sandra; Modis, Yorgo; MacDonald, Andrew S; Jackson, Andrew P

    2014-01-01

    The sensing of nucleic acids by receptors of the innate immune system is a key component of antimicrobial immunity. RNA:DNA hybrids, as essential intracellular replication intermediates generated during infection, could therefore represent a class of previously uncharacterised pathogen-associated molecular patterns sensed by pattern recognition receptors. Here we establish that RNA:DNA hybrids containing viral-derived sequences efficiently induce pro-inflammatory cytokine and antiviral type I interferon production in dendritic cells. We demonstrate that MyD88-dependent signalling is essential for this cytokine response and identify TLR9 as a specific sensor of RNA:DNA hybrids. Hybrids therefore represent a novel molecular pattern sensed by the innate immune system and so could play an important role in host response to viruses and the pathogenesis of autoimmune disease. PMID:24514026

  5. 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

  6. Through-Solvent Tunneling in Donor-Bridge-Acceptor Molecules Containing a Molecular Cleft.

    PubMed

    Graff, B M; Lamont, D N; Parker, M F L; Bloom, B P; Schafmeister, C E; Waldeck, D H

    2016-08-01

    Photoinduced electron transfer is used to investigate the solvent-mediated electron tunneling between electron donor and acceptor groups in polar solvents. Bis-peptide scaffolds are used to control the spatial positioning of electron donor and acceptor groups and create a molecular cleft. The photoinduced electron transfer is studied for two different cleft sizes, and the electronic coupling is found to be controlled by the nature of the solvent and the ability of the molecular cleft to accommodate it, as well as interact directly with it. These studies demonstrate the importance of electron tunneling through nonbonded contacts and reveal a strategy for examining such tunneling pathways in polar solvents. PMID:27401503

  7. 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

  8. 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...

  9. Molecular aptamer beacon tuned DNA strand displacement to transform small molecules into DNA logic outputs.

    PubMed

    Zhu, Jinbo; Zhang, Libing; Zhou, Zhixue; Dong, Shaojun; Wang, Erkang

    2014-03-28

    A molecular aptamer beacon tuned DNA strand displacement reaction was introduced in this work. This strand displacement mode can be used to transform the adenosine triphosphate (ATP) input into a DNA strand output signal for the downstream gates to process. A simple logic circuit was built on the basis of this mechanism.

  10. 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.)

  11. 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.

  12. 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

  13. The hydrogen molecule and the H+2 molecular ion inside padded prolate spheroidal cavities with arbitrary nuclear positions

    NASA Astrophysics Data System (ADS)

    Colín-Rodríguez, R.; Díaz-García, C.; Cruz, S. A.

    2011-12-01

    A generalization of previous theoretical studies of molecular confinement based on the molecule-in-a-box model for the H+2 and H2 systems whereby the confining cavity is assumed to be prolate spheroidal in shape is presented. A finite height for the confining barrier potential is introduced and the independent variation of the nuclear positions from the cavity size and shape is allowed. Within this scheme, the non-separable Schrödinger problem for the confined H+2 and H2 molecules in their ground states is treated variationally. In both cases, an important dependence of the equilibrium bond length and total energy on the confining barrier height is observed for fixed cavity sizes and shapes. It is also shown that—given a barrier height—as the cavity size is reduced, the limit of stability of the confined molecule is attained for a critical size. The results of this work suggest the adequacy of the proposed method for more realistic studies of electronic and vibrational properties of confined one- and two-electron diatomics for proper comparison with experiment.

  14. 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.

  15. 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

  16. Experimental results on the dissociation of molecular iodine in the presence of singlet oxygen molecules

    NASA Astrophysics Data System (ADS)

    Zagidullin, M. V.; Khvatov, N. A.; Malyshev, M. S.; Svistun, M. I.

    2016-08-01

    The experimental results on the dissociation of iodine molecules in the presence of single oxygen molecules under a widerange variation of the oxygen-iodine composition are presented. The rate constants are determined as 4.3 × 10-17 cm3 s-1 for the reaction O2(1Δ) + O2(1Δ) → O2(1Σ) + O2(3Σ) (reaction 1), 2.8 × 10-13 cm3 s-1 for the reaction O2(1Δ) + I(2P1/2) → O2(1Σ) + I(2P3/2) (4) and 8.3 × 10-11 cm3 s-1 for the reaction O2(1Σ) + I2 → O2(3Σ) + 2I (2). The analysis of the experimental results shows that for different compositions of the active medium of the oxygen-iodine laser the iodine dissociation occurs via the chain of reactions 1, 2, O2(1Δ) + I(2P3/2) → O2(3Σ) + I(2P1/2), 4 and in the cascade process I2 + I(2P1/2) → I2(u) + I(2P3/2), I2(u) + O2(1Δ) → 2I + O2(3Σ). For typical active medium compositions of the supersonic chemical oxygen-iodine laser, the contributions of each of the mechanisms to the dissociation are comparable. The experiments carried out did not reveal any contribution from the vibrationally excited oxygen molecules to the iodine dissociation. Thus, the performed experiments and the conclusions drawn from them completely confirm the mechanism of iodine dissociation, proposed earlier.

  17. Experimental results on the dissociation of molecular iodine in the presence of singlet oxygen molecules

    NASA Astrophysics Data System (ADS)

    Zagidullin, M. V.; Khvatov, N. A.; Malyshev, M. S.; Svistun, M. I.

    2016-08-01

    The experimental results on the dissociation of iodine molecules in the presence of single oxygen molecules under a widerange variation of the oxygen–iodine composition are presented. The rate constants are determined as 4.3 × 10-17 cm3 s-1 for the reaction O2(1Δ) + O2(1Δ) → O2(1Σ) + O2(3Σ) (reaction 1), 2.8 × 10-13 cm3 s-1 for the reaction O2(1Δ) + I(2P1/2) → O2(1Σ) + I(2P3/2) (4) and 8.3 × 10-11 cm3 s-1 for the reaction O2(1Σ) + I2 → O2(3Σ) + 2I (2). The analysis of the experimental results shows that for different compositions of the active medium of the oxygen–iodine laser the iodine dissociation occurs via the chain of reactions 1, 2, O2(1Δ) + I(2P3/2) → O2(3Σ) + I(2P1/2), 4 and in the cascade process I2 + I(2P1/2) → I2(u) + I(2P3/2), I2(u) + O2(1Δ) → 2I + O2(3Σ). For typical active medium compositions of the supersonic chemical oxygen–iodine laser, the contributions of each of the mechanisms to the dissociation are comparable. The experiments carried out did not reveal any contribution from the vibrationally excited oxygen molecules to the iodine dissociation. Thus, the performed experiments and the conclusions drawn from them completely confirm the mechanism of iodine dissociation, proposed earlier.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

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

    PubMed

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

    2013-05-01

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

  4. Parafermion excitations in superfluid of quasi-molecular chains formed by dipolar molecules or indirect excitons

    NASA Astrophysics Data System (ADS)

    Kuklov, Anatoly; Tsvelik, Alexei

    2013-03-01

    We study a quantum phase transition in a system of dipoles confined in a stack of N identical 1D lattices (tubes) polarized perpendicularly to the lattices. The dipoles may represent polar molecules or indirect excitons. The transition separates two phases; in one of them superfluidity takes place in each individual lattice, in the other (chain superfluid) the order parameter is the product of bosonic operators from all lattices. We argue that in the presence of finite inter-lattice tunneling the transition belongs to the universality class of the q = N two-dimensional classical Potts model. For N = 2 , 3 , 4 the corresponding low energy field theory is the model of ZN parafermions perturbed by the thermal operator. Results of Monte Carlo simulations are consistent with these predictions. The detection schemes for the chain superfluid of dipolar molecules and indirect excitons are outlined. ABK was supported by the NSF under Grant No.PHY1005527; AMT acknowledges a support from US DOE under contract DE-AC02-98 CH108

  5. Optimization of molecular design in the evolution of metabolism: the glycogen molecule.

    PubMed Central

    Meléndez-Hevia, E; Waddell, T G; Shelton, E D

    1993-01-01

    The animal glycogen molecule has to be designed in accordance with its metabolic function as a very effective fuel store allowing quick release of large amounts of glucose. In addition, the design should account for a high capacity of glucose storage in the least possible space. We have studied the optimization of these variables by means of a mathematical model of the glycogen molecule. Our results demonstrate that the structure is optimized to maximize (a) the total glucose stored in the smallest possible volume, (b) the proportion of it that can be directly released by phosphorylase before any debranching occurs, and (c) the number of non-reducing ends (points of attack for phosphorylase), which maximizes the speed of fuel release. The optimization of these four variables is achieved with appropriate values for two key parameters in glycogen design: the degree of branching and the length of the chains. The optimal values of these two parameters are precisely those found in cellular glycogen. PMID:8240246

  6. Improving Signal/Noise Resolution in Single-Molecule Experiments Using Molecular Constructs with Short Handles

    PubMed Central

    Forns, N.; de Lorenzo, S.; Manosas, M.; Hayashi, K.; Huguet, J.M.; Ritort, F.

    2011-01-01

    We investigate unfolding/folding force kinetics in DNA hairpins exhibiting two and three states with newly designed short dsDNA handles (29 bp) using optical tweezers. We show how the higher stiffness of the molecular setup moderately enhances the signal/noise ratio (SNR) in hopping experiments as compared to conventional long-handled constructs (≅700 bp). The shorter construct results in a signal of higher SNR and slower folding/unfolding kinetics, thereby facilitating the detection of otherwise fast structural transitions. A novel analysis, as far as we are aware, of the elastic properties of the molecular setup, based on high-bandwidth measurements of force fluctuations along the folded branch, reveals that the highest SNR that can be achieved with short handles is potentially limited by the marked reduction of the effective persistence length and stretch modulus of the short linker complex. PMID:21463590

  7. 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.

  8. Dual reorientation relaxation routes of water molecules in oxyanion's hydration shell: A molecular geometry perspective.

    PubMed

    Xie, Wen Jun; Yang, Yi Isaac; Gao, Yi Qin

    2015-12-14

    In this study, we examine how complex ions such as oxyanions influence the dynamic properties of water and whether differences exist between simple halide anions and oxyanions. Nitrate anion is taken as an example to investigate the hydration properties of oxyanions. Reorientation relaxation of its hydration water can occur through two different routes: water can either break its hydrogen bond with the nitrate to form one with another water or switch between two oxygen atoms of the same nitrate. The latter molecular mechanism increases the residence time of oxyanion's hydration water and thus nitrate anion slows down the translational motion of neighbouring water. But it is also a "structure breaker" in that it accelerates the reorientation relaxation of hydration water. Such a result illustrates that differences do exist between the hydration of oxyanions and simple halide anions as a result of different molecular geometries. Furthermore, the rotation of the nitrate solute is coupled with the hydrogen bond rearrangement of its hydration water. The nitrate anion can either tilt along the axis perpendicularly to the plane or rotate in the plane. We find that the two reorientation relaxation routes of the hydration water lead to different relaxation dynamics in each of the two above movements of the nitrate solute. The current study suggests that molecular geometry could play an important role in solute hydration and dynamics.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. Complex materials for molecular spintronics applications: cobalt bis(dioxolene) valence tautomers, from molecules to polymers.

    PubMed

    Calzolari, Arrigo; Chen, Yifeng; Lewis, Geoffrey F; Dougherty, Daniel B; Shultz, David; Nardelli, Marco Buongiorno

    2012-11-01

    Using first principles calculations, we predict a complex multifunctional behavior in cobalt bis(dioxolene) valence tautomeric compounds. Molecular spin-state switching is shown to dramatically alter electronic properties and corresponding transport properties. This spin state dependence has been demonstrated for technologically relevant coordination polymers of valence tautomers as well as for novel conjugated polymers with valence tautomeric functionalization. As a result, these materials are proposed as promising candidates for spintronic devices that can couple magnetic bistability with novel electrical and spin conduction properties. Our findings pave the way to the fundamental understanding and future design of active multifunctional organic materials for spintronics applications.

  16. Torsion-Inversion Tunneling Patterns in the Ch-Stretch Vibrationally Excited States of the G{_1}{_2} Molecules

    NASA Astrophysics Data System (ADS)

    Dawadi, Mahesh B.; Bhatta, Ram S.; Perry, David S.

