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1

Algorithm for Reconstruction of 3D Molecular Structure from Diffraction Patterns of Laser-Aligned Molecules  

NASA Astrophysics Data System (ADS)

Ultrafast electron diffraction from laser-aligned gas molecules is a promising method for the determination of 3D molecular structures. Reconstruction algorithms for diffraction patterns of perfectly aligned molecules have been widely studied theoretically. However, under experimental conditions only partial alignment can be achieved and the existing algorithms do not perform well when the alignment is not perfect. We develop a method to reconstruct the 3D structure of molecules with cylindrical symmetry from electron diffraction patterns of partially-aligned molecules. The evolutionary algorithm assumes a known angular distribution, which can be calculated numerically using existing theory for laser-alignment and verified by comparison with the data. Selecting CF3I as the cylindrically symmetric molecule, diffraction patterns from multiple alignment angles are used to reconstruct a single diffraction pattern corresponding to perfect alignment. The molecular structure can then be recovered from this pattern with no prior structural information required. Our results are in good agreement with previous models of CF3I structure.

Yang, Jie; Hensley, Christopher; Centurion, Martin

2012-06-01

2

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

PubMed Central

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

Sangiuliano, Beatriz; Perez, Nancy Marcela; Moreira, Dayson F.; Belizario, Jose E.

2014-01-01

3

Molecular structure determination from x-ray scattering patterns of laser-aligned symmetric-top molecules  

SciTech Connect

We investigate the molecular structure information contained in the x-ray diffraction patterns of an ensemble of rigid CF{sub 3}Br molecules aligned by an intense laser pulse at finite rotational temperature. The diffraction patterns are calculated at an x-ray photon energy of 20 keV to probe molecular structure at angstrom-scale resolution. We find that a structural reconstruction algorithm based on iterative phase retrieval fails to extract a reliable structure. However, the high atomic number of Br compared with C or F allows each diffraction pattern to be treated as a hologram. Using this approach, the azimuthal projection of the molecular electron density about the alignment axis may be retrieved.

Ho, P. J. [Argonne National Laboratory, Argonne, Illinois 60439 (United States); Starodub, D. [Department of Physics, Arizona State University, Tempe, Arizona 85287 (United States); Saldin, D. K.; Shneerson, V. L.; Ourmazd, A. [Department of Physics, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201 (United States); Santra, R. [Argonne National Laboratory, Argonne, Illinois 60439 (United States); Department of Physics, University of Chicago, Chicago, Illinois 60637 (United States)

2009-10-07

4

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

PubMed Central

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 aureus. Discovery of these KD-specific molecules might offer novel insight into the diagnosis and management of KD as well as its pathogenesis. PMID:25411968

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

5

Molecular structure determination from x-ray scattering patterns of laser-aligned symmetric-top molecules  

E-print Network

are calculated at an x-ray photon energy of 20 keV to probe molecular structure at angstrom-scale resolution. We pattern to be treated as a hologram. Using this approach, the azimuthal projection of the molecular

Saldin, Dilano

6

Molecular biomechanics of collagen molecules  

E-print Network

Collagenous tissues, made of collagen molecules, such as tendon and bone, are intriguing materials that have the ability to respond to mechanical forces by altering their structures from the molecular level up, and convert ...

Chang, Shu-Wei

7

Line defects guided molecular patterning on graphene  

NASA Astrophysics Data System (ADS)

Graphene emerges as a candidate scaffold for patterning molecules. Despite existing progresses, it still remains unclear how to achieve molecular self-assembly in domains of desirable geometry. We reveal a barrier effect of line defects (e.g., open slits) in graphene, which can potentially enable molecular confining and patterning in a domain of desirable geometry. Using molecular dynamics simulations, we demonstrate that fullerene molecules can be readily patterned into a stable cluster of various shapes and sizes. Such a strategy is expected to be applicable to pattern various types of molecules that interact with graphene via van der Waals force.

Huang, Yinjun; Zhu, Shuze; Li, Teng

2014-03-01

8

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

PubMed Central

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

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

2012-01-01

9

Structure factor and rheology of chain molecules from molecular dynamics  

NASA Astrophysics Data System (ADS)

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

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

2013-05-01

10

Molecular Cloning, Expression Pattern, and Immunocytochemical Localization of a Gonadotropin-Releasing Hormone-like Molecule in the Gastropod Mollusk, Aplysia californica  

PubMed Central

Successful reproduction in vertebrates depends upon the actions of gonadotropin-releasing hormone (GnRH). Despite the wide presence of GnRH in Phylum Chordata, GnRH has not been isolated in protostomes other than the common octopus. To provide information on the evolution of this critical hormone, we isolated the full-length cDNA of a GnRH-like molecule from the central nervous system of a gastropod mollusk, the sea hare Aplysia californica. The open reading frame of this cDNA encodes a protein of 147 amino acids. The molecular architecture of the deduced protein is highly homologous to that reported for the prepro-octopus GnRH (oct-GnRH) and consists of a putative signal peptide, a GnRH dodecapeptide, a downstream processing site, and a GnRH-associated peptide (GAP). The deduced amino acid sequence of the Aplysia GnRH (ap-GnRH) is QNYHFSNGWYAG and differs from oct-GnRH by only two amino acids. The transcript for ap-GnRH is widely expressed in the central nervous system (CNS), the ovotestis, and the atrial gland, an exocrine gland. Immunocytochemistry (ICC) using an antiserum against oct-GnRH detected immunoreactive neurons in all CNS ganglia examined, and the staining was abolished by the preadsorption of the antiserum with synthetic ap-GnRH. In sum, ap-GnRH sequence is the first gastropod GnRH-like molecule to be elucidated. Further, it represents one of the only two GnRH-like molecules found outside Phylum Chordata. These data refute the possibility that oct-GnRH arose singly in cephalopods by convergent evolution and provide valuable support for an ancient origin of GnRH during metazoan evolution. PMID:18178211

Zhang, Lihong; Tello, Javier A.; Zhang, Weimin; Tsai, Pei-San

2008-01-01

11

DAMP molecule S100A9 acts as a molecular pattern to enhance inflammation during influenza A virus infection: role of DDX21-TRIF-TLR4-MyD88 pathway.  

PubMed

Pathogen-associated molecular patterns (PAMPs) trigger host immune response by activating pattern recognition receptors like toll-like receptors (TLRs). However, the mechanism whereby several pathogens, including viruses, activate TLRs via a non-PAMP mechanism is unclear. Endogenous "inflammatory mediators" called damage-associated molecular patterns (DAMPs) have been implicated in regulating immune response and inflammation. However, the role of DAMPs in inflammation/immunity during virus infection has not been studied. We have identified a DAMP molecule, S100A9 (also known as Calgranulin B or MRP-14), as an endogenous non-PAMP activator of TLR signaling during influenza A virus (IAV) infection. S100A9 was released from undamaged IAV-infected cells and extracellular S100A9 acted as a critical host-derived molecular pattern to regulate inflammatory response outcome and disease during infection by exaggerating pro-inflammatory response, cell-death and virus pathogenesis. Genetic studies showed that the DDX21-TRIF signaling pathway is required for S100A9 gene expression/production during infection. Furthermore, the inflammatory activity of extracellular S100A9 was mediated by activation of the TLR4-MyD88 pathway. Our studies have thus, underscored the role of a DAMP molecule (i.e. extracellular S100A9) in regulating virus-associated inflammation and uncovered a previously unknown function of the DDX21-TRIF-S100A9-TLR4-MyD88 signaling network in regulating inflammation during infection. PMID:24391503

Tsai, Su-Yu; Segovia, Jesus A; Chang, Te-Hung; Morris, Ian R; Berton, Michael T; Tessier, Philippe A; Tardif, Mélanie R; Cesaro, Annabelle; Bose, Santanu

2014-01-01

12

DAMP Molecule S100A9 Acts as a Molecular Pattern to Enhance Inflammation during Influenza A Virus Infection: Role of DDX21-TRIF-TLR4-MyD88 Pathway  

PubMed Central

Pathogen-associated molecular patterns (PAMPs) trigger host immune response by activating pattern recognition receptors like toll-like receptors (TLRs). However, the mechanism whereby several pathogens, including viruses, activate TLRs via a non-PAMP mechanism is unclear. Endogenous “inflammatory mediators” called damage-associated molecular patterns (DAMPs) have been implicated in regulating immune response and inflammation. However, the role of DAMPs in inflammation/immunity during virus infection has not been studied. We have identified a DAMP molecule, S100A9 (also known as Calgranulin B or MRP-14), as an endogenous non-PAMP activator of TLR signaling during influenza A virus (IAV) infection. S100A9 was released from undamaged IAV-infected cells and extracellular S100A9 acted as a critical host-derived molecular pattern to regulate inflammatory response outcome and disease during infection by exaggerating pro-inflammatory response, cell-death and virus pathogenesis. Genetic studies showed that the DDX21-TRIF signaling pathway is required for S100A9 gene expression/production during infection. Furthermore, the inflammatory activity of extracellular S100A9 was mediated by activation of the TLR4-MyD88 pathway. Our studies have thus, underscored the role of a DAMP molecule (i.e. extracellular S100A9) in regulating virus-associated inflammation and uncovered a previously unknown function of the DDX21-TRIF-S100A9-TLR4-MyD88 signaling network in regulating inflammation during infection. PMID:24391503

Tsai, Su-Yu; Segovia, Jesus A.; Chang, Te-Hung; Morris, Ian R.; Berton, Michael T.; Tessier, Philippe A.; Tardif, Melanie R.; Cesaro, Annabelle; Bose, Santanu

2014-01-01

13

Molecular-beam spectroscopy of interhalogen molecules  

SciTech Connect

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.

Sherrow, S.A.

1983-08-01

14

Molecular forms, binding functions, and developmental expression patterns of cytotactin and cytotactin-binding proteoglycan, an interactive pair of extracellular matrix molecules  

Microsoft Academic Search

Cytotactin is an extracellular matrix protein that is found in a restricted distribution and is related to developmental patterning at a number of neural and non-neural sites. It has been shown to bind specifically to other extracellular matrix components including a chondroitin sulfate proteoglycan (cytotactin-binding (CTB) proteoglycan) and fibronectin. Cell binding ex- periments have revealed that cytotactin interacts with neurons

Stanley Hoffman; Kathryn L. Crossin; Gerald M. Edelman

1988-01-01

15

Single molecular spectroscopy: identification of individual fullerene molecules.  

PubMed

We report the molecule-by-molecule spectroscopy of individual fullerenes by means of electron spectroscopy based on scanning transmission electron microscopy. Electron energy-loss fine structure analysis of carbon 1s absorption spectra is used to discriminate carbon allotropes with known symmetries. C_{60} and C_{70} molecules randomly stored inside carbon nanotubes are successfully identified at a single-molecular basis. We show that a single molecule impurity is detectable, allowing the recognition of an unexpected contaminant molecule with a different symmetry. Molecules inside carbon nanotubes thus preserve their intact molecular symmetry. In contrast, molecules anchored at or sandwiched between atomic BN layers show spectral modifications possibly due to a largely degraded structural symmetry. Moreover, by comparing the spectrum from a single C_{60} molecule and its molecular crystal, we find hints of the influence of solid-state effects on its electronic structure. PMID:25396379

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

2014-10-31

16

Single Molecular Spectroscopy: Identification of Individual Fullerene Molecules  

NASA Astrophysics Data System (ADS)

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

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

2014-10-01

17

Single Molecule Approaches Embrace Molecular Cohorts  

PubMed Central

Enormous mechanistic insight has been gained by studying the behavior of single molecules. The same approaches used to study proteins in isolation are now being leveraged to examine the changes in functional behavior that emerge when single molecules have company. PMID:23953107

Ha, Taekjip

2013-01-01

18

Conformational flexibility and hydrogen-bonding patterns of the neotame molecule in its various solid forms.  

PubMed

The conformational flexibility and the molecular packing patterns of the neotame molecule in its various crystal forms, including neotame monohydrate, methanol solvate, ethanol solvate, benzene solvate, and anhydrate polymorph G, are analyzed in this work. The Cerius2 molecular modeling program with the Dreiding 2.21 force field was employed to calculate the most stable conformations of neotame molecules in the gaseous state and to analyze the conformations of the neotame molecule in its various crystal forms. Using graph set analysis, the hydrogen bond patterns of these crystal forms were compared. The neotame molecule takes different conformations in its crystal forms and in the free gaseous state. Cerius2 found 10 conformers with lower conformational energies than those in the actual crystal structures, which represent an energetic compromise. The relatively large differences between the energies of the conformers indicate the necessity for rewriting or customizing the force field for neotame. The hydrogen bonding patterns of the neotame methanol and ethanol solvates are identical, but different from those of the other three forms, which also differ from each other. The neotame molecule in its various crystal forms takes different conformations that differ from those in the gaseous state because of the influence of crystal packing. The intramolecular ring, S5, is present in all the crystal forms. The following hydrogen bonding patterns occur in some of the crystal forms: diad, D; intramolecular rings, S(6) and S(7); chains, C(5) and C(6); and an intermolecular ring, R2(2)(12). PMID:12210051

Dong, Zedong; Munson, Eric J; Schroeder, Steve A; Prakash, Indra; Grant, David J W

2002-09-01

19

Ion-molecule reactions and fragmentation patterns in helium nanodroplets.  

PubMed

A study has been made of the ion chemistry of a series of small molecules that have been embedded in helium nanodroplets. In most instances, the molecules H2O, SO2, CO2, CH3OH, C2H5OH, C3H7OH, CH3F, and CH3Cl have been allowed to form clusters, and reactivity within these has been initiated through electron impact ionization. For two of the molecules studied, CF2Cl2 and CF3I, reactivity is believed to originate from single molecules embedded in the droplets. Electron impact on the droplets is thought to first create a helium ion, and formation of molecular ions is then assumed to proceed via a charge hopping mechanism that propagates though the droplet and terminates with charge-transfer to a molecule or cluster. The chemistry exhibited by many of the cluster ions and at least one of the single molecular ions is very different from that observed for the same species in isolation. In most cases, reactivity appears to be dominated by high-energy bond breaking processes as opposed to, in the case of the clusters, ion-molecule reactions. Overall, charge-transfer from He+ does not appear to be a "soft" ionization mechanism. PMID:17585742

Boatwright, Adrian; Jeffs, Jay; Stace, Anthony J

2007-08-01

20

Mitochondrial damage-associated molecular patterns and vascular function.  

PubMed

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

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

2014-05-01

21

Molecular mechanisms of vascular pattern formation  

Microsoft Academic Search

Vascular plants have developed a complex network of vascular systems through the plant body, allowing efficient transport of water, nutrients and signals. To understand molecular mechanisms of vascular pattern formation, we have made two approaches. First we have isolated Arabidopsis mutants with defects in vascular pattern formation. Microscopic and genetic examination of the cotyledonary venation of 3400 M3 lines led

Hiroo Fukuda; Koji Koizumi; Kenji Motomatsu; Hiroyasu Motose; Munetaka Sugiyama

2001-01-01

22

Ultracold Giant Polyatomic Rydberg Molecules: Coherent Control of Molecular Orientation  

NASA Astrophysics Data System (ADS)

We predict the existence of a class of ultracold giant molecules formed from trapped ultracold Rydberg atoms and polar molecules. The interaction which leads to the formation of such molecules is the anisotropic, long-range charge-dipole interaction. We show that prominent candidate molecules such as deuterated hydroxyl (OD) and KRb should bind to Rydberg rubidium atoms, with energies Eb?5-25GHz at distances R?0.1-1?m. These molecules form in double wells, mimicking chiral molecules, with each well containing a particular dipole orientation. We prepare a set of correlated dressed electron-dipole eigenstates which are used in an on-resonance Raman scheme to coherently control the molecular dipole orientation.

Rittenhouse, Seth T.; Sadeghpour, H. R.

2010-06-01

23

Identifying molecular signatures in metal-molecule-metal junctions  

NASA Astrophysics Data System (ADS)

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 ?-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.

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

2009-09-01

24

Molecule-electrode interfaces in molecular electronic devices.  

PubMed

Understanding charge transport of single molecules or a small collection of molecules sandwiched between electrodes is of fundamental importance for molecular electronics. This requires the fabrication of reliable devices, which depend on several factors including the testbed architectures used, the molecule number and defect density being tested, and the nature of the molecule-electrode interface. On the basis of significant progresses achieved in both experiments and theory over the past decade, in this tutorial review, we focus on new insights into the influence of the nature of the molecule-electrode interface, the most critical issue hindering the development of reliable devices, on the conducting properties of molecules. We summarize the strategies developed for controlling the interfacial properties and how the coupling strength between the molecules and the electrodes modulates the device properties. These analyses should be valuable for deeply understanding the relationship between the contact interface and the charge transport mechanism, which is of crucial importance for the development of molecular electronics, organic electronics, nanoelectronics, and other interface-related optoelectronic devices. PMID:23571285

Jia, Chuancheng; Guo, Xuefeng

2013-07-01

25

Reconstruction from a single diffraction pattern of azimuthally projected electron density of molecules aligned parallel to a single axis.  

PubMed

Diffraction from the individual molecules of a molecular beam, aligned parallel to a single axis by a strong electric field or other means, has been proposed as a means of structure determination of individual molecules. As in fiber diffraction, all the information extractable is contained in a diffraction pattern from incidence of the diffracting beam normal to the molecular alignment axis. The limited size of the object results in continuous diffraction patterns characterized by neither Bragg spots nor layer lines. Equations relating the scattered amplitudes to the molecular electron density may be conveniently formulated in terms of cylindrical harmonics. For simulated diffraction patterns from short C nanotubes aligned along their axes, iterative solution of the equation for the zeroth-order cylindrical harmonic and its inverse with appropriate constraints in real and reciprocal space enables the phasing of the measured amplitudes, and hence a reconstruction of the azimuthal projection of the molecule. PMID:20029131

Saldin, D K; Shneerson, V L; Starodub, D; Spence, J C H

2010-01-01

26

Mechanically controlled molecular orbital alignment in single molecule junctions.  

PubMed

Research in molecular electronics often involves the demonstration of devices that are analogous to conventional semiconductor devices, such as transistors and diodes, but it is also possible to perform experiments that have no parallels in conventional electronics. For example, by applying a mechanical force to a molecule bridged between two electrodes, a device known as a molecular junction, it is possible to exploit the interplay between the electrical and mechanical properties of the molecule to control charge transport through the junction. 1,4'-Benzenedithiol is the most widely studied molecule in molecular electronics, and it was shown recently that the molecular orbitals can be gated by an applied electric field. Here, we report how the electromechanical properties of a 1,4'-benzenedithiol molecular junction change as the junction is stretched and compressed. Counterintuitively, the conductance increases by more than an order of magnitude during stretching, and then decreases again as the junction is compressed. Based on simultaneously recorded current-voltage and conductance-voltage characteristics, and inelastic electron tunnelling spectroscopy, we attribute this finding to a strain-induced shift of the highest occupied molecular orbital towards the Fermi level of the electrodes, leading to a resonant enhancement of the conductance. These results, which are in agreement with the predictions of theoretical models, also clarify the origins of the long-standing discrepancy between the calculated and measured conductance values of 1,4'-benzenedithiol, which often differ by orders of magnitude. PMID:22138861

Bruot, Christopher; Hihath, Joshua; Tao, Nongjian

2012-01-01

27

Photoactive molecules for applications in molecular imaging and cell biology  

E-print Network

Xing* Received 26th November 2009 First published as an Advance Article on the web 17th May 2010 DOI or signals, mechanisms in cell biology can be investigated at the molecular level with spatial and temporal resolution. In this tutorial review, we aim to introduce the important applications of photoactive molecules

Xing, Bengang

28

Molecular electronics--resonant transport through single molecules.  

PubMed

The mechanically controllable break-junction technique (MCBJ) enables us to investigate charge transport through an individually contacted and addressed molecule in ultra-high vacuum (UHV) environment at variable temperature ranging from room temperature down to 4 K. Using a statistical measurement and analysis approach, we acquire current-voltage (I-V) characteristics during the repeated formation, manipulation, and breaking of a molecular junction. At low temperatures, voltages accessing the first molecular orbitals in resonance can be applied, providing spectroscopic information about the junction's energy landscape, in particular about the molecular level alignment in respect to the Fermi energy of the electrodes. Thereby, we can investigate the non-linear transport properties of various types of functional molecules and explore their potential use as functional building blocks for future nano-electronics. An example will be given by the reversible and controllable switching between two distinct conductive states of a single molecule. As a proof-of-principle for functional molecular devices, a single-molecule memory element will be demonstrated. PMID:21137712

Lörtscher, Emanuel; Riel, Heike

2010-01-01

29

Resolution-associated molecular patterns (RAMP): RAMParts defending immunological homeostasis?  

PubMed Central

The resolution of inflammation is central to the maintenance of good health and immune homeostasis. Recently, several intracellular stress proteins have been described as having extracellular properties that are anti-inflammatory or favour the resolution of inflammation. We propose that these molecules should be defined as resolution-associated molecular patterns (RAMPs). RAMPs are released at times of cellular stress and help to counterbalance the inflammatory effects of pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns. We propose that heat shock protein 10 (HSP10), ?B-crystallin (?BC), HSP27 and binding immunoglobulin protein (BiP) should be considered founding members of the RAMP family. A greater understanding of RAMP biology may herald the development of novel immunotherapies. PMID:21671907

Shields, A M; Panayi, G S; Corrigall, V M

2011-01-01

30

Complex Molecules in the L1157 Molecular Outflow  

E-print Network

We report the detection of complex organic molecules in the young protostellar outflow L1157. We identify lines from HCOOCH3, CH3CN, HCOOH and C2H5OH at the position of the B1 shock in the blueshifted lobe, making it the first time that complex species have been detected towards a molecular outflow powered by a young low-mass protostar. The time scales associated with the warm outflow gas (< 2,000 yr) are too short for the complex molecules to have formed in the gas phase after the shock-induced sputtering of the grain mantles. It is more likely that the complex species formed in the surface of grains and were then ejected from the grain mantles by the shock. The formation of complex molecules in the grains of low-mass star forming regions must be relatively efficient, and our results show the importance of considering the impact of outflows when studying complex molecules around protostars. The relative abundance with respect to methanol of most of the detected complex molecules is similar to that of hot cores and molecular clouds in the galactic center region, which suggests that the mantle composition of the dust in the L1157 dark cloud is similar to dust in those regions.

Héctor G. Arce; Joaquín Santiago-García; Jes K. J\\orgensen; Mario Tafalla; Rafael Bachiller

2008-05-16

31

An extracellular adhesion molecule complex patterns dendritic branching and morphogenesis  

PubMed Central

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

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

2014-01-01

32

An extracellular adhesion molecule complex patterns dendritic branching and morphogenesis.  

PubMed

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

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

2013-10-10

33

Molecular Analysis of Thymopentin Binding to HLA-DR Molecules  

Microsoft Academic Search

Thymopentin (TP5) triggers an immune response by contacting with T cells; however the molecular basis of how TP5 achieves this process remains incompletely understood. According to the main idea of immunomodulation, we suppose that it would be necessary for TP5 to form complex with human class II major histocompatibility complex DR molecules (HLA-DR) before TP5 interacts with T cells. The

Zuojia Liu; Xiliang Zheng; Jin Wang; Erkang Wang; Martin Egli

2007-01-01

34

Apparatus and method of determining molecular weight of large molecules  

DOEpatents

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.

Fuerstenau, Stephen (Montrose, CA); Benner, W. Henry (Danville, CA); Madden, Norman (Livermore, CA); Searles, William (Fremont, CA)

1998-01-01

35

Apparatus and method of determining molecular weight of large molecules  

DOEpatents

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.

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

1998-06-23

36

Theoretical investigation of the molecular structure of the isoquercitrin molecule  

NASA Astrophysics Data System (ADS)

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.

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

1999-09-01

37

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

NASA Astrophysics Data System (ADS)

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

Ohishi, Masatoshi

2008-10-01

38

Small-Molecule Hormones: Molecular Mechanisms of Action  

PubMed Central

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

Budzinska, Monika

2013-01-01

39

Molecular dynamics simulation of paracetamol molecules ordering around glycogen  

NASA Astrophysics Data System (ADS)

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

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

2005-05-01

40

Polarizable Atomic Multipole-based Molecular Mechanics for Organic Molecules  

PubMed Central

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

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

2011-01-01

41

Rapid searches for complex patterns in biological molecules.  

PubMed Central

The intrinsic redundancy of genetic information makes searching for patterns in biological sequences a difficult task. We have designed an interactive self-documenting computer program called QUEST that allows rapid searching of large DNA and protein data banks for highly redundant consensus sequences or character patterns. QUEST uses a concise language for specifying character patterns containing several levels of ambiguity and pattern arrangement. Examples of the use of this program for sequence data are given. Details of the algorithm and pattern optimization are explained. PMID:6546419

Abarbanel, R M; Wieneke, P R; Mansfield, E; Jaffe, D A; Brutlag, D L

1984-01-01

42

Patterns of energy levels and spectra for polyatomic molecules  

SciTech Connect

Laser spectroscopy has revealed a remarkable intricacy in the rotational, vibrational, and electronic energy levels for polyatomic molecules. The infrared spectra of SF/sub 6/, CF/sub 4/, and related molecules contain several levels of structure on top of structure which resembles a fractal in some ways. The purpose of this article will be to exhibit some of this structure and introduce the simplest theoretical interpretations of it which are presently available.

Harter, W.G.

1983-01-01

43

Sensing of protein molecules through nanopores: a molecular dynamics study.  

PubMed

Solid-state nanopores have been shown to be suitable for single molecule detection. While numerous modeling investigations exist for DNA within nanopores, there are few simulations of protein translocations. In this paper, we use atomistic molecular dynamics to investigate the translocation of proteins through a silicon nitride nanopore. The nanopore dimensions and profile are representative of experimental systems. We are able to calculate the change in blockade current and friction coefficient for different positions of the protein within the pore. The change in ionic current is found to be negligible until the protein is fully within the pore and the current is lowest when the protein is in the pore center. Using a simple theory that gives good quantitative agreement with the simulation results we are able to show that the variation in current with position is a function of the pore shape. In simulations that guide the protein through the nanopore we identify the effect that confinement has on the friction coefficient of the protein. This integrated view of translocation at the nanoscale provides useful insights that can be used to guide the design of future devices. PMID:24651263

Kannam, Sridhar Kumar; Kim, Sung Cheol; Rogers, Priscilla R; Gunn, Natalie; Wagner, John; Harrer, Stefan; Downton, Matthew T

2014-04-18

44

Exploration of target molecules for molecular imaging of inflammatory bowel disease  

SciTech Connect

Highlights: {sup {yields}18}F-FDG PET could discriminate each inflamed area of IBD model mice clearly. {sup {yields}18}F-FDG PET could not discriminate the difference of pathogenic mechanism. {yields} Cytokines and cytokine receptors expression was different by pathogenic mechanism. {yields} Cytokines and cytokine receptors would be new target molecules for IBD imaging. -- Abstract: Molecular imaging technology is a powerful tool for the diagnosis of inflammatory bowel disease (IBD) and the efficacy evaluation of various drug therapies for it. However, it is difficult to elucidate directly the relationships between the responsible molecules and IBD using existing probes. Therefore, the development of an alternative probe that is able to elucidate the pathogenic mechanism and provide information on the appropriate guidelines for treatment is earnestly awaited. In this study, we investigated pathognomonic molecules in the intestines of model mice. The accumulation of fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) in the inflamed area of the intestines of dextran sulfate sodium (DSS)- or indomethacin (IND)-induced IBD model mice was measured by positron emission tomography (PET) and autoradiography to confirm the inflamed area. The results suggested that the inflammation was selectively induced in the colons of mice by the administration of DSS, whereas it was induced mainly in the ilea and the proximal colons of mice by the administration of IND. To explore attractive target molecules for the molecular imaging of IBD, we evaluated the gene expression levels of cytokines and cytokine receptors in the inflamed area of the intestines of both model mice. We found that the expression levels of cytokines and cytokine receptors were significantly increased during the progression of IBD, whereas the expression levels were decreased as the mucosa began to heal. In particular, the expression levels of these molecules had already changed before the symptoms of IBD appeared. In 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.

Higashikawa, Kei; Akada, Naoki; Yagi, Katsuharu [Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530 (Japan)] [Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530 (Japan); Watanabe, Keiko; Kamino, Shinichiro; Kanayama, Yousuke; Hiromura, Makoto [Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe 650-0047 (Japan)] [Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe 650-0047 (Japan); Enomoto, Shuichi, E-mail: senomoto@pharm.okayama-u.ac.jp [Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530 (Japan) [Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530 (Japan); Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe 650-0047 (Japan)

2011-07-08

45

MOLECULAR PHYSICS, 2003, VOL. 101, NOS. 45, 697704 Silicon molecules in space and in the laboratory  

E-print Network

of astronomical data, we discovered that small reactive silicon bearing molecules such as SiC, SiC2, and SiO couldMOLECULAR PHYSICS, 2003, VOL. 101, NOS. 4­5, 697­704 Silicon molecules in space of Si, silicon bearing molecules are a significant trace constituent of the gas associated with late

46

Transcriptional expression patterns triggered by chemically distinct neuroprotective molecules  

PubMed Central

Glutamate mediated excitotoxicity has been purported to underlie many neurodegenerative disorders. A subtype of glutamate receptors, namely N-methyl-D-aspartate (NMDA) receptors, has been recognized as potential targets for neuroprotection. To increase our understanding of the mechanisms that underlie this neuroprotection, we employed a mouse model of glutamate receptor induced excitotoxic injury. Primary cortical neurons derived from postnatal day-0 CD-1 mice were cultured in the presence or absence of neuroprotective molecules and exposed to NMDA. Following a recovery period, whole genome expression was measured by microarray analysis. We used a combination of database and text mining, as well as systems modeling to identify signatures within the differentially expressed genes. While molecules differed in their mechanisms of action, we found significant overlap in the expression of a core group of genes and pathways. Many of these molecules have clear links to neuronal protection and survival, including ion channels, transporters, as well as signaling pathways including the mitogen-activated protein kinase (MAPK), the Toll-like receptor (TLR), and the hypoxic inducible factor (HIF). Within the TLR pathway, we also discovered a significant enrichment of interferon regulatory factor 7 (IRF7) regulated genes. Knockdown of Irf7 by RNA interference resulted in reduced survival following NMDA treatment. Given the prominent role that IRF7 plays in the transduction of type-I interferons (IFN), we also tested whether type-I IFNs alone functioned as neuroprotective agents and found that type-I IFNs were sufficient to promote neuronal survival. Our data suggest that the TLR/IRF7/IFN axis plays a significant role in recovery from glutamate induced excitotoxicity. PMID:22986168

Pappas, D.J.; Gabatto, P.A.; Oksenberg, D; Khankhanian, P.; Baranzini, S.E.; Gan, L.; Oksenberg, J.R.

2012-01-01

47

Tunable organic hetero-patterns via molecule diffusion control.  

PubMed

A simple, scalable method is reported to fabricate ordered hetero-structures of organic materials using template-directed growth. The 3D extension of the structures is firstly determined by pre-pattern size and deposition amount, and can further be in situ tuned by annealing at appropriate temperature. PMID:24729306

Wang, Hong; Wang, Wenchong; Li, Liqiang; Hirtz, Michael; Wang, C G; Wang, Yue; Xie, Zhaoxiong; Fuchs, Harald; Chi, Lifeng

2014-08-01

48

Elements of the theory of molecular spectra. [multiatomic molecules  

NASA Technical Reports Server (NTRS)

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

Gribov, L. A.

1979-01-01

49

Fluorescence of complex molecules in crossed electron and molecular beams  

Microsoft Academic Search

UDC 535.371:621.378 Investigation of the interaction of various particles with polyatomic molecules is a complex problem having fundamental and applied significance. Complex organic molecules serve as transformers of various types of excitation into spontaneous and stimulated emission of light [ 1 ]; a low-temperature plasma in the vapors of complex organic compounds is used, for example, in plasmachemistry 12 I.

I. Yu. Baranov; M. L. Burshtein; V. V. Gruzinskii; M. N. Kaputerko; V. P. Prosikhin

1995-01-01

50

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

SciTech Connect

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.

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

2009-04-02

51

Particle-Induced Desorption of Kilodalton Molecules Embedded in a Matrix: A Molecular Dynamics Study  

E-print Network

Particle-Induced Desorption of Kilodalton Molecules Embedded in a Matrix: A Molecular Dynamics and the mechanistic analysis of representative trajectories help us understand the main features of molecular significantly progressed with the development of sophisticated molecular dynamics (MD) simulation codes.1

52

Speckle Patterns with Atomic and Molecular de Broglie Waves  

SciTech Connect

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

Patton, Forest S.; Deponte, Daniel P.; Kevan, Stephen D. [Department of Physics, University of Oregon, Eugene, Oregon 97403-1274 (United States); Elliott, Greg S. [Department of Physics, University of Puget Sound, Tacoma, Washington 98416 (United States)

2006-07-07

53

Biogeographical patterns of soil molecular microbial biomass as  

E-print Network

organization of soil microbial communities on large scales and the identification of environmental factorsRESEARCH PAPER Biogeographical patterns of soil molecular microbial biomass as influenced by soil was to determine the spatial patterning of microbial biomass in soils over a wide extent and to rank the envi

Thioulouse, Jean

54

Molecular Physiology of Protein Kinases (and Phosphatases): Molecules, mechanisms, medicines  

NSDL National Science Digital Library

This powerpoint presentation from the 2011 EB Refresher Course on CellPhysiology:Intracellular Signaling addressed protein kinase structure, conformational changes, molecular domains, activation, and inhibition.

Michael Eck (Harvard University)

2011-04-09

55

Molecular Physiology of Protein Kinases (and Phosphatases): Molecules, mechanisms, medicines  

NSDL National Science Digital Library

This recorded presentation from the 2011 EB Refresher Course on CellPhysiology:Intracellular Signaling addressed protein kinase structure, conformational changes, molecular domains, activation, and inhibition.

Michael Eck (Harvard University)

2011-04-09

56

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

NASA Astrophysics Data System (ADS)

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.

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

2014-10-01

57

Progress in Biophysics & Molecular Biology 74 (2000) 115140 Twisting and stretching single DNA molecules  

E-print Network

Progress in Biophysics & Molecular Biology 74 (2000) 115­140 Review Twisting and stretching single and tools for the study of single-molecule biophysics. Methods as diverse as optical and magnetic tweezers

Levine, Alex J.

58

Probing molecular frame photoelectron angular distributions via high-order harmonic generation from aligned molecules  

E-print Network

. In recent years, using high-energy XUV or x-ray photons, fixed-in-space PI has been investigated by using the inner orbital of a molecule and the molecular ion dissociates after photoabsorption. If the dissociation

Lin, Chii-Dong

59

A molecular dynamics simulation of the destruction of explosive molecules at high-velocity collisions  

Microsoft Academic Search

The infrared spectra and the energies of dissociation of R-NO2 bonds (R?C, N, and O) were calculated for explosive molecules (trinitrotoluene, hexogen, octogen, pentaerythrityl tetranitrate,\\u000a triaminotrinitrobenzene, and nitromethane). The time of kinetic energy redistribution over intramolecular vibrational modes\\u000a for these molecules (the V-V relaxation time) was calculated by the molecular dynamics simulation method. Molecular dynamics simulations were also used\\u000a to

A. A. Selezenev; A. Yu. Aleinikov; I. V. Briginas

2008-01-01

60

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

ERIC Educational Resources Information Center

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…

Barak, Phillip; Nater, Edward A.

2005-01-01

61

The Hedgehog (Hh) family of signaling molecules are key agents in patterning numerous types of tissues. Mutations in Hh  

E-print Network

of secreted signaling molecules as key organizers of tissue patterning. Initially discovered in Drosophila, Hh503 The Hedgehog (Hh) family of signaling molecules are key agents in patterning numerous types of tissues. Mutations in Hh and its downstream signaling molecules are also associated with numerous

Perrimon, Norbert

62

Heteroduplex molecules cause sexing errors in a standard molecular protocol for avian sexing.  

PubMed

Molecular methods are a necessary tool for sexing monomorphic birds. These molecular approaches are usually reliable, but sexing protocols should be evaluated carefully because biochemical interactions may lead to errors. We optimized laboratory protocols for genetic sexing of a monomorphic shorebird, the upland sandpiper (Bartramia longicauda), using two independent sets of primers, P2/P8 and 2550F/2718R, to amplify regions of the sex-linked CHD-Z and CHD-W genes. We discovered polymorphisms in the region of the CHD-Z intron amplified by the primers P2/P8 which caused four males to be misidentified as females (n = 90 mated pairs). We cloned and sequenced one CHD-W allele (370 bp) and three CHD-Z alleles in our population: Z° (335 bp), Z' (331 bp) and Z? (330 bp). Normal (Z°Z°) males showed one band in agarose gel analysis and were easily differentiated from females (Z°W), which showed two bands. However, males heterozygous for CHD-Z alleles (Z'Z?) unexpectedly showed two bands in a pattern similar to females. While the Z' and Z? fragments contained only short deletions, they annealed together during the polymerase chain reaction (PCR) process and formed heteroduplex molecules that were similar in size to the W fragment. Errors previously reported for molecular sex-assignment have usually been due to allelic dropout, causing females to be misidentified as males. Here, we report evidence that events in PCRs can lead to the opposite error, with males misidentified as females. We recommend use of multiple primer sets and large samples of known-sex birds for validation when designing protocols for molecular sex analysis. PMID:21564567

Casey, Ashley E; Jones, Kenneth L; Sandercock, Brett K; Wisely, Samantha M

2009-01-01

63

Molecular forces for the binding and condensation of DNA molecules.  

PubMed Central

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

Cai, Xian-E; Yang, Jie

2002-01-01

64

Molecular vortex generated from an atom-molecule dark state  

SciTech Connect

We consider a Raman photoassociation model in a field configuration in which a Gaussian and a first-order Laguerre Gaussian laser field are applied between the bound-bound and free-bound transitions, respectively. We show that such a configuration can lead to a coherent population trapping superposition of an atomic condensate and a ground molecular vortex of unit winding number. We develop stimulated Raman adiabatic passages that minimize the effect of mean-field shifts due to collisions, for optimal conversion of an atomic condensate into a ground molecular vortex.

Ling, H. Y. [Key Laboratory of Optical and Magnetic Resonance Spectroscopy (Ministry of Education), Department of Physics, East China Normal University, Shanghai 200062 (China); Department of Physics and Astronomy, Rowan University, Glassboro, New Jersey 08028-1700 (United States); Yi, S. [Department of Physics and Astronomy, and Rice Quantum Institute, Rice University, Houston, Texas 77251-1892 (United States); Institute of Theoretical Physics, The Chinese Academy of Science, Beijing 100080 (China); Pu, H. [Department of Physics and Astronomy, and Rice Quantum Institute, Rice University, Houston, Texas 77251-1892 (United States); Grochowski, D. E. [Department of Physics and Astronomy, Rowan University, Glassboro, New Jersey 08028-1700 (United States); Zhang Weiping [Key Laboratory of Optical and Magnetic Resonance Spectroscopy (Ministry of Education), Department of Physics, East China Normal University, Shanghai 200062 (China)

2006-05-15

65

Molecular Recognition of DNA by Small Molecules Peter B. Dervan*  

E-print Network

Engineering, California Institute of Technology, Pasadena, CA 91125, USA Accepted 17 July 2001 Chemists, like in the mind of a person. I became interested in creating novel molecular shapes with properties differ- ent approach. One has the benefit of look- ing back and understanding in hindsight which were pivotal decision

Dervan, Peter B.

66

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

SciTech Connect

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.

Sotthewes, Kai; Heimbuch, René, E-mail: r.heimbuch@utwente.nl; Kumar, Avijit; Zandvliet, Harold J. W. [Physics of Interfaces and Nanomaterials, MESA Institute for Nanotechnology, University of Twente, P.O. Box 217, 7500AE Enschede (Netherlands); Geskin, Victor [Service de Chimie des Materiaux Nouveaux, University of Mons, Mons (Belgium)

2014-01-01

67

Probing molecular frame photoionization via laser generated high-order harmonics from aligned molecules.  

PubMed

Present experiments cannot measure molecular frame photoelectron angular distributions (MFPAD) for ionization from the outermost valence orbitals of molecules. We show that the details of MFPAD can be retrieved with high-order harmonics generated by infrared lasers from aligned molecules. Using accurately calculated photoionization transition dipole moments for fixed-in-space molecules, we show that the dependence of the magnitude and phase of the high-order harmonics on the alignment angle of the molecules observed in recent experiments can be quantitatively reproduced. This result provides the needed theoretical basis for ultrafast dynamic chemical imaging using infrared laser pulses. PMID:19519025

Le, Anh-Thu; Lucchese, R R; Lee, M T; Lin, C D

2009-05-22

68

Expression pattern of epithelial cell adhesion molecule on normal and malignant colon tissues  

PubMed Central

AIM: To investigate the expression pattern of epithelial cell adhesion molecule (Ep-CAM) on normal and malignant colon tissues to evaluate its diagnostic and therapeutic significance. METHODS: cDNA encoding Ep-CAM extracellular domain was cloned by reverse transcription-polymerase chain reaction (RT-PCR) from excised malignant colon tissues and inserted into a glutathione S-transferase (GST)-tagged vector. Ep-CAM-GST fusion protein was induced by isopropyl-?-D-thiogalactopyranoside (IPTG) and purified with glutathione-sepharose. The Ep-CAM-GST fusion protein was mixed with Freund’s adjuvant and Balb/c mice were immunized with it. Sp2/0 myeloma cells were fused with the spleen cells of the immunized mice. After having selected by indirect ELISA, the anti-Ep-CAM monoclonal antibodies (MAbs) were generated and the corresponding ascites were obtained. Finally, the human colon carcinoma tissue array prepared from seventy individual patients was stained with the anti-Ep-CAM MAbs. RESULTS: The isolated Ep-CAM cDNA sequence was identical to the data in GenBank. The expressed fusion protein was almost soluble and had a molecular weight (MW) of 53 ku. Four MAbs against Ep-CAM were obtained and designated as FMU-Ep1, FMU-Ep2, FMU-Ep3 and FMU-Ep4 respectively. Among them, FMU-Ep4 could recognize the natural Ep-CAM on Colo205 and SW480 cells, and all of them could be used for immunohistochemical staining of tissue sections. It was found that Ep-CAM was distributed differently in normal and various malignant colon tissues, including squamous cell carcinoma, signet-ring cell carcinoma and adenocarcinoma. In normal colon gland epithelia, Ep-CAM antigen was mainly distributed on the basolateral membrane and in the region between the basolateral membrane and the cytoplastic part near the nuclei, whereas the expression pattern of colon malignancies was mainly on the whole surface of epithelia and the expression was much higher than the normal colon tissues. The staining pattern of tissue array showed in adenocarcinoma and papillary adenocarcinoma, and the expression of Ep-CAM was increased from grade I to grade III. CONCLUSION: MAbs against Ep-CAM might be useful for research on the structure and function of Ep-CAM and may have diagnostic and therapeutic value to various colon carcinomas. PMID:15637741

Xie, Xin; Wang, Chun-Yan; Cao, Yun-Xin; Wang, Wei; Zhuang, Ran; Chen, Li-Hua; Dang, Na-Na; Fang, Liang; Jin, Bo-Quan

2005-01-01

69

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

PubMed

Cruciform-like molecules with two orthogonally placed ?-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

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

70

Molecular dynamics study of water molecule diffusion in oil-paper insulation materials  

NASA Astrophysics Data System (ADS)

Moisture is an important factor that influences the safe operation of transformers. In this study, molecular dynamics was employed to investigate the diffusion behavior of water molecules in the oil-paper insulation materials of transformers. Two oil-cellulose models were built. In the first model, water molecules were initially distributed in oil, and in the second model, water molecules were distributed in cellulose. The non-bonding energies of interaction between water molecules and oil, and between water molecules and cellulose, were calculated by the Dreiding force field. The interaction energy was found to play a dominant role in influencing the equilibrium distribution of water molecules. The radial direction functions of water molecules toward oil and cellulose indicate that the hydrogen bonds between water molecules and cellulose are sufficiently strong to withstand the operating temperature of the transformer. Mean-square displacement analysis of water molecules diffusion suggests that water molecules initially distributed in oil showed anisotropic diffusion; they tended to diffuse toward cellulose. Water molecules initially distributed in cellulose diffused isotropically. This study provides a theoretical contribution for improvements in online monitoring of water in transformers, and for subsequent research on new insulation materials.

