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Sample records for molecular pattern molecules

  1. Self-assembled molecular magnets on patterned silicon substrates: bridging bio-molecules with nanoelectronics.

    PubMed

    Chang, Chia-Ching; Sun, Kien Wen; Lee, Shang-Fan; Kan, Lou-Sing

    2007-04-01

    The paper reports the methods of preparing molecular magnets and patterning of the molecules on a semiconductor surface. A highly magnetically aligned metallothionein containing Mn and Cd (Mn,Cd-MT-2) is first synthesized, and the molecules are then placed into nanopores prepared on silicon (001) surfaces using electron beam lithography and reactive ion-etching techniques. We have observed the self-assemble growth of the MT molecules on the patterned Si surface such that the MT molecules have grown into rod or ring type three-dimensional nanostructures, depending on the patterned nanostructures on the surface. We also provide scanning electron microscopy, atomic force microscopy, and magnetic force microscope studies of the molecular nanostructures. This engineered molecule shows molecular magnetization and is biocompatible with conventional semiconductors. These features make Mn,Cd-MT-2 a good candidate for biological applications and sensing sources of new nanodevices. Using molecular self-assembly and topographical patterning of the semiconductor substrate, we can close the gap between bio-molecules and nanoelectronics built into the semiconductor chip.

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

    PubMed Central

    Srikrishna, Geetha; Freeze, Hudson H

    2009-01-01

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

  3. Endogenous Molecules Induced by a Pathogen-Associated Molecular Pattern (PAMP) Elicit Innate Immunity in Shrimp

    PubMed Central

    Chen, Yu-Yuan; Chen, Jiann-Chu; Lin, Yong-Chin; Kitikiew, Suwaree; Li, Hui-Fang; Bai, Jia-Chin; Tseng, Kuei-Chi; Lin, Bo-Wei; Liu, Po-Chun; Shi, Yin-Ze; Kuo, Yi-Hsuan; Chang, Yu-Hsuan

    2014-01-01

    Invertebrates rely on an innate immune system to combat invading pathogens. The system is initiated in the presence of cell wall components from microbes like lipopolysaccharide (LPS), β-1,3-glucan (βG) and peptidoglycan (PG), altogether known as pathogen-associated molecular patterns (PAMPs), via a recognition of pattern recognition protein (PRP) or receptor (PRR) through complicated reactions. We show herein that shrimp hemocytes incubated with LPS, βG, and PG caused necrosis and released endogenous molecules (EMs), namely EM-L, EM-β, and EM-P, and found that shrimp hemocytes incubated with EM-L, EM-β, and EM-P caused changes in cell viability, degranulation and necrosis of hemocytes, and increased phenoloxidase (PO) activity and respiratory burst (RB) indicating activation of immunity in vitro. We found that shrimp receiving EM-L, EM-β, and EM-P had increases in hemocyte count and other immune parameters as well as higher phagocytic activity toward a Vibrio pathogen, and found that shrimp receiving EM-L had increases in proliferation cell ratio and mitotic index of hematopoietic tissues (HPTs). We identified proteins of EMs deduced from SDS-PAGE and LC-ESI-MS/MS analyses. EM-L and EM-P contained damage-associated molecular patterns (DAMPs) including HMGBa, HMGBb, histone 2A (H2A), H2B, and H4, and other proteins including proPO, Rab 7 GPTase, and Rab 11 GPTase, which were not observed in controls (EM-C, hemocytes incubated in shrimp salt solution). We concluded that EMs induced by PAMPs contain DAMPs and other immune molecules, and they could elicit innate immunity in shrimp. Further research is needed to identify which individual molecule or combined molecules of EMs cause the results, and determine the mechanism of action in innate immunity. PMID:25517999

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

    PubMed Central

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

    2014-01-01

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

  5. Extracellular Mitochondria and Mitochondrial Components Act as Damage-Associated Molecular Pattern Molecules in the Mouse Brain.

    PubMed

    Wilkins, Heather M; Koppel, Scott J; Weidling, Ian W; Roy, Nairita; Ryan, Lauren N; Stanford, John A; Swerdlow, Russell H

    2016-12-01

    Mitochondria and mitochondrial debris are found in the brain's extracellular space, and extracellular mitochondrial components can act as damage associated molecular pattern (DAMP) molecules. To characterize the effects of potential mitochondrial DAMP molecules on neuroinflammation, we injected either isolated mitochondria or mitochondrial DNA (mtDNA) into hippocampi of C57BL/6 mice and seven days later measured markers of inflammation. Brains injected with whole mitochondria showed increased Tnfα and decreased Trem2 mRNA, increased GFAP protein, and increased NFκB phosphorylation. Some of these effects were also observed in brains injected with mtDNA (decreased Trem2 mRNA, increased GFAP protein, and increased NFκB phosphorylation), and mtDNA injection also caused several unique changes including increased CSF1R protein and AKT phosphorylation. To further establish the potential relevance of this response to Alzheimer's disease (AD), a brain disorder characterized by neurodegeneration, mitochondrial dysfunction, and neuroinflammation we also measured App mRNA, APP protein, and Aβ1-42 levels. We found mitochondria (but not mtDNA) injections increased these parameters. Our data show that in the mouse brain extracellular mitochondria and its components can induce neuroinflammation, extracellular mtDNA or mtDNA-associated proteins can contribute to this effect, and mitochondria derived-DAMP molecules can influence AD-associated biomarkers.

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

    PubMed

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

    2016-03-01

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

  7. Sequence-Specific Molecular Lithography on Single DNA Molecules

    NASA Astrophysics Data System (ADS)

    Keren, Kinneret; Krueger, Michael; Gilad, Rachel; Ben-Yoseph, Gdalyahu; Sivan, Uri; Braun, Erez

    2002-07-01

    Recent advances in the realization of individual molecular-scale electronic devices emphasize the need for novel tools and concepts capable of assembling such devices into large-scale functional circuits. We demonstrated sequence-specific molecular lithography on substrate DNA molecules by harnessing homologous recombination by RecA protein. In a sequence-specific manner, we patterned the coating of DNA with metal, localized labeled molecular objects and grew metal islands on specific sites along the DNA substrate, and generated molecularly accurate stable DNA junctions for patterning the DNA substrate connectivity. In our molecular lithography, the information encoded in the DNA molecules replaces the masks used in conventional microelectronics, and the RecA protein serves as the resist. The molecular lithography works with high resolution over a broad range of length scales from nanometers to many micrometers.

  8. Integrated Analysis Identifies Interaction Patterns between Small Molecules and Pathways

    PubMed Central

    Li, Yan; Li, Weiguo; Chen, Xin; Sun, Jiatong; Chen, Huan; Lv, Sali

    2014-01-01

    Previous studies have indicated that the downstream proteins in a key pathway can be potential drug targets and that the pathway can play an important role in the action of drugs. So pathways could be considered as targets of small molecules. A link map between small molecules and pathways was constructed using gene expression profile, pathways, and gene expression of cancer cell line intervened by small molecules and then we analysed the topological characteristics of the link map. Three link patterns were identified based on different drug discovery implications for breast, liver, and lung cancer. Furthermore, molecules that significantly targeted the same pathways tended to treat the same diseases. These results can provide a valuable reference for identifying drug candidates and targets in molecularly targeted therapy. PMID:25114931

  9. 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

    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

    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

  10. Molecular-beam spectroscopy of interhalogen molecules

    SciTech Connect

    Sherrow, S.A.

    1983-08-01

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

  11. Patterns and conformations in molecularly thin films

    NASA Astrophysics Data System (ADS)

    Basnet, Prem B.

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

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

    PubMed

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

    2014-10-07

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    PubMed

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

    2014-03-25

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

  15. Method for patterning stretched DNA molecules on mica surfaces by soft lithography.

    PubMed

    Gad, M; Sugiyama, Shigeru; Ohtani, Toshio

    2003-12-01

    Lambda DNA was stretched and patterned on mica surface using soft lithography. A highly diluted solution of amino propyl trimethoxy silane in hexane was deposited on a line patterned polydimethylsiloxane (PDMS) stamp. The functionalized stamp was then used to pick up DNA by molecular combing while the line patterns are parallel to the liquid surface. The stamp was then microcontact printed on freshly cleaved mica. We successfully obtained stretched DNA pattern on mica surface. DNA was found to be stretched in patterns perpendicular to those carved on the stamp. The stretched DNA population was large enough to be used for molecular biology mapping studies. Furthermore, the possibility of locating stretched DNA molecules in the desired position by stamping makes this method a good candidate for assembling non-semiconductor molecular devices.

  16. Molecular machines: Molecules bearing robotic arms

    NASA Astrophysics Data System (ADS)

    Aprahamian, Ivan

    2016-02-01

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

  17. Probing molecular choreography through single-molecule biochemistry.

    PubMed

    van Oijen, Antoine M; Dixon, Nicholas E

    2015-12-01

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

  18. Molecular orbital imaging for partially aligned molecules

    NASA Astrophysics Data System (ADS)

    Qin, Meiyan; Zhu, Xiaosong

    2017-01-01

    We investigate molecular orbital reconstruction using high-order harmonic emissions from partially aligned molecular ensembles. By carrying out the reconstruction procedure using the harmonic sampling with or without the spectral minimum, the roles of the harmonic phase and amplitude modulation due to the partial alignment can be separately studied. It is found that with the prior knowledge of the orbital symmetry, the reconstructed result is very sensitive to the modulation of the harmonic phase for the πg orbital, while in the case of σg orbital, the reconstructed result is mainly determined by the harmonic amplitude. These results can provide an important reference for the future experiment of molecular orbital imaging.

  19. Molecular electronics: the single-molecule switch and transistor

    NASA Astrophysics Data System (ADS)

    Sotthewes, Kai; Geskin, Victor; Heimbuch, Rene; Kumar, Avijit; Zandvliet, Harold

    2014-03-01

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

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

    PubMed

    Rapenne, Gwénaël; Joachim, Christian

    2014-01-01

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

  1. Molecular targets for small-molecule modulators of circadian clocks

    PubMed Central

    He, Baokun; Chen, Zheng

    2016-01-01

    Background Circadian clocks are endogenous timing systems that regulate various aspects of mammalian metabolism, physiology and behavior. Traditional chronotherapy refers to the administration of drugs in a defined circadian time window to achieve optimal pharmacokinetic and therapeutic efficacies. In recent years, substantial efforts have been dedicated to developing novel small-molecule modulators of circadian clocks. Methods Here, we review the recent progress in the identification of molecular targets of small-molecule clock modulators and their efficacies in clock-related disorders. Specifically, we examine the clock components and regulatory factors as possible molecular targets of small molecules, and we review several key clock-related disorders as promising venues for testing the preventive/therapeutic efficacies of these small molecules. Finally, we also discuss circadian regulation of drug metabolism. Results Small molecules can modulate the period, phase and/or amplitude of the circadian cycle. Core clock proteins, nuclear hormone receptors, and clock-related kinases and other epigenetic regulators are promising molecular targets for small molecules. Through these targets small molecules exert protective effects against clock-related disorders including the metabolic syndrome, immune disorders, sleep disorders and cancer. Small molecules can also modulate circadian drug metabolism and response to existing therapeutics. Conclusion Small-molecule clock modulators target clock components or diverse cellular pathways that functionally impinge upon the clock. Target identification of new small-molecule modulators will deepen our understanding of key regulatory nodes in the circadian network. Studies of clock modulators will facilitate their therapeutic applications, alone or in combination, for clock-related diseases. PMID:26750111

  2. Single-Molecule Reaction Chemistry in Patterned Nanowells

    PubMed Central

    2016-01-01

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

  3. Orienting single-molecule diffraction patterns from XFELs using heavy-metal explosion fragments

    NASA Astrophysics Data System (ADS)

    Jurek, Zoltán; Faigel, Gyula

    2013-01-01

    Single-molecule imaging is one of the main target areas of X-ray free-electron lasers. It relies on the possibility of orienting the large number of low-counting-statistics 2D diffraction patterns taken at random orientations of identical replicas of the sample. This is a difficult process and the low statistics limits the usability of orientation methods and ultimately it could prevent single-molecule imaging. We suggest a new approach, which avoids the orientation process from the diffraction patterns. We propose to determine sample orientation through identifying the direction of ejection fragments. The orientation of the sample is measured together with the diffraction pattern by detecting some fragments of the Coulomb explosion. We show by molecular-dynamics simulations that from the angular distribution of the fragments one can obtain the orientation of the samples.

  4. Tailoring Ferromagnet-Molecule Interfaces: Towards Molecular Spintronics

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  6. Photocleavable linker for the patterning of bioactive molecules

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  7. Fast 3D molecular superposition and similarity search in databases of flexible molecules

    NASA Astrophysics Data System (ADS)

    Krämer, Andreas; Horn, Hans W.; Rice, Julia E.

    2003-01-01

    We present a new method (fFLASH) for the virtual screening of compound databases that is based on explicit three-dimensional molecular superpositions. fFLASH takes the torsional flexibility of the database molecules fully into account, and can deal with an arbitrary number of conformation-dependent molecular features. The method utilizes a fragmentation-reassembly approach which allows for an efficient sampling of the conformational space. A fast clique-based pattern matching algorithm generates alignments of pairs of adjacent molecular fragments on the rigid query molecule that are subsequently reassembled to complete database molecules. Using conventional molecular features (hydrogen bond donors and acceptors, charges, and hydrophobic groups) we show that fFLASH is able to rapidly produce accurate alignments of medium-sized drug-like molecules. Experiments with a test database containing a diverse set of 1780 drug-like molecules (including all conformers) have shown that average query processing times of the order of 0.1 seconds per molecule can be achieved on a PC.

  8. Effect of asymmetric molecule-electrode coupling and molecular bias on rectification in molecular junctions

    NASA Astrophysics Data System (ADS)

    Kaur, Rupan Preet; Sawhney, Ravinder Singh; Engles, Derick

    2016-12-01

    In this research work, we compare the rectification trends of two symmetrical and one asymmetrical molecular junction formed with gold and silver electrodes bridging benzenedithiol molecule. The origin of rectification is attributed to both molecular bias drop and asymmetric molecule-electrode coupling. The electronic transport properties are computed by using semi-empirical extended Huckel method combined with non-equilibrium Green's function framework. The results are fully rationalized by analysing the distribution of molecular orbitals with changing bias voltage, available density of states and area of transmission spectra spanned within bias window, transmission eigenstates and transmission pathways. We deduce through this work that the molecular rectification is not only the property of asymmetric molecule-metal coupling, but molecular bias also plays vital role in stemming asymmetric I- V characteristics. Our results suggest how to realize molecular rectification by using different electrode materials which act as Schottky barriers in molecular junctions that emulate p-n junction diode in semiconductor electronics.

  9. Molecular orbital theory of ballistic electron transport through molecules

    NASA Astrophysics Data System (ADS)

    Ernzerhof, Matthias; Rocheleau, Philippe; Goyer, Francois

    2009-03-01

    Electron transport through molecules occurs, for instance, in STM imaging and in conductance measurements on molecular electronic devices (MEDs). To model these phenomena, we use a non-Hermitian model Hamiltonian [1] for the description of open systems that exchange current density with their environment. We derive qualitative, molecular-orbital-based rules relating molecular structure and conductance. We show how side groups attached to molecular conductors [2] can completely suppress the conductance. We discuss interference effects in aromatic molecules [3] that can also inhibit electron transport. Rules are developed [1] for the prediction of Fano resonances. All these phenomena are explained with a molecular orbital theory [1,4] for molecules attached to macroscopic reservoirs. [1] F. Goyer, M. Ernzerhof, and M. Zhuang, JCP 126, 144104 (2007); M. Ernzerhof, JCP 127, 204709 (2007). [2] M. Ernzerhof, M. Zhuang, and P. Rocheleau, JCP 123, 134704 (2005); G. C. Solomon, D Q. Andrews, R P. Van Duyne, and M A. Ratner, JACS 130, 7788 (2008). [3] M. Ernzerhof, H. Bahmann, F. Goyer, M. Zhuang, and P. Rocheleau, JCTC 2, 1291 (2006); G. C. Solomon, D. Q. Andrews, R. P. Van Duyne, and M. A. Ratner, JCP 129, 054701 (2008). [4] B.T. Pickup, P.W. Fowler, CPL 459, 198 (2008); P. Rocheleau and M. Ernzerhof, JCP, submitted.

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

    PubMed Central

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

    2014-01-01

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

  11. Studies of the Pattern Recognition Molecule H-ficolin

    PubMed Central

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

    2012-01-01

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

  12. Photoactive molecules for applications in molecular imaging and cell biology.

    PubMed

    Shao, Qing; Xing, Bengang

    2010-08-01

    Photoactive technology has proven successful for non-invasive regulation of biological activities and processes in living cells. With the light-directed generation of biomaterials 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 for elucidating cell biology on aspects of protein engineering, fluorescence labelling, gene regulation and cell physiological functions.

  13. Variational path integral molecular dynamics study of a water molecule

    NASA Astrophysics Data System (ADS)

    Miura, Shinichi

    2013-08-01

    In the present study, a variational path integral molecular dynamics method developed by the author [Chem. Phys. Lett. 482, 165 (2009)] is applied to a water molecule on the adiabatic potential energy surface. The method numerically generates an exact wavefunction using a trial wavefunction of the target system. It has been shown that even if a poor trial wavefunction is employed, the exact quantum distribution is numerically extracted, demonstrating the robustness of the variational path integral method.

  14. Patterning Biomaterials for the Spatiotemporal Delivery of Bioactive Molecules

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. Thermodynamics of hydrogen bond patterns in supramolecular assemblies of water molecules.

    PubMed

    Henry, Marc

    2002-07-02

    The PACHA (Partial Atomic Charges and Hardnesses Analysis) formalism is applied to various supramolecular assemblies of water molecules. After a detailed study of all available crystal structures for ice polymorphs, we shown that the hydrogen bond strength is roughly constant below 1 GPa and considerably weakened above that value. New hydrogen bond patterns are proposed for ice IV, V, and VI after (EB) (electrostatic balance) minimization. For other polymorphs, there is an almost perfect coincidence between experimental and predicted hydrogen bond patterns. The evolution of hydrogen bond energy as a function of molecular geometry in water clusters with up to 280 water molecules and in large supramolecular compounds is quantitatively described. Intermolecular hydrogen bonds are found to lie between -9 and -32 kJ mol-1, the stronger interaction occurs within the spherical fully disordered water droplet buried at the heart of Müller's superfullerene keplerate. The weakest one occurs in a chiral molecular snub cube built from six calix[4]resorcinarene and eight water molecules. Intramolecular hydrogen bonds are found in the range -10-100 kJ mol-1 and can thus be considerably stronger than intermolecular bonds. Finally, through the investigation of a clathrate type I compound, it was possible to obtain a deep insight of the host-guest interactions and self-assembly rules of water cages in these materials.

  17. The molecular regulation of vertebrate limb patterning.

    PubMed

    Butterfield, Natalie C; McGlinn, Edwina; Wicking, Carol

    2010-01-01

    The limb has long been considered a paradigm for organogenesis because of its simplicity and ease of manipulation. However, it has become increasingly clear that the processes required to produce a perfectly formed limb involve complex molecular interactions across all three axes of limb development. Old models have evolved with acquisition of molecular knowledge, and in more recent times mathematical modeling approaches have been invoked to explain the precise spatio-temporal regulation of gene networks that coordinate limb patterning and outgrowth. This review focuses on recent advances in our understanding of vertebrate limb development, highlighting the signaling interactions required to lay down the pattern on which the processes of differentiation will act to ultimately produce the final limb.

  18. Patterned gallium surfaces as molecular mirrors.

    PubMed

    Bossi, Alessandra; Rivetti, Claudio; Mangiarotti, Laura; Whitcombe, Michael J; Turner, Anthony P F; Piletsky, Sergey A

    2007-09-30

    An entirely new means of printing molecular information on a planar film, involving casting nanoscale impressions of the template protein molecules in molten gallium, is presented here for the first time. The metallic imprints not only replicate the shape and size of the proteins used as template. They also show specific binding for the template species. Such a simple approach to the creation of antibody-like properties in metallic mirrors can lead to applications in separations, microfluidic devices, and the development of new optical and electronic sensors, and will be of interest to chemists, materials scientists, analytical specialists, and electronic engineers.

  19. Central pattern generators deciphered by molecular genetics.

    PubMed

    Kiehn, Ole; Kullander, Klas

    2004-02-05

    Central pattern generators (CPGs) are localized neuronal networks that have the ability to produce rhythmic movements even in the absence of movement-related sensory feedback. They are found in all animals, including man, and serve as informative model systems for understanding how neuronal networks produce behavior. Traditionally, CPGs have been investigated with electrophysiological techniques. Here we review recent molecular and genetic approaches for dissecting the organization and development of CPGs.

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

    SciTech Connect

    Genson, Kirsten Larson

    2005-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

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

    DOEpatents

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

    1998-06-23

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

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

    DOEpatents

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

    1998-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1999-09-01

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

  5. Molecular Responses to Small Regulating Molecules against Huanglongbing Disease

    PubMed Central

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

    2016-01-01

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

  6. Small-Molecule Hormones: Molecular Mechanisms of Action

    PubMed Central

    Budzińska, Monika

    2013-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  8. Molecular patterning of the mammalian dentition.

    PubMed

    Lan, Yu; Jia, Shihai; Jiang, Rulang

    2014-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

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

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

    SciTech Connect

    MUCKERMAN,J.T.

    1999-06-09

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

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

    PubMed

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

    2015-05-26

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

  12. A novel Sec14 phospholipid transfer protein from Nicotiana benthamiana is up-regulated in response to Ralstonia solanacearum infection, pathogen associated molecular patterns and effector molecules and involved in plant immunity.

    PubMed

    Kiba, Akinori; Nakano, Masahito; Vincent-Pope, Patrick; Takahashi, Hirotaka; Sawasaki, Tatsuya; Endo, Yaeta; Ohnishi, Kouhei; Yoshioka, Hirofumi; Hikichi, Yasufumi

    2012-07-01

    To elucidate the molecular mechanisms of plant immune responses, we isolated genes whose expression was regulated by inoculation with Ralstonia solanacearum. Here, we report the characterization of Nicotiana benthamiana belonging to the SEC14-gene superfamily designated as Nicotiana benthamiana SEC14 (NbSEC14). NbSEC14 rescued growth defects and impaired invertase secretion associated with the yeast sec14p temperature-sensitive mutant, while recombinant NbSec14 protein had phospholipids transfer activity. NbSEC14 expression was up-regulated in N. benthamiana leaves after inoculation with virulent or avirulent R. solanacearum. Expression of NbSEC14 was induced by treatment with chitin, flg22, and by Agrobacterium-mediated transient expression of INF1 elicitin, AvrA from R. solanacearum, and co-expression of the capsid protein from Tobacco mild green mosaic virus with its cognate resistance L1 protein. NbSEC14-silenced plants showed accelerated growth of both the virulent and avirulent R. solanacearum as well as acceleration of disease development. This study may provide useful information for the further analysis of the function of plant Sec14 protein homologs in the regulation of plant immune responses.

  13. Synthesis of technomimetic molecules: towards rotation control in single-molecular machines and motors.

    PubMed

    Rapenne, Gwénaël

    2005-04-07

    Technomimetic molecules are molecules designed to imitate macroscopic objects at the molecular level, also transposing the motions that these objects are able to undergo. This article focuses on technomimetic molecules with rotary motions, including gears, wheelbarrows and motors. Following the bottom-up approach the synthesis of technomimetic molecules grants access to the study of mechanical properties at the molecular level. These molecules are designed to operate as single molecules on surfaces under the control of the tip of a scanning tunneling microscope or atomic force microscope.

  14. Molecular multipole moments of water molecules in ice Ih

    NASA Astrophysics Data System (ADS)

    Batista, Enrique R.; Xantheas, Sotiris S.; Jónsson, Hannes

    1998-09-01

    We have used an induction model including dipole, dipole-quadrupole, quadrupole-quadrupole polarizability and first hyperpolarizability as well as fixed octopole and hexadecapole moments to study the electric field in ice. The self-consistent induction calculations gave an average total dipole moment of 3.09 D, a 67% increase over the dipole moment of an isolated water molecule. A previous, more approximate induction model study by Coulson and Eisenberg [Proc. R. Soc. Lond. A 291, 445 (1966)] suggested a significantly smaller average value of 2.6 D. This value has been used extensively in recent years as a reference point in the development of various polarizable interaction potentials for water as well as for assessment of the convergence of water cluster properties to those of bulk. The reason for this difference is not due to approximations made in the computational scheme of Coulson and Eisenberg but rather due to the use of less accurate values for the molecular multipoles in these earlier calculations.

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

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

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

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

    SciTech Connect

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

    2011-07-08

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

  18. Molecular self-organization: Predicting the pattern diversity and lowest energy state of competing ordering motifs

    NASA Astrophysics Data System (ADS)

    Hermann, B. A.; Rohr, C.; Balbás Gambra, M.; Malecki, A.; Malarek, M. S.; Frey, E.; Franosch, T.

    2010-10-01

    Self-organized monolayers of highly flexible Fréchet dendrons were deposited on graphite surfaces by solution casting. Scanning tunneling microscopy (STM) reveals an unprecedented variety of patterns with up to seven stable hierarchical ordering motifs allowing us to use these molecules as a versatile model system. The essential molecular properties determined by molecular mechanics simulations are condensed to a coarse grained interaction-site model of various chain configurations. In a Monte Carlo approach with random starting configurations, the experimental pattern diversity can be reproduced in all facets of the local and global ordering. Based on an energy analysis of the Monte Carlo and molecular mechanics modeling, the thermodynamically most stable pattern is predicted and shown to coincide with the pattern which dominates the STM images after several hours or upon moderate heating.

  19. Information theory, atoms in molecules, and molecular similarity

    NASA Astrophysics Data System (ADS)

    Nalewajski, Roman F.; Parr, Robert G.

    2000-08-01

    Using information theory, it is argued that from among possible definitions of what an atom is when it is in a molecule, a particular one merits special attention. Namely, it is the atom defined by the "stockholders partitioning" of a molecule invented by Hirshfeld [(1977) Theor. Chim. Acta 44, 129]. The theoretical tool used is the minimum entropy deficiency principle (minimum missing information principle) of Kullback and Liebler [(1951) Ann. Math. Stat. 22, 79]. A corresponding analysis is given of the problem of assessing similarity between molecules or pieces of molecules.

  20. Characterization and improvements of presumptive molecular switch molecules

    NASA Astrophysics Data System (ADS)

    Broo, Anders; Hagen, Sigurd

    1992-08-01

    Organic donor—bridge—acceptor (D—B—A) molecules are studied using experimental and theoretical methods. Solvatochromic shifts of the spectra for both series of molecules were interpreted using a Lippert analysis. In the conjugated D—B—A systems the charge separation upon excitation is found to be about 30%-40%. In the non-conjugated molecules the charge separation was only about 7%-14%. Quantum-chemical calculations of spectra and geometry for some not yet synthesized molecules were performed in order to seek to increase the amount of direct charge separation upon excitation.

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

    NASA Technical Reports Server (NTRS)

    Gribov, L. A.

    1979-01-01

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

  2. Ultracold Molecules in Optical Lattices: Efficient Production and Application to Molecular Clocks

    DTIC Science & Technology

    2015-05-03

    SECURITY CLASSIFICATION OF: We have established the strontium molecular clock as the leading ultracold-molecule precision measurement platform. We...Production And Application to Molecular Clocks Report Title We have established the strontium molecular clock as the leading ultracold-molecule precision...experiment are creation and precise spectroscopy of ultracold alkaline-earth- metal atom dimers composed of two bosonic isotopes of strontium , 88Sr2. The

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

    NASA Technical Reports Server (NTRS)

    Eglinton, G.

    1983-01-01

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

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

    PubMed

    Bernath, P F

    1995-03-01

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

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

    SciTech Connect

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

    2009-04-02

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

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

    SciTech Connect

    Iancu, Violeta

    2006-08-01

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

  7. Molecular analyses of dinosaur osteocytes support the presence of endogenous molecules.

    PubMed

    Schweitzer, Mary Higby; Zheng, Wenxia; Cleland, Timothy P; Bern, Marshall

    2013-01-01

    The discovery of soft, transparent microstructures in dinosaur bone consistent in morphology with osteocytes was controversial. We hypothesize that, if original, these microstructures will have molecular features in common with extant osteocytes. We present immunological and mass spectrometry evidence for preservation of proteins comprising extant osteocytes (Actin, Tubulin, PHEX, Histone H4) in osteocytes recovered from two non-avian dinosaurs. Furthermore, antibodies to DNA show localized binding to these microstructures, which also react positively with DNA intercalating stains propidium iodide (PI) and 4',6'-diamidino-2-phenylindole dihydrochloride (DAPI). Each antibody binds dinosaur cells in patterns similar to extant cells. These data are the first to support preservation of multiple proteins and to present multiple lines of evidence for material consistent with DNA in dinosaurs, supporting the hypothesis that these structures were part of the once living animals. We propose mechanisms for preservation of cells and component molecules, and discuss implications for dinosaurian cellular biology.

  8. The boundary molecules in a lysozyme pattern exhibit preferential antibody binding.

    PubMed

    Gao, Pei; Cai, Yuguang

    2008-09-16

    Lysozyme was immobilized on a prefabricated carboxylic acid terminated chemical template, forming a tightly packed, one monolayer thick lysozyme pattern. Polyclonal anti-lysozyme antibodies can bind to the immobilized lysozyme pattern. Atomic force microscope (AFM) observation reveals that the antibodies bind to the lysozyme molecules on the pattern edge before they bind to the lysozyme molecules in the pattern interior. Better spatial accessibility and flexibility of the lysozyme molecules on the pattern edge are used to explain the observed antibody binding preference. The topographies of the lysozyme pattern also affect the antibody binding. The antibodies bind to the edge lysozyme from the top if the lysozyme pattern is half-buried in a 10 A deep channel, whereas the antibodies bind to the edge lysozyme from the side if the lysozyme pattern is immobilized on a protruding terrace. The observed "edge effect" suggests that, for the same protein coverage, reducing the protein pattern feature to the nanoscale will improve the overall binding activity of the immobilized protein toward the antibody.

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

    PubMed

    Lépinay, Sandrine; Ianoul, Anatoli; Albert, Jacques

    2014-10-01

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

  10. Scanning probe microscopy of atoms and molecules on insulating films: from imaging to molecular manipulation.

    PubMed

    Meyer, Gerhard; Gross, Leo; Mohn, Fabian; Repp, Jascha

    2012-01-01

    Scanning tunneling microscopy (STM) and atomic force microscopy (AFM) of single atoms and molecules on ultrathin insulating films have led to a wealth of novel observations and insights. Based on the reduced electronic coupling to the metallic substrate, these techniques allow the charge state of individual atoms to be controlled, orbitals of individual molecules to be imaged and metal-molecule complexes to be built up. Near-contact AFM adds the unique capabilities of imaging and probing the chemical structure of single molecules with atomic resolution. With the help of atomic/molecular manipulation techniques, chemical binding processes and molecular switches can be studied in detail.

  11. Ultrafast electron diffraction from aligned molecules

    SciTech Connect

    Centurion, Martin

    2015-08-17

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

  12. Nanomechanical recognition measurements of individual DNA molecules reveal epigenetic methylation patterns

    NASA Astrophysics Data System (ADS)

    Zhu, Rong; Howorka, Stefan; Pröll, Johannes; Kienberger, Ferry; Preiner, Johannes; Hesse, Jan; Ebner, Andreas; Pastushenko, Vassili Ph.; Gruber, Hermann J.; Hinterdorfer, Peter

    2010-11-01

    Atomic force microscopy (AFM) is a powerful tool for analysing the shapes of individual molecules and the forces acting on them. AFM-based force spectroscopy provides insights into the structural and energetic dynamics of biomolecules by probing the interactions within individual molecules, or between a surface-bound molecule and a cantilever that carries a complementary binding partner. Here, we show that an AFM cantilever with an antibody tether can measure the distances between 5-methylcytidine bases in individual DNA strands with a resolution of 4 Å, thereby revealing the DNA methylation pattern, which has an important role in the epigenetic control of gene expression. The antibody is able to bind two 5-methylcytidine bases of a surface-immobilized DNA strand, and retracting the cantilever results in a unique rupture signature reflecting the spacing between two tagged bases. This nanomechanical approach might also allow related chemical patterns to be retrieved from biopolymers at the single-molecule level.

  13. Direct Photoalignment and Optical Patterning of Molecular Thin Films.

    PubMed

    Pithan, Linus; Beyer, Paul; Bogula, Laura; Zykov, Anton; Schäfer, Peter; Rawle, Jonathan; Nicklin, Chris; Opitz, Andreas; Kowarik, Stefan

    2017-02-01

    A novel strategy for direct photoalignment of molecular materials using optothermal re-orientation is introduced. Photoalignment for molecular materials such as the organic semiconductor tetracene is shown, without relying on additional photoreactive dopants or alignment layers. Patterning and polarized light emission, e.g., for polarized organic light emitting diodes is demonstrated.

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

    PubMed Central

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

    Barak, Phillip; Nater, Edward A.

    2005-01-01

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

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

    ERIC Educational Resources Information Center

    Verkade, John G.

    1987-01-01

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

  17. Molecular basis of vertebrate limb patterning.

    PubMed

    Tickle, Cheryll

    2002-10-15

    Mechanisms of limb development are common to all higher vertebrates. The current understanding of how vertebrate limbs develop comes mainly from studies on chick embryos, which are classical models for experimental manipulation, and mouse embryos, which can be genetically manipulated. Work on chick and mouse embryos is often complementary and has direct implications for human limb development. Analysis has moved to the molecular level, which allows direct links to genetics. Even though genes involved in limb development have been discovered by basic scientists through different routes to that taken by clinical geneticists, many of the same genes have been identified. Thus, the fields of embryology and clinical medicine increasingly converge. The next challenge will be to go back to animal models to begin to dissect how particular gene mutations lead to specific limb phenotypes.

  18. Complexity of danger: the diverse nature of damage-associated molecular patterns.

    PubMed

    Schaefer, Liliana

    2014-12-19

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

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

    SciTech Connect

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

    2014-01-01

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

  20. On the accurate molecular dynamics analysis of biological molecules

    NASA Astrophysics Data System (ADS)

    Yamashita, Takefumi

    2016-12-01

    As the evolution of computational technology has now enabled long molecular dynamics (MD) simulation, the evaluation of many physical properties shows improved convergence. Therefore, we can examine the detailed conditions of MD simulations and perform quantitative MD analyses. In this study, we address the quantitative and accuracy aspects of MD simulations using two example systems. First, it is found that several conditions of the MD simulations influence the area/lipid of the lipid bilayer. Second, we successfully detect the small but important differences in antibody motion between the antigen-bound and unbound states.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Jaross, Werner

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    PubMed

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

    2015-07-31

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

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

    SciTech Connect

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

    2015-07-07

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

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

    PubMed

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

    2015-07-07

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

  8. Patterning protein molecules on poly(ethylene glycol) coated Si(111).

    PubMed

    Jun, Yongseok; Cha, Taewoon; Guo, Athena; Zhu, X-Y

    2004-08-01

    We demonstrate spatially localized immobilization of protein molecules on high-density poly(ethylene glycol) (PEG) coated Si(111). Patterns of HO- and CH3O-terminated PEG regions are formed on silicon surfaces based on soft lithography techniques and an efficient reaction between alcohol functional groups and chlorine-terminated silicon. Activation of the HO-terminated PEG brush is achieved via either partial oxidation to form aldehyde groups or via attachment of efficient leaving groups. Protein molecules are covalently immobilized to these activated regions on the PEG/Si surface.

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

    PubMed Central

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Miller, Michael Stephen

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

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

    PubMed Central

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

    2015-01-01

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

  12. Molecular Water Lilies: Orienting Single Molecules in a Polymer Film by Solvent Vapor Annealing.

    PubMed

    Würsch, Dominik; Hofmann, Felix J; Eder, Theresa; Aggarwal, A Vikas; Idelson, Alissa; Höger, Sigurd; Lupton, John M; Vogelsang, Jan

    2016-11-17

    The microscopic orientation and position of photoactive molecules is crucial to the operation of optoelectronic devices such as OLEDs and solar cells. Here, we introduce a shape-persistent macrocyclic molecule as an excellent fluorescent probe to simply measure (i) its orientation by rotating the excitation polarization and recording the strength of modulation in photoluminescence (PL) and (ii) its position in a film by analyzing the overall PL brightness at the molecular level. The unique shape, the absorption and the fluorescence properties of this probe yield information on molecular orientation and position. We control orientation and positioning of the probe in a polymer film by solvent vapor annealing (SVA). During the SVA process the molecules accumulate at the polymer/air interface, where they adopt a flat orientation, much like water lilies on the surface of a pond. The results are potentially significant for OLED fabrication and single-molecule spectroscopy (SMS) in general.

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

    PubMed

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

    2009-01-12

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

  14. Vibrational properties of fractionally charged molecules and their relevance for molecular electronics and electrochemistry

    NASA Astrophysics Data System (ADS)

    Bâldea, Ioan

    2017-01-01

    Important insight into the charge transfer across interfaces can be gained in situations wherein, for given adsorbate and substrate species, the (fractional) charge state of the adsorbed molecules can be varied in a controlled way. Applied biases can continuously tune the charge of molecules embedded in nanojunctions and/or in electrochemical setups but information on the fractional charges of the corresponding partial oxidized/reduced states cannot be directly accessed in experiments. Here, we present theoretical results revealing that information on the fractional molecular charge can be obtained by monitoring molecular vibrational properties, which can be measured by means of surface enhanced Raman spectroscopy (SERS). To this aim, we performed DFT calculations for the benchmark 1,4-benzenedithiol molecule. The changes in the vibrational frequencies are considerably larger than those recently measured in combined transport-SERS studies on molecular junctions based on fullerene. We believe that this theoretical result is an encouraging message to experimentalists.