    2013-06-01

    Torsion-inversion tunneling models have been developed for CH-stretch vibrationally excited states in G{_1}{_2} molecules, including 2-methylmalonaldehyde (2-MMA), 5-methyltropolone (5-MT), and methylamine. These models are extensions of the group theoretical approach of Hougen and the internal coordinate model of Wang and Perry in which the inversion motion is included in addition to the torsion and the small-amplitude (e.g., CH stretch) vibrations. The present models incorporate torsion-inversion tunneling parameters {_2}{_V} and {_3}{_V}, respectively and a number of low-order terms couplings to the CH-stretch vibrations. Of the three methyl CH stretch vibrations, Model I includes only the two asymmetric stretches that correlate to the E-type degenerate CH stretch in a symmetric rotor; Model II includes all three. The models yield the torsion-inversion tunneling patterns of the four symmetry species, A, B, E{_1} and E{_2}, in the CH-stretch excited states. The principal results are as follows. (i) Both models and each of the coupling terms considered yield the same tunneling patterns, which are different in the asymmetric CH stretch excited states as compared to those in the ground state. (ii) In Model I, the magnitude of the tunneling splittings in the two asymmetric CH stretch excited states is exactly half of that in the ground state. (iii) In Model II, the relative magnitude of these splittings depends on the ratio \\vertμ\\vert/(\\vert{_2}{_V}\\vert+\\vert{_3}{_V}\\vert) where μ is the torsion-inversion-vibration coupling parameter. This ratio varies from 3 to 308 across the series methanol, methylamine, 2-methylmalonaldehyde and 5-methyltropolone, with a consequent variation in the magnitude of the tunneling splittings. J. T. HougenJ. Mol. Spectrosc. {207}, 60, (2001). X. Wang and D. S. PerryJ. Chem. Phys. {109}, 10795, (1998).

  17. Oligogalacturonides: plant damage-associated molecular patterns and regulators of growth and development.

    PubMed

    Ferrari, Simone; Savatin, Daniel V; Sicilia, Francesca; Gramegna, Giovanna; Cervone, Felice; Lorenzo, Giulia De

    2013-01-01

    Oligogalacturonides (OGs) are oligomers of alpha-1,4-linked galacturonosyl residues released from plant cell walls upon partial degradation of homogalacturonan. OGs are able to elicit defense responses, including accumulation of reactive oxygen species and pathogenesis-related proteins, and protect plants against pathogen infections. Recent studies demonstrated that OGs are perceived by wall-associated kinases and share signaling components with microbe-associated molecular patterns. For this reason OGs are now considered true damage-associated molecular patterns that activate the plant innate immunity and may also be involved in the activation of responses to mechanical wounding. Furthermore, OGs appear to modulate developmental processes, likely through their ability to antagonize auxin responses. Here we review our current knowledge on the role and mode of action of this class of oligosaccharides in plant defense and development.

  18. Nonadiabatic Excited-State Molecular Dynamics Modeling of Photoinduced Dynamics in Conjugated Molecules

    SciTech Connect

    Nelson, Tammie; Fernandez-Alberti, Sebastian; Chernyak, Vladimir; Roitberg, Adrian E.; Tretiak, Sergei

    2011-01-10

    Nonadiabatic dynamics generally defines the entire evolution of electronic excitations in optically active molecular materials. It is commonly associated with a number of fundamental and complex processes such as intraband relaxation, energy transfer, and light harvesting influenced by the spatial evolution of excitations and transformation of photoexcitation energy into electrical energy via charge separation (e.g., charge injection at interfaces). To treat ultrafast excited-state dynamics and exciton/charge transport we have developed a nonadiabatic excited-state molecular dynamics (NA-ESMD) framework incorporating quantum transitions. Our calculations rely on the use of the Collective Electronic Oscillator (CEO) package accounting for many-body effects and actual potential energy surfaces of the excited states combined with Tully’s fewest switches algorithm for surface hopping for probing nonadiabatic processes. This method is applied to model the photoinduced dynamics of distyrylbenzene (a small oligomer of polyphenylene vinylene, PPV). Our analysis shows intricate details of photoinduced vibronic relaxation and identifies specific slow and fast nuclear motions that are strongly coupled to the electronic degrees of freedom, namely, torsion and bond length alternation, respectively. Nonadiabatic relaxation of the highly excited mA{sub g} state is predicted to occur on a femtosecond time scale at room temperature and on a picosecond time scale at low temperature.

  19. Nonadiabatic excited-state molecular dynamics modeling of photoinduced dynamics in conjugated molecules.

    PubMed

    Nelson, Tammie; Fernandez-Alberti, Sebastian; Chernyak, Vladimir; Roitberg, Adrian E; Tretiak, Sergei

    2011-05-12

    Nonadiabatic dynamics generally defines the entire evolution of electronic excitations in optically active molecular materials. It is commonly associated with a number of fundamental and complex processes such as intraband relaxation, energy transfer, and light harvesting influenced by the spatial evolution of excitations and transformation of photoexcitation energy into electrical energy via charge separation (e.g., charge injection at interfaces). To treat ultrafast excited-state dynamics and exciton/charge transport we have developed a nonadiabatic excited-state molecular dynamics (NA-ESMD) framework incorporating quantum transitions. Our calculations rely on the use of the Collective Electronic Oscillator (CEO) package accounting for many-body effects and actual potential energy surfaces of the excited states combined with Tully's fewest switches algorithm for surface hopping for probing nonadiabatic processes. This method is applied to model the photoinduced dynamics of distyrylbenzene (a small oligomer of polyphenylene vinylene, PPV). Our analysis shows intricate details of photoinduced vibronic relaxation and identifies specific slow and fast nuclear motions that are strongly coupled to the electronic degrees of freedom, namely, torsion and bond length alternation, respectively. Nonadiabatic relaxation of the highly excited mA(g) state is predicted to occur on a femtosecond time scale at room temperature and on a picosecond time scale at low temperature. PMID:21218841

  20. 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

  1. 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

  2. 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

  3. The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection.

    PubMed

    Jaillon, Sébastien; Moalli, Federica; Ragnarsdottir, Bryndis; Bonavita, Eduardo; Puthia, Manoj; Riva, Federica; Barbati, Elisa; Nebuloni, Manuela; Cvetko Krajinovic, Lidija; Markotic, Alemka; Valentino, Sonia; Doni, Andrea; Tartari, Silvia; Graziani, Giorgio; Montanelli, Alessandro; Delneste, Yves; Svanborg, Catharina; Garlanda, Cecilia; Mantovani, Alberto

    2014-04-17

    Immunity in the urinary tract has distinct and poorly understood pathophysiological characteristics and urinary tract infections (UTIs) are important causes of morbidity and mortality. We investigated the role of the soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective control of UTIs and exacerbated inflammation. Expression of PTX3 was induced in uroepithelial cells by uropathogenic Escherichia coli (UPEC) in a Toll-like receptor 4 (TLR4)- and MyD88-dependent manner. PTX3 enhanced UPEC phagocytosis and phagosome maturation by neutrophils. PTX3 was detected in urine of UTI patients and amounts correlated with disease severity. In cohorts of UTI-prone patients, PTX3 gene polymorphisms correlated with susceptibility to acute pyelonephritis and cystitis. These results suggest that PTX3 is an essential component of innate resistance against UTIs. Thus, the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against UTIs.

  4. The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection.

    PubMed

    Jaillon, Sébastien; Moalli, Federica; Ragnarsdottir, Bryndis; Bonavita, Eduardo; Puthia, Manoj; Riva, Federica; Barbati, Elisa; Nebuloni, Manuela; Cvetko Krajinovic, Lidija; Markotic, Alemka; Valentino, Sonia; Doni, Andrea; Tartari, Silvia; Graziani, Giorgio; Montanelli, Alessandro; Delneste, Yves; Svanborg, Catharina; Garlanda, Cecilia; Mantovani, Alberto

    2014-04-17

    Immunity in the urinary tract has distinct and poorly understood pathophysiological characteristics and urinary tract infections (UTIs) are important causes of morbidity and mortality. We investigated the role of the soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective control of UTIs and exacerbated inflammation. Expression of PTX3 was induced in uroepithelial cells by uropathogenic Escherichia coli (UPEC) in a Toll-like receptor 4 (TLR4)- and MyD88-dependent manner. PTX3 enhanced UPEC phagocytosis and phagosome maturation by neutrophils. PTX3 was detected in urine of UTI patients and amounts correlated with disease severity. In cohorts of UTI-prone patients, PTX3 gene polymorphisms correlated with susceptibility to acute pyelonephritis and cystitis. These results suggest that PTX3 is an essential component of innate resistance against UTIs. Thus, the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against UTIs. PMID:24745336

  5. Si-BEARING MOLECULES TOWARD IRC+10216: ALMA UNVEILS THE MOLECULAR ENVELOPE OF CWLeo

    SciTech Connect

    Prieto, L. Velilla; Cernicharo, J.; Quintana-Lacaci, G.; Agúndez, M.; Fonfría, J. P.; Marcelino, N.; Zúñiga, J.; Requena, A.; Bastida, A.; Lique, F.

    2015-06-01

    We report the detection of SiS rotational lines in high-vibrational states as well as SiO and SiC{sub 2} 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 SiC{sub 2} and also proves the existence of an increase in the SiC{sub 2} 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.

  6. 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

  7. 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

  8. 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.

  9. Reconciling patterns of inter-ocean molecular variance from four classes of molecular markers in blue marlin (Makaira nigricans).

    PubMed

    Buonaccorsi, V P; McDowell, J R; Graves, J E

    2001-05-01

    Different classes of molecular markers occasionally yield discordant views of population structure within a species. Here, we examine the distribution of molecular variance from 14 polymorphic loci comprising four classes of molecular markers within approximately 400 blue marlin individuals (Makaira nigricans). Samples were collected from the Atlantic and Pacific Oceans over 5 years. Data from five hypervariable tetranucleotide microsatellite loci and restriction fragment length polymorphism (RFLP) analysis of whole molecule mitochondrial DNA (mtDNA) were reported and compared with previous analyses of allozyme and single-copy nuclear DNA (scnDNA) loci. Temporal variance in allele frequencies was nonsignificant in nearly all cases. Mitochondrial and microsatellite loci revealed striking phylogeographic partitioning among Atlantic and Pacific Ocean samples. A large cluster of alleles was present almost exclusively in Atlantic individuals at one microsatellite locus and for mtDNA, suggesting that, if gene flow occurs, it is likely to be unidirectional from Pacific to Atlantic oceans. Mitochondrial DNA inter-ocean divergence (FST) was almost four times greater than microsatellite or combined nuclear divergences including allozyme and scnDNA markers. Estimates of Neu varied by five orders of magnitude among marker classes. Using mathematical and computer simulation approaches, we show that substantially different distributions of FST are expected from marker classes that differ in mode of inheritance and rate of mutation, without influence of natural selection or sex-biased dispersal. Furthermore, divergent FST values can be reconciled by quantifying the balance between genetic drift, mutation and migration. These results illustrate the usefulness of a mitochondrial analysis of population history, and relative precision of nuclear estimates of gene flow based on a mean of several loci.

  10. Excited-State Structure Modifications Due to Molecular Substituents and Exciton Scattering in Conjugated Molecules.

    PubMed

    Li, Hao; Catanzaro, Michael J; Tretiak, Sergei; Chernyak, Vladimir Y

    2014-02-20

    Attachment of chemical substituents (such as polar moieties) constitutes an efficient and convenient way to modify physical and chemical properties of conjugated polymers and oligomers. Associated modifications in the molecular electronic states can be comprehensively described by examining scattering of excitons in the polymer's backbone at the scattering center representing the chemical substituent. Here, we implement effective tight-binding models as a tool to examine the analytical properties of the exciton scattering matrices in semi-infinite polymer chains with substitutions. We demonstrate that chemical interactions between the substitution and attached polymer are adequately described by the analytical properties of the scattering matrices. In particular, resonant and bound electronic excitations are expressed via the positions of zeros and poles of the scattering amplitude, analytically continued to complex values of exciton quasi-momenta. We exemplify the formulated concepts by analyzing excited states in conjugated phenylacetylenes substituted by perylene. PMID:26270830

  11. Molecular Dynamics simulations of Inhibitor of Apoptosis Proteins and identification of potential small molecule inhibitors.

    PubMed

    Jayakumar, Jayanthi; Anishetty, Sharmila

    2014-05-01

    Chemotherapeutic resistance due to over expression of Inhibitor of Apoptosis Proteins (IAPs) XIAP, survivin and livin has been observed in various cancers. In the current study, Molecular Dynamics (MD) simulations were carried out for all three IAPs and a common ligand binding scaffold was identified. Further, a novel sequence based motif specific to these IAPs was designed. SMAC is an endogenous inhibitor of IAPs. Screening of ChemBank for compounds similar to lead SMAC-non-peptidomimetics yielded a cemadotin related compound NCIMech_000654. Cemadotin is a derivative of natural anti-tumor peptide dolastatin-15; hence these compounds were docked against all three IAPs. Based on our analysis, we propose that NCIMech_000654/dolastatin-15/cemadotin derivatives may be investigated for their potential in inhibiting XIAP, survivin and livin.

  12. 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.