Liao, Rui-Jin; Zhu, Meng-Zhao; Yang, Li-Jun; Zhou, Xin; Gong, Chun-Yan

2011-03-01

71

Electronic continuum model for molecular dynamics simulations of biological molecules  

PubMed Central

Electronic polarizability is an important factor in molecular interactions. In the conventional force fields such as AMBER or CHARMM, however, there is inconsistency in how the effect of electronic dielectric screening of Coulombic interactions, inherent for the condensed phase media, is treated. Namely, the screening appears to be accounted for via effective charges only for neutral moieties, whereas the charged residues are treated as if they were in vacuum. As a result, the electrostatic interactions between ionized groups are exaggerated in molecular simulations by the factor of about 2. The discussed here MDEC (Molecular Dynamics in Electronic Continuum) model provides a theoretical framework for modification of the standard non-polarizable force fields to make them consistent with the idea of uniform electronic screening of partial atomic charges. The present theory states that the charges of ionized groups and ions should be scaled; i.e. reduced by a factor of about 0.7. In several examples, including the interaction between Na+ ions, which is of interest for ion-channel simulations, and the dynamics of an important salt-bride in Cytochrome c Oxidase, we compared the standard non-polarizable MD simulations with MDEC simulations, and demonstrated that MDEC charge scaling procedure results in more accurate interactions. The inclusion of electronic screening for charged moieties is shown to result in significant changes in protein dynamics and can give rise to new qualitative results compared with the traditional non-polarizable force fields simulations.

Leontyev, I. V.; Stuchebrukhov, A. A.

2010-01-01

72

Molecular topology analysis of the differences between drugs, clinical candidate compounds, and bioactive molecules.  

PubMed

A new method to decompose molecules is proposed and used to analyze drugs, clinical candidate compounds and bioactive molecules. The method classifies a set of molecules into a few well-defined classes based on their molecular framework. It is then possible to use these classes to investigate differences between drugs, clinical candidates and bioactive molecules. The analysis shows that in comparison with clinical candidates and bioactive compounds, drugs have a higher fraction of compounds with only one ring system. This conclusion is still valid after correcting for lipophilicity (ClogP) and molecular size, as well as any potential protein target bias in the data sets. Furthermore the molecular bridge part of compounds in the drug set has on average fewer ring systems than molecules from the other sets. The ring system complexity (RSC) was also investigated and for most topological classes drugs have a lower RSC than the clinical candidates and bioactive molecules. Hence, this study highlights differences in topology between drugs, clinical candidate compounds and bioactive molecules. PMID:21077637

Chen, Hongming; Yang, Yidong; Engkvist, Ola

2010-12-27

73

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

NASA Astrophysics Data System (ADS)

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 candidates for bottom electrodes within SAM-based molecular electronic tunnel junctions. Chapter 8 investigates the charge transport properties of new diphenyldithiophosphinic acid (Ph 2DTPA) SAMs on TS gold within metal-SAM//Ga2O3/EGaIn molecular tunnel junctions. A computational investigation provides insight into the electronic structure of the junction.

Miller, Michael Stephen

74

Using the first steps of hydration for the determination of molecular conformation of a single molecule.  

PubMed

Determination of the exact structure of individual molecules is the ultimate goal of high-resolution microscopy. However, the resolution of scanning tunneling microscopy (STM) is intrinsically limited to the extent of molecular orbitals, which frequently do not differ for small changes in the molecular conformation. Here we use the position of water molecules during the first hydration steps of an azobenzene derivative on Au(111) to determine not only the orientation of the end groups with respect to the phenyl rings but also the orientation of the two phenyl rings with respect to the azo group. We investigate the co-adsorption of 4,4'-hydroxy-azobenzene and water molecules on Au(111) by low-temperature STM. The water molecules are attached exclusively to the hydroxyl end groups of the azobenzene derivatives. Predominantly the trans-azobenzene molecule with the two hydroxyl groups pointing into opposite directions is adsorbed. As corroborated by the attachment of a single water molecule to 4-anilino-4'-nitro azobenzene on the same inert surface, the method is generally applicable for structure determination of molecules with appropriate end groups. Our study thus gives unprecedented information about the intramolecular orientation based on the first real space observation of the hydration of a functional molecule. PMID:25180814

Henzl, Jörg; Boom, Konrad; Morgenstern, Karina

2014-09-24

75

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

Microsoft Academic Search

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 amyloid peptides, 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

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

2011-01-01

76

Geometric structure of a molecule of Epitalon tetrapeptide: A molecular-dynamics simulation  

Microsoft Academic Search

Variation of the geometric parameters of a molecule of Epitalon tetrapeptide (Ala-Glu-Asp-Gly) over a period of 1500 ps was\\u000a simulated by the method of molecular dynamics using AMBER force field. The structure of the molecule is stabilized by two\\u000a salt bridges formed by the N-terminal nitrogen atom and oxygen atoms of Asp and Glu side chains. The biological effect of

I. V. Rogachevskii; B. F. Shchegolev; V. Kh. Khavinson

2006-01-01

77

Role of molecule flexibility on the nucleation of dislocations in molecular crystals  

NASA Astrophysics Data System (ADS)

We show that a molecule's flexibility described by changes to its conformation and orientation during deformation is vital for the proper representation of dislocation nucleation in molecular crystals. This is shown for the molecular crystal hexahydro-1,3,5-trinitro-s-triazine (RDX) by comparing direct atomistic simulations to two alternate forms of a continuum dislocation nucleation model for a crack tip loaded in pure shear. The atomistic simulations show the emission of partial dislocations. These are compared to continuum dislocation nucleation models based on generalized stacking fault (GSF) energy surfaces where the molecules are allowed to be either rigid or flexible. The rigid molecules are unable to represent the partial dislocations whereas the flexible molecules agree with the direct atomistic model to within 17% of the stress intensity factor for emission of the first partial dislocation and to within 1% for the second partial. This agreement first indicates that the molecule flexibility serves a critical role in the ductile behavior of the molecular crystal and, second, the continuum dislocation nucleation model represents the correct atomistic behavior, showing two partial dislocations connected by a stacking fault, when parameterized with GSF energy surfaces that account for the molecule flexibility.

Munday, Lynn B.; Mitchell, Robert L.; Knap, Jaroslaw; Chung, Peter W.

2013-10-01

78

Molecular biology, genetics and biochemistry of the repulsive guidance molecule family  

PubMed Central

RGMs (repulsive guidance molecules) comprise a recently discovered family of GPI (glycosylphosphatidylinositol)-linked cell-membrane-associated proteins found in most vertebrate species. The three proteins, RGMa, RGMb and RGMc, products of distinct single-copy genes that arose early in vertebrate evolution, are ~ 40–50%identical to each other in primary amino acid sequence, and share similarities in predicted protein domains and overall structure, as inferred by ab initio molecular modelling; yet the respective proteins appear to undergo distinct biosynthetic and processing steps, whose regulation has not been characterized to date. Each RGM also displays a discrete tissue-specific pattern of gene and protein expression, and each is proposed to have unique biological functions, ranging from axonal guidance during development (RGMa) to regulation of systemic iron metabolism (RGMc). All three RGM proteins appear capable of binding selected BMPs (bone morphogenetic proteins), and interactions with BMPs mediate at least some of the biological effects of RGMc on iron metabolism, but to date no role for BMPs has been defined in the actions of RGMa or RGMb. RGMa and RGMc have been shown to bind to the transmembrane protein neogenin, which acts as a critical receptor to mediate the biological effects of RGMa on repulsive axonal guidance and on neuronal survival, but its role in the actions of RGMc remains to be elucidated. Similarly, the full spectrum of biological functions of the three RGMs has not been completely characterized yet, and will remain an active topic of ongoing investigation. PMID:19698085

Severyn, Christopher J.; Shinde, Ujwal; Rotwein, Peter

2014-01-01

79

Carbon Nanotube Biosensors for Space Molecule Detection and Clinical Molecular Diagnostics  

NASA Technical Reports Server (NTRS)

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.

Han, Jie

2001-01-01

80

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

PubMed Central

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

Hentabli, Hamza; Abdo, Ammar; Salim, Naomie

2014-01-01

81

Extended orientational correlation study for molecular liquids containing distorted tetrahedral molecules: Application to methylene halides  

NASA Astrophysics Data System (ADS)

The method of Rey [Rey, J. Chem. Phys. 126, 164506 (2007)] for describing how molecules orient toward each other in systems with perfect tetrahedral molecules is extended to the case of distorted tetrahedral molecules of c2v symmetry by means of introducing 28 subgroups. Additionally, the original analysis developed for perfect tetrahedral molecules, based on six groups, is adapted for molecules with imperfect tetrahedral shape. Deriving orientational correlation functions have been complemented with detailed analyses of dipole-dipole correlations. This way, (up to now) the most complete structure determination can be carried out for such molecular systems. In the present work, these calculations have been applied for particle configurations resulting from reverse Monte Carlo computer modeling. These particle arrangements are fully consistent with structure factors from neutron and x-ray diffraction measurements. Here we present a complex structural study for methylene halide (chloride, bromide, and iodide) molecular liquids, as possibly the best representative examples. It has been found that the most frequent orientations of molecules are of the 2:2 type over the entire distance range in these liquids. Focusing on the short range orientation, neighboring molecules turn toward each other with there ``H,Y''-``H,Y'' (Y: Cl, Br, I) edges, apart from CH2Cl2 where the H,H-H,Cl arrangement is the most frequent. In general, the structure of methylene chloride appears to be different from the structure of the other two liquids.

Pothoczki, Szilvia; Temleitner, László; Pusztai, László

2010-04-01

82

Atomistic theory of mesoscopic pattern formation induced by bimolecular surface reactions between oppositely charged molecules  

NASA Astrophysics Data System (ADS)

The kinetics of mesoscopic pattern formation is studied for a reversible A+B?0 reaction between mobile oppositely charged molecules at the interface. Using formalism of the joint correlation functions, non-equilibrium charge screening and reverse Monte Carlo methods, it is shown that labyrinth-like percolation structure induced by (even moderate-rate) reaction is principally non-steady-state one and is associated with permanently growing segregation of dissimilar reactants and aggregation of similar reactants into mesoscopic size domains. A role of short-range and long-range reactant interactions in pattern formation is discussed.

Kuzovkov, V. N.; Kotomin, E. A.; Zvejnieks, G.

2011-12-01

83

Length-dependent conductance of molecular wires and contact resistance in metal-molecule-metal junctions.  

PubMed

Molecular wires are covalently bonded to gold electrodes--to form metal-molecule-metal junctions--by functionalizing each end with a -SH group. The conductance of a wide variety of molecular junctions is studied theoretically by using first-principles density functional theory (DFT) combined with the nonequilibrium Green's function (NEGF) formalism. Based on the chain-length-dependent conductance of the series of molecular wires, the attenuation factor beta is obtained and compared with the experimental data. The beta value is quantitatively correlated to the molecular HOMO-LUMO gap. Coupling between the metallic electrode and the molecular bridge plays an important role in electron transport. A contact resistance of 6.0+/-2.0 Kohms is obtained by extrapolating the molecular-bridge length to zero. This value is of the same magnitude as the quantum resistance. PMID:18512822

Liu, Hongmei; Wang, Nan; Zhao, Jianwei; Guo, Yan; Yin, Xing; Boey, Freddy Y C; Zhang, Hua

2008-07-14

84

Molecular dynamics simulations of small molecule diffusion in hydrogels  

NASA Astrophysics Data System (ADS)

Solute diffusion across polymer matrices is important in several technological applications such as controlled drug delivery, gel electrophoresis and gas separation. Our primary objective is to investigate the effect of size-exclusion on solute diffusion in polymer matrices with a focus on crosslinked hydrogel networks. The diffusion co-efficient of a solute in a hydrogel depends on the free-volume available as determined by the solute size and the polymer concentration. However, hydrogels have a highly disordered pore structure due to the random nature of the crosslinking techniques used in their preparation. The characterization of the free-volume of this pore structure by experimental techniques or mathematical modeling is not straightforward. Consequently, this precludes a direct testing of the correlation between diffusion and free-volume. In this thesis, we prepare simple, defect-free, end-crosslinked polymer networks via computer simulation. We choose a coarse-grained bead-spring representation for our polymer chains. In addition to crosslinked networks, we also prepare other host matrices: polymer solutions composed of flexible chains and fibrous matrices composed of interpenetrating rods. The free-volume available to a solute of a given size in these host matrices is characterized by calculating the so-called accessible volume fraction. Subsequently, the solute diffusion coefficients are computed by performing Molecular Dynamics (MD) simulations. Our general finding is that the solute diffusion coefficients in these host matrices correlate well with the accessible volume fraction, which collapses onto one single variable the twin effects of solute size and polymer concentration. In the case of a crosslinked network with a given crosslinking density, solute diffusivities are a unique function of the accessible volume fraction. We also conclude that the mobility of the chains in the polymer matrix has a significant effect on solute diffusion, even at high accessible volume fraction. We have also investigated the effect of attractive solute-polymer interactions on solute partitioning and diffusion in crosslinked networks. A solute with specific interactions diffuses faster than an inert solute of the same size. We attribute this to the active partitioning of solutes across the bottlenecks in the network that the solute encounters during diffusion.

Sivasubramanian, Arvind

85

Adsorption of water molecules inside a Au nanotube: a molecular dynamics study.  

PubMed

A molecular dynamics simulation of water molecules through a Au nanotube with a diameter of 20 A at bulk densities 0.8, 1, and 1.2 gcm(3) has been carried out. The water molecules inside a nanoscale tube, unlike those inside a bulk tube, have a confined effect. The interaction energy of the Au nanotube wall has a direct influence on the distribution of water molecules inside the Au tube in that the adsorption of the water molecules creates shell-like formations of water. Moreover, the high number of adsorbed molecules has already achieved saturation at the wall of the Au nanotube at three bulk densities. This work compares the distribution percentage profiles of hydrogen bonds for different regions inside the tube. The structural characteristics of water molecules inside the tube have also been studied. The results reveal that the numbers of hydrogen bonds per water molecule influence the orientational order parameter q. In addition, the phenomenon of a group of molecules bonded inside the tube can be observed as the number of hydrogen bonds increase. PMID:18465934

Weng, Meng-Hsiung; Lee, Wen-Jay; Ju, Shin-Pon; Chao, Chien-Hsiang; Hsieh, Nan-Kai; Chang, Jee-Gong; Chen, Hui-Lung

2008-05-01

86

Decomposition Mechanism Studies of Energetic Molecules Using HOMO and LUMO Orbital Energy Driven Molecular Dynamics  

Microsoft Academic Search

In this paper, we present decomposition mechanism studies of energetic molecules using HOMO and LUMO orbital energy gap driven molecular dynamics (MD) method. Under frozen orbital approximation, this is an `electronic excitation' MD, where electrons is excited from HOMO to LUMO orbitals Meanwhile, the HOMO and LUMO orbital energy gap is taken as a biasing potential to accelerate chemical reactions,

Yanhua Dong; Yanfeng Song; Hakima Abou-Rachid

2009-01-01

87

Above-threshold ionization of diatomic molecules in an intense laser field: Molecular alignment effects  

NASA Astrophysics Data System (ADS)

In this work, we study the photoelectron spectra of the diatomic molecule O2 in the direction perpendicular to the laser polarization. Compared with atoms, molecules have additional parameters, e.g., the orientation of the molecule and the symmetry of the initial electronic state, and thus give rise to richer strong-field phenomena. Our simulations show that for parallel and perpendicular alignments of the laser polarization with respect to the molecular axis, the photoelectron spectra display above-threshold ionization (ATI) peaks with a specific 2?? separation in which the absorption of an even number of photons is absent. However, for other alignment angles, the even-order ATI peaks appear. According to our analysis, the physical mechanism of the alignment effect of the even-order ATI peaks can be attributed to the symmetry of the molecular ground-state wave function with respect to the photoelectron emission direction.

Hu, ZiLong; Lai, XuanYang; Liu, XiaoJun; Chen, Jing

2014-04-01

88

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

PubMed

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. PMID:24963600

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

2014-01-01

89

Magneto-transport through single-molecule magnets: Kondo-peaks, zero-bias dips, molecular symmetry and Berry's phase  

E-print Network

Magneto-transport through single-molecule magnets: Kondo-peaks, zero-bias dips, molecular symmetry-molecule magnets: Kondo-peaks, zero-bias dips, molecular symmetry and Berry's phase Maarten R Wegewijs, Christian of the results of sections 4 and 5 of [1] confirms one of the central conclusions, namely, that the excited

90

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

NASA Astrophysics Data System (ADS)

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

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

2014-09-01

91

Structural and electronic properties of pentacene molecule and molecular pentacene solid  

E-print Network

The structural and electronic properties of a single pentacene molecule and a pentacene molecular crystal, an organic semiconductor, are examined by a first-principles method based on the generalized gradient approximation of density functional theory. Calculations were carried out for a triclinic unit cell containing two pentacene molecules. The bandwidths of the valence and conduction bands which determine the charge migration mechanism are found to depend strongly on the crystallographic direction. Along the triclinic reciprocal lattice vectors A and B which are orientated approximately perpendicular to the molecular axes the maximal valence (conduction) band width amounts to only 75 (59) meV, even smaller values are obtained for the C direction parallel to molecular axes even less. Along the stacking directions A+B and A-B, however, the maximal valence (conduction) band width is found to reach 145 (260) meV. The value for the conduction band width is larger than estimates for the polaron binding energy but significantly smaller than recent results obtained by semiempirical methods. The single molecule has a HOMO-LUMO gap of about 1.1 eV as deduced from the Kohn-Sham eigenvalue differences. When using the self-consistent field method, which is expected to yield more reliable results, a value of 1.64 eV is obtained. The theoretical value for the band gap in the molecular solid amounts to 1.0 eV at the Gamma-point.

R. G. Endres; C. Y. Fong; L. H. Yang; G. Witte; Ch. Woll

2002-11-19

92

Molecular Dynamics Simulation of Multivalent-Ion Mediated Attraction between DNA Molecules  

NASA Astrophysics Data System (ADS)

All atom molecular dynamics simulations with explicit water were done to study the interaction between two parallel double-stranded DNA molecules in the presence of the multivalent counterions putrescine (2+), spermidine (3+), spermine (4+) and cobalt hexamine (3+). The inter-DNA interaction potential is obtained with the umbrella sampling technique. The attractive force is rationalized in terms of the formation of ion bridges, i.e., multivalent ions which are simultaneously bound to the two opposing DNA molecules. The lifetime of the ion bridges is short on the order of a few nanoseconds.

Dai, Liang; Mu, Yuguang; Nordenskiöld, Lars; van der Maarel, Johan R. C.

2008-03-01

93

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

PubMed Central

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

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

2013-01-01

94

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

NASA Astrophysics Data System (ADS)

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.

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

2014-10-01

95

Femtosecond photoelectron diffraction on laser-aligned molecules: Towards time-resolved imaging of molecular structure  

NASA Astrophysics Data System (ADS)

We demonstrate an experimental method to record snapshot diffraction images of polyatomic gas-phase molecules, which can, in a next step, be used to probe time-dependent changes in the molecular geometry during photochemical reactions with femtosecond temporal and angstrom spatial resolution. Adiabatically laser-aligned 1-ethynyl-4-fluorobenzene (C8H5F) molecules were imaged by diffraction of photoelectrons with kinetic energies between 31 and 62 eV, created from core ionization of the fluorine (1s) level by ?80 fs x-ray free-electron-laser pulses. Comparison of the experimental photoelectron angular distributions with density functional theory calculations allows relating the diffraction images to the molecular structure.

Boll, R.; Anielski, D.; Bostedt, C.; Bozek, J. D.; Christensen, L.; Coffee, R.; De, S.; Decleva, P.; Epp, S. W.; Erk, B.; Foucar, L.; Krasniqi, F.; Küpper, J.; Rouzée, A.; Rudek, B.; Rudenko, A.; Schorb, S.; Stapelfeldt, H.; Stener, M.; Stern, S.; Techert, S.; Trippel, S.; Vrakking, M. J. J.; Ullrich, J.; Rolles, D.

2013-12-01

96

Accessory proteins and the assembly of human class I MHC molecules: a molecular and structural perspective.  

PubMed

The cell-surface presentation of antigenic peptides by class I major histocompatibility complex (MHC) molecules to CD8+ T-cell receptors is part of an immune surveillance mechanism aimed at detecting foreign antigens. This process is initiated in the endoplasmic reticulum (ER) with the folding and assembly of class I MHC molecules which are then transported to the cell surface via the secretory pathway. In recent years, several accessory proteins have been identified as key components of the class I maturation process in the ER. These proteins include the lectin chaperones calnexin (CNX) and calreticulin (CRT), the thiol-dependent oxidoreductase ERp57, the transporter associated with antigen processing (TAP), and the protein tapasin. This review presents the most recent advances made in characterizing the biochemical and structural properties of these proteins, and discusses how this knowledge advances our current understanding of the molecular events underlying the folding and assembly of human class I MHC molecules in the ER. PMID:12531281

Bouvier, Marlene

2003-01-01

97

Molecular effects in the neutrino mass determination from beta-decay of the tritium molecule  

SciTech Connect

Molecular final state energies and transition probabilities have been computed for beta-decay of the tritium molecule. The results are of sufficient accuracy to make a determination of the electron neutrino rest mass with an error not exceeding a few tenths of an electron volt. Effects of approximate models of tritium beta-decay on the neutrino mass determination are discussed. 14 refs., 3 figs., 1 tab.

Fackler, O.; Jeziorski, B.; Kolos, W.; Szalewicz, K.; Monkhorst, H.J.; Mugge, M.

1986-03-01

98

Interactions of Liquid Crystal-Forming Molecules with Phospholipid Bilayers Studied by Molecular Dynamics Simulations  

Microsoft Academic Search

Recent experiments have shown that liquid crystals can be used to image mammalian cell membranes and to amplify structural reorganization in phospholipid-laden liquid crystal-aqueous interfaces. In this work, molecular dynamics simulations were employed to explore the interactions between commonly used liquid crystal-forming molecules and phospholipid bilayers. In particular, umbrella sampling was used to obtain the potential of mean force of

Evelina B. Kim; Nathan Lockwood; Manan Chopra; Orlando Guzmán; Nicholas L. Abbott; Juan J. de Pablo

2005-01-01

99

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

PubMed

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

Ozcan, Nergiz; Mareš, Ji?í; Sundholm, Dage; Vaara, Juha

2014-09-24

100

Single-molecule toroics in Ising-type lanthanide molecular clusters.  

PubMed

Single-molecule toroics (SMTs) are defined, by analogy with single-molecule magnets, as bistable molecules with a toroidal magnetic state, and seem to be most promising for future applications in quantum computing and information storage and use as multiferroic materials with magnetoelectric effect. As an interdisciplinary research area that spans chemistry, physics and material sciences, synthetic chemists have produced systems suitable for detailed study by physicists and materials scientists, while ab initio calculations have been playing a major role in the detection of toroidal magnetization and the advancement of this field. In this tutorial review, we demonstrate the research developed in the fascinating and challenging field of molecular-based SMTs with particular focus on how recent studies tend to address the issue of toroidal arrangement of the magnetic moment in these systems. Herein, nine typical SMTs are summarized, showing that the assembly of wheel-shaped complexes with the high symmetry of the molecule unit and strong intra-molecular dipolar interactions using strong anisotropy metal ions represents the most promising route toward the design of a toroidal moment. Furthermore, the linkage of such robust toroidal moment units with ferromagnetic type through appropriate bridging ligands enhances the toroidal magnetic moment per unit cell. PMID:24975197

Ungur, Liviu; Lin, Shuang-Yan; Tang, Jinkui; Chibotaru, Liviu F

2014-09-22

101

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

PubMed

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

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

2014-02-01

102

Can azulene-like molecules function as substitution-free molecular rectifiers?  

PubMed

The feasibility of employing azulene-like molecules as a new type of high performance substitution-free molecular rectifier has been explored using NEGF-DFT calculation. The electronic transport behaviors of metal-molecule-metal junctions consisting of various azulene-like dithiol molecules are investigated, which reveals that the azulene-like molecules exhibit high conductance and bias-dependent rectification effects. Among all the substitution-free azulene-like structures, cyclohepta[b]cyclopenta[g]naphthalene exhibits the highest rectification ratio, revealing that the all fused aromatic ring structure and an appropriate separation between the pentagon and heptagon rings are essential for achieving both high conductance and high rectification ratio. The rectification ratio can be increased by substituting the pentagon ring with electron-withdrawing group and/or the heptagon ring with electron donating groups. Further increase of the rectification ratio may also be obtained by lithium adsorption on the pentagon ring. This work reveals that azulene-like molecules may be used as a new class of highly conductive unimolecular rectifiers. PMID:21822508

Zhou, Kai-Ge; Zhang, Yong-Hui; Wang, Le-Jia; Xie, Ke-Feng; Xiong, Yu-Qing; Zhang, Hao-Li; Wang, Cheng-Wei

2011-09-21

103

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

NASA Astrophysics Data System (ADS)

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

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

2012-08-01

104

Molecular-crowding effects on single-molecule RNA folding/unfolding thermodynamics and kinetics.  

PubMed

The effects of "molecular crowding" on elementary biochemical processes due to high solute concentrations are poorly understood and yet clearly essential to the folding of nucleic acids and proteins into correct, native structures. The present work presents, to our knowledge, first results on the single-molecule kinetics of solute molecular crowding, specifically focusing on GAAA tetraloop-receptor folding to isolate a single RNA tertiary interaction using time-correlated single-photon counting and confocal single-molecule FRET microscopy. The impact of crowding by high-molecular-weight polyethylene glycol on the RNA folding thermodynamics is dramatic, with up to ??G° ? -2.5 kcal/mol changes in free energy and thus >60-fold increase in the folding equilibrium constant (Keq) for excluded volume fractions of 15%. Most importantly, time-correlated single-molecule methods permit crowding effects on the kinetics of RNA folding/unfolding to be explored for the first time (to our knowledge), which reveal that this large jump in Keq is dominated by a 35-fold increase in tetraloop-receptor folding rate, with only a modest decrease in the corresponding unfolding rate. This is further explored with temperature-dependent single-molecule RNA folding measurements, which identify that crowding effects are dominated by entropic rather than enthalpic contributions to the overall free energy change. Finally, a simple "hard-sphere" treatment of the solute excluded volume is invoked to model the observed kinetic trends, and which predict ??G° ? -5 kcal/mol free-energy stabilization at excluded volume fractions of 30%. PMID:24850865

Dupuis, Nicholas F; Holmstrom, Erik D; Nesbitt, David J

2014-06-10

105

Structural distributions from single-molecule measurements as a tool for molecular mechanics  

NASA Astrophysics Data System (ADS)

A mechanical view provides an attractive alternative for predicting the behavior of complex systems since it circumvents the resource-intensive requirements of atomistic models; however, it remains extremely challenging to characterize the mechanical responses of a system at the molecular level. Here, the structural distribution is proposed to be an effective means to extracting the molecular mechanical properties. End-to-end distance distributions for a series of short poly-L-proline peptides with the sequence PnCG3K-biotin (n = 8, 12, 15 and 24) were used to experimentally illustrate this new approach. High-resolution single-molecule Förster-type resonance energy transfer (FRET) experiments were carried out and the conformation-resolving power was characterized and discussed in the context of the conventional constant-time binning procedure for FRET data analysis. It was shown that the commonly adopted theoretical polymer models—including the worm-like chain, the freely jointed chain, and the self-avoiding chain—could not be distinguished by the averaged end-to-end distances, but could be ruled out using the molecular details gained by conformational distribution analysis because similar polymers of different sizes could respond to external forces differently. Specifically, by fitting the molecular conformational distribution to a semi-flexible polymer model, the effective persistence lengths for the series of short poly-L-proline peptides were found to be size-dependent with values of ˜190 Å, ˜67 Å, ˜51 Å, and ˜76 Å for n = 8, 12, 15, and 24, respectively. A comprehensive computational modeling was carried out to gain further insights for this surprising discovery. It was found that P8 exists as the extended all-trans isomaer whereas P12 and P15 predominantly contained one proline residue in the cis conformation. P24 exists as a mixture of one-cis (75%) and two-cis (25%) isomers where each isomer contributes to an experimentally resolvable conformational mode. This work demonstrates the resolving power of the distribution-based approach, and the capacity of integrating high-resolution single-molecule FRET experiments with molecular modeling to reveal detailed structural information about the conformation of molecules on the length scales relevant to the study of biological molecules.

Hanson, Jeffrey A.; Brokaw, Jason; Hayden, Carl C.; Chu, Jhih-Wei; Yang, Haw

2012-03-01

106

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

PubMed Central

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

2012-01-01

107

Molecular dynamics simulations of flexible liquid crystal molecules using a Gay-Berne/Lennard-Jones model  

NASA Astrophysics Data System (ADS)

Molecular dynamics simulations are described for liquid crystal molecules composed of two Gay-Berne particles connected by an eight-site Lennard-Jones alkyl chain. Calculations have been carried out for 512 molecules in the NVE and NPT ensembles for simulation times of up to 6.4 ns. The system exhibits the sequence of phases: isotropic liquid, smectic-A, smectic-B, and the simulations demonstrate the spontaneous growth of a smectic-A liquid crystal over a period of approximately 6 ns on cooling from the isotropic liquid. Model molecules are seen to remain flexible and able to change conformation in the smectic-A phase. As temperature is reduced molecules become elongated as the number of gauche conformations drops, leading to a small increase in the spacing of smectic layers. The latter is seen through the temperature dependence of the Gay-Berne radial distribution function resolved parallel to the direction of orientational order. Results are presented which show an odd-even variation of orientational order parameters for bonds in the alkyl chain, and a change in effective torsional potentials as the system is cooled from isotropic liquid to a smectic-A phase.

Wilson, Mark R.

1997-11-01

108

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

NASA Technical Reports Server (NTRS)

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

Srivastava, Deepak; Saini, Subhash (Technical Monitor)

1998-01-01

109

Molecular Dynamics Study of Small PNA Molecules in Lipid-Water System Pawe1 Weronski,*y  

E-print Network

Mexico ABSTRACT We present the results of molecular dynamics simulations of small peptide nucleic acid of several tens of kT per PNA molecule in both cases. INTRODUCTION Peptide nucleic acids (PNA) are lab salt, and in the NPngT ensemble, two similar PNA molecules (6-mers) with the same nucleic base sequence

Jiang, Yi

110

The quest for probiotic effector molecules--unraveling strain specificity at the molecular level.  

PubMed

Pharmaceutical agents are widely applied for the treatment of gastrointestinal (and systemic) disorders and their role as modulators of host cell responses is relatively well characterized. By contrast, we are only beginning to understand the molecular mechanisms by which health-promoting, probiotic bacteria act as host cell modulators. The last decade has seen a rapid development of the genomics field for the widely applied probiotic genus Lactobacillus, and nowadays dozens of full genome sequences are available, as well as sophisticated post genomic and genetic engineering tools. This development has enabled comparative (functional) genomics approaches to identify the bacterial effector molecules involved in molecular communication with the host system that may underlie the probiotic effects observed. These efforts can also be complemented with dedicated mutagenesis approaches to eliminate or alter these effector molecules, followed by assessment of the host interaction consequences thereof, allowing the elucidation of the molecular mechanisms involved in probiotic health effects. Many of these approaches have pinpointed that the Lactobacillus cell envelope contains several effector molecules that are pivotal in the direct signaling capacity of these bacteria that underlies their immunomodulatory effects, including lipoteichoic acid, peptidoglycan, and (glyco)proteins. Moreover, the cell envelope contains several compounds such as wall teichoic acid and capsular polysaccharides that may not be involved in direct signaling to the host cell, but still affect signaling through shielding of other bacterial effector molecules. Initial structural studies revealed subtle strain- and species-specific biochemical differences in the canonical cell envelope compounds that are involved in these host interactions. These biochemical variations include the degree and positioning of d-alanyl and glycosyl substitution in lipoteichoic acids, and acetylation of peptidoglycan. Furthermore, specific peptides derived from peptidoglycan and envelope associated (glyco)proteins were recently identified as potent immunomodulators. The latter findings are exciting in the light of the possibility of more pharmacological application of these bioactive probiotic molecules, and especially cost-effective production and targeted delivery of bioactive peptides seems to emerge as a feasible strategy to harness this knowledge. PMID:23059538

Lee, I-Chiao; Tomita, Satoru; Kleerebezem, Michiel; Bron, Peter A

2013-03-01

111

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

PubMed

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 ?m 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. PMID:21692179

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

2011-08-22

112

Molecular dynamics simulations of amphiphilic graft copolymer molecules at a water/air interface  

NASA Astrophysics Data System (ADS)

Fully atomistic molecular dynamics simulations of amphiphilic graft copolymer molecules have been performed at a range of surface concentrations at a water/air interface. These simulations are compared to experimental results from a corresponding system over a similar range of surface concentrations. Neutron reflectivity data calculated from the simulation trajectories agrees well with experimentally acquired profiles. In particular, excellent agreement in neutron reflectivity is found for lower surface concentration simulations. A simulation of a poly(ethylene oxide) (PEO) chain in aqueous solution has also been performed. This simulation allows the conformational behavior of the free PEO chain and those tethered to the interface in the previous simulations to be compared.

Anderson, Philip M.; Wilson, Mark R.

2004-11-01

113

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

PubMed

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. PMID:2793523

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

1989-06-01

114

Surface patterns on co-assembled fibers from charged, amphiphilic molecules  

NASA Astrophysics Data System (ADS)

We analyze local segregation of species in charged multicomponent cylindrical micelles. In particular, we consider co-assemblies of cationic and anionic heterogeneous molecules such as lipids and peptide amphiphiles. Charge heterogeneities can develop at the surface of the fibers due to the competition between the short-range incompatibility of the co-assembled components and the electrostatic interactions. The system can be described by a line tension between domains ?, which favors growth of the domains of segregated components, and the electrostatic energy of the domains with charge density ?, which increases rapidly with the size of the segregated domain L. The competition results in the formation of domains with a characteristic size Lo=(??/2circ)^1/2. In stoichiometric mixtures the constraints of the geometry and the long range correlations lead to lamellar stripes of different pitch. We present results on the different orientations of the lamellar patterns as a function of the ratio between the lamellar size and the cylinder radius. We find the critical salt concentration, which is a function of radius and lamellar size, at which the patterns grow to macroscopic sizes due to the screening of the Coulomb interactions.

Kohlstedt, Kevin; Solis, Francisco; Olvera de La Cruz, Monica

2006-03-01

115

Time reversible and symplectic integrators for molecular dynamics simulations of rigid molecules.  

PubMed

Molecular dynamics integrators are presented for translational and rotational motion of rigid molecules in microcanonical, canonical, and isothermal-isobaric ensembles. The integrators are all time reversible and are also, in some approaches, symplectic for the microcanonical ensembles. They are developed utilizing the quaternion representation on the basis of the Trotter factorization scheme using a Hamiltonian formalism. The structure is similar to that of the velocity Verlet algorithm. Comparison is made with standard integrators in terms of stability and it is found that a larger time step is stable with the new integrators. The canonical and isothermal-isobaric molecular dynamics simulations are defined by using a chain thermostat approach according to generalized Nosé-Hoover and Andersen methods. PMID:15974658

Kamberaj, H; Low, R J; Neal, M P

2005-06-01

116

Bicelles: A natural ‘molecular goniometer’ for structural, dynamical and topological studies of molecules in membranes  

PubMed Central

Major biological processes occur at the biological membrane. One of the great challenges is to understand the function of chemical or biological molecules inside the membrane; as well of those involved in membrane trafficking. This requires obtaining a complete picture of the in situ structure and dynamics as well as the topology and orientation of these molecules in the membrane lipid bilayer. These led to the creation of several innovative models of biological membranes in order to investigate the structure and dynamics of amphiphilic molecules, as well as integral membrane proteins having single or multiple transmembrane segments. Because the determination of the structure, dynamics and topology of molecules in membranes requires a macroscopic alignment of the system, a new membrane model called ‘bicelles’ that represents a crossover between lipid vesicles and classical micelles has become very popular due to its property of spontaneous self-orientation in magnetic fields. In addition, crucial factors involved in mimicking natural membranes, such as sample hydration, pH and salinity limits, are easy to control in bicelle systems. Bicelles are composed of mixtures of long chain (14–18 carbons) and short chain phospholipids (6–8 carbons) hydrated up to 98% with buffers and may adopt various morphologies depending on lipid composition, temperature and hydration. We have been developing bicelle systems under the form of nano-discs made of lipids with saturated or biphenyl-containing fatty acyl chains. Depending on the lipid nature, these membranous nano-discs may be macroscopically oriented with their normal perpendicular or parallel to the magnetic field, providing a natural ‘molecular goniometer’ for structural and topological studies, especially in the field of NMR. Bicelles can also be spun at the magic angle and lead to the 3D structural determination of molecules in membranes. PMID:19248817

Diller, Anna; Loudet, Cécile; Aussenac, Fabien; Raffard, Gérard; Fournier, Sylvie; Laguerre, Michel; Grélard, Axelle; Opella, Stanley J.; Marassi, Francesca M.; Dufourc, Erick J.

2010-01-01

117

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

NASA Astrophysics Data System (ADS)

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.

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

2014-09-01

118

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

NASA Astrophysics Data System (ADS)

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.

Granot, Ori; Amirav, Aviv

2005-06-01

119

Circular dichroism in molecular-frame photoelectron angular distributions in the dissociative photoionization of H2 and D2 molecules  

NASA Astrophysics Data System (ADS)

The presence of net circular dichroism in the photoionization of nonchiral homonuclear molecules has been put in evidence recently through the measurement of molecular-frame photoelectron angular distributions in dissociative photoionization of H2 [Dowek et al., Phys. Rev. Lett. 104, 233003 (2010), 10.1103/PhysRevLett.104.233003]. In this work we present a detailed study of circular dichroism in the photoelectron angular distributions of H2 and D2 molecules, oriented perpendicularly to the propagation vector of the circularly polarized light, at different photon energies (20, 27, and 32.5 eV). Circular dichroism in the angular distributions at 20 and to a large extent 27 eV exhibits the usual pattern in which inversion symmetry is preserved. In contrast, at 32.5 eV, the inversion symmetry breaks down, which eventually leads to total circular dichroism after integration over the polar emission angle. Time-dependent ab initio calculations support and explain the observed results for H2 in terms of quantum interferences between direct photoionization and delayed autoionization from the Q1 and Q2 doubly excited states into ionic states (1 s ?g and 2 p ?u ) of different inversion symmetry. Nevertheless, for D2 at 32.5 eV, there is a particular case where theory and experiment disagree in the magnitude of the symmetry breaking: when D+ ions are produced with an energy of around 5 eV. This reflects the subleties associated to such simple molecules when exposed to this fine scrutiny.

Pérez-Torres, J. F.; Sanz-Vicario, J. L.; Veyrinas, K.; Billaud, P.; Picard, Y. J.; Elkharrat, C.; Poullain, S. Marggi; Saquet, N.; Lebech, M.; Houver, J. C.; Martín, F.; Dowek, D.

2014-10-01

120

Elastic properties, Young's modulus determination and structural stability of the tropocollagen molecule: a computational study by steered molecular dynamics  

Microsoft Academic Search

The aim of this report is to investigate at microscopic level the elastic properties of a tropocollagen-like molecule submitted to linear traction along its longitudinal axis. For this purpose, we performed steered molecular dynamics (SMD) simulations for a wide range of spring constants in order to test the molecular response based on a two-spring model connected in series. An elastic

Alicia Claudia Lorenzo; Ernesto Raúl Caffarena

2005-01-01

121

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

PubMed Central

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

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

2014-01-01

122

Modulation by cytokines of HLA antigens, intercellular adhesion molecule 1 and high molecular weight melanoma associated antigen expression and of immune lysis of clones derived from the melanoma cell line MeM 50-10  

Microsoft Academic Search

Summary Clones were isolated from the cultured human melanoma cell line MeM 50-10, which metastasizes in nude mice with a pattern similar to that in patients with melanoma. Analysis with monoclonal antibodies detected heterogeneity among the clones in the expression of HLA class I antigens, HLA class II antigens, intercellular adhesion molecule 1 and high molecular weight melanoma associated antigen.

Michele Maio; Beena Gulwani; Sandra Tombesi; Soldano Ferrone

1989-01-01

123

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

NASA Astrophysics Data System (ADS)

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 [1] and to demonstrate unprecedented degrees of laser alignment and mixed-field orientation of these molecules [2]. 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 [3] 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 Berlin, and SLAC Menlo Park, CA, USA. The experiments were carried out using CAMP (designed and built by the MPG-ASG at CFEL) [4] at the LCLS (operated by Stanford University on behalf of the US DOE) [5]. [4pt] [1] Filsinger, Erlekam, von Helden, Küpper, Meijer, Phys. Rev. Lett. 100, 133003 (2008); Filsinger, Küpper, Meijer, Hansen, Maurer, Nielsen, Holmegaard, Stapelfeldt, Angew. Chem. Int. Ed. 48, 6900 (2009)[0pt] [2] Holmegaard, Nielsen, Nevo, Stapelfeldt, Filsinger, Küpper, Meijer, Phys. Rev. Lett. 102, 023001 (2009); Filsinger, Küpper, Meijer, Holmegaard, Nielsen, Nevo, Hansen, Stapelfeldt, J. Chem. Phys. 131, 064309, (2009); Nevo, Holmegaard, Nielsen, Hansen, Stapelfeldt, Filsinger, Meijer, Küpper, Phys. Chem. Chem. Phys. 11, 9912 (2009)[0pt] [3] Holmegaard, Hansen, Kalhøj, Kragh, Stapelfeldt, Filsinger, Küpper, Meijer, Dimitrovski, Abu-samha, Martiny, Madsen, Nature Phys. 6, 428 (2010)[0pt] [4] Strüder et al. Nucl Instrum Meth A 614, 483 (2010)[0pt] [5] Emma et al. Nat Photonics 4, 641 (2010)

Küpper, Jochen

2011-06-01

124

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

PubMed

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. PMID:20212333

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

2010-01-01

125

Molecular Motions of Small Molecules in Porous Silica Sol-Gel Glass.  