  15. Nonadiabatic molecular alignment of linear molecules probed by strong-field ionization yields of photoelectrons

    NASA Astrophysics Data System (ADS)

    Kaya, G.; Kaya, N.; Strohaber, J.; Hart, N. A.; Kolomenskii, A. A.; Schuessler, H. A.

    2016-12-01

    The dynamics of rotational wave packets of laser-aligned linear molecules were studied with femtosecond laser-driven strong-field ionization (SFI). The dynamics were observed as a function of the delay between a femtosecond probe pulse and a linearly polarized aligning pump pulse. The induced nonadiabatic molecular alignment was directly monitored by the total SFI yield. The measured revival signatures were compared to the calculated degree of molecular alignment taking into account the effects of electronic structure and symmetry of the molecules. By fitting the calculated alignment parameter to the measured experimental data, we also determined the molecular rotational constants of N2, CO, O2, and C2H2 gas molecules.

  16. The particle size magnifier closing the gap between measurement of molecules, molecular clusters and aerosol particles

    NASA Astrophysics Data System (ADS)

    Mikkilä, Jyri; Lehtipalo, Katrianne; Kangasluoma, Juha; Franchin, Alessandro; Sipilä, Mikko; Jokinen, Tuija; Sarnela, Nina; Schobesberger, Siegfried; Junninen, Heikki; Kulmala, Markku; Worsnop, Douglas; Petäjä, Tuukka

    2013-05-01

    The Particle Size Magnifier lowers the cut-off size of a Condensation Particle Counter even down to about 1 nm in mobility diameter. By scanning the supersaturation also size information of the particles can be gained. We demonstrated that the PSM can detect particles starting from molecular sizes. By combining the data with newly developed mass spectrometric methods particle formation and growth can be followed molecule by molecule.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

    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.

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

    NASA Technical Reports Server (NTRS)

    Han, Jie

    2001-01-01

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

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

    PubMed

    Galstian, Tigran; Allahverdyan, Karen

    2015-06-07

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

  1. Future challenges in single-molecule fluorescence and laser trap approaches to studies of molecular motors.

    PubMed

    Elting, Mary Williard; Spudich, James A

    2012-12-11

    Single-molecule analysis is a powerful modern form of biochemistry, in which individual kinetic steps of a catalytic cycle of an enzyme can be explored in exquisite detail. Both single-molecule fluorescence and single-molecule force techniques have been widely used to characterize a number of protein systems. We focus here on molecular motors as a paradigm. We describe two areas where we expect to see exciting developments in the near future: first, characterizing the coupling of force production to chemical and mechanical changes in motors, and second, understanding how multiple motors work together in the environment of the cell.

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

    NASA Astrophysics Data System (ADS)

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

    2011-04-01

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

  3. A quantum mechanical/molecular mechanical approach to the investigation of particle-molecule interactions

    NASA Astrophysics Data System (ADS)

    Sloth, Marianne; Bilde, Merete; Mikkelsen, Kurt V.

    2003-06-01

    A quantum mechanical/molecular mechanical aerosol model is developed to describe the interaction between gas phase molecules and atmospheric particles. The model enables the calculation of interaction energies and time-dependent properties. We use the model to investigate how a succinic acid molecule interacts with an aqueous particle. We show how the interaction energies and linear response properties (excitation energies, transition moments, and polarizabilities) depend on the distance between aerosol particle and molecule and on their relative orientation. The results are compared with those obtained previously using a dielectric continuum model [Sloth et al., J. Phys. Chem. (submitted)].

  4. Dielectrophoretic Relay Assisted Molecular Communication for In-Sequence Molecule Delivery.

    PubMed

    Manocha, Puneet; Chandwani, Gitanjali; Das, Soumen

    2016-10-01

    With current research focus to interconnect the molecular communication environment with external environment, it is imperative to design external devices working on molecular communication schemes to be interfaced with in-vivo molecular network. Recently, efforts have been made to integrate molecular communication with Lab-on-chip (LOC); one of the techniques used in LOC for manipulation and transportation of molecules is Dielctrophoresis (DEP). We propose the use of DEP in molecular communication to maintain in-sequence delivery of molecules. DEP planar electrodes are modeled as relays used in telecommunications. We describe the theoretical system model and analyze the effect of introducing DEP relays in diffusive channel in terms of probability of in-sequence delivery of molecules. Information rate of DEP-based channel is analytically obtained for in-sequence delivery. The numerical results obtained show that the information rate for in-sequence delivery of molecules through diffusive channel increases by 26% if DEP relays are used in the channel. Though the system is sensitive to noise variance, incorporation of DEP relay results in a substantial improvement in the capacity of the channel.

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

    PubMed

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

    2014-01-01

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

  6. Molecular structure matching by simulated annealing. IV. Classification of atom correspondences in sets of dissimilar molecules

    NASA Astrophysics Data System (ADS)

    Papadopoulos, M. C.; Dean, P. M.

    1991-04-01

    A set of 6 molecules, active at the benzodiazepine GABAA site are matched pairwise with one member of the set in turn. Matchings are performed by simulated annealing using null correspondences to reject poorly matched atom positions. Cluster analysis is employed to identify molecular similarities after an optimal molecular superimposition has been discovered. A statistic for the compactness of clustered atom positions is suggested. The introduction of null correspondences causes the clusters of matched atoms to become more compact.

  7. Molecular Dynamics Simulations of Motion of Paramagnetic Oxygen Molecules in Air by Magnetic Force

    NASA Astrophysics Data System (ADS)

    Takezawa, Nobuhisa; Fukushima, Kimichika

    2000-03-01

    Oxygen molecules with integer spin in air move upward to higher magnetic fields along magnetic field gradient. This motion is disturbed by the collisions between oxygen molecules and other diamagnetic molecules. To magnetically separate oxygen molecules in air, it is necessary to suppress the collisions with diamagnetic molecules and enhance the transport by magnetic force. In our study, molecular dynamics calculations were carried out to investigate temperature and pressure dependence of the ratio of oxygen molecules to air transported along magnetic field gradient. At temperature T=300K, pressure P=0.1MPa and magnetic field H=20T, the ratio of oxygen molecules to air transported along magnetic field gradient increased from 20% without magnetic fields to about 22% in magnetic fields; at T=200K and P=0.1MPa, to 25%; at T=300K and P=0.005MPa, to 24%. This indicates that the transport of oxygen molecules in air by magnetic force was promoted at lower temperature and pressure.

  8. Patterns of molecular motors that guide and sort filaments.

    PubMed

    Rupp, Beat; Nédélec, François

    2012-11-21

    Molecular motors can be immobilized to transport filaments and loads that are attached to these filaments inside a nano-device. However, if motors are distributed uniformly over a flat surface, the motility is undirected, and the filaments move equally in all directions. For many applications it is important to control the direction in which the filaments move, and two strategies have been explored to achieve this: applying external forces and confining the filaments inside channels. In this article, we discuss a third strategy in which the topography of the sample remains flat, but the motors are distributed non-uniformly over the surface. Systems of filaments and patterned molecular motors were simulated using a stochastic engine that included Brownian motion and filament bending elasticity. Using an evolutionary algorithm, patterns were optimized for their capacity to precisely control the paths of the filaments. We identified patterns of motors that could either direct the filaments in a particular direction, or separate short and long filaments. These functionalities already exceed what has been achieved with confinement. The patterns are composed of one or two types of motors positioned in lines or along arcs and should be easy to manufacture. Finally, these patterns can be easily combined into larger designs, allowing one to precisely control the motion of microscopic objects inside a device.

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

    PubMed

    Dauga, Catherine

    2002-03-01

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

  10. Streching of (DNA/functional molecules) complex between electrodes towards DNA molecular wire

    NASA Astrophysics Data System (ADS)

    Kobayashi, Norihisa; Nishizawa, Makoto; Inoue, Shintarou; Nakamura, Kazuki

    2009-08-01

    DNA/functional molecules such as (Ru(bpy)32+ complex, conducting polymer etc.) complex was prepared to study molecular structure and I-V characteristics towards DNA molecular wire. For example, Ru(bpy)32+ was associated with duplex of DNA by not only electrostatic interaction but also intercalation in the aqueous solution. Singlemolecular structure of DNA/Ru(bpy)32+ complex was analyzed with AFM. We found a network structure of DNA/Ru(bpy)32+ complex on the mica substrate, which is similar to native DNA. The height of DNA/Ru(bpy)32+ complex on the mica substrate was ranging from 0.8 to 1.6 nm, which was higher than the naked DNA (0.5-1.0 nm). This indicates that single-molecular DNA/Ru(bpy)32+ complex also connects to each other to form network structure on a mica substrate. In order to stretch DNA complex between electrodes, we employed high frequency and high electric field stretching method proposed by Washizu et al. We stretched and immobilized DNA single molecules between a pair of electrodes and its structures were analyzed with AFM technique. The I-V characteristics of DNA single molecules between electrodes were improved by the association of functional molecules with DNA. The molecular structure and I-V characteristics of DNA complex were discussed.

  11. Hydration shells of molecules in molecular association: A mechanism for biomolecular recognition.

    PubMed

    Lim, Valery I; Curran, James F; Garber, Maria B

    2012-05-21

    It has become clear that water should not be treated as an inert environment, but rather as an integral and active component of molecules. Here, we consider molecules and their hydration shells together as single entities. We show that: (1) the rate of association of molecules should be determined by the energetic barriers arising from interactions between their hydration shells; (2) replacing non-polar atoms of molecular surfaces with polar atoms increases these barriers; (3) reduction of the hydration shells during molecular association is the driving force for association not only of non-polar, but of polar molecules as well; (4) in most cases the dehydration of polar atoms during molecular association thermodynamically counteracts association; (5) on balance the thermodynamic stability of associated complexes is basically determined by the action of these two opposing factors: reduction of the hydration shells and dehydration of polar atoms; (6) molecular crowding reduces the energetic barriers counteracting association and changes the thermodynamic stability of associated complexes. These results lead to a mechanism for biomolecular recognition in the context of which the formation of unique structures is provided by rapidly forming kinetic traps with a biologically necessary lifetime but with a marginal thermodynamic stability. The mechanism gives definitive answers to questions concerning the heart of specific interactions between biomolecules, their folding and intracellular organization. Predictions are given that can be subjected to direct experimental tests.

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

    PubMed

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

    2014-06-25

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

  13. Diffusion of molecules in the bulk of a low density amorphous ice from molecular dynamics simulations.

    PubMed

    Ghesquière, P; Mineva, T; Talbi, D; Theulé, P; Noble, J A; Chiavassa, T

    2015-05-07

    The diffusion of molecules in interstellar ice is a fundamental phenomenon to take into account while studying the formation of complex molecules in this ice. This work presents a theoretical study on the diffusion of H2O, NH3, CO2, CO, and H2CO in the bulk of a low density amorphous (LDA) ice, while taking into account the physical conditions prevailing in space, i.e. temperatures below 150 K and extremely low pressure. This study was undertaken by means of molecular dynamics simulations. For CO2 for which no experimental data were available we conducted our own experiments. From our calculations we show that, at low temperatures, the diffusion of molecules in the bulk of a LDA ice is driven by the self-diffusion of water molecules in the ice. With this study we demonstrate that molecular dynamics allows the calculation of diffusion coefficients for small molecules in LDA ice that are convincingly comparable to experimentally measured diffusion coefficients. We also provide diffusion coefficients for a series of molecules of astrochemical interest.

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

    PubMed

    Kleppmann, Nicola; Klapp, Sabine H L

    2015-02-14

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

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

    NASA Astrophysics Data System (ADS)

    Kleppmann, Nicola; Klapp, Sabine H. L.

    2015-02-01

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

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

    NASA Technical Reports Server (NTRS)

    Byer, R. L.

    1982-01-01

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

  17. Ab initio path integral ring polymer molecular dynamics: Vibrational spectra of molecules

    NASA Astrophysics Data System (ADS)

    Shiga, Motoyuki; Nakayama, Akira

    2008-01-01

    The path integral ring polymer molecular dynamics method is combined with 'on-the-fly' ab initio electronic structure calculations and applied to vibrational spectra of small molecules, LiH and H 2O, at the room temperature. The results are compared with those of the numerically exact solution and ab initio path integral centroid molecular dynamics calculation. The peak positions in the calculated spectra are found to be reasonable, showing the red-shift due to potential anharmonicity. This unification enables the investigation of real-time quantum dynamics of chemically complex molecular systems on the ab initio Born-Oppenheimer potential energy surface.

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

    NASA Astrophysics Data System (ADS)

    Harter, William; Mitchell, Justin

    2009-06-01

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

  19. Self-organized patterns of fullerene on molecular nanotemplate

    NASA Astrophysics Data System (ADS)

    Jin, Jing; Song, Xin; Wang, Zhongping; Liu, Xiaoqing; Wang, Li

    2017-02-01

    Row structures and close packed islands of fullerenes controlled by a stable molecular nanotemplate formed via rubrene on Au(111) have been investigated by scanning tunneling microscopy. The fullerene rows are made up of short chains linked by two to four molecules at low fullerene coverage, while they consisted of dimers or trimers with the increase of the coverage and the assistance of further annealing. The close-packed islands of fullerene are described as a hexagonal cubic structure. The growth of the islands can overcome the hindrance of the terrace edges and expand from one terrace to the other without breaking their periodic structures.

  20. Shifting molecular localization by plasmonic coupling in a single-molecule mirage

    NASA Astrophysics Data System (ADS)

    Raab, Mario; Vietz, Carolin; Stefani, Fernando Daniel; Acuna, Guillermo Pedro; Tinnefeld, Philip

    2017-01-01

    Over the last decade, two fields have dominated the attention of sub-diffraction photonics research: plasmonics and fluorescence nanoscopy. Nanoscopy based on single-molecule localization offers a practical way to explore plasmonic interactions with nanometre resolution. However, this seemingly straightforward technique may retrieve false positional information. Here, we make use of the DNA origami technique to both control a nanometric separation between emitters and a gold nanoparticle, and as a platform for super-resolution imaging based on single-molecule localization. This enables a quantitative comparison between the position retrieved from single-molecule localization, the true position of the emitter and full-field simulations. We demonstrate that plasmonic coupling leads to shifted molecular localizations of up to 30 nm: a single-molecule mirage.

  1. Shifting molecular localization by plasmonic coupling in a single-molecule mirage.

    PubMed

    Raab, Mario; Vietz, Carolin; Stefani, Fernando Daniel; Acuna, Guillermo Pedro; Tinnefeld, Philip

    2017-01-11

    Over the last decade, two fields have dominated the attention of sub-diffraction photonics research: plasmonics and fluorescence nanoscopy. Nanoscopy based on single-molecule localization offers a practical way to explore plasmonic interactions with nanometre resolution. However, this seemingly straightforward technique may retrieve false positional information. Here, we make use of the DNA origami technique to both control a nanometric separation between emitters and a gold nanoparticle, and as a platform for super-resolution imaging based on single-molecule localization. This enables a quantitative comparison between the position retrieved from single-molecule localization, the true position of the emitter and full-field simulations. We demonstrate that plasmonic coupling leads to shifted molecular localizations of up to 30 nm: a single-molecule mirage.

  2. Collective Molecular Superrotation: A Model for Extremely Flexible Molecules Applied to Protonated Methane

    NASA Astrophysics Data System (ADS)

    Schmiedt, Hanno; Jensen, Per; Schlemmer, Stephan

    2016-11-01

    The concept of molecular structure is traditionally considered to be virtually fundamental. However, it breaks down in extremely flexible molecules, whose dynamics are governed by large-amplitude motions. For the dynamics of molecules with free internal rotations, we therefore propose a five-dimensional rigid rotor model, with states characterized by two generalized angular momentum quantum numbers and a rotational constant B . The quantum numbers characterize a 5D angular-momentum vector, super-j , which describes collective rotations that involve both the internal and the overall rotation. This model predicts the lowest energy states of the prototypical, extremely flexible molecule, CH5+ . Both energies and symmetries compare very favorably to recent experimental results. The respective assignment to the new quantum numbers indicates the validity of our concept of collective rotations in extremely flexible molecules.

  3. Contactless experiments on individual DNA molecules show no evidence for molecular wire behavior

    PubMed Central

    Gómez-Navarro, C.; Moreno-Herrero, F.; de Pablo, P. J.; Colchero, J.; Gómez-Herrero, J.; Baró, A. M.

    2002-01-01

    A fundamental requirement for a molecule to be considered a molecular wire (MW) is the ability to transport electrical charge with a reasonably low resistance. We have carried out two experiments that measure first, the charge transfer from an electrode to the molecule, and second, the dielectric response of the MW. The latter experiment requires no contacts to either end of the molecule. From our experiments we conclude that adsorbed individual DNA molecules have a resistivity similar to mica, glass, and silicon oxide substrates. Therefore adsorbed DNA is not a conductor, and it should not be considered as a viable candidate for MW applications. Parallel studies on other nanowires, including single-walled carbon nanotubes, showed conductivity as expected. PMID:12070346

  4. Molecular threading: mechanical extraction, stretching and placement of DNA molecules from a liquid-air interface.

    PubMed

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

    2013-01-01

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

  5. Study of the betulin molecule in a water environment; ab initio and molecular simulation calculations.

    PubMed

    Pospíšil, Miroslav; Kovář, Petr; Vácha, Robert; Svoboda, Michal

    2012-01-01

    Ab initio and molecular simulation methods were used in calculations of the neutral individual betulin molecule, and molecular simulations were used to optimize the betulin molecule immersed in various amounts of water. Individual betulin was optimized in different force fields to find the one exhibiting best agreement with ab initio calculations obtained in the Gaussian03 program. Dihedral torsions of active groups of betulin were determined for both procedures, and related calculated structures were compared successfully. The selected force field was used for subsequent optimization of betulin in a water environment, and a conformational search was performed using quench molecular dynamics. The total energies of betulin and its interactions in water bulk were calculated, and the influence of water on betulin structure was investigated.

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

    PubMed Central

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

    2015-01-01

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

  7. Limb patterning: from signaling gradients to molecular oscillations.

    PubMed

    Sheeba, Caroline J; Andrade, Raquel P; Palmeirim, Isabel

    2014-02-20

    The developing forelimb is patterned along the proximal-distal and anterior-posterior axes by opposing gradients of retinoic acid and fibroblast growth factors and by graded sonic hedgehog signaling, respectively. However, how coordinated patterning along both axes is accomplished with temporal precision remains unknown. The limb molecular oscillator hairy2 was recently shown to be a direct readout of the combined signaling activities of retinoic acid, fibroblast growth factor and sonic hedgehog in the limb mesenchyme. Herein, an integrated time-space model is presented to conciliate the progress zone and two-signal models for limb patterning. We propose that the limb clock may allow temporal information to be decoded into positional information when the distance between opposing signaling gradients is no longer sufficient to provide distinct cell fate specification.

  8. Molecular Dynamics Simulation Suggests Possible Interaction Patterns at Early Steps of β2-Microglobulin Aggregation

    PubMed Central

    Fogolari, Federico; Corazza, Alessandra; Viglino, Paolo; Zuccato, Pierfrancesco; Pieri, Lidia; Faccioli, Pietro; Bellotti, Vittorio; Esposito, Gennaro

    2007-01-01

    Early events in aggregation of proteins are not easily accessible by experiments. In this work, we perform a 5-ns molecular dynamics simulation of an ensemble of 27 copies of β2-microglobulin in explicit solvent. During the simulation, the formation of intermolecular contacts is observed. The simulation highlights the importance of apical residues and, in particular, of those at the N-terminus end of the molecule. The most frequently found pattern of interaction involves a head-to-head contact arrangement of molecules. Hydrophobic contacts appear to be important for the establishment of long-lived (on the simulation timescale) contacts. Although early events on the pathway to aggregation and fibril formation are not directly related to the end-state of the process, which is reached on a much longer timescale, simulation results are consistent with experimental data and in general with a parallel arrangement of intermolecular β-strand pairs. PMID:17158575

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

    PubMed Central

    Cutler, Sean

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2003-03-01

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

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

    PubMed

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

    2015-09-15

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

  13. ATOMIC AND MOLECULAR PHYSICS: A Novel Mirror for Cold Molecules with a Semi-Gaussian Beam

    NASA Astrophysics Data System (ADS)

    Yin, Ya-Ling; Zhou, Qi; Xia, Yong; Yin, Jian-Ping

    2008-09-01

    We propose a novel mirror for cold molecules with a blue-detuned semi-Gaussian beam and study the dynamic reflection process of cold molecules by Monte Carlo simulation. Our study shows that this mirror can realize a specular reflection of cold iodine molecular beam with a temperature of 30 mK by a reflectivity of 58.2% when the semi-Gaussian laser power is 1.0kW. When a semi-Gaussian CO2 laser beam with a power of 5.8 kW is used, the reflectivity of this mirror can reach about 100%.

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

    NASA Astrophysics Data System (ADS)

    Lin, C. D.; Jin, Cheng; Le, Anh-Thu; Lucchese, R. R.

    2012-10-01

    We analyse the theory of single photoionization (PI) and high-order harmonic generation (HHG) by intense lasers from aligned molecules. We show that molecular-frame photoelectron angular distributions can be extracted from these measurements. We also show that, under favourable conditions, the phase of PI transition dipole matrix elements can be extracted from the HHG spectra. Furthermore, by varying the polarization axis of the HHG generating laser with respect to the polarization axis of the aligning laser, it is possible to extract angle-dependent tunnelling ionization rates for different subshells of the molecules.

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

    DOE R&D Accomplishments Database

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

    1964-01-29

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

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

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  18. Molecular Dynamics Study of Small PNA Molecules in Lipid-Water System

    PubMed Central

    Weroński, Paweł; Jiang, Yi; Rasmussen, Steen

    2007-01-01

    We present the results of molecular dynamics simulations of small peptide nucleic acid (PNA) molecules, synthetic analogs of DNA, at a lipid bilayer in water. At neutral pH, without any salt, and in the NPnγT ensemble, two similar PNA molecules (6-mers) with the same nucleic base sequence and different terminal groups are investigated at the interface between water and a 1-palmitoyl-2-oleoylphosphatidylcholine lipid bilayer. The results of our simulations suggest that at low ionic strength of the solution, both PNA molecules adsorb at the lipid-water interface. In the case where the PNA molecule has charged terminal groups, the main driving force of adsorption is the electrostatic attraction between the charged groups of PNA and the lipid heads. The main driving force of adsorption of the PNA molecule with neutral terminal groups is the hydrophobic interaction of the nonpolar groups. Our simulations suggest that the system free energy change associated with PNA adsorption at the lipid-water interface is on the order of several tens of kT per PNA molecule in both cases. PMID:17307825

  19. Molecule-lead coupling at molecular junctions: relation between the real- and state-space perspectives.

    PubMed

    Zelovich, Tamar; Kronik, Leeor; Hod, Oded

    2015-10-13

    We present insights into the lead-molecule coupling scheme in molecular electronics junctions. Using a "site-to-state" transformation that provides direct access to the coupling matrix elements between the molecular states and the eigenstate manifold of each lead, we find coupling bands whose character depends on the geometry and dimensionality of the lead. We use a standard tight-binding model to elucidate the origin of the coupling bands and explain their nature via simple "particle-in-a-box" type considerations. We further show that these coupling bands can shed light on the charge transport behavior of the junction. The picture presented in this study is not limited to the case of molecular electronics junctions and is relevant to any scenario where a finite molecular entity is coupled to a (semi)infinite system.

  20. Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs).

    PubMed

    Turner, Neil A

    2016-05-01

    Cardiac fibroblasts (CF) are well-established as key regulators of extracellular matrix (ECM) turnover in the context of myocardial remodelling and fibrosis. Recently, this cell type has also been shown to act as a sensor of myocardial damage by detecting and responding to damage-associated molecular patterns (DAMPs) upregulated with cardiac injury. CF express a range of innate immunity pattern recognition receptors (TLRs, NLRs, IL-1R1, RAGE) that are stimulated by a host of different DAMPs that are evident in the injured or remodelling myocardium. These include intracellular molecules released by necrotic cells (heat shock proteins, high mobility group box 1 protein, S100 proteins), proinflammatory cytokines (interleukin-1α), specific ECM molecules up-regulated in response to tissue injury (fibronectin-EDA, tenascin-C) or molecules modified by a pathological environment (advanced glycation end product-modified proteins observed with diabetes). DAMP receptor activation on fibroblasts is coupled to altered cellular function including changes in proliferation, migration, myofibroblast transdifferentiation, ECM turnover and production of fibrotic and inflammatory paracrine factors, which directly impact on the heart's ability to respond to injury. This review gives an overview of the important role played by CF in responding to myocardial DAMPs and how the DAMP/CF axis could be exploited experimentally and therapeutically.

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

    PubMed

    Kronforst, Marcus R; Papa, Riccardo

    2015-05-01

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

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

    PubMed Central

    Kronforst, Marcus R.; Papa, Riccardo

    2015-01-01

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

  3. Studies of the pattern recognition molecule H-ficolin: specificity and purification.

    PubMed

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

    2012-03-09

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

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

    PubMed Central

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

    2007-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-04-01

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

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

    SciTech Connect

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

    2014-10-14

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

  7. A Modified Shake Algorithm for Maintaining Rigid Bonds in Molecular Dynamics Simulations of Large Molecules

    NASA Astrophysics Data System (ADS)

    Lambrakos, S. G.; Boris, J. P.; Oran, E. S.; Chandrasekhar, I.; Nagumo, M.

    1989-12-01

    We present a new modification of the SHAKE algorithm, MSHAKE, that maintains fixed distances in molecular dynamics simulations of polyatomic molecules. The MSHAKE algorithm, which is applied by modifying the leapfrog algorithm to include forces of constraint, computes an initial estimate of constraint forces, then iteratively corrects the constraint forces required to maintain the fixed distances. Thus MSHAKE should always converge more rapidly than SHAKE. Further, the explicit determination of the constraint forces at each timestep makes MSHAKE convenient for use in molecular dynamics simulations where bond stress is a significant dynamical quantity.

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

    PubMed Central

    2016-01-01

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

  9. Dynamic decomposition of aliphatic molecules on Al(111) from ab initio molecular dynamics

    SciTech Connect

    Zhong Jun; Hector, Louis G. Jr.; Adams, James B.

    2009-03-15

    Ab initio molecular dynamics based on density functional theory within the generalized gradient approximation was used to explore decomposition on Al(111) of butanol-alcohol and butanoic-acid, two important boundary additives in Al processing. Each molecule was oriented with its functional group closest to the surface and then given an initial velocity toward the surface. Decomposition occurred upon collision with Al(111) resulting in the formation of adhered fragments that represent the very initial stages in additive film formation during plastic deformation where nascent Al is liberated. Bonding interactions over the simulation time frames were explored with contours of the electron localization function. Results of the simulations were compared with existing experimental studies of chemical decomposition on clean Al surfaces and found to be in qualitative accord. The effects of other initial molecular orientations on decomposition were explored in ancillary calculations where the molecules were rotated through 90 deg. and 180 deg. prior to collision with Al(111)

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

    PubMed Central

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

    2016-01-01

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

  11. Discriminating single-molecule sensing by crown-ether-based molecular junctions

    NASA Astrophysics Data System (ADS)

    Ismael, Ali K.; Al-Jobory, Alaa; Grace, Iain; Lambert, Colin J.

    2017-02-01

    Crown-ether molecules are well known to selectively bind alkali atoms, so by incorporating these within wires, any change in electrical conductance of the wire upon binding leads to discriminating sensing. Using a density functional theory-based approach to quantum transport, we investigate the potential sensing capabilities of single-molecule junctions formed from crown ethers attached to anthraquinone units, which are in turn attached to gold electrodes via alkyl chains. We calculate the change in electrical conductance for binding of three different alkali ions (lithium, sodium, and potassium). Depending on the nature of the ionic analyte, the conductance is enhanced by different amounts. This change in electrical conductance is due to charge transfer from the ion to molecular wire causing the molecular resonances to shift closer to the electrode Fermi energy.

  12. [Current progress in functions of axon guidance molecule Robo and underlying molecular mechanism].

    PubMed

    Li, Xiao-Tong; Zhou, Qi-Sheng; Yu, Qi; Zhao, Xiao; Liu, Qing-Xin

    2014-06-25

    The axon guidance molecule Robo is a transmembrane protein which is conserved during evolution. Robo and its ligand, Slit, have been implicated in regulating many developmental processes, such as axon guidance, neuronal migration, tumor metastasis, angiogenesis, lung morphogenesis, kidney morphogenesis, heart morphogenesis, ovary development and gonad development. Robo function mainly depends on the binding of its Ig1 domain to the LRR-2 domain of Slit ligand. Meanwhile, Robo function is also mediated by binding to some signaling molecules, including the heparan sulfate proteoglycans (HSPGs), GTPase-activating proteins (GAPs) and tyrosine kinase Abelson. Several transcription factors, including Hox, Midline and Nkx2.9, were shown to regulate robo expression. In addition, alternative splicing and transport regulation also affect Robo function. In this review, we summarized the studies on the molecular structure, functions and molecular mechanism of Robo, which would propose a novel strategy for the research of neural development, as well as prevention and treatment of nervous system diseases and cancers.

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

    PubMed

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

    2015-06-24

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

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

    PubMed

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

    2015-04-03

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

  15. Microbe Associated Molecular Pattern Signaling in Guard Cells

    PubMed Central

    Ye, Wenxiu; Murata, Yoshiyuki

    2016-01-01

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

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

    PubMed Central

    Diau, Eric W.-G.; Casanova, Joseph; Roberts, John D.; Zewail, Ahmed H.

    2000-01-01

    In this communication, we report our femtosecond real-time observation of the dynamics for the three didehydrobenzene molecules (p-, m-, and o-benzyne) generated from 1,4-, 1,3-, and 1,2-dibromobenzene, respectively, in a molecular beam, by using femtosecond time-resolved mass spectrometry. The time required for the first and the second C-Br bond breakage is less than 100 fs; the benzyne molecules are produced within 100 fs and then decay with a lifetime of 400 ps or more. Density functional theory and high-level ab initio calculations are also reported herein to elucidate the energetics along the reaction path. We discuss the dynamics and possible reaction mechanisms for the disappearance of benzyne intermediates. Our effort focuses on the isolated molecule dynamics of the three isomers on the femtosecond time scale. PMID:10660684

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

    PubMed

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

    2000-02-15

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

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

    PubMed Central

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

    2016-01-01

    Molecular recognition is often driven by transient processes beyond the reach of detection. Single-molecule fluorescence microscopy methods are uniquely suited for detecting such non-accumulating intermediates, yet achieving the time resolution and statistics to realize this potential has proven challenging. Here, we present a single-molecule fluorescence resonance energy transfer (smFRET) imaging and analysis platform leveraging advances in scientific complementary metal-oxide semiconductor (sCMOS) detectors that enable the imaging of more than 10,000 individual molecules simultaneously at millisecond rates. The utility of this advance is demonstrated through quantitative measurements of previously obscured processes relevant to the fidelity mechanism in protein synthesis. PMID:26878382

  19. Detecting differential patterns of interaction in molecular pathways

    PubMed Central

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

    2015-01-01

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

  20. The Design of a Molecular Assembly Line Based on Biological Molecules

    DTIC Science & Technology

    2003-06-01

    and will demonstrate how one can construct a purely synthetic analogue of a polyketide synthase . 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF...scaffold in programmed assembly and molecular electronics. It is based on the principles of the biological molecules polyketide synthase and kinesin, and in...stereoselective centers) with any reasonable yield, not including the R&D and process development time. Figure 1.6 shows how a polyketide synthase

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

    SciTech Connect

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

    1986-03-01

    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.

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

    PubMed

    Kim, Yu Jin; Park, Chan Eon

    2016-04-14

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

  3. Mechanics and chemistry: single molecule bond rupture forces correlate with molecular backbone structure.

    PubMed

    Frei, Michael; Aradhya, Sriharsha V; Koentopp, Max; Hybertsen, Mark S; Venkataraman, L

    2011-04-13

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

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

    SciTech Connect

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

    2004-12-15

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

  5. An anchor-dependent molecular docking process for docking small flexible molecules into rigid protein receptors.

    PubMed

    Lin, Thy-Hou; Lin, Guan-Liang

    2008-08-01

    A molecular docking method designated as ADDock, anchor-dependent molecular docking process for docking small flexible molecules into rigid protein receptors, is presented in this article. ADDock makes the bond connection lists for atoms based on anchors chosen for building molecular structures for docking small flexible molecules or ligands into rigid active sites of protein receptors. ADDock employs an extended version of piecewise linear potential for scoring the docked structures. Since no translational motion for small molecules is implemented during the docking process, ADDock searches the best docking result by systematically changing the anchors chosen, which are usually the single-edge connected nodes or terminal hydrogen atoms of ligands. ADDock takes intact ligand structures generated during the docking process for computing the docked scores; therefore, no energy minimization is required in the evaluation phase of docking. The docking accuracy by ADDock for 92 receptor-ligand complexes docked is 91.3%. All these complexes have been docked by other groups using other docking methods. The receptor-ligand steric interaction energies computed by ADDock for some sets of active and inactive compounds selected and docked into the same receptor active sites are apparently separated. These results show that based on the steric interaction energies computed between the docked structures and receptor active sites, ADDock is able to separate active from inactive compounds for both being docked into the same receptor.

  6. Molecular release from patterned nanoporous gold thin films

    NASA Astrophysics Data System (ADS)

    Kurtulus, Ozge; Daggumati, Pallavi; Seker, Erkin

    2014-05-01

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

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

    NASA Astrophysics Data System (ADS)

    Küpper, Jochen

    2011-05-01

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

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

    SciTech Connect

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

    1994-12-31

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

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

    NASA Astrophysics Data System (ADS)

    Garcia, Hernan

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

  10. Targeting the molecular chaperone SlyD to inhibit bacterial growth with a small molecule

    PubMed Central

    Kumar, Amit; Balbach, Jochen

    2017-01-01

    Molecular chaperones are essential molecules for cell growth, whereby they maintain protein homeostasis. Because of their central cellular function, bacterial chaperones might be potential candidates for drug targets. Antimicrobial resistance is currently one of the greatest threats to human health, with gram-negative bacteria being of major concern. We found that a Cu2+ complex readily crosses the bacterial cell wall and inhibits SlyD, which is a molecular chaperone, cis/trans peptidyl prolyl isomerise (PPIase) and involved in various other metabolic pathways. The Cu2+ complex binds to the active sites of SlyD, which suppresses its PPIase and chaperone activities. Significant cell growth retardation could be observed for pathogenic bacteria (e.g., Staphylococcus aureus and Pseudomonas aeruginosa). We anticipate that rational development of drugs targeting molecular chaperones might help in future control of pathogenic bacterial growth, in an era of rapidly increasing antibiotic resistance. PMID:28176839

  11. Finite temperature infrared spectroscopy of polycyclic aromatic hydrocarbon molecules: Path-integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Calvo, F.; Parneix, P.; Van-Oanh, N.-T.

    2010-03-01

    The vibrational spectra of the naphthalene, pyrene, and coronene molecules have been computed in the 0-3500 cm-1 infrared range using classical and quantum molecular dynamics simulations based on a dedicated tight-binding potential energy surface. The ring-polymer molecular dynamics (RPMD) and partially adiabatic centroid molecular dynamics (CMD) methods have been employed to account for quantum nuclear effects. The contributions of quantum delocalization to the line shift and broadening are significant in the entire spectral range and of comparable magnitude as pure thermal effects. While the two methods generally produce similar results, the CMD method may converge slower at low temperature with increasing Trotter discretization number. However, and contrary to the CMD method, the RPMD approach suffers from serious resonance problems at high frequencies and low temperatures.

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

    PubMed

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

    2014-06-10

    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 ΔΔG° ∼ -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 ΔΔG° ∼ -5 kcal/mol free-energy stabilization at excluded volume fractions of 30%.

  13. Reverse engineering of an affinity-switchable molecular interaction characterized by atomic force microscopy single-molecule force spectroscopy.

    PubMed

    Anselmetti, Dario; Bartels, Frank Wilco; Becker, Anke; Decker, Björn; Eckel, Rainer; McIntosh, Matthew; Mattay, Jochen; Plattner, Patrik; Ros, Robert; Schäfer, Christian; Sewald, Norbert

    2008-02-19

    Tunable and switchable interaction between molecules is a key for regulation and control of cellular processes. The translation of the underlying physicochemical principles to synthetic and switchable functional entities and molecules that can mimic the corresponding molecular functions is called reverse molecular engineering. We quantitatively investigated autoinducer-regulated DNA-protein interaction in bacterial gene regulation processes with single atomic force microscopy (AFM) molecule force spectroscopy in vitro, and developed an artificial bistable molecular host-guest system that can be controlled and regulated by external signals (UV light exposure and thermal energy). The intermolecular binding functionality (affinity) and its reproducible and reversible switching has been proven by AFM force spectroscopy at the single-molecule level. This affinity-tunable optomechanical switch will allow novel applications with respect to molecular manipulation, nanoscale rewritable molecular memories, and/or artificial ion channels, which will serve for the controlled transport and release of ions and neutral compounds in the future.

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

    PubMed

    Lee, Cheng-Kuang; Pao, Chun-Wei

    2016-08-17

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

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

    NASA Astrophysics Data System (ADS)

    Schmiedt, Hanno; Schlemmer, Stephan; Jensen, Per

    2015-10-01

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

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

    NASA Astrophysics Data System (ADS)

    Langhoff, Peter; Mills, Jeffrey; Boatz, Jerry

    2016-05-01

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

  17. Expression patterns of WNT/β-CATENIN signaling molecules during human tooth development.

    PubMed

    Wang, Bingmei; Li, Hanliang; Liu, Ying; Lin, Xin; Lin, Yao; Wang, Ye; Hu, Xuefeng; Zhang, Yanding

    2014-10-01

    The WNT/β-CATENIN signaling has been demonstrated to play critical roles in mouse tooth development, but little is known about the status of these molecules in human embryonic tooth. In this study, expression patterns of WNT/β-CATENIN signaling components, including WNT ligands (WNT3, WNT5A), receptors (FZD4, FZD6, LRP5), transducers (β-CATENIN), transcription factors (TCF4, LEF1) and antagonists (DKK1, SOSTDC1) were investigated in human tooth germ at the bud, cap and bell stages by in situ hybridization. All these genes exhibited similar but slightly distinct expression patterns in human tooth germ in comparison with mouse. Furthermore the mRNA expression of these genes in incisors and molars at the bell stage was also examined by real-time PCR. Our results reveal the status of active WNT/β-CATENIN signaling in the human tooth germ and suggest these components may also play an essential role in the regulation of human tooth development.