  13. Molecular final states after. beta. decay of tritium-substituted molecules

    SciTech Connect

    Claxton, T.A.; Schafroth, S.; Meier, P.F. )

    1992-05-01

    Calculations on the ground state of HT and CH{sub 3}T and the excited states of HHe{sup +} and CH{sub 3}He{sup +} have been carried out within the sudden approximation to test alternative approaches to existing problems, with the ultimate aim of studying the effects of a molecular environment on the detailed energetics of tritium {beta} decay. By using an appropriate projection operator most of the transition probability has been accounted for. Commonly used sum rules are shown to have limited utility. The inaccuracies introduced by describing an excited state by a single spin-adapted configuration are discussed. The problem of determining transition probabilities from configuration-interaction wave functions is highlighted and some solutions are proposed.

  14. bcl::Cluster : A method for clustering biological molecules coupled with visualization in the Pymol Molecular Graphics System

    PubMed Central

    Alexander, Nathan; Woetzel, Nils; Meiler, Jens

    2016-01-01

    Clustering algorithms are used as data analysis tools in a wide variety of applications in Biology. Clustering has become especially important in protein structure prediction and virtual high throughput screening methods. In protein structure prediction, clustering is used to structure the conformational space of thousands of protein models. In virtual high throughput screening, databases with millions of drug-like molecules are organized by structural similarity, e.g. common scaffolds. The tree-like dendrogram structure obtained from hierarchical clustering can provide a qualitative overview of the results, which is important for focusing detailed analysis. However, in practice it is difficult to relate specific components of the dendrogram directly back to the objects of which it is comprised and to display all desired information within the two dimensions of the dendrogram. The current work presents a hierarchical agglomerative clustering method termed bcl::Cluster. bcl::Cluster utilizes the Pymol Molecular Graphics System to graphically depict dendrograms in three dimensions. This allows simultaneous display of relevant biological molecules as well as additional information about the clusters and the members comprising them.

  15. 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

  16. 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.

  17. Bulk and single-molecule characterization of an improved molecular beacon utilizing H-dimer excitonic behavior.

    PubMed

    Conley, Nicholas R; Pomerantz, Andrea Kurtz; Wang, Hui; Twieg, Robert J; Moerner, W E

    2007-07-19

    Pairs of fluorophores in close proximity often show self-quenching of fluorescence by the well-known H-dimer mechanism. We use a pair of fluorophores in the new dicyanomethylenedihydrofuran (DCDHF) dye family in the design and characterization of a new fluorescent probe for nucleic acid detection, which we refer to as a self-quenched intramolecular dimer (SQuID) molecular beacon (MB). We obtain a quenching efficiency of 97.2%, higher than the only other reported value for a MB employing fluorophore self-quenching by H-dimer formation. Furthermore, the excellent single-molecule (SM) emitter characteristics of the DCDHF dyes allow observation of individual SQuID MB-target complexes immobilized on a surface, where the doubled SM emission intensity of our target-bound beacon ensures a higher signal-to-background ratio than conventional fluorophore-quencher MBs. Additional advantages of the SQuID MB are single-pot labeling, visible colorimetric detection of the target, and intrinsic single-molecule two-step photobleaching behavior, which offers a specific means of discriminating between functional MBs and spurious fluorescence.

  18. Molecular and biochemical characterization of human galactokinase and its small molecule inhibitors.

    PubMed

    Tang, M; Wierenga, K; Elsas, L J; Lai, K

    2010-12-01

    Human galactokinase (GALK) is the first enzyme in the Leloir pathway, converting α-d-galactose into galactose-1-phosphate (Gal-1-P). Recently, there is increasing interest in targeting GALK as a novel therapy to ameliorate the disease manifestations in patients with Classic Galactosemia as it would, in combination with (ga-)lactose restriction reduce accumulation of Gal-1-P, a cytotoxic agent. Previously, we identified 34 small molecule compounds that inhibited GALK in vitro using experimental high-throughput screening. In order to isolate useful lead compounds, we characterized these hits with regards to their kinase selectivity profiles, potency and capability to reduce Gal-1-P accumulation in patient cell lines, and their modes of action. We found that the majority of these compounds had IC(50)s ranging from 0.7μM to 33.3μM. When tested against other members of the GHMP kinase family, three compounds (1, 4, and 24) selectively inhibited GALK with high potency. Through alignment of GALK and mevalonate kinase (MVK) crystal structures, we identified that eight amino acid residues and an L1 loop were different within the ATP-binding pockets of these two closely related kinases. By site-directed mutagenesis experiments, we identified one amino acid residue required for the inhibitory function of two of the three selective compounds. Based on these results, we generated binding models of these two compounds using a high-precision docking program. Compounds 4 and 24 inhibited GALK in a mixed model, while compound 1 exhibited parabolic competitive inhibition. Most importantly, using cells from galactosemic patients we found that selected compounds lowered Gal-1-P concentrations.

  19. 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

  20. ATOMIC AND MOLECULAR PHYSICS: Interference of dissociating wave packets in the I2 molecule driven by femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Han, Yong-Chang; Hu, Wen-Hui; Yu, Jie; Cong, Shu-Lm

    2009-11-01

    The interference between two dissociating wave packets of the I2 molecule driven by femtosecond laser pulses is theoretically studied by using the time-dependent quantum wave packet method. Both the internuclear distance- and velocity-dependent density functions are calculated and discussed. It is demonstrated that the interference pattern is determined by the phase difference and the delay time between two pump pulses. With two identical pulses with a delay time of 305 fs and a FWHM of 20 fs, more interference fringes can be observed, while with two pump pulses with a delay time of 80 fs and a FWHM of 20 fs, only a few interference fringes can be observed.

  1. 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.

  2. 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.

  3. Molecular motion, dielectric response, and phase transition of charge-transfer crystals: acquired dynamic and dielectric properties of polar molecules in crystals.

    PubMed

    Harada, Jun; Ohtani, Masaki; Takahashi, Yukihiro; Inabe, Tamotsu

    2015-04-01

    Molecules in crystals often suffer from severe limitations on their dynamic processes, especially on those involving large structural changes. Crystalline compounds, therefore, usually fail to realize their potential as dielectric materials even when they have large dipole moments. To enable polar molecules to undergo dynamic processes and to provide their crystals with dielectric properties, weakly bound charge-transfer (CT) complex crystals have been exploited as a molecular architecture where the constituent polar molecules have some freedom of dynamic processes, which contribute to the dielectric properties of the crystals. Several CT crystals of polar tetrabromophthalic anhydride (TBPA) molecules were prepared using TBPA as an electron acceptor and aromatic hydrocarbons, such as coronene and perylene, as electron donors. The crystal structures and dielectric properties of the CT crystals as well as the single-component crystal of TBPA were investigated at various temperatures. Molecular reorientation of TBPA molecules did not occur in the single-component crystal, and the crystal did not show a dielectric response due to orientational polarization. We have found that the CT crystal formation provides a simple and versatile method to develop molecular dielectrics, revealing that the molecular dynamics of the TBPA molecules and the dielectric property of their crystals were greatly changed in CT crystals. The TBPA molecules underwent rapid in-plane reorientations in their CT crystals, which exhibited marked dielectric responses arising from the molecular motion. An order-disorder phase transition was observed for one of the CT crystals, which resulted in an abrupt change in the dielectric constant at the transition temperature.

  4. 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

  5. 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.

  6. 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

  7. 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.

  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. The Use of Molecular Modeling and VSEPR Theory in the Undergraduate Curriculum to Predict the Three-Dimensional Structure of Molecules

    NASA Astrophysics Data System (ADS)

    Pfennig, Brian W.; Frock, Richard L.

    1999-07-01

    This paper illustrates how valence shell electron pair repulsion (VSEPR) theory and molecular modeling can be used in a complimentary fashion in the undergraduate curriculum to predict the three-dimensional structure of molecules. Students use the familiar VSEPR model to sketch the three-dimensional structures of molecules predicted by a comparison of the relative magnitudes of electrostatic repulsion between electron pair domains on the central atom. Despite the simplicity and elegance of the VSEPR model, however, students often have difficulty visualizing the three-dimensional shapes of molecules and learning the more subtle features of the model, such as the bond length and bond angle deviations from ideal geometry that accompany the presence of lone pair or multiple bond domains or that result from differences in the electronegativity of the bonded atoms, partial charges and molecular dipole moments, and site preferences in the trigonal bipyramidal electron geometry. Students therefore also employ a molecular modeling approach to predict the three-dimensional shapes of molecules by performing both molecular mechanics and semiempirical quantum mechanical calculations to minimize the structures of these molecules. A major strength of the molecular modeling approach is that it allows students to quantitatively explore the more subtle implications of VSEPR theory using an alternative model. Student responses on end-of-the-semester evaluations ranked this exercise highly among the seven projects performed during the semester, commenting specifically on how the software allowed them to visualize the three-dimensional aspects of molecules more effectively than simple ball-and-stick models and on how the molecular modeling helped them to explore the more detailed structural features predicted by VSEPR theory.

  10. Molecular patterns of X chromosome-linked color vision genes among 134 menof European ancestry

    SciTech Connect

    Drummond-Borg, M.; Deeb, S.S.; Motulsky, A.G. )

    1989-02-01

    The authors 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. Characteristic anomalous patterns were seen in 15 (11.2%) individuals: 7 (5.2%) had patterns characteristic of deuteranomaly, 2 (1.5%) had patterns characteristic of deuteranopia, and 6 (4.5%) had protan patterns. 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%). Thus, DNA testing detected anomalous color vision pigment genes at a higher frequency than expected from phenotypic color vision tests.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. Molecular bioelectricity: how endogenous voltage potentials control cell behavior and instruct pattern regulation in vivo.

    PubMed

    Levin, Michael

    2014-12-01

    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

  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. 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

  18. Molecular Framework of a Regulatory Circuit Initiating Two-Dimensional Spatial Patterning of Stomatal Lineage.

    PubMed

    Horst, Robin J; Fujita, Hironori; Lee, Jin Suk; Rychel, Amanda L; Garrick, Jacqueline M; Kawaguchi, Masayoshi; Peterson, Kylee M; Torii, Keiko U

    2015-07-01

    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

  19. 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.

  20. Single Molecule Fluorescence Image Patterns Linked to Dipole Orientation and Axial Position: Application to Myosin Cross-Bridges in Muscle Fibers

    PubMed Central

    Burghardt, Thomas P.

    2011-01-01

    Background Photoactivatable fluorescent probes developed specifically for single molecule detection extend advantages of single molecule imaging to high probe density regions of cells and tissues. They perform in the native biomolecule environment and have been used to detect both probe position and orientation. Methods and Findings Fluorescence emission from a single photoactivated probe captured in an oil immersion, high numerical aperture objective, produces a spatial pattern on the detector that is a linear combination of 6 independent and distinct spatial basis patterns with weighting coefficients specifying emission dipole orientation. Basis patterns are tabulated for single photoactivated probes labeling myosin cross-bridges in a permeabilized muscle fiber undergoing total internal reflection illumination. Emitter proximity to the glass/aqueous interface at the coverslip implies the dipole near-field and dipole power normalization are significant affecters of the basis patterns. Other characteristics of the basis patterns are contributed by field polarization rotation with transmission through the microscope optics and refraction by the filter set. Pattern recognition utilized the generalized linear model, maximum likelihood fitting, for Poisson distributed uncertainties. This fitting method is more appropriate for treating low signal level photon counting data than χ2 minimization. Conclusions Results indicate that emission dipole orientation is measurable from the intensity image except for the ambiguity under dipole inversion. The advantage over an alternative method comparing two measured polarized emission intensities using an analyzing polarizer is that information in the intensity spatial distribution provides more constraints on fitted parameters and a single image provides all the information needed. Axial distance dependence in the emission pattern is also exploited to measure relative probe position near focus. Single molecule images from axial

  1. 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.

  2. 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

  3. 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

  4. Molecular basis of natural variation and environmental control of trichome patterning

    PubMed Central

    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

  5. (Questions)n on phloem biology. 2. Mass flow, molecular hopping, distribution patterns and macromolecular signalling.

    PubMed

    van Bel, Aart J E; Furch, Alexandra C U; Hafke, Jens B; Knoblauch, Michael; Patrick, John W

    2011-10-01

    This review speculates on correlations between mass flow in sieve tubes and the distribution of photoassimilates and macromolecular signals. Since micro- (low-molecular compounds) and macromolecules are withdrawn from, and released into, the sieve-tube sap at various rates, distribution patterns of these compounds do not strictly obey mass-flow predictions. Due to serial release and retrieval transport steps executed by sieve tube plasma membranes, micromolecules are proposed to "hop" between sieve element/companion cell complexes and phloem parenchyma cells under source-limiting conditions (apoplasmic hopping). Under sink-limiting conditions, micromolecules escape from sieve tubes via pore-plasmodesma units and are temporarily stored. It is speculated that macromolecules "hop" between sieve elements and companion cells using plasmodesmal trafficking mechanisms (symplasmic hopping). We explore how differential tagging may influence distribution patterns of macromolecules and how their bidirectional movement could arise. Effects of exudation techniques on the macromolecular composition of sieve-tube sap are discussed. PMID:21889037

  6. Structures of pattern recognition receptors reveal molecular mechanisms of autoinhibition, ligand recognition and oligomerization.