NASA Astrophysics Data System (ADS)

Monolithic samples of sol-gel glass of pore diameters varing form 10 to 100 A have been produced. The highly porous samples have been impregnated by different fluids and molecular motions of confined molecules have been studied using Raman spectroscopy. Some studies have been extended to silica sol-gel glass of modified surfaces. The prefferential adsorption and translational diffusion have been investigated in mixtures of pyridine with polar and non-polar solvents. It has been confirmed that pyridine can be preferentially adsorbed on silica, and it has been suggested that the process results in a bilayer structure of the interface. Rotational relaxation of carbon disulfide, chloroform, acetonitrile, and sulfur hexafluoride inside pores of diameter a couple of times larger than diameter of molecules has been studied. High temperature and pressure study have been employed for SF_6 measurements. The effect of pore diameters and different surface coverage on rotational diffusion has been discussed. It has been shown that surface interactions, in particular, hydrogen bonding between the imbedded molecules and silanols groups, were responsible for slowing down the rotational relaxations within small pores. The experimental results have been compared with EDJ and FPL theoretical models. Vibrational dephasing, intermolecular energy exchange and intramolecular energy coupling have been investigated in chloroform, acetonitrile, nitromethane, acetone, and methyl iodide. The vibrational modulation times were obtained from the Kubo theoretical function and used to analyze molecular interactions near the silica surface. The Fermi resonance effect has been studied in acetonitrile and the coupling constant has been obtained from the standard quantum mechanics analysis. The non-coincidence effect has been measured in acetone within pores of different surface structure under different concentrations. The Schweizer-Chandler dephasing model and energy exchange model have been tested for methyl iodide. It has been found that the Harris energy exchange model cannot explain the mechanism responsible for the band shapes of any of the modes of methyl iodide adsorbed on silica.

Nikiel, Leszek

1991-05-01

126

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

SciTech Connect

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.

Hasovic, E. [Faculty of Science, University of Sarajevo, Zmaja od Bosne 35, BA-71000 Sarajevo (Bosnia and Herzegowina); Max-Born-Institut, Max-Born-Strasse 2a, DE-12489 Berlin (Germany); Busuladzic, M. [Medical Faculty, University of Sarajevo, Cekalusa 90, BA-71000 Sarajevo (Bosnia and Herzegowina); Becker, W. [Max-Born-Institut, Max-Born-Strasse 2a, DE-12489 Berlin (Germany); Milosevic, D. B. [Faculty of Science, University of Sarajevo, Zmaja od Bosne 35, BA-71000 Sarajevo (Bosnia and Herzegowina); Max-Born-Institut, Max-Born-Strasse 2a, DE-12489 Berlin (Germany); Academy of Sciences and Arts of Bosnia and Herzegovina, Bistrik 7, BA-71000 Sarajevo (Bosnia and Herzegowina)

2011-12-15

127

Conserved water molecules in family 1 glycosidases: a DXMS and molecular dynamics study.  

PubMed

By taking advantage of the wealth of structural data available for family 1 glycoside hydrolases, a study of the conservation of internal water molecules found in this ubiquitous family of enzymes was undertaken. Strikingly, seven water molecules are observed in more than 90% of the known structures. To gain insight into their possible function, the water dynamics inside Thermus thermophilus ?-glycosidase was probed using deuterium exchange mass spectroscopy, allowing the pinpointing of peptide L117-A125, which exchanges most of its amide hydrogens quickly in spite of the fact that it is for the most part buried in the crystal structure. To help interpret this result, a molecular dynamics simulation was performed whose analysis suggests that two water channels are involved in the process. The longest one (?16 Å) extends between the protein surface and W120, whose side chain interacts with E164 (the acid-base residue involved in the catalytic mechanism), whereas the other channel allows for the exchange with the bulk of the highly conserved water molecules belonging to the hydration shell of D121, a deeply buried residue. Our simulation also shows that another chain of highly conserved water molecules, going from the protein surface to the bottom of the active site cleft close to the nucleophile residue involved in the catalytic mechanism, is able to exchange with the bulk on the nanosecond time scale. It is tempting to speculate that at least one of these three water channels could be involved in the function of family 1 glycoside hydrolases. PMID:23895259

Teze, David; Hendrickx, Johann; Dion, Michel; Tellier, Charles; Woods, Virgil L; Tran, Vinh; Sanejouand, Yves-Henri

2013-08-27

128

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

PubMed

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. PMID:24671142

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

2014-05-01

129

Molecular Dynamics Study of the Disruption of H-BONDS by Water Molecules and its Diffusion Behavior in Amorphous Cellulose  

NASA Astrophysics Data System (ADS)

Hydrolysis is an important component of the aging of cellulose, and it severely affects the insulating performance of cellulosic materials. The diffusion behavior of water molecules in amorphous cellulose and their destructive effect on the hydrogen bonding structure of cellulose were investigated by molecular dynamics. The change in the hydrogen bonding structure indicates that water molecules have a considerable effect on the hydrogen bonding structure within cellulose: both intermolecular and intramolecular hydrogen bonds decreased with an increase in ingressive water molecules. Moreover, the stabilities of the cellulose molecules were disrupted when the number of intermolecular hydrogen bonds declined to a certain degree. Both the free volumes of amorphous cells and water molecule-cellulose interaction affect the diffusion of water molecules. The latter, especially the hydrogen bonding interaction between water molecules and cellulose, plays a predominant role in the diffusion behavior of water molecules in the models of which the free volume rarely varies. The diffusion coefficient of water molecules has an excellent correlation with water molecule-cellulose interaction and the average hydrogen bonds between each water molecule and cellulose; however, this relationship was not apparent between the diffusion coefficient and free volume.

Liao, Ruijin; Zhu, Mengzhao; Zhou, Xin; Zhang, Fuzhou; Yan, Jiaming; Zhu, Wenbin; Gu, Chao

2012-06-01

130

Catalytic and Molecular Beacons for Amplified Detection of Metal Ions and Organic Molecules with High Sensitivity  

PubMed Central

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. Based on 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 Pb2+ with a high sensitivity (LOD=600 pM). Furthermore, 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. PMID:20481627

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

2010-01-01

131

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

SciTech Connect

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.

Chu, P.M.Y.

1991-10-01

132

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

PubMed Central

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

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

2009-01-01

133

The pattern recognition molecule deleted in malignant brain tumors 1 (DMBT1) and synthetic mimics inhibit liposomal nucleic acid delivery.  

PubMed

Liposomal nucleic acid delivery is a preferred option for therapeutic settings. The cellular pattern recognition molecule DMBT1, secreted at high levels in various diseases, and synthetic mimics efficiently inhibit liposomal nucleic acid delivery to human cells. These findings may have relevance for therapeutic nucleic acid delivery strategies. PMID:20830348

Hansen, Pernille Lund; Blaich, Stephanie; End, Caroline; Schmidt, Steffen; Moeller, Jesper B; Holmskov, Uffe; Mollenhauer, Jan

2011-01-01

134

Characteristics in Molecular Vibrational Frequency Patterns between Agonists and Antagonists of Histamine Receptors  

PubMed Central

To learn the differences between the structure-activity relationship and molecular vibration-activity relationship in the ligand-receptor interaction of the histamine receptor, 47 ligands of the histamine receptor were analyzed by structural similarity and molecular vibrational frequency patterns. The radial tree that was produced by clustering analysis of molecular vibrational frequency patterns shows its potential for the functional classification of histamine receptor ligands. PMID:23105941

2012-01-01

135

Testosterone Induces Molecular Changes in Dopamine Signaling Pathway Molecules in the Adolescent Male Rat Nigrostriatal Pathway  

PubMed Central

Adolescent males have an increased risk of developing schizophrenia, implicating testosterone in the precipitation of dopamine-related psychopathology. Evidence from adult rodent brain indicates that testosterone can modulate nigrostriatal dopamine. However, studies are required to understand the role testosterone plays in maturation of dopamine pathways during adolescence and to elucidate the molecular mechanism(s) by which testosterone exerts its effects. We hypothesized that molecular indices of dopamine neurotransmission [synthesis (tyrosine hydroxylase), breakdown (catechol-O-methyl transferase; monoamine oxygenase), transport [vesicular monoamine transporter (VMAT), dopamine transporter (DAT)] and receptors (DRD1-D5)] would be changed by testosterone or its metabolites, dihydrotestosterone and 17?-estradiol, in the nigrostriatal pathway of adolescent male rats. We found that testosterone and dihydrotestosterone increased DAT and VMAT mRNAs in the substantia nigra and that testosterone increased DAT protein at the region of the cell bodies, but not in target regions in the striatum. Dopamine receptor D2 mRNA was increased and D3 mRNA was decreased in substantia nigra and/or striatum by androgens. These data suggest that increased testosterone at adolescence may change dopamine responsivity of the nigrostriatal pathway by modulating, at a molecular level, the capacity of neurons to transport and respond to dopamine. Further, dopamine turnover was increased in the dorsal striatum following gonadectomy and this was prevented by testosterone replacement. Gene expression changes in the dopaminergic cell body region may serve to modulate both dendritic dopamine feedback inhibition and reuptake in the dopaminergic somatodendritic field as well as dopamine release and re-uptake dynamics at the presynaptic terminals in the striatum. These testosterone-induced changes of molecular indices of dopamine neurotransmission in males are primarily androgen receptor-driven events as estradiol had minimal effect. We conclude that nigrostriatal responsivity to dopamine may be modulated by testosterone acting via androgen receptors to alter gene expression of molecules involved in dopamine signaling during adolescence. PMID:24618531

Purves-Tyson, Tertia D.; Owens, Samantha J.; Double, Kay L.; Desai, Reena; Handelsman, David J.; Weickert, Cynthia Shannon

2014-01-01

136

Molecular glass photoresists containing photoacid generator functionality: a route to a single-molecule photoresist  

NASA Astrophysics Data System (ADS)

A single molecule photoresist composed of tris(4-(tert-butoxycarbonyloxy)-3,5-dimethylphenyl) sulfonium hexafluoroantimonate (TAS-tBoc) was successfully synthesized and characterized. The synthesized triarylsulfonium was found to perform comparably to a commercial triphenylsulfonium triflate photoacid generator (PAG) when used purely as a PAG in blended molecular glass resist. TAS-tBoc formed excellent amorphous films when spin-coated out of solution. When exposed to 248 nm UV radiation, TAS-tBoc showed a sensitivity of 4 mJ/cm2 and a contrast ratio between 6 and 15, depending on development conditions. Its etch rate under standard silicon dioxide etch conditions was 0.87 as standardized to that of tBoc-PHOST in the same RIE plasma conditions. The outgassing level of the resist under EUV exposure was determined to be 1.08 x 10 13 molecules/cm2, well below the maximum outgassing cutoff that is considered acceptable for EUV imaging. When imaged by e-beam, TAS-tBoc showed a relatively high dose-to-clear of 150 ?C/cm2 as compared to conventional chemically amplified photoresists. Lines down to 50 nm wide with aspect ratios of 2.5:1 were imaged using e-beam. These lines exhibited an LER of only 3.96 nm, significantly better than the typical LER for polymeric chemically amplified resist, even when imaged using e-beam, and also one of the lowest values reported for molecular glass materials in general.

Lawson, Richard A.; Lee, Cheng-Tsung; Whetsell, Robert; Yueh, Wang; Roberts, Jeanette; Tolbert, Laren; Henderson, Clifford L.

2007-03-01

137

Prediction of metabolic reactions based on atomic and molecular properties of small-molecule compounds  

PubMed Central

Motivation: Our knowledge of the metabolites in cells and their reactions is far from complete as revealed by metabolomic measurements that detect many more small molecules than are documented in metabolic databases. Here, we develop an approach for predicting the reactivity of small-molecule metabolites in enzyme-catalyzed reactions that combines expert knowledge, computational chemistry and machine learning. Results: We classified 4843 reactions documented in the KEGG database, from all six Enzyme Commission classes (EC 1–6), into 80 reaction classes, each of which is marked by a characteristic functional group transformation. Reaction centers and surrounding local structures in substrates and products of these reactions were represented using SMARTS. We found that each of the SMARTS-defined chemical substructures is widely distributed among metabolites, but only a fraction of the functional groups in these substructures are reactive. Using atomic properties of atoms in a putative reaction center and molecular properties as features, we trained support vector machine (SVM) classifiers to discriminate between functional groups that are reactive and non-reactive. Classifier accuracy was assessed by cross-validation analysis. A typical sensitivity [TP/(TP+FN)] or specificity [TN/(TN+FP)] is ?0.8. Our results suggest that metabolic reactivity of small-molecule compounds can be predicted with reasonable accuracy based on the presence of a potentially reactive functional group and the chemical features of its local environment. Availability: The classifiers presented here can be used to predict reactions via a web site (http://cellsignaling.lanl.gov/Reactivity/). The web site is freely available. Contact: fmu@lanl.gov Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21478194

Mu, Fangping; Unkefer, Clifford J.; Unkefer, Pat J.; Hlavacek, William S.

2011-01-01

138

A novel cadherin cell adhesion molecule: its expression patterns associated with implantation and organogenesis of mouse embryos  

PubMed Central

The Ca2+-dependent cell adhesion molecules, termed cadherins, were previously divided into two subclasses, E- and N-types, with different adhesive specificity. In this study, we identified a novel class of cadherin, termed P-cadherin, using a visceral endoderm cell line PSA5- E. This cadherin was a 118,000-D glycoprotein and distinct from E- and N-cadherins in immunological specificity and molecular mass. In accord with these findings, cells with P-cadherin did not cross-adhere with cells with E-cadherin. P-Cadherin first appeared in developing mouse embryos in the extraembryonic ectoderm and the visceral endoderm at the egg cylinder stage and later was expressed in various tissues. The placenta and the uterine decidua most abundantly expressed this cadherin. The expression of P-cadherin was transient in many tissues, and its permanent expression was limited to certain tissues such as the epidermis, the mesothelium, and the corneal endothelium. When the tissue distribution of P-cadherin was compared with that of E-cadherin, we found that: each cadherin displayed a unique spatio-temporal pattern of expression; P-cadherin was co-expressed with E-cadherin in local regions of various tissues; and onset or termination of expression of P- cadherin was closely associated with connection or segregation of cell layers, as found with other cadherins. These results suggested that differential expression of multiple classes of cadherins play a role in implantation and morphogenesis of embryos by providing cells with heterogenous adhesive specificity. PMID:3539943

1986-01-01

139

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

PubMed

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. PMID:23540644

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

140

Patterns of molecular genetic variation among African elephant populations  

Microsoft Academic Search

The highly threatened African elephants have recently been subdivided into two species, Loxodonta africana (savannah or bush elephant) and L. cyclotis (forest elephant) based on morphological and molecular studies. A molecular genetic assessment of 16 microsatellite loci across 20 populations (189 individuals) affirms species level genetic differentiation and provides robust genotypic assessment of species affiliation. Savannah elephant popula- tions show

Kenine E. Comstock; Nicholas Georgiadis; Jill Pecon-Slattery; Alfred L. Roca; Elaine A. Ostrander; Stephen J. O'Brien; Samuel K. Wasser

2002-01-01

141

Researchers use changes in the patterns of sugar molecules to detect cells before they develop into esophageal cancer:  

Cancer.gov

Scientists working at Britain's Medical Research Council, in collaboration with researchers from New York University, have identified changes in the patterns of sugar molecules that line pre-cancerous cells in the esophagus, a condition called Barrett’s dysplasia, making it much easier to detect and remove these cells before they develop into esophageal cancer. These findings, reported in the journal Nature Medicine, have important implications for patients and may help to monitor their condition and prevent the development of cancer.

142

Matrix and substrate effects on the sputtering of a 2 kDa molecule: Insights from molecular dynamics  

E-print Network

and substrate effects in organic sputtering, we report on molecular dynamics simulations of the desorption induced by 500 eV Ar projectiles bombarding samples composed of polystyrene (PS) oligomers embedded of the concerted upward motion of several metal atoms underneath the molecule. Finally, the comparison between a ma

143

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

NASA Astrophysics Data System (ADS)

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 of detection of analytes can be decreased down to sub-nanomolar by controlling the MIP layers thickness. Finally, it is shown that such an approach offers potentials and opportunities for miniaturization to fulfill workspace constraints inherent to space exploration. Indeed, electrode arrays grafted with MIPs are prepared for portable sensor devices design. This work undoubtedly highlights molecularly imprinting in tandem with electrochemical detection as a very promising approach for sensing organic matter in a fast, highly sensitive and specific way. MIP-based biomimetic materials and their applications of as recognition layers within sensors are increasingly considered and it is expected that MIP will become a generic sensing technology This work is funded by the French National Research Agency (ANR) References: [1] C. Ayela, F. Roquet, L. Valera, C. Granier, L. Nicu, M. Pugnière, M. Biosensors and Bioelectronics 22 (2007) 3113. [2] M.A. Sephton, M.R. Sims, R.W. Court, D. Luong, D.C. Cullen, Planetary and Space Science 86 (2013) 66. [3] S. Lepinay, K. Khémara, M.-C. Millot, B. Carbonnier, Chem. Pap. 66 (2012) 340. [4] Y. Fuchs, O. Soppera, K. Haupt, Anal. Chim. Acta, 717 (2012) 7. [5] C. Malitesta, E. Mazzotta, R. A. Picca, A. Poma, I. Chianella, S. A. Piletsky, Anal. Bioanal. Chem. 402 (2012) 1827

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

144

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

PubMed Central

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

Beh, Cyrus Weijie; Zhou, Weizhuang

2013-01-01

145

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

NASA Astrophysics Data System (ADS)

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

Wang, Guan M.; Sandberg, William C.

2007-04-01

146

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

PubMed

Flow fractionation of cells using physical fields to achieve lateral displacement finds wide applications, but its extension to surface molecule-specific separation requires labeling. Here we demonstrate affinity flow fractionation (AFF) where weak, short-range interactions with asymmetric molecular patterns laterally displace cells in a continuous, label-free process. We show that AFF can directly draw neutrophils out of a continuously flowing stream of blood with an unprecedented 400,000-fold depletion of red blood cells, with the sorted cells being highly viable, unactivated, and functionally intact. The lack of background erythrocytes enabled the use of AFF for direct enumeration of neutrophils by a downstream detector, which could distinguish the activation state of neutrophils in blood. The compatibility of AFF with capillary microfluidics and its ability to directly separate cells with high purity and minimal sample preparation will facilitate the design of simple and portable devices for point-of-care diagnostics and quick, cost-effective laboratory analysis. PMID:23900203

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

2013-01-01

147

Unravelling the molecular structure and packing of a planar molecule by combining nuclear magnetic resonance and scanning tunneling microscopy.  

PubMed

The determination of the molecular structure of a porphyrin is achieved by using nuclear magnetic resonance (NMR) and scanning tunneling microscopy (STM) techniques. Since macroscopic crystals cannot be obtained in this system, this combination of techniques is crucial to solve the molecular structure without the need for X-ray crystallography. For this purpose, previous knowledge of the flatness of the reagent molecules (a porphyrin and its functionalizing group, a naphthalimide) and the resulting molecular structure obtained by a force-field simulation are used. The exponents of the I-V curves obtained by scanning tunneling spectroscopy (STS) allow us to check whether the thickness of the film of molecules is greater than a monolayer, even when there is no direct access to the exposed surface of the metal substrate. Photoluminescence (PL), optical absorption, infrared (IR) reflectance and solubility tests are used to confirm the results obtained here with this NMR/STM/STS combination. PMID:24192713

Sáfar, Gustavo A M; Malachias, Angelo; Magalhães-Paniago, Rogério; Martins, Dayse C S; Idemori, Ynara M

2013-12-21

148

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

SciTech Connect

'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.'

Wasielewski, M.R.

1997-01-01

149

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

PubMed

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

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

2008-05-14

150

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

Microsoft Academic Search

A comprehensive review is presented of single-molecule junction conductance measurements across families of molecules measured while breaking a gold point contact in a solution of molecules with amine end groups. A theoretical framework unifies the picture for the amine–gold link bonding and the tunnel coupling through the junction using density functional theory based calculations. The reproducible electrical characteristics and utility

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

2008-01-01

151

Different molecular patterns in glioblastoma multiforme subtypes upon recurrence  

Microsoft Academic Search

One of the hallmarks of glioblastoma is its inherent tendency to recur. At this point patients with relapsed GBM show a survival\\u000a time of only few months. The molecular basis of the recurrence process in GBM is still poorly understood. The aim of the present\\u000a study was to investigate the genetic profile of relapsed GBM compared to their respective primary

Ramon Martinez; Veit Rohde; Gabriele Schackert

2010-01-01

152

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

NASA Astrophysics Data System (ADS)

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.

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

2010-10-01

153

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

NASA Astrophysics Data System (ADS)

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 emphasized in the next three years, including experimentation with other discharge sources and the use of an electrical discharge in combination with laser ablation to increase the production of metal-bearing species. A mass spectrometer may allow in situ optimization and monitoring of ion abundances. Another important objective of the proposed work are studies of abundant interstellar or circumstellar species, motivated by recent spectral line surveys in sources such as IRC+10216 and VY CMa that indicate the presence of many new unidentified lines. Interferometric observations suggest that a substantial fraction of these lines originate in the inner circumstellar envelope and have high excitation temperatures. Measurements of the rotational spectra of several metal oxides such as ScO, ZrO, and YO are needed now that TiO and TiO2 have been found, as are rotational satellite transitions from vibrationally excited states of species like SiCC. The research proposed here should have an impact on a number of areas of astronomical research. Our broad laboratory program is well aligned with NASA's overall mission because we seek to understand the role of the chemical bond on a cosmic scale and to provide a firm chemical foundation by which more complicated questions of biological origins can be addressed. The work here also provides much basic information to aid subsequent astronomical searches, particularly in the infrared. Finally, our research program is an excellent vehicle for integrating research and education. It provides exposure to quite diverse areas of science in a setting which encourages student initiative and independent investigation.

McCarthy, Michael

154

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

SciTech Connect

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.

Champion, C.; Dal Cappello, C. [Universite Paul Verlaine-Metz, Laboratoire de Physique Moleculaire et des Collisions, ICPMB (FR CNRS 2843), Institut de Physique, 57078 Metz, Cedex 3 (France); Oubaziz, D.; Aouchiche, H. [Universite M. Mammeri, Laboratoire de Mecanique, Structure et Energetique, Tizi-Ouzou 15000 (Algeria); Popov, Yu. V. [Nuclear Physics Institute, Moscow State University, Moscow 119991 (Russian Federation)

2010-03-15

155

Molecular dynamics simulation of complex molecules at interfaces: dendritic surfactants in clay and amyloid peptides near lipid bilayers  

E-print Network

at interface play an important role in the nano-scale science characterizing the macroscopic behaviors. We, therefore, have been seeking to apply the powerful molecular simulation tools to study complex molecules at interfaces and selected two applications...-clay nanocomposites over traditional polymers such as greater mechanical strength and higher heat resistance have led to research interest for a variety of applications (Carrado, 2000; Jacob et al., 2003; Kojima et al., 1993; Krishnamoorti et al., 1996; Manias et...

Han, Kunwoo

2009-06-02

156

A molecular dynamics study of the swelling patterns of Na/Cs-montmorillonites and the hydration of interlayer cations  

NASA Astrophysics Data System (ADS)

We report on a molecular dynamics study of the swelling patterns of an Na-rich/Cs-poor montomorillonite and a Cs-montomorillonite. The recently developed CLAYFF force field is used to predict the basal spacing as a function of the water content in the interlayer. The simulations reproduce the swelling patterns of the Na and Cs-montomorillonite, suggesting a mechanism of its hydration different from that of the montomorillonite. In addition, we find that the differences in size and hydration energy of Na and Cs ions have strong implications for the structure and the internal energy of interlayer water. In particular, our results indicate that the hydrate difference in the presence of coexistent Na and Cs has a larger influence on the behavior of a clay—water system. For Na-rich/Cs-poor montomorillonite, the hydration energy values of Na ions and water molecules each have a dramatic increase compared with those in Na-montomorillonite on the interlayer spacing, and the hydration energy values of Cs ions and water molecules decrease somewhat compared with those in Cs-montomorillonite.

Liu, Tao; Chen, Yu-Qing

2013-02-01

157

Pattern recognition analysis in complex molecule synthesis and the preparation of iso-Diels-Alder motifs  

PubMed Central

The identification of synthesizable substructural domains within more complex structural targets is of significant value in designing a workable plan of synthesis. We term this process “pattern recognition analysis” (PRA). In this paper we continued to build on the theme of PRA as a potential resource in retrosynthetic blueprints to reach highly challenging targets. The paper operates at two levels. First, there is provided a clear sense of definitions of categories by which patterns are related to hypothetical reaction types. Although the required reaction type may for the moment not exist, we believe that this method of analysis is likely to promote innovation that identifies unmet needs and opportunities to advance the cause of complex target synthesis. In addition, we describe reductions to practice in expanding the menu of achievable patterns. It is likely that the future value of PRA will be associated with its utility in leading the way to new and exploitable chemical innovation. PMID:23784777

Peng, Feng; Grote, Robin E.; Wilson, Rebecca M.; Danishefsky, Samuel J.

2013-01-01

158

Dynamical coupling and negative differential resistance from interactions across the molecule-electrode interface in molecular junctions  

NASA Astrophysics Data System (ADS)

Negative differential resistance - a decrease in current with increasing bias voltage - is a counter-intuitive effect that is observed in various molecular junctions. Here, we present a novel mechanism that may be responsible for such an effect, based on strong Coulomb interaction between electrons in the molecule and electrons on the atoms closest to the molecule. The Coulomb interaction induces electron-hole binding across the molecule-electrode interface, resulting in a renormalized and enhanced molecule-electrode coupling. Using a self-consistent non-equilibrium Green's function approach, we show that the effective coupling is non-monotonic in bias voltage, leading to negative differential resistance. The model is in accord with recent experimental observations that showed a correlation between the negative differential resistance and the coupling strength. We provide detailed suggestions for experimental tests which may help to shed light on the origin of the negative differential resistance. Finally, we demonstrate that the interface Coulomb interaction affects not only the I-V curves but also the thermoelectric properties of molecular junctions.

Dubi, Yonatan

2013-10-01

159

Layer-by-layer self-assembly and disassembly of single charged inorganic small molecules: towards surface patterning.  

PubMed

The patterning of layer-by-layer (LbL) polyelectrolyte multilayers with metal ions is important for the facile fabrication of circuits or selective catalysis. The strategy includes two issues: the incorporation of metal ions and their controlled assembly-disassembly, which require a good understanding of the assembly mechanism. Therefore, we explored the LbL assembly between a polycation, poly-(diallyldimethylammonium chloride) (PDDA) and an inorganic single charged molecule, [AuCl4](-), which could assemble at pH = 3.7 and disassemble at lower pH values. Moreover, we have demonstrated that the driving force in the assembly is a ligand-to-metal charge transfer interaction. Combining the controlled assembly-disassembly of PDDA-[AuCl4](-) multilayers and photolithography, we obtained a surface pattern of PDDA-[AuCl4](-) multilayers. PMID:23925457

Cheng, Mengjiao; Jiang, Chao; Ding, Zhiyi; Zhang, Yajun; Fu, Yu; Shi, Feng

2013-09-28

160

The molecular Zeeman effect in diamagnetic molecules and the determination of molecular magnetic moments (g values), magnetic susceptibilities, and molecular quadrupole moments  

Microsoft Academic Search

The experimental and theoretical literature on the molecular Zeeman effect is surveyed. The observation of the linear (H) and quadratic (H ) Zeeman effect leads to a direct determination of the molecular g values, magnetic susceptibility anisotropies and molecular quadrupole moments. The recent results are discussed and the available molecular g values, magnetic susceptibility anisotropies, and molecular quadrupole moments are

W. H. Flygare; R. C. Benson

1971-01-01

161

APS/123-QED Field-free molecular alignment of asymmetric top molecules using elliptically  

E-print Network

], or Coulomb explosion. Aligning or orient- ing molecules is interesting for study of stereodynamic effects of a reaction can be enhanced by manipulating the relative orientation of reagents. One reaction channel can polarized lasers have been used to align the strongest polarizability axis of asymmetric top molecules right

Paris-Sud XI, Université de

162

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

Microsoft Academic Search

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

Paul K. Hansma

2000-01-01

163

The role of pathogen-associated molecular patterns in inflammatory responses against alginate based microcapsules.  

PubMed

Alginate-based microcapsules are used for immunoisolation of cells to release therapeutics on a minute-to-minute basis. Unfortunately, alginate-based microcapsules are suffering from varying degrees of success, which is usually attributed to differences in tissue responses. This results in failure of the therapeutic cells. In the present study we show that commercial, crude alginates may contain pathogen-associated molecular patterns (PAMPs), which are recognized by the sensors of the innate immune system. Known sensors are Toll-like receptors (TLRs), NOD receptors, and C-type lectins. By using cell-lines with a non-functional adaptor molecule essential in Toll-like receptor signaling, i.e. MyD88, we were able to show that alginates signal mainly via MyD88. This was found for low-G, intermediate-G, and high-G alginates applied in calcium-beads, barium-beads as well as in alginate-PLL-alginate capsules. These alginates did stimulate TLRs 2, 5, 8, and 9 but not TLR4 (LPS receptor). Upon implantation in rats these alginates provoked a strong inflammatory response resulting in fibrosis of the capsules. Analysis demonstrated that commercial alginates contain the PAMPs peptidoglycan, lipoteichoic acid, and flagellin. By applying purification procedures, these PAMPs were largely removed. This was associated with deletion of the inflammatory tissue responses as confirmed by an implantation experiment in rats. Our data also show that alginate itself does not provoke TLR mediated responses. We were able to unravel the sensor mechanism by which contaminants in alginates may provoke inflammatory responses. PMID:24051034

Paredes-Juarez, Genaro A; de Haan, Bart J; Faas, Marijke M; de Vos, Paul

2013-12-28

164

Genetic basis of dental agenesis - molecular genetics patterning clinical dentistry  

PubMed Central

Tooth agenesis is one of the most common congenital malformations in humans. Hypodontia can either occur as an isolated condition (non-syndromic hypodontia) or can be associated with a syndrome (syndromic hypodontia), highlighting the heterogeneity of the condition. Though much progress has been made to identify the developmental basis of tooth formation, knowledge of the etiological basis of inherited tooth loss is still lacking. To date, the mutation spectra of non-syndromic form of familial and sporadic tooth agenesis in humans have revealed defects in various such genes that encode transcription factors, MSX1 and PAX9 or genes that code for a protein involved in canonical Wnt signaling (AXIN2), and a transmembrane receptor of fibroblast growth factors (FGFR1). The aim of this paper is to review the current literature on the molecular mechanisms responsible for selective hypodontia in humans and to present a detailed overview of causative genes and syndromes associated with hypodontia. Key words:Tooth agenesis, hypodontia, growth factors, mutations. PMID:24121910

Goswami, Mridula; Chhabra, Anuj

2014-01-01

165

Imaging Molecular Structure through Femtosecond Photoelectron Diffraction on Aligned and Oriented Gas-Phase Molecules  

E-print Network

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 (C8H5F) and dissociating, laseraligned 1,4-dibromobenzene (C6H4Br2) 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.

Boll, R; Adolph, M; Anielski, D; Aquila, A; Bari, S; Bomme, C; Bostedt, C; Bozek, J D; Chapman, H N; Christensen, L; Coffee, R; Coppola, N; De, S; Decleva, P; Epp, S W; Erk, B; Filsinger, F; Foucar, L; Gorkhover, T; Gumprecht, L; Hoemke, A; Holmegaard, L; Johnsson, P; Kienitz, J S; Kierspel, T; Krasniqi, F; Kuehnel, K -U; Maurer, J; Messerschmidt, M; Moshammer, R; Mueller, Nele L M; Rudek, B; Savelyev, E; Schlichting, I; Schmidt, C; Scholz, F; Schorb, S; Schulz, J; Seltmann, J; Stener, M; Stern, S; Techert, S; Thogersen, J; Trippel, S; Viefhaus, J; Vrakking, M; Stapelfeldt, H; Kuepper, J; Ullrich, J; Rudenko, A; Rolles, D

2014-01-01

166

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

NASA Technical Reports Server (NTRS)

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.

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

2011-01-01

167

Bench-to-bedside review: Damage-associated molecular patterns in the onset of ventilator-induced lung injury  

PubMed Central

Mechanical ventilation (MV) has the potential to worsen pre-existing lung injury or even to initiate lung injury. Moreover, it is thought that injurious MV contributes to the overwhelming inflammatory response seen in patients with acute lung injury or acute respiratory distress syndrome. Ventilator-induced lung injury (VILI) is characterized by increased endothelial and epithelial permeability and pulmonary inflammation, in which the innate immune system plays a key role. A growing body of evidence indicates that endogenous danger molecules, also termed damage-associated molecular patterns (DAMPs), are released upon tissue injury and modulate the inflammatory response. DAMPs activate pattern recognition receptors, may induce the release of proinflammatory cytokines and chemokines, and have been shown to initiate or propagate inflammation in non-infectious conditions. Experimental and clinical studies demonstrate the presence of DAMPs in bronchoalveolar lavage fluid in patients with VILI and the upregulation of pattern recognition receptors in lung tissue by MV. The objective of the present article is to review research in the area of DAMPs, their recognition by the innate immune system, their role in VILI, and the potential utility of blocking DAMP signaling pathways to reduce VILI in the critically ill. PMID:22216838

2011-01-01

168

Tauopathy differentially affects cell adhesion molecules in mouse brain: early down-regulation of nectin-3 in stratum lacunosum moleculare.  

PubMed

Cell adhesion molecules are important structural substrates, required for synaptic plasticity and synaptogenesis. CAMs differ widely in their expression throughout different brain regions and their specific structural and functional roles in the brain remain to be elucidated. Here, we investigated selected cell adhesion molecules for alterations in expression levels and neuronal localization in validated mouse models for Alzheimer's disease that mimic the age-related progression of amyloid accumulation and tauopathy. Among the cell adhesion molecules analyzed, Nectin-3 expression was affected most and specifically in all mouse models with tauopathy. In particular was Nectin-3 depleted from the specific region of the hippocampus, known as the stratum lacunosum and moleculare, in mice that express wild-type or mutant human protein Tau, either chronically or sub-acutely. Tauopathy progresses from the entorhinal cortex to the hippocampus by unknown mechanisms that could involve transport by the myelinated axons of the temporoammonic and perforant pathways. The decreased expression of Nectin-3 in the stratum lacunosum moleculare is an early marker of impaired transport, and eventual synaptic problems, caused by beginning tauopathy. PMID:23704923

Maurin, Hervé; Seymour, Claire Marie; Lechat, Benoit; Borghgraef, Peter; Devijver, Herman; Jaworski, Tomasz; Schmidt, Mathias V; Kuegler, Sebastian; Van Leuven, Fred

2013-01-01

169

Growth patterns and interfacial kinetic supercooling at ice/water interfaces at which anti-freeze glycoprotein molecules are adsorbed  

NASA Astrophysics Data System (ADS)

Ice crystal growth in a supercooled solution containing proteins such as anti-freeze glycoproteins (AFGPs) is inhibited by its adsorption at the ice/water interface. Although these proteins have dramatic consequences for natural biological processes and technological applications, little is known about the dynamic mechanism of ice growth inhibition. One-directional growth experiments were carried out to observe the pattern formation at the ice/water interface growing from an aqueous AFGP solution. Typical zigzag patterns composed of flat prismatic {1 0 1¯ 0} interfaces were observed in the final quasi-stable growth state. By analyzing the zigzag patterns, we were able to directly determine the interfacial kinetic supercooling, ?T, at the interfaces of prismatic faces as a function of growth rate. ?T linearly increased with increasing growth rate in the range below a critical growth rate, but its dependence showed the reversed relationship above the critical growth rate. This growth rate dependency of ?T was qualitatively explained by the interaction between the rejection and incorporation rates of AFGP molecules at the growing interface.

Furukawa, Yoshinori; Inohara, Naomi; Yokoyama, Etsuro

2005-02-01

170

Calculating Structures and Free Energies of Complex Molecules:  Combining Molecular Mechanics and Continuum Models  

Microsoft Academic Search

A historical perspective on the application of molecular dynamics (MD) to biological macromolecules is presented. Recent develop- ments combining state-of-the-art force fields with continuum solvation calculations have allowed us to reach the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynam- ics trajectories. We illustrate such applications

Peter A. Kollman; Irina Massova; Carolina Reyes; Bernd Kuhn; Shuanghong Huo; Lillian Chong; Matthew Lee; Taisung Lee; Yong Duan; Wei Wang; Oreola Donini; Piotr Cieplak; Jaysharee Srinivasan; David A. Case; Thomas E. Cheatham

2000-01-01

171

Red Fluorescent Line Emission from Hydrogen Molecules in Diffuse Molecular Clouds  

Microsoft Academic Search

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

David A. Neufeld; Marco Spaans

1996-01-01

172

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

PubMed Central

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

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

2014-01-01

173

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

PubMed Central

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

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

2012-01-01

174

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

EPA Science Inventory

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

175

Patterns of molecular evolution and diversification in a biodiversity hotspot: the California Floristic Province  

Microsoft Academic Search

The California Floristic Province harbours more endemic plant and animal taxa and more identifiable subspecies than any other area of comparable size in North America. We present evidence that physical historical processes have resulted in congruent patterns of genetic diversity over the past 2—10 million years. Using a molecular clock approach we show that diversification and establishment of spatial genetic

Ryan Calsbeek; John N. Thompson; James E. Richardson

2003-01-01

176

Biogeographic patterns and current distribution of molecular-genetic variation among populations of speckled dace,  

E-print Network

Biogeographic patterns and current distribution of molecular-genetic variation among populations. Keywords: Biogeography; Cyprinids; Genetic diversity; mtDNA; Population genetics; Population subdivision divergent mtDNA lineages were found to co-occur in populations in the Klamath Basin. This result may

Pfrender, Michael

177

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

NASA Astrophysics Data System (ADS)

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

Debolt, Stephen Edward

178

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

PubMed

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

Ishizuka, Ryosuke; Yoshida, Norio

2013-08-28

179

Ab initio and semi-empirical Molecular Dynamics simulations of chemical reactions in isolated molecules and in clusters.  

PubMed

Recent progress in "on-the-fly" trajectory simulations of molecular reactions, using different electronic structure methods is discussed, with analysis of the insights that such calculations can provide and of the strengths and limitations of the algorithms available. New developments in the use of both ab initio and semi-empirical electronic structure algorithms are described. The emphasis is on: (i) calculations of electronic properties along the reactive trajectories and the unique insights this can contribute to the processes; (ii) electronic structure methods recently introduced to this topic to improve accuracy, extend applicability or enhance computational efficiency. The methods are presented with examples, including new results, of reactions of both isolated molecules and of molecules in media, mostly clusters. Possible future directions for this fast growing field are suggested. PMID:24569494

Gerber, R B; Shemesh, D; Varner, M E; Kalinowski, J; Hirshberg, B

2014-06-01

180

Strigolactone analogs as molecular probes in chasing the (SLs) receptor/s: design and synthesis of fluorescent labeled molecules.  

PubMed

Originally identified as allelochemicals involved in plant-parasite interactions, more recently, Strigolactones (SLs) have been shown to play multiple key roles in the rhizosphere communication between plants and mycorrhizal fungi. Even more recent is the hormonal role ascribed to SLs which broadens the biological impact of these relatively simple molecules. In spite of the crucial and multifaceted biological role of SLs, there are no data on the receptor(s) which bind(s) such active molecules, neither in the producing plants nor in parasitic weeds or AM fungi. Information about the putative receptor of SLs can be gathered by means of structural, molecular, and genetic approaches. Our contribution on this topic is the design and synthesis of fluorescent labeled SL analogs to be used as probes for the detection in vivo of the receptor(s). Knowledge of the putative receptor structure will boost the research on analogs of the natural substrates as required for agricultural applications. PMID:23180673

Prandi, Cristina; Rosso, Helèna; Lace, Beatrice; Occhiato, Ernesto G; Oppedisano, Alberto; Tabasso, Silvia; Alberto, Gabriele; Blangetti, Marco

2013-01-01

181

Modeling Molecules  

NASA Technical Reports Server (NTRS)

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.

2000-01-01

182

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

PubMed

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

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

2014-03-18

183

Peripheral Neural Detection of Danger-Associated and Pathogen-Associated Molecular Patterns  

PubMed Central

Objective: Bidirectional links between the nervous and immune systems modulate inflammation. The cellular mechanisms underlying the detection of danger-associated molecular patterns and pathogen-associated molecular patterns by the nervous system are not well understood. We hypothesized that the carotid body, a tissue of neural crest origin, detect pathogen associated molecular patterns and danger associated molecular patterns via an inflammasome-dependent mechanism similar to that described in immune cells. Design: Randomized, controlled laboratory investigation. Setting: University laboratory. Subjects: C57Bl/6J mice; juvenile Sprague-Dawley rats, primary human neutrophils. Interventions: Rat carotid body chemosensitive cells, and human neutrophils, were treated with TLR agonists to activate inflammasome-dependent pathways. In mice, systemic inflammation was induced by the pathogen associated molecular pattern zymosan (intraperitoneal injection; 500 mg/kg). Isolated carotid body/carotid sinus nerve preparations were used to assess peripheral chemoafferent activity. Ventilation was measured by whole-body plethysmography. Measurements and Main Results: Chemosensitive carotid body glomus cells exhibited toll-like receptor (TLR-2 and TLR-4), NLRP1, and NLRP3 inflammasome immunoreactivities. Zymosan increased NLRP3 inflammasome and interleukin-1? expression in glomus cells (p < 0.01). Human neutrophils demonstrated similar LPS-induced changes in inflammasome expression. Carotid body glomus cells also expressed IL-1 receptor and responded to application of IL-1? with increases in intracellular [Ca2+]. Four hours after injection of zymosan carotid sinus nerve chemoafferent discharge assessed in vitro (i.e., in the absence of acidosis/circulating inflammatory mediators) was increased five-fold (p < 0.001). Accordingly, zymosan-induced systemic inflammation was accompanied by enhanced respiratory activity. Conclusions: In carotid body chemosensitive glomus cells, activation of toll-like receptors increases NLRP3 inflammasome expression, and enhances IL-1? production, which is capable of acting in an autocrine manner to enhance peripheral chemoreceptor drive. PMID:23507714

Kazymov, Vitaly; Marina, Nephtali; Singer, Mervyn; Gourine, Alexander V.

2013-01-01

184

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

PubMed

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

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

2014-08-29

185

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

NASA Astrophysics Data System (ADS)

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.

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

2014-08-01

186

Signaling Molecules in Membrane Lipid Rafts and Caveolae 181 From: Methods in Molecular Biology, vol. 332: Transmembrane Signaling Protocols, Second Edition  

E-print Network

to contain PM lipid rafts (7), only cells expressing caveolins express caveolae (for example, leukocytesSignaling Molecules in Membrane Lipid Rafts and Caveolae 181 181 From: Methods in Molecular Biology Press Inc., Totowa, NJ 10 Methods for the Study of Signaling Molecules in Membrane Lipid Rafts

Ostrom, Rennolds

187

Templating effects in molecular growth of blended films for efficient small-molecule photovoltaics.  

PubMed

A strategy to control the molecular growth of coevaporated zinc phthalocyanine (ZnPc) and fullerene (C60) blended films for efficient organic photovoltaic (OPV) cells was demonstrated. Introduction of a 2,5-bis(4-biphenylyl)-bithiophene (BP2T) film or a ZnPc film on BP2T as nanostructured templates not only results in phase-separated domains in blended films with clear interpenetrating networks but also improves the crystallinity of ZnPc domains, both of which enhance photocurrent generation and charge carrier transport. Such morphology is strongly associated with the molecular growth of the templating layers. Roughness and adhesion of the templating layers are of great importance for the molecular growth of the blended films and in turn for cell characteristics. By carefully regulating the molecular growth of the blended films, the power conversion efficiency was improved by 125%, from 1.85 to 4.15% under 1 sun. PMID:24712371

Wang, Zhiping; Miyadera, Tetsuhiko; Yamanari, Toshihiro; Yoshida, Yuji

2014-05-14

188

Tonal Interface to MacroMolecules (TIMMol): A Textual and Tonal Tool for Molecular Visualization  

ERIC Educational Resources Information Center

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…

Cordes, Timothy J.; Carlson, C. Britt; Forest, Katrina T.