  18. Molecular tailoring approach for geometry optimization of large molecules: energy evaluation and parallelization strategies.

    PubMed

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

    2006-09-14

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-09-01

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

  20. Practical Calculation of Molecular Acidity with the Aid of a Reference Molecule

    SciTech Connect

    Burger, Steven K; Liu, Shubin; Ayers, Paul W

    2011-02-24

    A set of linear free energy models are presented for determining the pK{sub a} values of amines, alcohols, and carboxylic acids. Models are determined from a series of pK{sub a} predictors, taken both from traditional natural atomic orbital analysis (NAO) and from a novel approach introduced here of using a reference molecule: an ammonium ion for amines and a hydrogen sulfide molecule for alcohols and carboxylic acids. Using these reference molecules, we calculate the barrier to proton transfer and show that a number of properties associated with the transition state are correlated with the pK{sub a}. By considering 38 predictors, we obtain a four-variable model for amines and a three-variable model for oxygen-containing compounds. The model for amines is based on 145 compounds and has a root mean squared error (RMSE) of 0.45 and R{sup 2} = 0.98. The oxygen set has 48 molecules: RMSE = 0.26, and R{sup 2} = 0.993. Similar, linear, and multilinear models are constructed after separating the sets into chemically similar categories: alcohols, carboxylic acids, and primary, secondary, tertiary, and aromatic amines. This separation gives simpler models with relatively low RMSE values, where the most important predictor of the pK{sub a} is the difference in energy between transferring the proton from the reference molecular base to the conjugate acid from the data set.

  1. Probing molecular adsorption and mechanics at the atomic scale: The Nanocar family of molecules

    NASA Astrophysics Data System (ADS)

    Osgood, Andrew J.

    Molecular machines, typically thought to be only the fanciful imaginings of speculative fiction, have taken great strides in recent years towards real-world viability and usefulness. Under variable temperature scanning tunneling microscopy, (STM) one family of these nascent devices is characterized with atomic resolution, and probed and manipulated with sub-angstrom precision, adding to the growing body of knowledge of how molecular devices behave and react at nanometer scales. Evidence of temperature-dependent rolling of wheel-like fullerene constituents on the Nanocar is discussed in light of newly developed image analysis techniques. Additionally, charge-transfer mediated behavior at step edges, both static and dynamic, is investigated on a Au(111) surface for a more complete understanding of translation and surface diffusion. Molecular flexibility is thought to aid in this three-dimensional atomic-step-crossing diffusion, and is explored and discussed across many species in the Nanocar family of molecules. In all, many similar molecules have been characterized and explored via STM with an eye towards their dynamic capabilities and surface behaviors, in the hopes that future, more complex versions can build on the nascent knowledge base beginning to be established here.

  2. Fast molecular shocks. I - Reformation of molecules behind a dissociative shock

    NASA Technical Reports Server (NTRS)

    Neufeld, David A.; Dalgarno, A.

    1989-01-01

    The physical and chemical processes that operate in the cooling gas behind a fast, dissociative, single-fluid shock propagating in a dense interstellar cloud are discussed. The treatment extends previous theoretical work on fast molecular shocks by including the effects of the conversion of Ly-alpha photons into radiation of the two-photon continuum and into H2 Lyman band emission lines, the effects of CO photodissociation following line absorption, and the formation and destruction of molecules containing the elements nitrogen, silicon, and sulphur, and of the complex hydrocarbons. Abundance profiles for the molecular species of interest are presented. After molecular hydrogen begins to reform, by means of gas phase and grain surface processes, the neutral species OH, H2O, O2, CO, CN, HCN, N2, NO, SO, and SiO reach substantial abundances. The molecular ions HeH(+), OH(+), SO(+), CH(+), H2(+), and H3(+), are produced while the gas is still hot and partially ionized. Emissions from them provide a possible diagnostic probe of fast molecular shocks.

  3. Quantum-interference-enhanced thermoelectricity in single molecules and molecular films

    NASA Astrophysics Data System (ADS)

    Lambert, Colin J.; Sadeghi, Hatef; Al-Galiby, Qusiy H.

    2016-12-01

    We provide a brief overview of recent measurements and predictions of thermoelectric properties of single-molecules and porous nanoribbons and discuss some principles underpinning strategies for enhancing their thermoelectric performance. The latter include (a) taking advantage of steep slopes in the electron transmission coefficient T (E), (b) creating structures with delta-function-like transmission coefficients and (c) utilising step-like features in T (E). To achieve high performance, we suggest that the latter may be the most fruitful, since it is less susceptible to inhomogeneous broadening. For the purpose of extrapolating thermoelectric properties of single or few molecules to monolayer molecular films, we also discuss the relevance of the conductance-weighted average Seebeck coefficient. xml:lang="fr"

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

    PubMed

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

    2015-03-01

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

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

    SciTech Connect

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

    2014-03-01

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

  6. Validation and extraction of molecular-geometry information from small-molecule databases

    PubMed Central

    Long, Fei; Emsley, Paul; Gražulis, Saulius; Merkys, Andrius; Vaitkus, Antanas

    2017-01-01

    A freely available small-molecule structure database, the Crystallography Open Database (COD), is used for the extraction of molecular-geometry information on small-molecule compounds. The results are used for the generation of new ligand descriptions, which are subsequently used by macromolecular model-building and structure-refinement software. To increase the reliability of the derived data, and therefore the new ligand descriptions, the entries from this database were subjected to very strict validation. The selection criteria made sure that the crystal structures used to derive atom types, bond and angle classes are of sufficiently high quality. Any suspicious entries at a crystal or molecular level were removed from further consideration. The selection criteria included (i) the resolution of the data used for refinement (entries solved at 0.84 Å resolution or higher) and (ii) the structure-solution method (structures must be from a single-crystal experiment and all atoms of generated molecules must have full occupancies), as well as basic sanity checks such as (iii) consistency between the valences and the number of connections between atoms, (iv) acceptable bond-length deviations from the expected values and (v) detection of atomic collisions. The derived atom types and bond classes were then validated using high-order moment-based statistical techniques. The results of the statistical analyses were fed back to fine-tune the atom typing. The developed procedure was repeated four times, resulting in fine-grained atom typing, bond and angle classes. The procedure will be repeated in the future as and when new entries are deposited in the COD. The whole procedure can also be applied to any source of small-molecule structures, including the Cambridge Structural Database and the ZINC database. PMID:28177306

  7. Molecular Spectra of RbSr: Helium Droplet Assisted Preparation of a Diatomic Molecule

    NASA Astrophysics Data System (ADS)

    Lackner, Florian; Krois, Günter; Buchsteiner, Thomas; Pototschnig, Johann V.; Ernst, Wolfgang E.

    2014-06-01

    We report on the first spectroscopic investigation of the ground and excited states of RbSr. The molecules are prepared in their vibronic ground state (X^2Σ^+1/2, ν" = 0) in a sequential pickup process on the surface of helium nanodroplets, confined in a cold (0.38 K) and weakly perturbing superfluid environment. Utilizing resonance-enhanced multi-photon ionization time-of-flight (REMPI-TOF) spectroscopy and laser induced fluorescence (LIF) spectroscopy our investigations cover the spectral regime of 11500 cm-1 - 23000 cm-1. The weak interaction between molecules and helium droplets causes a broadening of the observed transitions. For spectrally resolved band systems the helium droplet isolation approach facilitates the determination of molecular constants. Our assignment is assisted by theoretical calculations of potential energy curves based on a multireference configuration interaction (MRCI) approach. Several strong transitions could be identified; the most prominent spectral feature is a vibrational resolved band system at 14000 cm-1. In contrast to the excitation spectra, dispersed fluorescence (DF) spectra are not influenced by the helium environment, because the molecules leave the droplets upon photoexcitation, revealing detailed insights into the electronic structure of the free RbSr molecule. G. Krois, J.V. Pototschnig, F. Lackner and W.E. Ernst, J. Phys. Chem. A, 117 (50), 13719-13731 (2013) C. Callegari and W. E. Ernst, Helium Droplets as Nanocryostats for Molecular Spectroscopy - from the Vacuum Ultraviolet to the Microwave Regime, in: Handbook of High-Resolution Spectroscopy, eds. M. Quack and F. Merkt, John Wiley & Sons, Chichester, (2011) P.S. Żuchowski, R. Guerout, and O. Dulieu, arXiv preprint arXiv:1402.0702 (2014) B. Pasquiou, A. Bayerle, S.M. Tzanova, S. Stellmer, J. Szczepkowski, M. Parigger, R. Grimm, and F. Schreck, Phys. Rev. A, 88 (2), 023601 (2013).

  8. Molecular Dynamics Simulation of Squeeze-Film Damping in the Free-Molecule Regime

    NASA Astrophysics Data System (ADS)

    Hong, Gang; Ye, Wenjing

    2008-12-01

    A molecular dynamics (MD) simulation tool was developed for the prediction of squeeze-film damping on a micro beam/plate resonator oscillating in a highly rarefied gas environment. This tool was then employed to identify important parameters that characterize the damping and to study the dependence of the quality factor of the resonator on these parameters. Particular focus is on air flows that are in the free-molecule regime. An excellent agreement between the predicted quality factor and the measurement data in the low pressure range has been achieved and favorable comparisons with other models have also been demonstrated.

  9. Time-reversible always stable predictor-corrector method for molecular dynamics of polarizable molecules.

    PubMed

    Kolafa, Jirí

    2004-02-01

    An improved method for classic molecular dynamics of polarizable molecules is proposed. The method uses a predictor, one evaluation of the electrostatic field per integration step, and relaxation (damping). The self-consistent solution is approximated with error of the second order (with respect to the timestep). The time reversibility (long-time energy conservation) error is of the (2n - 1)th order, where n is the predictor length. The method is easy to implement, efficient, accurate, and suitable for any model of polarizability.

  10. Localization of open-shell molecular orbitals via least change from fragments to molecule

    NASA Astrophysics Data System (ADS)

    Li, Hongyang; Liu, Wenjian; Suo, Bingbing

    2017-03-01

    Both top-down and bottom-up localization schemes are proposed for constructing localized molecular orbitals (LMOs) of open-shell systems, via least change from fragments to molecule. The success of both schemes stems from (1) the primitive fragment LMOs that are local not only in space but also in energy and (2) the "conquer step" that allows arbitrary assignment of the unpaired electrons to fragments. Moreover, integral occupations are retained, so as to facilitate subsequent treatment of electron correlation and excitation.

  11. Distance-dependent patterns of molecular divergences in tuatara mitogenomes

    PubMed Central

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

    2015-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    DOE PAGES

    Wang, Xu; Le, Anh -Thu; Yu, Chao; ...

    2016-03-30

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

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

    SciTech Connect

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

    2016-03-30

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

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

    PubMed Central

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

    2016-01-01

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

  16. Molecular structure and the EPR calculation of the gas phase succinonitrile molecule

    NASA Astrophysics Data System (ADS)

    Kepceoǧlu, A.; Kılıç, H. Ş.; Dereli, Ö.

    2017-02-01

    Succinonitrile (i.e. butanedinitrile) is a colorless nitrile compound that can be used in the gel polymer batteries as a solid-state solvent electrolytes and has a plastic crystal structure. Prior to the molecular structure calculation of the succinonitrile molecule, the conformer analysis were calculated by using semi empirical method PM3 core type Hamiltonian and eight different conformer structures were determined. Molecular structure with energy related properties of these conformers having the lowest energy was calculated by using DFT (B3LYP) methods with 6-311++G(d,p) basis set. Possible radicals, can be formed experimentally, were modeled in this study. EPR parameters of these model radicals were calculated and then compared with that obtained experimentally.

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

    PubMed

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

    2015-01-22

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

  18. Probing the emitter site of Renilla luciferase using small organic molecules; an attempt to understand the molecular architecture of the emitter site.

    PubMed

    Salehi, Farajollah; Emamzadeh, Rahman; Nazari, Mahboobeh; Rasa, Seyed Mohammad Mahdi

    2016-12-01

    Renilla luciferase is a sensitive enzyme and has wide applications in biotechnology such as drug screening. Previous studies have tried to show the catalytic residues, nevertheless, the accurate architecture and molecular behavior of its emitter site remains uncharacterized. In this study, the activity of Renilla luciferase, in the presence of two small organic molecules including dimethyl sulfoxide (DMSO) and isopropanol was considered and the structure was studied by circular dichroism (CD) and fluorescence spectroscopy. Moreover, the interaction of small organic molecules with the Renilla luciferase was studied using molecular dynamics simulations. Kinetics studies showed that at low concentration of DMSO (16.6-66mM) and isopropanol (19.3-76mM) the Km changed and a competitive inhibition pattern was observed. Moreover, spectroscopy studies reveled that the changes of activity of Renilla luciferase in the presence of low concentrations of small organic molecules was not associated with structural collapse or severe changes in the enzyme conformation. Molecular dynamics simulations indicated that DMSO and isopropanol, as probing molecules, were both able to bind to the emitter site and remained with the residues of the emitter site. Based on the probing data, the architecture of the emitter site in the "non-binding" model was proposed.

  19. Deep immune profiling by mass cytometry links human T and NK cell differentiation and cytotoxic molecule expression patterns.

    PubMed

    Bengsch, Bertram; Ohtani, Takuya; Herati, Ramin Sedaghat; Bovenschen, Niels; Chang, Kyong-Mi; Wherry, E John

    2017-03-19

    The elimination of infected or tumor cells by direct lysis is a key T and NK cell effector function. T and NK cells can kill target cells by coordinated secretion of cytotoxic granules containing one or both pore-forming proteins, perforin and granulysin and combinations of granzyme (Gzm) family effector proteases (in humans: Gzm A, B, K, M and H). Understanding the pattern of expression of cytotoxic molecules and the relationship to different states of T and NK cells may have direct relevance for immune responses in autoimmunity, infectious disease and cancer. Approaches capable of simultaneously evaluating expression of multiple cytotoxic molecules with detailed information on T and NK differentiation state, however, remain limited. Here, we established a high dimensional mass cytometry approach to comprehensively interrogate single cell proteomic expression of cytotoxic programs and lymphocyte differentiation. This assay identified a coordinated expression pattern of cytotoxic molecules linked to CD8 T cell differentiation stages. Coordinated high expression of perforin, granulysin, Gzm A, Gzm B and Gzm M was associated with markers of late effector memory differentiation and expression of chemokine receptor CX3CR1. However, classical gating and dimensionality reduction approaches also identified other discordant patterns of cytotoxic molecule expression in CD8 T cells, including reduced perforin, but high Gzm A, Gzm K and Gzm M expression. When applied to non-CD8 T cells, this assay identified different patterns of cytotoxic molecule co-expression by CD56(hi) versus CD56(dim) defined NK cell developmental stages; in CD4 T cells, low expression of cytotoxic molecules was found mainly in TH1 phenotype cells, but not in Tregs or T follicular helper cells (TFH). Thus, this comprehensive, single cell, proteomic assessment of cytotoxic protein co-expression patterns demonstrates specialized cytotoxic programs in T cells and NK cells linked to their differentiation

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

    SciTech Connect

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

    2014-09-28

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

  1. Characterization of Plant Cell Wall Damage-Associated Molecular Patterns Regulating Immune Responses.

    PubMed

    Bacete, Laura; Mélida, Hugo; Pattathil, Sivakumar; Hahn, Michael G; Molina, Antonio; Miedes, Eva

    2017-01-01

    The plant cell wall is one of the first defensive barriers that pathogens need to overcome to successfully colonize plant tissues. Plant cell wall is considered a dynamic structure that regulates both constitutive and inducible defense mechanisms. The wall is a potential source of a diverse set of Damage-Associated Molecular Patterns (DAMPs), which are signalling molecules that trigger immune responses. However, just a few active wall ligands, such as oligogalacturonic acids (OGs), have been characterized so far. To identify additional wall-derived DAMPs, we obtained different plant wall fractions and tested their capacity to trigger immune responses using a calcium read-out system. To characterize the active DAMPs structures present in these fractions, we applied Glycome Profiling, a technology that uses a large and diverse set of specific monoclonal antibodies against wall carbohydrate ligands. The methods describe here can be used in combination with other biochemical approaches to identify and purify new plant cell wall DAMPs.

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

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

    NASA Astrophysics Data System (ADS)

    Granot, Ori; Amirav, Aviv

    2005-06-01

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

  4. Investigation of the influence factors of polyethylene molecule encapsulated into carbon nanotubes by molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Li, Qun; He, Guofang; Zhao, Rengao; Li, Yanfei

    2011-09-01

    In this work, the influence factors, namely chirality, temperature, radius and surface chemical modification, of the interaction energy for polyethylene (PE) molecule encapsulated into single-walled carbon nanotubes (SWNTs) had been investigated by molecular mechanics (MM) and molecular dynamics (MD) simulation. The results showed that all these factors would influence the interaction energy between PE and SWNTs. The interaction energy between PE molecule and the armchair SWNTs is largest among eight kinds of chiral SWNTs. The interaction energy decreases with the increase of temperature or the SWNT radius. The methyl, phenyl, hydroxyl, carboxyl, -F, and amino groups, have been introduced onto the surface of the SWNTs by the simulation software and the influence of SWNT chemical modification has also been investigated. The interaction energy between PE and chemically modified SWNTs is larger than that between PE and pristine SWNTs, and increases with increasing the concentration of the modified groups monotonously. In addition, the group electronegativity and van der Waals force will affect the interaction energy between PE and chemically modified SWNTs greatly, which can be attributed to the electronic structures of the chemically modified groups. This study can provide some useful suggestions for the composite material design and drug transport.

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

    PubMed

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

    2015-02-01

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

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

    NASA Astrophysics Data System (ADS)

    Cernicharo, Jose

    2016-06-01

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

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

    PubMed

    Rocha, Maria Victoria; Nerli, Bibiana Beatriz

    2013-10-01

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

  8. Theoretical descriptions of electron transport through single molecules: Developing design tools for molecular electronic devices

    NASA Astrophysics Data System (ADS)

    Carroll, Natalie R.

    There are vast numbers of organic compounds that could be considered for use in molecular electronics. Hence there is a need for efficient and economical screening tools. Here we develop theoretical methods to describe electron transport through individual molecules, the ultimate goal of which is to establish design tools for molecular electronic devices. To successfully screen a compound for its use as a device component requires a proper representation of the quantum mechanics of electron transmission. In this work we report the development of tools for the description of electron transmission that are: Charge self-consistent, valid in the presence of a finite applied potential field and (in some cases) explicitly time-dependent. In addition, the tools can be extended to any molecular system, including biosystems, because they are free of restrictive parameterizations. Two approaches are explored: (1) correlation of substituent parameter values (sigma), (commonly found in organic chemistry textbooks) to properties associated with electron transport, (2) explicit tracking of the time evolution of the wave function of a nonstationary electron. In (1) we demonstrate that the a correlate strongly with features of the charge migration process, establishing them as useful indicators of electronic properties. In (2) we employ a time-dependent description of electron transport through molecular junctions. To date, the great majority of theoretical treatments of electron transport in molecular junctions have been of the time-independent variety. Time dependence, however, is critical to such properties as switching speeds in binary computer components and alternating current conductance, so we explored methods based on time-dependent quantum mechanics. A molecular junction is modeled as a single molecule sandwiched between two clusters of close-packed metal atoms or other donor and acceptor groups. The time dependence of electron transport is investigated by initially

  9. Preface - From molecules to molecular materials, biological molecular systems and nanostructures: A collection of contributions presented at the XIIIth International Conference on Molecular Spectroscopy

    NASA Astrophysics Data System (ADS)

    Ratajczak, Henryk; Drozd, Marek; Fausto, Rui

    2016-12-01

    This volume contains a series of selected contributions presented at the XIIIth International Conference on Molecular Spectroscopy (ICMS): "From Molecules to Molecular Materials, Biological Molecular Systems and Nanostructures" held in Wrocław, Poland, 9-12 September 2015, under the auspices of the Mayor of Wrocław and the European Academy of Sciences, Arts and Humanities. Wrocław was chosen not accidentally as venue for the conference. With more than a thousand years of history, Wrocław is the location of one of the oldest universities in Central Europe. Being a place where education and science play major roles in the daily life of its inhabitants, Wrocław is also a privileged center for spectroscopy in Poland.

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

    PubMed

    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

    2009-02-04

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

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

    NASA Astrophysics Data System (ADS)

    Shirota, Hideaki

    2005-01-01

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

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

    PubMed

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

    2013-08-27

    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 β-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.

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

    PubMed Central

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

    2015-01-01

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

  15. Room-temperature dynamic correlation between methylammonium molecules in lead-iodine based perovskites: An ab initio molecular dynamics perspective

    NASA Astrophysics Data System (ADS)

    Lahnsteiner, Jonathan; Kresse, Georg; Kumar, Abhinav; Sarma, D. D.; Franchini, Cesare; Bokdam, Menno

    2016-12-01

    The high efficiency of lead organo-metal-halide perovskite solar cells has raised many questions about the role of the methylammonium (MA) molecules in the Pb-I framework. Experiments indicate that the MA molecules are able to "freely" spin around at room temperature even though they carry an intrinsic dipole moment. We have performed large supercell (2592 atoms) finite-temperature ab initio molecular dynamics calculations to study the correlation between the molecules in the framework. An underlying long-range antiferroelectric ordering of the molecular dipoles is observed. The dynamical correlation between neighboring molecules shows a maximum around room temperature in the mid-temperature phase. In this phase, the rotations are slow enough to (partially) couple to neighbors via the Pb-I cage. This results in a collective motion of neighboring molecules in which the cage acts as the mediator. At lower and higher temperatures, the motions are less correlated.

  16. The role of molecular dipole orientation in single-molecule fluorescence microscopy and implications for super-resolution imaging.

    PubMed

    Backlund, Mikael P; Lew, Matthew D; Backer, Adam S; Sahl, Steffen J; Moerner, W E

    2014-03-17

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

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

    SciTech Connect

    Chu, P.M.Y.

    1991-10-01

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

  18. Hairpin-bisulfite PCR: Assessing epigenetic methylation patterns on complementary strands of individual DNA molecules

    PubMed Central

    Laird, Charles D.; Pleasant, Nicole D.; Clark, Aaron D.; Sneeden, Jessica L.; Hassan, K. M. Anwarul; Manley, Nathan C.; Vary, Jay C.; Morgan, Todd; Hansen, R. Scott; Stöger, Reinhard

    2004-01-01

    Epigenetic inheritance, the transmission of gene expression states from parent to daughter cells, often involves methylation of DNA. In eukaryotes, cytosine methylation is a frequent component of epigenetic mechanisms. Failure to transmit faithfully a methylated or an unmethylated state of cytosine can lead to altered phenotypes in plants and animals. A central unresolved question in epigenetics concerns the mechanisms by which a locus maintains, or changes, its state of cytosine methylation. We developed “hairpin-bisulfite PCR” to analyze these mechanisms. This method reveals the extent of methylation symmetry between the complementary strands of individual DNA molecules. Using hairpin-bisulfite PCR, we determined the fidelity of methylation transmission in the CpG island of the FMR1 gene in human lymphocytes. For the hypermethylated CpG island of this gene, characteristic of inactive-X alleles, we estimate a maintenance methylation efficiency of ≈0.96 per site per cell division. For de novo methylation efficiency (Ed), remarkably different estimates were obtained for the hypermethylated CpG island (Ed = 0.17), compared with the hypomethylated island on the active-X chromosome (Ed < 0.01). These results clarify the mechanisms by which the alternative hypomethylated and hypermethylated states of CpG islands are stably maintained through many cell divisions. We also analyzed a region of human L1 transposable elements. These L1 data provide accurate methylation patterns for the complementary strand of each repeat sequence analyzed. Hairpin-bisulfite PCR will be a powerful tool in studying other processes for which genetic or epigenetic information differs on the two complementary strands of DNA. PMID:14673087

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

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2015-08-04

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  4. Kinetics of molecular transitions with dynamic disorder in single-molecule pulling experiments

    NASA Astrophysics Data System (ADS)

    Zheng, Yue; Li, Ping; Zhao, Nanrong; Hou, Zhonghuai

    2013-05-01

    Macromolecular transitions are subject to large fluctuations of rate constant, termed as dynamic disorder. The individual or intrinsic transition rates and activation free energies can be extracted from single-molecule pulling experiments. Here we present a theoretical framework based on a generalized Langevin equation with fractional Gaussian noise and power-law memory kernel to study the kinetics of macromolecular transitions to address the effects of dynamic disorder on barrier-crossing kinetics under external pulling force. By using the Kramers' rate theory, we have calculated the fluctuating rate constant of molecular transition, as well as the experimentally accessible quantities such as the force-dependent mean lifetime, the rupture force distribution, and the speed-dependent mean rupture force. Particular attention is paid to the discrepancies between the kinetics with and without dynamic disorder. We demonstrate that these discrepancies show strong and nontrivial dependence on the external force or the pulling speed, as well as the barrier height of the potential of mean force. Our results suggest that dynamic disorder is an important factor that should be taken into account properly in accurate interpretations of single-molecule pulling experiments.

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

    NASA Astrophysics Data System (ADS)

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

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

  6. Rotation-vibration motion of extremely flexible molecules - The molecular superrotor

    NASA Astrophysics Data System (ADS)

    Schmiedt, Hanno; Jensen, Per; Schlemmer, Stephan

    2017-03-01

    This paper treats the low energy rotation-vibration problem in CH5+, an extremely flexible molecule lacking a well-defined structure. Using SO(5) symmetry it determines zeroth order energies, and complete nuclear permutation S5 symmetries, using a five-dimensional model involving rotation and two vibrations (which one might imagine as two different ;cooperative; HCH bends). These two vibrations are presumed to be unhindered by the molecular potential function and their analytical form is not determined. The other ten vibrational degrees of freedom are presumed to be ;rigid; (or averaged over). The general energy expression for this ;rigid superrotor; is obtained as (B / 2) [n1 (n1 + 3) +n2 (n2 + 1) ] where B is the rotational constant and the non-negative integers n1 and n2 satisfy n2 ⩽n1 . The superrotor predictions agree favourably with the available experimental data. Applications of the superrotor model to extremely flexible molecules other than CH5+ are discussed.

  7. Nonadiabatic quantum molecular dynamics with hopping. III. Photoinduced excitation and relaxation of organic molecules

    NASA Astrophysics Data System (ADS)

    Fischer, M.; Handt, J.; Schmidt, R.

    2014-07-01

    Photoinduced excitation and relaxation of organic molecules (C2H4 and CH2NH2+) are investigated by means of nonadiabatic quantum molecular dynamics with hopping (NA-QMD-H), developed recently [Fischer, Handt, and Schmidt, paper I of this series, Phys. Rev. A 90, 012525 (2014), 10.1103/PhysRevA.90.012525]. This method is first applied to molecules assumed to be initially ad hoc excited to an electronic surface. Special attention is drawn to elaborate the role of electron-nuclear correlations, i.e., of quantum effects in the nuclear dynamics. It is found that they are essential for a realistic description of the long-time behavior of the electronic relaxation process, but only of minor importance to portray the short-time scenario of the nuclear dynamics. Migration of a hydrogen atom, however, is identified as a quantum effect in the nuclear motion. Results obtained with explicit inclusion of an fs-laser field are presented as well. It is shown that the laser-induced excitation process generally leads to qualitatively different gross features of the relaxation dynamics, as compared to the field-free case. Nevertheless, the nuclear wave packet contains all subtleties of the cis-trans isomerization mechanism as observed without a laser field.

  8. The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases

    PubMed Central

    Nakahira, Kiichi; Hisata, Shu

    2015-01-01

    Abstract Significance: Mitochondria, vital cellular power plants to generate energy, are involved in immune responses. Mitochondrial damage-associated molecular patterns (DAMPs) are molecules that are released from mitochondria to extracellular space during cell death and include not only proteins but also DNA or lipids. Mitochondrial DAMPs induce inflammatory responses and are critically involved in the pathogenesis of various diseases. Recent Advances: Recent studies elucidate the molecular mechanisms by which mitochondrial DAMPs are released and initiate immune responses by use of genetically modulated cells or animals. Importantly, the levels of mitochondrial DAMPs in patients are often associated with severity and prognosis of human diseases, such as infection, asthma, ischemic heart disease, and cancer. Critical Issues: Although mitochondrial DAMPs can represent proinflammatory molecules in various experimental models, their roles in human diseases may be multifunctional and complex. It remains unclear where and how mitochondrial DAMPs are liberated into extracellular spaces and exert their biological functions particularly in vivo. In addition, while mitochondria can secrete several types of DAMPs during cell death, the interaction of each mitochondrial DAMP (e.g., synergistic effects) remains unclear. Future Directions: Regulation of mitochondrial DAMP-mediated immune responses may be important to alter the progression of human diseases. In addition, measuring mitochondrial DAMPs in patients may be clinically useful as biomarkers to predict prognosis or response to therapies. Further studies of the mechanisms by which mitochondrial DAMPs impact the initiation and progression of diseases may lead to the development of therapeutics specifically targeting this pathway. Antioxid. Redox Signal. 23, 1329–1350. PMID:26067258

  9. Formation of novel rare-gas-containing molecules by molecular photodissociation in clusters.

    PubMed

    Cohen, A; Niv, M Y; Gerber, R B

    2001-01-01

    Recent work by Räsänen and coworkers showed that photolysis of hydrides in rare-gas matrices results in part in formation of novel, rare-gas-containing molecules. Thus, photolysis of HCl in Xe and of H2O in Xe result respectively in formation of HXeCl and HXeOH in the Xe matrices. Ab initio calculations show that the compounds HRgY so formed are stable in isolation, and that by the strength and nature of the bonding these are molecules, very different from the corresponding weakly bound clusters Rg...HY. This paper presents a study of the formation mechanism of HRgY following the photolysis of HY in clusters Rgn(HY). Calculations are described for HXeCl, as a representative example. Potential energy surfaces that govern the formation of HXeCl in the photolysis of HCl in xenon clusters are obtained, and the dynamics on these surfaces is analyzed, partly with insight from trajectories of molecular dynamics simulations. The potential surfaces are obtained by a new variant of the DIM (diatomics in molecules) and DIIS (diatomics in ionic systems) models. Non-adiabatic couplings are also obtained. The main results are: (1) Properties of HXeCl predicted by the DIM-DIIS model are in reasonable accord with results of ab initio calculations. (2) The potential along the isomerization path HXeCl-->Xe...HCl predicted by DIM is in semiquantitative accord with the ab initio results. (3) Surface-hopping molecular dynamics simulations of the process in clusters, with "on the fly" calculations of the DIM-DIIS potentials and non-adiabatic couplings are computationally feasible. (4) Formation of HXeCl, following photolysis of HCl in Xe54(HCl), requires cage-exit of the H atom as a precondition. The H atom and the Cl can then attack the same Xe atom on opposite sides, leading to charge transfer and production of the ionic HXeCl. (5) Non-adiabatic processes play an important role, both in the reagent configurations, and at the charge-transfer stage. The results open the way to

  10. Acidity Constant (pKa ) Calculation of Large Solvated Dye Molecules: Evaluation of Two Advanced Molecular Dynamics Methods.

    PubMed

    De Meyer, Thierry; Ensing, Bernd; Rogge, Sven M J; De Clerck, Karen; Meijer, Evert Jan; Van Speybroeck, Veronique

    2016-11-04

    pH-Sensitive dyes are increasingly applied on polymer substrates for the creation of novel sensor materials. Recently, these dye molecules were modified to form a covalent bond with the polymer host. This had a large influence on the pH-sensitive properties, in particular on the acidity constant (pKa ). Obtaining molecular control over the factors that influence the pKa value is mandatory for the future intelligent design of sensor materials. Herein, we show that advanced molecular dynamics (MD) methods have reached the level at which the pKa values of large solvated dye molecules can be predicted with high accuracy. Two MD methods were used in this work: steered or restrained MD and the insertion/deletion scheme. Both were first calibrated on a set of phenol derivatives and afterwards applied to the dye molecule bromothymol blue. Excellent agreement with experimental values was obtained, which opens perspectives for using these methods for designing dye molecules.

  11. Characterization of phospholipid molecular species and peptide molecules in wheat sprout hydroalcoholic extract.

    PubMed

    Lucci, Paolo; Pacetti, Deborah; Calzuola, Isabella; Marsili, Valeria; Perni, Stefano; Giavarini, Flavio; Frega, Natale Giuseppe; Gianfranceschi, Gian Luigi

    2013-11-27

    The phospholipid molecular species and the main peptide molecules of wheat sprout hydroalcoholic extract have been fully characterized by normal-phase high performance liquid chromatography coupled online with positive electrospray ionization tandem mass spectrometry. The extract that resulted was rich in phospholipid molecular species formed by the combination of the two essential fatty acids (α-linoleic and α-linolenic). These species accounted for 51.7% of total phosphatidic acid, 47.3% of total phosphatidylethanolamine, 37.7% of total phosphatidylcholine, and 14.1% of total phosphatidylinositol. The last one showed the highest amounts of species containing palmitic acid, thus representing the most saturated phospholipid class. The extract was also shown to contain several peptide sequences with both potential antioxidant domains and interaction sites for phospholipids (i.e., H-Ala-Gly-Ser-Met-Met-Cys-NH2, H-Tyr-Met-Thr-Val-Val-Ala-Cys-NH2, etc.); this latter finding can have a highly positive impact on the poor peptides bioavailability. Because of the presence of essential fatty acids-rich phospholipids and bioactive peptides, wheat sprout hydroalcoholic extract can be considered a potential functional food ingredient.

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

    PubMed

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

    2016-08-10

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

  13. Planar microdevices enhance transport of large molecular weight molecules across retinal pigment epithelial cells.

    PubMed

    Wade, Jennifer S; Desai, Tejal A

    2014-08-01

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

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

    PubMed

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

    2011-01-01

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

  15. Molecular Quantum Spintronics: Supramolecular Spin Valves Based on Single-Molecule Magnets and Carbon Nanotubes

    PubMed Central

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

    2011-01-01

    We built new hybrid devices consisting of chemical vapor deposition (CVD) grown carbon nanotube (CNT) transistors, decorated with TbPc2 (Pc = phthalocyanine) rare-earth based single-molecule magnets (SMMs). The drafting was achieved by tailoring supramolecular π-π interactions between CNTs and SMMs. The magnetoresistance hysteresis loop measurements revealed steep steps, which we can relate to the magnetization reversal of individual SMMs. Indeed, we established that the electronic transport properties of these devices depend strongly on the relative magnetization orientations of the grafted SMMs. The SMMs are playing the role of localized spin polarizer and analyzer on the CNT electronic conducting channel. As a result, we measured magneto-resistance ratios up to several hundred percent. We used this spin valve effect to confirm the strong uniaxial anisotropy and the superparamagnetic blocking temperature (TB ~ 1 K) of isolated TbPc2 SMMs. For the first time, the strength of exchange interaction between the different SMMs of the molecular spin valve geometry could be determined. Our results introduce a new design for operable molecular spintronic devices using the quantum effects of individual SMMs. PMID:22072910

  16. The interplay between pathogen-associated and danger-associated molecular patterns: an inflammatory code in cancer?

    PubMed

    Escamilla-Tilch, Monica; Filio-Rodríguez, Georgina; García-Rocha, Rosario; Mancilla-Herrera, Ismael; Mitchison, Nicholas Avrion; Ruiz-Pacheco, Juan Alberto; Sánchez-García, Francisco Javier; Sandoval-Borrego, Daniela; Vázquez-Sánchez, Ernesto Antonio

    2013-01-01

    There is increasing evidence of a close link between inflammation and cancer, and at the core of inflammation there are both pathogen-associated molecular patterns (PAMPs) and danger (or damage)-associated molecular patterns (DAMPs). Microorganisms harbor molecules structurally conserved within groups called PAMPs that are recognized by specific receptors present on immune cells, such as monocytes and dendritic cells (DCs); these are the pattern recognition receptors (PRRs). Activation through different PRRs leads to production of pro-inflammatory cytokines. A robust immune response also requires the presence of endogenous molecules that pose 'danger' to self-tissues and are produced by damaged or stressed cells; these are the DAMPs, which act also as inducers of inflammation. PAMPs and DAMPs are each recognized by a limited set of receptors that in number probably do not exceed 100. PAMPs and DAMPs interact with each other, and a single PRR can bind to a PAMP as well as a DAMP. Within this framework, we propose that PAMPs and DAMPs act in synchrony, modifying the activation threshold of one another. Thus, the range of PAMP-DAMP partnerships defines the course of inflammation, in a predictable manner, in an 'inflammatory code'. The definition of relevant PAMP-DAMP complexes is important for the understanding of inflammatory disorders in general, and of cancer in particular. Here, we review relevant findings that support the notion of a PAMP-DAMP-based inflammatory code, with emphasis on cancer immunology and immunotherapy.

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    SciTech Connect

    Obaid, R.; Leibscher, M.

    2015-02-14

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

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

    DOE PAGES

    Yu, Chao; Wei, Hui; Wang, Xu; ...

    2015-10-27

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    NASA Astrophysics Data System (ADS)

    Gao, Yi; Galperin, Michael; Nitzan, Abraham

    2016-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

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

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

    PubMed

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

    2016-12-21

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

  6. Molecular interactions of organic molecules at the air/water interface investigated by sum frequency generation vibrational spectroscopy.