    PubMed

    Chuenchor, Watchalee; Jin, Tengchuan; Ravilious, Geoffrey; Xiao, T Sam

    2014-02-01

    Pattern recognition receptors (PRRs) are essential sentinels for pathogens or tissue damage and integral components of the innate immune system. Recent structural studies have provided unprecedented insights into the molecular mechanisms of ligand recognition and signal transduction by several PRR families at distinct subcellular compartments. Here we highlight some of the recent discoveries and summarize the common themes that are emerging from these exciting studies. Better mechanistic understanding of the structure and function of the PRRs will improve future prospects of therapeutic targeting of these important innate immune receptors.

  7. 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

  8. Guided Cell Patterning On Gold-Silicon Dioxide Substrates by Surface Molecular Engineering

    SciTech Connect

    Veiseh, Mandana; Wickes, Bronwyn; Castner, David G.; Zhang, Miqin

    2004-07-01

    We report an effective approach to patterning cells on a gold-silicon substrate with high precision, selectivity, stability, and reproducibility. This technique is based on photolithography and surface molecular engineering and does not involve a cell positioning or delivery device, thus reducing potential damage to cells. Cell patterning is achieved by activating the gold regions with functionalized thiols that covalently bind proteins to guide the subsequent cell adhesion and passivating the silicon regions with polyethylene glycol (PEG) to resist cell adhesion. Time-of-light secondary ion mass spectrometry (TOF-SIMS), a powerful surface chemical state imaging technique that allows simultaneous chemical and spatial characterization, was used to characterize the chemistry of the cell-adhesive and cell-resistant regions of the surface at key stages in the device fabrication. Fourier transform infrared (FTIR) reflectance spectroscopy was used to verify the immobilization of proteins on model surfaces. Proteins were tagged with Rhodamine fluorescent probes to characterize patterned surfaces by fluorescence microscopy. Finally, 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 numerous medical, environmental, and defense applications.

  9. Cholesterol-Induced Membrane Microvesicles As Novel Carriers of Damage–Associated Molecular Patterns Mechanisms of Formation, Action, and Detoxification

    PubMed Central

    Liu, Ming-Lin; Scalia, Rosario; Mehta, Jawahar L.; Williams, Kevin Jon

    2014-01-01

    Objective Cholesterol enrichment occurs in vivo when phagocytes ingest retained and aggregated lipoproteins, damaged or senescent cells, and related debris. We previously reported that enrichment of human monocyte/macrophages with unesterified cholesterol (UC) triggers the release of highly procoagulant microvesicles ([MVs], also called microparticles) through induction of apoptosis. We determined whether UC-induced MVs (UCMVs) might transmit endogenous danger signals and, if so, what molecular processes might be responsible for their production, recognition, and detoxification. Methods and Results Injection of UCMVs into rats provoked extensive leukocyte rolling and adherence to postcapillary venules in vivo. Likewise, exposure of mouse aortic explants or cultured human endothelial cells to UCMVs augmented the adhesion of human monocytes by several fold and increased endothelial cell intercellular adhesion molecule-1 via nuclear factor-κB activation. To explore molecular mechanisms, we found that UC enrichment of human monocytes, in the absence of other stimuli, induced mitochondrial complex II–dependent accumulation of superoxide and peroxides. A subset of these moieties was exported on UCMVs and mediated endothelial activation. Strikingly, aortic explants from mice lacking lectin–like oxidized low–density lipoprotein receptor-1, a pattern-recognition receptor, were essentially unable to respond to UCMVs, whereas simultaneously treated explants from wild-type mice responded robustly by increasing monocyte recruitment. Moreover, high-density lipoprotein and its associated enzyme paraoxonase-1 exerted unexpected roles in the detoxification of UCMVs. Conclusion Overall, our study implicates MVs from cholesterol–loaded human cells as novel carriers of danger signals. By promoting maladaptive immunologic and thrombotic responses, these particles may contribute to atherothrombosis and other conditions in vivo. PMID:22814745

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. Limits on the Natural Oxygen-18 Abundance of Cellulose: Intra-molecular Patterns

    NASA Astrophysics Data System (ADS)

    Sternberg, L.; Jahren, H.; Anderson, W.; Pinzon, M. C.

    2005-12-01

    The oxygen isotope composition of tree-ring cellulose is an often-invoked quantitative proxy for multiple environmental factors, including paleotemperature, paleohumidity and paleoprecipitation patterns. A broad survey of aerial and aquatic plants reveals an upper limit to the 18O enrichment of cellulose relative to water at the site of cellulose synthesis, which we explain via the comparison of individual oxygen atoms within the cellulose molecule. We collected stems from various geographical regions, extracted stem water and cellulose and determined the oxygen isotope ratios of these two components. The cellulose was hydrolyzed to its glucose moieties and derivatized to determine the oxygen isotope ratios of the oxygens attached to carbon 3, 4, 5, 6 of the glucose moieties, which allowed us to calculate the oxygen isotope ratios of the oxygen attached to the carbon 2 of the glucose moieties. A compilation of results from our collection and from previous publications shows that δ18O values of cellulose increase with δ18O values of stem water only for samples having stem water with δ18O values below -10‰ (SMOW). However, the δ18O values of stem cellulose levels off and remains constant for stems having water with δ18O values greater than -10‰. This pattern suggests a limit on the enrichment of stem (and by inference tree ring) cellulose. This limitation had previously been ascribed to environmental factors affecting leaf water (e.g., humidity, stomatal conductance, solute potential). A compilation of the δ18O values of cellulose from aquatic plants versus that of their ambient water, however, shows the same general pattern which has been previously explained on the basis of evaporation rates and heterogeneities of lake water. We disprove the previous explanations by demonstrating differential isotopic effects on the oxygen atoms of the cellulose molecule. Our observation on the δ18O values of oxygen attached to carbon 2 versus those attached to carbon 3

  15. 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.

  16. 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.

  17. 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

  18. Versatile piezoelectric pulsed molecular beam source for gaseous compounds and organic molecules with femtomole accuracy for UHV and surface science applications

    SciTech Connect

    Schiesser, Alexander; Schaefer, Rolf

    2009-08-15

    This note describes the construction of a piezoelectric pulsed molecular beam source based upon a design presented in an earlier work [D. Proch and T. Trickl, Rev. Sci. Instrum. 60, 713 (1988)]. The design features significant modifications that permit the determination of the number of molecules in a beam pulse with an accuracy of 1x10{sup 11} molecules per pulse. The 21 cm long plunger-nozzle setup allows the molecules to be brought to any point of the UHV chamber with very high intensity. Furthermore, besides typical gaseous compounds, also smaller organic molecules with a vapor pressure higher than 0.1 mbar at room temperature may serve as feed material. This makes the new design suitable for various applications in chemical and surface science studies.

  19. 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

  20. 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

  1. 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

  2. Brassinosteroids modulate the efficiency of plant immune responses to microbe-associated molecular patterns.

    PubMed

    Belkhadir, Youssef; Jaillais, Yvon; Epple, Petra; Balsemão-Pires, Emilia; Dangl, Jeffery L; Chory, Joanne

    2012-01-01

    Metazoans and plants use pattern recognition receptors (PRRs) to sense conserved microbial-associated molecular patterns (MAMPs) in the extracellular environment. In plants, the bacterial MAMPs flagellin and elongation factor Tu (EF-Tu) activate distinct, phylogenetically related cell surface pattern recognition receptors of the leucine-rich repeat receptor kinase (LRR-RK) family called FLS2 and EF-Tu receptor, respectively. BAK1 is an LRR-RK coreceptor for both FLS2 and EF-Tu receptor. BAK1 is also a coreceptor for the plant brassinosteroid (BR) receptor, the LRR-RK BRI1. Binding of BR to BRI1 primarily promotes cell elongation. Here, we tune the BR pathway response to establish how plant cells can generate functionally different cellular outputs in response to MAMPs and pathogens. We demonstrate that BR can act antagonistically or synergistically with responses to MAMPs. We further show that the synergistic activities of BRs on MAMP responses require BAK1. Our results highlight the importance of plant steroid homeostasis as a critical step in the establishment of plant immunity. We propose that tradeoffs associated with plasticity in the face of infection are layered atop plant steroid developmental programs.

  3. 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

  4. Beyond the molecular orbital conception of electronically excited states through the quantum theory of atoms in molecules.

    PubMed

    Ferro-Costas, David; Pendás, Angel Martín; González, Leticia; Mosquera, Ricardo A

    2014-05-28

    We show that the use of the quantum theory of atoms in molecules (QTAIM) in electronically excited states allows expanding the knowledge that the molecular orbital (MO) framework provides about electronic rearrangements. Despite that historical prejudice seemed to preclude the use of QTAIM beyond the electronic ground state, this paper evidences that QTAIM is versatile enough to deal with excited states. As an example, the paradigmatic n → π* electronic transition of formaldehyde is analyzed. Using QTAIM, an energy partition of excited state energies into atomic and diatomic energies is carried out for the first time. This partition shows that upon electronic excitation the atoms of the CO bond experience a stabilization in their net energies, accompanied by a destabilization in their interaction, a fact which is in accordance with the idea of populating an antibonding π* MO. The associated C-O bond elongation in the nπ* state does not involve a change in the π atomic populations - as one would expect from a π* orbital - but in the σ ones. Moreover, it is also found that the nπ* state is characterized by a weaker C-O interaction energy in comparison to that in the electronic ground state. In order to strengthen this interaction, the electron-electron repulsion between C and O is reduced via a symmetry-breaking of the electron density, causing the C pyramidalization. A topological analysis based on the Laplacian of the electron density and on the electron localization function (ELF) reveals that the n → π* transition can be visualized as a rotation of 90° of the oxygen lone pairs.

  5. 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

  6. Walking molecules.

    PubMed

    von Delius, Max; Leigh, David A

    2011-07-01

    Movement is intrinsic to life. Biologists have established that most forms of directed nanoscopic, microscopic and, ultimately, macroscopic movements are powered by molecular motors from the dynein, myosin and kinesin superfamilies. These motor proteins literally walk, step by step, along polymeric filaments, carrying out essential tasks such as organelle transport. In the last few years biological molecular walkers have inspired the development of artificial systems that mimic aspects of their dynamics. Several DNA-based molecular walkers have been synthesised and shown to walk directionally along a track upon sequential addition of appropriate chemical fuels. In other studies, autonomous operation--i.e. DNA-walker migration that continues as long as a complex DNA fuel is present--has been demonstrated and sophisticated tasks performed, such as moving gold nanoparticles from place-to-place and assistance in sequential chemical synthesis. Small-molecule systems, an order of magnitude smaller in each dimension and 1000× smaller in molecular weight than biological motor proteins or the walker systems constructed from DNA, have also been designed and operated such that molecular fragments can be progressively transported directionally along short molecular tracks. The small-molecule systems can be powered by light or chemical fuels. In this critical review the biological motor proteins from the kinesin, myosin and dynein families are analysed as systems from which the designers of synthetic systems can learn, ratchet concepts for transporting Brownian substrates are discussed as the mechanisms by which molecular motors need to operate, and the progress made with synthetic DNA and small-molecule walker systems reviewed (142 references). PMID:21416072

  7. Time dependent chemistry in dense molecular clouds. III - Infrared band cross sections of molecules in the solid state at 10 K

    NASA Technical Reports Server (NTRS)

    Dhendecourt, L. B.; Allamandola, L. J.

    1986-01-01

    Thin film transmission infrared spectra and a list of integrated absorbance values (band strengths) of bands in the 2.5 to 20 micron range of various molecular solids deposited on a CsI window cooled to 10 K are presented. These solids include molecules known or suspected to be present on interstellar grains such as H2O, CO, NH3 and CH4 and mixtures of these molecules as well as various hydrocarbons. The method is described by which the absorbance values derived can be used to estimate column densities of species adsorbed on interstellar grains and other solids associated with celestial IR sources.