2008-01-01

189

Molecular insights into the self-aggregation of aromatic molecules in the synthesis of nanoporous aluminophosphates: a multilevel approach.  

PubMed

Fluorescence spectroscopy and a range of computer simulation techniques are used to study the structure directing effect of benzylpyrrolidine (BP) and (S)-(-)-N-benzylpyrrolidine-2-methanol (BPM) in the synthesis of nanoporous aluminophosphate frameworks with AFI (one-dimensional channels) and SAO (three-dimensional interconnected channels) topologies. We study the supramolecular chemistry of BP and BPM molecules in aqueous solution and compare it with the aggregation state of the molecules found when they are inside the AlPO nanopores after crystallization. The aggregation of the molecules within the structures can be explained by a combination of thermodynamic and kinetic effects. The former are given by the stability of the molecular species interacting with the oxide networks relative to their stability in solution; the latter depend on the aggregation behavior of the molecules in the synthesis gels prior to crystallization. Whereas BPM only forms one type of aggregate in solution, which has the appropriate conformation to match the empty channels of the forming nanoporous frameworks, BP forms aggregates with different molecular orientations, of which only one matches the framework interstices. This different supramolecular chemistry, together with the higher interaction of BPM with the oxide networks, makes BPM a better structure directing agent (SDA); it is also responsible for the higher incorporation of BPM as dimers in the frameworks, especially in the AFI structure, observed experimentally. The concentration of the SDA molecules in the gels, and so the density per volume of the SDAs, determines the exclusion zone from which the pores and/or cavities of the framework will arise, and so the porous network of the formed material. A clear relationship between the SDA density in solution and in the framework is observed, thus enabling an eventual control of the material density by adjusting the SDA concentration in the gels. The topological instability intrinsic to these open framework structures is compensated by a high host-guest interaction energy; the SAO topology is further stabilized by doping with Zn. Our computational results account for and rationalize all the effects observed experimentally, providing a complete picture of the mode of structure direction of these aromatic molecules in the synthesis of nanoporous aluminophosphates. PMID:19852487

Gómez-Hortigüela, Luis; Hamad, Said; López-Arbeloa, Fernando; Pinar, Ana B; Pérez-Pariente, Joaquín; Corà, Furio

2009-11-18

190

Water-inducing molecular self-assembly of amphiphilic molecules into nanofibers  

SciTech Connect

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.

Zhang, Weiguang [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, Huaiyin Normal University, Huaian, Jiangsu 223300 (China)] [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, Huaiyin Normal University, Huaian, Jiangsu 223300 (China); Zhao, Pusu, E-mail: zhaopusu@qust.edu.cn [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, Huaiyin Normal University, Huaian, Jiangsu 223300 (China)] [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, Huaiyin Normal University, Huaian, Jiangsu 223300 (China); Song, Jie, E-mail: songjiesj@163.com [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, Huaiyin Normal University, Huaian, Jiangsu 223300 (China) [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, Huaiyin Normal University, Huaian, Jiangsu 223300 (China); Materials Chemistry Laboratory, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094 (China)

2011-12-15

191

The nociceptin receptor (NOPR) and its interaction with clinically important agonist molecules: a membrane molecular dynamics simulation study.  

PubMed

The nociceptin receptor (NOPR) is an orphan G protein-coupled receptor that contains seven transmembrane helices. NOPR has a distinct mechanism of activation, though it shares a significant homology with other opioid receptors. Previously there have been reports on homology modeling of NOPR and also molecular dynamics simulation studies for a short period. Recently the crystal structure of NOPR was reported. In this study, we analyzed the time dependent behavior of NOPR docked with clinically important agonist molecules such as NOP (natural agonist) peptide and compound 10 (SCH-221510 derivative) using molecular dynamics simulations (MDS) for 100 ns. Molecular dynamics simulations of NOPR-agonist complexes allowed us to refine the system and to also identify stable structures with better binding modes. Structure activity relationships (SAR) for SCH221510 derivatives were investigated and reasons for the activities of these derivatives were determined. Our molecular dynamics trajectory analysis of NOPR-peptide and NOPR-compound 10 complexes found residues to be crucial for binding. Mutagenesis studies on the residues identified from our analysis could prove useful. Our results could also provide useful information in the structure-based drug design of novel and potent agonists targeting NOPR. PMID:25259728

Kothandan, Gugan; Gadhe, Changdev G; Balupuri, Anand; Ganapathy, Jagadeesan; Cho, Seung Joo

2014-12-28

192

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

PubMed

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

Chowdhury, Debashish

2013-06-01

193

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

PubMed

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. PMID:16990998

Guo, Xiaojian; Zhou, Xueping

2006-12-01

194

Ultrafine Membrane Compartments for Molecular Diffusion as Revealed by Single Molecule Techniques  

PubMed Central

Plasma membrane compartments, delimited by transmembrane proteins anchored to the membrane skeleton (anchored-protein picket model), would provide the membrane with fundamental mosaicism because they would affect the movement of practically all molecules incorporated in the cell membrane. Understanding such basic compartmentalized structures of the cell membrane is critical for further studies of a variety of membrane functions. Here, using both high temporal-resolution single particle tracking and single fluorescent molecule video imaging of an unsaturated phospholipid, DOPE, we found that plasma membrane compartments generally exist in various cell types, including CHO, HEPA-OVA, PtK2, FRSK, HEK293, HeLa, T24 (ECV304), and NRK cells. The compartment size varies from 30 to 230 nm, whereas the average hop rate of DOPE crossing the boundaries between two adjacent compartments ranges between 1 and 17 ms. The probability of passing a compartment barrier when DOPE is already at the boundary is also cell-type dependent, with an overall variation by a factor of ?7. These results strongly indicate the necessity for the paradigm shift of the concept on the plasma membrane: from the two-dimensional fluid continuum model to the compartmentalized membrane model in which its constituent molecules undergo hop diffusion over the compartments. PMID:15189902

Murase, Kotono; Fujiwara, Takahiro; Umemura, Yasuhiro; Suzuki, Kenichi; Iino, Ryota; Yamashita, Hidetoshi; Saito, Mihoko; Murakoshi, Hideji; Ritchie, Ken; Kusumi, Akihiro

2004-01-01

195

Recognizing molecular patterns by machine learning: an agnostic structural definition of the hydrogen bond  

E-print Network

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 ...

Gasparotto, Piero

2014-01-01

196

Lubrication by physisorbed molecules in equilibrium with vapor at ambient condition: effects of molecular structure and substrate chemistry.  

PubMed

The effects of physisorbed organic vapor molecules on friction and wear were studied for various materials with different surface chemistries (metals, ceramics, glasses, carbons, polymers) and adsorbed species with distinct functional groups (short linear-chain, branched, and fluorinated alcohols with alkyl chain lengths up to five carbons as well as acetone and n-decane). Friction test results of stainless steel under equilibrium vapor adsorption conditions indicated that the longer chain length of the adsorbed alcohols results in lower friction and that n-pentanol gives the lowest friction and wear among the molecules investigated. The adsorption isotherm measurements revealed that the functional groups of the adsorbed molecules appear to play important roles in lubrication. Friction coefficients that ranged from 0.02 to 0.9 for the various materials in dry and humid environments converged to ?0.15 for the inorganic solid materials tested in n-pentanol. These findings indicate that the molecular lubrication by the physisorbed species dominates the tribological behaviors of the inorganic solid materials, regardless of bulk mechanical properties. Tribotests using polymeric materials did not show the same lubricating effects for n-pentanol vapor. The failure of n-pentanol to lubricate polymeric materials may be due to vapor ingress into the polymer and the absence of an adsorbed surface layer. PMID:24827583

Barthel, Anthony J; Kim, Seong H

2014-06-10

197

High-throughput screen for small molecules that modulate the ATPase activity of the molecular chaperone DnaK.  

PubMed

DnaK is a molecular chaperone of Escherichia coli that belongs to a family of conserved 70-kDa heat shock proteins. The Hsp70 chaperones are well known for their crucial roles in regulating protein homeostasis, preventing protein aggregation, and directing subcellular traffic. Given the complexity of functions, a chemical method for controlling the activities of these chaperones might provide a useful experimental tool. However, there are only a handful of Hsp70-binding molecules known. To build this area, we developed a robust, colorimetric, high-throughput screening (HTS) method in 96-well plates that reports on the ATPase activity of DnaK. Using this approach, we screened a 204-member focused library of molecules that share a dihydropyrimidine core common to known Hsp70-binding leads and uncovered seven new inhibitors. Intriguingly, the candidates do not appear to bind the hydrophobic groove that normally interacts with peptide substrates. In sum, we have developed a reliable HTS method that will likely accelerate discovery of small molecules that modulate DnaK/Hsp70 function. Moreover, because this family of chaperones has been linked to numerous diseases, this platform might be used to generate new therapeutic leads. PMID:17904512

Chang, Lyra; Bertelsen, Eric B; Wisén, Susanne; Larsen, Erik M; Zuiderweg, Erik R P; Gestwicki, Jason E

2008-01-15

198

Matrix and substrate effects on the sputtering of a 2 kDa molecule: Insights from molecular dynamics  

NASA Astrophysics Data System (ADS)

In an effort towards a more accurate theoretical description of matrix and substrate effects in organic sputtering, we report on molecular dynamics simulations of the desorption induced by 500 eV Ar projectiles bombarding samples composed of polystyrene (PS) oligomers embedded in a trimethylbenzene matrix or cast on a silver substrate. The ejection of intact PS molecules, sometimes accompanied by matrix molecules/silver atoms, is observed in the first 10 ps following the impact. For the "matrix" sample, the results indicate that the emission of large amounts of organic material is mostly vibrationally induced. Extended calculations show that matrix:analyte clusters decay after emission, liberating the analyte in flight. In the case of the "substrate" sample, the emission is oftentimes the result of the concerted upward motion of several metal atoms underneath the molecule. Finally, the comparison between a matrix:analyte sample confined in a nanostructured silver crystal and a purely organic sample under identical bombardment conditions shows that the presence of the silver medium significantly enhances the desorption yields.

Delcorte, A.; Arezki, B.; Garrison, B. J.

2003-12-01

199

A Novel Approach for Characterizing Protein Ligand Complexes: Molecular Basis for Specificity of Small-Molecule  

E-print Network

of this inhibitor family. Introduction Apoptosis is a process of tightly regulated energy-dependent cellular suicide years molecular mechanisms of apoptosis have been investigated, and the members of the Bcl-2 family have emerged as key regulators of apoptotic pathways. The levels of the antiapoptotic Bcl-2 family proteins

200

Friction and energy dissipation mechanisms in adsorbed molecules and molecularly thin films  

Microsoft Academic Search

This review provides an overview of recent advances that have been achieved in understanding the basic physics of friction and energy dissipation in molecularly thin adsorbed films and the associated impact on friction at microscopic and macroscopic length scales. Topics covered include a historical overview of the fundamental understanding of macroscopic friction, theoretical treatments of phononic and electronic energy dissipation

Jacqueline Krim

2012-01-01

201

Red Fluorescent Line Emission from Hydrogen Molecules in Diffuse Molecular Clouds  

NASA Technical Reports Server (NTRS)

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.

Neufeld, David A.; Spaans, Marco

1996-01-01

202

Sputtering of a polycyclic hydrocarbon molecule: TOFSIMS experiments and molecular dynamic simulations  

E-print Network

analyses were conducted using a PHI-EVANS time-of-flight SIMS (TRIFT1) equipped with a 15 keV Gaþ beam (FEI and molecular dynamic (MD) simulations. The mass spectra and kinetic energy distribution (KED) measurements were and challenges of the method are illustrated by experimental and calculated mass and kinetic energy spectra

203

Macrophage migration inhibitory factor: molecular, cellular and genetic aspects of a key neuroendocrine molecule  

Microsoft Academic Search

The immunological and neuroendocrine properties of macrophage migration inhibitory factor (MIF) are diverse. In this article we review the known cellular, molecular and genetic properties of MIF that place it as a key regulatory cytokine, acting within both the innate and adaptive immune responses. The unexpected and paradoxical induction of MIF secretion by low concentrations of glucocorticoids is explored. The

R P Donn; D W Ray

2004-01-01

204

Meet the Molecules in Chocolate: Informal Opportunities for Building Thematic Molecular Models with Children  

ERIC Educational Resources Information Center

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.)

Amey, Jennifer R.; Fletcher, Matthew D.; Fletcher, Rachael V.; Jones, Alison; Roberts, Erica W.; Roberts, Ieuan O.

2008-01-01

205

Proton Donor/acceptor Propensities of Ammonia: Rotational Studies of its Molecular Complexes with Organic Molecules  

NASA Astrophysics Data System (ADS)

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\\cdots?) 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

Giuliano, Barbara M.; Maris, Assimo; Melandri, Sonia; Favero, Laura B.; Evangelisti, Luca; Caminati, Walther

2009-06-01

206

Molecular Mechanisms of T cell Receptor and Costimulatory Molecule Ligation/Blockade in Autoimmune Disease Therapy  

PubMed Central

Pro-inflammatory CD4+ T cell mediated autoimmune diseases, such as multiple sclerosis and type 1 diabetes, are hypothesized to be initiated and maintained by activated antigen presenting cells (APCs) presenting self-antigen to self-reactive interferon-gamma (IFN-?) and interleukin-17 (IL-17) producing CD4+ Th1/17 cells. To date, the majority of FDA approved therapies for autoimmune disease primarily focus on the global inhibition of immune inflammatory activity. The goal of ongoing research in this field is to develop both therapies that inhibit/eliminate activated autoreactive cells as well as antigen-specific treatments which allow for the directed blockade of the deleterious effects of self-reactive immune cell function. According to the two-signal hypothesis, activation of a naïve antigen-specific CD4+ T cell requires both stimulation of the T cell receptor (TCR) (signal 1), and stimulation of costimulatory molecules (signal 2). There also exists a balance between pro-inflammatory and anti-inflammatory immune cell activity, which is regulated by the type and strength of the activating signal as well as the local cytokine milieu in which the naïve CD4+ T cell is activated. To this end, the majority of ongoing research is focused on the delivery of suboptimal TCR stimulation in the absence of costimulatory molecule stimulation, or potential blockade of stimulatory accessory molecules. Therefore, the signaling pathways involved in the induction of CD4+ T cell anergy, as apposed to activation, are topics of intense interest. PMID:19426232

Podojil, Joseph R.; Miller, Stephen D.

2010-01-01

207

Universal scaling behavior of molecular electronic stopping cross section for protons colliding with small molecules and nucleobases  

NASA Astrophysics Data System (ADS)

The electronic stopping cross section and mean excitation energy for molecules and 5 nucleobases have been calculated within the first Born approximation in terms of an orbital decomposition to take into account the molecular structure. The harmonic oscillator (HO) description of the stopping cross section together with a Floating Spherical Gaussian Orbital (FSGO) model is implemented to account for the chemical composition of the target. This approach allows us to use bonds, cores, and lone pairs as HO basis to describe the ground state molecular structure. In the HO model, the orbital angular frequency is the only parameter that connects naturally with the mean excitation energy. As a result, we obtain a simple expression for the equivalent mean excitation energy in terms of the orbital radius parameter, as well as an analytical expression of the stopping cross section. For gas phase molecular targets, we provide HO based orbital mean excitation energies to describe any molecule containing C, N, O, H, and P atoms. We present results for protons colliding with H2, N2, O2, H2O, CO2, propylene (C3H6), methane (CH4), ethylene (C2H4) and the nucleobases - guanine (C5H5N5O), cytosine (C4H5N2O2), thymine (C5H6N2O2), adenine (C5H5N5) and uracil (C4H4N2O2). The results for the stopping cross section are compared with available experimental and theoretical data showing good to excellent agreement in the region of validity of the model. The HO approach allows us to obtain a universal stopping cross section formula to describe a universal scaling behavior for the energy loss process. The universal scaled curve is confirmed by the experimental data.

Trujillo-López, L. N.; Martínez-Flores, C.; Cabrera-Trujillo, R.

2013-10-01

208

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

PubMed Central

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. PMID:23493833

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

2013-01-01

209

Time-dependent density-functional theory for molecules and molecular solids  

Microsoft Academic Search

Time-dependent density-functional theory (TDDFT) has become a well-established part of the modern theoretical chemist’s toolbox for treating electronic excited states. Yet, though applications of TDDFT abound in quantum chemistry, review articles specifically focusing on TDDFT for chemical applications are relatively rare. This article helps to fill the void by first giving a historical review of TDDFT, with emphasis on molecular

Mark E. Casida

2009-01-01

210

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

Microsoft Academic Search

The vibrational to translational (VâT) 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

P. M. Y

1991-01-01

211

Molecular mapping of the immunologic surface of the hCG molecule by monoclonal antibodies (MCA)  

Microsoft Academic Search

The 2-site IRMA-design with MCA is demonstrated to be superior over conventional “l-site”-RIA with polyclonal antibodies since it clearly distinguishes different molecular species of a hormone, especially hCG. Such parallel measurements are considered to be of diagnostic value for screening and therapeutic monitoring of tumor patients who produce freea- and\\/or freeß-subunits early in the course of the disease, or exclusively

S. Schwarz; P. Berger; G. Wick

1984-01-01

212

Molecular understanding of atmospheric particle formation from sulfuric acid and large oxidized organic molecules  

PubMed Central

Atmospheric aerosols formed by nucleation of vapors affect radiative forcing and therefore climate. However, the underlying mechanisms of nucleation remain unclear, particularly the involvement of organic compounds. Here, we present high-resolution mass spectra of ion clusters observed during new particle formation experiments performed at the Cosmics Leaving Outdoor Droplets chamber at the European Organization for Nuclear Research. The experiments involved sulfuric acid vapor and different stabilizing species, including ammonia and dimethylamine, as well as oxidation products of pinanediol, a surrogate for organic vapors formed from monoterpenes. A striking resemblance is revealed between the mass spectra from the chamber experiments with oxidized organics and ambient data obtained during new particle formation events at the Hyytiälä boreal forest research station. We observe that large oxidized organic compounds, arising from the oxidation of monoterpenes, cluster directly with single sulfuric acid molecules and then form growing clusters of one to three sulfuric acid molecules plus one to four oxidized organics. Most of these organic compounds retain 10 carbon atoms, and some of them are remarkably highly oxidized (oxygen-to-carbon ratios up to 1.2). The average degree of oxygenation of the organic compounds decreases while the clusters are growing. Our measurements therefore connect oxidized organics directly, and in detail, with the very first steps of new particle formation and their growth between 1 and 2 nm in a controlled environment. Thus, they confirm that oxidized organics are involved in both the formation and growth of particles under ambient conditions. PMID:24101502

Schobesberger, Siegfried; Junninen, Heikki; Bianchi, Federico; Lonn, Gustaf; Ehn, Mikael; Lehtipalo, Katrianne; Dommen, Josef; Ehrhart, Sebastian; Ortega, Ismael K.; Franchin, Alessandro; Nieminen, Tuomo; Riccobono, Francesco; Hutterli, Manuel; Duplissy, Jonathan; Almeida, Joao; Amorim, Antonio; Breitenlechner, Martin; Downard, Andrew J.; Dunne, Eimear M.; Flagan, Richard C.; Kajos, Maija; Keskinen, Helmi; Kirkby, Jasper; Kupc, Agnieszka; Kurten, Andreas; Kurten, Theo; Laaksonen, Ari; Mathot, Serge; Onnela, Antti; Praplan, Arnaud P.; Rondo, Linda; Santos, Filipe D.; Schallhart, Simon; Schnitzhofer, Ralf; Sipila, Mikko; Tome, Antonio; Tsagkogeorgas, Georgios; Vehkamaki, Hanna; Wimmer, Daniela; Baltensperger, Urs; Carslaw, Kenneth S.; Curtius, Joachim; Hansel, Armin; Petaja, Tuukka; Kulmala, Markku; Donahue, Neil M.; Worsnop, Douglas R.

2013-01-01

213

Systematic theoretical investigation of a positron binding to amino acid molecules using the ab initio multi-component molecular orbital approach  

NASA Astrophysics Data System (ADS)

The feature of positron binding to twenty neutral amino acid molecules with the global minimum (GM) and intramoleculear hydrogen-bonded (HB) structures was analysed using the ab initio multi-component molecular orbital method. All amino acid molecules in the intramoleculear HB structures have positive positron affinity (PA, the binding energy of a positron) values, which means that a positron can be attached to parent molecules, while in the GM structures only three amino acid molecules of Gln, Trp, and His have positive PA values. Analysing the positronic orbitals of each positronic amino acid molecule and the electrostatic potential maps of the corresponding parent molecules, we found that long-range electrostatic interaction is the most crucial role in positron binding to neutral amino acid molecules. The strong correlation is observed between the PA and dipole moment, that is, a polar molecule with a large dipole moment has a large PA value. The critical dipole moment of neutral amino acid molecules for binding a positron was found at about 3.46 Debye. From the systematic analysis of twenty kinds of amino acid molecule, we theoretically confirmed the possibility of positron binding to conformers of amino acid molecules with strong dipole moment.

Koyanagi, K.; Kita, Y.; Tachikawa, M.

2012-05-01

214

A Molecular Signaling Approach to Linking Intraspecific Variation and Macro-evolutionary Patterns.  

PubMed

Macro-evolutionary comparisons are a valued tool in evolutionary biology. Nevertheless, our understanding of how systems involved in molecular signaling change in concert with phenotypic diversification has lagged. We argue that integrating our understanding of the evolution of molecular signaling systems with phylogenetic comparative methods is an important step toward understanding the processes linking variation among individuals with variation among species. Focusing mostly on the endocrine system, we discuss how the complexity and mechanistic nature of molecular signaling systems may influence the application and interpretation of macro-evolutionary comparisons. We also detail five hypotheses concerning the role that physiological mechanisms can play in shaping macro-evolutionary patterns, and discuss ways in which these hypotheses could influence phenotypic diversification. Finally, we review a series of tools able to analyze the complexity of physiological systems and the way they change in concert with the phenotypes for which they coordinate development. PMID:24899365

Swanson, Eli M; Snell-Rood, Emilie C

2014-11-01

215

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

PubMed

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

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

2011-05-12

216

UCLA's Molecular Screening Shared Resource: enhancing small molecule discovery with functional genomics and new technology.  

PubMed

The Molecular Screening Shared Resource (MSSR) offers a comprehensive range of leading-edge high throughput screening (HTS) services including drug discovery, chemical and functional genomics, and novel methods for nano and environmental toxicology. The MSSR is an open access environment with investigators from UCLA as well as from the entire globe. Industrial clients are equally welcome as are non-profit entities. The MSSR is a fee-for-service entity and does not retain intellectual property. In conjunction with the Center for Environmental Implications of Nanotechnology, the MSSR is unique in its dedicated and ongoing efforts towards high throughput toxicity testing of nanomaterials. In addition, the MSSR engages in technology development eliminating bottlenecks from the HTS workflow and enabling novel assays and readouts currently not available. PMID:24661210

Damoiseaux, Robert

2014-05-01

217

Organic molecules in the atmosphere of Jupiter. [low molecular weight hydrocarbons  

NASA Technical Reports Server (NTRS)

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.

Ponnamperuma, C. A.

1978-01-01

218

Molecular Dynamics Simulation of Dextran Extension by Constant Force in Single Molecule AFM  

PubMed Central

The extension of 1–6 polysaccharides has been studied in a series of recent single molecule AFM experiments. For dextran, a key finding was the existence of a plateau in the force-extension curve at forces between 700 and 1000 pN. We studied the extension of the dextran 10-mer under constant force using atomistic simulation with various force fields. All the force fields reproduce the experimental plateau on the force-extension curve. With AMBER94 and AMBER-GLYCAM04 force fields the plateau can be explained by a transition of the glucopyranose rings in the dextran monomers from the chair (4C1) to the inverted chair (1C4) conformation while other processes occur at smaller (rotation around C5-C6 bond) or higher (chairs to boat transitions) forces. The CHARMM force field provides a different picture which associates the occurrence of the plateau to chair-boat transitions of the glucopyranose rings. PMID:16950842

Neelov, Igor M.; Adolf, David B.; McLeish, Tom C. B.; Paci, Emanuele

2006-01-01

219

Synthesis and molecular recognition studies on small-molecule inhibitors for thioredoxin reductase.  

PubMed

Thioredoxin reductase (TrxR), which is overexpressed in many aggressive cancers, plays a crucial role in redox balance and antioxidant function, including defense of oxidative stress, control of cell proliferation, and regulation of cell apoptosis. Deactivation of TrxR can destroy the homeostasis of the cancer cells, inducing elevation of reactive oxygen species (ROS) levels and the oxidation of enzymatic substrates. Here, we synthesized and identified a new gold(I) small molecule (D9) that possesses two strong electron-donating moieties, i.e., 4-methylphenyl alkynyl and thionyldiphenyl phosphine, exhibiting an enhanced p-? conjunction effect. The resulting compound shows the increased soft Lewis acids and the stability of gold(I). And we demonstrated that D9 could efficiently and specifically inhibit the activity of TrxR in vitro and in vivo, and it could effectively avoid the ligand exchange with albumin that was one of the most abundant proteins in blood. We believe that these comprehensive studies on the relationship between the structure and performance will provide inspiring information on the precise synthesis and design of new compounds for targeting TrxR. PMID:25249032

Zhang, Di; Xu, Zhonghe; Yuan, Jia; Zhao, Ying-Xi; Qiao, Zeng-Ying; Gao, Yu-Juan; Yu, Guang-Ao; Li, Jingyuan; Wang, Hao

2014-10-01

220

Recognizing molecular patterns by machine learning: An agnostic structural definition of the hydrogen bond.  

PubMed

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

Gasparotto, Piero; Ceriotti, Michele

2014-11-01

221

Molecular Population Genetics of the Male and Female Mitochondrial DNA Molecules of the California Sea Mussel, Mytilus californianus  

PubMed Central

The presence of two gender-associated mitochondrial genomes in marine mussels provides a unique opportunity to investigate the dynamics of mtDNA evolution without complications inherent in interspecific comparisons. Here, we assess the relative importance of selection, mutation, and differential constraint in shaping the patterns of polymorphism within and divergence between the male (M) and female (F) mitochondrial genomes of the California sea mussel, Mytilus californianus. Partial sequences were obtained from homologous regions of four genes (nad2, cox1, atp6, and nad5) totaling 2307 bp in length. The M and F mtDNA molecules of M. californianus exhibited extensive levels of nucleotide polymorphism and were more highly diverged than observed in other mytilids (overall Tamura–Nei distances >40%). Consistent with previous studies, the M molecule had significantly higher levels of silent and replacement polymorphism relative to F. Both genomes possessed large numbers of singleton and low-frequency mutations that gave rise to significantly negative Tajima's D values. Mutation-rate scalars estimated for silent and replacement mutations were elevated in the M genome but were not sufficient to account for its higher level of polymorphism. McDonald–Kreitman tests were highly significant at all loci due to excess numbers of fixed replacement mutations between molecules. Strong purifying selection was evident in both genomes in keeping the majority of replacement mutations at low population frequencies but appeared to be slightly relaxed in M. Our results suggest that a reduction in selective constraint acting on the M genome remains the best explanation for its greater levels of polymorphism and faster rate of evolution. PMID:17720935

Ort, Brian S.; Pogson, Grant H.

2007-01-01

222

Imaging the molecular dimensions and oligomerization of protein molecules at the solid-liquid interface by surface oriented molecular sizing (SOMS) microscopy  

NASA Astrophysics Data System (ADS)

The structure and behavior of proteins at the solid/liquid interface is of great scientific interest. It has application both to fundamental biochemical understanding, as well as to biotechnological purposes. Interfaces play a critical role in many physiological processes. The mechanism of protein adsorption to surfaces is not very well understood. The current model put forth in much of the literature assumes a two step model. In the first step of this model the protein collides with the surface and adsorbs if its energy is sufficient to overcome the free energy of desorption of surface adsorbed solvent. The second step is often assumed to involve significant conformational change of the secondary and tertiary structure of the protein or enzyme, akin to denaturation. This unfolding of the protein would tend to indicate that loss of function would occur concomitantly, but studies have found very little loss in activity upon adsorption for a number of different protein systems. The recent development of the atomic force microscope (AFM) offers another tool for the examination of protein structure at liquid/solid interfaces. For atomically flat crystals the AFM has been used to determine atomic positions to <1 A resolution. In the case of samples with topographic features larger than atoms, the probe tip of the AFM 'convolutes' with the size and shape of surface features. This has hindered the use of AFM for molecular level structural determination of proteins at the liquid/solid interface. The work presented in this dissertation covers the development of the surface oriented molecular sizing (SOMS) technique which makes use of the angstrom height resolution of the AFM and a physically based mathematical framework for the analysis of the height distribution of adsorbed protein molecules. The surface adsorption and orientation (SAO) model is developed using statistical thermodynamics to model the expected height distributions for molecules adsorbed on a surface. The SOMS technique will be shown to be viable through studies of ferritin and concanavalin A (Con A) at the water/mica interface. Using this technique we are able to determine both the three-dimensional size and the oligomerization state of the adsorbed molecules. This technique will then be utilized for the examination of denaturation of Con A at the interface, by a number of mechanisms. Further, the structural and orientational changes in Con A as a function of pH will also be presented. The final chapter of this dissertation will present an extension of these studies to the deposition and structure of Con A thin films on mica.

Waner, Mark Joseph

223

Molecular and Biochemical Characterization of Human Galactokinase and its small molecule inhibitors  

PubMed Central

Human galactokinase (GALK) is the first enzyme in the Leloir pathway, converting ?-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 IC50s ranging from 0.7?M to 33.3?M. 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. PMID:20696150

M, Tang; K, Wierenga; LJ, Elsas; K, Lai

2010-01-01

224

Ion and molecule sensors using molecular recognition in luminescent, conductive polymers. 1998 annual progress report  

SciTech Connect

'The purpose of this project is to develop sensor technology for detecting specific heavy metal ions, such as transition metals, lead, lanthanides, and actinides in waste streams. The sensing strategy uses molecular recognition of the metal ions by polymers that change their luminescence and conductivity properties upon metal binding. Research problems that are being addressed by this project include: (1) designing molecular recognition sites that are highly selective for the metal ions of interest in the presence of a large background of other chemical species, (2) finding ways to incorporate many different selective groups into a single polymer, (3) fabricating polymer films, strips, sheets, and coatings that can be applied to other materials, such as fiber optics and surfaces, (4) developing interfaces between the polymers and substrates that can be used to produce prototype arrays of many sensor elements for rapid multi-contaminant detection and quantitation, and (5) developing multiplexed data collection techniques to rapidly process the data obtained from many polymer sensors into a chemical profile of a waste stream or waste site in real time. As of June 1, 1998, the authors have prepared several polymers based on the incorporation of 2,2{prime}-bipyridine into poly(phenylenevinylene) polymers. The central idea, illustrated in Figure 1, is to prepare a pseudoconjugated, ligand-containing polymer that upon incorporating metal ions undergoes a conformational change, thus converting the initial partially conjugated polymer to a fully or near fully conjugated one. Such conjugation enhancement,along with the simultaneous electron density change caused by incorporating metal ions onto the backbone of polymers, dramatically changes the optical and conductivity properties of the polymer. These property changes are used to signal the presence of the metal ion analyte. The authors have developed several synthetic routes to these polymers and have demonstrated that they exhibit selective binding properties when exposed to transition metals and lanthanides. In addition, the authors have developed a new polymer that gives us the versatility that they need for rapid attachment of ligands that bind heavy metals, such as lead and plutonium.'

Wasielewski, M.R. [Argonne National Lab., IL (US). Chemistry Div.; Raymond, K. [Univ. of California, Berkeley, CA (US). Dept. of Chemistry; Walt, D.E. [Tufts Univ., Medford, MA (US). Dept. of Chemistry

1998-06-01

225

[Diagnostic and prognostic possibilities of using the indicators of blood serum middle molecule and medium-molecular peptide levels in inflammatory diseases of the small-pelvic organs].  

PubMed

Analysis of the diagnostic and prognostic potentialities of measurements of blood serum medium molecules and medium-molecular peptides in women with inflammatory diseases of the small pelvis organs has been carried out, involving 60 patients and 10 healthy women. Medium molecule levels were estimated with the use of Gabrielyan and Lipatova's method, the level of medium-molecular peptides by the biuret method. The results recommend these measurements to be included in the complex of clinical laboratory investigations carried out in patients with pelvic inflammations for the early detection of purulent ++tubo-ovarian inflammations, endogenous intoxication, and a more rational treatment. PMID:1481962

Medvedev, B I; Kazachkova, E A; Astakhova, T V; Popova, A S

1992-01-01

226

A Molecular Dynamics Study on the Confinement of Carbon Dioxide Molecules in Carbon Nanotubes  

NASA Astrophysics Data System (ADS)

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.

Lazor, Meagan; Rende, Deniz; Baysal, Nihat; Ozisik, Rahmi

2012-02-01

227

Core molecule dependence of energy migration in phenylacetylene nanostar dendrimers: Ab initio molecular orbital-configuration interaction based quantum master equation study  

Microsoft Academic Search

The core molecule dependence of energy (exciton) migration in phenylacetylene nanostar dendrimers is investigated using the ab initio molecular orbital (MO)-configuration interaction based quantum master equation approach. We examine three kinds of core molecular species, i.e., benzene, anthracene, and pentacene, with different highest occupied MO-lowest unoccupied MO (HOMO-LUMO) gaps, which lead to different orbital interactions between the dendron parts and

Ryohei Kishi; Takuya Minami; Hitoshi Fukui; Hideaki Takahashi; Masayoshi Nakano

2008-01-01

228

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

PubMed

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

Hauser, Marie-Theres

2014-01-01

229

CD24-Siglec G/10 discriminates danger- from pathogen-associated molecular patterns  

PubMed Central

It is now well accepted that the innate immune system recognizes both damage (or danger)- and pathogen-associated molecular patterns (DAMP and PAMP, respectively) through pattern recognition receptors, such as Toll-like receptors (TLR) and/or Nod-like receptors (NLR). Less clear are whether and how the response to PAMP and DAMP are differentially regulated. The answers may reveal whether the primary goal of the immune system is to defend against infections or to alert the host of tissue injuries. We demonstrated recently that the host response to DAMP is controlled by a DAMP-CD24-Siglec axis. Here we propose a key role for the CD24-Siglec pathway in discriminating between DAMPs and PAMPs. PMID:19786366

Liu, Yang; Chen, Guo-Yun; Zheng, Pan

2009-01-01

230

Patterns  

NSDL National Science Digital Library

Directions: Play the games that are listed. Do not go to another site. Be sure to take turns with your partner. First, learn to complete a pattern by playing "Which One?." Next, keep practicing patterns by playing "Pattern Mania." Finally, determine what type of pattern each set is by playing "Which pattern is it?." ...

Hinson, Mrs.

2011-10-03

231

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

SciTech Connect

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.

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

2004-07-01

232

Design and analysis of small-molecule antineoplastic agents targeting brain tumors by utilizing pattern recognition methods and in silico optimized pharmaceutical properties  

Microsoft Academic Search

The purpose of this work is the in silico design and characterization of small-molecule anticancer agents that target the\\u000a central nervous system. All agents are cytotoxic nitrogen mustard agents, a class of drugs widely used in the clinical treatment\\u000a of cancer. Molecular properties such as polar surface area, log P, and formula weight have previously been shown to be highly

Ronald Bartzatt

2007-01-01

233

Application of pattern recognition in molecular spectroscopy: Automatic line search in high-resolution spectra  

NASA Astrophysics Data System (ADS)

An expert system has been developed for the initial analysis of a recorded spectrum, namely, for the line search and the determination of line positions and intensities. The expert system is based on pattern recognition algorithms. Object recognition learning allows the system to achieve the needed flexibility and automatically detect groups of overlapping lines, whose profiles should be fit together. Gauss, Lorentz, and Voigt profiles are used as model profiles to which spectral lines are fit. The expert system was applied to processing of the Fourier transform spectrum of the D2O molecule in the region 3200-4200 cm-1, and it detected 4670 lines in the spectrum, which consisted of 439000 dots. No one experimentally observed line exceeding the noise level was missed.

Bykov, A. D.; Pshenichnikov, A. M.; Sinitsa, L. N.; Shcherbakov, A. P.

2004-07-01

234

Contrasted Patterns of Molecular Evolution in Dominant and Recessive Self-Incompatibility Haplotypes in Arabidopsis  

PubMed Central

Self-incompatibility has been considered by geneticists a model system for reproductive biology and balancing selection, but our understanding of the genetic basis and evolution of this molecular lock-and-key system has remained limited by the extreme level of sequence divergence among haplotypes, resulting in a lack of appropriate genomic sequences. In this study, we report and analyze the full sequence of eleven distinct haplotypes of the self-incompatibility locus (S-locus) in two closely related Arabidopsis species, obtained from individual BAC libraries. We use this extensive dataset to highlight sharply contrasted patterns of molecular evolution of each of the two genes controlling self-incompatibility themselves, as well as of the genomic region surrounding them. We find strong collinearity of the flanking regions among haplotypes on each side of the S-locus together with high levels of sequence similarity. In contrast, the S-locus region itself shows spectacularly deep gene genealogies, high variability in size and gene organization, as well as complete absence of sequence similarity in intergenic sequences and striking accumulation of transposable elements. Of particular interest, we demonstrate that dominant and recessive S-haplotypes experience sharply contrasted patterns of molecular evolution. Indeed, dominant haplotypes exhibit larger size and a much higher density of transposable elements, being matched only by that in the centromere. Overall, these properties highlight that the S-locus presents many striking similarities with other regions involved in the determination of mating-types, such as sex chromosomes in animals or in plants, or the mating-type locus in fungi and green algae. PMID:22457631

Goubet, Pauline M.; Berges, Helene; Bellec, Arnaud; Prat, Elisa; Helmstetter, Nicolas; Mangenot, Sophie; Gallina, Sophie; Holl, Anne-Catherine; Fobis-Loisy, Isabelle; Vekemans, Xavier; Castric, Vincent

2012-01-01

235

Contrasted patterns of molecular evolution in dominant and recessive self-incompatibility haplotypes in Arabidopsis.  

PubMed

Self-incompatibility has been considered by geneticists a model system for reproductive biology and balancing selection, but our understanding of the genetic basis and evolution of this molecular lock-and-key system has remained limited by the extreme level of sequence divergence among haplotypes, resulting in a lack of appropriate genomic sequences. In this study, we report and analyze the full sequence of eleven distinct haplotypes of the self-incompatibility locus (S-locus) in two closely related Arabidopsis species, obtained from individual BAC libraries. We use this extensive dataset to highlight sharply contrasted patterns of molecular evolution of each of the two genes controlling self-incompatibility themselves, as well as of the genomic region surrounding them. We find strong collinearity of the flanking regions among haplotypes on each side of the S-locus together with high levels of sequence similarity. In contrast, the S-locus region itself shows spectacularly deep gene genealogies, high variability in size and gene organization, as well as complete absence of sequence similarity in intergenic sequences and striking accumulation of transposable elements. Of particular interest, we demonstrate that dominant and recessive S-haplotypes experience sharply contrasted patterns of molecular evolution. Indeed, dominant haplotypes exhibit larger size and a much higher density of transposable elements, being matched only by that in the centromere. Overall, these properties highlight that the S-locus presents many striking similarities with other regions involved in the determination of mating-types, such as sex chromosomes in animals or in plants, or the mating-type locus in fungi and green algae. PMID:22457631

Goubet, Pauline M; Bergès, Hélène; Bellec, Arnaud; Prat, Elisa; Helmstetter, Nicolas; Mangenot, Sophie; Gallina, Sophie; Holl, Anne-Catherine; Fobis-Loisy, Isabelle; Vekemans, Xavier; Castric, Vincent

2012-01-01

236

Properties and Reactivity Patterns of AsP3: An Experimental and Computational Study of Group 15 Elemental Molecules  

E-print Network

Facile synthetic access to the isolable, thermally robust AsP3 molecule has allowed for a thorough study of its physical properties and reaction chemistry with a variety of transition-metal and organic fragments. The ...

Cossairt, Brandi M.

237

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

SciTech Connect

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.

Schiesser, Alexander; Schaefer, Rolf [Eduard-Zintl-Institut fuer Anorganische und Physikalische Chemie, Technische Universitaet Darmstadt, Petersenstrasse 20, 64287 Darmstadt (Germany)

2009-08-15

238

A coarse-grained method based on the analysis of short molecular dynamics trajectories for the simulation of non-Markovian dynamics of molecules adsorbed in microporous materials.  

PubMed

We developed a coarse-grained model suitable for the study of adsorbed molecules in microporous materials. A partition of the space available to the motion of adsorbed molecules was carried out, which allows to formulate the dynamics in terms of jumps between discrete regions. The probabilities of observing given pairs of successive jumps were calculated from Molecular Dynamics (MD) simulations, performed on small systems, and used to drive the motion of molecules in a lattice-gas model. Dynamics is thus reformulated in terms of event-space dynamics and this allows to treat the system despite its inherent non markovity. Despite the assumptions enforced in the algorithm, results show that it can be applied to various spherical molecules adsorbed in the all-silica zeolite ITQ-29, establishing a suitable direct bridge between MD simulation results and coarse-grained models. PMID:25149777

Pintus, Alberto M; Gabrieli, Andrea; Pazzona, Federico G; Demontis, Pierfranco; Suffritti, Giuseppe B

2014-08-21

239

A coarse-grained method based on the analysis of short molecular dynamics trajectories for the simulation of non-Markovian dynamics of molecules adsorbed in microporous materials  

NASA Astrophysics Data System (ADS)

We developed a coarse-grained model suitable for the study of adsorbed molecules in microporous materials. A partition of the space available to the motion of adsorbed molecules was carried out, which allows to formulate the dynamics in terms of jumps between discrete regions. The probabilities of observing given pairs of successive jumps were calculated from Molecular Dynamics (MD) simulations, performed on small systems, and used to drive the motion of molecules in a lattice-gas model. Dynamics is thus reformulated in terms of event-space dynamics and this allows to treat the system despite its inherent non markovity. Despite the assumptions enforced in the algorithm, results show that it can be applied to various spherical molecules adsorbed in the all-silica zeolite ITQ-29, establishing a suitable direct bridge between MD simulation results and coarse-grained models.

Pintus, Alberto M.; Gabrieli, Andrea; Pazzona, Federico G.; Demontis, Pierfranco; Suffritti, Giuseppe B.

2014-08-01

240

Immobilization of hydrophilic low molecular-weight molecules in nanoparticles of chitosan/poly(sodium 4-styrenesulfonate) assisted by aromatic-aromatic interactions.  