    PubMed

    Wang, Wenting; Ye, Shuji

    2017-02-08

    The molecular structure and dynamics of organic molecules at the aqueous interface have attracted a number of investigations owing to their importance and specific nature. However, there are relatively few studies on the direct characterization of the molecular interactions at the air/water interface because they are extremely difficult to measure in experiments. In this study, we use dibutyl ester molecules (R1CO2R2O2CR1) as a model of organic molecules, and investigate their molecular structure and interactions using sum frequency generation vibrational spectroscopy. We demonstrate that the molecular interactions can be estimated by measuring the intensity ratio of the symmetric stretching (ν1) and Fermi resonant bands (2ν2) of methyl groups. Here, dibutyl ester molecules are widely used as plasticizers in polymers to improve the properties of the plastics and polymers. It is found that the orientation angles of the tailed methyl groups at the air/water interface decrease from 34° to 19° when the chain length of R2 increases from 0 to 8. The total intermolecular interactions of the dibutyl ester molecules decrease as the chain length of R2 increases because the van der Waals interactions between the hydrocarbon chains increase, while the hydrogen bond interactions between the carbonyl group and water molecules decrease. Our study demonstrates the stability of ester-based plasticizers in polymers can be well predicted from the intensity ratio of the ν1 and 2ν2 bands of methyl group. Such an intensity ratio can be thus used as an effective vibrational optical ruler for characterizing molecular interactions between plasticizers and polymers.

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

    PubMed

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

    2012-10-21

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

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

    PubMed Central

    Beh, Cyrus Weijie; Zhou, Weizhuang

    2013-01-01

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

  9. Probing ion-molecule structure and dynamics in isolated molecular clusters and proteins

    NASA Astrophysics Data System (ADS)

    Abate, Yohannes

    Ion-molecule interactions in isolated molecular clusters and proteins are studied in this work using experimental and theoretical methods. Photodissociation spectroscopy and chemical dynamics of several metal ion-molecule clusters are studied. The experimental tool used for these studies is an Angular Reflectron Time Of Flight Mass Spectrometer (ARTOFMS). The experimental work is supported by ab initio electronic structure calculations on the Gaussian and GAMESS platforms. This work also describes a computational study of the interaction of protonated histidine with other aromatic residues in proteins. We have studied the photodissociation spectroscopy of weakly bound Zn +(H2O) and Zn+(D2O) bimolecular complexes. We assign two molecular absorption bands in the near UV correlating to Zn+ (4s-4p)-metal centered transitions, and identify vibrational progressions associated with both intermolecular and intramolecular vibrational modes of the cluster. Partially resolved rotational structure is consistent with a C2 V equilibrium complex geometry. The photodissociation spectroscopy and chemical dynamics of Zn +-formaldehyde and Zn+-acetaldehyde clusters are investigated in the near UV spectral range. The work is also supported by ab initio electronic structure calculations to study the ground-state bonding and interactions in the low-lying doublet excited states. We identify absorption bands corresponding to photoinduced charge transfer, Zn+(4s-4p)-based transitions, and aldehyde-based excitations. We propose a reaction mechanism for the reactive dissociation that proceeds via H-atom abstraction on the charge-transfer surface. This work shows important differences with results from earlier experiments on Mg+- and Ca+-aldehyde complexes despite the similar valence character for these metal ions. In the study of Mg+-acetic acid we observe three distinct absorption bands, two red-shifted and one blue-shifted from the Mg +(3s ← 3p) resonance at 280 nm (35714 cm-1). We

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

    NASA Astrophysics Data System (ADS)

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

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

  11. Direct Molecular Simulation of Gradient-Driven Diffusion of Large Molecules using Constant Pressure

    SciTech Connect

    Heffelfinger, G.S.; Thompson, A.P.

    1998-12-23

    Dual control volume grand canonical molecular dynamics (DCV-GCMD) is a boundary-driven non-equilibrium molecular dynamics technique for simulating gradient driven diffusion in multi-component systems. Two control volumes are established at opposite ends of the simulation box. Constant temperature and chemical potential of diffusing species are imposed in the control volumes. This results in stable chemical potential gradients and steady-state diffusion fluxes in the region between the control volumes. We present results and detailed analysis for a new constant-pressure variant of the DCV-GCMD method in which one of the diffusing species for which a steady-state diffusion flux exists does not have to be inserted or deIeted. Constant temperature, pressure and chemical potential of all diffusing species except one are imposed in the control volumes. The constant-pressure method can be applied to situations in which insertion and deletion of large molecules would be prohibitively difficult. As an exampIe, we used the method to shnulate diffusion in a biruuy mixture of spherical particles with a 2:1 size ratio. Steady-state diffusion fluxes of both diffbsi.ng species were established. The constant-pressure diffision coefficients agreed closely with the results of the standard constant-volume calculations. In addition, we show how the concentration, chemical potential and flux profiles can be used to calculate kwd binary and Maxwell-Stefim diffusion coefficients. In the case of the 2:1 size ratio mixture, we found that the binary dlffision coefficients were asymmetric and composition dependent, whereas the Maxwell-Stefan diffision coefficients changed very little with composition and were symmetric. This last result verified that the Gibbs-Duhem relation was satisfied locally, thus validating the assumption of local equilibrium.

  12. Molecular orbital studies of gas-phase interactions between complex molecules.

    PubMed

    Gaudreault, Roger; Whitehead, M A; van de Ven, Theo G M

    2006-03-16

    Describing interactions among large molecules theoretically is a challenging task. As an example, we investigated gas-phase interactions between a linear nonionic oligomer and various model compounds (cofactors), which have been reported to associate experimentally, using PM3 semiempirical molecular orbital theory. As oligomer, we studied the hexamer of poly(ethylene oxide) (PEO), and as cofactors, we studied corilagin and related compounds containing phenolic groups (R-OH). These systems are of interest because they are models for PEO/cofactor flocculation systems, used in industrial applications. The PM3 delocalized molecular orbitals (DLMO) describe the bonding between (PEO)6 and cofactors, and some of them cover the complete complex. The DLMOs which cover the traditionally considered hydrogen bonds R-OH...O or R-CH...O show a distinct "pinch", a decrease of the electron density, between the H...O atoms. Calculations of Gibbs free energy, entropy, and enthalpy show that the PEO/cofactor complexes do not form at room temperature, because the loss of entropy exceeds the increase in enthalpy. The change in enthalpy is linearly related to the change in entropy for the different complexes. Even though bond lengths, bond angles, DLMOs, and electron densities for the PEO/cofactor complexes are consistent with the definition of hydrogen bonds, the number of intermolecular R-OH...O and R-CH...O bonds does not correlate with the enthalpy of association, indicating that the bonding mechanism for these systems is the sum of many small contributions of many delocalized orbitals.

  13. Hierarchical protein patterning by meso to molecular scale self-assembly

    NASA Astrophysics Data System (ADS)

    Andersen, Andreas S.; Sutherland, Duncan S.; Ogaki, Ryosuke

    2015-10-01

    Numerous protein patterning methodologies are used extensively for biomedical research and development. We have developed a novel bottom-up protein patterning method using a combination of self-assembly processes in the meso to molecular scale range to allow hierarchical protein patterns to be straightforwardly fabricated with low cost over large areas. As a proof of principle, we patterned vitronectin in various dimensional hierarchies using meso to nanoscale colloids and self-assembled monolayers.

  14. Development of the relaxation-assisted 2DIR method for accessing structures of molecules and its application for studying the energy transport on a molecular level

    NASA Astrophysics Data System (ADS)

    Kasyanenko, Valeriy Mitrofanovich

    Measuring the three-dimensional structure of molecules, dynamics of structural changes, and energy transport on a molecular scale is important for many areas of natural science. Supplementing the widely used methods of x-ray diffraction, NMR, and optical spectroscopies, a two-dimensional infrared spectroscopy (2DIR) method was introduced about a decade ago. The 2DIR method measures pair-wise interactions between vibrational modes in molecules, thus acquiring molecular structural constraints such as distances between vibrating groups and the angles between their transition dipoles. The 2DIR method has been applied to a variety of molecular systems but in studying larger molecules such as proteins and peptides the method is facing challenges associated with the congestion of their vibrational spectra and delocalized character of their vibrational modes. To help extract structural information from such spectra and make efficient use of vibrational modes separated by large distances, a novel relaxation-assisted 2DIR method (RA 2DIR) has recently been proposed, which exploits the transport of excess vibrational energy from the initially excited mode. With the goal of further development of RA 2DIR, we applied it to a variety of molecular systems, including model compounds, transition-metal complexes, and isomers. The experiments revealed several novel effects which both enhance the power of RA 2DIR and bring a deeper understanding to the fundamental process of energy transport on a molecular level. We demonstrated that RA 2DIR can enhance greatly (27-fold) the cross-peak amplitude among spatially remote modes, which leads to an increase of the range of distances accessible for structural measurements by several fold. We demonstrated that the energy transport time correlates with the intermode distance. This correlation offers a new way for identifying connectivity patterns in molecules. We developed two models of energy transport in molecules. In one, a spatial overlap

  15. Small molecule kinase inhibitors alleviate different molecular features of myotonic dystrophy type 1.

    PubMed

    Wojciechowska, Marzena; Taylor, Katarzyna; Sobczak, Krzysztof; Napierala, Marek; Krzyzosiak, Wlodzimierz J

    2014-01-01

    Expandable (CTG)n repeats in the 3' UTR of the DMPK gene are a cause of myotonic dystrophy type 1 (DM1), which leads to a toxic RNA gain-of-function disease. Mutant RNAs with expanded CUG repeats are retained in the nucleus and aggregate in discrete inclusions. These foci sequester splicing factors of the MBNL family and trigger upregulation of the CUGBP family of proteins resulting in the mis-splicing of their target transcripts. To date, many efforts to develop novel therapeutic strategies have been focused on disrupting the toxic nuclear foci and correcting aberrant alternative splicing via targeting mutant CUG repeats RNA; however, no effective treatment for DM1 is currently available. Herein, we present results of culturing of human DM1 myoblasts and fibroblasts with two small-molecule ATP-binding site-specific kinase inhibitors, C16 and C51, which resulted in the alleviation of the dominant-negative effects of CUG repeat expansion. Reversal of the DM1 molecular phenotype includes a reduction of the size and number of foci containing expanded CUG repeat transcripts, decreased steady-state levels of CUGBP1 protein, and consequent improvement of the aberrant alternative splicing of several pre-mRNAs misregulated in DM1.

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

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

    PubMed

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

    2015-07-07

    DNA origami has been used to orchestrate reactions with nano-precision using a variety of biomolecules. Here, the dynamics of albumin-assisted, localized single-molecule DNA polymerization by terminal deoxynucleotidyl transferase on a 2D DNA origami are monitored using AFM in liquid. Direct visualization of the surface activity revealed the mechanics of growth.

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

    PubMed

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

    2014-05-23

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

  20. Geometrical and algebraic approach to central molecular chirality: a chirality index and an Aufbau description of tetrahedral molecules.

    PubMed

    Capozziello, Salvatore; Lattanzi, Alessandra

    2006-08-01

    On the basis of empirical Fischer projections, we develop an algebraic approach to the central molecular chirality of tetrahedral molecules. The elements of such an algebra are obtained from the 24 projections which a single chiral tetrahedron can generate in S and R absolute configurations. They constitute a matrix representation of the O4 orthogonal group. According to this representation, given a molecule with n chiral centres, it is possible to define an "index of chirality chi identical with {n, p}", where n is the number of stereogenic centres of the molecule and p the number of permutations observed under rotations and superimpositions of the tetrahedral molecule to its mirror image. The chirality index not only assigns the global chirality of a given tetrahedral chain, but indicates also a way to predict the same property for new compounds, which can be built up consistently.

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

    PubMed

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

    2013-12-21

    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.

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

    SciTech Connect

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

    2015-09-11

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

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

    PubMed Central

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

    2015-01-01

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

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

    DOE PAGES

    Song, Zhuonan; Huang, Yi; Xu, Weiwei L.; ...

    2015-09-11

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

  5. Single-molecule imaging of organic semiconductors: Toward nanoscale insights into photophysics and molecular packing

    NASA Astrophysics Data System (ADS)

    Shepherd, W. E. B.; Grollman, R.; Robertson, A.; Paudel, K.; Hallani, R.; Loth, M. A.; Anthony, J. E.; Ostroverkhova, O.

    2015-06-01

    Photophysical properties of functionalized anthradithiophene (ADT) and pentacene (Pn) derivatives, as well as energy and charge transfer properties of donor-acceptor (D/A) pairs of these derivatives, are presented. The molecules studied were imaged on the single-molecule level in a polymeric and in a functionalized benzothiophene (BTBTB) crystalline host using room-temperature wide-field epifluorescence microscopy. The BTBTB host imposed orientational constraints on the guest molecules, depending on their functionalization. Flexibility of functionalization of both guest (ADT, Pn) and host (BTBTB) molecules can be used for systematic studies of nanoscale morphology and photophysics of D/A organic semiconductor bulk heterojunctions using single-molecule fluorescence microscopy.

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  7. The discovery of novel auxin transport inhibitors by molecular modeling and three-dimensional pattern analysis

    NASA Astrophysics Data System (ADS)

    Bures, Mark G.; Black-Schaefer, Candace; Gardner, Gary

    1991-08-01

    Molecular modeling techniques and three-dimensional (3D) pattern analysis have been used to investigate the chemical and steric properties of compounds that inhibit transport of the plant hormone auxin. These compounds bind to a specific site on the plant plasma membrane characterized by its affinity for the herbicide N-1-naphthylphthalamic acid (NPA). A 3D model was derived from critical features of a set of ligands for the NPA receptor, a suggested binding conformation is proposed, and implications for the topographical features of the NPA receptor are discussed. This model, along with 3D structural analysis techniques, was then used to search the Abbott corporate database of chemical structures. Of the 467 compounds that satisfied the criteria of the model, 77 representative molecules were evaluated for their ability to compete for the binding of [3H]NPA to corn microsomal membranes. Nineteen showed activity that ranged from 16 to 85% of the maximum NPA binding. Four of the most active of these, representing chemical classes not included in the original compound set, were also found to inhibit polar auxin transport through corn coleoptile sections. Thus, this study demonstrates that 3D analysis techniques can identify active, novel ligands for biochemical target sites with concomitant physiological activity.

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  11. Theoretical investigation of interaction of sorbitol molecules with alcohol dehydrogenase in aqueous solution using molecular dynamics simulation.

    PubMed

    Bahrami, Homayoon; Zahedi, Mansour; Moosavi-Movahedi, Ali Akbar; Azizian, Homa; Amanlou, Massoud

    2011-03-01

    The nature of protein-sorbitol-water interaction in solution at the molecular level, has been investigated using molecular dynamics simulations. In order to do this task, two molecular dynamics simulations of the protein ADH in solution at room temperature have been carried out, one in the presence (about 0.9 M) and another in the absence of sorbitol. The results show that the sorbitol molecules cluster and move toward the protein, and form hydrogen bonds with protein. Also, coating by sorbitol reduces the conformational fluctuations of the protein compared to the sorbitol-free system. Thus, it is concluded that at moderate concentration of sorbitol solution, sorbitol molecules interact with ADH via many H-bonds that prevent the protein folding. In fact, at more concentrated sorbitol solution, water and sorbitol molecules accumulate around the protein surface and form a continuous space-filling network to reduce the protein flexibility. Namely, in such solution, sorbitol molecules can stabilize a misfolded state of ADH, and prevent the protein from folding to its native structure.

  12. Pattern Formations in Polymer-Molecular Motor Networks

    NASA Astrophysics Data System (ADS)

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

    2001-03-01

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

  13. (Bio)molecular surface patterning by phototriggered oxime ligation.

    PubMed

    Pauloehrl, Thomas; Delaittre, Guillaume; Bruns, Michael; Meißler, Maria; Börner, Hans G; Bastmeyer, Martin; Barner-Kowollik, Christopher

    2012-09-03

    Making light work of ligation: A novel method utilizes light for oxime ligation chemistry. A quantitative, low-energy photodeprotection generates aldehyde, which subsequently reacts with aminooxy moieties. The spatial control allows patterning on surfaces with a fluoro marker and GRGSGR peptide, and can be imaged by time-of-flight secondary-ion mass spectrometry.

  14. Nanoscale patterning of a self-assembled monolayer by modification of the molecule-substrate bond.

    PubMed

    Shen, Cai; Buck, Manfred

    2014-01-01

    The intercalation of Cu at the interface of a self-assembled monolayer (SAM) and a Au(111)/mica substrate by underpotential deposition (UPD) is studied as a means of high resolution patterning. A SAM of 2-(4'-methylbiphenyl-4-yl)ethanethiol (BP2) prepared in a structural phase that renders the Au substrate completely passive against Cu-UPD, is patterned by modification with the tip of a scanning tunneling microscope. The tip-induced defects act as nucleation sites for Cu-UPD. The lateral diffusion of the metal at the SAM-substrate interface and, thus, the pattern dimensions are controlled by the deposition time. Patterning down to the sub-20 nm range is demonstrated. The difference in strength between the S-Au and S-Cu bond is harnessed to develop the latent Cu-UPD image into a patterned binary SAM. Demonstrated by the exchange of BP2 by adamantanethiol (AdSH) this is accomplished by a sequence of reductive desorption of BP2 in Cu free areas followed by adsorption of AdSH. The appearance of Au adatom islands upon the thiol exchange suggests that the interfacial structures of BP2 and AdSH SAMs are different.

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

    PubMed

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

    2012-06-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. Molecular Patterns and Biology of HPV-Associated HNSCC.

    PubMed

    Brakenhoff, Ruud H; Wagner, Steffen; Klussmann, Jens P

    Head and neck cancer is the sixth most common cancer worldwide. The large majority are squamous cell carcinomas (HNSCC) that develop in the mucosal linings of the upper aerodigestive tract. These tumors develop either by exogenous carcinogen exposure (smoking, alcohol drinking) or by human papillomavirus (HPV) infection, particularly those in the oropharynx (OPSCC). HPV-positive (HPV+ve) and HPV-negative (HPV-ve) OPSCC are considered different disease entities. HPV+ve tumors are different at the molecular level and likely as a consequence have a much more favorable prognosis than HPV-ve tumors, despite their generally advanced stage at presentation. In general, HNSCCs develop in precancerous mucosal changes, and the apparent lack of precancerous HPV+ve mucosal changes is therefore remarkable. In this Chapter, head and neck carcinogenesis is discussed and the molecular differences between HPV+ve and HPV-ve tumors are outlined.

  18. Azobenzenes as light-controlled molecular electronic switches in nanoscale metal-molecule-metal junctions.

    PubMed

    Mativetsky, Jeffrey M; Pace, Giuseppina; Elbing, Mark; Rampi, Maria A; Mayor, Marcel; Samorì, Paolo

    2008-07-23

    Conductance switching associated with the photoisomerization of azobenzene-based (Azo) molecules was observed in nanoscopic metal-molecule-metal junctions. The junctions were formed by using a conducting atomic force microscope (C-AFM) approach, where a metallic AFM tip was used to electrically contact a gold-supported Azo self-assembled monolayer. The measured 30-fold increase in conductance is consistent with the expected decrease in tunneling barrier length resulting from the conformational change of the Azo molecule.

  19. DNA-Mediated Patterning of Single Quantum Dot Nanoarrays: A Reusable Platform for Single-Molecule Control

    PubMed Central

    Huang, Da; Freeley, Mark; Palma, Matteo

    2017-01-01

    We present a facile strategy of general applicability for the assembly of individual nanoscale moieties in array configurations with single-molecule control. Combining the programming ability of DNA as a scaffolding material with a one-step lithographic process, we demonstrate the patterning of single quantum dots (QDs) at predefined locations on silicon and transparent glass surfaces: as proof of concept, clusters of either one, two, or three QDs were assembled in highly uniform arrays with a 60 nm interdot spacing within each cluster. Notably, the platform developed is reusable after a simple cleaning process and can be designed to exhibit different geometrical arrangements. PMID:28349982

  20. DNA-Mediated Patterning of Single Quantum Dot Nanoarrays: A Reusable Platform for Single-Molecule Control.

    PubMed

    Huang, Da; Freeley, Mark; Palma, Matteo

    2017-03-28

    We present a facile strategy of general applicability for the assembly of individual nanoscale moieties in array configurations with single-molecule control. Combining the programming ability of DNA as a scaffolding material with a one-step lithographic process, we demonstrate the patterning of single quantum dots (QDs) at predefined locations on silicon and transparent glass surfaces: as proof of concept, clusters of either one, two, or three QDs were assembled in highly uniform arrays with a 60 nm interdot spacing within each cluster. Notably, the platform developed is reusable after a simple cleaning process and can be designed to exhibit different geometrical arrangements.

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

    PubMed

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

    2016-01-01

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

  2. Practical Approaches for Mining Frequent Patterns in Molecular Datasets

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    McCarthy, Michael

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

  4. Single molecule PCR reveals similar patterns of non-homologous DSB repair in tobacco and Arabidopsis.

    PubMed

    Lloyd, Andrew H; Wang, Dong; Timmis, Jeremy N

    2012-01-01

    DNA double strand breaks (DSBs) occur constantly in eukaryotes. These potentially lethal DNA lesions are repaired efficiently by two major DSB repair pathways: homologous recombination and non-homologous end joining (NHEJ). We investigated NHEJ in Arabidopsis thaliana and tobacco (Nicotiana tabacum) by introducing DNA double-strand breaks through inducible expression of I-SceI, followed by amplification of individual repair junction sequences by single-molecule PCR. Using this process over 300 NHEJ repair junctions were analysed in each species. In contrast to previously published variation in DSB repair between Arabidopsis and tobacco, the two species displayed similar DSB repair profiles in our experiments. The majority of repair events resulted in no loss of sequence and small (1-20 bp) deletions occurred at a minority (25-45%) of repair junctions. Approximately ~1.5% of the observed repair events contained larger deletions (>20 bp) and a similar percentage contained insertions. Strikingly, insertion events in tobacco were associated with large genomic deletions at the site of the DSB that resulted in increased micro-homology at the sequence junctions suggesting the involvement of a non-classical NHEJ repair pathway. The generation of DSBs through inducible expression of I-SceI, in combination with single molecule PCR, provides an effective and efficient method for analysis of individual repair junctions and will prove a useful tool in the analysis of NHEJ.

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

    SciTech Connect

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

    2010-08-15

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

  6. Proteomics: how to control highly dynamic patterns of millions of molecules and interpret changes correctly?

    PubMed

    Schrattenholz, André

    2004-09-01

    "Proteomics" is essentially protein analysis and, until recently, could be described as an umbrella for a set of technology and bioinformatic platforms aimed at the comprehensive molecular description of the actual protein complement of a given sample. Today, it is typically associated with systems biology. In this context, powerful new technologies for differential complexity reduction promise to solve some of the most pressing problems in drug development. The resulting analytical challenges of unprecedented complexity are emerging as one of the last frontiers of molecular biology. Considerable progress has been made in characterizing rapid post-translational protein modifications in highly complex molecular signatures as key disease-related biomarkers from experimental model systems or clinical samples.: Section Editors: Wolfgang Fischer, Rob Hooft, and Michael Walker Identifying a potential protein drug target within a cell is a major challenge in modern drug discovery; techniques for screening the proteome are, therefore, an important tool. Major difficulties for target identification include the separation of proteins and their detection. The latest developments in techniques that master these challenges, such as SDS-PAGE and liquid chromatography in combination with isotopic labeling and staining techniques, are highlighted in this review. The authors evaluate the applicability of these approaches for specific tasks.

  7. Virtual screening of molecular properties of chitosan and derivatives in search for druggable molecules.

    PubMed

    Hassan, Basila; Shireen, Ajmala; Muraleedharan, K; Mujeeb, V M Abdul

    2015-03-01

    Druggability of chitosan monomer and Schiff bases as well as reduced Schiff base derivatives of chitosan were examined. Oral bioavailability and bioactivity of all these molecules against selected drug targets as well as ADME/Tox studies were conducted. All the molecules satisfied Lipinski's rule of five confirming their oral bioavailability. They also show good bioactivity score for protease and enzyme inhibition. ADME/Tox studies conducted shows that almost all the derivatives are free from toxicity risks. It is observed that these molecules exhibit fairly good drug score and are orally viable molecules. Chelation of chitosan and its derivatives with essential metal ions might be the mechanism driving their bioactivity. Thus chitosan monomer and the derivatives studied, can serve as good lead molecules for further research.

  8. A graphene-based affinity nanosensor for detection of low-charge and low-molecular-weight molecules

    NASA Astrophysics Data System (ADS)

    Zhu, Yibo; Hao, Yufeng; Adogla, Enoch A.; Yan, Jing; Li, Dachao; Xu, Kexin; Wang, Qian; Hone, James; Lin, Qiao

    2016-03-01

    This paper presents a graphene nanosensor for affinity-based detection of low-charge, low-molecular-weight molecules, using glucose as a representative. The sensor is capable of measuring glucose concentration in a practically relevant range of 2 μM to 25 mM, and can potentially be used in noninvasive glucose monitoring.This paper presents a graphene nanosensor for affinity-based detection of low-charge, low-molecular-weight molecules, using glucose as a representative. The sensor is capable of measuring glucose concentration in a practically relevant range of 2 μM to 25 mM, and can potentially be used in noninvasive glucose monitoring. Electronic supplementary information (ESI) available: Further details on experiments, materials, fabrication, and data analysis. See DOI: 10.1039/c5nr08866f

  9. Numerical analysis on gas-surface interaction by molecular dynamics method. I - Simulation with Lennard-Jones molecules

    NASA Astrophysics Data System (ADS)

    Matsumoto, Yoichiro; Matsui, Jun; Ohashi, Hideo

    1992-07-01

    Rarefied gas flows in various situations are calculated successfully by the direct simulation Monte Carlo method. In the simulation, the Maxwell model, where a gas molecule reflects diffusely with the probability alpha and reflects specularly with the probability 1 - alpha, is widely used for boundary conditions on solid surfaces. However, the value of alpha is determined empirically and varies greatly with conditions such as degree of contamination and temperature of the surface. Rational prediction of the value and analysis of the interaction between gas and solid surface are required. In this paper, the behavior of a gas molecule with collides onto the solid surface is simulated by the molecular dynamics method. The numerical results reveal that the scattering behavior of the gas molecule is neither specular, diffuse, nor Maxwell-type reflection, and that the sticking probability is affected by the initial gas velocity and the potential well depth.

  10. In situ formation and photo patterning of emissive quantum dots in small organic molecules

    NASA Astrophysics Data System (ADS)

    Bansal, Ashu K.; Sajjad, Muhammad T.; Antolini, Francesco; Stroea, Lenuta; Gečys, Paulius; Raciukaitis, Gediminas; André, Pascal; Hirzer, Andreas; Schmidt, Volker; Ortolani, Luca; Toffanin, Stefano; Allard, Sybille; Scherf, Ullrich; Samuel, Ifor D. W.

    2015-06-01

    Nanostructured composites of inorganic and organic materials are attracting extensive interest for electronic and optoelectronic device applications. Here we report a novel method for the fabrication and patterning of metal selenide nanoparticles in organic semiconductor films that is compatible with solution processable large area device manufacturing. Our approach is based upon the controlled in situ decomposition of a cadmium selenide precursor complex in a film of the electron transporting material 1,3,5-tris(N-phenyl-benzimidazol-2-yl)-benzene (TPBI) by thermal and optical methods. In particular, we show that the photoluminescence quantum yield (PLQY) of the thermally converted CdSe quantum dots (QDs) in the TPBI film is up to 15%. We also show that laser illumination can form the QDs from the precursor. This is an important result as it enables direct laser patterning (DLP) of the QDs. DLP was performed on these nanocomposites using a picosecond laser. Confocal microscopy shows the formation of emissive QDs after laser irradiation. The optical and structural properties of the QDs were also analysed by means of UV-Vis, PL spectroscopy and transmission electron microscopy (TEM). The results show that the QDs are well distributed across the film and their emission can be tuned over a wide range by varying the temperature or irradiated laser power on the blend films. Our findings provide a route to the low cost patterning of hybrid electroluminescent devices.

  11. H2 Molecular Clusters with Embedded Molecules and Atoms as the Source of the Diffuse Interstellar Bands

    NASA Astrophysics Data System (ADS)

    Bernstein, L. S.; Clark, F. O.; Lynch, D. K.

    2013-05-01

    We suggest that the diffuse interstellar bands (DIBs) arise from absorption lines of electronic transitions in molecular clusters primarily composed of a single molecule, atom, or ion ("seed"), embedded in a single-layer shell of H2 molecules. Less abundant variants of the cluster, including two seed molecules and/or a two-layer shell of H2 molecules, may also occur. The lines are broadened, blended, and wavelength-shifted by interactions between the seed and surrounding H2 shell. We refer to these clusters as contaminated H2 clusters (CHCs). We show that CHC spectroscopy matches the diversity of observed DIB spectral profiles and provides good fits to several DIB profiles based on a rotational temperature of 10 K. CHCs arise from ~centimeter-sized, dirty H2 ice balls, called contaminated H2 ice macro-particles (CHIMPs), formed in cold, dense, giant molecular clouds (GMCs), and later released into the interstellar medium (ISM) upon GMC disruption. Attractive interactions, arising from Van der Waals and ion-induced dipole potentials, between the seeds and H2 molecules enable CHIMPs to attain centimeter-sized dimensions. When an ultraviolet (UV) photon is absorbed in the outer layer of a CHIMP, it heats the icy matrix and expels CHCs into the ISM. While CHCs are quickly destroyed by absorbing UV photons, they are replenished by the slowly eroding CHIMPs. Since CHCs require UV photons for their release, they are most abundant at, but not limited to, the edges of UV-opaque molecular clouds, consistent with the observed, preferred location of DIBs. An inherent property of CHCs, which can be characterized as nanometer size, spinning, dipolar dust grains, is that they emit in the radio-frequency region. We also show that the CHCs offer a natural explanation for the anomalous microwave emission feature in the ~10-100 GHz spectral region.

  12. Enumerating molecules.

    SciTech Connect

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

    2004-04-01

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

  13. Acidity Constant (pK a) Calculation of Large Solvated Dye Molecules: Evaluation of Two Advanced Molecular Dynamics Methods

    PubMed Central

    De Meyer, Thierry; Ensing, Bernd; Rogge, Sven M. J.; De Clerck, Karen

    2016-01-01

    Abstract pH‐Sensitive dyes are increasingly applied on polymer substrates for the creation of novel sensor materials. Recently, these dye molecules were modified to form a covalent bond with the polymer host. This had a large influence on the pH‐sensitive properties, in particular on the acidity constant (pK a). Obtaining molecular control over the factors that influence the pK a value is mandatory for the future intelligent design of sensor materials. Herein, we show that advanced molecular dynamics (MD) methods have reached the level at which the pK a values of large solvated dye molecules can be predicted with high accuracy. Two MD methods were used in this work: steered or restrained MD and the insertion/deletion scheme. Both were first calibrated on a set of phenol derivatives and afterwards applied to the dye molecule bromothymol blue. Excellent agreement with experimental values was obtained, which opens perspectives for using these methods for designing dye molecules. PMID:27570194

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

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

    PubMed

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

    2016-02-01

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

  16. Direct prediction of residual dipolar couplings of small molecules in a stretched gel by stochastic molecular dynamics simulations.

    PubMed

    Frank, Andreas O; Freudenberger, J Christoph; Shaytan, Alexey K; Kessler, Horst; Luy, Burkhard

    2015-03-01

    Residual dipolar couplings are highly useful NMR parameters for calculating and refining molecular structures, dynamics, and interactions. For some applications, however, it is inevitable that the preferred orientation of a molecule in an alignment medium is calculated a priori. Several methods have been developed to predict molecular orientations and residual dipolar couplings. Being beneficial for macromolecules and selected small-molecule applications, such approaches lack sufficient accuracy for a large number of organic compounds for which the fine structure and eventually the flexibility of all involved molecules have to be considered or are limited to specific, well-studied liquid crystals. We introduce a simplified model for detailed all-atom molecular dynamics calculations with a polymer strand lined up along the principal axis as a new approach to simulate the preferred orientation of small to medium-sized solutes in polymer-based, gel-type alignment media. As is shown by a first example of strychnine in a polystyrene/CDCl3 gel, the simulations potentially enable the accurate prediction of residual dipolar couplings taking into account structural details and dynamic averaging effects of both the polymer and the solute.

  17. The expression pattern of classical MHC class I molecules in the development of mouse central nervous system.

    PubMed

    Liu, Jiane; Shen, Yuqing; Li, Mingli; Shi, Qian; Zhang, Aifeng; Miao, Fengqin; Liu, Junhua; Wu, Xiaojing; He, Youji; Zhang, Jianqiong

    2013-02-01

    Classical major histocompatibility complex (MHC) class I, first identified in the immune system, is also expressed in the developing and adult central nervous system (CNS). Although the MHC class I molecules have been found to be expressed in the CNS of different species, a necessary step to elucidate the temporal and spatial expression patterns of MHC class I molecules in the brain development has never been taken. Frozen sections were made from the brains of embryonic and postnatal C57BL/6 J mice, and the expression of H-2D(b) mRNA was examined by in situ hybridization. Immunofluorescence was also performed to define the cell types that express H2-D(b) in P15 mice. At E10.5, the earliest stage we examined, H2-D(b) was expressed in neuroepithelium of the brain vesicles. From E12.5 to P0, H2-D(b) expression was mainly located at cerebral cortex, neuroepithelium of the lateral ventricle, neuroepithelium of aquaeductus and developing cerebellum. From P4 to adult, H2-D(b) mRNA was detected at olfactory bulb, hippocampus, cerebellum and some nerve nuclei. The major cell types expressing H-2D(b) in P15 hippocampus, cerebral cortex and olfactory bulb were neuron. H2-K(b) signal paralleled that of H2-D(b) and the expression levels of the two molecules were comparable throughout the brain. The investigation of the expression pattern of H-2D(b) at both embryonic and postnatal stages is important for further understanding the physiological and pathological roles of H2-D(b) in the developing CNS.

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

    PubMed

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

    1994-02-15

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

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

    PubMed

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

    2016-08-25

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

  20. Molecular analysis of different classes of RNA molecules from formalin-fixed paraffin-embedded autoptic tissues: a pilot study.

    PubMed

    Muciaccia, Barbara; Vico, Carmen; Aromatario, Mariarosaria; Fazi, Francesco; Cecchi, Rossana

    2015-01-01

    For a long time, it has been thought that fresh and frozen tissues are the only possible source of biological material useful to extract nucleic acids suitable for downstream molecular analysis. Recently, for forensic purpose such as personal identification, also fixed tissues have been used to recover DNA molecules, whereas RNA extracted from such material is still considered too degraded for gene expression studies. In the present pilot study, we evaluated the possibility to use forensic formalin-fixed paraffin-embedded (FFPE) samples, collected at autopsy at different postmortem intervals (PMI) from four individuals, to perform advanced molecular analyses. In particular, we performed qualitative and quantitative analyses of total RNAs extracted from different FFPE tissues and put expression profiles in relation with the organ type and the duration of PMI. Different classes of RNA molecular targets were studied by real-time quantitative RT-PCR. We report molecular evidence that small RNAs are the only RNA molecules still detectable in all the FFPE autoptic tissues. In particular, microRNAs (miRNAs) represent a consistent, stable, and well-preserved molecular target detectable even from tissue sources displaying signs of ongoing putrefaction at autopsy. In this pilot study, we show that miRNAs could represent a highly sensitive and potentially useful forensic marker. Amplification of specific miRNAs using paraffin-embedded blocks could facilitate retrospective molecular analysis using specific forensic-archived tissues chosen as most suitable according to PMI, and this approach would address molecular evidence in forensic cases in which fresh or frozen material is no longer available.

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

    PubMed

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

    2013-01-01

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

  2. Analysis of HLA class I alterations in tumors: choosing a strategy based on known patterns of underlying molecular mechanisms.

    PubMed

    Cabrera, T; Maleno, I; Collado, A; Lopez Nevot, M A; Tait, B D; Garrido, F

    2007-04-01

    The application of peptide-based immunotherapy in the treatment of cancer has known limitations in patients with loss or downregulation of human leukocyte antigen (HLA) class I expression on tumor cells. These alterations diminish the ability of cancer cells to present tumor peptides to T cells and therefore lead to failure of peptide-based cancer vaccination. Abnormal expression of HLA class I molecules in malignant cells is a frequent event that ranges from total loss of class I molecules to partial loss of HLA-specific haplotypes or alleles. Different mechanisms underlie these alterations and might require different therapeutic approaches. A complete characterization of molecular defects may suggest strategies for the selection and follow-up of patients undergoing T-cell based immunotherapy. Moreover, a precise identification of the mechanism leading to HLA class I defects in patients with cancer will help develop new, personalized patient-tailored treatment protocols. Here, we describe several examples showing the necessity and feasibility of making detailed individual analysis of HLA alteration mechanisms based on previously described molecular patterns in different types of malignancy. We recommend using this approach, at least in some patients, to enhance the therapeutic benefit of cancer immunotherapy.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

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

    SciTech Connect

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

    2010-09-15

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

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

    PubMed

    Colomb, Warren; Sarkar, Susanta K

    2015-06-01

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

  8. PRO_LIGAND: An approach to de novo molecular design. 1. Application to the design of organic molecules

    NASA Astrophysics Data System (ADS)

    Clark, David E.; Frenkel, David; Levy, Stephen A.; Li, Jin; Murray, Christopher W.; Robson, Barry; Waszkowycz, Bohdan; Westhead, David R.

    1995-02-01

    An approach to de novo molecular design, PRO_LIGAND, has been developed that, in the environment of a large, integrated molecular design and simulation system, provides a unified framework for the generation of novel molecules which are either similar or complementary to a specified target. The approach is based on a methodology that has proved to be effective in other studies-placing molecular fragments upon target interaction sites-but incorporates many novel features such as the use of a rapid graph-theoretical algorithm for fragment placing, a generalised driver for structure generation which offers a large variety of fragment assembly strategies to the user and the pre-screening of library fragments. After a detailed description of the relevant modules of the package, PRO_LIGAND's efficacy in aiding rational drug design is demonstrated by its ability to design mimics of methotrexate and potential inhibitors for dihydrofolate reductase and HIV-1 protease.