  8. 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

  9. Damage-associated molecular patterns and their pathological relevance in diabetes mellitus.

    PubMed

    Shin, Jung Jae; Lee, Eun Kyung; Park, Tae Joo; Kim, Wook

    2015-11-01

    Diabetes, a group of metabolic and age-related diseases, is a major global health problem, the incidence of which has increased dramatically in recent decades. Type 1 diabetes mellitus (T1DM) is a complex, T cell-mediated autoimmune disease characterized by immune cell infiltration and chronic inflammation in the islets of Langerhans. Type 2 diabetes mellitus (T2DM) is a complex metabolic disease characterized by hyperglycemia (high blood sugar) resulting from insulin resistance and β-cell dysfunction. The involvement of inflammatory processes, such as immune cell infiltration, and chronic inflammation in the pathogenesis of diabetes is less well understood in T2DM than in T1DM. However, studies conducted in the past decade have shown a strong link between inflammation and metabolic dysfunction. They have also shown that chronic inflammation plays a key role in the pathogenesis of both T1DM and T2DM. Two immunological factors commonly contribute to the pathogenesis of diabetes: the activation of inflammasomes and the release of proinflammatory cytokines in response to damage-associated molecular patterns (DAMPs). Inflammasomes are intracellular multiprotein molecular platforms. DAMPs act as endogenous danger signals. Here, we review current research on the function(s) of inflammasomes and DAMPs and discuss their pathological relevance and therapeutic implications in diabetes.

  10. Molecular phylogeny of echiuran worms (Phylum: Annelida) reveals evolutionary pattern of feeding mode and sexual dimorphism.

    PubMed

    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.

  11. Pathogen Associated Molecular Pattern (PAMP)-Triggered Immunity Is Compromised under C-Limited Growth

    PubMed Central

    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

    2015-01-01

    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

  12. Molecular insights into the origin of the Hox-TALE patterning system.

    PubMed

    Hudry, Bruno; Thomas-Chollier, Morgane; Volovik, Yael; Duffraisse, Marilyne; Dard, Amélie; Frank, Dale; Technau, Ulrich; Merabet, Samir

    2014-03-18

    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.

  13. 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.

  14. Molecular fingerprinting of lacustrian cyanobacterial communities: regional patterns in summer diversity.

    PubMed

    Touzet, Nicolas; McCarthy, David; Fleming, Gerard T A

    2013-12-01

    The assessment of lacustrian water quality is necessary to comply with environmental regulations. At the regional scale, difficulties reside in the selection of representative lakes. Given the risks towards water quality associated with phytoplankton blooms, a mesoscale survey was carried out in Irish lakes to identify patterns in the distribution and diversity of planktonic cyanobacteria. A stratified sampling strategy was carried out via geographic information systems (GIS) analysis of river catchment attributes due to the range of hydrogeomorphological features and the high number of lakes within the study area. 16S rRNA gene denaturing gradient gel electrophoresis analysis showed variation between the cyanobacterial communities sampled, with lower occurrence of cyanobacteria in August concomitant to increased wind and precipitation regimes. Multivariate analysis delineated three ecoregions based on land cover typology and revealed significant patterns in the distribution of cyanobacterial diversity. A majority of filamentous cyanobacteria genotypes occurred in larger lakes contained river catchments with substantial forest cover. In contrast, higher diversity of spherical cyanobacteria genotypes was observed in lakes of lesser trophic state. In the context of aquatic resource management, the combined use of GIS-based sampling strategy and molecular methods offers promising prospects for assessing microbial community structure at varying scales of space and time. PMID:23802655

  15. 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

  16. 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

  17. 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.

  18. Molecular analysis of geographic patterns of eukaryotic diversity in Antarctic soils.

    PubMed

    Lawley, Blair; Ripley, Sarah; Bridge, Paul; Convey, Peter

    2004-10-01

    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 degrees 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 degrees S). Rather, we found the reverse pattern, with highest diversity at sites on Alexander Island (ca. 72 degrees 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.

  19. 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.

  20. 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

  1. Evolution of Surface Morphology of Patterned GaAs(100) during Molecular Beam Epitaxial Growth

    NASA Astrophysics Data System (ADS)

    Kan, Hung-Chih; Shah, Sonam; Tadayyon-Eslami, Tabassom; Phaneuf, Raymond

    2003-03-01

    We report the results of an investigation of the evolution of the surface morphology during molecular beam epitaxial growth on a patterned GaAs(100) surface. The initial GaAs(100) surfaces were patterned lithographically with arrays of cylindrical pits whose diameters and center-to-center distances are varied in a combinatorial manner. Using atomic force microscopy (AFM), we characterized the evolution of the corrugation throughout the growth. We compare the measured height profiles with simulations from various continuum models[1]. This comparison allows us to discriminate between various continuum modes of growth. * Work supported by the Minta-Martin Foundation, the Laboratory for Physical Sciences, and an NSF-MRSEC, DMR 00-8008. Reference 1 Mehran Kardar, Giorgio Parisi, and Yi-Cheng Zhang, Physical Review Letters 56 (9), 889 (1986); Tao Sun, Hong Guo, and Martin Grant, Physical Review A 40 (11), 6763 (1989); Z.-W. Lai and S. Das Sarma, Physical Review Letters 66 (18), 2348 (1991); M. D. Johnson, C. Orme, A. W. Hunt et al., Physical Review Letters 72 (1), 116 (1994).

  2. Controlling molecular assemblies

    NASA Astrophysics Data System (ADS)

    Dameron, Arrelaine A.

    Using molecules designed to have only specific differences in their functionality, we have explored the influence of molecular conformation on the structural, electronic, and physical properties of self-assembled monolayers using both scanning probe and ensemble techniques. In the former case, we used two structurally similar molecules that differ in the degrees of freedom afforded to each. We found that this influenced the degree of order and conductance of self-assembled monolayers of each molecule, but had little influence of conductance switching of individual molecules inserted in alkanethiolate self-assembled monolayers. We further demonstrated how molecular structure influences phase separation, displace-ability, and molecular mobility of self-assembled monolayers by assembling 1-adamantanethiol on Au{111}. Molecular-resolution imaging of the self-assembled monolayers with the scanning tunneling microscopy confirmed a highly ordered hexagonally close-packed molecular lattice. We found that the 1-adamantanethiolate self-assembled monolayers were susceptible to replacement by the presence of another thiolated species, both from solution and vapor phases. Additionally, we determined that the displacement process is a nucleation and growth mechanism and the structure of the resulting self-assembled monolayers is dependent on the strength of the intermolecular interactions of the displacing molecules. It was hypothesized that 1-adamantanethiolate displacement was driven by a combination of energies gained from the exchange of one self-assembled monolayer for a denser self-assembled monolayer and from the increased stability due to intermolecular interaction forces. Exploiting the susceptibility of the 1-adamantanethiolate self-assembled monolayers to displacement, we have designed a novel patterning strategy, termed 'microdisplacement printing', by combining these sacrificial self-assembled monolayers with microcontact printing. During microdisplacement printing

  3. 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

  4. Phylogenetic Analysis and Molecular Evolution Patterns in the MIR482-MIR1448 Polycistron of Populus L

    PubMed Central

    Zhao, Jia-Ping; Diao, Shu; Zhang, Bing-Yu; Niu, Bao-Qing; Wang, Qing-Ling; Wan, Xian-Chong; Luo, You-Qing

    2012-01-01

    The microRNAs (miRNAs) miR482 and miR1448 are disease resistance-related miRNAs; the former is ubiquitously distributed in seed plants whereas the latter has only been reported in Populus trichocarpa. The precursor and mature sequences of poplar miR1448 are highly homologous to those of poplar miR482, and these two miRNAs are located in one transcript as a polycistron. Therefore, we hypothesized that the MIR1448 gene may have evolved from the MIR482 gene in poplar. However, the molecular evolution patterns of this process remain unclear. In this study, utilizing cloning and Blast analysis in NCBI ESTs and whole-genome shotgun contigs (WGS) dataset, we determined that the MIR482-MIR1448 polycistron is a family-specific clustered miRNA in Salicaceae. Moreover, phylogenetic analysis illustrated that MIR1448 is the product of a tandem duplication event from MIR482. Nucleotide substitution analysis revealed that both MIR482 and MIR1448 have more rapid evolution ratios than ribosomal DNA (rDNA) genes, and that compensatory mutations that occurred in the stem region of the secondary structure were the main mechanisms that drove the evolution of these MIRNA genes. Furthermore, by comparing the substitution patterns in the miRNA-target complexes of miR482 and miR1448, we inferred that co-evolution between miRNAs and their targets was the major force that drove the “duplicated MIR482” evolve to MIR1448. We propose a novel miRNA-target pairing pattern called the “frameshift targeted mechanism” to explain the gain of target genes by miR1448. The results also imply that the major role of miR482 was in resistance to disease or other stresses via NBS-LRR proteins, whereas the biological functions of miR1448 are more diverse. PMID:23094096

  5. Calculated Dipole Moments and Resulting Column Densities of Long Carbon Chain Molecules in TAURUS-MOLECULAR-CLOUD-1

    NASA Astrophysics Data System (ADS)

    Snyder, L. E.; Dykstra, C. E.; Bernholdt, D.

    A number of long carbon chain molecules have been detected in TMC-1 and many of these have no measured or calculated dipole moment. To remedy this, ab initio self-consistent field calculations with small empirical adjustments and extrapolation were used to find the dipole moments of molecules which are of interest for current or future TMC-1 observations.

  6. 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

  7. Single-Molecule Enzymology

    SciTech Connect

    Xie, Xiaoliang; Lu, H PETER.

    1999-06-04

    Viewing a movie of an enzyme molecule made from molecular dynamics (MD) simulation, we see incredible details of molecular motions, be it a change of the conformation or the action of a chemical reaction.

  8. Cyclodextrin-supported organic matrix for application of MALDI-MS for forensics. Soft-ionization to obtain protonated molecules of low molecular weight compounds

    NASA Astrophysics Data System (ADS)

    Yonezawa, Tetsu; Asano, Takashi; Fujino, Tatsuya; Nishihara, Hiroshi

    2013-06-01

    A mass measurement technique for detecting low-molecular-weight drugs with a cyclodextrin-supported organic matrix was investigated. By using cyclodextrin-supported 2,4,6-trihydroxyacetophenone (THAP), the matrix-related peaks of drugs were suppressed. The peaks of protonated molecules of the sample and THAP were mainly observed, and small fragments were detected in a few cases. Despite the Na+ and K+ peaks were observed in the spectrum, Na+ or K+ adduct sample molecules were undetected, owing to the sugar units of cyclodextrin. The advantages of MALDI-MS with cyclodextrin-supported matrices as an analytical tool for forensic samples are discussed. The suppression of alkali adducted molecules and desorption process are also discussed.

  9. 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

  10. Distinct molecular structures and hydrogen bond patterns of α,α-diethyl-substituted cyclic imide, lactam, and acetamide derivatives in the crystalline phase

    NASA Astrophysics Data System (ADS)

    Krivoshein, Arcadius V.; Ordonez, Carlos; Khrustalev, Victor N.; Timofeeva, Tatiana V.

    2016-10-01

    α,α-Dialkyl- and α-alkyl-α-aryl-substituted cyclic imides, lactams, and acetamides show promising anticonvulsant, anxiolytic, and anesthetic activities. While a number of crystal structures of various α-substituted cyclic imides, lactams, and acetamides were reported, no in-depth comparison of crystal structures and solid-state properties of structurally matched compounds have been carried out so far. In this paper, we report molecular structure and intermolecular interactions of three α,α-diethyl-substituted compounds - 3,3-diethylpyrrolidine-2,5-dione, 3,3-diethylpyrrolidin-2-one, and 2,2-diethylacetamide - in the crystalline phase, as studied using single-crystal X-ray diffraction and IR spectroscopy. We found considerable differences in the patterns of H-bonding and packing of the molecules in crystals. These differences correlate with the compounds' melting points and are of significance to physical pharmacy and formulation development of neuroactive drugs.

  11. Multiscale Modeling of Cellular Epigenetic States: Stochasticity in Molecular Networks, Chromatin Folding in Cell Nuclei, and Tissue Pattern Formation of Cells.

    PubMed

    Liang, Jie; Cao, Youfang; Gursoy, Gamze; Naveed, Hammad; Terebus, Anna; Zhao, Jieling

    2015-01-01

    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.

  12. 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.

  13. Molecular profiling of experimental endometriosis identified gene expression patterns in common with human disease

    PubMed Central

    Flores, Idhaliz; Rivera, Elizabeth; Ruiz, Lynnette A.; Santiago, Olga I.; Vernon, Michael W.; Appleyard, Caroline B.