PubMed

The immobilization of the hydrophilic low molecular-weight cationic molecules rhodamine 6G, methylene blue, and citidine in nanoparticles composed of two opposite charged polyelectrolytes, poly(sodium 4-styrenesulfonate) and chitosan, is studied, and the results correlated with their physicochemical properties. Nanoparticles containing both polyelectrolytes have been synthesized showing hydrodynamic diameters of around 200 nm and tunable zeta potential. It was found that the strength of binding of the cationic molecules to the polyanion bearing charged aromatic groups poly(sodium 4-styrenesulfonate) by means of short-range aromatic-aromatic interactions increases with their hydrophobicity and polarizability, as seen by (1)H NMR and UV-vis spectroscopies, and diafiltration. Consequently, association efficiencies of 45, 21, and 12% have been found for the three molecules, respectively, revealing the different ability of the molecules to be immobilized in the nanoparticles. These results provide a proof of concept on a new strategy of immobilization of hydrophilic low molecular-weight molecules based on aromatic-aromatic interactions between polyelectrolytes and their aromatic counterions. PMID:25054833

Fuenzalida, Juan Pablo; Flores, Mario E; Móniz, Inés; Feijoo, Miguel; Goycoolea, Francisco; Nishide, Hiroyuki; Moreno-Villoslada, Ignacio

2014-08-14

241

Molecular characterization and clinical implications of spindle cells in nasopharyngeal carcinoma: a novel molecule-morphology model of tumor progression proposed.  

PubMed

Up to now, the precise molecular and morphological changes underlying the invasive and metastatic properties of nasopharyngeal carcinoma (NPC) remain largely unresolved. We speculate that neoplastic spindle cells, which are prominently found in the invasive tumor front and the surrounding stroma, might be responsible for the aggressive patterns. Expression profiling of various biomarkers relevant to cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) was performed by tissue microarray-based immunohistochemistry in NPC samples. The expression of EBER and LMP1 was detected by in situ hybridization and immunohistochemistry, respectively. We found that overexpression of CSCs-related markers (ALDH1, Nanog and ABCG2) and up-regulation of EMT markers (Fibronectin, MMP-2, Periostin, SPARC, Snail and Slug), together with E- to N-cadherin switching, occurred preferentially in tumors containing a large proportion of spindle-shaped malignant cells. Furthermore, CSCs-like properties were highly present in spindle cells compared with non-spindle cells of tumors, and correlated strongly with EMT features. In addition, EBV-related factors EBER and LMP1 were highly expressed and correlated strongly with CSCs and EMT characteristics in neoplastic spindle cells. Importantly, high proportion of spindle cells (?20%) correlated significantly with various aggressive aspects including lymph node metastasis (P = 0.031) and local recurrence (P = 0.014). Patients with high proportion of spindle cells had poor survival (P = 0.004), though it was not an independent value. In conclusion, we demonstrate that spindle cells could be valuable morphological indicators of tumor progression and unfavorable prognosis of NPC. An integrated molecule-morphology model of NPC firstly constructed may shed significant light on the metastatic cascade and clinical relevance of patients. PMID:24349446

Luo, Weiren; Yao, Kaitai

2013-01-01

242

Metalorganic molecular beam epitaxy growth of GaAs on patterned GaAs substrates  

NASA Astrophysics Data System (ADS)

GaAs layers were grown on etch-patterned (100) GaAs substrates by MOMBE (metalorganic molecular beam epitaxy) using TEGa (triethylgallium) and thermally cracked TEAs (triethylarsine). Morphology and orientation dependencies of the grown facets on the growth temperature (400-630°C) and V/III ratio (2-4) are investigated. Good morphology of grown layers was obtained on (111)A side facets at a low V/III ratio of 3 and low growth temperatures of 450-500°C. We also found strong evidence that the formation of facets is not only governed by the migration of Ga precursors and/or Ga atoms, but also by a preferential catalytic decomposition of Ga precursors on the facet edges.

Marx, D.; Asahi, H.; Liu, X. F.; Okuno, Y.; Inoue, K.; Gonda, S.; Shimomura, S.; Hiyamizu, S.

1994-03-01

243

Molecular layer deposition of functional thin films for advanced lithographic patterning.  

PubMed

Photoresist materials comprise one of the main challenges faced by lithography to meet the requirements of electronic device size scaling. Here we report for the first time the use of molecular layer deposition (MLD) to produce photoresist materials with controllable placement of functional moieties. Polyurea resists films are deposited by MLD using urea coupling reactions between 1,4-phenylene diisocyanate (PDIC) and ethylenediamine (ED) or 2,2'-(propane-2,2-diylbis(oxy))diethanamine (PDDE) monomers in a layer-by-layer fashion with a linear growth rate, allowing acid-labile groups to be incorporated into the film at well-controlled positions. The films are deposited with stoichiometric compositions and have highly uniform surface morphology as investigated using atomic force microscopy. We show that acid treatment can cleave the backbone of the polyurea film at positions where the acid-labile groups are embedded. We further show that after soaking the polyurea film with photoacid generator (PAG), it acts as a photoresist material and we present several UV patterning demonstrations. This approach presents a new way to make molecularly designed resist films for lithography. PMID:21302918

Zhou, Han; Bent, Stacey F

2011-02-01

244

Binding Specificity of Philyra pisum Lectin to Pathogen-Associated Molecular Patterns, and Its Secondary Structure  

PubMed Central

We recently reported a Philyra pisum lectin (PPL) that exerts mitogenic effects on human lymphocytes, and its molecular characterization. The present study provides a more detailed characterization of PPL based on the results from a monosaccharide analysis indicating that PPL is a glycoprotein, and circular dichroism spectra revealing its estimated ?-helix, ?-sheet, ?-turn, and random coil contents to be 14.0%, 39.6%, 15.8%, and 30.6%, respectively. These contents are quite similar to those of deglycosylated PPL, indicating that glycans do not affect its intact structure. The binding properties to different pathogen-associated molecular patterns were investigated with hemagglutination inhibition assays using lipoteichoic acid from Gram-positive bacteria, lipopolysaccharide from Gram-negative bacteria, and both mannan and ?-1,3-glucan from fungi. PPL binds to lipoteichoic acids and mannan, but not to lipopolysaccharides or ?-1,3-glucan. PPL exerted no significant antiproliferative effects against human breast or bladder cancer cells. These results indicate that PPL is a glycoprotein with a lipoteichoic acid or mannan-binding specificity and which contains low and high proportions of ?-helix and ?-structures, respectively. These properties are inherent to the innate immune system of P. pisum and indicate that PPL could be involved in signal transmission into Gram-positive bacteria or fungi. PMID:24381505

Park, Byung Tae; Kim, Byung Sun; Park, Heajin; Jeong, Jaehoon; Hyun, Hanbit; Hwang, Hye Seong

2013-01-01

245

Characterization of currently marketed heparin products: analysis of molecular weight and heparinase-I digest patterns.  

PubMed

We evaluated polyacrylamide gel electrophoresis (PAGE) and size exclusion chromatography coupled with multi-angle laser light scattering (SEC-MALLS) approaches to determine weight-average molecular weight (M(w)) and polydispersity (PD) of heparins. A set of unfractionated heparin sodium (UFH) and low-molecular-weight heparin (LMWH) samples obtained from nine manufacturers which supply the US market were assessed. For SEC-MALLS, we measured values for water content, refractive index increment (dn/dc), and the second virial coefficient (A(2)) for each sample prior to molecular weight assessment. For UFH, a mean ± standard deviation value for M(w) of 16,773 ± 797 was observed with a range of 15,620 to 18,363 (n = 20, run in triplicate). For LMWHs by SEC-MALLS, we measured mean M(w) values for dalteparin, tinzaparin, and enoxaparin of 6,717 ± 71 (n = 4), 6,670 ± 417 (n = 3), and 3,959 ± 145 (n = 3), respectively. PAGE analysis of the same UFH, dalteparin, tinzaparin, and enoxaparin samples showed values of 16,135 ± 643 (n = 20), 5,845 ± 45 (n = 4), 6,049 ± 95 (n = 3), and 4,772 ± 69 (n = 3), respectively. These orthogonal measurements are the first M(w) results obtained with a large heparin sample set on product being marketed after the heparin crisis of 2008 changed the level of scrutiny of this drug class. In this study, we compare our new data set to samples analyzed over 10 years earlier. In addition, we found that the PAGE analysis of heparinase digested UFH and neat LMWH samples yield characteristic patterns that provide a facile approach for identification and assessment of drug quality and uniformity. PMID:21901459

Sommers, Cynthia D; Ye, Hongping; Kolinski, Richard E; Nasr, Moheb; Buhse, Lucinda F; Al-Hakim, Ali; Keire, David A

2011-11-01

246

Analysis of molecular expression patterns and integration with other knowledge bases using probabilistic Bayesian network models  

SciTech Connect

How can molecular expression experiments be interpreted with greater than ten to the fourth measurements per chip? How can one get the most quantitative information possible from the experimental data with good confidence? These are important questions whose solutions require an interdisciplinary combination of molecular and cellular biology, computer science, statistics, and complex systems analysis. The explosion of data from microarray techniques present the problem of interpreting the experiments. The availability of large-scale knowledge bases provide the opportunity to maximize the information extracted from these experiments. We have developed new methods of discovering biological function, metabolic pathways, and regulatory networks from these data and knowledge bases. These techniques are applicable to analyses for biomedical engineering, clinical, and fundamental cell and molecular biology studies. Our approach uses probabilistic, computational methods that give quantitative interpretations of data in a biological context. We have selected Bayesian statistical models with graphical network representations as a framework for our methods. As a first step, we use a nave Bayesian classifier to identify statistically significant patterns in gene expression data. We have developed methods which allow us to (a) characterize which genes or experiments distinguish each class from the others, (b) cross-index the resulting classes with other databases to assess biological meaning of the classes, and (c) display a gross overview of cellular dynamics. We have developed a number of visualization tools to convey the results. We report here our methods of classification and our first attempts at integrating the data and other knowledge bases together with new visualization tools. We demonstrate the utility of these methods and tools by analysis of a series of yeast cDNA microarray data and to a set of cancerous/normal sample data from colon cancer patients. We discuss extending our methods to inferring biological pathways and networks using more complex dynamic Bayesian networks.

Moler, Edward J.; Mian, I.S.

2000-03-01

247

Electron beam irradiation for structuring of molecular assemblies  

Microsoft Academic Search

Nontraditional applications of electron beam irradiation for patterning of molecular assemblies are considered. The electron beam can have the following effects on molecular layers: destruction of molecular structure under e-beam irradiation with a successive formation of new molecular system when the irradiation is stopped; variation of the properties of the layer after e-beam irradiation; crosslinking of molecules in the layer

Victor Erokhin; Tatiana Berzina; M. P. Fontana

2004-01-01

248

The Relation between Recombination Rate and Patterns of Molecular Evolution and Variation in Drosophila melanogaster  

PubMed Central

Genetic recombination associated with sexual reproduction increases the efficiency of natural selection by reducing the strength of Hill–Robertson interference. Such interference can be caused either by selective sweeps of positively selected alleles or by background selection (BGS) against deleterious mutations. Its consequences can be studied by comparing patterns of molecular evolution and variation in genomic regions with different rates of crossing over. We carried out a comprehensive study of the benefits of recombination in Drosophila melanogaster, both by contrasting five independent genomic regions that lack crossing over with the rest of the genome and by comparing regions with different rates of crossing over, using data on DNA sequence polymorphisms from an African population that is geographically close to the putatively ancestral population for the species, and on sequence divergence from a related species. We observed reductions in sequence diversity in noncrossover (NC) regions that are inconsistent with the effects of hard selective sweeps in the absence of recombination. Overall, the observed patterns suggest that the recombination rate experienced by a gene is positively related to an increase in the efficiency of both positive and purifying selection. The results are consistent with a BGS model with interference among selected sites in NC regions, and joint effects of BGS, selective sweeps, and a past population expansion on variability in regions of the genome that experience crossing over. In such crossover regions, the X chromosome exhibits a higher rate of adaptive protein sequence evolution than the autosomes, implying a Faster-X effect. PMID:24489114

Campos, Jose L.; Halligan, Daniel L.; Haddrill, Penelope R.; Charlesworth, Brian

2014-01-01

249

Morphologic and molecular evaluation of Chlamydia trachomatis growth in human endocervix reveals distinct growth patterns  

PubMed Central

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 IFN?. 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 IFN?-induced persistence. PMID:24959423

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

250

Molecular dynamics of single-particle impacts predicts phase diagrams for large scale pattern formation.  

PubMed

Energetic particle irradiation can cause surface ultra-smoothening, self-organized nanoscale pattern formation or degradation of the structural integrity of nuclear reactor components. A fundamental understanding of the mechanisms governing the selection among these outcomes has been elusive. Here we predict the mechanism governing the transition from pattern formation to flatness using only parameter-free molecular dynamics simulations of single-ion impacts as input into a multiscale analysis, obtaining good agreement with experiment. Our results overturn the paradigm attributing these phenomena to the removal of target atoms via sputter erosion: the mechanism dominating both stability and instability is the impact-induced redistribution of target atoms that are not sputtered away, with erosive effects being essentially irrelevant. We discuss the potential implications for the formation of a mysterious nanoscale topography, leading to surface degradation, of tungsten plasma-facing fusion reactor walls. Consideration of impact-induced redistribution processes may lead to a new design criterion for stability under irradiation. PMID:21505432

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

251

The pattern recognition molecule ficolin-1 exhibits differential binding to lymphocyte subsets, providing a novel link between innate and adaptive immunity.  

PubMed

Ficolin-1 is a soluble pattern recognition molecule synthesized by myeloid cells and capable of activating the lectin pathway of complement on the surface of pathogens. It is tethered to the membranes of monocytes and granulocytes; however, the biological significance of cell-associated ficolin-1 is unknown. Recognition of healthy host cells by a pattern recognition molecule constitutes a potential hazard to self cells and tissues, emphasizing the importance of further elucidating the reported self-recognition. In the current study we investigated the potential recognition of lymphocytes by ficolin-1 and demonstrated that CD56(dim) NK-cells and both CD4(+) and CD8(+) subsets of activated T-cells were recognized by ficolin-1. In contrast we did not detect binding of ficolin-1 to CD56(bright) NK-cells, NKT-cells, resting T-cells or B-cells. Furthermore, we showed that the protein-lymphocyte interaction occurred via the pathogen-recognition domain of ficolin-1 to sialic acid on the cell surface. Thus, the differential binding of ficolin-1 to lymphocyte subsets suggests ficolin-1 as a novel link between innate and adaptive immunity. Our results provide new insight about the recognition properties of ficolin-1 and point toward additional immune modulating functions of the molecule besides its role in pathogen recognition. PMID:24161415

Genster, Ninette; Ma, Ying Jie; Munthe-Fog, Lea; Garred, Peter

2014-02-01

252

Adapting SAFT-? perturbation theory to site-based molecular dynamics simulation. III. Molecules with partial charges at bulk phases, confined geometries and interfaces  

NASA Astrophysics Data System (ADS)

In Paper I [A. F. Ghobadi and J. R. Elliott, J. Chem. Phys. 139(23), 234104 (2013)], we showed that how a third-order Weeks-Chandler-Anderson (WCA) Thermodynamic Perturbation Theory and molecular simulation can be integrated to characterize the repulsive and dispersive contributions to the Helmholtz free energy for realistic molecular conformations. To this end, we focused on n-alkanes to develop a theory for fused and soft chains. In Paper II [A. F. Ghobadi and J. R. Elliott, J. Chem. Phys. 141(2), 024708 (2014)], we adapted the classical Density Functional Theory and studied the microstructure of the realistic molecular fluids in confined geometries and vapor-liquid interfaces. We demonstrated that a detailed consistency between molecular simulation and theory can be achieved for both bulk and inhomogeneous phases. In this paper, we extend the methodology to molecules with partial charges such as carbon dioxide, water, 1-alkanols, nitriles, and ethers. We show that the electrostatic interactions can be captured via an effective association potential in the framework of Statistical Associating Fluid Theory (SAFT). Implementation of the resulting association contribution in assessing the properties of these molecules at confined geometries and interfaces presents satisfactory agreement with molecular simulation and experimental data. For example, the predicted surface tension deviates less than 4% comparing to full potential simulations. Also, the theory, referred to as SAFT-? WCA, is able to reproduce the specific orientation of hydrophilic head and hydrophobic tail of 1-alkanols at the vapor-liquid interface of water.

Ghobadi, Ahmadreza F.; Elliott, J. Richard

2014-09-01

253

Sensing of 'danger signals' and pathogen-associated molecular patterns defines binary signaling pathways 'upstream' of Toll  

Microsoft Academic Search

In drosophila, molecular determinants from fungi and Gram-positive bacteria are detected by circulating pattern-recognition receptors. Published findings suggest that such pattern-recognition receptors activate as-yet-unidentified serine-protease cascades that culminate in the cleavage of Spätzle, the endogenous Toll receptor ligand, and trigger the immune response. We demonstrate here that the protease Grass defines a common activation cascade for the detection of fungi

Laure El Chamy; Vincent Leclerc; Isabelle Caldelari; Jean-Marc Reichhart

2008-01-01

254

A domain decomposition molecular dynamics program for the simulation of flexible molecules with an arbitrary topology of Lennard-Jones and/or Gay-Berne sites  

NASA Astrophysics Data System (ADS)

We describe a new parallel molecular dynamics program GBMOLDD which uses the domain decomposition algorithm. The program is designed to simulate molecular systems composed of both spherically-symmetric and anisotropic sites connected via arbitrary topology and described by standard force fields. The program is oriented mainly towards simulations of liquid crystalline systems including mixtures of mesogenic molecules and mesogens confined in host media. Benchmark results are presented for a model liquid crystal dimer composed of two mesogenic units linked via a flexible alkyl chain. The benchmarks compare favorably to those obtained via a parallel replicated data algorithm.

Ilnytskyi, Jaroslav; Wilson, Mark R.

2001-02-01

255

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)

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.

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

2013-06-01

256

Influence of the molecular-scale structures of 1-dodecanethiol and 4-methylbenzenethiol self-assembled monolayers on gold nanoparticles adsorption pattern.  

PubMed

In an effort to understand the effects of the molecular structures of self-assembled monolayers on the patterns formed by immobilized Au nanoparticles (AuNPs), we characterized and compared the morphologies and properties of AuNPs adsorbed onto self-assembled monolayers formed by 1-dodecanethiol (DDT-SAM) or 4-methylbenzenethiol (MBT-SAM) assembled on Au(111) surfaces. The AuNP adsorption pattern on the MBT-SAM surface was well-dispersed and characterized by a low degree of corrugation. By contrast, an aggregated and highly corrugated AuNP pattern was observed on the surface of the DDT-SAM. This difference was attributed to the retention or removal of citrate anions present on the AuNPs during adsorption onto the SAM surface. Direct interactions between the AuNPs and the highly corrugated hydrophobic surfaces of the DDT-SAMs could strip the citrate layers from the AuNP surfaces, leading to aggregated adsorption. The water molecules appeared to mediate the adsorption of the AuNPs by reducing the hydrophobicity of the MBT-SAM surface and promoting a more dispersed adsorption configuration. PMID:24776667

Mamun, Abdulla Hel Al; Yoon, Sangwoon; Hahn, Jae Ryang

2014-07-01

257

Inorganic Molecules; A Visual Database  

NSDL National Science Digital Library

Inorganic Molecules: A Visual Data Base contains text and graphics describing 66 molecules and ions commonly used as examples in general chemistry courses. For each molecule, fifteen molecular properties are presented visually by eight or nine different molecular models created by the CAChe Scientific Molecular Modeling program.

258

Strontium mono-chloride - A new molecule for the determination of chlorine using high-resolution graphite furnace molecular absorption spectrometry and direct solid sample analysis  

NASA Astrophysics Data System (ADS)

A new method has been developed for the determination of chlorine in biological reference materials using high-resolution continuum source graphite furnace molecular absorption spectrometry (HR-CS GF MAS) of the strontium mono-chloride (SrCl) molecule and direct solid sample analysis. The use of the SrCl molecule for high-temperature MAS was not described up to now in the literature. Preliminary time-dependent density functional theory calculations of the SrCl structure were carried out in order to obtain reasonable estimates of the absorption spectrum of the target molecule. The calculations, which were carried out at BHandHLyp/def2-QZVP level of theory, proved a very accurate and inexpensive way to get information about the spectrum of the SrCl molecule, which enabled us to perform the Cl determination with good sensitivity and specificity. The molecular absorption of the SrCl molecule has been measured using the wavelength at 635.862 nm, and zirconium and palladium have been evaluated as the chemical modifiers in order to increase the sensitivity of the gaseous SrCl molecule generated in the graphite furnace. The pyrolysis and vaporization temperatures were 600 °C and 2300 °C, respectively. Accuracy and precision of the method have been evaluated using biological certified reference materials of both animal and plant origins, showing good agreement with the informed and certified values. Limit of detection and characteristic mass were 1.0 and 2.2 ng, respectively. The results found using HR-CS GF MAS were in agreement (95% confidence level) compared to those obtained by electrothermal vaporization-inductively coupled plasma mass spectrometry.

Pereira, Éderson R.; Welz, Bernhard; Lopez, Alfredo H. D.; de Gois, Jefferson S.; Caramori, Giovanni F.; Borges, Daniel L. G.; Carasek, Eduardo; de Andrade, Jailson B.

2014-12-01

259

Patterns of integration of DNA microinjected into cultured mammalian cells: evidence for homologous recombination between injected plasmid DNA molecules.  

PubMed

We examined the fate of DNA microinjected into nuclei of cultured mammalian cells. The sequence composition and the physical form of the vector carrying the selectable gene affected the efficiency of DNA-mediated transformation. Introduction of sequences near the simian virus 40 origin of DNA replication or in the long terminal repeat of avian sarcoma provirus into a recombinant plasmid containing the herpes simplex virus thymidine kinase gene. (pBR322/HSV-tk) enhanced the frequency of transformation of LMtk- and RAT-2tk- cells to the TK+ phenotype 20- to 40-fold. In cells receiving injections of only a few plasmid DNA molecules, the transformation frequency was 40-fold higher after injection of linear molecules than after injection of supercoiled molecules. By controlling the number of gene copies injected into a recipient cell, we could obtain transformants containing a single copy or as many as 50 to 100 copies of the selectable gene. Multiple copies of the transforming gene were not scattered throughout the host genome but were integrated as a concatemer at one or a very few sites in the host chromosome. Independent transformants contained the donated genes in different chromosomes. The orientation of the gene copies within the concatemer was not random; rather, the copies were organized as tandem head-to-tail arrays. By analyzing transformants obtained by coinjecting two vectors which were identical except that in one a portion of the vector was inverted, we were able to conclude that the head-to-tail concatemers were generated predominantly by homologous recombination. Surprisingly, these head-to-tail concatemers were found in transformants obtained by injecting either supercoiled or linear plasmid DNA. Even though we demonstrated that cultured mammalian cells contain the enzymes for ligating two DNA molecules very efficiently irrespective of the sequences or topology at their ends, we found that even linear plasmid DNA was recruited into the concatemer by homologous recombination. PMID:6298598

Folger, K R; Wong, E A; Wahl, G; Capecchi, M R

1982-11-01

260

Spin relaxation of fullerene C70 photoexcited triplet in molecular glasses: Evidence for onset of fast orientational motions of molecules in the matrix near 100 K  

NASA Astrophysics Data System (ADS)

Electron spin echo (ESE) was applied to study transversal spin relaxation of photoexcited triplet state of fullerene C70 molecules in glassy o-terphenyl and cis-/trans-decalin matrices (glass transition temperatures of 243 and 137 K, respectively). The relaxation rate T2-1 was found to increase sharply above 110 K in o-terphenyl and above 100 K in decalin. It is suggested that this increase arises from interaction of 3C70 pseudorotation with fast molecular librations in the matrix. Both these types of motion involve atomic vibrations and are uniaxial in their nature, the known literature data on Raman light scattering and others indicate that molecular librations may be thermally activated in glasses just near 100 K. The increase in T2-1 near 100 K is not observed for photoexcited triplet state of fullerene C60, for which pseudorotation is not uniaxial. As the fullerene molecule has a size much larger than that for glass solvent molecules, it is likely that molecular librations in the matrix are of collective nature.

Uvarov, Mikhail N.; Kulik, Leonid V.; Dzuba, Sergei A.

2009-10-01

261

Moving Molecules!  

NSDL National Science Digital Library

In this activity about molecular diffusion (located on page 2 of the PDF), learners will make predictions and move molecules of iodine through a seemingly solid plastic sandwich bag. The process of diffusion will be visually indicated by a color change when the iodine reacts with starch inside the bag. Information in the resource explains how this activity relates to nanoparticles and research. Related to linked video, DragonflyTV Nano: Nanosilver.

Twin Cities Public Television, Inc.

2008-01-01

262

Spectroscopic and Theoretical Study on the Structures and Dynamics of Functional Molecules - Towards AN Understanding of the Molecular Recognition for Encapsulation Complexes  

NASA Astrophysics Data System (ADS)

Functional molecules, such as crown ethers and calixarenes, can act as hosts for encapsulating guest species through non-covalent interactions. Applications of crown ethers and calixarenes as molecular receptors, metal cation extraction agents, fluoro-ionophores and phase transfer catalytic media have been previously reported in a number of studies in the literature. One of the important aspects of these host/guest molecular assemblies is their selectivity in the encapsulation of guest species. Two important factors that control this selectivity are: (1) the size and the flexibility of the host cavity and (2) the properties of solvent molecules. Molecular complexes formed in supersonic jets provide ideal systems for the selective study of the conformational preference and micro-solvated effects under solvent-controlled conditions. This talk will review our spectroscopic and theoretical studies of the structures of dibenzo-18-crown-6-ether (DB18C6), benzo-18-crown-6-ether (B18C6), calix[4]arene (C4A) and their complexes with guest molecules. We apply laser-induced fluorescence (LIF), resonance enhanced two-photon ionization (R2PI) and UV-UV hole-burning (HB) spectroscopy for obtaining electronic spectra and IR-UV doubleresonance and IR photodissociation (IRPD) spectroscopy for the IR spectra. The electronic and IR spectra are compared with the corresponding results obtained by DFT calculations and high-level first principles electronic structure calculations [MP2 and CCSD(T)]. Based on these joint studies we can elucidate the nature of interactions that control the encapsulation of a guest molecular species as well as how the host can adjust its conformation to accommodate a specific guest, leading to the molecular recognition.

Ebata, Takayuki; Kusaka, Ryoji; Inokuchi, Yoshiya; Xantheas, Sotiris S.

2011-06-01

263

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

PubMed Central

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

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

2014-01-01

264

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

PubMed

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

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

2014-01-01

265

Simulation of single DNA molecule stretching and immobilization in a de-wetting two-phase flow over micropillar-patterned surface  

PubMed Central

We investigate single DNA stretching dynamics in a de-wetting flow over micropillars using Brownian dynamics simulation. The Brownian dynamics simulation is coupled with transient flow field computation through a numerical particle tracking algorithm. The droplet formation on the top of the micropillar during the de-wetting process creates a flow pattern that allows DNA to stretch across the micropillars. It is found that DNA nanowire forms if DNA molecules could extend across the stagnation point inside the connecting water filament before its breakup. It also shows that DNA locates closer to the top wall of the micropillar has higher chance to enter the flow pattern of droplet formation and thus has higher chance to be stretched across the micropillars. Our simulation tool has the potential to become a design tool for DNA manipulation in complex biomicrofluidic devices. PMID:24404023

Liao, Wei-Ching; Hu, Xin; Wang, Weixiong; James Lee, L.

2013-01-01

266

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

PubMed

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. PMID:24007119

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

2013-08-01

267

Oxaliplatin induces different cellular and molecular chemoresistance patterns in colorectal cancer cell lines of identical origins  

PubMed Central

Background Cancer cells frequently adopt cellular and molecular alterations and acquire resistance to cytostatic drugs. Chemotherapy with oxaliplatin is among the leading treatments for colorectal cancer with a response rate of 50%, inducing intrastrand cross-links on the DNA. Despite of this drug’s efficiency, resistance develops in nearly all metastatic patients. Chemoresistance being of crucial importance for the drug’s clinical efficiency this study aimed to contribute to the identification and description of some cellular and molecular alterations induced by prolonged oxaliplatin therapy. Resistance to oxaliplatin was induced in Colo320 (Colo320R) and HT-29 (HT-29R) colorectal adenocarcinoma cell lines by exposing the cells to increasing concentrations of the drug. Alterations in morphology, cytotoxicity, DNA cross-links formation and gene expression profiles were assessed in the parental and resistant variants with microscopy, MTT, alkaline comet and pangenomic microarray assays, respectively. Results Morphology analysis revealed epithelial-to-mesenchymal transition in the resistant vs parental cells suggesting alterations of the cells’ adhesion complexes, through which they acquire increased invasiveness and adherence. Cytotoxicity measurements demonstrated resistance to oxaliplatin in both cell lines; Colo320 being more sensitive than HT-29 to this drug (P?molecular chemoresistance patterns induced by prolonged treatment with oxaliplatin in cell lines with identical origins (colorectal adenocarcinomas). PMID:23865481

2013-01-01

268

Molecular characterization, phylogeny, and expression pattern of c-type lysozyme in kelp grouper, Epinephelus bruneus.  

PubMed

Lysozymes are the key molecules in innate immune system and possess high bactericidal properties. In the present study, a full-length c-type lysozyme cDNA has been cloned and characterized by expressed sequence tag (EST) and rapid amplification of cDNA ends (RACE) techniques from kelp grouper, Epinephelus bruneus (Eb-CTL). The cDNA consists of 753 base pairs (bp) with a 432 bp open reading frame (ORF) that encodes 144 amino acids (aa) residues and polyadenylation signal sequence AATAAA. The deduced aa sequence polypeptide had a predicted molecular weight of 16 kDa and theoretical isoelectric point of 7.3. The deduced aa sequence have a long lysozyme domain which contains all catalytic sites and other conserved residues required for lysozyme activity. Pair-wise alignments showed a higher identity (76.4%) with Psetta maxima lysozyme and low identity (38.9%) with lysozymes of insect Bombyx mori. Interestingly, phylogenetic analysis revealed that the kelp grouper lysozyme was more closely related to other fish and vertebrate lysozymes. Quantitative real-time reverse transcriptase-PCR analysis showed that Eb-CTL transcripts are constitutively expressed in hematopoietic organs such as heart, spleen, and kidney after stimulation with LPS or infection with Vibrio anguillarum, indicating the involvement of Eb-CTL in the innate immunity of kelp grouper. This study is a first step on the genetics and functions of the c-type lysozyme in kelp grouper, and their role in anti-bacterial activity with reference to immunological properties which might have biotechnological applications. PMID:21752343

Harikrishnan, Ramasamy; Kim, Ju-Sang; Kim, Man-Chul; Balasundaram, Chellam; Heo, Moon-Soo

2011-10-01

269

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

PubMed Central

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 behaviour 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 spatio-temporal 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 towards the anatomical needs of the host organism is electrical; this blurs the line between memory and decision-making in neural networks and morphogenesis in non-neural 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

Levin, Michael

2013-01-01

270

Entropy-driven pattern formation of hybrid vesicular assemblies made from molecular and nanoparticle amphiphiles.  

PubMed

Although an analogy has been drawn between them, organic molecular amphiphiles (MAMs) and inorganic nanoparticle (NP) amphiphiles (NPAMs) are significantly different in dimension, geometry, and composition as well as their assembly behavior. Their concurrent assembly can synergetically combine the inherent properties of both building blocks, thus leading to new hybrid materials with increasing complexity and functionality. Here we present a new strategy to fabricate hybrid vesicles with well-defined shape, morphology, and surface pattern by coassembling MAMs of block copolymers (BCPs) and NPAMs comprising inorganic NPs tethered with amphiphilic BCPs. The assembly of binary mixtures generated unique hybrid Janus-like vesicles with different shapes, patchy vesicles, and heterogeneous vesicles. Our experimental and computational studies indicate that the different nanostructures arise from the delicate interplay between the dimension mismatch of the two types of amphiphiles, the entanglement of polymer chains, and the mobility of NPAMs. In addition, the entropic attraction between NPAMs plays a dominant role in controlling the lateral phase separation of the two types of amphiphiles in the membranes. The ability to utilize multiple distinct amphiphiles to construct discrete assemblies represents a promising step in the self-assembly of structurally complex functional materials. PMID:24447129

Liu, Yijing; Li, Yanchun; He, Jie; Duelge, Kaleb John; Lu, Zhongyuan; Nie, Zhihong

2014-02-12

271

Formation of Ga droplets on patterned GaAs (100) by molecular beam epitaxy  

PubMed Central

In this paper, the formation of Ga droplets on photo-lithographically patterned GaAs (100) and the control of the size and density of Ga droplets by droplet epitaxy using molecular beam epitaxy are demonstrated. In extension of our previous result from the journal Physical Status Solidi A, volume 209 in 2012, the sharp contrast of the size and density of Ga droplets is clearly observed by high-resolution scanning electron microscope, atomic force microscope, and energy dispersive X-ray spectrometry. Also, additional monolayer (ML) coverage is added to strength the result. The density of droplets is an order of magnitude higher on the trench area (etched area), while the size of droplets is much larger on the strip top area (un-etched area). A systematic variation of ML coverage results in an establishment of the control of size and density of Ga droplets. The cross-sectional line profile analysis and root mean square roughness analysis show that the trench area (etched area) is?approximately?six times rougher. The atomic surface roughness is suggested to be the main cause of the sharp contrast of the size and density of Ga droplets and is discussed in terms of surface diffusion. PMID:23033893

2012-01-01

272

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

PubMed Central

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 ?-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

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

2010-01-01

273

Innate immune responses activated in Arabidopsis roots by microbe-associated molecular patterns.  

PubMed

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 beta-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

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

2010-03-01

274

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

PubMed Central

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

Ramirez-Gomez, Francisco; Aponte-Rivera, Francisco; Mendez-Castaner, Lumen; Garcia-Arraras, Jose E.

2010-01-01

275

IONIZATION OF NITROGEN MOLECULES BY NITROGEN MOLECULES  

Microsoft Academic Search

The ionization cross section for Nâ molecules on impact with N\\/sub ; 2\\/ molecules was measured over the laboratory energy range from 30 to 1000 ev. ; The incident molecular beam was produced by the technique of ionization by ; electron impact, electrostatic acceleration and neutralization by charge transfer. ; The measurements were carried out in a low-pressure parallel plate

Nyle Utterback; Glenn Miller

1961-01-01

276

Microbe associated molecular patterns from rhizosphere bacteria trigger germination and Papaver somniferum metabolism under greenhouse conditions.  

PubMed

Ten PGPR from different backgrounds were assayed on Papaver somniferum var. Madrigal to evaluate their potential as biotic elicitors to increase alkaloid content under the rationale that some microbe associated molecular patterns (MAMPs) are able to trigger plant metabolism. First, the 10 strains and their culture media at two different concentrations were tested for their ability to trigger seed germination. Then, the best three strains were tested for their ability to increase seedling growth and alkaloid levels under greenhouse conditions. Only three strains and their culture media enhanced germination. Then, germination enhancing capacity of these best three strains, N5.18 Stenotrophomonas maltophilia, Aur9 Chryseobacterium balustinum and N21.4 Pseudomonas fluorescens was evaluated in soil. Finally, the three strains were applied on seedlings at two time points, by soil drench or by foliar spray. Photosynthesis was measured, plant height was recorded, capsules were weighted and alkaloids analyzed by HPLC. Only N5.18 delivered by foliar spray significantly increased plant height coupled to an increase in total alkaloids and a significant increase in opium poppy straw dry weight; these increases were supported by a better photosynthetic efficiency. The relative contents of morphine, thebaine, codeine and oripavine were affected by this treatment causing a significant increase in morphine coupled to a decrease in thebaine, demonstrating the effectivity of MAMPs from N5.18 in this plant species. Considering the increase in capsule biomass and alkaloids together with the acceleration of germination, strain N5.18 appears as a good candidate to elicit plant metabolism and consequently, to increase productivity of Papaver somniferum. PMID:24296249

Bonilla, A; Sarria, A L F; Algar, E; Muñoz Ledesma, F J; Ramos Solano, B; Fernandes, J B; Gutierrez Mañero, F J

2014-01-01

277

Danger-associated molecular patterns and danger signals in idiopathic pulmonary fibrosis.  

PubMed

The chronic debilitating lung disease, idiopathic pulmonary fibrosis (IPF), is characterized by a progressive decline in lung function, with a median mortality rate of 2-3 years after diagnosis. IPF is a disease of unknown cause and progression, and multiple pathways have been demonstrated to be activated in the lungs of these patients. A recent genome-wide association study of more than 1,000 patients with IPF identified genes linked to host defense, cell-cell adhesion, and DNA repair being altered due to fibrosis (Fingerlin, et al. Nat Genet 2013;45:613-620). Further emerging data suggest that the respiratory system may not be a truly sterile environment, and it exhibits an altered microbiome during fibrotic disease (Molyneaux and Maher. Eur Respir Rev 2013;22:376-381). These altered host defense mechanisms might explain the increased susceptibility of patients with IPF to microbial- and viral-induced exacerbations. Moreover, chronic epithelial injury and apoptosis are key features in IPF, which might be mediated, in part, by both pathogen-associated (PA) and danger-associated molecular patterns (MPs). Emerging data indicate that both PAMPs and danger-associated MPs contribute to apoptosis, but not necessarily in a manner that allows for the removal of dying cells, without further exacerbating inflammation. In contrast, both types of MPs drive cellular necrosis, leading to an exacerbation of lung injury and/or infection as the debris promotes a proinflammatory response. Thus, this Review focuses on the impact of MPs resulting from infection-driven apoptosis and necrosis during chronic fibrotic lung disease. PMID:24749648

Ellson, Christian D; Dunmore, Rebecca; Hogaboam, Cory M; Sleeman, Matthew A; Murray, Lynne A

2014-08-01

278

Hierarchy and roles of pathogen-associated molecular pattern-induced responses in Nicotiana benthamiana.  

PubMed

Our current understanding of pathogen-associated molecular pattern (PAMP)-triggered immunity signaling pathways in plants is limited due to the redundancy of several components or the lethality of mutants in Arabidopsis (Arabidopsis thaliana). To overcome this, we used a virus-induced gene silencing-based approach in combination with pharmacological studies to decipher links between early PAMP-triggered immunity events and their roles in immunity following PAMP perception in Nicotiana benthamiana. Two different calcium influx inhibitors suppressed the reactive oxygen species (ROS) burst: activation of the mitogen-activated protein kinases (MAPKs) and PAMP-induced gene expression. The calcium burst was unaffected in plants specifically silenced for components involved in ROS generation or for MAPKs activated by PAMP treatment. Importantly, the ROS burst still occurred in plants silenced for the two major defense-associated MAPK genes NbSIPK (for salicylic acid-induced protein kinase) and NbWIPK (for wound-induced protein kinase) or for both genes simultaneously, demonstrating that these MAPKs are dispensable for ROS production. We further show that NbSIPK silencing is sufficient to prevent PAMP-induced gene expression but that both MAPKs are required for bacterial immunity against two virulent strains of Pseudomonas syringae and their respective nonpathogenic mutants. These results suggest that the PAMP-triggered calcium burst is upstream of separate signaling branches, one leading to MAPK activation and then gene expression and the other to ROS production. In addition, this study highlights the essential roles of NbSIPK and NbWIPK in antibacterial immunity. Unexpectedly, negative regulatory mechanisms controlling the intensity of the PAMP-triggered calcium and ROS bursts were also revealed by this work. PMID:21478366

Segonzac, Cécile; Feike, Doreen; Gimenez-Ibanez, Selena; Hann, Dagmar R; Zipfel, Cyril; Rathjen, John P

2011-06-01

279

Selective catalysts for the hydrogen oxidation and oxygen reduction reactions by patterning of platinum with calix[4]arene molecules  

NASA Astrophysics Data System (ADS)

The design of new catalysts for polymer electrolyte membrane fuel cells must be guided by two equally important fundamental principles: optimization of their catalytic behaviour as well as the long-term stability of the metal catalysts and supports in hostile electrochemical environments. The methods used to improve catalytic activity are diverse, ranging from the alloying and de-alloying of platinum to the synthesis of platinum core-shell catalysts. However, methods to improve the stability of the carbon supports and catalyst nanoparticles are limited, especially during shutdown (when hydrogen is purged from the anode by air) and startup (when air is purged from the anode by hydrogen) conditions when the cathode potential can be pushed up to 1.5V (ref. 11). Under the latter conditions, stability of the cathode materials is strongly affected (carbon oxidation reaction) by the undesired oxygen reduction reaction (ORR) on the anode side. This emphasizes the importance of designing selective anode catalysts that can efficiently suppress the ORR while fully preserving the Pt-like activity for the hydrogen oxidation reaction. Here, we demonstrate that chemically modified platinum with a self-assembled monolayer of calix[4]arene molecules meets this challenging requirement.

Genorio, Bostjan; Strmcnik, Dusan; Subbaraman, Ram; Tripkovic, Dusan; Karapetrov, Goran; Stamenkovic, Vojislav R.; Pejovnik, Stane; Markovi?, Nenad M.