  9. Molecular phylogeny and patterns of diversification in syngnathid fishes.

    PubMed

    Hamilton, Healy; Saarman, Norah; Short, Graham; Sellas, Anna B; Moore, Beth; Hoang, Tinya; Grace, Christopher L; Gomon, Martin; Crow, Karen; Brian Simison, W

    2017-02-01

    The family Syngnathidae is a large and diverse clade of morphologically unique bony fishes, with 57 genera and 300 described species of seahorses, pipefishes, pipehorses, and seadragons. They primarily inhabit shallow coastal waters in temperate and tropical oceans, and are characterized by a fused jaw, male brooding, and extraordinary crypsis. Phylogenetic relationships within the Syngnathidae remain poorly resolved due to lack of generic taxon sampling, few diagnostic morphological characters, and limited molecular data. The phylogenetic placement of the threatened, commercially exploited seahorses remains a topic of intense interest, with conflicting topologies based on morphology and predominantly mitochondrial genetic data. In this study, we integrate eight nuclear and mitochondrial markers and 17 morphological characters to investigate the phylogenetic structure of the family Syngnathidae at the generic level. We include 91 syngnathid species representing 48 of the 57 recognized genera, all major ocean basins, and a broad array of temperate and tropical habitats including rocky and coral reefs, sand and silt, mangroves, seagrass beds, estuaries, and rivers. Maximum likelihood and Bayesian analyses of 5160bp from eight loci produced high congruence among alternate topologies, defining well-supported and sometimes novel clades. We present a hypothesis that confirms a deep phylogenetic split between lineages with trunk- or tail-brood pouch placement, and provides significant new insights into the morphological evolution and biogeography of this highly derived fish clade. Based on the fundamental division between lineages - the tail brooding "Urophori" and the trunk brooding "Gastrophori" - we propose a revision of Syngnathidae classification into only two subfamilies: the Nerophinae and the Syngnathinae. We find support for distinct principal clades within the trunk-brooders and tail-brooders, the latter of which include seahorses, seadragons, independent

  10. Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules

    PubMed Central

    2016-01-01

    We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development. PMID:28000444

  11. Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules.

    PubMed

    Nakhleh, Morad K; Amal, Haitham; Jeries, Raneen; Broza, Yoav Y; Aboud, Manal; Gharra, Alaa; Ivgi, Hodaya; Khatib, Salam; Badarneh, Shifaa; Har-Shai, Lior; Glass-Marmor, Lea; Lejbkowicz, Izabella; Miller, Ariel; Badarny, Samih; Winer, Raz; Finberg, John; Cohen-Kaminsky, Sylvia; Perros, Frédéric; Montani, David; Girerd, Barbara; Garcia, Gilles; Simonneau, Gérald; Nakhoul, Farid; Baram, Shira; Salim, Raed; Hakim, Marwan; Gruber, Maayan; Ronen, Ohad; Marshak, Tal; Doweck, Ilana; Nativ, Ofer; Bahouth, Zaher; Shi, Da-You; Zhang, Wei; Hua, Qing-Ling; Pan, Yue-Yin; Tao, Li; Liu, Hu; Karban, Amir; Koifman, Eduard; Rainis, Tova; Skapars, Roberts; Sivins, Armands; Ancans, Guntis; Liepniece-Karele, Inta; Kikuste, Ilze; Lasina, Ieva; Tolmanis, Ivars; Johnson, Douglas; Millstone, Stuart Z; Fulton, Jennifer; Wells, John W; Wilf, Larry H; Humbert, Marc; Leja, Marcis; Peled, Nir; Haick, Hossam

    2017-01-24

    We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development.

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  14. Dimeric and trimeric triazole based molecules as a new class of Hsp90 molecular chaperone inhibitors.

    PubMed

    Terracciano, Stefania; Chini, Maria Giovanna; Piaz, Fabrizio Dal; Vassallo, Antonio; Riccio, Raffaele; Bruno, Ines; Bifulco, Giuseppe

    2013-07-01

    In the last decade Hsp90 inhibitors have emerged as attractive candidates for the development of new potent anticancer therapeutics. In order to identify novel agents able to block the chaperone activity, following a structure-based approach, we used in silico screening to direct the synthesis of potential inhibitors bearing the triazole scaffold, a widespread motif in drug-like molecules. Docking results, performed on a larger collection of dimeric and trimeric triazole derivatives, suggested the synthesis of some molecules showing different calculated binding energies and modes. Surface Plasmon Resonance Binding assay, performed on the synthesized compounds, allow to identify a series of molecules able to potently interact with the target enzyme and to disclose an interesting hit: compound 2b showed to interact with the ATP binding site in the N-terminus domain of Hsp90 and to efficiently inhibit the chaperone activity.

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

    PubMed

    Wang, Bin; Guo, Cunlan; Zhang, Mengmeng; Park, Bosoon; Xu, Bingqian

    2012-05-03

    We studied the molecular details of DNA aptamer-ricin interactions. The toxic protein ricin molecules were immobilized on a Au(111) surface using a N-hydroxysuccinimide (NHS) ester to specifically react with lysine residues located on the ricin B chains. A single ricin molecule was visualized in situ using the AFM tip modified with an antiricin aptamer. Computer simulation was used to illustrate the protein and aptamer structures, the single-molecule ricin images on a Au(111) surface, and the binding conformations of ricin-aptamer and ricin-antibody complexes. The various ricin conformations on a Au(111) surface were caused by the different lysine residues reacting with the NHS ester. It was also observed that most of the binding sites for aptamer and antibody on the A chains of ricin molecules were not interfered by the immobilization reaction. The different locations of the ricin binding sites to aptamer and antibody were also distinguished by AFM recognition images and interpreted by simulations.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-06-20

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

  18. Single molecule diffraction.

    PubMed

    Spence, J C H; Doak, R B

    2004-05-14

    For solving the atomic structure of organic molecules such as small proteins which are difficult to crystallize, the use of a jet of doped liquid helium droplets traversing a continuous high energy electron beam is proposed as a means of obtaining electron diffraction patterns (serial crystallography). Organic molecules (such as small proteins) within the droplet (and within a vitreous ice jacket) may be aligned by use of a polarized laser beam. Iterative methods for solving the phase problem are indicated. Comparisons with a related plan for pulsed x-ray diffraction from single proteins in a molecular beam are provided.

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

    PubMed

    Katoh, Keiichi; Komeda, Tadahiro; Yamashita, Masahiro

    2016-04-01

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

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

    NASA Astrophysics Data System (ADS)

    Debolt, Stephen Edward

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

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

    PubMed

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

    2015-11-01

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

  2. The role of molecular electron distribution in strong-field ionization and dissociation of heteronuclear molecules

    NASA Astrophysics Data System (ADS)

    Lai, Wei; Guo, Chunlei

    2016-11-01

    A comparison study of double-ionization induced dissociation in strong laser fields between a homonuclear diatomic molecule, O2, and a heteronuclear diatomic molecule, NO, shows that two electrons can easily be removed from one O atom of O2 to form a O2++O, however, two electrons can hardly be removed from the O atom of NO to form a N+O2+. Instead, for NO, two electrons are preferentially removed from the N atom to form a N2++O, even though the N atom requires higher ionization energy than the O atom. This indicates that atomic ionization energy does not play a significant role here. Our further study on the formation dynamics of the N2++O channel shows that the initial electron distribution of the NO molecule plays an important role in influencing the strong-field ionization and dissociation of NO and this effect seems to commonly exist in heteronuclear molecules when interacting with strong laser fields.

  3. In Touch with Molecules: Improving Student Learning with Innovative Molecular Models

    ERIC Educational Resources Information Center

    Davenport, Jodi; Silberglitt, Matt; Olson, Arthur

    2013-01-01

    How do viruses self-assemble? Why do DNA bases pair the way they do? What factors determine whether strands of proteins fold into sheets or helices? Why does handedness matter? A deep understanding of core issues in biology requires students to understand both complex spatial structures of molecules and the interactions involved in dynamic…

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

    ERIC Educational Resources Information Center

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

    2008-01-01

    We developed the three-dimensional visualization software, Tonal Interface to MacroMolecules or TIMMol, for studying atomic coordinates of protein structures. Key features include audio tones indicating x, y, z location, identification of the cursor location in one-dimensional and three-dimensional space, textual output that can be easily linked…

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

    PubMed

    Guo, Zong-Ru

    2008-03-01

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

  6. Toward molecular mechanism of xenon anesthesia: a link to studies of xenon complexes with small aromatic molecules.

    PubMed

    Andrijchenko, Natalya N; Ermilov, Alexander Yu; Khriachtchev, Leonid; Räsänen, Markku; Nemukhin, Alexander V

    2015-03-19

    The present study illustrates the steps toward understanding molecular mechanism of xenon anesthesia by focusing on a link to the structures and spectra of intermolecular complexes of xenon with small aromatic molecules. A primary cause of xenon anesthesia is attributed to inhibition of N-methyl-D-aspartate (NMDA) receptors by an unknown mechanism. Following the results of quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics (MD) calculations we report plausible xenon action sites in the ligand binding domain of the NMDA receptor, which are due to interaction of xenon atoms with aromatic amino-acid residues. We rely in these calculations on computational protocols adjusted in combined experimental and theoretical studies of intermolecular complexes of xenon with phenol. Successful reproduction of vibrational shifts in molecular species upon complexation with xenon measured in low-temperature matrices allowed us to select a proper functional form in density functional theory (DFT) approach for use in QM subsystems, as well as to calibrate force field parameters for MD simulations. The results of molecular modeling show that xenon atoms can compete with agonists for a place in the corresponding protein cavity, thus indicating their active role in anesthetic action.

  7. Modeling Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

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

  8. Molecularly imprinted polymeric micro- and nano-particles for the targeted delivery of active molecules.

    PubMed

    Gagliardi, Mariacristina; Mazzolai, Barbara

    2015-01-01

    Molecular imprinting (MI) represents a strategy to introduce a 'molecular memory' in a polymeric system obtaining materials with specific recognition properties. MI particles can be used as drug delivery systems providing a targeted release and thus reducing the side effects. The introduction of molecular recognition properties on a polymeric drug carrier represents a challenge in the development of targeted delivery systems to increase their efficiency. This review will summarize the limited number of drug delivery MI particles described in the literature along with an overview of potential solutions for a larger exploitation of MI particles as targeted drug delivery carriers. Molecularly imprinted drug carriers can be considered interesting candidates to significantly improve the efficiency of a controlled drug treatment.

  9. Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids

    DOE PAGES

    Aradi, Bálint; Niklasson, Anders M. N.; Frauenheim, Thomas

    2015-06-26

    A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born–Oppenheimer molecular dynamics. Furthermore, for systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can also be applied to a broad range of problems in materialsmore » science, chemistry, and biology.« less

  10. Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids

    SciTech Connect

    Aradi, Bálint; Niklasson, Anders M. N.; Frauenheim, Thomas

    2015-06-26

    A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born–Oppenheimer molecular dynamics. Furthermore, for systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can also be applied to a broad range of problems in materials science, chemistry, and biology.

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

    PubMed Central

    2011-01-01

    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

  12. Design and development of a field-deployable single-molecule detector (SMD) for the analysis of molecular markers†

    PubMed Central

    Emory, Jason M.; Peng, Zhiyong; Young, Brandon; Hupert, Mateusz L.; Rousselet, Arnold; Patterson, Donald; Ellison, Brad; Soper, Steven A.

    2012-01-01

    Single-molecule detection (SMD) has demonstrated some attractive benefits for many types of biomolecular analyses including enhanced processing speed by eliminating processing steps, elimination of ensemble averaging and single-molecule sensitivity. However, it's wide spread use has been hampered by the complex instrumentation required for its implementation when using fluorescence as the readout modality. We report herein a simple and compact fluorescence single-molecule instrument that is straightforward to operate and consisted of fiber optics directly coupled to a microfluidic device. The integrated fiber optics served as waveguides to deliver the laser excitation light to the sample and collecting the resulting emission, simplifying the optical requirements associated with traditional SMD instruments by eliminating the need for optical alignment and simplification of the optical train. Additionally, the use of a vertical cavity surface emitting laser and a single photon avalanche diode serving as the excitation source and photon transducer, respectively, as well as a field programmable gate array (FPGA) integrated into the processing electronics assisted in reducing the instrument footprint. This small footprint SMD platform was tested using fluorescent microspheres and single AlexaFluor 660 molecules to determine the optimal operating parameters and system performance. As a demonstration of the utility of this instrument for biomolecular analyses, molecular beacons (MBs) were designed to probe bacterial cells for the gene encoding Gram-positive species. The ability to monitor biomarkers using this simple and portable instrument will have a number of important applications, such as strain-specific detection of pathogenic bacteria or the molecular diagnosis of diseases requiring rapid turn-around-times directly at the point-of-use. PMID:22005669

  13. Musical molecules: the molecular junction as an active component in audio distortion circuits

    NASA Astrophysics Data System (ADS)

    Bergren, Adam Johan; Zeer-Wanklyn, Lucas; Semple, Mitchell; Pekas, Nikola; Szeto, Bryan; McCreery, Richard L.

    2016-03-01

    Molecular junctions that have a non-linear current-voltage characteristic consistent with quantum mechanical tunneling are demonstrated as analog audio clipping elements in overdrive circuits widely used in electronic music, particularly with electric guitars. The performance of large-area molecular junctions fabricated at the wafer level is compared to currently standard semiconductor diode clippers, showing a difference in the sound character. The harmonic distributions resulting from the use of traditional and molecular clipping elements are reported and discussed, and differences in performance are noted that result from the underlying physics that controls the electronic properties of each clipping component. In addition, the ability to tune the sound using the molecular junction is demonstrated. Finally, the hybrid circuit is compared to an overdriven tube amplifier, which has been the standard reference electric guitar clipped tone for over 60 years. In order to investigate the feasibility of manufacturing molecular junctions for use in commercial applications, devices are fabricated using a low-density format at the wafer level, where 38 dies per wafer, each containing two molecular junctions, are made with exceptional non-shorted yield (99.4%, representing 718 out of 722 tested devices) without requiring clean room facilities.

  14. Musical molecules: the molecular junction as an active component in audio distortion circuits.

    PubMed

    Bergren, Adam Johan; Zeer-Wanklyn, Lucas; Semple, Mitchell; Pekas, Nikola; Szeto, Bryan; McCreery, Richard L

    2016-03-09

    Molecular junctions that have a non-linear current-voltage characteristic consistent with quantum mechanical tunneling are demonstrated as analog audio clipping elements in overdrive circuits widely used in electronic music, particularly with electric guitars. The performance of large-area molecular junctions fabricated at the wafer level is compared to currently standard semiconductor diode clippers, showing a difference in the sound character. The harmonic distributions resulting from the use of traditional and molecular clipping elements are reported and discussed, and differences in performance are noted that result from the underlying physics that controls the electronic properties of each clipping component. In addition, the ability to tune the sound using the molecular junction is demonstrated. Finally, the hybrid circuit is compared to an overdriven tube amplifier, which has been the standard reference electric guitar clipped tone for over 60 years. In order to investigate the feasibility of manufacturing molecular junctions for use in commercial applications, devices are fabricated using a low-density format at the wafer level, where 38 dies per wafer, each containing two molecular junctions, are made with exceptional non-shorted yield (99.4%, representing 718 out of 722 tested devices) without requiring clean room facilities.

  15. An Estimation of Hybrid Quantum Mechanical Molecular Mechanical Polarization Energies for Small Molecules Using Polarizable Force-Field Approaches

    DOE PAGES

    Huang, Jing; Mei, Ye; König, Gerhard; ...

    2017-01-24

    Here in this work, we report two polarizable molecular mechanics (polMM) force field models for estimating the polarization energy in hybrid quantum mechanical molecular mechanical (QM/MM) calculations. These two models, named the potential of atomic charges (PAC) and potential of atomic dipoles (PAD), are formulated from the ab initio quantum mechanical (QM) response kernels for the prediction of the QM density response to an external molecular mechanical (MM) environment (as described by external point charges). The PAC model is similar to fluctuating charge (FQ) models because the energy depends on external electrostatic potential values at QM atomic sites; the PADmore » energy depends on external electrostatic field values at QM atomic sites, resembling induced dipole (ID) models. To demonstrate their uses, we apply the PAC and PAD models to 12 small molecules, which are solvated by TIP3P water. The PAC model reproduces the QM/MM polarization energy with a R2 value of 0.71 for aniline (in 10,000 TIP3P water configurations) and 0.87 or higher for other eleven solute molecules, while the PAD model has a much better performance with R2 values of 0.98 or higher. The PAC model reproduces reference QM/MM hydration free energies for 12 solute molecules with a RMSD of 0.59 kcal/mol. The PAD model is even more accurate, with a much smaller RMSD of 0.12 kcal/mol, with respect to the reference. Lastly, this suggests that polarization effects, including both local charge distortion and intramolecular charge transfer, can be well captured by induced dipole type models with proper parametrization.« less

  16. An Estimation of Hybrid Quantum Mechanical Molecular Mechanical Polarization Energies for Small Molecules Using Polarizable Force-Field Approaches.

    PubMed

    Huang, Jing; Mei, Ye; König, Gerhard; Simmonett, Andrew C; Pickard, Frank C; Wu, Qin; Wang, Lee-Ping; MacKerell, Alexander D; Brooks, Bernard R; Shao, Yihan

    2017-02-14

    In this work, we report two polarizable molecular mechanics (polMM) force field models for estimating the polarization energy in hybrid quantum mechanical molecular mechanical (QM/MM) calculations. These two models, named the potential of atomic charges (PAC) and potential of atomic dipoles (PAD), are formulated from the ab initio quantum mechanical (QM) response kernels for the prediction of the QM density response to an external molecular mechanical (MM) environment (as described by external point charges). The PAC model is similar to fluctuating charge (FQ) models because the energy depends on external electrostatic potential values at QM atomic sites; the PAD energy depends on external electrostatic field values at QM atomic sites, resembling induced dipole (ID) models. To demonstrate their uses, we apply the PAC and PAD models to 12 small molecules, which are solvated by TIP3P water. The PAC model reproduces the QM/MM polarization energy with a R(2) value of 0.71 for aniline (in 10,000 TIP3P water configurations) and 0.87 or higher for other 11 solute molecules, while the PAD model has a much better performance with R(2) values of 0.98 or higher. The PAC model reproduces reference QM/MM hydration free energies for 12 solute molecules with a RMSD of 0.59 kcal/mol. The PAD model is even more accurate, with a much smaller RMSD of 0.12 kcal/mol, with respect to the reference. This suggests that polarization effects, including both local charge distortion and intramolecular charge transfer, can be well captured by induced dipole type models with proper parametrization.

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

    PubMed

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

    2012-07-01

    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.

  18. Quantum molecular dynamics of hydrogen bonded complexes of rigid molecules using the semiclassical initial value representation in Cartesian coordinates.

    PubMed

    Issack, Bilkiss B; Roy, Pierre-Nicholas

    2007-08-07

    Semiclassical initial value representation calculations are performed for the constrained water dimer in Cartesian coordinates. The study represents the first application of a previously reported method [Issak and Roy, J. Chem. Phys. 123, 084103 (2005); 126, 024111 (2007)] to a molecular cluster. Bound state energies are calculated for a dimer of rigid water molecules (H2O)2 as well as its deuterated form (D2O)2. The results show that the approach fares well with respect to accuracy in capturing quantum effects in intermolecular interactions.

  19. Molecular analogs of the hemihelix: A computational study of chain molecules containing left- and right-handed helices

    NASA Astrophysics Data System (ADS)

    Pichierri, Fabio

    2014-08-01

    Using density functional theory (DFT) we design two novel chain molecules containing a left-handed (thia)helicene unit connected to a right-handed (thia)helicene unit via a phosphoroussbnd phosphorous (Psbnd P) bond. These chains represent the molecular analogs of the novel hemihelix structure recently discovered by a group of Harvard University scientists. The HOMO and LUMO levels of the heterochiral chains, termed hemihelicenes, are localized on the left- and right-handed blocks, respectively. In contrast, the frontier orbitals of the chains containing homochiral (thia)helicenes connected by a Psbnd P bond are delocalized all over the chain.

  20. Comment on “The Molecular Evolutionary Patterns of the Insulin/FOXO Signaling Pathway”

    PubMed Central

    Alvarez-Ponce, David; Aguadé, Montserrat; Rozas, Julio

    2013-01-01

    Letter to the Editor on Wang M, Wang Q, Wang Z, Zhang X, Pan Y. The molecular evolutionary patterns of the insulin/FOXO signaling pathway. Evol Bioinform. 2013;9:1–16. doi: 10.4137/EBO.S10539. PMID:23818748

  1. Strong-field approximation for above-threshold ionization of polyatomic molecules. II. The role of electron rescattering off the molecular centers

    NASA Astrophysics Data System (ADS)

    Hasović, E.; Milošević, D. B.

    2014-05-01

    We consider high-order above-threshold ionization of polyatomic molecules by a strong laser field. An improved molecular strong-field approximation which takes into account the electron rescattering off the molecular centers is developed. The presented theory is applied to calculate the photoelectron energy and angular distributions for the ozone molecule. The obtained spectra exhibit pronounced minima, and this is explained as a three-point destructive interference of the rescattered electron wave packets.

  2. Phospholipid Membrane Protection by Sugar Molecules during Dehydration—Insights into Molecular Mechanisms Using Scattering Techniques

    PubMed Central

    Garvey, Christopher J.; Lenné, Thomas; Koster, Karen L.; Kent, Ben; Bryant, Gary

    2013-01-01

    Scattering techniques have played a key role in our understanding of the structure and function of phospholipid membranes. These techniques have been applied widely to study how different molecules (e.g., cholesterol) can affect phospholipid membrane structure. However, there has been much less attention paid to the effects of molecules that remain in the aqueous phase. One important example is the role played by small solutes, particularly sugars, in protecting phospholipid membranes during drying or slow freezing. In this paper, we present new results and a general methodology, which illustrate how contrast variation small angle neutron scattering (SANS) and synchrotron-based X-ray scattering (small angle (SAXS) and wide angle (WAXS)) can be used to quantitatively understand the interactions between solutes and phospholipids. Specifically, we show the assignment of lipid phases with synchrotron SAXS and explain how SANS reveals the exclusion of sugars from the aqueous region in the particular example of hexagonal II phases formed by phospholipids. PMID:23584028

  3. Phospholipid Membrane Protection by Sugar Molecules during Dehydration-Insights into Molecular Mechanisms Using Scattering Techniques

    SciTech Connect

    Garvey, Christopher J.; Lenné, Thomas; Koster, Karen L.; Kent, Ben; Bryant, Gary

    2014-09-24

    Scattering techniques have played a key role in our understanding of the structure and function of phospholipid membranes. These techniques have been applied widely to study how different molecules (e.g., cholesterol) can affect phospholipid membrane structure. However, there has been much less attention paid to the effects of molecules that remain in the aqueous phase. One important example is the role played by small solutes, particularly sugars, in protecting phospholipid membranes during drying or slow freezing. In this paper, we present new results and a general methodology, which illustrate how contrast variation small angle neutron scattering (SANS) and synchrotron-based X-ray scattering (small angle (SAXS) and wide angle (WAXS)) can be used to quantitatively understand the interactions between solutes and phospholipids. Specifically, we show the assignment of lipid phases with synchrotron SAXS and explain how SANS reveals the exclusion of sugars from the aqueous region in the particular example of hexagonal II phases formed by phospholipids.

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

    NASA Astrophysics Data System (ADS)

    Hansma, Paul K.

    2000-03-01

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

  5. Molecular orientation and lattice ordering of C60 molecules on the polar FeO/Pt(111) surface.

    PubMed

    Qin, Zhihui; Liu, Cunding; Chen, Jian; Guo, Qinmin; Yu, Yinghui; Cao, Gengyu

    2012-01-14

    C(60) molecules assemble into close packing layer under the domination of the intermolecular interaction when deposited onto Pt(111)-supported FeO layer kept at 400 K. From corresponding high resolution scanning tunneling microscopy (STM) image, a kind of C(60) molecular orientational ordering stabilized by the intermolecular interaction is revealed as C(60)/FeO(111)-(√133 × √133) R17.5° structure and determined from the commensurability between the C(60) nearest-neighbor distance and the lattice of the underlying oxygen layer. Moreover, due to the inhomogeneously distributed work function of the underlying FeO layer, the C(60) molecular electronic state is periodically modulated resulting in a bright-dim STM contrast. In addition, one coincidence lattice ordering is determined as 8 × 8 superstructure with respect to the C(60) primitive cell, which overlays a 3 × 3 moiré cell of the underlying FeO layer.

  6. Molecular orientation and lattice ordering of C60 molecules on the polar FeO/Pt(111) surface

    NASA Astrophysics Data System (ADS)

    Qin, Zhihui; Liu, Cunding; Chen, Jian; Guo, Qinmin; Yu, Yinghui; Cao, Gengyu

    2012-01-01

    C60 molecules assemble into close packing layer under the domination of the intermolecular interaction when deposited onto Pt(111)-supported FeO layer kept at 400 K. From corresponding high resolution scanning tunneling microscopy (STM) image, a kind of C60 molecular orientational ordering stabilized by the intermolecular interaction is revealed as C60/FeO(111)-(√133 × √133) R17.5° structure and determined from the commensurability between the C60 nearest-neighbor distance and the lattice of the underlying oxygen layer. Moreover, due to the inhomogeneously distributed work function of the underlying FeO layer, the C60 molecular electronic state is periodically modulated resulting in a bright-dim STM contrast. In addition, one coincidence lattice ordering is determined as 8 × 8 superstructure with respect to the C60 primitive cell, which overlays a 3 × 3 moiré cell of the underlying FeO layer.

  7. Modeling Stochastic Kinetics of Molecular Machines at Multiple Levels: From Molecules to Modules

    PubMed Central

    Chowdhury, Debashish

    2013-01-01

    A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here. PMID:23746505

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

    PubMed

    Chowdhury, Debashish

    2013-06-04

    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.

  9. Multicomponent redox catalysts for reduction of large biological molecules using molecular hydrogen as the reductant

    SciTech Connect

    Chao, S.; Simon, R.A.; Mallouk, T.E.; Wrighton, M.S.

    1988-03-30

    One-electron reduction of the large biological molecules horse heart cytochrome c, sperm whale myoglobin, and horseradish peroxidase using H/sub 2/ as the reductant can be catalyzed by two-component, high surface area heterogeneous catalysts. The catalysts can be prepared by first functionalizing high surface area SiO/sub 2/ with a polycationic polymer into which is dispersed MCl/sub 4//sup 2 -/ (M = Pd, Pt). Reduction with H/sub 2/ yields elemental Pd or Pt dispersed in the polymer. The particles are finally functionalized with a redox polymer derived from hydrolysis of Si(OR)/sub 3/ groups of an N,N'-dialkyl-4,4'-bipyridinium- or from a cobalticenium-based monomer. The two components of the heterogeneous catalysts are the buried noble metal capable of activating the H/sub 2/ and the redox polymer, which can equilibrate both with the noble metal and with the large biological molecule. Reduction of the large biological molecules in aqueous solution can be effected at room temperature and 1 atm H/sub 2/ using the catalysts under conditions where the biological materials would not be reducible with H/sub 2/ alone or when the noble metal alone would be used as the catalyst.

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

    PubMed

    Guo, Xiaojian; Zhou, Xueping

    2006-12-01

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

  11. Initiating Molecular Growth in the Interstellar Medium via Dimeric Complexes of Observed Ions and Molecules

    NASA Technical Reports Server (NTRS)

    Bera, Partha P.; Head-Gordon, Martin; Lee, Timothy J.

    2011-01-01

    A feasible initiation step for particle growth in the interstellar medium (ISM) is simulated by means of ab quantum chemistry methods. The systems studied are dimer ions formed by pairing nitrogen containing small molecules known to exist in the ISM with ions of unsaturated hydrocarbons or vice versa. Complexation energies, structures of ensuing complexes and electronic excitation spectra of the encounter complexes are estimated using various quantum chemistry methods. Moller-Plesset perturbation theory (MP2, Z-averaged perturbation theory (ZAP2), coupled cluster singles and doubles with perturbative triples corrections (CCSD(T)), and density functional theory (DFT) methods (B3LYP) were employed along with the correlation consistent cc-pVTZ and aug-cc-pVTZ basis sets. Two types of complexes are predicted. One type of complex has electrostatic binding with moderate (7-20 kcal per mol) binding energies, that are nonetheless significantly stronger than typical van der Waals interactions between molecules of this size. The other type of complex develops strong covalent bonds between the fragments. Cyclic isomers of the nitrogen containing complexes are produced very easily by ion-molecule reactions. Some of these complexes show intense ultraviolet visible spectra for electronic transitions with large oscillator strengths at the B3LYP, omegaB97, and equations of motion coupled cluster (EOM-CCSD) levels. The open shell nitrogen containing carbonaceous complexes especially exhibit a large oscillator strength electronic transition in the visible region of the electromagnetic spectrum.

  12. Molecular mimicry of substrate oxygen atoms by water molecules in the beta-amylase active site.

    PubMed

    Pujadas, G; Palau, J

    2001-08-01

    Soybean beta-amylase (EC 3.2.1.2) has been crystallized both free and complexed with a variety of ligands. Four water molecules in the free-enzyme catalytic cleft form a multihydrogen-bond network with eight strategic residues involved in enzyme-ligand hydrogen bonds. We show here that the positions of these four water molecules are coincident with the positions of four potential oxygen atoms of the ligands within the complex. Some of these waters are displaced from the active site when the ligands bind to the enzyme. How many are displaced depends on the shape of the ligand. This means that when one of the four positions is not occupied by a ligand oxygen atom, the corresponding water remains. We studied the functional/structural role of these four waters and conclude that their presence means that the conformation of the eight side chains is fixed in all situations (free or complexed enzyme) and preserved from unwanted or forbidden conformational changes that could hamper the catalytic mechanism. The water structure at the active pocket of beta-amylase is therefore essential for providing the ligand recognition process with plasticity. It does not affect the protein active-site geometry and preserves the overall hydrogen-bonding network, irrespective of which ligand is bound to the enzyme. We also investigated whether other enzymes showed a similar role for water. Finally, we discuss the potential use of these results for predicting whether water molecules can mimic ligand atoms in the active center.

  13. Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation

    PubMed Central

    Niessen, Carien M.; Leckband, Deborah; Yap, Alpha S.

    2013-01-01

    This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields. PMID:21527735

  14. Spectroscopic [FT-IR and FT-Raman] and molecular modeling (MM) study of benzene sulfonamide molecule using quantum chemical calculations

    NASA Astrophysics Data System (ADS)

    Vinod, K. S.; Periandy, S.; Govindarajan, M.

    2016-07-01

    The spectroscopic and molecular modeling (MM) study includes, FT-IR, FT-Raman and 13C NMR and 1H NMR spectra of the Benzene sulfonamide were recorded for the analysis. The observed experimental and theoretical frequencies (IR and Raman) were assigned according to their distinctive region. The present study of this title molecule have been carried out by hybrid computational calculations of HF and DFT (B3LYP) methods with 6-311+G(d,p) and 6-311++G(d,p) basis sets and the corresponding results are tabulated. The structural modifications of the compound due to the substitutions of NH2 and SO2 were investigated. The minimum energy conformers of the compound were studied using conformational analysis. The alternations of the vibrational pattern of the base structure related to the substitutions were analyzed. The thermodynamic parameters (such as zero-point vibrational energy, thermal energy, specific heat capacity, rotational constants, entropy, and dipole moment) of Benzene sulfonamide have been calculated. The donor acceptor interactions of the compound and the corresponding UV transitions are found out using NBO analysis. The NMR spectra were simulated by using the gauge independent atomic orbital (GIAO) method with B3LYP methods and the 6-311++G(d,p) basis set and their spectra were simulated and the chemical shifts related to TMS were compared. A quantum computational study on the electronic and optical properties absorption wavelengths, excitation energy, dipole moment and frontier molecular orbital energies, were performed by HF and DFT methods. The energy gap of the present compound was calculated related to HOMO and LUMO energies which confirm the occurring of charge transformation between the base and ligand group. Besides frontier molecular orbitals (FMO), molecular electrostatic potential (MEP) was performed. The thermodynamic properties (heat capacity, entropy, and enthalpy) of the title compound at different temperatures were calculated in gas phase and

  15. Rotation mechanism of methylammonium molecules in organometal halide perovskite in cubic phase: An ab initio molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Shimamura, Kohei; Hakamata, Tomoya; Shimojo, Fuyuki; Kalia, Rajiv K.; Nakano, Aiichiro; Vashishta, Priya

    2016-12-01

    Rotation of methylammonium (CH3NH3 or MA) molecules is believed to govern the excellent transport properties of photocarriers in the MA lead iodide (MAPbI3) perovskite. Of particular interest is its cubic phase, which exists in industrially important films at room temperature. In order to investigate the rotational behaviors of the MA molecules, we have performed ab initio molecular dynamics simulations of cubic-MAPbI3 at room temperature. There are two types of rotational motions of MA molecules in a crystalline PbI3 cage: reorientation of a whole molecule and intramolecular rotation around the C-N bond within MA molecules. Using a cubic symmetry-assisted analysis (CSAA), we found that the prominent orientation of the C-N bond is the crystalline ⟨110 ⟩ directions, rather than the ⟨100 ⟩ and ⟨111 ⟩ directions. Rapid rotation around the C-N bond is also observed, which easily occurs when the rotational axis is parallel to the ⟨110 ⟩ directions according to the CSAA. To explain the atomistic mechanisms underlying these CSAA results, we have focused on the relation between H-I hydrogen bonds and the orientation of an MA molecule. Here, the hydrogen bonds were defined by population analysis, and it has been found that, while H atoms in the CH3 group (HC) hardly interacts with I atoms, those in the NH3 group (HN) form at least one hydrogen bond with I atoms and their interatomic distances are in a wide range, 2.2-3.7 Å. Based on these findings, we have given a possible explanation to why the ⟨110 ⟩ directions are preferred. Namely, the atomic arrangement and interatomic distance between MA and surrounding I atoms are most suitable for the formation of hydrogen bonds. In addition to films, these results are potentially applicable to the rotational behaviors in bulk MAPbI3 as well, considering that the atomistic structure and time constants regarding the rotation of MA molecules statistically agree with bulk experiments.

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

    ERIC Educational Resources Information Center

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

    2008-01-01

    We describe the development and use of a molecular model building activity with a chocolate theme, suitable for a public presentation of chemistry through interaction with visitors to science festivals and museums, and as a special classroom activity during science weeks, and so forth. (Contains 3 figures.)

  17. Molecular entomology: analyzing tiny molecules to answer big questions about disease vectors and their biology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The entomologists at the Arthropod-Borne Animal Diseases Research Unit at USDA-Agricultural Research Service are tasked with protecting the nation’s livestock from domestic, foreign and emerging vector-borne diseases. To accomplish this task, a vast array of molecular techniques are being used in pr...

  18. Engineering the magnetic coupling and anisotropy at the molecule-magnetic surface interface in molecular spintronic devices

    NASA Astrophysics Data System (ADS)

    Campbell, Victoria E.; Tonelli, Monica; Cimatti, Irene; Moussy, Jean-Baptiste; Tortech, Ludovic; Dappe, Yannick J.; Rivière, Eric; Guillot, Régis; Delprat, Sophie; Mattana, Richard; Seneor, Pierre; Ohresser, Philippe; Choueikani, Fadi; Otero, Edwige; Koprowiak, Florian; Chilkuri, Vijay Gopal; Suaud, Nicolas; Guihéry, Nathalie; Galtayries, Anouk; Miserque, Frederic; Arrio, Marie-Anne; Sainctavit, Philippe; Mallah, Talal

    2016-12-01

    A challenge in molecular spintronics is to control the magnetic coupling between magnetic molecules and magnetic electrodes to build efficient devices. Here we show that the nature of the magnetic ion of anchored metal complexes highly impacts the exchange coupling of the molecules with magnetic substrates. Surface anchoring alters the magnetic anisotropy of the cobalt(II)-containing complex (Co(Pyipa)2), and results in blocking of its magnetization due to the presence of a magnetic hysteresis loop. In contrast, no hysteresis loop is observed in the isostructural nickel(II)-containing complex (Ni(Pyipa)2). Through XMCD experiments and theoretical calculations we find that Co(Pyipa)2 is strongly ferromagnetically coupled to the surface, while Ni(Pyipa)2 is either not coupled or weakly antiferromagnetically coupled to the substrate. These results highlight the importance of the synergistic effect that the electronic structure of a metal ion and the organic ligands has on the exchange interaction and anisotropy occurring at the molecule-electrode interface.

  19. Mechanical operation and intersubunit coordination of ring-shaped molecular motors: insights from single-molecule studies.

    PubMed

    Liu, Shixin; Chistol, Gheorghe; Bustamante, Carlos

    2014-05-06

    Ring NTPases represent a large and diverse group of proteins that couple their nucleotide hydrolysis activity to a mechanical task involving force generation and some type of transport process in the cell. Because of their shape, these enzymes often operate as gates that separate distinct cellular compartments to control and regulate the passage of chemical species across them. In this manner, ions and small molecules are moved across membranes, biopolymer substrates are segregated between cells or moved into confined spaces, double-stranded nucleic acids are separated into single strands to provide access to the genetic information, and polypeptides are unfolded and processed for recycling. Here we review the recent advances in the characterization of these motors using single-molecule manipulation and detection approaches. We describe the various mechanisms by which ring motors convert chemical energy to mechanical force or torque and coordinate the activities of individual subunits that constitute the ring. We also examine how single-molecule studies have contributed to a better understanding of the structural elements involved in motor-substrate interaction, mechanochemical coupling, and intersubunit coordination. Finally, we discuss how these molecular motors tailor their operation-often through regulation by other cofactors-to suit their unique biological functions.