    2007-01-01

    OBJECTIVE To validate a rat model of endometriosis using cDNA microarrays by identifying common gene expression patterns beween experimental and natural disease. DESIGN Autotransplantation rat model. SETTING Medical school department. ANIMALS Female Sprague-Dawley rats. INTERVENTIONS Endometriosis was surgically-induced by suturing uterine horn implants next to the small intestine’s mesentery. Control rats received sutures with no implants. After 60 days, endometriotic implants and uterine horn were obtained. MAIN OUTCOME MEASURES Gene expression levels determined by cDNA microarrays and QRT-PCR. METHODS Cy5-labeled cDNA was synthesized from total RNA obtained from endometriotic implants. Cy3-labeled cDNA was synthesized using uterine RNA from a control rat. Gene expression levels were analyzed after hybridizing experimental and control labeled cDNA to PIQOR™ Toxicology Rat Microarrays (Miltenyi Biotec) containing 1,252 known genes. Cy5/Cy3 ratios were determined and genes with >2-fold higher or <0.5-fold lower expression levels were selected. Microarray results were validated by QRT-PCR. RESULTS We observed differential expression of genes previously shown to be upregulated in patients, including growth factors, inflammatory cytokines/receptors, tumor invasion/metastasis factors, adhesion molecules, and anti-apoptotic factors. CONCLUSIONS This study presents evidence in support of using this rat model to study the natural history of endometriosis and test novel therapeutics for this incurable disease. PMID:17478174

  14. Differential tapasin dependence of MHC class I molecules correlates with conformational changes upon peptide dissociation: A molecular dynamics simulation study

    SciTech Connect

    Sieker, Florian; Straatsma, TP; Springer, Sebastian; Zacharias, Martin W

    2008-08-01

    Efficiency of peptide loading to MHC class I molecules in the endoplasmatic reticulum depends on the class I allele and can involve interaction with tapasin and other proteins of the loading complex. Allele HLA-B*4402 (Asp at position 116) depends on tapasin for efficient peptide loading whereas HLA-B*4405 (identical to B*4402 except for Tyr116) can efficiently load peptides in the absence of tapasin. Both alleles adopt very similar structures in the presence of the same peptide. Molecular dynamics (MD) simulations on induced peptide termini dissociation from the α1/α2 peptide binding domains have been performed to characterize free energy changes and associated structural changes in the two alleles. A smooth free energy change along the distance dissociation coordinate was obtained for N terminus dissociation. A different shape and magnitude of the calculated free energy change and was obtained for induced peptide C terminus dissociation in case of the tapasin independent allele B*4405 compared to B*4402. Structural changes during C terminus dissociation occurred mainly in the first segment of the α2-1 helix that flanks the peptide C-terminus binding region (F-pocket) and contacts residue 116. This segment is also close to the proposed tapasin contact region. For B*4402, a stable shift towards an altered open F-pocket structure deviating significantly from the bound form was observed. In contrast, B*4405 showed only a transient opening of the F-pocket followed by relaxation towards a structure close to the bound form upon C terminus dissociation. The greater tendency for peptide-receptive conformation in the absence of peptide combined with a more long-range character of the interactions with the peptide C terminus facilitates peptide binding to B*4405 and could be responsible for the tapasin independence of this allele. A possible role of tapasin in case of HLA-B*4402 and other tapasin-dependent alleles could be the stabilization of a peptide receptive class I

  15. Discovery and validation of small-molecule heat-shock protein 90 inhibitors through multimodality molecular imaging in living subjects.

    PubMed

    Chan, Carmel T; Reeves, Robert E; Geller, Ron; Yaghoubi, Shahriar S; Hoehne, Aileen; Solow-Cordero, David E; Chiosis, Gabriela; Massoud, Tarik F; Paulmurugan, Ramasamy; Gambhir, Sanjiv S

    2012-09-11

    Up-regulation of the folding machinery of the heat-shock protein 90 (Hsp90) chaperone protein is crucial for cancer progression. The two Hsp90 isoforms (α and β) play different roles in response to chemotherapy. To identify isoform-selective inhibitors of Hsp90(α/β)/cochaperone p23 interactions, we developed a dual-luciferase (Renilla and Firefly) reporter system for high-throughput screening (HTS) and monitoring the efficacy of Hsp90 inhibitors in cell culture and live mice. HTS of a 30,176 small-molecule chemical library in cell culture identified a compound, N-(5-methylisoxazol-3-yl)-2-[4-(thiophen-2-yl)-6-(trifluoromethyl)pyrimidin-2-ylthio]acetamide (CP9), that binds to Hsp90(α/β) and displays characteristics of Hsp90 inhibitors, i.e., degradation of Hsp90 client proteins and inhibition of cell proliferation, glucose metabolism, and thymidine kinase activity, in multiple cancer cell lines. The efficacy of CP9 in disrupting Hsp90(α/β)/p23 interactions and cell proliferation in tumor xenografts was evaluated by non-invasive, repetitive Renilla luciferase and Firefly luciferase imaging, respectively. At 38 h posttreatment (80 mg/kg × 3, i.p.), CP9 led to selective disruption of Hsp90α/p23 as compared with Hsp90β/p23 interactions. Small-animal PET/CT in the same cohort of mice showed that CP9 treatment (43 h) led to a 40% decrease in (18)F-fluorodeoxyglucose uptake in tumors relative to carrier control-treated mice. However, CP9 did not lead to significant degradation of Hsp90 client proteins in tumors. We performed a structural activity relationship study with 62 analogs of CP9 and identified A17 as the lead compound that outperformed CP9 in inhibiting Hsp90(α/β)/p23 interactions in cell culture. Our efforts demonstrated the power of coupling of HTS with multimodality molecular imaging and led to identification of Hsp90 inhibitors.

  16. Molecular characterization of novel H-2 class I molecules expressed by a C3H UV-induced fibrosarcoma.

    PubMed Central

    McMillan, M; Lewis, K D; Rovner, D M

    1985-01-01

    Two novel class I-like molecules expressed on tumor 1591, a C3H UV-induced fibrosarcoma, are biochemically characterized using two-dimensional gel electrophoresis, a cross-blocking RIA, and tryptic peptide mapping. One novel molecule that reacts with CP28, a syngeneic tumor-specific monoclonal antibody, appears mosaic because it possesses characteristics of both Kk and Dk class I molecules. The second molecule is closely related but not identical to the bona fide Ld molecule expressed on BALB/c spleen. Thus 1591 expresses at least two novel class I molecules and is vigorously rejected by normal C3H mice, while a variant tumor derived from 1591, termed AS7, does not express these two class I molecules although it still expresses Kk and Dk. The significance of these observations to the immunobiology and genetics of the UV-induced fibrosarcoma system is discussed. Speculations on the role that the major histocompatibility complex may play in the immunosurveillance of neoplasms are also presented. Images PMID:3860872

  17. How dependent are molecular and atomic properties on the electronic structure method? Comparison of Hartree-Fock, DFT, and MP2 on a biologically relevant set of molecules.

    PubMed

    Matta, Chérif F

    2010-04-30

    This article compares molecular properties and atomic properties defined by the quantum theory of atoms in molecules (QTAIM) obtained from three underlying levels of theory: MP2(full), density functional theory (DFT) (B3LYP), and Hartree-Fock (H-F). The same basis set (6-311++G(d,p)) has been used throughout the study. The calculations and comparisons were applied to a set of 30 small molecules representing common fragments of biological molecules. The molecular properties investigated are the energies and the electrostatic moments (up to and including the quadrupoles), and the atomic properties include electron populations (and atomic charge), atomic dipolar and quadrupolar polarizations, atomic volumes, and corrected and raw atomic energies. The Cartesian distance between dipole vectors and the Frobenius distance between the quadrupole tensors calculated at the three levels of theory provide a measure of their correlation (or lack thereof). With the exception of energies (atomic and molecular), it is found that both DFT and H-F are in excellent agreement with MP2, especially with regards to the electrostatic mutipoles up to the quadrupoles, but DFT and MP2 agree better in almost all studied properties (with the exception of molecular geometries). QTAIM properties whether obtained from H-F, DFT(B3LYP), or MP2 calculations when used in the construction of empirical correlations with experiment such as quantitative structure-activity-(or property)-relationships (QSAR/QSPR) are equivalent (because the properties calculated at the three levels are very highly correlated among themselves with r(2) typically >0.95, and therefore preserving trends). These results suggest that the massive volume of results that were published in the older literature at the H-F level is valid especially when used to study trends or in QSAR or QSPR studies, and, as long as our test set of molecules is representative, there is no pressing need to re-evaluate them at other levels of theory

  18. Properties and reactivity patterns of AsP(3): an experimental and computational study of group 15 elemental molecules.

    PubMed

    Cossairt, Brandi M; Cummins, Christopher C

    2009-10-28

    Facile synthetic access to the isolable, thermally robust AsP(3) molecule has allowed for a thorough study of its physical properties and reaction chemistry with a variety of transition-metal and organic fragments. The electronic properties of AsP(3) in comparison with P(4) are revealed by DFT and atoms in molecules (AIM) approaches and are discussed in relation to the observed electrochemical profiles and the phosphorus NMR properties of the two molecules. An investigation of the nucleus independent chemical shifts revealed that AsP(3) retains spherical aromaticity. The thermodynamic properties of AsP(3) and P(4) are described. The reaction types explored in this study include the thermal decomposition of the AsP(3) tetrahedron to its elements, the synthesis and structural characterization of [(AsP(3))FeCp*(dppe)][BPh(4)] (dppe = 1,2-bis(diphenylphosphino)ethane), 1, selective single As-P bond cleavage reactions, including the synthesis and structural characterization of AsP(3)(P(N((i)Pr)(2))N(SiMe(3))(2))(2), 2, and activations of AsP(3) by reactive early transition-metal fragments including Nb(H)(eta(2)-(t)Bu(H)C horizontal lineNAr)(N[CH(2)(t)Bu]Ar)(2) and Mo(N[(t)Bu]Ar)(3) (Ar = 3,5-Me(2)C(6)H(3)). In the presence of reducing equivalents, AsP(3) was found to allow access to [Na][E(3)Nb(ODipp)(3)] (Dipp = 2,6-diisopropylphenyl) complexes (E = As or P) which themselves allow access to mixtures of As(n)P(4-n) (n = 1-4).

  19. A molecular dynamics study of the lateral free energy profile of a pair of cholesterol molecules as a function of their distance in phospholipid bilayers

    NASA Astrophysics Data System (ADS)

    Andoh, Yoshimichi; Oono, Kimiko; Okazaki, Susumu; Hatta, Ichiro

    2012-04-01

    Free energy profile of a pair of cholesterol molecules in a leaflet of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayers in the liquid-crystalline phase has been calculated as a function of their lateral distance using a combination of NPT-constant atomistic molecular dynamics calculations (P = 1 atm and T = 310.15 K) and the thermodynamic integration method. The calculated free energy clearly shows that the two cholesterol molecules form a dimer separated by a distance of 1.0-1.5 nm in POPC bilayers. Well depth of the free energy profile is about 3.5 kJ/mol, which is comparable to the thermal energy kBT at 310.15 K. This indicates that the aggregation of cholesterol molecules in the bilayers depends on the temperature as well as the concentration of the system. The free energy function obtained here may be used as a reference when coarse grained potential model is investigated for this two-component system. Local structure of POPC molecules around two cholesterol molecules has also been investigated.

  20. DG-AMMOS: A New tool to generate 3D conformation of small molecules using Distance Geometry and Automated Molecular Mechanics Optimization for in silico Screening

    PubMed Central

    2009-01-01

    Background Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. Results Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. Conclusion DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods. PMID:19912625

  1. The influence of the surface state onto the distance distribution of single molecules and small molecular clusters

    NASA Astrophysics Data System (ADS)

    Mehlhorn, Michael; Simic-Milosevic, Violeta; Jaksch, Stefan; Scheier, Paul; Morgenstern, Karina

    2010-09-01

    We investigate the distance distribution of two anorganic molecules (CO, H 2O), one organic radical ( para-benzyne), and one strongly dipolar molecule ( ortho-dinitrobenzene) on the (111) faces of copper and silver. Above the onset of diffusion, their distribution is influenced by the surface state and oscillates. While CO, H 2O, and para-benzyne show the expected oscillation period of ≈λ/2, ortho-dinitrobenzene oscillates with λ/4. The position of the first maximum in these oscillations is consistent with a perfect scatterer for the anorganic molecules, but inconsistent for the radical and the dipolar molecule. This observation is utilized to explain the double periodicity observed in the distance distribution of ortho-dinitrobenzene.

  2. Nucleation of Mixed Nitric Acid-Water Ice Nanoparticles in Molecular Beams that Starts with a HNO3 Molecule.

    PubMed

    Lengyel, Jozef; Pysanenko, Andriy; Kočišek, Jaroslav; Poterya, Viktoriya; Pradzynski, Christoph C; Zeuch, Thomas; Slavíček, Petr; Fárník, Michal

    2012-11-01

    Mixed (HNO3)m(H2O)n clusters generated in supersonic expansion of nitric acid vapor are investigated in two different experiments, (1) time-of-flight mass spectrometry after electron ionization and (2) Na doping and photoionization. This combination of complementary methods reveals that only clusters containing at least one acid molecule are generated, that is, the acid molecule serves as the nucleation center in the expansion. The experiments also suggest that at least four water molecules are needed for HNO3 acidic dissociation. The clusters are undoubtedly generated, as proved by electron ionization; however, they are not detected by the Na doping due to a fast charge-transfer reaction between the Na atom and HNO3. This points to limitations of the Na doping recently advocated as a general method for atmospheric aerosol detection. On the other hand, the combination of the two methods introduces a tool for detecting molecules with sizable electron affinity in clusters.