2010-12-01

280

Molecular preservation by extraction and fixation, mPREF: a method for small molecule biomarker analysis and histology on exactly the same tissue  

PubMed Central

Background Histopathology is the standard method for cancer diagnosis and grading to assess aggressiveness in clinical biopsies. Molecular biomarkers have also been described that are associated with cancer aggressiveness, however, the portion of tissue analyzed is often processed in a manner that is destructive to the tissue. We present here a new method for performing analysis of small molecule biomarkers and histology in exactly the same biopsy tissue. Methods Prostate needle biopsies were taken from surgical prostatectomy specimens and first fixed, each in a separate vial, in 2.5 ml of 80% methanol:water. The biopsies were fixed for 24 hrs at room temperature and then removed and post-processed using a non-formalin-based fixative (UMFIX), embedded, and analyzed by hematoxylin and eosin (H&E) and by immunohistochemical (IHC) staining. The retained alcohol pre-fixative was analyzed for small molecule biomarkers by mass spectrometry. Results H&E analysis was successful following the pre-fixation in 80% methanol. The presence or absence of tumor could be readily determined for all 96 biopsies analyzed. A subset of biopsy sections was analyzed by IHC, and cancerous and non-cancerous regions could be readily visualized by PIN4 staining. To demonstrate the suitability for analysis of small molecule biomarkers, 28 of the alcohol extracts were analyzed using a mass spectrometry-based metabolomics platform. All extracts tested yielded successful metabolite profiles. 260 named biochemical compounds were detected in the alcohol extracts. A comparison of the relative levels of compounds in cancer containing vs. non-cancer containing biopsies showed differences for 83 of the compounds. A comparison of the results with prior published reports showed good agreement between the current method and prior reported biomarker discovery methods that involve tissue destructive methods. Conclusions The Molecular Preservation by Extraction and Fixation (mPREF) method allows for the analysis of small molecule biomarkers from exactly the same tissue that is processed for histopathology. PMID:22188997

2011-01-01

281

Small molecule chemokine mimetics suggest a molecular basis for the observation that CXCL10 and CXCL11 are allosteric ligands of CXCR3  

PubMed Central

BACKGROUND AND PURPOSE The chemokine receptor CXCR3 directs migration of T-cells in response to the ligands CXCL9/Mig, CXCL10/IP-10 and CXCL11/I-TAC. Both ligands and receptors are implicated in the pathogenesis of inflammatory disorders, including atherosclerosis and rheumatoid arthritis. Here, we describe the molecular mechanism by which two synthetic small molecule agonists activate CXCR3. EXPERIMENTAL APPROACH As both small molecules are basic, we hypothesized that they formed electrostatic interactions with acidic residues within CXCR3. Nine point mutants of CXCR3 were generated in which an acidic residue was mutated to its amide counterpart. Following transient expression, the ability of the constructs to bind and signal in response to natural and synthetic ligands was examined. KEY RESULTS The CXCR3 mutants D112N, D195N and E196Q were efficiently expressed and responsive in chemotaxis assays to CXCL11 but not to CXCL10 or to either of the synthetic agonists, confirmed with radioligand binding assays. Molecular modelling of both CXCL10 and CXCR3 suggests that the small molecule agonists mimic a region of the ‘30s loop’ (residues 30–40 of CXCL10) which interacts with the intrahelical CXCR3 residue D112, leading to receptor activation. D195 and E196 are located in the second extracellular loop and form putative intramolecular salt bridges required for a CXCR3 conformation that recognizes CXCL10. In contrast, CXCL11 recognition by CXCR3 is largely independent of these residues. CONCLUSION AND IMPLICATIONS We provide here a molecular basis for the observation that CXCL10 and CXCL11 are allosteric ligands of CXCR3. Such findings may have implications for the design of CXCR3 antagonists. LINKED ARTICLE This article is commented on by O'Boyle, pp. 895–897 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01759.x PMID:21895630

Nedjai, Belinda; Li, Hubert; Stroke, Ilana L; Wise, Emma L; Webb, Maria L; Merritt, J Robert; Henderson, Ian; Klon, Anthony E; Cole, Andrew G; Horuk, Richard; Vaidehi, Nagarajan; Pease, James E

2012-01-01

282

Charge Storage Behavior of Nanowire Transistors Functionalized with Bis(terpyridine)-Fe(II) Molecules: Dependence on Molecular Structure  

E-print Network

, Daihua Zhang, Jie Han, M. Meyyappan, and Chongwu Zhou*, Center for Nanotechnology, NASA Ames Research,11 The molecular coverage density was measured using a quartz crystal microbalance (QCM) to be 5.2, 5.1, and 6

Zhou, Chongwu

283

Force Spectroscopy with a Small Dithering of AFM Tip: A Method of Direct and Continuous Measurement of the Spring Constant of Single Molecules and Molecular Complexes  

PubMed Central

A new method of direct and continuous measurement of the spring constant of single molecule or molecular complex is elaborated. To that end the standard force spectroscopy technique with functionalized tips and samples is combined with a small dithering of the tip. The change of the dithering amplitude as a function of the pulling force is measured to extract the spring constant of the complex. The potentialities of this method are illustrated for the experiments with single bovine serum albumin—its polyclonal antibody (Ab-BSA) and fibrinogen—fibrinogen complexes. PMID:14747352

Chtcheglova, Lilia A.; Shubeita, George T.; Sekatskii, Sergey K.; Dietler, Giovanni

2004-01-01

284

An application of a statistical model for the calculation of the logarithmic mean excitation energy of molecules Molecular hydrogen  

NASA Technical Reports Server (NTRS)

A statistical model, the local plasma approximation, is considered for the calculation of the logarithmic mean excitation energy for stopping power of chemically bound particles by taking into consideration chemical bonding. This statistical model is applied to molecular hydrogen and leads to results that suggest a value for the logarithmic mean excitation energy of molecular hydrogen that is larger than the accepted experimental and theoretical values.

Kamaratos, E.

1985-01-01

285

Synthesis of new type of dendritic molecule and its columnar self-assembly having a potential as molecular cavity  

NASA Astrophysics Data System (ADS)

In this study, we synthesized the first generation aromatic polyamide dendron having one trioxyethylene chain at the top of the dendron and six octadecyl chains at the other terminals. This material forms two types of crystals, K 1 and K 2 crystals. The K 1 crystal is obtained on cooling from the isotropic melt at a normal rate, while the K 2 crystal grows only when the isotropic melt is retained at around 70 °C for long duration, i.e. 1 day. The K 2 crystal melts at 78 °C which is higher than 59 °C of the K 1 crystal, and has a well-defined packing structure with a huge hexagonal lattice ( a= b=69.8 and c=4.24 Å) that includes five molecules. Such a characteristic hexagonal structure is produced by a columnar association of molecules, in such a way that five molecules aggregate to form a disk, the disks are stacked into a column and the columns are packed into a hexagonal lattice. The microsegregation of chemically different components is responsible for the columnar association of molecules since in this column aromatic groups construct the cylindrical core tube with hydrophilic trioxyethylene chains inside and hydrophilic alkyl tail groups outside the tube.

Fu, K.; Nakasugi, S.; Takagawara, Y.; Li, L.; Hayakawa, T.; Jikei, M.; Tokita, M.; Kakimoto, M.; Watanabe, J.

2005-04-01

286

EXPRESSION OF PATTERN IN PLANTS: COMBINING MOLECULAR AND CALCULUS-BASED BIOPHYSICAL PARADIGMS1  

Microsoft Academic Search

Pattern formation in plant meristems occurs across a broad scale. At the topographical level (large scale), tissue folding in the meristem is responsible for the initiation of new organs in specific phyllotactic patterns and also determines organ shape. At the cellular level (small scale), oriented cell division and microtubule-based cellulose reinforcement control cell pattern and growth direction. I argue here

PAUL B. GREEN

287

Cellular/Molecular The Endurance and Selectivity of Spatial Patterns of  

E-print Network

potentiation/depression (LTP/LTD), and negative-feedback, homeostatic synaptic plasticity (HSP). A detailed may have an important role in selecting which spatial patterns of LTP/LTD are to last. Several spatial pattern of LTP/LTD. Under a local dendritic HSP mechanism, sparse patterns of LTP/LTD, which we

Segev, Idan

288

MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns  

PubMed Central

Macrophage C-type lectin (MCL) and macrophage inducible C-type lectin (Mincle) comprise part of an extensive repertoire of pattern recognition receptors with the ability to sense damage-associated and pathogen-associated molecular patterns. In this review, we cover the discovery and molecular characterization of these C-type lectin receptors, and highlight recent advances in the understanding of their roles in orchestrating the response of the immune system to bacterial and fungal infection, and damaged self. We also discuss the identification and structure–activity relationships of activating ligands, particularly trehalose dimycolate and related mycobacterial glycolipids, which have significant potential in the development of TH1/TH17 vaccination strategies. PMID:25002863

Richardson, Mark B.; Williams, Spencer J.

2014-01-01

289

Interaction of para-tert-butylcalix[6]arene molecules in Langmuir films with cadmium ions and their effects on molecular conformation and surface potential.  

PubMed

In this paper, we employ the surface-specific polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) and sum-frequency generation (SFG) methods with surface pressure and surface potential isotherms to determine the organization of p-tert-butylcalix[6]arene molecules and their interaction with Cd(2+) ions in Langmuir monolayers. The area per molecule was estimated to be 135 Å(2), which corresponds to the Calix6 axis perpendicular to the air-water interface with most OH groups parallel to the interface. This area is larger than predicted by molecular modeling with quantum chemical calculations with a PM3 Hamiltonian (109 Å(2)), which is ascribed to the repulsion between Calix6 molecules. The incorporation of Cd(2+) ions in the subphase leads to drastic changes in the dipole moment contribution of the monolayer surface potential. Rather than increasing with incorporation of Cd(2+) ions owing to a decrease in the negative double-layer potential, the measured surface potential decreased monotonically with increasing ion concentration. This unexpected result was ascribed to a strong interaction with Cd(2+) ions that induced the calyx of the molecule to adopt a more open conformation at the air/water interface and affected the orientation of hydration water molecules, according to the SFG data. This finding allows us to understand the reason why the Gouy-Chapman model fails to explain surface potential results for subphases containing divalent or trivalent ions, and may be relevant for the application of calixarenes in sensing. PMID:25360537

Wrobel, Ellen C; Santos, Poliana M; Lazzarotto, Márcio; Oliveira, Osvaldo N; Uehara, Thiers M; Miranda, Paulo B; Caseli, Luciano; Garcia, Jarem R; de Lázaro, Sérgio R; Camilo, Alexandre; Wohnrath, Karen

2014-12-21

290

Role of hydrogen bonds in molecular packing of photoreactive crystals: templating photodimerization of protonated stilbazoles in crystalline state with a combination of water molecules and chloride ions.  

PubMed

A difference in photobehavior and molecular packing between hydrated and anhydrous crystals of protonated trans-stilbazoles has been identified. While stilbazoles are not photoreactive in the crystalline state, upon protonation with HCl in the solid state they dimerized to a single dimer (anti-head-tail) when exposed to UV light. In these photoreactive crystals the protonated stilbazole molecules are arranged in a ladder-like format with the rungs made up of water molecules and chloride ions. A combination of water and chloride ion holds the protonated trans-stilbazoles through either N-HO or N-HCl(-) interactions. Anhydrous protonated stilbazole crystals prepared by heating the 'wet' crystals under reduced pressure were inert upon exposure to UV light. As per X-ray crystal structure analyses these light stable crystals did not contain water molecules in their lattice. The current investigation has established that water molecules are essential for photodimerization of crystalline protonated trans-stilbazoles. To compare the reactivity of protonated trans-stilbazoles with that of protonated cis-stilbazoles, photoreactivity and packing arrangement of cis-4-iodo stilbazole·HCl salt was examined. This molecule in the crystalline state only isomerized to the trans isomer and did not dimerize. Thus, while the trans isomer dimerized and did not isomerize, the cis isomer only isomerized and did not dimerize in the crystalline state. To probe the role of cation? interaction in the packing of protonated trans-stilbazoles, energies of various types of packing in the gas phase were estimated by MP-2 calculations and cation? interaction was found to be unimportant in the packing of protonated trans-stilbazole crystals investigated here. PMID:25096970

Mondal, Barnali; Zhang, Tingting; Prabhakar, Rajeev; Captain, Burjor; Ramamurthy, V

2014-10-15

291

Molecular eigenstate spectroscopy: Application to the intramolecular dynamics of some polyatomic molecules in the 3000 to 7000 cm{sup {minus}1} region  

SciTech Connect

Intramolecular vibrational redistribution (IVR) appears to be a universal property of polyatomic molecules in energy regions where the vibrational density of states is greater than about 5 to 30 states per cm{sup {minus}1}. Interest in IVR stems from its central importance to the spectroscopy, photochemistry, and reaction kinetics of these molecules. A bright state, {var_phi}{sub s}, which may be a C-H stretching vibration, carries the oscillator strength from the ground state. This bright state may mix with bath rotational-vibrational levels to form a clump of molecular eigenstates, each of which carries a portion of the oscillator strength from the ground state. In this work the authors explicitly resolve transitions to each of these molecular eigenstates. Detailed information about the nature of IVR is contained in the frequencies and intensities of the observed discrete transitions. The primary goal of this research is to probe the coupling mechanisms by which IVR takes place. The most fundamental distinction to be made is between anharmonic coupling which is independent of molecular rotation and rotationally-mediated coupling. The authors are also interested in the rate at which IVR takes place. Measurements are strictly in the frequency domain but information is obtained about the decay of the zero order state, {var_phi}{sub s}, which could be prepared in a hypothetical experiment as a coherent excitation of the clump of molecular eigenstates. As the coherent superposition dephases, the energy would flow from the initially prepared mode into nearby overtones and combinations of lower frequency vibrational modes. The decay of the initially prepared mode is related to a pure sequence infrared absorption spectrum by a Fourier transform.

Perry, D.S. [Univ. of Akron, OH (United States)

1993-12-01

292

Time-Resolved Electron Diffraction from Selectively Aligned Molecules  

SciTech Connect

We experimentally demonstrate ultrafast electron diffraction from transiently aligned molecules in the absence of external (aligning) fields. A sample of aligned molecules is generated through photodissociation with femtosecond laser pulses, and the diffraction pattern is captured by probing the sample with picosecond electron pulses shortly after dissociation - before molecular rotation causes the alignment to vanish. In our experiments the alignment decays with a time constant of 2.6{+-}1.2 ps.

Reckenthaeler, Peter; Krausz, Ferenc [Max-Planck-Institut fuer Quantenoptik, Hans-Kopfermann-Strasse 1, D-85748 Garching (Germany); Ludwig-Maximilians-Universitaet Muenchen, Am Coulombwall 1, D-85748 Garching (Germany); Centurion, Martin; Fuss, Werner; Trushin, Sergei A.; Fill, Ernst E. [Max-Planck-Institut fuer Quantenoptik, Hans-Kopfermann-Strasse 1, D-85748 Garching (Germany)

2009-05-29

293

Formation of molecular species of mitochondrial cardiolipin 2. A mathematical model of pattern formation by phospholipid transacylation.  

PubMed

Formation of the unique molecular species of mitochondrial cardiolipin requires tafazzin, a transacylase that exchanges acyl groups between phospholipid molecular species without strict specificity for acyl groups, head groups, or carbon positions. However, it is not known whether phospholipid transacylations can cause the accumulation of specific fatty acids in cardiolipin. Here, a model is shown in linear algebra representation, in which acyl specificity emerges from the transacylation equilibrium of multiple molecular species, provided that different species have different free energies. The model defines the conditions and energy terms, under which transacylations may generate the characteristic composition of mitochondrial cardiolipin. It is concluded that acyl-specific cardiolipin patterns could arise from phospholipid transacylations in the tafazzin domain, even if tafazzin itself does not have substrate specificity. PMID:19416646

Schlame, Michael

2009-04-01

294

Feshbach resonances, molecular bound states and prospects of ultracold molecule formation in mixtures of ultracold K and Cs  

E-print Network

We consider the possibilities for producing ultracold mixtures of K and Cs and forming KCs molecules by magnetoassociation. We carry out coupled-channel calculations of the interspecies scattering length for $^{39}$KCs, $^{41}$KCs and $^{40}$KCs and characterize Feshbach resonances due to s-wave and d-wave bound states, with widths ranging from below 1 nG to 5 G. We also calculate the corresponding bound-state energies as a function of magnetic field. We give a general discussion of the combinations of intraspecies and interspecies scattering lengths needed to form low-temperature atomic mixtures and condensates and identify promising strategies for cooling and molecule formation for all three isotopic combinations of K and Cs.

Patel, Hannah J; Cornish, Simon L; Hutson, Jeremy M

2014-01-01

295

Natural orbital functional calculations of molecular polarizabilities and second hyperpolarizabilities. The hydrogen molecule as a test case  

NASA Astrophysics Data System (ADS)

The longitudinal polarizability (?) and second hyperpolarizability (?) of the H2 molecule as a function of the internuclear distance are calculated using the PNOF5 level of theory. It is shown that PNOF5 gives accurate results for the longitudinal ? and ? over the whole curve range, even for those structures exhibiting a high degree of diradical character. The good agreement between these results and reference full-CI data highlights the adequacy of PNOF5 to treat electronic systems exhibiting large static electron correlation and shows a promising accuracy in calculating nonlinear optical properties for systems covering a large range of diradical character. The results further support the paradigm of using molecules with intermediate diradical character to enhance the second hyperpolarizabilities.

Lopez, Xabier; Piris, Mario; Nakano, Masayoshi; Champagne, Benoît

2014-01-01

296

The molecular basis for venation patterning of pigmentation and its effect on pollinator attraction in flowers of Antirrhinum.  

PubMed

Pigment stripes associated with veins (venation) is a common flower colour pattern. The molecular genetics and function of venation were investigated in the genus Antirrhinum, in which venation is determined by Venosa (encoding an R2R3MYB transcription factor). Pollinator preferences were measured by field tests with Antirrhinum majus. Venosa function was examined using in situ hybridization and transient overexpression. The origin of the venation trait was examined by molecular phylogenetics. Venation and full-red flower colouration provide a comparable level of advantage for pollinator attraction relative to palely pigmented or white lines. Ectopic expression of Venosa confers pigmentation outside the veins. Venosa transcript is produced only in small areas of the corolla between the veins and the adaxial epidermis. Phylogenetic analyses suggest that venation patterning is an ancestral trait in Antirrhinum. Different accessions of three species with full-red pigmentation with or without venation patterning have been found. Epidermal-specific venation is defined through overlapping expression domains of the MYB (myoblastoma) and bHLH (basic Helix-Loop-Helix) co-regulators of anthocyanin biosynthesis, with the bHLH providing epidermal specificity and Venosa vein specificity. Venation may be the ancestral trait, with full-red pigmentation a derived, polyphyletic trait. Venation patterning is probably not fixed once species evolve full-red floral pigmentation. PMID:21039563

Shang, Yongjin; Venail, Julien; Mackay, Steve; Bailey, Paul C; Schwinn, Kathy E; Jameson, Paula E; Martin, Cathie R; Davies, Kevin M

2011-01-01

297

Porphyrin nanofiber patterning by air/water interfacial assembly: effect of molecular structure, surface pressure, and ionic liquid doped subphase.  

PubMed

Porphyrin nanofiber patterning was generated by air/water interfacial assembly. The air/water interfacial aggregation behavior of two prophyrins, both of which contain two hydrophobic alkyl chains and two carboxylic acid substituent groups at different positions, was investigated using UV spectra, FT-IR spectra, and AFM measurements on the corresponding transferred films. The porphyrin nanofiber patterning can only be produced on ionic liquid (IL) doped water subphases by the assembly of the building blocks with two carboxylic acids located at the para-position (TPPA2b-A). The results suggest that the bulky cations of ionic liquids (ILs) can interact with the carboxylate of porphyrin electrostatically. The appropriate molecular geometries, ionic liquid (IL) doped water subphases, and relatively high surface pressures help the TPPA2b-A to form nanofiber patterns. PMID:22221339

Liu, Xufei; Wang, Tianyu; Liu, Minghua

2012-03-01

298

New application of the mechanical model of molecules. Calculation of the molecular configurations of transition metal. pi. -complexes  

SciTech Connect

The mechanical model of molecules (MMM), which makes it possible to reproduce and predict the geometric characteristics and relative energies of isomers and conformations, is widely used in the stereochemistry of organic and coordinate compounds. In this communication, the first step in extending the MMM to metal ..pi..-complexes, the authors present the result of geometry calculations of a number of such molecules. The optimal energy of ..pi..-complex molecules was obtained by minimization of the conformational energy U/sub conf/ = U/sub nov/ + U/sub bo/ + U/sub ang/ + U/sub nopl/, where U/sub nov/ is the nonvalence interaction energy calculated using the 6-exp potentials and parameters proposed by Kitaigorodskii; U/sub bo/ and U/sup ang/ are the energies of change of the bond lengths and valence angles calculated from Hooke's law; and U/sub nopl/ is the energy of violation of the planarity of the conjugated systems, in this case the cyclopentadienyl rings.

Timofeeva, T.V.; Solovokhotov, Yu.L.; Struchkov, Yu.T.

1987-12-01

299

Directional correlation between the primary particle and ejected molecular ions in electronic sputtering of large organic molecules  

NASA Astrophysics Data System (ADS)

Fission fragments from a 252Cf source and 72-MeV 127I ions from an EN-tandem accelerator have been used to sputter secondary ions electronically from samples of biomolecules like bovine insulin (5733 u). It is found that intact molecular ions of insulin are ejected from the surface at an angle which correlates with the incident ion direction. This study shows that from the ionized cylindrical region produced by the passage of a fast ion there is a direct radial momentum transfer, i.e., a nondiffusive process, which ejects large molecular ions.

Ens, Werner; Sundqvist, Bo U. R.; Hkansson, Per; Hedin, Allan; Jonsson, Gunnar

1989-01-01

300

Single-Molecule X-Ray Interferometry: Controlling Coupled Electron-Nuclear Quantum Dynamics and Imaging Molecular Potentials by Ultrahigh-Resolution Resonant Photoemission and Ab Initio Calculations  

NASA Astrophysics Data System (ADS)

This paper reports an advanced study of the excited ionic states of the gas-phase nitrogen molecule in the binding-energy region of 22-34 eV, combining ultrahigh-resolution resonant photoemission (RPE) and ab initio configuration-interaction calculations. The RPE spectra are recorded for nine photon energies within the N 1s??* absorption resonance of N2 by using a photon bandwidth that is considerably smaller than lifetime broadening, and the dependence on excitation energy of the decay spectra is analyzed and used for the first assignment of 12 highly overlapped molecular states. The effect on the RPE profile of avoided curve crossings between the final N2+ ionic states is discussed, based on theoretical simulations that account for vibronic coupling, and compared with the experimental data. By use of synchrotron radiation with high spectral brightness, it is possible to selectively promote the molecule to highly excited vibrational sublevels of a core-excited electronic state, thereby controlling the spatial distribution of the vibrational wave packets, and to accurately image the ionic molecular potentials. In addition, the mapping of the vibrational wave functions of the core-excited states using the bound final states with far-from-equilibrium bond lengths has been achieved experimentally for the first time. Theoretical analysis has revealed the rich femtosecond nuclear dynamics underlying the mapping phenomenon.

Kimberg, V.; Lindblad, A.; Söderström, J.; Travnikova, O.; Nicolas, C.; Sun, Y. P.; Gel'mukhanov, F.; Kosugi, N.; Miron, C.

2013-01-01

301

PATTERNS OF GENETIC ARCHITECTURE FOR LIFE-HISTORY TRAITS AND MOLECULAR MARKERS IN A SUBDIVIDED SPECIES  

Microsoft Academic Search

Understanding the utility and limitations of molecular markers for predicting the evolutionary potential of natural populations is important for both evolutionary and conservation genetics. To address this issue, the distribution of genetic variation for quantitative traits and molecular markers is estimated within and among 14 permanent lake populations of Daphnia pulicaria representing two regional groups from Oregon. Estimates of population

Kendall K. Morgan; Justin Hicks; Ken Spitze; Leigh Latta; Michael E. Pfrender; Casse S. Weaver; Marco Ottone; Michael Lynch

2001-01-01

302

Molecular dynamics simulation study of the ejection and transport of polymer molecules in matrix-assisted pulsed laser evaporation  

E-print Network

-assisted pulsed laser evaporation Elodie Leveugle and Leonid V. Zhigileia Department of Materials Science the regime where molecular ejection is limited to matrix evaporation from the surface up to more than twice of the simulations are related to experimental observations obtained in matrix-assisted pulsed laser evaporation

Zhigilei, Leonid V.

303

Binding of atoms and stability of molecules in Hartree and Thomas-Fermi type theories. Part I: A necessary and sufficient condition for the stability of general molecular systems  

SciTech Connect

The authors study here the binding of atoms and molecules and the stability of general molecular systems including molecular ions. This is the first paper of a series devoted to the study of these general problems. The authors obtain here a general necessary and sufficient condition for the stability of a general molecular system in the context of Thomas-Fermi-Von Weizsaecker, Thomas-Fermi-Dirac-Von Weizsaecker, Hartree or Hartree-Fock theories. 20 refs.

Catto, I.; Lions, P.L. (Universite Paris-Dauphine (France))

1992-01-01

304

Onset of Patterns in an Ocillated Granular Layer: Continuum and Molecular Dynamics Simulations  

E-print Network

waves form stripe patterns above a critical acceleration of the cell. Changing the frequency of oscillation of the cell changes the wavelength of the resulting pattern; MD and continuum simulations both.54.+r I. INTRODUCTION A. Background A successful hydrodynamic theory of granular media could allow

Texas at Austin. University of

305

Discrimination of herbal medicines by molecular spectroscopy and chemical pattern recognition  

NASA Astrophysics Data System (ADS)

The molecular spectroscopy (including near infrared diffuse reflection spectroscopy, Raman spectroscopy and infrared spectroscopy) with OPUS/Ident software was applied to clustering ginsengs according to species and processing methods. The results demonstrate that molecular spectroscopic analysis could provide a rapid, nondestructive and reliable method for identification of Chinese traditional medicine. It's found that the result of Raman spectroscopic analysis was the best one among these three methods. Comparing with traditional methods, which are laborious and time consuming, the molecular spectroscopic analysis is more effective.

Mao, Jianjiang; Xu, Jingwei

2006-10-01

306

L1 cell adhesion molecule found in human CSF varies as a function of age  

PubMed Central

Differences in the pattern and quantity of high molecular weight isoforms of L1 neural cell adhesion molecule were found between premature and term newborns compared to children and adults. These patterns were disrupted in two patients with neurologic disease. PMID:16859685

Nock, Mary L.; O'Riordan, Mary Ann; Tang, Ningfeng; Bearer, Cynthia F.

2014-01-01

307

Pores in Bilayer Membranes of Amphiphilic Molecules: Coarse-Grained Molecular Dynamics Simulations Compared with Simple Mesoscopic Models  

E-print Network

We investigate pores in fluid membranes by molecular dynamics simulations of an amphiphile-solvent mixture, using a molecular coarse-grained model. The amphiphilic membranes self-assemble into a lamellar stack of amphiphilic bilayers separated by solvent layers. We focus on the particular case of tension less membranes, in which pores spontaneously appear because of thermal fluctuations. Their spatial distribution is similar to that of a random set of repulsive hard discs. The size and shape distribution of individual pores can be described satisfactorily by a simple mesoscopic model, which accounts only for a pore independent core energy and a line tension penalty at the pore edges. In particular, the pores are not circular: their shapes are fractal and have the same characteristics as those of two dimensional ring polymers. Finally, we study the size-fluctuation dynamics of the pores, and compare the time evolution of their contour length to a random walk in a linear potential.

Claire Loison; Michel Mareschal; Friederike Schmid

2005-01-05

308

Selective binding and enrichment for low-molecular weight biomarker molecules in human plasma after exposure to nanoporous silica particles.  

PubMed

The present manuscript describes a biomarker capturing strategy based on nanoporous silica particles. The method is shown to enrich the yield of species in the low-molecular weight proteome (LMWP), allowing detection of small peptides in the low-nanomolar range. Plasma samples were exposed to the silica particles, and the captured molecular species were profiled using MALDI-TOF. Mass spectra of the silica-treated human plasma samples showed a significant enrichment in MALDI-TOF protein profiles in the LMWP. Preliminary results indicated good level of reproducibility in plasma profiles with CVs on peak heights ranging from 6.3 to 14.7%. The MALDI-TOF signature changed significantly when the characteristics of the nanoporous silica were altered. The facile sample pretreatment before MS analysis, coupled to the potential for tailoring the surface properties of silica supports, hold promise for improving the recovery of low-abundance serum biomarkers. PMID:16645983

Terracciano, Rosa; Gaspari, Marco; Testa, Flaviano; Pasqua, Luigi; Tagliaferri, Pierosandro; Cheng, Mark Ming-Cheng; Nijdam, A Jasper; Petricoin, Emanuel F; Liotta, Lance A; Cuda, Giovanni; Ferrari, Mauro; Venuta, Salvatore

2006-06-01

309

Molecular mechanisms of regeneration initiation and dorsal-ventral patterning in planarians  

E-print Network

Regeneration is widespread among animals, yet very little is known about the molecular mechanisms that govern regenerative processes. Planarians have emerged in recent years as a powerful model for studying regeneration ...

Gaviño, Michael A. (Michael Alexander)

2013-01-01

310

STUDIES OF RELATIONSHIPS BETWEEN MOLECULAR STRUCTURE AND BIOLOGICAL ACTIVITY BY PATTERN RECOGNITION METHODS  

EPA Science Inventory

The attempt to rationalize the connections between the molecular structures of organic compounds and their biological activities comprises the field of structure-activity relations (SAR) studies. Correlations between structure and activity are important for the understanding and ...

311

Isolation and Molecular Characterization of Biofouling Bacteria and Profiling of Quorum Sensing Signal Molecules from Membrane Bioreactor Activated Sludge  

PubMed Central

The formation of biofilm in a membrane bioreactor depends on the production of various signaling molecules like N-acyl homoserine lactones (AHLs). In the present study, a total of 200 bacterial strains were isolated from membrane bioreactor activated sludge and screened for AHLs production using two biosensor systems, Chromobacterium violaceum CV026 and Agrobacterium tumefaciens A136. A correlation between AHLs production and biofilm formation has been made among screened AHLs producing strains. The 16S rRNA gene sequence analysis revealed the dominance of Aeromonas and Enterobacter sp. in AHLs production; however few a species of Serratia, Leclercia, Pseudomonas, Klebsiella, Raoultella and Citrobacter were also identified. The chromatographic characterization of sludge extract showed the presence of a broad range of quorum sensing signal molecules. Further identification of sludge AHLs by thin layer chromatography bioassay and high performance liquid chromatography confirms the presence of C4-HSL, C6-HSL, C8-HSL, 3-oxo-C8-HSL, C10-HSL, C12-HSL, 3-oxo-C12-HSL and C14-HSL. The occurrence of AHLs in sludge extract and dominance of Aeromonas and Enterobacter sp. in activated sludge suggests the key role of these bacterial strains in AHLs production and thereby membrane fouling. PMID:24499972

Lade, Harshad; Paul, Diby; Kweon, Ji Hyang

2014-01-01

312

Molecular identification of Ageratum enation virus, betasatellite and alphasatellite molecules isolated from yellow vein diseased Amaranthus cruentus in India.  

PubMed

Natural occurrence of yellow vein disease on Amaranthus cruentus was observed at Lucknow, India in the year 2008. The causal virus was successfully transmitted through whiteflies (Bemisia tabaci) from diseased A. cruentus to healthy seedlings of A. cruentus and other test species which indicated begomovirus infection. The begomovirus DNA-A, betasatellite, and alphasatellite components associated with yellow vein disease were amplified by rolling circle amplification using Ø-29 DNA polymerase from diseased A. cruentus and characterized by their sequence analyses. The begomovirus DNA-A genome contained six ORFs: AV2 and AV1 in virion sense and AC3, AC2, AC1, and AC4 in complementary sense strand; and a non-translated intergenic region having the conserved geminiviral nonanucleotide sequence. The virus isolate showed 97-99% sequence identities and close phylogenetic relationships with various isolates of Ageratum enation virus (AgEV); therefore, the isolate under study was identified as AgEV. The beta- and alphasatellite molecules were also identified to be associated with the disease based on their high sequence identities and close phylogenetic relationships with the respective molecules reported worldwide. Co-infiltration of agro-infectious clones of AgEV DNA-A and its betasatellite DNA induced leaf curl and enation symptoms after 25-35 days on A. cruentus, Nicotiana benthamiana, and N. glutinosa plants. We report the association of AgEV, betasatellite and alphasatellite components with yellow vein disease of A. cruentus from India. PMID:23963765

Srivastava, Ashish; Raj, Shri Krishana; Kumar, Susheel; Snehi, Sunil Kumar; Kulshreshtha, Aditya; Hallan, Vipin; Pande, Sunil Sohanlal

2013-12-01

313

I. Microlithographic process for patterning conjugated emissive polymers. II. Fluorinated distyrylbenzene chromophores: Effect of fluorine regiochemistry on molecular properties and solid state organization  

NASA Astrophysics Data System (ADS)

Microlithographic techniques were developed for the spatially controlled light-directed synthesis of poly(p-phenylenevinylene) (PPV). Microscalar linear and circular patterns can be prepared in the 25 mum range. The procedure relies on the photogeneration of triflic acid to catalyze the formation of PPV. This site specific conversion gives complete control over pattern design and can be used to fabricate pixel-like electroluminescent devices. Microlithographic patterning of blends of poly [2-(2'-ethylhexyloxy)-5-methoxy-1,4-phenylenevinylene] (MEH-PPV) and poly(paracyclophene) was successfully used to create multi-colored emissive patterns within a continuous polymer film. Microlithographic techniques were also used to control the shapes and sizes of polymer light emitting diodes by patterning an insulating layer of novolac photoresist onto the electrode surface. A series of fluorinated distyrylbenzene (DSB) derivatives were synthesized and studied to probe the effect of fluorine substitution on molecular properties and on the arrangement of molecules in the solid state. Trans-trans-bis(4-fluorostyryl)benzene (2Ft), 1,4-bis(styryl)-2,5-difluorobenzene ( 2Fc), 1,4-bis(4-fluorostyryl)-2,5-difluorobenzene ( 2Fc2Ft), (2,5-difluorostyryl)benzene ( 4Ft), trans-trans-1,4-bis(pentaflourostyryl)-benzene ( 10Ft) and 1,4-bis(pentafluorostyryl)-2,5-difluorobenzene (2Fc10Ft) were prepared by Heck and Wittig coupling reactions. Absorption spectroscopy shows that DSB, 2F t, 2Fc, 2Fc2Ft, 4Ft, 10F t, and 2Fc10Ft have a lambda max at approximately 350 nm. Cyclic voltammetry shows that as the fluorine load increases, the reduction of the DSB framework becomes more facile. It is also shown that the regiochemistry of substitution makes an impact on the inductive ability of fluorine to facilitate reduction. The lattice properties of 2Fc, 2Fc2Ft, 4Ft, 10F t, and 2Fc10Ft were determined by X-ray diffraction experiments. Two structural motifs emerge from these studies. One is the tendency of the DSB framework to stack cofacially and form vertical "columns" within the crystal. The second motif is the alignment of these "columns" to maximize C-H···F electrostatic registry. Exciplex formation between all of the distyrylbenzene derivatives and dimethylaniline were also observed and studied spectroscopically.

Renak, Michelle Lee

314

Nitrogen-containing compounds in two CR2 meteorites: 15N composition, molecular distribution and precursor molecules  

NASA Astrophysics Data System (ADS)

Amino acids, amines and aldehydes were obtained from the water extracts of two CR2 carbonaceous chondrites from Antarctica and analyzed for their molecular and 15N isotopic content. These compounds were found to differ significantly from those of CM chondrites in both overall abundances and molecular distribution. The amino acids suites comprise a preponderant abundance of linear, 2-H amino acids, show rapid non-linear decrease with the compounds' increasing chain length and include protein amino acids never identified in meteorites before, such as threonine, tyrosine and phenylalanine. The presence of tertiary amines as well as a diverse, large abundance of aldehydes and ketones also distinguishes both CR2 organic suites. The ? 15N values determined for CR2 amino acids have a distribution between molecular subgroups that is opposite to the one of their ?D values, with 2-H amino acids having higher ? 15N and lower ?D values than 2-methyl amino acids, while the opposite is true for 2-methyl amino acids. Based on theoretical data, these isotopic findings would place the formation of the two amino acid groups or their direct precursors at different ISM stages of star formation.

Pizzarello, Sandra; Holmes, William

2009-04-01

315

Discovering Interstellar Molecules  

Microsoft Academic Search

This paper describes how high resolution spectroscopy has been the key for discovering interstellar molecules and for studying the interstellar medium. The development of radioastronomy in the 1950's has led to the detection of many interstellar molecules in the 1960s and 1970s, and the construction of a new field of research, astrochemistry. The discovery of molecular ions has confirmed the

M. Gerin

2006-01-01

316

Molecular characterization of Chilli leaf curl virus and satellite molecules associated with leaf curl disease of Amaranthus spp.  

PubMed

Amaranthus, collectively known as amaranth, is an annual or short-lived perennial plant used as leafy vegetables, cereals and for ornamental purposes in many countries including India. During 2011, leaf samples of Amaranthus plants displaying leaf curling, leaf distortion, leaf crinkling and yellow leaf margins were collected from Banswara district, Rajasthan in India. Full-length clones of a monopartite begomovirus, a betasatellite and an alphasatellite were characterized. The complete nucleotide sequence of the isolated begomovirus features as a typical 'Old World' begomovirus with the highest nucleotide per cent identity with Chilli leaf curl virus and hence, considered as an isolate of Chilli leaf curl virus. The complete nucleotide sequences of betasatellite and alphasatellite possess maximum nucleotide identity with Tomato yellow leaf curl Thailand betasatellite and Chilli leaf curl alphasatellite, respectively. This is the first report of the association of chilli-infecting begomovirus and satellite molecules infecting a new host, Amaranthus, causing leaf curl disease. PMID:24368759

George, B; Kumar, R Vinoth; Chakraborty, S

2014-04-01

317

A Family of Helminth Molecules that Modulate Innate Cell Responses via Molecular Mimicry of Host Antimicrobial Peptides  

PubMed Central

Over the last decade a significant number of studies have highlighted the central role of host antimicrobial (or defence) peptides in modulating the response of innate immune cells to pathogen-associated ligands. In humans, the most widely studied antimicrobial peptide is LL-37, a 37-residue peptide containing an amphipathic helix that is released via proteolytic cleavage of the precursor protein CAP18. Owing to its ability to protect against lethal endotoxaemia and clinically-relevant bacterial infections, LL-37 and its derivatives are seen as attractive candidates for anti-sepsis therapies. We have identified a novel family of molecules secreted by parasitic helminths (helminth defence molecules; HDMs) that exhibit similar biochemical and functional characteristics to human defence peptides, particularly CAP18. The HDM secreted by Fasciola hepatica (FhHDM-1) adopts a predominantly ?-helical structure in solution. Processing of FhHDM-1 by F. hepatica cathepsin L1 releases a 34-residue C-terminal fragment containing a conserved amphipathic helix. This is analogous to the proteolytic processing of CAP18 to release LL-37, which modulates innate cell activation by classical toll-like receptor (TLR) ligands such as lipopolysaccharide (LPS). We show that full-length recombinant FhHDM-1 and a peptide analogue of the amphipathic C-terminus bind directly to LPS in a concentration-dependent manner, reducing its interaction with both LPS-binding protein (LBP) and the surface of macrophages. Furthermore, FhHDM-1 and the amphipathic C-terminal peptide protect mice against LPS-induced inflammation by significantly reducing the release of inflammatory mediators from macrophages. We propose that HDMs, by mimicking the function of host defence peptides, represent a novel family of innate cell modulators with therapeutic potential in anti-sepsis treatments and prevention of inflammation. PMID:21589904

Hutchinson, Andrew T.; To, Joyce; Taylor, Nicole L.; Norton, Raymond S.; Perugini, Matthew A.

2011-01-01

318

VUV Photolysis of NH_3: a Matrix Isolation Study of the Molecular Interactions Between Amidogen Radical and Ammonia Molecules  

NASA Astrophysics Data System (ADS)

The presence of NH_3 in the interstellar medium is very promising in terms of possible exobiologically-relevant reactions. This is the reason why numerous laboratory investigations on reactions involving NH_3 were carried out in the context of astrochemistry. Among other reactions, the photolysis of NH_3 was widely investigated. IR spectroscopy in solid phase as well as in rare-gas matrices suggested the formation of NH_2 radicals. In most of these experiments, samples containing NH_3 were prepared at cryogenic temperatures and further irradiated. On the other hand, since the penetration of the photons inside the solid ices as well as inside matrices is limited, the concentration of the photoproducts is weak, thus hindering possible secondary reaction studies. Furthermore, in addition with ice-grain irradiations, in the interstellar clouds, the gaseous species may be subjected to irradiation during their condensation on ice grains. In order to reproduce this effect, instead of irradiating samples obtained by condensation of NH_3 or NH_3/Ne gases at low temperatures, we carried experiments in which irradiation was carried out during the sample deposition. Thus, the amidogen radical and complexes between this radical and ammonia molecules were prepared and isolated in a neon matrix. The formation of (NH_2)(NH_3), (NH_2)(NH_3)_2 and (NH_2)(NH_3)_3 was clearly established thanks to the comparison between the theoretical and the experimental vibrational frequencies. Thus, such ammonia-containing aggregates may be formed in the interstellar clouds. These complexes, as solvated radicals, may further react with carbon- and oxygen-containing species present on the surface of ice grains. Such reactions may be a first step toward the formation of prebiotic molecules.

Krim, L.; Zins, E. L.

2013-06-01

319

A theoretical and experimental study on the molecular and electronic structures of artemisinin and related drug molecules  

NASA Astrophysics Data System (ADS)

The equilibrium structures of artemisinin and a selection of its derivatives (potent antimalarial drugs) have been studied with the density functional theory ansatz B3LYP. Of the five rings of the artemisinin framework, it is only the pyranose ring B that exhibits a marked conformational flexibility, especially on addition of a pendant side chain at C-10. For the derivatives, the ? isomer with the axial substituent group is found to be energetically more stable than the ? isomer with the equatorial group. The assignment of the vibrational fundamentals has been supported by calculations on related model molecules and a normal coordinate analysis. This allows for a reliable characterization of the normal modes, mainly involving the peroxide linkage, in the claimed fingerprint region of 1,2,4-trioxanes. The electronic structures have also been studied by measuring and calculating significant features of the NMR, photoelectron and electron transmission spectra. In particular, a representative set of NMR chemical shifts and nuclear spin-spin coupling constants, obtained with DFT formalisms, compares favourably with experiment and fits expectation in terms of stereoelectronic effects of the vicinal oxygen lone pairs. Based on ab initio outer valence Green's function calculations, a consistent interpretation of the uppermost bands in the photoelectron spectra of artemisinin and derivatives has been advanced. The top ionization energies reflect a complex interaction of the various oxygen lone pair orbitals. Electron transmission spectroscopy is applied for the first time to compounds containing the peroxide bond and elucidates the empty level electronic structure of artemisinin and derivatives in the 0-6 eV energy range, with the support of MO calculations and comparison with the spectra of reference molecules. Electron attachment to the lowest-lying empty ?? MO, mainly localized on the O-O bridge, occurs at an energy (1.7 eV) exceptionally low for compounds not containing third-row or heavier elements.

Galasso, V.; Kova?, B.; Modelli, A.

2007-06-01

320

TLR2, TLR4 and CD14 Recognize Venom-Associated Molecular Patterns from Tityus serrulatus to Induce Macrophage-Derived Inflammatory Mediators  

PubMed Central

Scorpion sting-induced human envenomation provokes an intense inflammatory reaction. However, the mechanisms behind the recognition of scorpion venom and the induction of mediator release in mammalian cells are unknown. We demonstrated that TLR2, TLR4 and CD14 receptors sense Tityus serrulatus venom (TsV) and its major component, toxin 1 (Ts1), to mediate cytokine and lipid mediator production. Additionally, we demonstrated that TsV induces TLR2- and TLR4/MyD88-dependent NF-?B activation and TLR4-dependent and TLR2/MyD88-independent c-Jun activation. Similar to TsV, Ts1 induces MyD88-dependent NF-?B phosphorylation via TLR2 and TLR4 receptors, while c-Jun activation is dependent on neither TLR2 nor TLR4/MyD88. Therefore, we propose the term venom-associated molecular pattern (VAMP) to refer to molecules that are introduced into the host by stings and are recognized by PRRs, resulting in inflammation. PMID:24516606

Zoccal, Karina Furlani; Bitencourt, Claudia da Silva; Paula-Silva, Francisco Wanderley Garcia; Sorgi, Carlos Arterio; de Castro Figueiredo Bordon, Karla; Arantes, Eliane Candiani; Faccioli, Lucia Helena

2014-01-01

321

Widespread Molecular Patterns Associated with Drug Sensitivity in Breast Cancer Cell Lines, with Implications for Human Tumors  

PubMed Central

Background Recent landmark studies have profiled cancer cell lines for molecular features, along with measuring the corresponding growth inhibitory effects for specific drug compounds. These data present a tool for determining which subsets of human cancer might be more responsive to particular drugs. To this end, the NCI-DREAM-sponsored DREAM7: Drug Sensitivity Prediction Challenge (sub-challenge 1) set out to predict the sensitivities of 18 breast cancer cell lines to 31 previously untested compounds, on the basis of molecular profiling data and a training subset of cell lines. Methods and Results With 47 teams submitting blinded predictions, team Creighton scored third in terms of overall accuracy. Team Creighton's method was simple and straightforward, incorporated multiple expression data types (RNA-seq, gene array, RPPA), and incorporated all profiled features (not only the “best” predictive ones). As an extension of the approach, cell line data, from public datasets of expression profiling coupled with drug sensitivities (Barretina, Garnett, Heiser) were used to “predict” the drug sensitivities in human breast tumors (using data from The Cancer Genome Atlas). Drug sensitivity correlations within human breast tumors showed differences by expression-based subtype, with many associations in line with the expected (e.g. Lapatinib sensitivity in HER2-enriched cancers) and others inviting further study (e.g. relative resistance to PI3K inhibitors in basal-like cancers). Conclusions Molecular patterns associated with drug sensitivity are widespread, with potentially hundreds of genes that could be incorporated into making predictions, as well as offering biological clues as to the mechanisms involved. Applying the cell line patterns to human tumor data may help generate hypotheses on what tumor subsets might be more responsive to therapies, where multiple cell line datasets representing various drugs may be used, in order to assess consistency of patterns. PMID:24386073

Creighton, Chad J.