  20. Crossed molecular beams study of O(1D) reactions with H2 molecules

    SciTech Connect

    Miau, Tzong -Tsong

    1995-05-01

    Reaction dynamics of O(1D) atoms with H2 molecules was reinvestigated using the crossed molecular beams technique with pulsed beams. The O(1D) beam was generated by photodissociating O3 molecules at 248 nm. Time-of-flight spectra and the laboratory angular distribution of the OH products were measured. The derived OH product center-of-mass flux-velocity contour diagram shows more backward scattered intensity with respect to the O(1D) beam. In contrast to previous studies which show that the insertion mechanism is the dominant process, our results indicate that the contribution from the collinear approach of the O(1D) atom to the H2 molecule on the first excited state potential energy surface is significant and the energy barrier for the collinear approach is therefore minimal. Despite the increased time resolution in this experiment, no vibrational structure in the OH product time-of-flight spectra was resolved. This is in agreement with LIF studies, which have shown that the rotational distributions of the OH products in all vibrational states are broad and highly inverted.

  1. Engineering the magnetic coupling and anisotropy at the molecule-magnetic surface interface in molecular spintronic devices.

    PubMed

    Campbell, Victoria E; Tonelli, Monica; Cimatti, Irene; Moussy, Jean-Baptiste; Tortech, Ludovic; Dappe, Yannick J; Rivière, Eric; Guillot, Régis; Delprat, Sophie; Mattana, Richard; Seneor, Pierre; Ohresser, Philippe; Choueikani, Fadi; Otero, Edwige; Koprowiak, Florian; Chilkuri, Vijay Gopal; Suaud, Nicolas; Guihéry, Nathalie; Galtayries, Anouk; Miserque, Frederic; Arrio, Marie-Anne; Sainctavit, Philippe; Mallah, Talal

    2016-12-08

    A challenge in molecular spintronics is to control the magnetic coupling between magnetic molecules and magnetic electrodes to build efficient devices. Here we show that the nature of the magnetic ion of anchored metal complexes highly impacts the exchange coupling of the molecules with magnetic substrates. Surface anchoring alters the magnetic anisotropy of the cobalt(II)-containing complex (Co(Pyipa)2), and results in blocking of its magnetization due to the presence of a magnetic hysteresis loop. In contrast, no hysteresis loop is observed in the isostructural nickel(II)-containing complex (Ni(Pyipa)2). Through XMCD experiments and theoretical calculations we find that Co(Pyipa)2 is strongly ferromagnetically coupled to the surface, while Ni(Pyipa)2 is either not coupled or weakly antiferromagnetically coupled to the substrate. These results highlight the importance of the synergistic effect that the electronic structure of a metal ion and the organic ligands has on the exchange interaction and anisotropy occurring at the molecule-electrode interface.

  2. Mechanical Operation and Intersubunit Coordination of Ring-Shaped Molecular Motors: Insights from Single-Molecule Studies

    PubMed Central

    Liu, Shixin; Chistol, Gheorghe; Bustamante, Carlos

    2014-01-01

    Ring NTPases represent a large and diverse group of proteins that couple their nucleotide hydrolysis activity to a mechanical task involving force generation and some type of transport process in the cell. Because of their shape, these enzymes often operate as gates that separate distinct cellular compartments to control and regulate the passage of chemical species across them. In this manner, ions and small molecules are moved across membranes, biopolymer substrates are segregated between cells or moved into confined spaces, double-stranded nucleic acids are separated into single strands to provide access to the genetic information, and polypeptides are unfolded and processed for recycling. Here we review the recent advances in the characterization of these motors using single-molecule manipulation and detection approaches. We describe the various mechanisms by which ring motors convert chemical energy to mechanical force or torque and coordinate the activities of individual subunits that constitute the ring. We also examine how single-molecule studies have contributed to a better understanding of the structural elements involved in motor-substrate interaction, mechanochemical coupling, and intersubunit coordination. Finally, we discuss how these molecular motors tailor their operation—often through regulation by other cofactors—to suit their unique biological functions. PMID:24806916

  3. Biomolecular Crowding Arising from Small Molecules, Molecular Constraints, Surface Packing, and Nano-Confinement.

    PubMed

    Hilaire, Mary Rose; Abaskharon, Rachel M; Gai, Feng

    2015-07-02

    The effect of macromolecular crowding on the structure, dynamics, and reactivity of biomolecules is well established and the relevant research has been extensively reviewed. Herein, we focus our discussion on crowding effects arising from small cosolvent molecules and densely packed surface conditions. In addition, we highlight recent efforts that capitalize on the excluded volume effect for various tailored biochemical and biophysical applications. Specifically, we discuss how a targeted increase in local mass density can be exploited to gain insight into the folding dynamics of the protein of interest and how confinement via reverse micelles can be used to study a range of biophysical questions, from protein hydration dynamics to amyloid formation.

  4. The RCSB PDB “Molecule of the Month”: Inspiring a Molecular View of Biology

    PubMed Central

    Goodsell, David S.; Dutta, Shuchismita; Zardecki, Christine; Voigt, Maria; Berman, Helen M.; Burley, Stephen K.

    2015-01-01

    The Research Collaboratory for Structural Bioinformatics (RCSB) Molecule of the Month series provides a curated introduction to the 3-D biomolecular structures available in the Protein Data Bank archive and the tools that are available at the RCSB website for accessing and exploring them. A variety of educational materials, such as articles, videos, posters, hands-on activities, lesson plans, and curricula, build on this series for use in a variety of educational settings as a general introduction to key topics, such as enzyme action, protein synthesis, and viruses. The series and associated educational materials are freely available at www.rcsb.org. PMID:25942442

  5. Molecular features of the prazosin molecule required for activation of Transport-P.

    PubMed

    da Silva, Joaquim Fernando Mendes; Walters, Marcus; Al-Damluji, Saad; Ganellin, C Robin

    2008-08-01

    Closely related structural analogues of prazosin have been synthesised and tested for inhibition and activation of Transport-P in order to identify the structural features of the prazosin molecule that appear to be necessary for activation of Transport-P. So far, all the compounds tested are less active than prazosin. It is shown that the structure of prazosin appears to be very specific for the activation. Only quinazolines have been found to activate, and the presence of the 6,7-dimethoxy and 4-amino groups appears to be critically important.

  6. The RCSB PDB "Molecule of the Month": Inspiring a Molecular View of Biology.

    PubMed

    Goodsell, David S; Dutta, Shuchismita; Zardecki, Christine; Voigt, Maria; Berman, Helen M; Burley, Stephen K

    2015-05-01

    The Research Collaboratory for Structural Bioinformatics (RCSB) Molecule of the Month series provides a curated introduction to the 3-D biomolecular structures available in the Protein Data Bank archive and the tools that are available at the RCSB website for accessing and exploring them. A variety of educational materials, such as articles, videos, posters, hands-on activities, lesson plans, and curricula, build on this series for use in a variety of educational settings as a general introduction to key topics, such as enzyme action, protein synthesis, and viruses. The series and associated educational materials are freely available at www.rcsb.org.

  7. Orbital tomography: Molecular band maps, momentum maps and the imaging of real space orbitals of adsorbed molecules.

    PubMed

    Offenbacher, Hannes; Lüftner, Daniel; Ules, Thomas; Reinisch, Eva Maria; Koller, Georg; Puschnig, Peter; Ramsey, Michael G

    2015-10-01

    The frontier orbitals of molecules are the prime determinants of their chemical, optical and electronic properties. Arguably, the most direct method of addressing the (filled) frontier orbitals is ultra-violet photoemission spectroscopy (UPS). Although UPS is a mature technique from the early 1970s on, the angular distribution of the photoemitted electrons was thought to be too complex to be analysed quantitatively. Recently angle resolved UPS (ARUPS) work on conjugated molecules both, in ordered thick films and chemisorbed monolayers, has shown that the angular (momentum) distribution of the photocurrent from orbital emissions can be simply understood. The approach, based on the assumption of a plane wave final state is becoming known as orbital tomography. Here we will demonstrate, with selected examples of pentacene (5A) and sexiphenyl (6P), the potential of orbital tomography. First it will be shown how the full angular distribution of the photocurrent (momentum map) from a specific orbital is related to the real space orbital by a Fourier transform. Examples of the reconstruction of 5A orbitals will be given and the procedure for recovering the lost phase information will be outlined. We then move to examples of sexiphenyl where we interrogate the original band maps of thick sexiphenyl in the light of our understanding of orbital tomography that has developed since then. With comparison to theoretical simulations of the molecular band maps, the molecular conformation and orientation will be concluded. New results for the sexiphenyl monolayer on Al(1 1 0) will then be presented. From the band maps it will be concluded that the molecule is planarised and adopts a tilted geometry. Finally the momentum maps down to HOMO-11 will be analysed and real space orbitals reconstructed.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-10-22

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

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

    PubMed Central

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

    1993-01-01

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

  11. Extraction of high-molecular-weight genomic DNA for long-read sequencing of single molecules.

    PubMed

    Mayjonade, Baptiste; Gouzy, Jérôme; Donnadieu, Cécile; Pouilly, Nicolas; Marande, William; Callot, Caroline; Langlade, Nicolas; Muños, Stéphane

    2016-10-01

    De novo sequencing of complex genomes is one of the main challenges for researchers seeking high-quality reference sequences. Many de novo assemblies are based on short reads, producing fragmented genome sequences. Third-generation sequencing, with read lengths >10 kb, will improve the assembly of complex genomes, but these techniques require high-molecular-weight genomic DNA (gDNA), and gDNA extraction protocols used for obtaining smaller fragments for short-read sequencing are not suitable for this purpose. Methods of preparing gDNA for bacterial artificial chromosome (BAC) libraries could be adapted, but these approaches are time-consuming, and commercial kits for these methods are expensive. Here, we present a protocol for rapid, inexpensive extraction of high-molecular-weight gDNA from bacteria, plants, and animals. Our technique was validated using sunflower leaf samples, producing a mean read length of 12.6 kb and a maximum read length of 80 kb.

  12. Molecular phylogeny of the phylum Gastrotricha: new data brings together molecules and morphology.

    PubMed

    Paps, Jordi; Riutort, Marta

    2012-04-01

    Gastrotricha is a species-rich phylum of microscopical animals that contains two main orders, Chaetonotida and Macrodasyida. Gastrotrichs are important members of the aquatic environment and significant players in the study of animal evolution. In spite of their ecological and evolutionary importance, their internal relationships are not yet well understood. We have produced new sequences for the 18S rDNA gene to improve both the quality and quantity of taxon sampling for the gastrotrichs. Our phylogeny recovers the monophyly of the two main Gastrotricha clades, in contrast to recent studies with similar sampling, but in agreement with morphology based analyses. However, our topology is not able to resolve the first branches of the macrodasyidans or settle the position of the puzzling Neodasys, a controversial genus classified as a chaetonotidan on morphological grounds but placed within macrodasyidans by molecular studies. This analysis is the most exhaustive molecular phylogeny of the phylum to date, and significantly increases our knowledge of gastrotrich evolution.

  13. Improving signal/noise resolution in single-molecule experiments using molecular constructs with short handles.

    PubMed

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

    2011-04-06

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

  14. Molecular complexes of organometallic molecules with noble gases: the rotational spectrum of dimethylsilane-argon.

    PubMed

    Ottaviani, Paolo; Melandri, Sonia; Caminati, Walther; Banser, Deike; Schnell, Melanie; Grabow, Jens-Uwe

    2004-11-12

    The rotational spectrum of the molecular complex dimethylsilane-argon was investigated by free-jet absorption millimeter-wave and molecular-beam Fourier transform spectroscopy. The absolute energy minimum corresponds to a conformation in which the argon atom lies in the plane of symmetry of dimethylsilane, perpendicular to the C-Si-C plane. The distance of Ar atom is tilted 14 degrees away from the Si atom. The zero-point dissociation energy was estimated from the centrifugal distortion constant D(J) to be 2.2 kJ mol(-1). Small splitting, due to tunneling of the Ar atom and internal rotation of the two methyl groups, was observed, measured, and used to determine the potential energy surface for these motions.

  15. Dust around AFGL 2688, molecular shielding, and the production of carbon chain molecules

    NASA Technical Reports Server (NTRS)

    Jura, M.; Kroto, H.

    1990-01-01

    The molecular, IR, and optical maps of the evolved carbon star AFGL 2688 (the 'Egg' Nebula) are all consistent with a model of a bipolar outflow of approximately 0.0001 solar masses/yr that stopped as this object evolved beyond the asymptotic giant branch about 200 years ago. In order to explain the extended HC7N emission around this star, it is proposed that carbon grains are collisionally fragmented as they supersonically steam through the circumstellar envelope.

  16. Healthy dietary patterns and risk of breast cancer by molecular subtype.

    PubMed

    Hirko, Kelly A; Willett, Walter C; Hankinson, Susan E; Rosner, Bernard A; Beck, Andrew H; Tamimi, Rulla M; Eliassen, A Heather

    2016-02-01

    We examined associations between dietary quality indices and breast cancer risk by molecular subtype among 100,643 women in the prospective Nurses' Health Study (NHS) cohort, followed from 1984 to 2006. Dietary quality scores for the Alternative Healthy Eating Index (AHEI), alternate Mediterranean diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) dietary patterns were calculated from semi-quantitative food frequency questionnaires collected every 2-4 years. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor status from immunostained tumor microarrays in combination with histologic grade. Cox proportional hazards models, adjusted for age and breast cancer risk factors, were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Competing risk analyses were used to assess heterogeneity by subtype. We did not observe any significant associations between the AHEI or aMED dietary patterns and risk of breast cancer by molecular subtype. However, a significantly reduced risk of HER2-type breast cancer was observed among women in 5th versus 1st quintile of the DASH dietary pattern [n = 134 cases, Q5 vs. Q1 HR (95 % CI) = 0.44 (0.25-0.77)], and the inverse trend across quintiles was significant (p trend = 0.02). We did not observe any heterogeneity in associations between AHEI (p het = 0.25), aMED (p het = 0.71), and DASH (p het = 0.12) dietary patterns and breast cancer by subtype. Adherence to the AHEI, aMED, and DASH dietary patterns was not strongly associated with breast cancer molecular subtypes.

  17. Healthy dietary patterns and risk of breast cancer by molecular subtype

    PubMed Central

    Hirko, Kelly A.; Willett, Walter C.; Hankinson, Susan E.; Rosner, Bernard A.; Beck, Andrew H.; Tamimi, Rulla M.; Eliassen, A. Heather

    2016-01-01

    Purpose We examined associations between dietary quality indices and breast cancer risk by molecular subtype among 100,643 women in the prospective Nurses' Health Study (NHS) cohort, followed from 1984 to 2006. Methods Dietary quality scores for the Alternative Healthy Eating Index (AHEI), alternate Mediterranean diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) dietary patterns were calculated from semi-quantitative food frequency questionnaires collected every 2-4 years. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR) status from immunostained tumor microarrays in combination with histologic grade. Cox proportional hazards models, adjusted for age and breast cancer risk factors, were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Competing risk analyses were used to assess heterogeneity by subtype. Results We did not observe any significant associations between the AHEI or aMED dietary patterns and risk of breast cancer by molecular subtype. However, a significant reduced risk of HER2-type breast cancer was observed among women in 5th vs. 1st quintile of the DASH dietary pattern (n=134 cases, Q5 vs. Q1 HR (95%CI) =0.44(0.25-0.77)), and the inverse trend across quintiles was significant (p-trend=0.02). We did not observe any heterogeneity in associations between AHEI (phet =0.25), aMED (phet =0.71) and DASH (phet =0.12) dietary patterns and breast cancer by subtype. Conclusions Adherence to the AHEI, aMED, and DASH dietary patterns was not strongly associated with breast cancer molecular subtypes. PMID:26872903

  18. Synergistic effect of high and low molecular weight molecules in the foamability and foam stability of sparkling wines.

    PubMed

    Coelho, Elisabete; Reis, Ana; Domingues, M Rosário M; Rocha, Sílvia M; Coimbra, Manuel A

    2011-04-13

    The foam of sparkling wines is a key parameter of their quality. However, the compounds that are directly involved in foam formation and stabilization are not yet completely established. In this work, seven sparkling wines were produced in Bairrada appellation (Portugal) under different conditions and their foaming properties evaluated using a Mosalux-based device. Fractionation of the sparkling wines into four independent fractions, (1) high molecular weight material, with molecular weight higher than 12 kDa (HMW), (2) hydrophilic material with molecular weigh between 1 and 12 kDa (AqIMW), (3) hydrophobic material with molecular weigh between 1 and 12 kDa (MeIMW), and (4) hydrophobic material with a molecular weight lower than 1 kDa (MeLMW), allowed the observation that the wines presenting the lower foam stability were those that presented lower amounts of the MeLMW fraction. The fraction that presented the best foam stability was HMW. When HMW is combined with MeLMW fraction, the foam stability largely increased. This increase was even larger, approaching the foam stability of the sparkling wine, when HMW was combined with the less hydrophobic subfraction of MeLMW (fraction 3). Electrospray tandem mass spectrometry (ESI-MS/MS) of fraction 3 allowed the assignment of polyethylene glycol oligomers (n = 5-11) and diethylene glycol 8-hydroxytridecanoate glyceryl acetate. To observe if these molecules occur in sparkling wine foam, the MeLMW was recovered directly from the sparkling wine foam and was also analyzed by ESI-MS/MS. The presence of monoacylglycerols of palmitic and stearic acids, as well as four glycerylethylene glycol fatty acid derivatives, was observed. These surface active compounds are preferentially partitioned by the sparkling wine foam rather than the liquid phase, allowing the inference of their role as key components in the promotion and stabilization of sparkling wine foam.

  19. Nonequilibrium molecular dynamics of the rheological and structural properties of linear and branched molecules. Simple shear and poiseuille flows; instabilities and slip.

    PubMed

    Castillo-Tejas, Jorge; Alvarado, Juan F J; González-Alatorre, Guillermo; Luna-Bárcenas, Gabriel; Sanchez, Isaac C; Macias-Salinas, Ricardo; Manero, Octavio

    2005-08-01

    Nonequilibrium molecular-dynamics simulations are performed for linear and branched chain molecules to study their rheological and structural properties under simple shear and Poiseuille flows. Molecules are described by a spring-monomer model with a given intermolecular potential. The equations of motion are solved for shear and Poiseuille flows with Lees and Edward's [A. W. Lees and S. F. Edwards, J. Phys. C 5, 1921 (1972)] periodic boundary conditions. A multiple time-scale algorithm extended to nonequilibrium situations is used as the integration method, and the simulations are performed at constant temperature using Nose-Hoover [S. Nose, J. Chem. Phys. 81, 511 (1984)] dynamics. In simple shear, molecules with flow-induced ellipsoidal shape, having significant segment concentrations along the gradient and neutral directions, exhibit substantial flow resistance. Linear molecules have larger zero-shear-rate viscosity than that of branched molecules, however, this behavior reverses as the shear rate is increased. The relaxation time of the molecules is associated with segment concentrations directed along the gradient and neutral directions, and hence it depends on structure and molecular weight. The results of this study are in qualitative agreement with other simulation studies and with experimental data. The pressure (Poiseuille) flow is induced by an external force F(e) simulated by confining the molecules in the region between surfaces which have attractive forces. Conditions at the boundary strongly influence the type of the slip flow predicted. A parabolic velocity profile with apparent slip on the wall is predicted under weakly attractive wall conditions, independent of molecular structure. In the case of strongly attractive walls, a layer of adhered molecules to the wall produces an abrupt distortion of the velocity profile which leads to slip between fluid layers with magnitude that depends on the molecular structure. Finally, the molecular deformation

  20. A Recombinant Horseshoe Crab Plasma Lectin Recognizes Specific Pathogen-Associated Molecular Patterns of Bacteria through Rhamnose

    PubMed Central

    Ng, Sim-Kun; Huang, Yu-Tsyr; Lee, Yuan-Chuan; Low, Ee-Ling; Chiu, Cheng-Hsun; Chen, Shiu-Ling; Mao, Liang-Chi; Chang, Margaret Dah-Tsyr

    2014-01-01

    Horseshoe crab is an ancient marine arthropod that, in the absence of a vertebrate-like immune system, relies solely on innate immune responses by defense molecules found in hemolymph plasma and granular hemocytes for host defense. A plasma lectin isolated from the hemolymph of Taiwanese Tachypleus tridentatus recognizes bacteria and lipopolysaccharides (LPSs), yet its structure and mechanism of action remain unclear, largely because of limited availability of horseshoe crabs and the lack of a heterogeneous expression system. In this study, we have successfully expressed and purified a soluble and functional recombinant horseshoe crab plasma lectin (rHPL) in an Escherichia coli system. Interestingly, rHPL bound not only to bacteria and LPSs like the native HPL but also to selective medically important pathogens isolated from clinical specimens, such as Gram-negative Pseudomonas aeruginosa and Klebsiella pneumoniae and Gram-positive Streptococcus pneumoniae serotypes. The binding was demonstrated to occur through a specific molecular interaction with rhamnose in pathogen-associated molecular patterns (PAMPs) on the bacterial surface. Additionally, rHPL inhibited the growth of P. aeruginosa PAO1 in a concentration-dependent manner. The results suggest that a specific protein-glycan interaction between rHPL and rhamnosyl residue may further facilitate development of novel diagnostic and therapeutic strategies for microbial pathogens. PMID:25541995

  1. A recombinant horseshoe crab plasma lectin recognizes specific pathogen-associated molecular patterns of bacteria through rhamnose.

    PubMed

    Ng, Sim-Kun; Huang, Yu-Tsyr; Lee, Yuan-Chuan; Low, Ee-Ling; Chiu, Cheng-Hsun; Chen, Shiu-Ling; Mao, Liang-Chi; Chang, Margaret Dah-Tsyr

    2014-01-01

    Horseshoe crab is an ancient marine arthropod that, in the absence of a vertebrate-like immune system, relies solely on innate immune responses by defense molecules found in hemolymph plasma and granular hemocytes for host defense. A plasma lectin isolated from the hemolymph of Taiwanese Tachypleus tridentatus recognizes bacteria and lipopolysaccharides (LPSs), yet its structure and mechanism of action remain unclear, largely because of limited availability of horseshoe crabs and the lack of a heterogeneous expression system. In this study, we have successfully expressed and purified a soluble and functional recombinant horseshoe crab plasma lectin (rHPL) in an Escherichia coli system. Interestingly, rHPL bound not only to bacteria and LPSs like the native HPL but also to selective medically important pathogens isolated from clinical specimens, such as Gram-negative Pseudomonas aeruginosa and Klebsiella pneumoniae and Gram-positive Streptococcus pneumoniae serotypes. The binding was demonstrated to occur through a specific molecular interaction with rhamnose in pathogen-associated molecular patterns (PAMPs) on the bacterial surface. Additionally, rHPL inhibited the growth of P. aeruginosa PAO1 in a concentration-dependent manner. The results suggest that a specific protein-glycan interaction between rHPL and rhamnosyl residue may further facilitate development of novel diagnostic and therapeutic strategies for microbial pathogens.

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

    PubMed

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

    2014-04-17

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

  3. Selective IR multiphoton dissociation of molecules in a pulsed gas-dynamically cooled molecular flow interacting with a solid surface as an alternative to low-energy methods of molecular laser isotope separation

    NASA Astrophysics Data System (ADS)

    Makarov, G. N.; Petin, A. N.

    2016-03-01

    We report the results of studies on the isotope-selective infrared multiphoton dissociation (IR MFD) of SF6 and CF3I molecules in a pulsed, gas-dynamically cooled molecular flow interacting with a solid surface. The productivity of this method in the conditions of a specific experiment (by the example of SF6 molecules) is evaluated. A number of low-energy methods of molecular laser isotope separation based on the use of infrared lasers for selective excitation of molecules are analysed and their productivity is estimated. The methods are compared with those of selective dissociation of molecules in the flow interacting with a surface. The advantages of this method compared to the low-energy methods of molecular laser isotope separation and the IR MPD method in the unperturbed jets and flows are shown. It is concluded that this method could be a promising alternative to the low-energy methods of molecular laser isotope separation.

  4. Self-structured surface patterns on molecular azo glass films induced by laser light irradiation.

    PubMed

    Yin, Jianjun; Ye, Gang; Wang, Xiaogong

    2010-05-04

    In this work, formation of photoinduced self-structured surface pattern and its correlation with chromophoric structures were studied by using a series of star-shaped azo compounds, which exist as stable molecular glass at room temperature. For the synthesis, a star-shaped precursor (Tr-AN) was prepared by a ring-open reaction between 1, 3, 5-triglycidyl isocyanurate and N-methylaniline. The star-shaped azo compounds were then synthesized through azo-coupling reactions between the precursor and diazonium salts of 4-nitroaniline, 2-methyl-4-nitroaniline, and 4-aminobenzonitrile, respectively. Through these steps, three azo compounds were obtained to bear different donor-acceptor type azo chromophores at the peripheral positions. The formation of the photoinduced self-structured patterns was investigated by irradiating solid thin films of the molecular azo glass with a uniform laser beam (532 nm, 200 mW/cm(2)) at normal incidence. For comparison, formation of surface-relief-gratings (SRGs) was also investigated by exposing the thin films to an interference pattern of the laser beams (532 nm, 80 mW/cm(2)). The results show that SRGs can be inscribed on the films of all three star-shaped azo compounds, but self-structured surface patterns is only observed on film of the azo compound containing 4-cyanoazobenzene moieties (Tr-AZ-CN) under the same irradiation condition. The electron-withdrawing groups, which control the absorption band position, show a significant influence on both the self-structured pattern formation and SRG inscription rate. Under proper experimental conditions, both self-structured surface pattern and SRG can simultaneously be observed on the Tr-AZ-CN films. The observations can lead to a deeper understanding of the photoinduced effects, especially their correlation with molecular structures.

  5. The mitochondrial DNA molecule of Sumatran orangutan and a molecular proposal for two (Bornean and Sumatran) species of orangutan.

    PubMed

    Xu, X; Arnason, U

    1996-11-01

    The complete mitochondrial DNA (mtDNA) molecule of Sumatran orangutan, plus the complete mitochondrial control region of another Sumatran specimen and the control regions and five protein-coding genes of two specimens of Bornean orangutan were sequenced and compared with a previously reported complete mtDNA of Bornean orangutan. The two orangutans are presently separated at the subspecies level. Comparison with five different species pairs-namely, harbor seal/grey seal, horse/donkey, fin whale/blue whale, common chimpanzee/pygmy chimpanzee, and Homo/common chimpanzee-showed that the molecular difference between Sumatran and Bornean orangutan is much greater than that between the seals, and greater than that between the two chimpanzees, but similar to that between the horse and the donkey and the fin and blue whales. Considering their limited morphological distinction the comparison revealed unexpectedly great molecular difference between the two orangutans. The nucleotide difference between the orangutans is about 75% of that between Homo and the common chimpanzee, whereas the amino acid difference exceeds that between Homo and the common chimpanzee. On the basis of their molecular distinction we propose that the two orangutans should be recognized as different species, Pongo pygmaeus, Bornean orangutan, and P. abelii, Sumatran orangutan.

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

    PubMed

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

    2012-11-01

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

  7. CONDORR--CONstrained Dynamics of Rigid Residues: a molecular dynamics program for constrained molecules.

    PubMed

    York, William S; Yi, Xiaobing

    2004-08-01

    A computer program CONDORR (CONstrained Dynamics of Rigid Residues) was developed for molecular dynamics simulations of large and/or constrained molecular systems, particularly carbohydrates. CONDORR efficiently calculates molecular trajectories on the basis of 2D or 3D potential energy maps, and can generate such maps based on a simple force field. The simulations involve three translational and three rotational degrees of freedom for each rigid, asymmetrical residue in the model. Total energy and angular momentum are conserved when no stochastic or external forces are applied to the model, if the time step is kept sufficiently short. Application of Langevin dynamics allows longer time steps, providing efficient exploration of conformational space. The utility of CONDORR was demonstrated by application to a constrained polysaccharide model and to the calculation of residual dipolar couplings for a disaccharide. [Figure: see text]. Molecular models (bottom) are created by cloning rigid residue archetypes (top) and joining them together. As defined here, the archetypes AX, HM and BG respectively correspond to an alpha-D-Xyl p residue, a hydroxymethyl group, and a beta-D-Glc p residue lacking O6, H6a and H6b. Each archetype contains atoms (indicated by boxes) that can be shared with other archetypes to form a linked structure. For example, the glycosidic link between the two D-Glc p residues is established by specifying that O1 of the nonreducing beta-D-Glc p (BG) residue (2) is identical to O4 of the reducing Glc p (BG) residue (1). The coordinates of the two residues are adjusted so as to superimpose these two (nominally distinct) atoms. Flexible hydroxymethyl (HM) groups (3 and 4) are treated as separate residues, and the torsional angles (normally indicated by the symbol omega) that define their geometric relationships to the pyranosyl rings of the BG residues are specified as psi3 and psi4, respectively. The torsional angles phi3 and phi4, defined solely to

  8. Conserved molecular mechanisms underlying the effects of small molecule xenobiotic chemotherapeutics on cells

    PubMed Central

    SARIN, HEMANT

    2016-01-01

    For proper determination of the apoptotic potential of chemoxenobiotics in synergism, it is important to understand the modes, levels and character of interactions of chemoxenobiotics with cells in the context of predicted conserved biophysical properties. Chemoxenobiotic structures are studied with respect to atom distribution over molecular space, the predicted overall octanol-to-water partition coefficient (Log OWPC; unitless) and molecular size viz a viz van der Waals diameter (vdWD). The Log OWPC-to-vdWD (nm−1) parameter is determined, and where applicable, hydrophilic interacting moiety/core-to-vdWD (nm−1) and lipophilic incorporating hydrophobic moiety/core-to-vdWD (nm−1) parameters of their part-structures are determined. The cellular and sub-cellular level interactions of the spectrum of xenobiotic chemotherapies have been characterized, for which a classification system has been developed based on predicted conserved biophysical properties with respect to the mode of chemotherapeutic effect. The findings of this study are applicable towards improving the effectiveness of existing combination chemotherapy regimens and the predictive accuracy of personalized cancer treatment algorithms as well as towards the selection of appropriate novel xenobiotics with the potential to be potent chemotherapeutics for dendrimer nanoparticle-based effective transvascular delivery. PMID:26998284

  9. Molecular detection of altered X-inactivation patterns in the diagnosis of genetic disease.

    PubMed

    Malcolm, S

    1992-01-01

    It is widely assumed that when a female carrier of a genetic disorder exhibits clinical signs of the disorder it is due to chance non-random X-inactivation in particular tissues. Recently molecular methods have become available for the analysis of X-chromosome inactivation status. These are based either on the methylation patterns of DNA from the active and inactive chromosomes or on the rescue of active X chromosomes in somatic cell hybrids. As a consequence of the molecular studies, it has become obvious that there are some special cases of non-random X-inactivation patterns. These include females carrying X-linked immunodeficiencies and, sometimes, one of a pair of identical female twins.

  10. Cellulose-Derived Oligomers Act as Damage-Associated Molecular Patterns and Trigger Defense-Like Responses.

    PubMed

    Souza, Clarice de Azevedo; Li, Shundai; Lin, Andrew Z; Boutrot, Freddy; Grossmann, Guido; Zipfel, Cyril; Somerville, Shauna C

    2017-04-01

    The plant cell wall, often the site of initial encounters between plants and their microbial pathogens, is composed of a complex mixture of cellulose, hemicellulose, and pectin polysaccharides as well as proteins. The concept of damage-associated molecular patterns (DAMPs) was proposed to describe plant elicitors like oligogalacturonides (OGs), which can be derived by the breakdown of the pectin homogalacturon by pectinases. OGs act via many of the same signaling steps as pathogen- or microbe-associated molecular patterns (PAMPs) to elicit defenses and provide protection against pathogens. Given both the complexity of the plant cell wall and the fact that many pathogens secrete a wide range of cell wall-degrading enzymes, we reasoned that the breakdown products of other cell wall polymers may be similarly biologically active as elicitors and may help to reinforce the perception of danger by plant cells. Our results indicate that oligomers derived from cellulose are perceived as signal molecules in Arabidopsis (Arabidopsis thaliana), triggering a signaling cascade that shares some similarities to responses to well-known elicitors such as chitooligomers and OGs. However, in contrast to other known PAMPs/DAMPs, cellobiose stimulates neither detectable reactive oxygen species production nor callose deposition. Confirming our idea that both PAMPs and DAMPs are likely to cooccur at infection sites, cotreatments of cellobiose with flg22 or chitooligomers led to synergistic increases in gene expression. Thus, the perception of cellulose-derived oligomers may participate in cell wall integrity surveillance and represents an additional layer of signaling following plant cell wall breakdown during cell wall remodeling or pathogen attack.

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

    SciTech Connect

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

    2015-06-01

    We report the detection of SiS rotational lines in high-vibrational states as well as SiO and SiC{sub 2} lines in their ground vibrational state toward IRC+10216 during the Atacama Large Millimeter Array Cycle 0. The spatial distribution of these molecules shows compact emission for SiS and a more extended emission for SiO and SiC{sub 2} and also proves the existence of an increase in the SiC{sub 2} emission at the outer shells of the circumstellar envelope (CSE). We analyze the excitation conditions of the vibrationally excited SiS using the population diagram technique, and we use a large velocity gradient model to compare with the observations. We found moderate discrepancies between the observations and the models that could be explained if SiS lines detected are optically thick. Additionally, the line profiles of the detected rotational lines in the high-energy vibrational states show a decreasing linewidth with increasing energy levels. This may be evidence that these lines could be excited only in the inner shells, i.e., the densest and hottest, of the CSE of IRC+10216.

  12. The Synthesis of Organic Molecules of Intrinsic Microporosity Designed to Frustrate Efficient Molecular Packing.

    PubMed

    Taylor, Rupert G D; Bezzu, C Grazia; Carta, Mariolino; Msayib, Kadhum J; Walker, Jonathan; Short, Rhys; Kariuki, Benson M; McKeown, Neil B

    2016-02-12

    Efficient reactions between fluorine-functionalised biphenyl and terphenyl derivatives with catechol-functionalised terminal groups provide a route to large, discrete organic molecules of intrinsic microporosity (OMIMs) that provide porous solids solely by their inefficient packing. By altering the size and substituent bulk of the terminal groups, a number of soluble compounds with apparent BET surface areas in excess of 600 m(2)  g(-1) are produced. The efficiency of OMIM structural units for generating microporosity is in the order: propellane>triptycene>hexaphenylbenzene>spirobifluorene>naphthyl=phenyl. The introduction of bulky hydrocarbon substituents significantly enhances microporosity by further reducing packing efficiency. These results are consistent with findings from previously reported packing simulation studies. The introduction of methyl groups at the bridgehead position of triptycene units reduces intrinsic microporosity. This is presumably due to their internal position within the OMIM structure so that they occupy space, but unlike peripheral substituents they do not contribute to the generation of free volume by inefficient packing.

  13. SI-BEARING MOLECULES TOWARD IRC+10216: ALMA UNVEILS THE MOLECULAR ENVELOPE OF CWLEO.

    PubMed

    Prieto, L Velilla; Cernicharo, J; Quintana-Lacaci, G; Agúndez, M; Castro-Carrizo, A; Fonfŕia, J P; Marcelino, N; Zúñiga, J; Requena, A; Bastida, A; Lique, F; Guélin, M

    2015-06-01

    We report the detection of SiS rotational lines in high-vibrational states as well as SiO and SiC2 lines in their ground vibrational state toward IRC+10216 during the Atacama Large Millimeter Array Cycle 0. The spatial distribution of these molecules shows compact emission for SiS and a more extended emission for SiO and SiC2, and also proves the existence of an increase in the SiC2 emission at the outer shells of the circumstellar envelope. We analyze the excitation conditions of the vibrationally excited SiS using the population diagram technique, and we use a large velocity gradient model to compare with the observations. We found moderate discrepancies between the observations and the models that could be explained if SiS lines detected are optically thick. Additionally, the line profiles of the detected rotational lines in the high energy vibrational states show a decreasing linewidth with increasing energy levels. This may be evidence that these lines could be excited only in the inner shells, i.e., the densest and hottest, of the circumstellar envelope of IRC+10216.

  14. SI-BEARING MOLECULES TOWARD IRC+10216: ALMA UNVEILS THE MOLECULAR ENVELOPE OF CWLEO

    PubMed Central

    Prieto, L. Velilla; Cernicharo, J.; Quintana–Lacaci, G.; Agúndez, M.; Castro–Carrizo, A.; Fonfŕia, J. P.; Marcelino, N.; Zúñiga, J.; Requena, A.; Bastida, A.; Lique, F.; Guélin, M.

    2015-01-01

    We report the detection of SiS rotational lines in high-vibrational states as well as SiO and SiC2 lines in their ground vibrational state toward IRC+10216 during the Atacama Large Millimeter Array Cycle 0. The spatial distribution of these molecules shows compact emission for SiS and a more extended emission for SiO and SiC2, and also proves the existence of an increase in the SiC2 emission at the outer shells of the circumstellar envelope. We analyze the excitation conditions of the vibrationally excited SiS using the population diagram technique, and we use a large velocity gradient model to compare with the observations. We found moderate discrepancies between the observations and the models that could be explained if SiS lines detected are optically thick. Additionally, the line profiles of the detected rotational lines in the high energy vibrational states show a decreasing linewidth with increasing energy levels. This may be evidence that these lines could be excited only in the inner shells, i.e., the densest and hottest, of the circumstellar envelope of IRC+10216. PMID:26688711

  15. Identification and molecular characterization of begomovirus and associated satellite DNA molecules infecting Cyamopsis tetragonoloba.