  3. Methanol and ethanol modulate responses to danger- and microbe-associated molecular patterns

    PubMed Central

    Hann, Claire T.; Bequette, Carlton J.; Dombrowski, James E.; Stratmann, Johannes W.

    2014-01-01

    Methanol is a byproduct of cell wall modification, released through the action of pectin methylesterases (PMEs), which demethylesterify cell wall pectins. Plant PMEs play not only a role in developmental processes but also in responses to herbivory and infection by fungal or bacterial pathogens. Molecular mechanisms that explain how methanol affects plant defenses are poorly understood. Here we show that exogenously supplied methanol alone has weak effects on defense signaling in three dicot species, however, it profoundly alters signaling responses to danger- and microbe-associated molecular patterns (DAMPs, MAMPs) such as the alarm hormone systemin, the bacterial flagellum-derived flg22 peptide, and the fungal cell wall-derived oligosaccharide chitosan. In the presence of methanol the kinetics and amplitudes of DAMP/MAMP-induced MAP kinase (MAPK) activity and oxidative burst are altered in tobacco and tomato suspension-cultured cells, in Arabidopsis seedlings and tomato leaf tissue. As a possible consequence of altered DAMP/MAMP signaling, methanol suppressed the expression of the defense genes PR-1 and PI-1 in tomato. In cell cultures of the grass tall fescue (Festuca arundinacea, Poaceae, Monocots), methanol alone activates MAPKs and increases chitosan-induced MAPK activity, and in the darnel grass Lolium temulentum (Poaceae), it alters wound-induced MAPK signaling. We propose that methanol can be recognized by plants as a sign of the damaged self. In dicots, methanol functions as a DAMP-like alarm signal with little elicitor activity on its own, whereas it appears to function as an elicitor-active DAMP in monocot grasses. Ethanol had been implicated in plant stress responses, although the source of ethanol in plants is not well established. We found that it has a similar effect as methanol on responses to MAMPs and DAMPs. PMID:25360141

  4. The molecular yo-yo method: Live jump detection improves throughput of single-molecule force spectroscopy for out-of-equilibrium transitions

    NASA Astrophysics Data System (ADS)

    Mack, A. H.; Schlingman, D. J.; Kamenetska, M.; Collins, R.; Regan, L.; Mochrie, S. G. J.

    2013-08-01

    By monitoring multiple molecular transitions, force-clamp, and trap-position-clamp methods have led to precise determinations of the free energies and free energy landscapes for molecular states populated in equilibrium at the same or similar forces. Here, we present a powerful new elaboration of the force-clamp and force-jump methods, applicable to transitions far from equilibrium. Specifically, we have implemented a live jump detection and force-clamp algorithm that intelligently adjusts and maintains the force on a single molecule in response to the measured state of that molecule. We are able to collect hundreds of individual molecular transitions at different forces, many times faster than previously, permitting us to accurately determine force-dependent lifetime distributions and reaction rates. Application of our method to unwinding and rewinding the nucleosome inner turn, using optical tweezers reveals experimental lifetime distributions that comprise a statistically meaningful number of transitions, and that are accurately single exponential. These measurements significantly reduce the error in the previously measured rates, and demonstrate the existence of a single, dominant free energy barrier at each force studied. A key benefit of the molecular yo-yo method for nucleosomes is that it reduces as far as possible the time spent in the tangentially bound state, which minimizes the loss of nucleosomes by dissociation.

  5. Additive and synergistic effects of a low-molecular-weight, heparin-like molecule and low doses of cyclosporin in preventing arterial graft rejection in rats.

    PubMed

    Plissonnier, D; Amichot, G; Lecagneux, J; Duriez, M; Gentric, D; Michel, J B

    1993-01-01

    Arteriosclerotic intimal proliferation is one of the main long-term complications of organ transplantation. Low-molecular-weight, heparin-like molecules prevent myointimal proliferation in arterial wall injury and limit rejection in skin allografts. Cyclosporin limits rejection but has no major effect on intimal proliferation. Therefore, an experimental protocol was designed to test whether heparin-like molecules interacted with low doses of cyclosporin to prevent arterial wall immune system injury and response in a model of arterial graft rejection in normotensive and hypertensive rats. Aortic allografts were performed in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) normotensive control rats. Four groups of 10 allografted (SHR and WKY) rats were used: one group was treated with placebo, one with low doses of cyclosporin (2 mg/kg body wt per day), one with low-molecular-weight, heparin-like molecule (1 mg/kg body wt per hour), and one with low doses of cyclosporin plus low-molecular-weight, heparin-like molecule. Ten SHRs and 10 WKYs were isografted and served as the control groups. All rats were killed 8 weeks after aortic grafting. Structural parameters of the grafted segment were measured by morphometric analysis on formalin-fixed sections with specific stains. The classical signs of immune system injury and response were present in the untreated allografts in SHRs and WKYs: inflammatory infiltration of the adventitia, medial injury, and intimal proliferative response. Low doses of cyclosporin had a significant beneficial effect on immune medial injury by increasing medial thickness and the number of remaining smooth muscle cells and decreasing the extracellular matrix injury. Cyclosporin had no protective effect on intimal proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Molecules between the Stars.

    ERIC Educational Resources Information Center

    Verschuur, Gerrit L.

    1987-01-01

    Provides a listing of molecules discovered to date in the vast interstellar clouds of dust and gas. Emphasizes the recent discoveries of organic molecules. Discusses molecular spectral lines, MASERs (microwave amplification by stimulated emission of radiation), molecular clouds, and star birth. (TW)

  7. Molecular dynamics simulations of trehalose as a 'dynamic reducer' for solvent water molecules in the hydration shell.

    PubMed

    Choi, Youngjin; Cho, Kum Won; Jeong, Karpjoo; Jung, Seunho

    2006-06-12

    Systematic computational work for a series of 13 disaccharides was performed to provide an atomic-level insight of unique biochemical role of the alpha,alpha-(1-->1)-linked glucopyranoside dimer over the other glycosidically linked sugars. Superior osmotic and cryoprotective abilities of trehalose were explained on the basis of conformational and hydration characteristics of the trehalose molecule. Analyses of the hydration number and radial distribution function of solvent water molecules showed that there was very little hydration adjacent to the glycosidic oxygen of trehalose and that the dynamic conformation of trehalose was less flexible than any of the other sugars due to this anisotropic hydration. The remarkable conformational rigidity that allowed trehalose to act as a sugar template was required for stable interactions with hydrogen-bonded water molecules. Trehalose made an average of 2.8 long-lived hydrogen bonds per each MD step, which was much larger than the average of 2.1 for the other sugars. The stable hydrogen-bond network is derived from the formation of long-lived water bridges at the expense of decreasing the dynamics of the water molecules. Evidence for this dynamic reduction of water by trehalose was also established based on each of the lowest translational diffusion coefficients and the lowest intermolecular coulombic energy of the water molecules around trehalose. Overall results indicate that trehalose functions as a 'dynamic reducer' for solvent water molecules based on its anisotropic hydration and conformational rigidity, suggesting that macroscopic solvent properties could be modulated by changes in the type of glycosidic linkages in sugar molecules.

  8. Integrating molecular, phenotypic and environmental data to elucidate patterns of crocodile hybridization in Belize

    PubMed Central

    Hekkala, Evon R.; Platt, Steven G.; Thorbjarnarson, John B.; Rainwater, Thomas R.; Tessler, Michael; Cunningham, Seth W.; Twomey, Christopher; Amato, George

    2015-01-01

    The genus Crocodylus comprises 12 currently recognized species, many of which can be difficult to differentiate phenotypically. Interspecific hybridization among crocodiles is known to occur in captivity and has been documented between some species in the wild. The identification of hybrid individuals is of importance for management and monitoring of crocodilians, many of which are Convention on International Trade in Endangered Species (CITES) listed. In this study, both mitochondrial and nuclear DNA markers were evaluated for their use in confirming a suspected hybrid zone between American crocodile (Crocodylus acutus) and Morelet’s crocodile (Crocodylus moreletii) populations in southern Belize where individuals and nests exhibiting atypical phenotypic features had previously been observed. Patterns observed in both phenotypic and molecular data indicate possible behavioural and ecological characteristics associated with hybridization events. The results of the combined analyses found that the majority of suspected hybrid samples represent crosses between female C. acutus and male C. moreletii. Phenotypic data could statistically identify hybrids, although morphological overlap between hybrids and C. moreletii reduced reliability of identification based solely on field characters. Ecologically, C. acutus was exclusively found in saline waters, whereas hybrids and C. moreletii were largely absent in these conditions. A hypothesized correlation between unidirectional hybridization and destruction of C. acutus breeding habitats warrants additional research. PMID:26473062

  9. Quantitative Analysis of Microbe-Associated Molecular Pattern (MAMP)-Induced Ca(2+) Transients in Plants.

    PubMed

    Trempel, Fabian; Ranf, Stefanie; Scheel, Dierk; Lee, Justin

    2016-01-01

    Ca(2+) is a secondary messenger involved in early signaling events triggered in response to a plethora of biotic and abiotic stimuli. In plants, environmental cues that induce cytosolic Ca(2+) elevation include touch, reactive oxygen species, cold shock, and salt or osmotic stress. Furthermore, Ca(2+) signaling has been implicated in early stages of plant-microbe interactions of both symbiotic and antagonistic nature. A long-standing hypothesis is that there is information encoded in the Ca(2+) signals (so-called Ca(2+) signatures) to enable plants to differentiate between these stimuli and to trigger the appropriate cellular response. Qualitative and quantitative measurements of Ca(2+) signals are therefore needed to dissect the responses of plants to their environment. Luminescence produced by the Ca(2+) probe aequorin upon Ca(2+) binding is a widely used method for the detection of Ca(2+) transients and other changes in Ca(2+) concentrations in cells or organelles of plant cells. In this chapter, using microbe-associated molecular patterns (MAMPs), such as the bacterial-derived flg22 or elf18 peptides as stimuli, a protocol for the quantitative measurements of Ca(2+) fluxes in apoaequorin-expressing seedlings of Arabidopsis thaliana in 96-well format is described.

  10. Global patterns of insect diversification: towards a reconciliation of fossil and molecular evidence?

    PubMed

    Condamine, Fabien L; Clapham, Matthew E; Kergoat, Gael J

    2016-01-18

    Macroevolutionary studies of insects at diverse taxonomic scales often reveal dynamic evolutionary patterns, with multiple inferred diversification rate shifts. Responses to major past environmental changes, such as the Cretaceous Terrestrial Revolution, or the development of major key innovations, such as wings or complete metamorphosis are usually invoked as potential evolutionary triggers. However this view is partially contradicted by studies on the family-level fossil record showing that insect diversification was relatively constant through time. In an attempt to reconcile both views, we investigate large-scale insect diversification dynamics at family level using two distinct types of diversification analyses on a molecular timetree representing ca. 82% of the extant families, and reassess the insect fossil diversity using up-to-date records. Analyses focusing on the fossil record recovered an early burst of diversification, declining to low and steady rates through time, interrupted by extinction events. Phylogenetic analyses showed that major shifts of diversification rates only occurred in the four richest holometabolous orders. Both suggest that neither the development of flight or complete metamorphosis nor the Cretaceous Terrestrial Revolution environmental changes induced immediate changes in diversification regimes; instead clade-specific innovations likely promoted the diversification of major insect orders.

  11. Caspase-dependent cell death-associated release of nucleosome and damage-associated molecular patterns

    PubMed Central

    Yoon, S; Park, S J; Han, J H; Kang, J H; Kim, J-h; Lee, J; Park, S; Shin, H-J; Kim, K; Yun, M; Chwae, Y-J

    2014-01-01

    Apoptosis, which is anti-inflammatory, and necrosis, which is pro-inflammatory, represent the extremes of the cell death spectrum. Cell death is complex and both apoptosis and necrosis can be observed in the same cells or tissues. Here, we introduce a novel combined mode of cellular demise – caspase-dependent regulated necrosis. Most importantly, it is mainly characterized with release of marked amount of oligo- or poly-nucleosomes and their attached damage-associated molecular patterns (DAMPs) and initiated by caspase activation. Caspase-activated DNase has dual roles in nucleosomal release as it can degrade extracellularly released chromatin into poly- or oligo-nucleosomes although it prohibits release of nucleosomes. In addition, osmotically triggered water movement following Cl− influx and subsequent Na+ influx appears to be the major driving force for nucleosomal and DAMPs release. Finally, Ca2+-activated cysteine protease, calpain, is an another essential factor in nucleosomal and DAMPs release because of complete reversion to apoptotic morphology from necrotic one and blockade of nucleosomal and DAMPs release by its inhibition. PMID:25356863

  12. Global patterns of insect diversification: towards a reconciliation of fossil and molecular evidence?

    PubMed Central

    Condamine, Fabien L.; Clapham, Matthew E.; Kergoat, Gael J.