2013-01-01

322

Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns  

PubMed Central

Clear cell renal cell carcinoma (ccRCC) is the predominant RCC subtype, but even within this classification, the natural history is heterogeneous and difficult to predict. A sophisticated understanding of the molecular features most discriminatory for the underlying tumor heterogeneity should be predicated on identifiable and biologically meaningful patterns of gene expression. Gene expression microarray data were analyzed using software that implements iterative unsupervised consensus clustering algorithms to identify the optimal molecular subclasses, without clinical or other classifying information. ConsensusCluster analysis identified two distinct subtypes of ccRCC within the training set, designated clear cell type A (ccA) and B (ccB). Based on the core tumors, or most well-defined arrays, in each subtype, logical analysis of data (LAD) defined a small, highly predictive gene set that could then be used to classify additional tumors individually. The subclasses were corroborated in a validation data set of 177 tumors and analyzed for clinical outcome. Based on individual tumor assignment, tumors designated ccA have markedly improved disease-specific survival compared to ccB (median survival of 8.6 vs 2.0 years, P = 0.002). Analyzed by both univariate and multivariate analysis, the classification schema was independently associated with survival. Using patterns of gene expression based on a defined gene set, ccRCC was classified into two robust subclasses based on inherent molecular features that ultimately correspond to marked differences in clinical outcome. This classification schema thus provides a molecular stratification applicable to individual tumors that has implications to influence treatment decisions, define biological mechanisms involved in ccRCC tumor progression, and direct future drug discovery. PMID:20871783

Brannon, A. Rose; Reddy, Anupama; Seiler, Michael; Arreola, Alexandra; Moore, Dominic T.; Pruthi, Raj S.; Wallen, Eric M.; Nielsen, Matthew E.; Liu, Huiqing; Nathanson, Katherine L.; Ljungberg, Borje; Zhao, Hongjuan; Brooks, James D.; Ganesan, Shridar; Bhanot, Gyan; Rathmell, W. Kimryn

2010-01-01

323

Hybrid diatomics-in-molecules-based quantum mechanical/molecular mechanical approach applied to the modeling of structures and spectra of mixed molecular clusters Arn(HCl)m and Arn(HF)m  

NASA Astrophysics Data System (ADS)

A new hybrid QM/DIM approach aimed at describing equilibrium structures and spectroscopic properties of medium size mixed molecular clusters is developed. This methodology is applied to vibrational spectra of hydrogen chloride and hydrogen fluoride clusters with up to four monomer molecules embedded in argon shells Arn(H(Cl/F))m (n=1-62, m=1-4). The hydrogen halide complexes (QM part) are treated at the MP2/aug-cc-pVTZ level, while the interaction between HX molecules and Ar atoms (MM part) is described in terms of the semiempirical DIM methodology, based on the proper mixing between neutral and ionic states of the system [Grigorenko et al., J. Chem. Phys. 104, 5510 (1996)]. A detailed analysis of the resulting topology of the QM/DIM potential energy (hyper-)surface in the triatomic subsystem Ar-HX reveals more pronounced nonadditive atomic induction and dispersion contributions to the total interaction energy in the case of the Ar-HCl system. An extension of the original analytical DIM-based potential in the frame of the present model as well as the current limitations of the method are discussed. A modified algorithm for the gradient geometry optimization, along with partly analytical force constant matrix evaluation, is developed to treat large cages of argon atoms around molecular clusters. Calculated frequency redshifts of HX stretching vibrations in the mixed clusters relative to the isolated hydrogen-bonded complexes are in good agreement with experimental findings.

Bochenkova, A. V.; Suhm, M. A.; Granovsky, A. A.; Nemukhin, A. V.

2004-02-01

324

Dynamic features of stimulated raman atomic-molecular conversion in a mixture of two bose gases with the formation of bose condensates of heteronuclear molecules  

SciTech Connect

Based on the mean-field approximation, a system of nonlinear differential equations is obtained which describes the dynamics of atomic-molecular conversion induced by two resonance Raman laser pulses. The obtained integrals of motion allow one to reduce the problem to one evolution equation for the density of molecules. The solutions of this equation show that different time evolution regimes of the system are possible, depending on the initial conditions: the periodic and aperiodic regimes and the rest. The dependences of the period and amplitude on the initial density of particles and the initial phase difference are studied in detail. The possibility of the phase control of the system dynamics is proved.

Khadzhi, P. I., E-mail: fmfdekan@spsu.ru; Zingan, A. P. [Academy of Sciences of Moldova, Institute of Applied Physics (Moldova, Republic of)

2011-04-15

325

Molecular deletion patterns in Duchenne and Becker muscular dystrophy patients from KwaZulu Natal  

Microsoft Academic Search

There exists much phenotypic heterogeneity in Duchenne muscular dystrophy and its allelic variant, Becker muscular dystrophy. The molecular findings on 53 patients with Duchenne and 15 patients with Becker type muscular dystrophy in KwaZulu Natal, South Africa are reported. Multiplex PCR was performed using primers targeting 18 hot-spot exons throughout the dystrophin gene. Analysis of the multiplex PCR data revealed

K. D. Hallwirth Pillay; P. L. A. Bill; S. Madurai; L. Mubaiwa; P. Rapiti

2007-01-01

326

Biological and molecular effects of small molecule kinase inhibitors on low-passage human colorectal cancer cell lines.  

PubMed

Low-passage cancer cell lines are versatile tools to study tumor cell biology. Here, we have employed four such cell lines, established from primary tumors of colorectal cancer (CRC) patients, to evaluate effects of the small molecule kinase inhibitors (SMI) vemurafenib, trametinib, perifosine, and regorafenib in an in vitro setting. The mutant BRAF (V600E/V600K) inhibitor vemurafenib, but also the MEK1/2 inhibitor trametinib efficiently inhibited DNA synthesis, signaling through ERK1/2 and expression of genes downstream of ERK1/2 in BRAF mutant cells only. In case of the AKT inhibitor perifosine, three cell lines showed a high or intermediate responsiveness to the drug while one cell line was resistant. The multikinase inhibitor regorafenib inhibited proliferation of all CRC lines with similar efficiency and independent of the presence or absence of KRAS, BRAF, PIK3CA, and TP53 mutations. Regorafenib action was associated with broad-range inhibitory effects at the level of gene expression but not with a general inhibition of AKT or MEK/ERK signaling. In vemurafenib-sensitive cells, the antiproliferative effect of vemurafenib was enhanced by the other SMI. Together, our results provide insights into the determinants of SMI efficiencies in CRC cells and encourage the further use of low-passage CRC cell lines as preclinical models. PMID:25309914

Lange, Falko; Franz, Benjamin; Maletzki, Claudia; Linnebacher, Michael; Hühns, Maja; Jaster, Robert

2014-01-01

327

Biological and Molecular Effects of Small Molecule Kinase Inhibitors on Low-Passage Human Colorectal Cancer Cell Lines  

PubMed Central

Low-passage cancer cell lines are versatile tools to study tumor cell biology. Here, we have employed four such cell lines, established from primary tumors of colorectal cancer (CRC) patients, to evaluate effects of the small molecule kinase inhibitors (SMI) vemurafenib, trametinib, perifosine, and regorafenib in an in vitro setting. The mutant BRAF (V600E/V600K) inhibitor vemurafenib, but also the MEK1/2 inhibitor trametinib efficiently inhibited DNA synthesis, signaling through ERK1/2 and expression of genes downstream of ERK1/2 in BRAF mutant cells only. In case of the AKT inhibitor perifosine, three cell lines showed a high or intermediate responsiveness to the drug while one cell line was resistant. The multikinase inhibitor regorafenib inhibited proliferation of all CRC lines with similar efficiency and independent of the presence or absence of KRAS, BRAF, PIK3CA, and TP53 mutations. Regorafenib action was associated with broad-range inhibitory effects at the level of gene expression but not with a general inhibition of AKT or MEK/ERK signaling. In vemurafenib-sensitive cells, the antiproliferative effect of vemurafenib was enhanced by the other SMI. Together, our results provide insights into the determinants of SMI efficiencies in CRC cells and encourage the further use of low-passage CRC cell lines as preclinical models. PMID:25309914

Lange, Falko; Franz, Benjamin; Maletzki, Claudia; Linnebacher, Michael; Huhns, Maja; Jaster, Robert

2014-01-01

328

Molecular deletion patterns in Turkish Duchenne and Becker muscular dystrophy patients  

Microsoft Academic Search

The dystrophin gene deletion patterns of Duchenne \\/ Becker muscular dystrophy were investigated in 57 DMD, 7 BMD and 1 DMD-BMD intermediate muscular dystrophy patients. Deletions, analyzed by multiplex amplification of selected exons, were observed in 58% (38 cases) of the patients. It was found that exon 48 was the most frequently affected, while exon 44 was the least frequently

Pervin Dinçer; ?ükrüye Ayter; Meral Özgüç; Yavuz Renda

1996-01-01

329

Onset of patterns in an oscillated granular layer: Continuum and molecular dynamics simulations  

E-print Network

of the cell. Changing the frequency of oscillation of the cell changes the wavelength of the resulting pattern. Background A successful hydrodynamic theory of granular media could allow scientists and engineers to exploit,2 and simulations 3 demon- strate the potential for hydrodynamic theory to describe granular media; however

Texas at Austin. University of

330

DISPERSAL PATTERN OF BLACK-BILLED MAGPIES (PICA HUDSONIA) MEASURED BY MOLECULAR GENETIC (RAPD) ANALYSIS  

Microsoft Academic Search

Black-billed Magpies (Pica hudsonia) are a relatively sedentary corvid, with greater dispersal of females than males. To genetically confirm that dispersal pattern, 29 reproductively active adults were captured over two years and were scored for primer-spe- cific random amplified polymorphic DNA (RAPD) bands (53 polymorphic bands in 1996 and 104 in 1997). In both years, we captured more previously banded

XIAO-HONG WANGAND; Charles H. Trost

2001-01-01

331

Simulating the Mammalian Blastocyst -Molecular and Mechanical Interactions Pattern the Embryo  

E-print Network

Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden Abstract the embryonic development, is an area of debate. We have developed a computational modeling framework proliferating cells. The exact nature of these interactions, which determine the lineage patterning

Adolphs, Ralph

332

Patterns of inheritance with RAPD molecular markers reveal novel types of polymorphism in the honey bee  

Microsoft Academic Search

The polymerase chain reaction (PCR) was used to generate random amplified polymorphic DNA (RAPD) from honey bee DNA samples in order to follow the patterns of inheritance of RAPD markers in a haplodiploid insect. The genomic DNA samples from two parental bees, a haploid drone and a diploid queen, were screened for polymorphism with 68 different tennucleotide primers of random

Greg J. Hunt; Robert E. Page

1992-01-01

333

HIV-1 entry inhibition by small-molecule CCR5 antagonists: A combined molecular modeling and mutant study using a high-throughput assay  

SciTech Connect

Based on the attrition rate of CCR5 small molecule antagonists in the clinic the discovery and development of next generation antagonists with an improved pharmacology and safety profile is necessary. Herein, we describe a combined molecular modeling, CCR5-mediated cell fusion, and receptor site-directed mutagenesis approach to study the molecular interactions of six structurally diverse compounds (aplaviroc, maraviroc, vicriviroc, TAK-779, SCH-C and a benzyloxycarbonyl-aminopiperidin-1-yl-butane derivative) with CCR5, a coreceptor for CCR5-tropic HIV-1 strains. This is the first study using an antifusogenic assay, a model of the interaction of the gp120 envelope protein with CCR5. This assay avoids the use of radioactivity and HIV infection assays, and can be used in a high throughput mode. The assay was validated by comparison with other established CCR5 assays. Given the hydrophobic nature of the binding pocket several binding models are suggested which could prove useful in the rational drug design of new lead compounds.

Labrecque, Jean [Department of Biology, AnorMED Inc. now Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142 (United States); Metz, Markus [Department of Chemistry, AnorMED Inc. now Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142 (United States); Lau, Gloria; Darkes, Marilyn C.; Wong, Rebecca S.Y. [Department of Biology, AnorMED Inc. now Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142 (United States); Bogucki, David; Carpenter, Bryon; Chen Gang; Li Tongshuang; Nan, Susan [Department of Chemistry, AnorMED Inc. now Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142 (United States); Schols, Dominique [Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000, Leuven (Belgium); Bridger, Gary J. [Department of Chemistry, AnorMED Inc. now Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142 (United States); Fricker, Simon P. [Department of Biology, AnorMED Inc. now Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142 (United States); Skerlj, Renato T., E-mail: renato.skerlj@genzyme.co [Department of Chemistry, AnorMED Inc. now Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142 (United States)

2011-05-10

334

Visualization and thermodynamic encoding of single-molecule partition functions  

E-print Network

Ensemble averaging of molecular states is fundamental for the experimental determination of thermodynamic quantities. A special case occurs for single-molecule investigations under equilibrium conditions, for which free energy, entropy and enthalpy at finite-temperatures are challenging to determine with ensemble-averaging alone. Here, we provide a method to access single-molecule thermodynamics, by confining an individual molecule to a nanoscopic pore of a two-dimensional metal-organic nanomesh, where we directly record finite-temperature time-averaged statistical weights using temperature-controlled scanning tunneling microscopy. The obtained patterns represent a real space equilibrium probability distribution. We associate this distribution with a partition function projection to assess spatially resolved thermodynamic quantities, by means of computational modeling. The presented molecular dynamics based Boltzmann weighting model is able to reproduce experimentally observed molecular states with high accur...

Palma, Carlos-Andres; Klappenberger, Florian; Arras, Emmanuel; Kühne, Dirk; Stafström, Sven; Barth, Johannes V

2014-01-01

335

Molecular Mechanisms of Wnt8a Regulation: Insights Into Vertebrate Mesoderm Development and Patterning  

E-print Network

region negatively impacts phase II expression driven by the proximal regulatory region, indicating a complex relationship of regulatory elements. v v ACKNOWLEDGEMENTS I am grateful to my PhD advisor, Dr. Arne Lekven..., for encouraging me to apply to the PhD program in the Department of Biology, accepting me in his lab, training me in molecular biology and teaching me developmental genetics. He has been an excellent mentor and a role model. His constant encouragement, support...

Narayanan, Anand

2012-07-16

336

Effect of Molecule-Surface Reaction Mechanism on the Electronic Characteristics and Photovoltaic Performance of Molecularly Modified Si  

PubMed Central

We report on the passivation properties of molecularly modified, oxide-free Si(111) surfaces. The reaction of 1-alcohol with the H-passivated Si(111) surface can follow two possible paths, nucleophilic substitution (SN) and radical chain reaction (RCR), depending on adsorption conditions. Moderate heating leads to the SN reaction, whereas with UV irradiation RCR dominates, with SN as a secondary path. We show that the site-sensitive SN reaction leads to better electrical passivation, as indicated by smaller surface band bending and a longer lifetime of minority carriers. However, the surface-insensitive RCR reaction leads to more dense monolayers and, therefore, to much better chemical stability, with lasting protection of the Si surface against oxidation. Thus, our study reveals an inherent dissonance between electrical and chemical passivation. Alkoxy monolayers, formed under UV irradiation, benefit, though, from both chemical and electronic passivation because under these conditions both SN and RCR occur. This is reflected in longer minority carrier lifetimes, lower reverse currents in the dark, and improved photovoltaic performance, over what is obtained if only one of the mechanisms operates. These results show how chemical kinetics and reaction paths impact electronic properties at the device level. It further suggests an approach for effective passivation of other semiconductors. PMID:24205409

2013-01-01

337

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

PubMed

We present a continuous pseudo-hard-sphere potential based on a cut-and-shifted Mie (generalized Lennard-Jones) potential with exponents (50, 49). Using this potential one can mimic the volumetric, structural, and dynamic properties of the discontinuous hard-sphere potential over the whole fluid range. The continuous pseudo potential has the advantage that it may be incorporated directly into off-the-shelf molecular-dynamics code, allowing the user to capitalise on existing hardware and software advances. Simulation results for the compressibility factor of the fluid and solid phases of our pseudo hard spheres are presented and compared both to the Carnahan-Starling equation of state of the fluid and published data, the differences being indistinguishable within simulation uncertainty. The specific form of the potential is employed to simulate flexible chains formed from these pseudo hard spheres at contact (pearl-necklace model) for m(c) = 4, 5, 7, 8, 16, 20, 100, 201, and 500 monomer segments. The compressibility factor of the chains per unit of monomer, m(c), approaches a limiting value at reasonably small values, m(c) < 50, as predicted by Wertheim's first order thermodynamic perturbation theory. Simulation results are also presented for highly asymmetric mixtures of pseudo hard spheres, with diameter ratios of 3:1, 5:1, 20:1 over the whole composition range. PMID:23061853

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

2012-10-14

338

Molecular Universe  

NSDL National Science Digital Library

This fantastic resource for college-level students of chemistry provides abundant images and explanatory text on molecules and molecular systems. The site's main provider is Richard Catlow, Director of the Davy Faraday Research Laboratory at the Royal Institution of Great Britain. Molecular Universe presents a collection of lessons, arranged into categories such as Building in Three Dimensions, Boundaries and Barriers, and The Molecules of Life. The sleek color illustrations demonstrate everything from diamond structure to a DNA molecule. Highlights of the site include a detailed look at protein folding, how molecules taste, and molecules and computers. Both students and professors should journey to the Molecular Universe.

Catlow, C. R. A. (Charles Richard Arthur), 1947-

2000-01-01

339

Computational mass spectrometry for small molecules  

PubMed Central

The identification of small molecules from mass spectrometry (MS) data remains a major challenge in the interpretation of MS data. This review covers the computational aspects of identifying small molecules, from the identification of a compound searching a reference spectral library, to the structural elucidation of unknowns. In detail, we describe the basic principles and pitfalls of searching mass spectral reference libraries. Determining the molecular formula of the compound can serve as a basis for subsequent structural elucidation; consequently, we cover different methods for molecular formula identification, focussing on isotope pattern analysis. We then discuss automated methods to deal with mass spectra of compounds that are not present in spectral libraries, and provide an insight into de novo analysis of fragmentation spectra using fragmentation trees. In addition, this review shortly covers the reconstruction of metabolic networks using MS data. Finally, we list available software for different steps of the analysis pipeline. PMID:23453222

2013-01-01

340

Computational mass spectrometry for small molecules.  

PubMed

: The identification of small molecules from mass spectrometry (MS) data remains a major challenge in the interpretation of MS data. This review covers the computational aspects of identifying small molecules, from the identification of a compound searching a reference spectral library, to the structural elucidation of unknowns. In detail, we describe the basic principles and pitfalls of searching mass spectral reference libraries. Determining the molecular formula of the compound can serve as a basis for subsequent structural elucidation; consequently, we cover different methods for molecular formula identification, focussing on isotope pattern analysis. We then discuss automated methods to deal with mass spectra of compounds that are not present in spectral libraries, and provide an insight into de novo analysis of fragmentation spectra using fragmentation trees. In addition, this review shortly covers the reconstruction of metabolic networks using MS data. Finally, we list available software for different steps of the analysis pipeline. PMID:23453222

Scheubert, Kerstin; Hufsky, Franziska; Böcker, Sebastian

2013-01-01

341

Viral Pathogen-Associated Molecular Patterns Regulate Blood-Brain Barrier Integrity via Competing Innate Cytokine Signals  

PubMed Central

ABSTRACT Pattern recognition receptor (PRR) detection of pathogen-associated molecular patterns (PAMPs), such as viral RNA, drives innate immune responses against West Nile virus (WNV), an emerging neurotropic pathogen. Here we demonstrate that WNV PAMPs orchestrate endothelial responses to WNV via competing innate immune cytokine signals at the blood-brain barrier (BBB), a multicellular interface with highly specialized brain endothelial cells that normally prevents pathogen entry. While Th1 cytokines increase the permeability of endothelial barriers, type I interferon (IFN) promoted and stabilized BBB function. Induction of innate cytokines by pattern recognition pathways directly regulated BBB permeability and tight junction formation via balanced activation of the small GTPases Rac1 and RhoA, which in turn regulated the transendothelial trafficking of WNV. In vivo, mice with attenuated type I IFN signaling or IFN induction (Ifnar?/? Irf7?/?) exhibited enhanced BBB permeability and tight junction dysregulation after WNV infection. Together, these data provide new insight into host-pathogen interactions at the BBB during neurotropic viral infection. PMID:25161189

Daniels, Brian P.; Holman, David W.; Cruz-Orengo, Lillian; Jujjavarapu, Harsha; Durrant, Douglas M.

2014-01-01

342

Heterogeneity of molecular resistance patterns in antimony-resistant field isolates of Leishmania species from the western Mediterranean area.  

PubMed

Antimonials remain the first-line treatment for the various manifestations of leishmaniasis in most areas where the disease is endemic, and increasing cases of therapeutic failure associated with parasite resistance have been reported. In this study, we assessed the molecular status of 47 clinical isolates of Leishmania causing visceral and cutaneous leishmaniasis from Algeria, Tunisia, and southern France. In total, we examined 14 genes that have been shown to exhibit significant variations in DNA amplification, mRNA levels, or protein expression with respect to resistance to antimonials. The gene status of each clinical isolate was assessed via qPCR and qRT-PCR. We then compared the molecular pattern against the phenotype determined via an in vitro sensitivity test of the clinical isolates against meglumine antimoniate, which is considered the reference technique. Our results demonstrate significant DNA amplification and/or RNA overexpression in 56% of the clinical isolates with the resistant phenotype. All clinical isolates that exhibited significant overexpression of at least 2 genes displayed a resistant phenotype. Among the 14 genes investigated, 10 genes displayed either significant amplification or overexpression in at least 1 clinical isolate; these genes are involved in several metabolic pathways. Moreover, various gene associations were observed depending on the clinical isolates, supporting the multifactorial nature of Leishmania resistance. Molecular resistance features were found in the 3 Leishmania species investigated (Leishmania infantum, Leishmania major, and Leishmania killicki). To our knowledge, this is the first report of the involvement of molecular resistance genes in field isolates of Leishmania major and Leishmania killicki with the resistance phenotype. PMID:24913173

Jeddi, Fakhri; Mary, Charles; Aoun, Karim; Harrat, Zoubir; Bouratbine, Aïda; Faraut, Françoise; Benikhlef, Rezika; Pomares, Christelle; Pratlong, Francine; Marty, Pierre; Piarroux, Renaud

2014-08-01

343

Enhancement in dissolution pattern of piribedil by molecular encapsulation with beta-cyclodextrin.  

PubMed

The aim of this study was to improve the dissolution behavior of piribedil by molecular encapsulation with beta-cyclodextrin (beta-CD). Toward this aim, physical mixing, co-grinding, and spray-drying methods were used to prepare solid binary systems. Differential scanning calorimetry, X-ray diffractometry, and particle size analysis were used to characterize the binary systems obtained. Complexes of piribedil and beta-CD could be prepared using the spray-drying method. Dissolution of piribedil was improved to a great extent by the complex prepared. PMID:16636717

Demirel, Muzeyyen; Buyukkoroglu, G; Kalava, B S; Yazan, Y

2006-03-01

344

Comparison of antibiotic susceptibility profiles and molecular typing patterns of clinical and environmental Salmonella enterica serotype Newport.  

PubMed

The genus Salmonella is composed of more than 2,400 serotypes, many of which cause enteric diseases in humans and animals. Several Salmonella serotypes are multidrug resistant, and there is evidence of the clonal spread of these strains from animals to humans. Salmonella enterica serotype Newport is one of the serotypes that increasingly present a multidrug-resistant phenotype. Source tracking and antibiotic resistance testing are important considerations for identifying the outbreak strain. The first goal of this study was to examine the antibiotic susceptibility patterns of clinical and environmental Salmonella Newport isolates from various geographic locations and to compare the discriminatory ability of two DNA fingerprinting techniques. The second goal was to determine whether the antibiotic resistance profiles and typing patterns correlated. Thirty Salmonella Newport isolates, including environmental and human clinical strains, were subjected to pulsed-field gel electrophoresis (PFGE), ribotyping, and antibiotic susceptibility testing. Eighty percent of the isolates showed total or intermediate resistance to one or more drugs; 75% of the isolates were multidrug resistant. Ribotyping with the EcoRI enzyme and PFGE with the XbaI enzyme each divided the isolates into 14 groups. Cluster analysis based on antibiotic susceptibility patterns generated 23 profiles. The susceptible and resistant isolates were not differentiated on the basis of either of the molecular typing techniques. Hence, no correlation was observed between the antibiotic resistance profiles and the DNA subtyping patterns. In conclusion, ribotyping is as discriminatory as PFGE and, when used in combination with antibiotic resistance profiles, provides a powerful tool for the source tracking of Salmonella Newport. PMID:16629015

Tatavarthy, Aparna; Peak, Kealy; Veguilla, William; Reeves, Frank; Cannons, Andrew; Amuso, Philip; Cattani, Jacqueline

2006-04-01

345

Elastic, Adhesive, and Charge Transport Properties of a Metal-molecule-metal Junction: the Role of Molecular Orientation, Order, and Coverage  

SciTech Connect

The elastic, adhesive, and charge transport properties of a metal-molecule-metal junction were studied via conducting-probe atomic force microscopy (AFM) and correlated with molecular structure by near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. The junctions consisted of Co-Cr-coated AFM tips in contact with methyl-terminated alkanethiols (CH{sub 3}(CH{sub 2}){sub n-1}SH, denoted by Cn, where n is the number of carbons in the molecular chain) on Au substrates. AFM contact data were analyzed with the Derjaguin-Muller-Toporov contact model, modified by a first-order elastic perturbation method to account for substrate effects, and a parabolic tunneling model, appropriate for a metal-insulator-metal junction in which the thickness of the insulator is comparable to the Fermi wavelength of the conducting electrons. NEXAFS carbon K-edge spectra were used to compute the dichroic ratio RI for each film, which provided a quantitative measure of the molecular structure as a function of n. As n decreased from 18 to 5, there was a change in the molecular phase from crystalline to amorphous (R{sub I} {yields} 0) and loss of surface coverage, and as a result, the work of adhesion w increased from 82.8 mJ m{sup -2} to 168.3 mJ m{sup -2}, the Young's modulus of the film E{sub film} decreased from 1.0 to 0.15 GPa, and the tunneling barrier height {psi}{sub 0} - E{sub F} decreased from 2.4 to 2.1 eV. For all n, the barrier thickness t decreased for small applied loads F and remained constant at {approx}2.2 nm for large F. The change in behavior was explained by the presence of two insulating layers: an oxide layer on the Co-Cr tip, and the alkanethiol monolayer on the Au surface. X-ray photoelectron spectroscopy confirmed the presence of an oxide layer on the Co-Cr tip, and by performing high-resolution region scans through the film, the thickness of the oxide layer t{sub oxide} was found to be between 1.9 and 3.9 nm. Finally, it was shown that {psi}{sub 0} - E{sub F} is strain-dependent, and the strain at which the film is completely displaced from under the tip is -0.17 for all values of n.

DelRio, F.; Steffens, K; Jaye, C; Fischer, D; Cook, R

2010-01-01

346

Mighty Molecules  

NSDL National Science Digital Library

In this activity, learners use marshmallows and gum drops to construct seven models of molecules. Learners classify (solid, liquid or gas) and draw diagrams of the molecules. Learners can also create a table showing the chemical formula for each molecule and identify a common use for each chemical. Use this activity to introduce learners to molecules, compounds, and bonds.

Little, Carlyn; Lahart, David; Meyers, Ted; Weisblat, Brooks

1997-01-01

347

Construction of Chiral Propeller Architectures from Achiral Molecules  

NASA Astrophysics Data System (ADS)

Achiral BPCA-Cn-PmOHs construct chiral propeller structures in an N phase. The origin of chiral N phases in these achiral molecules comes from the twisted conformation of head-to-head dimers, indicating that neither molecular chirality, nor molecular bends, nor molecular tilting is necessary to form a chiral phase. The Frank-Pryce spherulitic N droplets and finger-print textures result from the single-twisting of chiral conformers, while the first-time observed propeller-patterned chiral N droplets are attributed to the double-twisting of chiral conformers in the N phase.

Jeong, Kwang-Un; Yang, Deng-Ke; Graham, Matthew J.; Knapp, Brian S.; Harris, Frank W.; Cheng, Stephen Z. D.

2007-03-01

348

Adsorption-geometry induced transformation of self-assembled nanostructures of an aldehyde molecule on Cu(110).  

PubMed

From an interplay of high-resolution STM imaging/manipulation and DFT calculations, we have revealed that different self-assembled nanostructures of BA molecules on Cu(110) are attributable to specific molecular adsorption geometries, and thus the corresponding intermolecular hydrogen bonding patterns. The STM manipulations demonstrate the feasibility of switching such weak-hydrogen-bonding patterns. PMID:25145767

Zhang, Chi; Sun, Qiang; Sheng, Kai; Tan, Qinggang; Xu, Wei

2014-10-01

349

MRCI study on the spectroscopic parameters and molecular constants of the X1?+, a3?+, A1? and C1?- electronic states of the SiO molecule.  

PubMed

The potential energy curves (PECs) of the X(1)?(+), a(3)?(+), A(1)? and C(1)?(-) electronic states of the SiO molecule are studied using an ab initio quantum chemical method. The calculations have been made employing the complete active space self-consistent field (CASSCF) method, which is followed by the valence internally contracted multireference configuration interaction (MRCI) approach in combination with several correlation-consistent basis sets. The effect on the PECs by the core-valence correlation and relativistic corrections is included. The way to consider the relativistic correction is to use the third-order Douglas-Kroll Hamiltonian approximation. The core-valence correlation correction is carried out with the cc-pCVQZ basis set, and the relativistic correction is performed at the level of the cc-pVQZ basis set. To obtain more reliable results, the PECs determined by the MRCI calculations are also corrected for size-extensivity errors by means of the Davidson modification (MRCI+Q). The PECs of these electronic states are extrapolated to the complete basis set limit by the total-energy extrapolation scheme. Employing these PECs, the spectroscopic parameters are calculated and compared with those reported in the literature. With these PECs determined by the MRCI+Q/CV+DK+56 calculations, by solving the radial Schrödinger equation of nuclear motion, 110 vibrational states for the X(1)?(+), 69 for the a(3)?(+), 54 for the A(1)? and 67 for the C(1)?(-) electronic state are predicted when the rotational quantum number J equals zero. The vibrational manifolds of the first 20 vibrational states are reported and compared with the available RKR data for each electronic state. On the whole, as expected, the most accurate spectroscopic parameters and molecular constants of the SiO molecule are obtained by the MRCI+Q/CV+DK+56 calculations. And the present molecular constants of the a(3)?(+), C(1)?(-) and A(1)? electronic states determined by the MRCI+Q/CV+DK+56 calculations should be good prediction for future laboratory experiment. PMID:22169566

Shi, Deheng; Li, Wentao; Sun, Jinfeng; Zhu, Zunlue

2012-02-15

350

Structure–function relationship for saponin effects on cell cycle arrest and apoptosis in the human 1547 osteosarcoma cells: a molecular modelling approach of natural molecules structurally close to diosgenin  

Microsoft Academic Search

In this paper, eight natural molecules structurally close to diosgenin (five saponins: diosgenin, hecogenin, tigogenin, sarsasapogenin, smilagenin; two steroidal alkaloids: solasodine, solanidine; one sterol: stigmasterol) have been tested for their biological activities on human 1547 osteosarcoma cells. Differences in activity were studied in term of proliferation rate, cell cycle distribution and apoptosis induction. By using molecular modelling, two structural characteristics

Patrick Trouillas; Cécile Corbière; Bertrand Liagre; Jean-Luc Duroux; Jean-Louis Beneytout

2005-01-01

351

Selective molecular assembly patterning at the nanoscale: a novel platform for producing protein patterns by electron-beam lithography on SiO2/indium tin oxide-coated glass substrates  

NASA Astrophysics Data System (ADS)

The creation of geometrically well-defined submicron structures on insulating substrates by e-beam lithography is hampered by surface charging. This problem becomes crucial when trying to create nanosized protein patterns by selective molecular assembly patterning (SMAP) on transparent glass substrates. In this paper we demonstrate that the use of thin films of conductive indium tin oxide resolves the issue of surface charging during e-beam writing while being compatible with the standard SMAP protocol for surface modification.

Lussi, Jost W.; Tang, Clarence; Kuenzi, Pierre-Andre; Staufer, Urs; Csucs, Gabor; Vörös, Janos; Danuser, Gaudenz; Hubbell, Jeffrey A.; Textor, Marcus

2005-09-01

352

Molecular inversion probes reveal patterns of 9p21 deletion and copy number aberrations in childhood leukemia  

PubMed Central

Childhood leukemia, which accounts for > 30% of newly diagnosed childhood malignancies, is one of the leading causes of death for children with cancer. Genome-wide studies using microarray chips to identify copy number changes in human cancer are becoming more common. In this pilot study, 45 pediatric leukemia samples were analyzed for gene copy aberrations using novel molecular inversion probe (MIP) technology. Acute leukemia subtypes included precursor B-cell acute lymphoblastic leukemia (ALL) (n = 23), precursor T-cell ALL (n = 6), and acute myeloid leukemia (n = 14). The MIP analysis identified 69 regions of recurring copy number changes, of which 41 have not been identified with other DNA microarray platforms. Copy number gains and losses were validated in 98% of clinical karyotypes and 100% of fluorescence in situ hybridization studies available. We report unique patterns of copy number loss in samples with 9p21.3 (CDKN2A) deletion in the precursor B-cell ALL patients, compared with the precursor T-cell ALL patients. MIPs represent an attractive technology for identifying novel copy number aberrations, validating previously reported copy number changes, and translating molecular findings into clinically relevant targets for further investigation. PMID:19602459

Schiffman, Joshua D.; Wang, Yuker; McPherson, Lisa A.; Welch, Katrina; Zhang, Nancy; Davis, Ronald; Lacayo, Norman J.; Dahl, Gary V.; Faham, Malek; Ford, James M.; Ji, Hanlee P.

2009-01-01

353

Molecular detection of hematozoa infections in tundra swans relative to migration patterns and ecological conditions at breeding grounds.  

PubMed

Tundra swans (Cygnus columbianus) are broadly distributed in North America, use a wide variety of habitats, and exhibit diverse migration strategies. We investigated patterns of hematozoa infection in three populations of tundra swans that breed in Alaska using satellite tracking to infer host movement and molecular techniques to assess the prevalence and genetic diversity of parasites. We evaluated whether migratory patterns and environmental conditions at breeding areas explain the prevalence of blood parasites in migratory birds by contrasting the fit of competing models formulated in an occupancy modeling framework and calculating the detection probability of the top model using Akaike Information Criterion (AIC). We described genetic diversity of blood parasites in each population of swans by calculating the number of unique parasite haplotypes observed. Blood parasite infection was significantly different between populations of Alaska tundra swans, with the highest estimated prevalence occurring among birds occupying breeding areas with lower mean daily wind speeds and higher daily summer temperatures. Models including covariates of wind speed and temperature during summer months at breeding grounds better predicted hematozoa prevalence than those that included annual migration distance or duration. Genetic diversity of blood parasites in populations of tundra swans appeared to be relative to hematozoa prevalence. Our results suggest ecological conditions at breeding grounds may explain differences of hematozoa infection among populations of tundra swans that breed in Alaska. PMID:23049862

Ramey, Andrew M; Ely, Craig R; Schmutz, Joel A; Pearce, John M; Heard, Darryl J

2012-01-01

354

Molecular Detection of Hematozoa Infections in Tundra Swans Relative to Migration Patterns and Ecological Conditions at Breeding Grounds  

PubMed Central

Tundra swans (Cygnus columbianus) are broadly distributed in North America, use a wide variety of habitats, and exhibit diverse migration strategies. We investigated patterns of hematozoa infection in three populations of tundra swans that breed in Alaska using satellite tracking to infer host movement and molecular techniques to assess the prevalence and genetic diversity of parasites. We evaluated whether migratory patterns and environmental conditions at breeding areas explain the prevalence of blood parasites in migratory birds by contrasting the fit of competing models formulated in an occupancy modeling framework and calculating the detection probability of the top model using Akaike Information Criterion (AIC). We described genetic diversity of blood parasites in each population of swans by calculating the number of unique parasite haplotypes observed. Blood parasite infection was significantly different between populations of Alaska tundra swans, with the highest estimated prevalence occurring among birds occupying breeding areas with lower mean daily wind speeds and higher daily summer temperatures. Models including covariates of wind speed and temperature during summer months at breeding grounds better predicted hematozoa prevalence than those that included annual migration distance or duration. Genetic diversity of blood parasites in populations of tundra swans appeared to be relative to hematozoa prevalence. Our results suggest ecological conditions at breeding grounds may explain differences of hematozoa infection among populations of tundra swans that breed in Alaska. PMID:23049862

Ramey, Andrew M.; Ely, Craig R.; Schmutz, Joel A.; Pearce, John M.; Heard, Darryl J.

2012-01-01

355

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)-adenine derivatives.  

PubMed

An investigation of the interactions of two novel and several known DBTAA-adenine conjugates with double-stranded DNA and RNA has revealed the DNA/RNA groove as the dominant binding site, which is in contrast to the majority of previously studied DBTAA analogues (DNA/RNA intercalators). Only DBTAA-propyladenine conjugates revealed the molecular recognition of AT-DNA by an ICD band pattern > 300 nm, whereas significant ICD bands did not appear for other ds-DNA/RNA. A structure-activity relation for the studied series of compounds showed that the essential structural features for the ICD recognition are a) the presence of DNA-binding appendages (adenine side chain and positively charged side chain) on both DBTAA side chains, and b) the presence of a short propyl linker, which does not support intramolecular aromatic stacking between DBTAA and adenine. The observed AT-DNA-ICD pattern differs from previously reported ss-DNA (poly dT) ICD recognition by a strong negative ICD band at 350 nm, which allows for the dynamic differentiation between ss-DNA (poly dT) and coupled ds-AT-DNA. PMID:25246976

Stojkovi?, Marijana Radi?; Skugor, Marko; Dudek, Lukasz; Grolik, Jaros?aw; Eilmes, Julita; Piantanida, Ivo

2014-01-01

356

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)-adenine derivatives  

PubMed Central

Summary An investigation of the interactions of two novel and several known DBTAA–adenine conjugates with double-stranded DNA and RNA has revealed the DNA/RNA groove as the dominant binding site, which is in contrast to the majority of previously studied DBTAA analogues (DNA/RNA intercalators). Only DBTAA–propyladenine conjugates revealed the molecular recognition of AT-DNA by an ICD band pattern > 300 nm, whereas significant ICD bands did not appear for other ds-DNA/RNA. A structure–activity relation for the studied series of compounds showed that the essential structural features for the ICD recognition are a) the presence of DNA-binding appendages (adenine side chain and positively charged side chain) on both DBTAA side chains, and b) the presence of a short propyl linker, which does not support intramolecular aromatic stacking between DBTAA and adenine. The observed AT-DNA-ICD pattern differs from previously reported ss-DNA (poly dT) ICD recognition by a strong negative ICD band at 350 nm, which allows for the dynamic differentiation between ss-DNA (poly dT) and coupled ds-AT-DNA.

Stojkovic, Marijana Radic; Skugor, Marko; Dudek, Lukasz; Grolik, Jaroslaw; Eilmes, Julita

2014-01-01

357

Molecular detection of hematozoa infections in tundra swans relative to migration patterns and ecological conditions at breeding grounds  

USGS Publications Warehouse

Tundra swans (Cygnus columbianus) are broadly distributed in North America, use a wide variety of habitats, and exhibit diverse migration strategies. We investigated patterns of hematozoa infection in three populations of tundra swans that breed in Alaska using satellite tracking to infer host movement and molecular techniques to assess the prevalence and genetic diversity of parasites. We evaluated whether migratory patterns and environmental conditions at breeding areas explain the prevalence of blood parasites in migratory birds by contrasting the fit of competing models formulated in an occupancy modeling framework and calculating the detection probability of the top model using Akaike Information Criterion (AIC). We described genetic diversity of blood parasites in each population of swans by calculating the number of unique parasite haplotypes observed. Blood parasite infection was significantly different between populations of Alaska tundra swans, with the highest estimated prevalence occurring among birds occupying breeding areas with lower mean daily wind speeds and higher daily summer temperatures. Models including covariates of wind speed and temperature during summer months at breeding grounds better predicted hematozoa prevalence than those that included annual migration distance or duration. Genetic diversity of blood parasites in populations of tundra swans appeared to be relative to hematozoa prevalence. Our results suggest ecological conditions at breeding grounds may explain differences of hematozoa infection among populations of tundra swans that breed in Alaska.

Ramey, Andrew M.; Ely, Craig R.; Schmutz, Joel A.; Pearce, John M.; Heard, Darryl J.

2012-01-01

358

Deposition patterns of molecular phase radon progeny (218Po) in lung bifurcations.  

PubMed

Indoor air contamination by radon and its decay products is currently the focus of considerable attention and is considered by many to be the greatest potential cause of lung cancer in the human environment next to smoking. The bifurcations of the human respiratory tract are regions in which enhanced local deposition of particles (hot spots) can occur. These hot spots are important in estimating the risk from radon exposure but existing mathematical models do not characterize them accurately. In this study, radon progeny in the molecular size range were sampled through an aluminium model of a lung bifurcation. The parent and secondary tube diameters used correspond to the third and fourth generations in Weibel's lung model. Steady state, nominally laminar flows were used in the study. Deposition was measured along the inside, outside, top, and bottom walls of the secondary tubes. Experimental results indicate that the deposition along the inside wall is noticeably higher than that along the other walls. The results also show that along the inside, top, and bottom walls the deposition has its overall maximum at the carina. Other maxima are also observed along the secondary tubes downstream from the carina. PMID:7860308

Kinsara, A A; Loyalka, S K; Tompson, R V; Miller, W H; Holub, R F

1995-03-01

359

Multivariate relationships between molecular descriptors and isomer distribution patterns of PCBs formed during household waste incineration.  

PubMed

The congener-specific concentrations of mono- to deca-chlorinated biphenyls (PC1-10B) in post-combustion zone flue gases from a laboratory-scale fluidized bed reactor were evaluated and correlated with a set of physicochemical properties and chlorine substitution descriptors. The objective was to identify parameters that affect post-combustion zone polychlorinated biphenyl (PCB) formation and interpreting observed correlations by using principal component analysis (PCA), and bidirectional orthogonal projections to latent structures (O2PLS). Both physicochemical variables and chlorine substitution descriptors were shown to have significant effects on the PCB congener distribution; however, the physicochemical descriptors were more influential in all-homologue models, whereas the chlorine substitution descriptors had a greater impact in single-homologue models, which suggests that PCB formation in general may be under thermodynamic control, whereas the distribution of isomers within homologues is more sensitive to chlorine substitution parameters. The EHOMO and ELUMO variables notably influenced both the PCA and the O2PLS models, which indicate that reactivity and polarization in the molecular structures of the PCBs is of importance. PMID:24194416

Jansson, Stina; Grabic, Roman

2014-02-01

360

Prevalence, antibiotic resistance patterns and molecular characterization of Escherichia coli from Austrian sandpits.  