    PubMed

    Kumar, J; Kumar, A; Roy, J K; Tuli, R; Khan, J A

    2010-08-01

    Monopartite begomoviruses comprise DNA-A as the main genome and associated satellite DNAs. Viral DNA extracted from guar (Cyamopsis tetragonoloba) showing leaf curl symptoms exhibited positive amplification of coat protein (CP) gene of DNA-A component, suggesting the presence of begomovirus. Full length DNA-A was amplified by primer pair re-designed from CP gene nucleotide sequence. The associated alphasatellite and betasatellite DNA molecules were amplified and sequenced, confirming the presence of monopartite begomovirus. Sequence comparisons showed 89% identity with other begomoviruses. The Neighbor-Joining tree based on full length DNA-A nucleotide sequence showed that the guar infecting begomovirus clustered separately from other known begomoviruses. The betasatellite shared a high (96%) nucleotide identity to Cotton leaf curl Multan betasatellites. The alphasatellite showed 91% nucleotide identity to alphasatellite associated with begomovirus infecting Okra. Recombination analyses showed three recombinant fragments in DNA-A, two in betasatellite, and four in alphasatellite. The results suggest that the begomovirus identified in this study was a new recombinant virus. Its name was proposed as Cyamopsis tetragonoloba leaf curl virus (CyTLCuV).

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

    NASA Technical Reports Server (NTRS)

    Ponnamperuma, C. A.

    1978-01-01

    Organic synthesis in the primitive solar system was simulated by Fischer Tropsch type experiments. Particular attention was given to the formation of lower molecular weight hydrocarbons. In a gas flow experiment, a gas mixture of H2 and CO was introduced into a heated reaction tube at a constant flow rate and passed through a catalyst (powdered Canyon Diablo). The products that emerged were directly analyzed by gas chromatography. The results of 21 runs under various gas mixing rations, reaction temperatures, and gas-catalyst contact times showed the predominance of the saturated hydrocarbon formation at C sub 4 and C sub 5 over the unsaturated ones. Saturate/unsaturate ratios were mostly less than 0.4 and none showed over 0.7.

  17. Molecular structure and vibrational analysis of 5-nitro-6-methyluracil molecule based on monomer, dimer and trimer calculations

    NASA Astrophysics Data System (ADS)

    Alam, M. J.; Bhat, S. A.; Ahmad, S.

    2016-05-01

    Molecular structure and vibrational spectra of 5-nitro-6-methyluracil molecule have been studied by the simulation of its monomer, dimer and trimer forms using DFT and MP2 methods with 6-311G(d,p) basis set. Anharmonic force field calculations have been carried out for the isolated monomer, while the calculations on dimer and trimer have been done in the harmonic approximation. An accurate numerical integration grid has been used for geometry optimization as well as frequency calculation. Anharmonic vibrational frequencies have been computed using VPT2 algorithm (Barone's method) as well as VSCF and VSCF-PT2 approaches. These methods yield results that are in remarkable agreement with the experiment. The coupling strengths between pair of modes have been also calculated using coupling integral based on 2MR-QFF approximation. The vibrational assignments have been made with the help of potential energy distribution values and animated modes.

  18. Features in the electronic structure and photoemission spectra of organic molecular semiconductors: The molecules of metal-phthalocyanines and PTCDA

    NASA Astrophysics Data System (ADS)

    Tikhonov, E. V.; Uspenskii, Yu. A.; Khokhlov, D. R.

    2013-09-01

    The role of many-electron effects in the formation of electronic quasiparticle spectra in organic molecular semiconductors (OMS) is analyzed. Many-body perturbation theory, ab initio calculations of metal phthalocyanines and PTCDA molecules, and experimental photoemission spectra are applied to this analysis. It is shown that density functional theory (DFT) poorly reproduces the electronic spectra of OMS. The use of a hybrid functional method (HFM) provides precise reproduction of both valence and conducting bands, while the HOMO-LUMO gap remains underestimated. The correct gap width is obtained in both DFT and HFM, when it is calculated through ionization and affinity energies. It is shown that such an approach gives a formula for gap correction due to electron correlations, which is close to an expression derived from the GW approximation.

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

    PubMed

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

    2001-05-01

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

  20. WebMTA: a web-interface for ab initio geometry optimization of large molecules using molecular tailoring approach.

    PubMed

    Kavathekar, Ritwik; Khire, Subodh; Ganesh, V; Rahalkar, Anuja P; Gadre, Shridhar R

    2009-05-01

    A web-interface for geometry optimization of large molecules using a linear scaling method, i.e., cardinality guided molecular tailoring approach (CG-MTA), is presented. CG-MTA is a cut-and-stitch, fragmentation-based method developed in our laboratory, for linear scaling of conventional ab initio techniques. This interface provides limited access to CG-MTA-enabled GAMESS. It can be used to obtain fragmentation schemes for a given spatially extended molecule depending on the maximum allowed fragment size and minimum cut radius values provided by the user. Currently, we support submission of single point or geometry optimization jobs at Hartree-Fock and density functional theory levels of theory for systems containing between 80 to 200 first row atoms and comprising up to 1000 basis functions. The graphical user interface is built using HTML and Python at the back end. The back end farms out the jobs on an in-house Linux-based cluster running on Pentium-4 Class or higher machines using an @Home-based parallelization scheme (http://chem.unipune.ernet.in/ approximately tcg/mtaweb/).

  1. Fe/C interactions during SWNT growth with C2 feedstock molecules: A quantum chemical molecular dynamics study.

    PubMed

    Zheng, Guishan; Irle, Stephan; Morokuma, Keiji

    2006-05-01

    We are presenting the first quantum chemical molecular dynamics (QM/MD) model simulations for iron catalyzed single-walled carbon nanotube (SWNT) growth based on the density functional tight binding (DFTB) quantum chemical potential. As model systems, open-ended (10,10) armchair tube fragments were selected with 0, 10, and 20 Fe atoms attached in 1,4-positions on the open rims, and ensembles of randomly oriented C2 molecules were included to simulate carbon plasma feedstock molecules. Isokinetic trajectories at 1500 K to 3000 K show that divalent Fe increases the number of coordination partners with carbon and/or Fe, depending on the Fe concentration. Fe/C interactions weaken the tube sidewall due to electron transfer from Fe into antibonding carbon orbitals, and C2 addition occurs mainly in an Fe-C2-Fe bridge addition mechanism, while growth of polyyne chains characteristic for high-temperature carbon systems is suppressed in the presence of Fe on the rims of the growing SWNT. Our findings are the first quantum chemical evidence for the importance of intermetallic interactions during SWNT growth.

  2. Fast and General Method To Predict the Physicochemical Properties of Druglike Molecules Using the Integral Equation Theory of Molecular Liquids.

    PubMed

    Palmer, David S; Mišin, Maksim; Fedorov, Maxim V; Llinas, Antonio

    2015-09-08

    We report a method to predict physicochemical properties of druglike molecules using a classical statistical mechanics based solvent model combined with machine learning. The RISM-MOL-INF method introduced here provides an accurate technique to characterize solvation and desolvation processes based on solute-solvent correlation functions computed by the 1D reference interaction site model of the integral equation theory of molecular liquids. These functions can be obtained in a matter of minutes for most small organic and druglike molecules using existing software (RISM-MOL) (Sergiievskyi, V. P.; Hackbusch, W.; Fedorov, M. V. J. Comput. Chem. 2011, 32, 1982-1992). Predictions of caco-2 cell permeability and hydration free energy obtained using the RISM-MOL-INF method are shown to be more accurate than the state-of-the-art tools for benchmark data sets. Due to the importance of solvation and desolvation effects in biological systems, it is anticipated that the RISM-MOL-INF approach will find many applications in biophysical and biomedical property prediction.

  3. Collectin liver 1 and collectin kidney 1 and other complement-associated pattern recognition molecules in systemic lupus erythematosus

    PubMed Central

    Troldborg, A; Thiel, S; Jensen, L; Hansen, S; Laska, M J; Deleuran, B; Jensenius, J C; Stengaard-Pedersen, K

    2015-01-01

    The objective of this study was to explore the involvement of collectin liver 1 (CL-L1) and collectin kidney 1 (CL-K1) and other pattern recognition molecules (PRMs) of the lectin pathway of the complement system in a cross-sectional cohort of systemic lupus erythematosus (SLE) patients. Concentrations in plasma of CL-L1, CL-K1, mannan-binding lectin (MBL), M-ficolin, H-ficolin and L-ficolin were determined in 58 patients with SLE and 65 healthy controls using time-resolved immunoflourometric assays. The SLE patients' demographic, diagnostic, clinical and biochemical data and collection of plasma samples were performed prospectively during 4 months. CL-L1, CL-K1 and M-ficolin plasma concentrations were lower in SLE patients than healthy controls (P-values < 0·001, 0·033 and < 0·001, respectively). H-ficolin concentration was higher in SLE patients (P < 0·0001). CL-L1 and CL-K1 plasma concentrations in the individuals correlated in both patients and controls. Patients with low complement component 3 (C3) demonstrated a negative correlation between C3 and CL-L1 and CL-K1 (P = 0·022 and 0.031, respectively). Patients positive for anti-dsDNA antibodies had lower levels of MBL in plasma than patients negative for anti-dsDNA antibodies (P = 0·02). In a cross-sectional cohort of SLE patients, we found differences in the plasma concentrations of CL-L1, CL-K1, M-ficolin and H-ficolin compared to a group of healthy controls. Alterations in plasma concentrations of the PRMs of the lectin pathway in SLE patients and associations to key elements of the disease support the hypothesis that the lectin pathway plays a role in the pathogenesis of SLE. PMID:26154564

  4. Molecular population genetics of the male and female mitochondrial DNA molecules of the California sea mussel, Mytilus californianus.

    PubMed

    Ort, Brian S; Pogson, Grant H

    2007-10-01

    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.

  5. Second virial coefficient of rod-shaped molecules and molecular dynamics simulations of the isotropic phase

    NASA Astrophysics Data System (ADS)

    Heyes, D. M.; Turner, P.; English, R. J.; Williams, R.; Brańka, A. C.

    2015-04-01

    The second virial coefficient, B2 is computed of linear rigid rods composed of m equally spaced sites interacting with sites on other rods via the hard-sphere or Weeks-Chandler-Andersen (WCA) pair potentials. The dependence of B2 on a wide range of separation distance between the sites L and m for both types of potential is computed. Molecular dynamics simulations were carried out of the thermodynamic, static, and percolation properties of the WCA rigid rods in the isotropic phase as a function of rod number density ρ . Simple scaling relationships are discovered between thermodynamic and other static properties as a function of ρ and m , which extend well into the semidilute density range. The percolation threshold distance (PTD) between the centers of mass of the rods complies well with a mean-field random orientation approximation from low density well into the semidilute regime. The corresponding site-site PTD proved more problematic to represent by simple functions, but at high rod density, scales better with the number of sites density rather than the rod number density.

  6. Second virial coefficient of rod-shaped molecules and molecular dynamics simulations of the isotropic phase.

    PubMed

    Heyes, D M; Turner, P; English, R J; Williams, R; Brańka, A C

    2015-04-01

    The second virial coefficient, B(2) is computed of linear rigid rods composed of m equally spaced sites interacting with sites on other rods via the hard-sphere or Weeks-Chandler-Andersen (WCA) pair potentials. The dependence of B(2) on a wide range of separation distance between the sites L and m for both types of potential is computed. Molecular dynamics simulations were carried out of the thermodynamic, static, and percolation properties of the WCA rigid rods in the isotropic phase as a function of rod number density ρ. Simple scaling relationships are discovered between thermodynamic and other static properties as a function of ρ and m, which extend well into the semidilute density range. The percolation threshold distance (PTD) between the centers of mass of the rods complies well with a mean-field random orientation approximation from low density well into the semidilute regime. The corresponding site-site PTD proved more problematic to represent by simple functions, but at high rod density, scales better with the number of sites density rather than the rod number density.

  7. Predicting Adsorption Affinities of Small Molecules on Carbon Nanotubes Using Molecular Dynamics Simulation.

    PubMed

    Comer, Jeffrey; Chen, Ran; Poblete, Horacio; Vergara-Jaque, Ariela; Riviere, Jim E

    2015-12-22

    Computational techniques have the potential to accelerate the design and optimization of nanomaterials for applications such as drug delivery and contaminant removal; however, the success of such techniques requires reliable models of nanomaterial surfaces as well as accurate descriptions of their interactions with relevant solutes. In the present work, we evaluate the ability of selected models of naked and hydroxylated carbon nanotubes to predict adsorption equilibrium constants for about 30 small aromatic compounds with a variety of functional groups. The equilibrium constants determined using molecular dynamics coupled with free-energy calculation techniques are directly compared to those derived from experimental measurements. The calculations are highly predictive of the relative adsorption affinities of the compounds, with excellent correlation (r ≥ 0.9) between calculated and measured values of the logarithm of the adsorption equilibrium constant. Moreover, the agreement in absolute terms is also reasonable, with average errors of less than one decade. We also explore possible effects of surface loading, although we demonstrate that they are negligible for the experimental conditions considered. Given the degree of reliability demonstrated, we move on to employing the in silico techniques in the design of nanomaterials, using the optimization of adsorption affinity for the herbacide atrazine as an example. Our simulations suggest that, compared to other modifications of graphenic carbon, polyvinylpyrrolidone conjugation gives the highest affinity for atrazine-substantially greater than that of graphenic carbon alone-and may be useful as a nanomaterial for delivery or sequestration of atrazine.

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

    The influence of atmospheric carbon dioxide (CO2) concentration on global warming is considered as one of the primary environmental issues of the past two decades. The main source of CO2 emission is human activity, such as the use of fossil fuels in transportation and industrial plants. Following the release of Kyoto Protocol in 1997, effective ways of controlling CO2 emissions received much attention. As a result, various materials such as activated carbon, zeolites, and carbon nanotubes (CNTs) were investigated for their CO2 adsorbing properties. CNTs were reported to have CO2 adsorption capability twice that of activated carbon, hence they received the most attention. In the current study, single walled carbon nanotubes (SWNTs) were used as one dimensional nanoporous materials and their CO2 adsorption capacity was analyzed with Molecular Dynamics simulations. Results indicated that SWNTs are excellent CO2 adsorbers and their effectiveness increase at low CO2 concentrations. In addition, we showed that by varying temperature, CO2 can be removed from the SWNTs, providing a simple method to reuse SWNTs.

  9. WaterLOGSY NMR experiments in conjunction with molecular-dynamics simulations identify immobilized water molecules that bridge peptide mimic MDWNMHAA to anticarbohydrate antibody SYA/J6.

    PubMed

    Szczepina, Monica G; Bleile, Dustin W; Müllegger, Johannes; Lewis, Andrew R; Pinto, B Mario

    2011-10-04

    X-ray crystallographic data of the carbohydrate mimic MDWNMHAA when bound to an anti-Shigella flexneri Y mAb SYA/J6 indicate the immobilization of water molecules, that is, the presence of "bound" waters, in the active site. Water Ligand Observed via Gradient Spectroscopy (WaterLOGSY) was used in conjunction with saturation transfer difference (STD)-NMR spectroscopy to probe the existence of immobilized water molecules in the complex of MDWNMHAA 1 bound to mAb SYA/J6. Molecular dynamics simulations using the ZymeCAD Molecular Dynamics platform were then used to specify the likely locations of these water molecules. Of note, those waters involved in providing complementarity between the peptide and mAb SYA/J6 remained throughout the course of the simulation. Together, the experimental and computational protocols have been used to identify the bound water molecules present in the antibody-peptide complex.

  10. Combined fragment molecular orbital cluster in molecule approach to massively parallel electron correlation calculations for large systems.

    PubMed

    Findlater, Alexander D; Zahariev, Federico; Gordon, Mark S

    2015-04-16

    The local correlation "cluster-in-molecule" (CIM) method is combined with the fragment molecular orbital (FMO) method, providing a flexible, massively parallel, and near-linear scaling approach to the calculation of electron correlation energies for large molecular systems. Although the computational scaling of the CIM algorithm is already formally linear, previous knowledge of the Hartree-Fock (HF) reference wave function and subsequent localized orbitals is required; therefore, extending the CIM method to arbitrarily large systems requires the aid of low-scaling/linear-scaling approaches to HF and orbital localization. Through fragmentation, the combined FMO-CIM method linearizes the scaling, with respect to system size, of the HF reference and orbital localization calculations, achieving near-linear scaling at both the reference and electron correlation levels. For the 20-residue alanine α helix, the preliminary implementation of the FMO-CIM method captures 99.6% of the MP2 correlation energy, requiring 21% of the MP2 wall time. The new method is also applied to solvated adamantine to illustrate the multilevel capability of the FMO-CIM method.

  11. Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques

    PubMed Central

    Macyszyn, Luke; Akbari, Hamed; Pisapia, Jared M.; Da, Xiao; Attiah, Mark; Pigrish, Vadim; Bi, Yingtao; Pal, Sharmistha; Davuluri, Ramana V.; Roccograndi, Laura; Dahmane, Nadia; Martinez-Lage, Maria; Biros, George; Wolf, Ronald L.; Bilello, Michel; O'Rourke, Donald M.; Davatzikos, Christos

    2016-01-01

    Background MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). Methods One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. Results Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. Conclusions By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood–brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients. PMID:26188015

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

    SciTech Connect

    Gasparotto, Piero; Ceriotti, Michele

    2014-11-07

    The concept of chemical bonding can ultimately be seen as a rationalization of the recurring structural patterns observed in molecules and solids. Chemical intuition is nothing but the ability to recognize and predict such patterns, and how they transform into one another. Here, we discuss how to use a computer to identify atomic patterns automatically, so as to provide an algorithmic definition of a bond based solely on structural information. We concentrate in particular on hydrogen bonding – a central concept to our understanding of the physical chemistry of water, biological systems, and many technologically important materials. Since the hydrogen bond is a somewhat fuzzy entity that covers a broad range of energies and distances, many different criteria have been proposed and used over the years, based either on sophisticate electronic structure calculations followed by an energy decomposition analysis, or on somewhat arbitrary choices of a range of structural parameters that is deemed to correspond to a hydrogen-bonded configuration. We introduce here a definition that is univocal, unbiased, and adaptive, based on our machine-learning analysis of an atomistic simulation. The strategy we propose could be easily adapted to similar scenarios, where one has to recognize or classify structural patterns in a material or chemical compound.

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

    PubMed

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

    2015-04-08

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

  14. Encapsulation and Diffraction-Pattern-Correction Methods to Reduce the Effect of Damage in X-Ray Diffraction Imaging of Single Biological Molecules

    SciTech Connect

    Hau-Riege, Stefan P.; London, Richard A.; Chapman, Henry N.; Szoke, Abraham; Timneanu, Nicusor

    2007-05-11

    Short and intense x-ray pulses may be used for atomic-resolution diffraction imaging of single biological molecules. Radiation damage and a low signal-to-noise ratio impose stringent pulse requirements. In this Letter, we describe methods for decreasing the damage and improving the signal by encapsulating the molecule in a sacrificial layer (tamper) that reduces atomic motion and by postprocessing the pulse-averaged diffraction pattern to correct for ionization damage. Simulations show that these methods greatly improve the image quality.

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

    PubMed Central

    Burghardt, Thomas P.

    2011-01-01

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

  16. Chemokine production and pattern recognition receptor (PRR) expression in whole blood stimulated with pathogen-associated molecular patterns (PAMPs).

    PubMed

    Møller, Anne-Sophie W; Ovstebø, Reidun; Haug, Kari Bente F; Joø, Gun Britt; Westvik, Ase-Brit; Kierulf, Peter

    2005-12-21

    Recognition of conserved bacterial structures called pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs), may lead to induction of a variety of "early immediate genes" such as chemokines. In the current study, we have in an ex vivo whole blood model studied the induction of the chemokines MIP-1alpha, MCP-1 and IL-8 by various PAMPs. The rate of appearance of Escherichia coli-Lipopolysaccharide (LPS) induced chemokines differed. The production of MIP-1alpha and IL-8 was after 1 h of stimulation significantly higher when compared to unstimulated whole blood, whereas MCP-1 was not significantly elevated until after 3 h. At peak levels the MIP-1alpha concentration induced by E. coli-LPS was 3-5-fold higher than MCP-1 and IL-8. By specific cell depletion, we demonstrated that all three chemokines were mainly produced by monocytes. However, the mRNA results showed that IL-8 was induced in both monocytes and granulocytes. The production of all three chemokines, induced by the E. coli-LPS and Neisseria meningitidis-LPS, was significantly inhibited by antibodies against CD14 and TLR4, implying these receptors to be of importance for the effects of LPS in whole blood. The chemokine production induced by lipoteichoic acid (LTA) and non-mannose-capped lipoarabinomannan (AraLAM) was, however, less efficiently blocked by antibodies against CD14 and TLR2. E. coli-LPS and LTA induced a dose-dependent increase of CD14, TLR2 and TLR4 expression on monocytes in whole blood. These data show that PAMPs may induce chemokine production in whole blood and that antibodies against PRRs inhibit the production to different extent.

  17. Prototropic tautomerism of 4-Methyl 1,2,4-Triazole-3-Thione molecule in solvent water medium: DFT and Car-Parrinello molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Dutta, Bipan; De, Rina; Chowdhury, Joydeep

    2015-12-01

    The ground state prototropic tautomerism of 4-Methyl 1,2,4-Triazole-3-Thione molecule in solvent water medium has been investigated with the aid of DFT and Car-Parrinello molecular dynamics (CPMD) simulation studies. The CPMD simulations envisage the possibility of proton transfer reactions of the molecule through the solvent water medium. Probable proton transfer pathways have been predicted from the DFT calculations which are substantiated by the natural bond orbital analyses. The evolution and breaking of the concerned bonds of the molecule for different proton transfer reaction pathways are also estimated.

  18. The toll of the gridiron: damage-associated molecular patterns and hypertension in American football

    PubMed Central

    McCarthy, Cameron G.; Webb, R. Clinton

    2016-01-01

    American football has unequivocally been linked to elevations in blood pressure and hypertension, especially in linemen. However, the mechanisms of this increase cannot be attributed solely to increased body weight and associated cardiometabolic risk factors (e.g.,dyslipidemia or hyperglycemia). Therefore, understanding the etiology of football-associated hypertension is essential for improving the quality of life in this mostly young population, as well as for lowering the potential for chronic disease in the future. We propose that inflammatogenic damage–associated molecular patterns (DAMPs) released into the circulation from football-induced musculoskeletal trauma activate pattern-recognition receptors of the innate immune system—specifically, high mobility group box 1 protein (HMGB1) and mitochondrial (mt)DNA which activate Toll-like receptor (TLR)4 and -9, respectively. Previously, we observed that circulating levels of these 2 DAMPs are increased in hypertension, and activation of TLR4 and -9 causes endothelial dysfunction and hypertension. Therefore, our novel hypothesis is that musculoskeletal injury from repeated hits in football players, particularly in linemen, leads to elevated circulating HMGB1 and mtDNA to activate TLRs on endothelial cells leading to impaired endothelium-dependent vasodilation, increased vascular tone, and hypertension.—McCarthy, C. G., Webb, R. C. The toll of the gridiron: damage-associated molecular patterns and hypertension in American football. PMID:26316270

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

    PubMed Central

    Levin, Michael

    2014-01-01

    In addition to biochemical gradients and transcriptional networks, cell behavior is regulated by endogenous bioelectrical cues originating in the activity of ion channels and pumps, operating in a wide variety of cell types. Instructive signals mediated by changes in resting potential control proliferation, differentiation, cell shape, and apoptosis of stem, progenitor, and somatic cells. Of importance, however, cells are regulated not only by their own Vmem but also by the Vmem of their neighbors, forming networks via electrical synapses known as gap junctions. Spatiotemporal changes in Vmem distribution among nonneural somatic tissues regulate pattern formation and serve as signals that trigger limb regeneration, induce eye formation, set polarity of whole-body anatomical axes, and orchestrate craniofacial patterning. New tools for tracking and functionally altering Vmem gradients in vivo have identified novel roles for bioelectrical signaling and revealed the molecular pathways by which Vmem changes are transduced into cascades of downstream gene expression. Because channels and gap junctions are gated posttranslationally, bioelectrical networks have their own characteristic dynamics that do not reduce to molecular profiling of channel expression (although they couple functionally to transcriptional networks). The recent data provide an exciting opportunity to crack the bioelectric code, and learn to program cellular activity at the level of organs, not only cell types. The understanding of how patterning information is encoded in bioelectrical networks, which may require concepts from computational neuroscience, will have transformative implications for embryogenesis, regeneration, cancer, and synthetic bioengineering. PMID:25425556

  20. Distinct carbohydrate and lipid-based molecular patterns within lipopolysaccharides from Burkholderia cepacia contribute to defense-associated differential gene expression in Arabidopsis thaliana.

    PubMed

    Madala, Ntakadzeni E; Molinaro, Antonio; Dubery, Ian A

    2012-02-01

    Lipopolysaccharides are structural components within the cell walls of Gram-negative bacteria. The LPSs as microbe-associated molecular pattern (MAMP) molecules can trigger defense-related responses involved in MAMP-triggered immunity and basal resistance in plants, presumably from an initial perception event. LPS from Burkholderia cepacia as well as two fragments, the glycolipid, lipid A and the polysaccharide (OPS-core) chain, were used to treat Arabidopsis thaliana seedlings to evaluate the eliciting activities of the individual LPS sub-domains by means of Annealing Control Primer-based Differential Display transcript profiling. Genes found to be up-regulated encode for proteins involved in signal perception and transduction, transcriptional regulation and defense - and stress responses. Furthermore, genes encoding proteins involved in chaperoning, secretion, protein-protein interactions and protein degradation were differentially expressed. It is concluded that intact LPS, as well as the two sub-components, induced the expression of a broad range of genes associated with perception and defense as well as metabolic reprogramming of cellular activities in support of immunity and basal resistance. Whilst the lipid A and OPS moieties were able to up-regulate sub-sets of defense-associated genes over the same spectrum of categories as intact LPS, the up-regulation observed with intact LPS was the more comprehensive, suggesting that the lipid A and glycan molecular patterns of the molecule act as partial agonists, but that the intact LPS structure is required for full agonist activity.

  1. Creating and Using a Consumer Chemical Molecular Graphics Database: The "Molecule of the Day" - A Great Way To Begin Your Lecture

    NASA Astrophysics Data System (ADS)

    Scharberg, Maureen A.; Cox, Oran E.; Barelli, Carl A.

    1997-07-01

    "The Molecule of the Day" consumer chemical database has been created to allow introductory chemistry students to explore molecular structures of chemicals in household products, and to provide opportunities in molecular modeling for undergraduate chemistry students. Before class begins, an overhead transparency is displayed which shows a three-dimensional molecular structure of a household chemical, and lists relevant features and uses of this chemical. Within answers to questionnaires, students have commented that this molecular graphics database has helped them to visually connect the microscopic structure of a molecule with its physical and chemical properties, as well as its uses in consumer products. It is anticipated that this database will be incorporated into a navigational software package such as Netscape.

  2. Combination of molecular dynamics method and 3D-RISM theory for conformational sampling of large flexible molecules in solution.

    PubMed

    Miyata, Tatsuhiko; Hirata, Fumio

    2008-04-30

    We have developed an algorithm for sampling the conformational space of large flexible molecules in solution, which combines the molecular dynamics (MD) method and the three-dimensional reference interaction site model (3D-RISM) theory. The solvent-induced force acting on solute atoms was evaluated as the gradient of the solvation free energy with respect to the solute-atom coordinates. To enhance the computation speed, we have applied a multiple timestep algorithm based on the RESPA (Reversible System Propagator Algorithm) to the combined MD/3D-RISM method. By virtue of the algorithm, one can choose a longer timestep for renewing the solvent-induced force compared with that of the conformational update. To illustrate the present MD/3D-RISM simulation, we applied the method to a model of acetylacetone in aqueous solution. The multiple timestep algorithm succeeded in enhancing the computation speed by 3.4 times for this model case. Acetylacetone possesses an intramolecular hydrogen-bonding capability between the hydroxyl group and the carbonyl oxygen atom, and the molecule is significantly stabilized due to this hydrogen bond, especially in gas phase. The intramolecular hydrogen bond was kept intact during almost entire course of the MD simulation in gas phase, while in the aqueous solutions the bond is disrupted in a significant number of conformations. This result qualitatively agrees with the behavior on a free energy barrier lying upon the process for rotating a torsional degree of freedom of the hydroxyl group, where it is significantly reduced in aqueous solution by a cancellation between the electrostatic interaction and the solvation free energy.

  3. The influence of temperature on the synthesis of molecules on icy grain mantles in dense molecular clouds

    NASA Astrophysics Data System (ADS)

    Garozzo, M.; La Rosa, L.; Kanuchova, Z.; Ioppolo, S.; Baratta, G. A.; Palumbo, M. E.; Strazzulla, G.

    2011-04-01

    Context. Infrared observations show the presence of icy mantles along the line of sight toward young stellar objects (YSOs), where a temperature gradient is expected and indirectly observed. In this environment, icy mantles are affected by ion and UV irradiation. Laboratory experiments show that molecules are formed after irradiation of icy mixtures. However, most of the experiments done so far have been performed in the temperatures range of 10-20 K. Aims: To extend previous work we irradiated some icy mixtures, namely H2O:CO=10:1, H2O:CH4=4:1, and H2O:CO2=3:1 at two different temperatures (12 K and 40 or 60 K) to study the effects of temperature on the synthesis of molecules and the decrease in their parent species after ion irradiation. Methods: The experiments were performed in a high-vacuum chamber (P < 10-7 mbar), where icy samples were irradiated with 30 keV He+ ions and analyzed by a FTIR spectrophotometer. Infrared spectra of the samples were recorded after various steps of irradiation. Results: We found that the temperature affects the behavior of the volatile species (i.e., CO and CH4) during irradiation. As a consequence, the production of molecular species is generally more prevalent at 12 K than at either 40 or 60 K, while the decrease in their parent volatile species is faster at high temperature. Conclusions: We conclude that the behavior of each species depends on the value of its sublimation temperature with respect to the temperature of the sample. If this latter is higher than the sublimation temperature of a given species, then the effects of thermal desorption compete with those due to irradiation.

  4. Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster

    PubMed Central

    Srinivasan, Naren; Gordon, Oliver; Ahrens, Susan; Franz, Anna; Deddouche, Safia; Chakravarty, Probir; Phillips, David; Yunus, Ali A; Rosen, Michael K; Valente, Rita S; Teixeira, Luis; Thompson, Barry; Dionne, Marc S; Wood, Will; Reis e Sousa, Caetano

    2016-01-01

    Damage-associated molecular patterns (DAMPs) are molecules released by dead cells that trigger sterile inflammation and, in vertebrates, adaptive immunity. Actin is a DAMP detected in mammals by the receptor, DNGR-1, expressed by dendritic cells (DCs). DNGR-1 is phosphorylated by Src-family kinases and recruits the tyrosine kinase Syk to promote DC cross-presentation of dead cell-associated antigens. Here we report that actin is also a DAMP in invertebrates that lack DCs and adaptive immunity. Administration of actin to Drosophila melanogaster triggers a response characterised by selective induction of STAT target genes in the fat body through the cytokine Upd3 and its JAK/STAT-coupled receptor, Domeless. Notably, this response requires signalling via Shark, the Drosophila orthologue of Syk, and Src42A, a Drosophila Src-family kinase, and is dependent on Nox activity. Thus, extracellular actin detection via a Src-family kinase-dependent cascade is an ancient means of detecting cell injury that precedes the evolution of adaptive immunity. DOI: http://dx.doi.org/10.7554/eLife.19662.001 PMID:27871362

  5. Mitochondrial Damage-Associated Molecular Patterns (MTDs) Are Released during Hepatic Ischemia Reperfusion and Induce Inflammatory Responses.

    PubMed

    Hu, Qianni; Wood, Caroline Ruth; Cimen, Sanem; Venkatachalam, Ananda Baskaran; Alwayn, Ian Patrick Joseph

    2015-01-01

    Ischemia / reperfusion injury (IRI) during the course of liver transplantation enhances the immunogenicity of allografts and thus impacts overall graft outcome. This sterile inflammatory insult is known to activate innate immunity and propagate organ damage through the recognition of damage-associate molecular pattern (DAMP) molecules. The purpose of the present study was to investigate the role of mitochondrial DAMPs (MTDs) in the pathogenesis of hepatic IRI. Using in vitro models we observed that levels of MTDs were significantly higher in both transplantation-associated and warm IR, and that co-culture of MTDs with human and rat hepatocytes significantly increased cell death. MTDs were also released in an in vivo rat model of hepatic IRI and associated with increased secretion of inflammatory cytokines (TNF-α, IL-6, and IL-10) and increased liver injury compared to the sham group. Our results suggest that hepatic IR results in a significant increase of MTDs both in vitro and in vivo suggesting that MTDs may serve as a novel marker in hepatic IRI. Co-culture of MTDs with hepatocytes showed a decrease in cell viability in a concentration dependent manner, which indicates that MTDs is a toxic mediator participating in the pathogenesis of liver IR injury.

  6. A molecular dynamics study of phobic/philic nano-patterning on pool boiling heat transfer

    NASA Astrophysics Data System (ADS)

    Diaz, Ricardo; Guo, Zhixiong

    2017-03-01

    Molecular dynamics (MD) simulations were employed to investigate the pool boiling heat transfer of a liquid argon thin film on a flat, horizontal copper wall structured with vertical nanoscale pillars. The efficacy of phobic/philic nano-patterning for enhancing boiling heat transfer was scrutinized. Both nucleate and explosive boiling modes were considered. An error analysis demonstrated that the typical 2.5σ cutoff in MD simulations could under-predict heat flux by about 8.7 %, and 6σ cutoff was chosen here in order to maintain high accuracy. A new coordination number criterion was also introduced to better quantify evaporation characteristics. Results indicate that the argon-phobic/philic patterning tends to either have no effect, or decrease overall boiling heat flux, while the argon-philic nano-pillar/argon-philic wall shows the best heat transfer performance.

  7. Molecular phylogenetics reveals a pattern of biome conservatism in New World anchovies (family Engraulidae).

    PubMed

    Bloom, Devin D; Lovejoy, N R

    2012-04-01

    Evolutionary transitions between marine and freshwater biomes are relatively rare events, yielding a widespread pattern of biome conservatism among aquatic organisms. We investigated biome transitions in anchovies (Engraulidae), a globally distributed clade of economically important fishes. Most anchovy species are near-shore marine fishes, but several exclusively freshwater species are known from tropical rivers of South America and were previously thought to be the product of six or more independent freshwater invasions. We generated a comprehensive molecular phylogeny for Engraulidae, including representatives from 15 of 17 currently recognized genera. Our data support previous hypotheses of higher-level relationships within Engraulidae, but show that most New World genera are not monophyletic and in need of revision. Ancestral character reconstruction reveals that New World freshwater anchovies are the product of a single marine to freshwater transition, supporting a pattern of biome conservatism. We argue that competition is the principal mechanism that regulates aquatic biome transitions on a continental scale.

  8. Intramolecular vibrations and noise effects on pattern formation in a molecular helix.

    PubMed

    Fouda, H P Ekobena; Tabi, C B; Mohamadou, A; Kofané, T C

    2011-09-21

    Modulational instability in a biexciton molecular chain is addressed. We show that the model can be reduced to a set of three coupled equations: two nonlinear Schrödinger equations and a Boussinesq equation. The linear stability analysis of continuous wave solutions of the coupled systems is performed and the growth rate of instability is found numerically. Simulations of the full discrete systems reveal some behaviors of modulational instability, since wave patterns are observed for the excitons and the phonon spectrum. We also take the effect of thermal fluctuations into account and we numerically study both the stability and the instability of the plane waves under 300 K. The plane wave is found to be stable under modulation, but displays a gradual increase of the wave amplitudes. Under modulation, the same behaviors are observed and wave patterns are found to resist thermal fluctuations, which is in agreement with earlier research on localized structure stability under thermal noise.

  9. Redox-derived damage-associated molecular patterns: Ligand function of lipid peroxidation adducts.

    PubMed

    Uchida, Koji

    2013-02-12

    Endogenous electrophiles, such as α,β-unsaturated aldehydes and ketones generated during lipid peroxidation, exhibit a facile reactivity with proteins, generating a variety of intra and intermolecular covalent adducts. It has been postulated that these host-derived, modified proteins with electrophiles, which constitute the products of diverse classes of oxidative reactions, represent damage-associated molecular patterns (DAMPs). The DAMPs, that occur in vivo, can be a ligand of multiple proteins, which in turn, may lead to the profound innate and adaptive immune responses and mediate homeostatic functions consequent to inflammation and cell death.

  10. Natural antibodies as a sensor of electronegative damage-associated molecular patterns (DAMPs).

    PubMed

    Uchida, Koji

    2014-07-01

    Natural antibodies (Abs), predominantly IgMs, play an important function in the host response to the recognition of endogenous danger signals called damage-associated molecular patterns (DAMPs). Many of the natural IgM Abs also show several different antigenic cross-reactivities toward covalently modified proteins, such as oxidized low-density lipoproteins and advanced glycation end products. Of interest, a recent study has shown that these DAMPs have several physicochemical characteristics that differ from native proteins, such as an increased negative charge due to modification of the lysine residues. This finding may provide a mechanistic insight into the multispecificity of the natural Abs.

  11. Thermal modulation of the monomer/excimer fluorescence for bispyrene molecules through the gel solution transition of an organogel: A thermo-driven molecular fluorescence switch

    NASA Astrophysics Data System (ADS)

    Wang, Cheng; Wang, Zhuo; Zhang, Deqing; Zhu, Daoben

    2006-09-01

    Reversible modulation of the monomer/excimer emission was observed for bispyrene molecules 1 and 2 through the solution-gel phase transition (with gelator 3 as the LMWG) and accordingly a thermo-driven molecular fluorescence switch can be established.

  12. Molecular and structural characterization of dissolved organic matter from the deep ocean by FTICR-MS, including hydrophilic nitrogenous organic molecules

    USGS Publications Warehouse

    Reemtsma, T.; These, A.; Linscheid, M.; Leenheer, J.; Spitzy, A.