    2016-01-01

    Macroevolutionary studies of insects at diverse taxonomic scales often reveal dynamic evolutionary patterns, with multiple inferred diversification rate shifts. Responses to major past environmental changes, such as the Cretaceous Terrestrial Revolution, or the development of major key innovations, such as wings or complete metamorphosis are usually invoked as potential evolutionary triggers. However this view is partially contradicted by studies on the family-level fossil record showing that insect diversification was relatively constant through time. In an attempt to reconcile both views, we investigate large-scale insect diversification dynamics at family level using two distinct types of diversification analyses on a molecular timetree representing ca. 82% of the extant families, and reassess the insect fossil diversity using up-to-date records. Analyses focusing on the fossil record recovered an early burst of diversification, declining to low and steady rates through time, interrupted by extinction events. Phylogenetic analyses showed that major shifts of diversification rates only occurred in the four richest holometabolous orders. Both suggest that neither the development of flight or complete metamorphosis nor the Cretaceous Terrestrial Revolution environmental changes induced immediate changes in diversification regimes; instead clade-specific innovations likely promoted the diversification of major insect orders. PMID:26778170

  13. Integrating molecular, phenotypic and environmental data to elucidate patterns of crocodile hybridization in Belize.

    PubMed

    Hekkala, Evon R; Platt, Steven G; Thorbjarnarson, John B; Rainwater, Thomas R; Tessler, Michael; Cunningham, Seth W; Twomey, Christopher; Amato, George

    2015-09-01

    The genus Crocodylus comprises 12 currently recognized species, many of which can be difficult to differentiate phenotypically. Interspecific hybridization among crocodiles is known to occur in captivity and has been documented between some species in the wild. The identification of hybrid individuals is of importance for management and monitoring of crocodilians, many of which are Convention on International Trade in Endangered Species (CITES) listed. In this study, both mitochondrial and nuclear DNA markers were evaluated for their use in confirming a suspected hybrid zone between American crocodile (Crocodylus acutus) and Morelet's crocodile (Crocodylus moreletii) populations in southern Belize where individuals and nests exhibiting atypical phenotypic features had previously been observed. Patterns observed in both phenotypic and molecular data indicate possible behavioural and ecological characteristics associated with hybridization events. The results of the combined analyses found that the majority of suspected hybrid samples represent crosses between female C. acutus and male C. moreletii. Phenotypic data could statistically identify hybrids, although morphological overlap between hybrids and C. moreletii reduced reliability of identification based solely on field characters. Ecologically, C. acutus was exclusively found in saline waters, whereas hybrids and C. moreletii were largely absent in these conditions. A hypothesized correlation between unidirectional hybridization and destruction of C. acutus breeding habitats warrants additional research. PMID:26473062

  14. Analysis of Microbe-Associated Molecular Pattern-Responsive Synthetic Promoters with the Parsley Protoplast System.

    PubMed

    Kanofsky, Konstantin; Lehmeyer, Mona; Schulze, Jutta; Hehl, Reinhard

    2016-01-01

    Plants recognize pathogens by microbe-associated molecular patterns (MAMPs) and subsequently induce an immune response. The regulation of gene expression during the immune response depends largely on cis-sequences conserved in promoters of MAMP-responsive genes. These cis-sequences can be analyzed by constructing synthetic promoters linked to a reporter gene and by testing these constructs in transient expression systems. Here, the use of the parsley (Petroselinum crispum) protoplast system for analyzing MAMP-responsive synthetic promoters is described. The synthetic promoter consists of four copies of a potential MAMP-responsive cis-sequence cloned upstream of a minimal promoter and the uidA reporter gene. The reporter plasmid contains a second reporter gene, which is constitutively expressed and hence eliminates the requirement of a second plasmid used as a transformation control. The reporter plasmid is transformed into parsley protoplasts that are elicited by the MAMP Pep25. The MAMP responsiveness is validated by comparing the reporter gene activity from MAMP-treated and untreated cells and by normalizing reporter gene activity using the constitutively expressed reporter gene.

  15. Innate Immune Responses Activated in Arabidopsis Roots by Microbe-Associated Molecular Patterns[W][OA

    PubMed Central

    Millet, Yves A.; Danna, Cristian H.; Clay, Nicole K.; Songnuan, Wisuwat; Simon, Matthew D.; Werck-Reichhart, Danièle; Ausubel, Frederick M.

    2010-01-01

    Despite the fact that roots are the organs most subject to microbial interactions, very little is known about the response of roots to microbe-associated molecular patterns (MAMPs). By monitoring transcriptional activation of β-glucuronidase reporters and MAMP-elicited callose deposition, we show that three MAMPs, the flagellar peptide Flg22, peptidoglycan, and chitin, trigger a strong tissue-specific response in Arabidopsis thaliana roots, either at the elongation zone for Flg22 and peptidoglycan or in the mature parts of the roots for chitin. Ethylene signaling, the 4-methoxy-indole-3-ylmethylglucosinolate biosynthetic pathway, and the PEN2 myrosinase, but not salicylic acid or jasmonic acid signaling, play major roles in this MAMP response. We also show that Flg22 induces the cytochrome P450 CYP71A12-dependent exudation of the phytoalexin camalexin by Arabidopsis roots. The phytotoxin coronatine, an Ile-jasmonic acid mimic produced by Pseudomonas syringae pathovars, suppresses MAMP-activated responses in the roots. This suppression requires the E3 ubiquitin ligase COI1 as well as the transcription factor JIN1/MYC2 but does not rely on salicylic acid–jasmonic acid antagonism. These experiments demonstrate the presence of highly orchestrated and tissue-specific MAMP responses in roots and potential pathogen-encoded mechanisms to block these MAMP-elicited signaling pathways. PMID:20348432

  16. Analysis of Microbe-Associated Molecular Pattern-Responsive Synthetic Promoters with the Parsley Protoplast System.

    PubMed

    Kanofsky, Konstantin; Lehmeyer, Mona; Schulze, Jutta; Hehl, Reinhard

    2016-01-01

    Plants recognize pathogens by microbe-associated molecular patterns (MAMPs) and subsequently induce an immune response. The regulation of gene expression during the immune response depends largely on cis-sequences conserved in promoters of MAMP-responsive genes. These cis-sequences can be analyzed by constructing synthetic promoters linked to a reporter gene and by testing these constructs in transient expression systems. Here, the use of the parsley (Petroselinum crispum) protoplast system for analyzing MAMP-responsive synthetic promoters is described. The synthetic promoter consists of four copies of a potential MAMP-responsive cis-sequence cloned upstream of a minimal promoter and the uidA reporter gene. The reporter plasmid contains a second reporter gene, which is constitutively expressed and hence eliminates the requirement of a second plasmid used as a transformation control. The reporter plasmid is transformed into parsley protoplasts that are elicited by the MAMP Pep25. The MAMP responsiveness is validated by comparing the reporter gene activity from MAMP-treated and untreated cells and by normalizing reporter gene activity using the constitutively expressed reporter gene. PMID:27557767

  17. Innate immune memory: Implications for host responses to damage-associated molecular patterns.

    PubMed

    Crișan, Tania O; Netea, Mihai G; Joosten, Leo A B

    2016-04-01

    Cells of the innate immune system build immunological memory via epigenetic reprogramming after stimulations with microbial ligands. This functional readjustment allows for enhanced nonspecific inflammatory responses upon secondary challenges, a process termed "trained immunity." The epigenomic blueprint of trained monocytes has been recently reported, which revealed several important immunologic and metabolic mechanisms that underlie these changes. Interestingly, similar long-term reprogramming of cytokine production has also been described to be induced by endogenous damage-associated molecular patterns (DAMPs). Here, we present an overview of the novel data showing that endogenous alarm signals associated with tissue damage and sterile inflammation can induce trained immunity through epigenetic regulation of transcriptional programs. We describe new and old evidence of persistent effects of DAMPs in driving inflammation and enforce the concept that the influence of tissue-derived signals is critical in adjusting the magnitude and type of immune response built by the host. The better characterization of trained immunity for the persistence of inflammation induced by DAMPs would provide new possibilities for intervention in aging and autoinflammatory disorders. PMID:26970440

  18. Changes in holothurian coelomocyte populations following immune stimulation with different molecular patterns

    PubMed Central

    Ramírez-Gómez, Francisco; Aponte-Rivera, Francisco; Méndez-Castaner, Lumen; García-Arrarás, Jose E.

    2010-01-01

    Echinoderms possess a variety of cells populating the coelomic fluid; these cells are responsible for mounting defense against foreign agents. In the sea cucumber Holothuria glaberrima, four different coelomocyte types were readily distinguished using morphological, histochemical and physiological (phagocytic activity) parameters: lymphocytes, phagocytes, spherulocytes and “giant” cells (listed in order of abundance). Monoclonal antibodies generated against sea cucumber tissues and one polyclonal against sea urchin mayor yolk protein (MYP) were also used to characterize these cell populations. The effects of several pathogen-associated molecular patterns (PAMPs): Lipopolysaccharides from E. coli (LPS), heat-killed Staphylococcus aureus (SA) and a synthetic dsRNA were studied on coelomocyte cell populations. PAMPs increased the phagocytic activity of the holothurian coelomocytes, and were able to induce selective immune responses in several of these populations, demonstrating the ability of the sea cucumber to respond to a different variety of immune challenges. Overall, these results show the variety of cells that populate the coelomic fluid of the holothurian and demonstrate their involvement in immune reactions. These animals represent an untapped resource for new findings into the evolution and development of the immune response not only in invertebrates but also in phylogenetically shared reactions with vertebrates. PMID:20412860

  19. Reprogramming cells and tissue patterning via bioelectrical pathways: molecular mechanisms and biomedical opportunities.

    PubMed

    Levin, Michael

    2013-01-01

    Transformative impact in regenerative medicine requires more than the reprogramming of individual cells: advances in repair strategies for birth defects or injuries, tumor normalization, and the construction of bioengineered organs and tissues all require the ability to control large-scale anatomical shape. Much recent work has focused on the transcriptional and biochemical regulation of cell behavior and morphogenesis. However, exciting new data reveal that bioelectrical properties of cells and their microenvironment exert a profound influence on cell differentiation, proliferation, and migration. Ion channels and pumps expressed in all cells, not just excitable nerve and muscle, establish resting potentials that vary across tissues and change with significant developmental events. Most importantly, the spatiotemporal gradients of these endogenous transmembrane voltage potentials (Vmem ) serve as instructive patterning cues for large-scale anatomy, providing organ identity, positional information, and prepattern template cues for morphogenesis. New genetic and pharmacological techniques for molecular modulation of bioelectric gradients in vivo have revealed the ability to initiate complex organogenesis, change tissue identity, and trigger regeneration of whole vertebrate appendages. A large segment of the spatial information processing that orchestrates individual cells' programs toward the anatomical needs of the host organism is electrical; this blurs the line between memory and decision-making in neural networks and morphogenesis in nonneural tissues. Advances in cracking this bioelectric code will enable the rational reprogramming of shape in whole tissues and organs, revolutionizing regenerative medicine, developmental biology, and synthetic bioengineering. PMID:23897652

  20. M-ficolin interacts with the long pentraxin PTX3: a novel case of cross-talk between soluble pattern-recognition molecules.

    PubMed

    Gout, Evelyne; Moriscot, Christine; Doni, Andrea; Dumestre-Pérard, Chantal; Lacroix, Monique; Pérard, Julien; Schoehn, Guy; Mantovani, Alberto; Arlaud, Gérard J; Thielens, Nicole M

    2011-05-15

    Ficolins and pentraxins are soluble oligomeric pattern-recognition molecules that sense danger signals from pathogens and altered self-cells and might act synergistically in innate immune defense and maintenance of immune tolerance. The interaction of M-ficolin with the long pentraxin pentraxin 3 (PTX3) has been characterized using surface plasmon resonance spectroscopy and electron microscopy. M-ficolin was shown to bind PTX3 with high affinity in the presence of calcium ions. The interaction was abolished in the presence of EDTA and inhibited by N-acetyl-D-glucosamine, indicating involvement of the fibrinogen-like domain of M-ficolin. Removal of sialic acid from the single N-linked carbohydrate of the C-terminal domain of PTX3 abolished the interaction. Likewise, an M-ficolin mutant with impaired sialic acid-binding ability did not interact with PTX3. Interaction was also impaired when using the isolated recognition domain of M-ficolin or the monomeric C-terminal domain of PTX3, indicating requirement for oligomerization of both proteins. Electron microscopy analysis of the M-ficolin-PTX3 complexes revealed that the M-ficolin tetramer bound up to four PTX3 molecules. From a functional point of view, immobilized PTX3 was able to trigger M-ficolin-dependent activation of the lectin