PubMed

The aim was to determine the prevalence of E. coli and coliform bacteria in playground sand of all public children's sandpits in Graz (n = 45), Austria, and to assess the frequency of antimicrobial resistance in E. coli. Molecular characterization included the discrimination of O-serotypes and H-antigens and the determination of virulence and resistance genes, using a microarray technology. E. coli isolates were tested for susceptibility to a set of antibiotics by VITEK2 system and disk diffusion method. In total, 22 (49%) and 44 (98%) sandpits were positive for E. coli and coliform bacteria. Median concentrations of E. coli and coliform bacteria in the sand samples were: 2.6 × 10(4) CFU/100 g and 3.0 × 10(5) CFU/100 g. Resistance rates were: ampicillin, 12.5%; piperacillin, 10.4%; amoxicillin/clavulanic acid, 9.4%; cotrimoxazole, 6.3%; tetracycline, 6.3%; piperacillin/tazobactam, 5.2%. No ESBL- or carbapenemase-producing isolates were found. The most prevalent serogroups were O15, O6 and O4. Isolates harbored 0 up to 16 different virulence genes. PMID:25089889

Badura, Alexandra; Luxner, Josefa; Feierl, Gebhard; Reinthaler, Franz F; Zarfel, Gernot; Galler, Herbert; Pregartner, Gudrun; Riedl, Regina; Grisold, Andrea J

2014-11-01

361

Molecular Properties by Quantum Monte Carlo: An Investigation on the Role of the Wave Function Ansatz and the Basis Set in the Water Molecule  

PubMed Central

Quantum Monte Carlo methods are accurate and promising many body techniques for electronic structure calculations which, in the last years, are encountering a growing interest thanks to their favorable scaling with the system size and their efficient parallelization, particularly suited for the modern high performance computing facilities. The ansatz of the wave function and its variational flexibility are crucial points for both the accurate description of molecular properties and the capabilities of the method to tackle large systems. In this paper, we extensively analyze, using different variational ansatzes, several properties of the water molecule, namely, the total energy, the dipole and quadrupole momenta, the ionization and atomization energies, the equilibrium configuration, and the harmonic and fundamental frequencies of vibration. The investigation mainly focuses on variational Monte Carlo calculations, although several lattice regularized diffusion Monte Carlo calculations are also reported. Through a systematic study, we provide a useful guide to the choice of the wave function, the pseudopotential, and the basis set for QMC calculations. We also introduce a new method for the computation of forces with finite variance on open systems and a new strategy for the definition of the atomic orbitals involved in the Jastrow-Antisymmetrised Geminal power wave function, in order to drastically reduce the number of variational parameters. This scheme significantly improves the efficiency of QMC energy minimization in case of large basis sets. PMID:24526929

Zen, Andrea; Luo, Ye; Sorella, Sandro; Guidoni, Leonardo

2014-01-01

362

Molecular dynamics simulations of the quasielastic neutron scattering from monolayer films of intermediate--length n -alkane molecules adsorbed on graphite.  

NASA Astrophysics Data System (ADS)

The quasielastic neutron scattering (QNS) intensity from monolayer films of tetracosane (n-C_24H_50) and dotriacontane (n-C_32H_66) adsorbed on graphite has been measured experimentally over a range of wavevector transfers Q at temperatures spanning the monolayer melting point. In addition, we have studied the origin of QNS in molecular dynamics (MD) simulations. The simulations allow separation of the contributions from the center--of--mass diffusive motion and intramolecular diffusive motion. The latter is a complicated type of motion involving a rolling motion around the long axis of the molecules with a distribution of gauche defects along the chain. Our analysis shows that all of these diffusive motions contribute to the QNS even at temperatures below the monolayer melting point. The QNS component from the intramolecular diffusive motions are more pronounced at large Q whereas the center--of--mass diffusive motion dominates the QNS at small Q. Thus the MD simulations have been very helpful in interpreting the experimental spectra.

Hansen, F. Y.; Herwig, K. W.; Taub, H.; Fuhrmann, D.; Criswell, L.

2000-03-01

363

Patterns of Molecular Variation and Evolution in Drosophila americana and Its Relatives  

PubMed Central

We present the results of a survey of DNA sequence variability at X-linked and autosomal loci in Drosophila americana and of patterns of DNA sequence evolution among D. americana and four other related species in the virilis group of Drosophila. D. americana shows a typical level of silent polymorphism for a Drosophila species, but has an unusually low ratio of nonsynonymous to silent variation. Both D. virilis and D. americana also show a low ratio of nonsynonymous to synonymous substitutions along their respective lineages since the split from their common ancestor. The proportion of amino acid substitutions between D. americana and its relatives that are caused by positive selection, as estimated by extensions of the McDonald–Kreitman test, appears to be unusually high. We cannot, however, exclude the possibility that this reflects a recent increase in the intensity of selection on nonsynonymous mutations in D. americana and D. virilis. We also find that base composition at neutral sites appears to be in overall equilibrium among these species, but there is evidence for departure from equilibrium for codon usage in some lineages. PMID:17507679

Maside, Xulio; Charlesworth, Brian

2007-01-01

364

Molecular signatures in childhood acute leukemia and their correlations to expression patterns in normal hematopoietic subpopulations  

PubMed Central

Global expression profiles of a consecutive series of 121 childhood acute leukemias (87 B lineage acute lymphoblastic leukemias, 11 T cell acute lymphoblastic leukemias, and 23 acute myeloid leukemias), six normal bone marrows, and 10 normal hematopoietic subpopulations of different lineages and maturations were ascertained by using 27K cDNA microarrays. Unsupervised analyses revealed segregation according to lineages and primary genetic changes, i.e., TCF3(E2A)/PBX1, IGH@/MYC, ETV6(TEL)/RUNX1(AML1), 11q23/MLL, and hyperdiploidy (>50 chromosomes). Supervised discriminatory analyses were used to identify differentially expressed genes correlating with lineage and primary genetic change. The gene-expression profiles of normal hematopoietic cells were also studied. By using principal component analyses (PCA), a differentiation axis was exposed, reflecting lineages and maturation stages of normal hematopoietic cells. By applying the three principal components obtained from PCA of the normal cells on the leukemic samples, similarities between malignant and normal cell lineages and maturations were investigated. Apart from showing that leukemias segregate according to lineage and genetic subtype, we provide an extensive study of the genes correlating with primary genetic changes. We also investigated the expression pattern of these genes in normal hematopoietic cells of different lineages and maturations, identifying genes preferentially expressed by the leukemic cells, suggesting an ectopic activation of a large number of genes, likely to reflect regulatory networks of pathogenetic importance that also may provide attractive targets for future directed therapies. PMID:16354839

Andersson, Anna; Olofsson, Tor; Lindgren, David; Nilsson, Bjorn; Ritz, Cecilia; Eden, Patrik; Lassen, Carin; Rade, Johan; Fontes, Magnus; Morse, Helena; Heldrup, Jesper; Behrendtz, Mikael; Mitelman, Felix; Hoglund, Mattias; Johansson, Bertil; Fioretos, Thoas

2005-01-01

365

Computer-assisted studies of molecular structure and genotoxic activity by pattern recognition techniques.  

PubMed Central

Often a compound's biological activity is determined by complex relationships between its structural components. Such a relationship often can only be adequately described and exploited by multivariate structure-activity relationship (SAR) studies that can deal with many variables simultaneously. Pattern recognition (PR) is a multivariate technique that is well suited for the qualitative, active-inactive, data that is often supplied by biological assays. PR studies of compounds of known activity can yield information that will allow the prediction of the activity of untested compounds. ADAPT is a computerized system that was developed for such PR-SAR studies. A general introduction to this field is presented and the methodology used for such a study is described in the context of an actual study of mutagenic compounds. The data requirements, descriptor generation, and the details of a PR study are discussed. In addition, the example study was chosen to highlight the problems that may occur if a study is not well formulated and carefully executed. Current work and future plans for computerized mutagen screening are discussed. PMID:3905380

Stouch, T R; Jurs, P C

1985-01-01

366

Molecular imaging coupled to pattern recognition distinguishes response to temozolomide in preclinical glioblastoma.  

PubMed

Non-invasive monitoring of response to treatment of glioblastoma (GB) is nowadays carried out using MRI. MRS and MR spectroscopic imaging (MRSI) constitute promising tools for this undertaking. A temozolomide (TMZ) protocol was optimized for GL261 GB. Sixty-three mice were studied by MRI/MRS/MRSI. The spectroscopic information was used for the classification of control brain and untreated and responding GB, and validated against post-mortem immunostainings in selected animals. A classification system was developed, based on the MRSI-sampled metabolome of normal brain parenchyma, untreated and responding GB, with a 93% accuracy. Classification of an independent test set yielded a balanced error rate of 6% or less. Classifications correlated well both with tumor volume changes detected by MRI after two TMZ cycles and with the histopathological data: a significant decrease (p?pattern of treated tumors, allowing the non-invasive classification of growing and responding GL261 GB. The methodology described can be applied to preclinical treatment efficacy studies to test new antitumoral drugs, and begets translational potential for early response detection in clinical studies. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25208348

Delgado-Goñi, Teresa; Julià-Sapé, Margarida; Candiota, Ana Paula; Pumarola, Martí; Arús, Carles

2014-11-01

367

Genomic profiling reveals distinctive molecular relapse patterns in IDH1/2 wild-type glioblastoma.  

PubMed

Molecular changes associated with the progression of glioblastoma after standard radiochemotherapy remain poorly understood. We compared genomic profiles of 27 paired primary and recurrent IDH1/2 wild-type glioblastomas by genome-wide array-based comparative genomic hybridization. By bioinformatic analysis, primary and recurrent tumor profiles were normalized and segmented, chromosomal gains and losses identified taking the tumor cell content into account, and difference profiles deduced. Seven of 27 (26%) pairs lacked DNA copy number differences between primary and recurrent tumors (equal pairs). The recurrent tumors in 9/27 (33%) pairs contained all chromosomal imbalances of the primary tumors plus additional ones, suggesting a sequential acquisition of and/or selection for aberrations during progression (sequential pairs). In 11/27 (41%) pairs, the profiles of primary and recurrent tumors were divergent, i.e., the recurrent tumors contained additional aberrations but had lost others, suggesting a polyclonal composition of the primary tumors and considerable clonal evolution (discrepant pairs). Losses on 9p21.3 harboring the CDKN2A/B locus were significantly more common in primary tumors from sequential and discrepant (nonequal) pairs. Nonequal pairs showed ten regions of recurrent genomic differences between primary and recurrent tumors harboring 46 candidate genes associated with tumor recurrence. In particular, copy numbers of genes encoding apoptosis regulators were frequently changed at progression. In summary, approximately 25% of IDH1/2 wild-type glioblastoma pairs have stable genomic imbalances. In contrast, approximately 75% of IDH1/2 wild-type glioblastomas undergo further genomic aberrations and alter their clonal composition upon recurrence impacting their genomic profile, a process possibly facilitated by 9p21.3 loss in the primary tumor. © 2014 Wiley Periodicals, Inc. PMID:24706357

Riehmer, Vera; Gietzelt, Jens; Beyer, Ulrike; Hentschel, Bettina; Westphal, Manfred; Schackert, Gabriele; Sabel, Michael C; Radlwimmer, Bernhard; Pietsch, Torsten; Reifenberger, Guido; Weller, Michael; Weber, Ruthild G; Loeffler, Markus

2014-07-01

368

Molecular characterization and expression patterns of the big defensin gene in freshwater mussel (Hyriopsis cumingii).  

PubMed

Antimicrobial peptides (AMPs), of which big defensins are examples, are an important component of the natural defenses of most living organisms, and possess remarkable microbicidal activities. In the present study, using expressed-sequence tag sequences from a cDNA library and RACE, the full-length cDNA sequence of the big defensin gene from the triangle-shell pearl mussel, Hyriopsis cumingii, (HcBD), was cloned. The gene consists of a 5'-untranslated region (UTR) of 166 bp, a 3'-UTR region of 96 bp, and an open reading frame of 342 bp that encodes 113 amino acids, consisting of a 23 amino acid signal peptide and a mature peptide of 90 amino acids with a molecular mass of 12.5 kDa. Amino acid sequence analysis showed that the sequence contained a transmembrane domain and a hydrophobic region. The full-length amino acid sequence showed the highest similarity to an amphioxus (Branchiostoma floridae) sequence (64%), and lower similarities to other known defensins (?-, ?-, and ?-defensins, and insect defensins). Expression of HcBD was relatively high in the mantle and blood, lower in other tested tissues, and absent in gill and foot tissues. Real-time quantitative PCR was used to investigate HcBD expression in various tissues at different time points after injection of Aeromonas hydrophila. At 4 h post-inoculation, HcBD expression in the mantle, liver, intestine, gill, and foot was greater than in the control, with the greatest expression at 72 h, while at 24 h, expression in the liver, intestine, gill, and foot were at their lowest levels. These results suggest that HcBD might play an important role in the host immune response. This study enriches the basic research on the big defensin family of antimicrobial peptides and lays foundations for further research on antimicrobial peptide expression and relevance to disease defense. PMID:24615035

Wang, G-L; Xia, X-L; Li, X-L; Dong, S-J; Li, J-L

2014-01-01

369

Molecular Evidence of the Toxic Effects of Diatom Diets on Gene Expression Patterns in Copepods  

PubMed Central

Background Diatoms are dominant photosynthetic organisms in the world's oceans and are considered essential in the transfer of energy through marine food chains. However, these unicellular plants at times produce secondary metabolites such as polyunsaturated aldehydes and other products deriving from the oxidation of fatty acids that are collectively termed oxylipins. These cytotoxic compounds are responsible for growth inhibition and teratogenic activity, potentially sabotaging future generations of grazers by inducing poor recruitment in marine organisms such as crustacean copepods. Principal Findings Here we show that two days of feeding on a strong oxylipin-producing diatom (Skeletonema marinoi) is sufficient to inhibit a series of genes involved in aldehyde detoxification, apoptosis, cytoskeleton structure and stress response in the copepod Calanus helgolandicus. Of the 18 transcripts analyzed by RT-qPCR at least 50% were strongly down-regulated (aldehyde dehydrogenase 9, 8 and 6, cellular apoptosis susceptibility and inhibitor of apoptosis IAP proteins, heat shock protein 40, alpha- and beta-tubulins) compared to animals fed on a weak oxylipin-producing diet (Chaetoceros socialis) which showed no changes in gene expression profiles. Conclusions Our results provide molecular evidence of the toxic effects of strong oxylipin-producing diatoms on grazers, showing that primary defense systems that should be activated to protect copepods against toxic algae can be inhibited. On the other hand other classical detoxification genes (glutathione S-transferase, superoxide dismutase, catalase, cytochrome P450) were not affected possibly due to short exposure times. Given the importance of diatom blooms in nutrient-rich aquatic environments these results offer a plausible explanation for the inefficient use of a potentially valuable food resource, the spring diatom bloom, by some copepod species. PMID:22046381

Lauritano, Chiara; Borra, Marco; Carotenuto, Ylenia; Biffali, Elio; Miralto, Antonio; Procaccini, Gabriele; Ianora, Adrianna

2011-01-01

370

Surface Patterning of Benzene Carboxylic Acids on Graphite: Influence of structure, solvent, and concentration on molecular self-assembly  

NASA Astrophysics Data System (ADS)

Scanning tunneling microscopy (STM) was used to investigate the molecular self-assembly of four different benzene carboxylic acid derivatives at the liquid/graphite interface: pyromellitic acid (1,2,4,5-benzenetetracarboxylic acid), trimellitic acid (1,2,4-benzenetricarboxylic acid), trimesic acid (1,3,5-benzenetricarboxylic acid), and 1,3,5-benzenetriacetic acid. A range of two dimensional networks are observed that depend sensitively on the number of carboxylic acids present, the nature of the solvent, and the solution concentration. We will describe our recent efforts to determine (a) the preferential two-dimensional structure(s) for each benzene carboxylic acid at the liquid/graphite interface, (b) the thermodynamic and kinetic factors influencing self-assembly (or lack thereof), (c) the role solvent plays in the assembly, (e) the effect of in situ versus ex situ dilution on surface packing density, and (f) the temporal evolution of the self-assembled monolayer. Results of computational analysis of analog molecules and model monolayer films will also be presented to aid assignment of network structures and to provide a qualitative picture of surface adsorption and network formation.

Florio, Gina; Stiso, Kimberly; Campanelli, Joseph; Dessources, Kimberly; Folkes, Trudi

2012-02-01

371

Magnetic resonance molecular imaging of vascular cell adhesion molecule-1 expression in inflammatory lesions using a peptide-vectorized paramagnetic imaging probe.  

PubMed

The vascular cell adhesion molecule-1 (VCAM-1) has distinct roles in inflammatory cell recruitment to the damaged vessel wall. In the present work, a cyclic heptapeptide phage displayed library was screened in vitro during four rounds of biopanning. On the basis of Kd and IC50 values, a peptide (encoded as R832) was selected for in vitro and in vivo validation. After conjugation to Gd-DOTA, VCAM-1 imaging was assessed by MRI on a model of T cell mediated hepatitis, induced in mice by concanavalin A. On histological samples, the location of biotinylated R832 (R832-Bt) around liver veins in hepatitis resembles the pattern of MRI enhancement. Gd-DOTA-R832 was then assessed on ApoE(-/-) mice and produced an important signal enhancement of the aortic wall, while R832-Bt interacted with morphologic structures comparable to those marked by anti-VCAM-1 antibody. In conclusion, the in vitro and in vivo evaluation of peptide R832 suggests a specific interaction with the targeted biomolecule. Its conjugation to imaging reporters could assist the diagnosis of inflammatory diseases. PMID:19580288

Burtea, Carmen; Laurent, Sophie; Port, Marc; Lancelot, Eric; Ballet, Sébastien; Rousseaux, Olivier; Toubeau, Gérard; Vander Elst, Luce; Corot, Claire; Muller, Robert N

2009-08-13

372

Molecular and Functional Characterization of Mouse Signaling Lymphocytic Activation Molecule (SLAM): Differential Expression and Responsiveness in Th1 and Th2 Cells1  

Microsoft Academic Search

Optimal T cell activation and expansion require engagement of the TCR plus costimulatory signals delivered through accessory molecules. SLAM (signaling lymphocytic activation molecule), a 70-kDa costimulatory molecule belonging to the Ig superfamily, was defined as a human cell surface molecule that mediated CD28-independent proliferation of human T cells and IFN-g pro- duction by human Th1 and Th2 clones. In this

Antonio G. Castro; Thomas M. Hauser; Benjamin G. Cocks; John Abrams; Sandra Zurawski; Tatyana Churakova; Francesca Zonin; Douglas Robinson; Stuart G. Tangye; Gregorio Aversa; Kim E. Nichols; Jan E. de Vries; Lewis L. Lanier; Anne O'Garra

373

Molecular dynamics investigations of ozone on an ab initio potential energy surface with the utilization of pattern-recognition neural network for accurate determination of product formation.  

PubMed

The singlet-triplet transformation and molecular dissociation of ozone (O(3)) gas is investigated by performing quasi-classical molecular dynamics (MD) simulations on an ab initio potential energy surface (PES) with visible and near-infrared excitations. MP4(SDQ) level of theory with the 6-311g(2d,2p) basis set is executed for three different electronic spin states (singlet, triplet, and quintet). In order to simplify the potential energy function, an approximation is adopted by ignoring the spin-orbit coupling and allowing the molecule to switch favorably and instantaneously to the spin state that is more energetically stable (lowest in energy among the three spin states). This assumption has previously been utilized to study the SiO(2) system as reported by Agrawal et al. (J. Chem. Phys. 2006, 124 (13), 134306). The use of such assumption in this study probably makes the upper limits of computed rate coefficients the true rate coefficients. The global PES for ozone is constructed by fitting 5906 ab initio data points using a 60-neuron two-layer feed-forward neural network. The mean-absolute error and root-mean-squared error of this fit are 0.0446 eV (1.03 kcal/mol) and 0.0756 eV (1.74 kcal/mol), respectively, which reveal very good fitting accuracy. The parameter coefficients of the global PES are reported in this paper. In order to identify the spin state with high confidence, we propose the use of a pattern-recognition neural network, which is trained to predict the spin state of a given configuration (with a prediction accuracy being 95.6% on a set of testing data points). To enhance the prediction effectiveness, a buffer series of five points are validated to confirm the spin state during the MD process to gain better confidence. Quasi-classical MD simulations from 1.2 to 2.4 eV of total internal energy (including zero-point energy) result in rate coefficients of singlet-triplet transformation in the range of 0.027 ps(-1) to 1.21 ps(-1). Also, we find very low dissociation probability up to 2.4 eV of internal energy during the investigating period (5 ps), which suggests that dissociation does not occur directly from the singlet ground-state, but it involves the excited triplet-state as an intermediate step and requires more reaction time to occur. PMID:21888438

Le, Hung M; Dinh, Thach S; Le, Hieu V

2011-10-13

374

Nanoscale fluid flows in the vicinity of patterned surfaces  

E-print Network

Molecular dynamics simulations of dense and rarefied fluids comprising small chain molecules in chemically patterned nano-channels predict a novel switching from Poiseuille to plug flow along the channel. We also demonstrate behavior akin to the lotus effect for a nanodrop on a chemically patterned substrate. Our results show that one can control and exploit the behavior of fluids at the nanoscale using chemical patterning.

Marek Cieplak; Joel Koplik; Jayanth R. Banavar

2006-03-18

375

Simulating the Mammalian Blastocyst - Molecular and Mechanical Interactions Pattern the Embryo  

PubMed Central

Mammalian embryogenesis is a dynamic process involving gene expression and mechanical forces between proliferating cells. The exact nature of these interactions, which determine the lineage patterning of the trophectoderm and endoderm tissues occurring in a highly regulated manner at precise periods during the embryonic development, is an area of debate. We have developed a computational modeling framework for studying this process, by which the combined effects of mechanical and genetic interactions are analyzed within the context of proliferating cells. At a purely mechanical level, we demonstrate that the perpendicular alignment of the animal-vegetal (a-v) and embryonic-abembryonic (eb-ab) axes is a result of minimizing the total elastic conformational energy of the entire collection of cells, which are constrained by the zona pellucida. The coupling of gene expression with the mechanics of cell movement is important for formation of both the trophectoderm and the endoderm. In studying the formation of the trophectoderm, we contrast and compare quantitatively two hypotheses: (1) The position determines gene expression, and (2) the gene expression determines the position. Our model, which couples gene expression with mechanics, suggests that differential adhesion between different cell types is a critical determinant in the robust endoderm formation. In addition to differential adhesion, two different testable hypotheses emerge when considering endoderm formation: (1) A directional force acts on certain cells and moves them into forming the endoderm layer, which separates the blastocoel and the cells of the inner cell mass (ICM). In this case the blastocoel simply acts as a static boundary. (2) The blastocoel dynamically applies pressure upon the cells in contact with it, such that cell segregation in the presence of differential adhesion leads to the endoderm formation. To our knowledge, this is the first attempt to combine cell-based spatial mechanical simulations with genetic networks to explain mammalian embryogenesis. Such a framework provides the means to test hypotheses in a controlled in silico environment. PMID:21573197

Krupinski, Pawel; Chickarmane, Vijay; Peterson, Carsten

2011-01-01

376

Domestication and the Mitochondrial Genome: Comparing Patterns and Rates of Molecular Evolution in Domesticated Mammals and Birds and Their Wild Relatives  

PubMed Central

Studies of domesticated animals have led to the suggestion that domestication could have significant effects on patterns of molecular evolution. In particular, analyses of mitochondrial genome sequences from domestic dogs and yaks have yielded higher ratios of non-synonymous to synonymous substitutions in the domesticated lineages than in their wild relatives. These results are important because they imply that changes to selection or population size operating over a short timescale can cause significant changes to the patterns of mitochondrial molecular evolution. In this study, our aim is to test whether the impact on mitochondrial genome evolution is a general feature of domestication or whether it is specific to particular examples. We test whether domesticated mammals and birds have consistently different patterns of molecular evolution than their wild relatives for 16 phylogenetically independent comparisons of mitochondrial genome sequences. We find no consistent difference in branch lengths or dN/dS between domesticated and wild lineages. We also find no evidence that our failure to detect a consistent pattern is due to the short timescales involved or low genetic distance between domesticated lineages and their wild relatives. However, removing comparisons where the wild relative may also have undergone a bottleneck does reveal a pattern consistent with reduced effective population size in domesticated lineages. Our results suggest that, although some domesticated lineages may have undergone changes to selective regime or effective population size that could have affected mitochondrial evolution, it is not possible to generalize these patterns over all domesticated mammals and birds. PMID:24459286

Moray, Camile; Lanfear, Robert; Bromham, Lindell

2014-01-01

377

Domestication and the mitochondrial genome: comparing patterns and rates of molecular evolution in domesticated mammals and birds and their wild relatives.  

PubMed

Studies of domesticated animals have led to the suggestion that domestication could have significant effects on patterns of molecular evolution. In particular, analyses of mitochondrial genome sequences from domestic dogs and yaks have yielded higher ratios of non-synonymous to synonymous substitutions in the domesticated lineages than in their wild relatives. These results are important because they imply that changes to selection or population size operating over a short timescale can cause significant changes to the patterns of mitochondrial molecular evolution. In this study, our aim is to test whether the impact on mitochondrial genome evolution is a general feature of domestication or whether it is specific to particular examples. We test whether domesticated mammals and birds have consistently different patterns of molecular evolution than their wild relatives for 16 phylogenetically independent comparisons of mitochondrial genome sequences. We find no consistent difference in branch lengths or dN/dS between domesticated and wild lineages. We also find no evidence that our failure to detect a consistent pattern is due to the short timescales involved or low genetic distance between domesticated lineages and their wild relatives. However, removing comparisons where the wild relative may also have undergone a bottleneck does reveal a pattern consistent with reduced effective population size in domesticated lineages. Our results suggest that, although some domesticated lineages may have undergone changes to selective regime or effective population size that could have affected mitochondrial evolution, it is not possible to generalize these patterns over all domesticated mammals and birds. PMID:24459286

Moray, Camile; Lanfear, Robert; Bromham, Lindell

2014-01-01

378

Toll-like receptor 9-mediated protection of enterovirus 71 infection in mice is due to the release of danger-associated molecular patterns.  

PubMed

Enterovirus 71 (EV71), a positive-stranded RNA virus, is the major cause of hand, foot, and mouth disease (HFMD) with severe neurological symptoms. Antiviral type I interferon (alpha/beta interferon [IFN-?/?]) responses initiated from innate receptor signaling are inhibited by EV71-encoded proteases. It is less well understood whether EV71-induced apoptosis provides a signal to activate type I interferon responses as a host defensive mechanism. In this report, we found that EV71 alone cannot activate Toll-like receptor 9 (TLR9) signaling, but supernatant from EV71-infected cells is capable of activating TLR9. We hypothesized that TLR9-activating signaling from plasmacytoid dendritic cells (pDCs) may contribute to host defense mechanisms. To test our hypothesis, Flt3 ligand-cultured DCs (Flt3L-DCs) from both wild-type (WT) and TLR9 knockout (TLR9KO) mice were infected with EV71. More viral particles were produced in TLR9KO mice than by WT mice. In contrast, alpha interferon (IFN-?), monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-?), IFN-?, interleukin 6 (IL-6), and IL-10 levels were increased in Flt3L-DCs from WT mice infected with EV71 compared with TLR9KO mice. Seven-day-old TLR9KO mice infected with a non-mouse-adapted EV71 strain developed neurological lesion-related symptoms, including hind-limb paralysis, slowness, ataxia, and lethargy, but WT mice did not present with these symptoms. Lung, brain, small intestine, forelimb, and hind-limb tissues collected from TLR9KO mice exhibited significantly higher viral loads than equivalent tissues collected from WT mice. Histopathologic damage was observed in brain, small intestine, forelimb, and hind-limb tissues collected from TLR9KO mice infected with EV71. Our findings demonstrate that TLR9 is an important host defense molecule during EV71 infection. Importance: The host innate immune system is equipped with pattern recognition receptors (PRRs), which are useful for defending the host against invading pathogens. During enterovirus 71 (EV71) infection, the innate immune system is activated by pathogen-associated molecular patterns (PAMPs), which include viral RNA or DNA, and these PAMPs are recognized by PRRs. Toll-like receptor 3 (TLR3) and TLR7/8 recognize viral nucleic acids, and TLR9 senses unmethylated CpG DNA or pathogen-derived DNA. These PRRs stimulate the production of type I interferons (IFNs) to counteract viral infection, and they are the major source of antiviral alpha interferon (IFN-?) production in pDCs, which can produce 200- to 1,000-fold more IFN-? than any other immune cell type. In addition to PAMPs, danger-associated molecular patterns (DAMPs) are known to be potent activators of innate immune signaling, including TLR9. We found that EV71 induces cellular apoptosis, resulting in tissue damage; the endogenous DNA from dead cells may activate the innate immune system through TLR9. Therefore, our study provides new insights into EV71-induced apoptosis, which stimulates TLR9 in EV71-associated infections. PMID:25078697

Hsiao, Hung-Bo; Chou, Ai-Hsiang; Lin, Su-I; Chen, I-Hua; Lien, Shu-Pei; Liu, Chia-Chyi; Chong, Pele; Liu, Shih-Jen

2014-10-01

379

Molecule nanoweaver  

SciTech Connect

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

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

2009-03-10

380

Two Metallothionein Genes in Oxya chinensis: Molecular Characteristics, Expression Patterns and Roles in Heavy Metal Stress  

PubMed Central

Metallothioneins (MTs) are small, cysteine-rich, heavy metal-binding proteins involved in metal homeostasis and detoxification in living organisms. In the present study, we cloned two MT genes (OcMT1 and OcMT2) from Oxya chinensis, analyzed the expression patterns of the OcMT transcripts in different tissues and at varying developmental stages using real-time quantitative PCR (RT-qPCR), evaluated the functions of these two MTs using RNAi and recombinant proteins in an E. coli expression system. The full-length cDNAs of OcMT1 and OcMT2 encoded 40 and 64 amino acid residues, respectively. We found Cys-Cys, Cys-X-Cys and Cys-X-Y-Z-Cys motifs in OcMT1 and OcMT2. These motifs might serve as primary chelating sites, as in other organisms. These characteristics suggest that OcMT1 and OcMT2 may be involved in heavy metal detoxification by capturing the metals. Two OcMT were expressed at all developmental stages, and the highest levels were found in the eggs. Both transcripts were expressed in all eleven tissues examined, with the highest levels observed in the brain and optic lobes, followed by the fat body. The expression of OcMT2 was also relatively high in the ovaries. The functions of OcMT1 and OcMT2 were explored using RNA interference (RNAi) and different concentrations and treatment times for the three heavy metals. Our results indicated that mortality increased significantly from 8.5% to 16.7%, and this increase was both time- and dose-dependent. To evaluate the abilities of these two MT proteins to confer heavy metal tolerance to E. coli, the bacterial cells were transformed with pET-28a plasmids containing the OcMT genes. The optical densities of both the MT-expressing and control cells decreased with increasing concentrations of CdCl2. Nevertheless, the survival rates of the MT-overexpressing cells were higher than those of the controls. Our results suggest that these two genes play important roles in heavy metal detoxification in O. chinensis. PMID:25391131

Liu, Yaoming; Wu, Haihua; Kou, Lihua; Liu, Xiaojian; Zhang, Jianzhen; Guo, Yaping; Ma, Enbo

2014-01-01

381

Phase-transfer energetics of small-molecule alcohols across the water-hexane interface: molecular dynamics simulations using charge equilibration models.  

PubMed

We study the water-hexane interface using molecular dynamics (MD) and polarizable charge equilibration (CHEQ) force fields. Bulk densities for TIP4P-FQ water and hexane, 1.0086±0.0002 and 0.6378±0.0001 g/cm(3), demonstrate excellent agreement with experiment. Interfacial width and interfacial tension are consistent with previously reported values. The in-plane component of the dielectric permittivity (?(||)) for water is shown to decrease from 81.7±0.04 to unity, transitioning longitudinally from bulk water to bulk hexane. ?(||) for hexane reaches a maximum in the interface, but this term represents only a small contribution to the total dielectric constant (as expected for a non-polar species). Structurally, net orientations of the molecules arise in the interfacial region such that hexane lies slightly parallel to the interface and water reorients to maximize hydrogen bonding. Interfacial potentials due to contributions of the water and hexane are calculated to be -567.9±0.13 and 198.7±0.01 mV, respectively, giving rise to a total potential in agreement with the range of values reported from previous simulations of similar systems. Potentials of mean force (PMF) calculated for methanol, ethanol, and 1-propanol for the transfer from water to hexane indicate an interfacial free energy minimum, corresponding to the amphiphilic nature of the molecules. The magnitudes of transfer free energies were further characterized from the solvation free energies of alcohols in water and hexane using thermodynamic integration. This analysis shows that solvation free energies for alcohols in hexane are 0.2-0.3 kcal/mol too unfavorable, whereas solvation of alcohols in water is approximately 1 kcal/mol too favorable. For the pure hexane-water interfacial simulations, we observe a monotonic decrease of the water dipole moment to near-vacuum values. This suggests that the electrostatic component of the desolvation free energy is not as severe for polarizable models than for fixed-charge force fields. The implications of such behavior pertain to the modeling of polar and charged solutes in lipidic environments. PMID:21414823

Bauer, Brad A; Zhong, Yang; Meninger, David J; Davis, Joseph E; Patel, Sandeep

2011-04-01

382

Correcting for bias of molecular confinement parameters induced by small-time-series sample sizes in single-molecule trajectories containing measurement noise  

NASA Astrophysics Data System (ADS)

Several single-molecule studies aim to reliably extract parameters characterizing molecular confinement or transient kinetic trapping from experimental observations. Pioneering works from single-particle tracking (SPT) in membrane diffusion studies [Kusumi , Biophys. J.BIOJAU0006-349510.1016/S0006-3495(93)81253-0 65, 2021 (1993)] appealed to mean square displacement (MSD) tools for extracting diffusivity and other parameters quantifying the degree of confinement. More recently, the practical utility of systematically treating multiple noise sources (including noise induced by random photon counts) through likelihood techniques has been more broadly realized in the SPT community. However, bias induced by finite-time-series sample sizes (unavoidable in practice) has not received great attention. Mitigating parameter bias induced by finite sampling is important to any scientific endeavor aiming for high accuracy, but correcting for bias is also often an important step in the construction of optimal parameter estimates. In this article, it is demonstrated how a popular model of confinement can be corrected for finite-sample bias in situations where the underlying data exhibit Brownian diffusion and observations are measured with non-negligible experimental noise (e.g., noise induced by finite photon counts). The work of Tang and Chen [J. Econometrics0304-407610.1016/j.jeconom.2008.11.001 149, 65 (2009)] is extended to correct for bias in the estimated “corral radius” (a parameter commonly used to quantify confinement in SPT studies) in the presence of measurement noise. It is shown that the approach presented is capable of reliably extracting the corral radius using only hundreds of discretely sampled observations in situations where other methods (including MSD and Bayesian techniques) would encounter serious difficulties. The ability to accurately statistically characterize transient confinement suggests additional techniques for quantifying confined and/or hop diffusion in complex environments.

Calderon, Christopher P.

2013-07-01

383

Molecular evolution of psbA gene in ferns: unraveling selective pressure and co-evolutionary pattern  

PubMed Central

Background The photosynthetic oxygen-evolving photo system II (PS II) produces almost the entire oxygen in the atmosphere. This unique biochemical system comprises a functional core complex that is encoded by psbA and other genes. Unraveling the evolutionary dynamics of this gene is of particular interest owing to its direct role in oxygen production. psbA underwent gene duplication in leptosporangiates, in which both copies have been preserved since. Because gene duplication is often followed by the non-fictionalization of one of the copies and its subsequent erosion, preservation of both psbA copies pinpoint functional or regulatory specialization events. The aim of this study was to investigate the molecular evolution of psbA among fern lineages. Results We sequenced psbA , which encodes D1 protein in the core complex of PSII, in 20 species representing 8 orders of extant ferns; then we searched for selection and convolution signatures in psbA across the 11 fern orders. Collectively, our results indicate that: (1) selective constraints among D1 protein relaxed after the duplication in 4 leptosporangiate orders; (2) a handful positively selected codons were detected within species of single copy psbA, but none in duplicated ones; (3) a few sites among D1 protein were involved in co-evolution process which may intimate significant functional/structural communications between them. Conclusions The strong competition between ferns and angiosperms for light may have been the main cause for a continuous fixation of adaptive amino acid changes in psbA , in particular after its duplication. Alternatively, a single psbA copy may have undergone bursts of adaptive changes at the molecular level to overcome angiosperms competition. The strong signature of positive Darwinian selection in a major part of D1 protein is testament to this. At the same time, species own two psbA copies hardly have positive selection signals among the D1 protein coding sequences. In this study, eleven co-evolving sites have been detected via different molecules, which may be more important than others. PMID:22899792

2012-01-01

384

Atoms, Molecules, and Ions  

NSDL National Science Digital Library

General chemistry WebCT exam/quiz questions. The Atoms, Molecules, and Ions topic covers the basics of the composition of atoms, including subatomic particles, elements, allotropes, and isotopes. Periodic placement and trends, molar mass, and molecular formulas and ions are also included.

2008-02-12

385

Expanding the repertoire of small molecule transcriptional activation domains.  

PubMed

Molecules that can reconstitute the function of transcriptional activators hold enormous potential as therapeutic agents and as mechanistic probes. Previously we described an isoxazolidine bearing functional groups similar to natural transcriptional activators that up-regulates transcription 80-fold at 1 microM in cell culture. In this study, we analyze analogs of this molecule to define key characteristics of small molecules that function as transcriptional activation domains in cells. Conformational rigidity is an important contributor to function as is an overall amphipathic substitution pattern. Using these criteria, we identified additional molecular scaffolds with excellent (approximately 60-fold) activity as transcriptional activation domains. These results point the way for the creation of new generations of small molecules with this function. PMID:18334300

Casey, Ryan J; Desaulniers, Jean-Paul; Hojfeldt, Jonas W; Mapp, Anna K

2009-02-01

386

The Destructive Citrus Pathogen, 'Candidatus Liberibacter asiaticus' Encodes a Functional Flagellin Characteristic of a Pathogen-Associated Molecular Pattern  

PubMed Central

Huanglongbing (HLB) is presently the most devastating citrus disease worldwide. As an intracellular plant pathogen and insect symbiont, the HLB bacterium, ‘Candidatus Liberibacter asiaticus’ (Las), retains the entire flagellum-encoding gene cluster in its significantly reduced genome. Las encodes a flagellin and hook-associated protein (Fla) of 452 amino acids that contains a conserved 22 amino acid domain (flg22) at positions 29 to 50 in the N-terminus. The phenotypic alteration in motility of a Sinorhizobium meliloti mutant lacking the fla genes was partially restored by constitutive expression of FlaLas. Agrobacterium-mediated transient expression in planta revealed that FlaLas induced cell death and callose deposition in Nicotiana benthamiana, and that the transcription of BAK1 and SGT1, which are associated with plant innate immunity, was upregulated. Amino acid substitution experiments revealed that residues 38 (serine) and 39 (aspartate) of FlaLas were essential for callose induction. The synthetic flg22Las peptide could not induce plant cell death but retained the ability to induce callose deposition at a concentration of 20 µM or above. This demonstrated that the pathogen-associated molecular pattern (PAMP) activity of flg22 in Las was weaker than those in other well-studied plant pathogenic bacteria. These results indicate that FlaLas acts as a PAMP and may play an important role in triggering host plant resistance to the HLB bacteria. PMID:23029520

Zou, Huasong; Gowda, Siddarame; Zhou, Lijuan; Hajeri, Subhas; Chen, Gongyou; Duan, Yongping

2012-01-01

387

S100B Protein, A Damage-Associated Molecular Pattern Protein in the Brain and Heart, and Beyond  

PubMed Central

S100B belongs to a multigenic family of Ca2+-binding proteins of the EF-hand type and is expressed in high abundance in the brain. S100B interacts with target proteins within cells thereby altering their functions once secreted/released with the multiligand receptor RAGE. As an intracellular regulator, S100B affects protein phosphorylation, energy metabolism, the dynamics of cytoskeleton constituents (and hence, of cell shape and migration), Ca2+ homeostasis, and cell proliferation and differentiation. As an extracellular signal, at low, physiological concentrations, S100B protects neurons against apoptosis, stimulates neurite outgrowth and astrocyte proliferation, and negatively regulates astrocytic and microglial responses to neurotoxic agents, while at high doses S100B causes neuronal death and exhibits properties of a damage-associated molecular pattern protein. S100B also exerts effects outside the brain; as an intracellular regulator, S100B inhibits the postinfarction hypertrophic response in cardiomyocytes, while as an extracellular signal, (high) S100B causes cardiomyocyte death, activates endothelial cells, and stimulates vascular smooth muscle cell proliferation. PMID:20827421

Sorci, Guglielmo; Bianchi, Roberta; Riuzzi, Francesca; Tubaro, Claudia; Arcuri, Cataldo; Giambanco, Ileana; Donato, Rosario

2010-01-01

388

Listeria monocytogenes-derived listeriolysin O has pathogen-associated molecular pattern-like properties independent of its hemolytic ability.  

PubMed

There is a constant need for improved adjuvants to augment the induction of immune responses against tumor-associated antigens (TAA) during immunotherapy. Previous studies have established that listeriolysin O (LLO), a cholesterol-dependent cytolysin derived from Listeria monocytogenes, exhibits multifaceted effects to boost the stimulation of immune responses to a variety of antigens. However, the direct ability of LLO as an adjuvant and whether it acts as a pathogen-associated molecular pattern (PAMP) have not been demonstrated. In this paper, we show that a detoxified, nonhemolytic form of LLO (dtLLO) is an effective adjuvant in tumor immunotherapy and may activate innate and cellular immune responses by acting as a PAMP. Our investigation of the adjuvant activity demonstrates that dtLLO, either fused to or administered as a mixture with a human papillomavirus type 16 (HPV-16) E7 recombinant protein, can augment antitumor immune responses and facilitate tumor eradication. Further mechanistic studies using bone marrow-derived dendritic cells suggest that dtLLO acts as a PAMP by stimulating production of proinflammatory cytokines and inducing maturation of antigen-presenting cells (APC). We propose that dtLLO is an effective adjuvant for tumor immunotherapy, and likely for other therapeutic settings. PMID:23136118

Wallecha, Anu; Wood, Laurence; Pan, Zhen-Kun; Maciag, Paulo C; Shahabi, Vafa; Paterson, Yvonne

2013-01-01

389

Molecular data and ecological niche modelling reveal the phylogeographic pattern of Cotinus coggygria (Anacardiaceae) in China's warm-temperate zone.  

PubMed

The phylogeography of common and widespread species helps to elucidate the history of local flora and vegetation. In this study, we selected Cotinus coggygria, a species widely distributed in China's warm-temperate zone. One chloroplast DNA (cpDNA) region and ecological niche modelling were used to examine the phylogeographic pattern of C. coggygria. The cpDNA data revealed two phylogeographic groups (Southern and Northern) corresponding to the geographic regions. Divergence time analyses revealed that divergence of the two groups occurred at approximately 147,000 years before the present (BP), which coincided with the formation of the downstream area of the Yellow River, indicating that the Yellow River was a weak phylogeographic divide for C. coggygria. The molecular data and ecological niche modelling also indicated that C. coggyria did not experience population expansion after glaciations. This study thus supports the fact that Pleistocene glacial cycles only slightly affected C. co