    2008-01-01

    Dissolved organic matter isolated from the deep Atlantic Ocean and fractionated into a so-called hydrophobic (HPO) fraction and a very hydrophilic (HPI) fraction was analyzed for the first time by Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) to resolve the molecular species, to determine their exact masses, and to calculate their molecular formulas. The elemental composition of about 300 molecules was identified. Those in the HPO fraction (14C age of 5100 year) are very similar to much younger freshwater fulvic acids, but less aromatic and more oxygenated molecules are more frequent. This trend continues toward the HPI fraction and may indicate biotic and abiotic aging processes that this material experienced since its primary production thousands of years ago. In the HPI fraction series of nitrogenous molecules containing one, two, or three nitrogens were identified by FTICR-MS. Product ion spectra of the nitrogenous molecules suggest that the nitrogen atoms in these molecules are included in the (alicyclic) backbone of these molecules, possibly in reduced form. These mass spectrometric data suggest that a large set of stable fulvic acids is ubiquitous in all aquatic compartments. Although sources may differ, their actual composition and structure appears to be quite similar and largely independent from their source, because they are the remainder of intensive oxidative degradation processes. ?? 2008 American Chemical Society.

  13. Activation of coherent lattice phonon following ultrafast molecular spin-state photo-switching: A molecule-to-lattice energy transfer

    PubMed Central

    Marino, A.; Cammarata, M.; Matar, S. F.; Létard, J.-F.; Chastanet, G.; Chollet, M.; Glownia, J. M.; Lemke, H. T.; Collet, E.

    2015-01-01

    We combine ultrafast optical spectroscopy with femtosecond X-ray absorption to study the photo-switching dynamics of the [Fe(PM-AzA)2(NCS)2] spin-crossover molecular solid. The light-induced excited spin-state trapping process switches the molecules from low spin to high spin (HS) states on the sub-picosecond timescale. The change of the electronic state (<50 fs) induces a structural reorganization of the molecule within 160 fs. This transformation is accompanied by coherent molecular vibrations in the HS potential and especially a rapidly damped Fe-ligand breathing mode. The time-resolved studies evidence a delayed activation of coherent optical phonons of the lattice surrounding the photoexcited molecules. PMID:26798836

  14. Theoretical study of quantum molecular reaction dynamics and of the effects of intense laser radiation on a diatomic molecule

    SciTech Connect

    Dardi, P.S.

    1984-11-01

    Within the very broad field of molecular dynamics, we have concentrated on two simple yet important systems. The systems are simple enough so that they are adequately described with a single Born-Oppenheimer potential energy surface and that the dynamics can be calculated accurately. They are important because they give insight into solving more complicated systems. First we discuss H + H/sub 2/ reactive scattering. We present an exact formalism for atom-diatom reactive scattering which avoids the problem of finding a coordinate system appropriate for both reactants and products. We present computational results for collinear H + H/sub 2/ reactive scattering which agree very well with previous calculations. We also present a coupled channel distorted wave Born approximation for atom-diatom reactive scattering which we show is a first order approximation to our exact formalism. We present coupled channel DWBA results for three dimensional H + H/sub 2/ reactive scattering. The second system is an isolated HF molecule in an intense laser field. Using classical trajectories and quantum dynamics, we look at energy absorbed and transition probabilities as a function of the laser pulse time and also averaged over the pulse time. Calculations are performed for both rotating and nonrotating HF. We examine one and two photon absorption about the fundamental frequency, multiphoton absorption, and overtone absorption. 127 references, 31 figures, 12 tables.

  15. Structure and energetics of model amphiphilic molecules at the water liquid-vapor interface - A molecular dynamics study

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew; Benjamin, Ilan

    1993-01-01

    A molecular dynamics study of adsorption of p-n-pentylphenol at infinite dilution at the water liquid-vapor interface is reported. The calculated free energy of adsorption is -8.8 +/- 0.7 kcal/mol, in good agreement with the experimental value of -7.3 kcal/mol. The transition between the interfacial region and the bulk solution is sharp and well-defined by energetic, conformational, and orientational criteria. At the water surface, the phenol head group is mostly immersed in aqueous solvent. The most frequent orientation of the hydrocarbon tail is parallel to the interface, due to dispersion interactions with the water surface. This arrangement of the phenol ring and the alkyl chain requires that the chain exhibits a kink. As the polar head group is being moved into the solvent, the chain length increases and the tail becomes increasingly aligned toward the surface normal, such that the nonpolar part of the molecule exposed to water is minimized. The same effect was achieved when phenol was replaced by a more polar head group, phenolate.

  16. Highly consistent patterns for inherited human diseases at the molecular level.

    PubMed

    López-Bigas, Núria; Blencowe, Benjamin J; Ouzounis, Christos A

    2006-02-01

    Over 1600 mammalian genes are known to cause an inherited disorder, when subjected to one or more mutations. These disease genes represent a unique resource for the identification and quantification of relationships between phenotypic attributes of a disease and the molecular features of the associated disease genes, including their ascribed annotated functional classes and expression patterns. Such analyses can provide a more global perspective and a deeper understanding of the probable causes underlying human hereditary diseases. In this perspective and critical view of disease genomics, we present a comparative analysis of genes reported to cause inherited diseases in humans in terms of their causative effects on physiology, their genetics and inheritance modes, the functional processes they are involved in and their expression profiles across a wide spectrum of tissues. Our analysis reveals that there are more extensive correlations between these attributes of genetic disease genes than previously appreciated. For instance, the functional pattern of genes causing dominant and recessive diseases is markedly different. Also, the function of the genes and their expression correlate with the type of disease they cause when mutated. The results further indicate that a comparative genomics approach for the analysis of genes linked to human genetic diseases will facilitate the elucidation of the underlying molecular and cellular mechanisms.

  17. Predicting molecular formulas of fragment ions with isotope patterns in tandem mass spectra.

    PubMed

    Zhang, Jingfen; Gao, Wen; Cai, Jinjin; He, Simin; Zeng, Rong; Chen, Runsheng

    2005-01-01

    A number of different approaches have been proposed to predict elemental component formulas (or molecular formulas) of molecular ions in low and medium resolution mass spectra. Most of them rely on isotope patterns, enumerate all possible formulas for an ion, and exclude certain formulas violating chemical constraints. However, these methods cannot be well generalized to the component prediction of fragment ions in tandem mass spectra. In this paper, a new method, FFP (Fragment ion Formula Prediction), is presented to predict elemental component formulas of fragment ions. In the FFP method, the prediction of the best formulas is converted into the minimization of the distance between theoretical and observed isotope patterns. And, then, a novel local search model is proposed to generate a set of candidate formulas efficiently. After the search, FFP applies a new multiconstraint filtering to exclude as many invalid and improbable formulas as possible. FFP is experimentally compared with the previous enumeration methods, and shown to outperform them significantly. The results of this paper can help to improve the reliability of de novo in the identification of peptide sequences.

  18. Nuclear Architecture and Patterns of Molecular Evolution Are Correlated in the Ciliate Chilodonella uncinata

    PubMed Central

    Maurer-Alcalá, Xyrus X.; Katz, Laura A.

    2016-01-01

    The relationship between nuclear architecture and patterns of molecular evolution in lineages across the eukaryotic tree of life is not well understood, partly because molecular evolution is traditionally explored as changes in base pairs along a linear sequence without considering the context of nuclear position of chromosomes. The ciliate Chilodonella uncinata is an ideal system to address the relationship between nuclear architecture and patterns of molecular evolution as the somatic macronucleus of this ciliate is composed of a peripheral DNA-rich area (orthomere) and a DNA-poor central region (paramere) to form a “heteromeric” macronucleus. Moreover, because the somatic chromosomes of C. uncinata are highly processed into “gene-sized” chromosomes (i.e., nanochromosomes), we can assess fine-scale relationships between location and sequence evolution. By combining fluorescence microscopy and analyses of transcriptome data from C. uncinata, we find that highly expressed genes have the greatest codon usage bias and are enriched in DNA-poor regions. In contrast, genes with less biased sequences tend to be concentrated in DNA abundant areas, at least during vegetative growth. Our analyses are consistent with recent work in plants and animals where nuclear architecture plays a role in gene expression. At the same time, the unusual localization of nanochromosomes suggests that the highly structured nucleus in C. uncinata may create a “gene bank” that facilitates rapid changes in expression of genes required only in specific life history stages. By using “nonmodel” organisms like C. uncinata, we can explore the universality of eukaryotic features while also providing examples of novel properties (i.e., the presence of a gene bank) that build from these features. PMID:27189988

  19. Combining geometric morphometrics, molecular phylogeny, and micropaleontology to assess evolutionary patterns in Mallomonas (Synurophyceae: Heterokontophyta).

    PubMed

    Siver, P A; Wolfe, A P; Rohlf, F J; Shin, W; Jo, B Y

    2013-03-01

    Synurophytes, also known as scaled chrysophytes, are ecologically important algae that produce an array of siliceous structures upon which their taxonomy is based. Despite occupying a key position within the photosynthetic heterokonts, the evolutionary history of synurophytes remains poorly constrained. Here, modern and Middle Eocene siliceous scales of the morphotaxon Mallomonas insignis are used as a model to investigate synurophyte evolutionary patterns. Structural details of scale morphology were examined comparatively with scanning electron microscopy and scored for geometric morphometric analyses to assess the stability of shape characters. Although consistent size differences exist (modern scales are larger than Eocene counterparts), the populations cannot be differentiated on the basis of shape or microstructural detail, implying considerable evolutionary stasis in scale morphology. A time-calibrated relaxed molecular clock analysis using a three-gene concatenated data set (27 strains) suggests that the M. insignis lineage predates the available fossil record, having diverged from closest congeneric taxa in the Cretaceous (≥94 Ma). However, the molecular analysis also implies that considerable genetic variability is present within several morphotaxa of Mallomonas, implying that substantial genetic variability has arisen despite the retention of uniform scale morphologies, and resulting in the widespread occurrence of cryptic taxa. Results from the synurophyte lineage are consistent with the notion of protracted ghost ranges (>10 Ma) implied by the molecular phylogenies of other algal groups, together pointing to the paucity of the fossil record of these organisms on these timescales.

  20. Rapid screening for citrus canker resistance employing pathogen-associated molecular pattern-triggered immunity responses

    PubMed Central

    Pitino, Marco; Armstrong, Cheryl M; Duan, Yongping

    2015-01-01

    Citrus canker, caused by the bacterial pathogen Xanthomonas citri ssp. citri (Xcc), has been attributed to millions of dollars in loss or damage to commercial citrus crops in subtropical production areas of the world. Since identification of resistant plants is one of the most effective methods of disease management, the ability to screen for resistant seedlings plays a key role in the production of a long-term solution to canker. Here, an inverse correlation between reactive oxygen species (ROS) production by the plant and the ability of Xcc to grow and form lesions on infected plants is reported. Based on this information, a novel screening method that can rapidly identify citrus seedlings that are less susceptible to early infection by Xcc was devised by measuring ROS accumulation triggered by a 22-amino acid sequence of the conserved N-terminal part of flagellin (flg22) from X. citri ssp. citri (Xcc-flg22). In addition to limiting disease symptoms, ROS production was also correlated with the expression of basal defense-related genes such as the pattern recognition receptors LRR8 and FLS2, the leucine-rich repeat receptor-like protein RLP12, and the defense-related gene PR1, indicating an important role for pathogen-associated molecular pattern-triggered immunity (PTI) in determining resistance to citrus canker. Moreover, the differential expression patterns observed amongst the citrus seedlings demonstrated the existence of genetic variations in the PTI response among citrus species/varieties. PMID:26504581

  1. Molecular phylogenetic relationships reveal contrasting evolutionary patterns in Gorgoniidae (Octocorallia) in the Eastern Pacific.

    PubMed

    Soler-Hurtado, M M; López-González, P J; Machordom, A

    2017-03-24

    The description and delimitation of species in an evolutionary framework is essential for understanding patterns of biodiversity and distribution, and in the assessment of conservation strategies for natural resources. This study seeks to clarify the evolutionary history and genetic variation within and between closely related octocoral species that are fundamental to benthic marine ecosystems for harbouring a high diversity of associated fauna. For our study system, we focused on members of the Gorgoniidae family in the Eastern Pacific, particularly of the Ecuadorian littoral, a less studied marine ecosystem. According to our results, the diagnosis of the genus Pacifigorgia is here amended to include species previously considered in the genus Leptogorgia. The genera Leptogorgia and Eugorgia are included within a single clade, and neither are recovered as monophyletic. In this case, according to the priority rule of the International Code of Zoological Nomenclature (ICZN), our proposal is to include the species considered in these two genera in Leptogorgia. In addition, we found evidence of interesting speciation patterns: morphological differentiation with no apparent genetic differentiation (in Pacifigorgia), and inconsistencies between mitochondrial and nuclear data that suggest a hybridisation phenomenon (in Leptogorgia). In the first case, recent radiation, ancient hybridisation, sympatric speciation, and in the second, reticulate evolution may have contributed to the evolutionary history of the studied taxa. Therefore, incongruences observed between morphological and molecular evidences in these octocorals, and in corals in general, may reveal the types of events/patterns that have influenced their evolution.

  2. Phases, line tension and pattern formation in molecularly thin films at the air-water interface

    NASA Astrophysics Data System (ADS)

    Mandal, Pritam

    A Langmuir film, which is a molecularly thin insoluble film on a liquid substrate, is one practical realization of a quasi-two dimensional matter. The major advantages of this system for the study of phase separation and phase co-existence are (a) it allows accurate control of the components and molecular area of the film and (b) it can be studied by various methods that require very flat films. Phase separation in molecularly thin films plays an important role in a range of systems from biomembranes to biosensors. For example, phase-separated lipid nano-domains in biomembranes are thought to play crucial roles in membrane function. I use Brewster Angel Microscopy (BAM) coupled with Fluorescence Microscopy (FM) and static Light Scattering Microscopy (LSM) to image phases and patterns within Langmuir films. The three microscopic techniques --- BAM, FM and LSM --- are complimentary to each other, providing distinct sets of information. They allow direct comparison with literature results in lipid systems. I have quantitatively validated the use of detailed hydrodynamic simulations to determine line tension in monolayers. Line tension decreases as temperature rises. This decrease gives us information on the entropy associated with the line, and thus about line structure. I carefully consider the thermodynamics of line energy and entropy to make this connection. In the longer run, LSM will be exploited to give us further information about line structure. I have also extended the technique by testing it on domains within the curved surface of a bilayer vesicle. I also note that in the same way that the presence of surface-active agents, known as surfactants, affects surface energy, the addiction of line active agents alters the inter-phase line energy. Thus my results set to stage to systematically study the influence of line active agents ---'linactants' --- on the inter-phase line energy. Hierarchal self-assembled chiral patterns were observed as a function of

  3. Aggregation of dipolar molecules in SiO2 hybrid organic-inorganic films: use of silver nanoparticles as inhibitors of molecular aggregation

    NASA Astrophysics Data System (ADS)

    Franco, Alfredo; García-Macedo, Jorge; Brusatin, Giovanna; Guglielmi, Massimo

    2013-04-01

    The technological implementation of hybrid organic-inorganic materials in second order nonlinear optical photonic devices depends strongly on the ability of the host matrixes to contain high loads of dipolar molecules without aggregation. Some organic molecules are often used to diminish the attracting interactions between dipolar molecules in such kind of materials, but their efficiency as inhibitors of molecular aggregation is limited by their polarizability. In this work, we report the use of silver nanoparticles as inhibitors of molecular aggregation in hybrid organic-inorganic films doped with dipolar molecules. The large polarizability of the silver nanoparticles makes them ideal moieties for the inhibition of the electrostatic interactions between dipolar nonlinear optical molecules. The average size of the silver nanoparticles in this work was 70.5 nm in diameter, they were synthesized using silver nitrate (AgNO3) as precursor and aminoethylaminopropyltrimethoxysilane as reducing agent. These nanoparticles were immersed in SiO2 hybrid organic-inorganic sol-gel films doped with dipolar chromophores to study their effect as inhibitors of dipolar chromophores aggregation. The presence of the silver nanoparticles in the solid films was confirmed by transmission electronic microscopy and UV-Visible spectroscopy. UV-Visible spectroscopy was also used to monitor the dipolar chromophores aggregation in the SiO2 films. We found that, at room temperature, silver nanoparticles are good inhibiting chromophores aggregation in comparison with the performance of organic inhibitors.

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

    PubMed Central

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

    2017-01-01

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

  5. Use of Mo/ller-Plesset perturbation theory in molecular calculations: Spectroscopic constants of first row diatomic molecules

    SciTech Connect

    Dunning, T.H. , Jr.; Peterson, K.A.

    1998-03-01

    The convergence of Mo/ller{endash}Plesset perturbation expansions (MP2{endash}MP4/MP5) for the spectroscopic constants of a selected set of diatomic molecules (BH, CH, HF, N{sub 2}, CO, and F{sub 2}) has been investigated. It was found that the second-order perturbation contributions to the spectroscopic constants are strongly dependent on basis set, more so for HF and CO than for BH. The MP5 contributions for HF were essentially zero for the cc-pVDZ basis set, but increased significantly with basis set illustrating the difficulty of using small basis sets as benchmarks for correlated calculations. The convergence behavior of the {ital exact} Mo/ller{endash}Plesset perturbation expansions were investigated using estimates of the {ital complete basis set limits} obtained using large correlation consistent basis sets. For BH and CH, the perturbation expansions of the spectroscopic constants converge monotonically toward the experimental values, while for HF, N{sub 2}, CO, and F{sub 2}, the expansions oscillate about the experimental values. The perturbation expansions are, in general, only slowly converging and, for HF, N{sub 2}, CO, and F{sub 2}, appear to be far from convergence at MP4. In fact, for HF, N{sub 2}, and CO, the errors in the calculated spectroscopic constants for the MP4 method are {ital larger} than those for the MP2 method (the only exception is D{sub e}). The current study, combined with other recent studies, raises serious doubts about the use of Mo/ller{endash}Plesset perturbation theory to describe electron correlation effects in atomic and molecular calculations. {copyright} {ital 1998 American Institute of Physics.}

  6. Molecular Characterization and Clinical Implications of Spindle Cells in Nasopharyngeal Carcinoma: A Novel Molecule-Morphology Model of Tumor Progression Proposed

    PubMed Central

    Luo, Weiren; Yao, Kaitai

    2013-01-01

    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

  7. Nanopolaritonics with a continuum of molecules: simulations of molecular-induced selectivity in plasmonics transport through a continuous Y-shape.

    PubMed

    Neuhauser, Daniel

    2011-11-28

    Using the recent NF (near-field) formulation for electrodynamics on the nanoscale, we simulate transport in a Y-shape gold nanostructure in the presence of 2-level molecules. NF is shown to be easily integrated with the Liouville equation, producing a simple and efficient nanopolaritons (plasmons-excitons) solver, with a large time step. Two cases are considered: coating of the gold structure with molecular layers thinner than the structure, and filling space with aligned molecules. In both cases significant effects on the radiation transport are obtained even for low molecular densities. At low densities the effects are primarily an overall reduction of the plasmonics peak, but at higher densities there is a significant selectivity control by the molecules. A redshift is predicted, especially for the space-filling case. The combined nanopolariton shows qualitative hybridization, and the spectral peaks separate with increasing coupling, i.e., with increasing molecular densities. The results open the way to "control of light by light," i.e., controlling plasmonic light transport by inducing a change in the direction of the guiding molecular dipoles through radiation or other means.

  8. Intensity enhancement and selective detection of proximate solvent molecules by molecular near-field effect in resonance hyper-Raman scattering

    NASA Astrophysics Data System (ADS)

    Shimada, Rintaro; Kano, Hideaki; Hamaguchi, Hiro-o.

    2008-07-01

    A new molecular phenomenon associated with resonance hyper-Raman (HR) scattering in solution has been discovered. Resonance HR spectra of all-trans-β-carotene and all-trans-lycopene in various solvents exhibited several extra bands that were not assignable to the solute but were unequivocally assigned to the solvents. Neat solvents did not show detectable HR signals under the same experimental conditions. Similar experiments with all-trans-retinal did not exhibit such enhancement either. All-trans-β-carotene and all-trans-lycopene have thus been shown to induce enhanced HR scattering of solvent molecules through a novel molecular effect that is not associated with all-trans-retinal. We call this new effect the "molecular near-field effect." In order to explain this newly found effect, an extended vibronic theory of resonance HR scattering is developed where the vibronic interaction including the proximate solvent molecule (intermolecular vibronic coupling) is explicitly introduced in the solute hyperpolarizability tensor. The potential of "molecular near-field HR spectroscopy," which selectively detects molecules existing in the close vicinity of a HR probe in complex chemical or biological systems, is discussed.

  9. Probing the interaction mechanism of small molecule inhibitors with matriptase based on molecular dynamics simulation and free energy calculations.

    PubMed

    Sun, Dong-Ru; Zheng, Qing-Chuan; Zhang, Hong-Xing

    2017-03-01

    Matriptase is a serine protease associated with a wide variety of human tumors and carcinoma progression. Up to now, many promising anti-cancer drugs have been developed. However, the detailed structure-function relationship between inhibitors and matriptase remains elusive. In this work, molecular dynamics simulation and binding free energy studies were performed to investigate the biochemistry behaviors of two class inhibitors binding to matriptase. The binding free energies predicted by MM/GBSA methods are in good agreement with the experimental bioactivities, and the analysis of the individual energy terms suggests that the van der Waals interaction is the major driving force for ligand binding. The key residues responsible for achieving strong binding have been identified by the MM/GBSA free energy decomposition analysis. Especially, Trp215 and Phe99 had an important impact on active site architecture and ligand binding. The results clearly identify the two class inhibitors exist different binding modes. Through summarizing the two different modes, we have mastered some important and favorable interaction patterns between matriptase and inhibitors. Our findings would be helpful for understanding the interaction mechanism between the inhibitor and matriptase and afford important guidance for the rational design of potent matriptase inhibitors.

  10. Metalorganic molecular beam epitaxy growth of GaAs on patterned GaAs substrates

    NASA Astrophysics Data System (ADS)

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

    1994-03-01

    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.

  11. Characterizing the Immune-Eliciting Activity of Putative Microbe-Associated Molecular Patterns in Tomato.

    PubMed

    Clarke, Christopher R; Vinatzer, Boris A

    2017-01-01

    Detection of conserved microbe-associated molecular patterns (MAMPs), such as bacterial flagellin, is the first line of active defense in plants against pathogenic invaders. Successful pathogens must subvert this immune response to grow to high population density and cause disease. Flagellin from the bacterial pathogen Pseudomonas was the first identified bacterial MAMP and many species across the plant kingdom have sensitive perception systems for detecting the 22-amino acid epitope known as flg22. Tomato and several other solanaceous plants are also able to independently detect a second epitope of flagellin known as flgII-28. This chapter details four experimental protocols to identify and confirm the immune response-eliciting activity of flagellin and putative MAMPs with focus on the Pseudomonas-tomato pathosystem.

  12. Damage-associated molecular patterns in cancer: A double-edged sword

    PubMed Central

    Hernandez, Celine; Huebener, Peter; Schwabe, Robert F.

    2016-01-01

    Damage-associated molecular patterns (DAMPs) are released in response to cell death and stress, and are potent triggers of sterile inflammation. Recent evidence suggests that DAMPs may also have a key role in the development of cancer as well as in the host response to cytotoxic anti-tumor therapy. As such, DAMPs may exert protective functions by alerting the immune system to the presence of dying tumor cells, thereby triggering immunogenic tumor cell death. On the other hand, cell death and release of DAMPs may also trigger chronic inflammation and thereby promote the development or progression of tumors. Here, we will review the contribution of candidate DAMPs and their receptors and discuss the evidence for DAMPs as tumor-promoting and anti-tumor effectors as well as unsolved questions such as DAMP release from non-tumor cells as well as the existence of tumor-specific DAMPs. PMID:27086930

  13. Biochips - Can molecules compute?

    NASA Astrophysics Data System (ADS)

    Tucker, J. B.

    1984-02-01

    In recent years the possibility has been considered to build 'biochip' computers, in which the silicon transistors of present machines would be replaced by large organic molecules or genetically engineered proteins. Two major advantages of such biochips over current devices would be related to vastly increased densities of computing elements, and entirely new styles of data processing, suited to such high-level tasks as pattern recognition and context-dependent analysis. The limitations of the semiconductor chip with respect to the density of elementary units due to size considerations and heat development could be overcome by making use of molecular switches. Attention is given to soliton switching, soliton logic, bulk molecular devices, analog biochips, 'intelligent' switches based on the employment of enzymes, robot vision, questions of biochip fabrication, protein engineering, and a strategy for the development of biochips.

  14. Electronic states of pyrene single crystal and of its single molecule inserted in a molecular vessel of cyclodextrin

    NASA Astrophysics Data System (ADS)

    Takahashi, Nobuaki; Gombojav, Bold; Yoshinari, Takehisa; Nagasaka, Shin-ichiro; Takahashi, Yoshio; Yamamoto, Aishi; Goto, Takenari; Kasuya, Atsuo

    2004-10-01

    Highly purified single crystals of pyrene were made by a gas phase crystal growth method from 180 times of zone-refined pyrene. The absorption spectra of the single crystal have been transformed from the reflection spectra between 2.5 and 6.5 eV at 2, 77 K and room temperature. The dry powder of β-cyclodextrin including pyrene single molecule were prepared in vacuum to investigate the electronic states of the isolated molecule. The absorption spectra of the single molecule show similar spectra to those of the single crystal. The pyrene molecule keeps its electronic character even in the single crystal.

  15. Selective IR multiphoton dissociation of molecules in a pulsed gas-dynamically cooled molecular flow interacting with a solid surface as an alternative to low-energy methods of molecular laser isotope separation

    SciTech Connect

    Makarov, G N; Petin, A N

    2016-03-31

    We report the results of studies on the isotope-selective infrared multiphoton dissociation (IR MFD) of SF{sub 6} and CF{sub 3}I molecules in a pulsed, gas-dynamically cooled molecular flow interacting with a solid surface. The productivity of this method in the conditions of a specific experiment (by the example of SF{sub 6} molecules) is evaluated. A number of low-energy methods of molecular laser isotope separation based on the use of infrared lasers for selective excitation of molecules are analysed and their productivity is estimated. The methods are compared with those of selective dissociation of molecules in the flow interacting with a surface. The advantages of this method compared to the low-energy methods of molecular laser isotope separation and the IR MPD method in the unperturbed jets and flows are shown. It is concluded that this method could be a promising alternative to the low-energy methods of molecular laser isotope separation. (laser separation of isotopes)

  16. Investigation of multi-state charge-storage properties of redox-active organic molecules in silicon-molecular hybrid devices for DRAM and Flash applications

    NASA Astrophysics Data System (ADS)

    Gowda, Srivardhan Shivappa

    Molecular electronics has recently spawned a considerable amount of interest with several molecules possessing charge-conduction and charge-storage properties proposed for use in electronic devices. Hybrid silicon-molecular technology has the promise of augmenting the current silicon technology and provide for a transitional path to future molecule-only technology. The focus of this dissertation work has been on developing a class of hybrid silicon-molecular electronic devices for DRAM and Flash memory applications utilizing redox-active molecules. This work exploits the ability of molecules to store charges with single-electron precision at room temperature. The hybrid devices are fabricated by forming self-assembled monolayers of redox-active molecules on Si and oxide (SiO2 and HfO2) surfaces via formation of covalent linkages. The molecules possess discrete quantum states from which electrons can tunnel to the Si substrate at discrete applied voltages (oxidation process, cell write), leaving behind a positively charged layer of molecules. The reduction (erase) process, which is the process of electrons tunneling back from Si to the molecules, neutralizes the positively charged molecular monolayer. Hybrid silicon-molecular capacitor test structures were electrically characterized with an electrolyte gate using cyclic voltammetry (CyV) and impedance spectroscopy (CV) techniques. The redox voltages, kinetics (write/erase speeds) and charge-retention characteristics were found to be strongly dependent on the Si doping type and densities, and ambient light. It was also determined that the redox energy states in the molecules communicate with the valence band of the Si substrate. This allows tuning of write and read states by modulating minority carriers in n- and p-Si substrates. Ultra-thin dielectric tunnel barriers (SiO2, HfO2) were placed between the molecules and the Si substrate to augment charge-retention for Flash memory applications. The redox response was

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

    PubMed

    Zhou, Han; Bent, Stacey F

    2011-02-01

    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.

  18. Rates and patterns of molecular evolution in freshwater versus terrestrial insects.

    PubMed

    Mitterboeck, T Fatima; Fu, Jinzhong; Adamowicz, Sarah J

    2016-11-01

    Insect lineages have crossed between terrestrial and aquatic habitats many times, for both immature and adult life stages. We explore patterns in molecular evolutionary rates between 42 sister pairs of related terrestrial and freshwater insect clades using publicly available protein-coding DNA sequence data from the orders Coleoptera, Diptera, Lepidoptera, Hemiptera, Mecoptera, Trichoptera, and Neuroptera. We furthermore test for habitat-associated convergent molecular evolution in the cytochrome c oxidase subunit I (COI) gene in general and at a particular amino acid site previously reported to exhibit habitat-linked convergence within an aquatic beetle group. While ratios of nonsynonymous-to-synonymous substitutions across available loci were higher in terrestrial than freshwater-associated taxa in 26 of 42 lineage pairs, a stronger trend was observed (20 of 31, pbinomial = 0.15, pWilcoxon = 0.017) when examining only terrestrial-aquatic pairs including fully aquatic taxa. We did not observe any widespread changes at particular amino acid sites in COI associated with habitat shifts, although there may be general differences in selection regime linked to habitat.

  19. Evolutionary animation: How do molecular phylogenies compare to Mayr's reconstruction of speciation patterns in the sea?

    PubMed Central

    Palumbi, Stephen R.; Lessios, H. A.

    2005-01-01

    Ernst Mayr used the geography of closely related species in various stages of increasing divergence to “animate” the process of geographic, or allopatric, speciation. This approach was applied to a wide set of taxa, and a seminal paper by Mayr used it to explore speciation patterns in tropical sea urchins. Since then, taxonomic information in several of these genera has been augmented by detailed molecular phylogenies. We compare Mayr's animation with the phylogenies of eight sea urchin genera placed by Mayr into four speciation groups. True to Mayr's predictions, early-stage genera have on average lower species divergence and more polytypic species than genera in later stages. For six of these genera, we also have information about the evolution of the gamete recognition protein bindin, which is critical to reproductive isolation. These comparisons show that later-stage genera with many sympatric species tend to be those with rapid bindin evolution. By contrast, early-stage genera with few sympatric species are not necessarily earlier in the divergence process; they happen to be those with slow rates of bindin evolution. These results show that the rate of speciation in sea urchins does not only depend on the steady accumulation of genome divergence over time, but also on the rate of evolution of gamete recognition proteins. The animation method used by Mayr is generally supported by molecular phylogenies. However, the existence of multiple rates in the acquisition of reproductive isolation complicates placement of different genera in an evolutionary series. PMID:15851681

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

    PubMed

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

    2015-11-01

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

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

    PubMed

    Goto, Ryutaro; Okamoto, Tomoko; Ishikawa, Hiroshi; Hamamura, Yoichi; Kato, Makoto

    2013-01-01

    The Echiura, or spoon worms, are a group of marine worms, most of which live in burrows in soft sediments. This annelid-like animal group was once considered as a separate phylum because of the absence of segmentation, although recent molecular analyses have placed it within the annelids. In this study, we elucidate the interfamily relationships of echiuran worms and their evolutionary pattern of feeding mode and sexual dimorphism, by performing molecular phylogenetic analyses using four genes (18S, 28S, H3, and COI) of representatives of all extant echiuran families. Our results suggest that Echiura is monophyletic and comprises two unexpected groups: [Echiuridae+Urechidae+Thalassematidae] and [Bonelliidae+Ikedidae]. This grouping agrees with the presence/absence of marked sexual dimorphism involving dwarf males and the paired/non-paired configuration of the gonoducts (genital sacs). Furthermore, the data supports the sister group relationship of Echiuridae and Urechidae. These two families share the character of having anal chaetae rings around the posterior trunk as a synapomorphy. The analyses also suggest that deposit feeding is a basal feeding mode in echiurans and that filter feeding originated once in the common ancestor of Urechidae. Overall, our results contradict the currently accepted order-level classification, especially in that Echiuroinea is polyphyletic, and provide novel insights into the evolution of echiuran worms.

  2. Molecular seasonality of Giardia lamblia in a cohort of Egyptian children: a circannual pattern.

    PubMed

    Ismail, Mousa A M; El-Akkad, Dina M H; Rizk, Enas M A; El-Askary, Hala M; El-Badry, Ayman A

    2016-11-01

    Giardia lamblia (G. lamblia) is the most worldwide prevailing intestinal parasite, notorious for its broad range of seasonal and age-related prevalence. The potentially lethal nature of giardiasis makes it essential that the seasonality, the groups at risk, and other potential risk factors are identified. The present molecular epidemiological study was designed to determine the genetic diversity of G. lamblia infection, taking into account seasonal peaks, age distribution, and associated symptoms in a cohort of Egyptian diarrheic patients. Stool samples were collected from 1187 diarrheic patients attending outpatient clinics of Cairo University hospitals, of all age groups over a 12-month period. The patients were examined microscopically for fecal G. lamblia cysts, and/or trophozoites, and for copro-DNA detection using nested polymerase chain reaction (nPCR) assays targeting beta giardin gene. PCR-positive samples were characterized molecularly by nPCR restriction fragment length polymorphism (RFLP) to determine Giardia assemblages. The findings revealed circannual prevalence of Giardia, with a seasonal pattern peaking in mid-summer and late winter, with the summer peak preceded by a peak in temperature. Infection was prevailing in 224 (18.9 %) cases, mainly assemblage B (81.2 %) followed by assemblage A (18.8 %). There were statistically significant associations between the detection of Giardia and flatulence, persistent diarrhea, vomiting, and abdominal pain, while gender and intermittent diarrhea showed no association. The pre-school age group was the most vulnerable. This is the first study of molecular characterization of Giardia to determine its circannual prevalence in Egypt, a finding which carries promising potential for the diagnosis, treatment, and elimination of the disease.

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

    PubMed

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

    2011-11-01

    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.

  4. Molecular Analysis of Geographic Patterns of Eukaryotic Diversity in Antarctic Soils

    PubMed Central

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

    2004-01-01

    We describe the application of molecular biological techniques to estimate eukaryotic diversity (primarily fungi, algae, and protists) in Antarctic soils across a latitudinal and environmental gradient between approximately 60 and 87°S. The data were used to (i) test the hypothesis that diversity would decrease with increasing southerly latitude and environmental severity, as is generally claimed for “higher” faunal and plant groups, and (ii) investigate the level of endemicity displayed in different taxonomic groups. Only limited support was obtained for a systematic decrease in diversity with latitude, and then only at the level of a gross comparison between maritime (Antarctic Peninsula/Scotia Arc) and continental Antarctic sites. While the most southerly continental Antarctic site was three to four times less diverse than all maritime sites, there was no evidence for a trend of decreasing diversity across the entire range of the maritime Antarctic (60 to 72°S). Rather, we found the reverse pattern, with highest diversity at sites on Alexander Island (ca. 72°S), at the southern limit of the maritime Antarctic. The very limited overlap found between the eukaryotic biota of the different study sites, combined with their generally low relatedness to existing sequence databases, indicates a high level of Antarctic site isolation and possibly endemicity, a pattern not consistent with similar studies on other continents. PMID:15466539

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

    PubMed Central

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

    2014-01-01

    Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior–posterior axis. Hox proteins exert their function by interaction with TALE transcription factors. Hox and TALE members are also present in some but not all non-bilaterian phyla, raising the question of how Hox–TALE interactions evolved to provide positional information. By using proteins from unicellular and multicellular lineages, we showed that these networks emerged from an ancestral generic motif present in Hox and other related protein families. Interestingly, Hox-TALE networks experienced additional and extensive molecular innovations that were likely crucial for differentiating Hox functions along body plans. Together our results highlight how homeobox gene families evolved during eukaryote evolution to eventually constitute a major patterning system in Eumetazoans. DOI: http://dx.doi.org/10.7554/eLife.01939.001 PMID:24642410

  6. The toll of the gridiron: damage-associated molecular patterns and hypertension in American football.

    PubMed

    McCarthy, Cameron G; Webb, R Clinton

    2016-01-01

    American football has unequivocally been linked to elevations in blood pressure and hypertension, especially in linemen. However, the mechanisms of this increase cannot be attributed solely to increased body weight and associated cardiometabolic risk factors (e.g.,dyslipidemia or hyperglycemia). Therefore, understanding the etiology of football-associated hypertension is essential for improving the quality of life in this mostly young population, as well as for lowering the potential for chronic disease in the future. We propose that inflammatogenic damage-associated molecular patterns (DAMPs) released into the circulation from football-induced musculoskeletal trauma activate pattern-recognition receptors of the innate immune system-specifically, high mobility group box 1 protein (HMGB1) and mitochondrial (mt)DNA which activate Toll-like receptor (TLR)4 and -9, respectively. Previously, we observed that circulating levels of these 2 DAMPs are increased in hypertension, and activation of TLR4 and -9 causes endothelial dysfunction and hypertension. Therefore, our novel hypothesis is that musculoskeletal injury from repeated hits in football players, particularly in linemen, leads to elevated circulating HMGB1 and mtDNA to activate TLRs on endothelial cells leading to impaired endothelium-dependent vasodilation, increased vascular tone, and hypertension.

  7. Pro-Coagulant Endothelial Dysfunction Results from EHEC Shiga Toxins and Host Damage-Associated Molecular Patterns

    PubMed Central

    Mayer, Chad L.; Parello, Caitlin S. L.; Lee, Benjamin C.; Itagaki, Kiyoshi; Kurosawa, Shinichiro; Stearns-Kurosawa, Deborah J.

    2015-01-01

    Hemolytic uremic syndrome (HUS) from enterohemorrhagic Escherichia coli infection is a leading cause of kidney failure in otherwise healthy U.S. children. The bacterial Shiga toxins (Stx) induce the characteristic coagulopathy of HUS, but the damage to toxin-receptor expressing cells and organ injury due to ischemia likely also releases inflammatory damage-associated molecular patterns (DAMPs), which may exacerbate injury along with the toxins. To examine this, human aortic and renal glomerular cell anti-coagulant and barrier functions were studied after in vitro challenge with Stx1, Stx2, and DAMPs. There was significant loss of surface anti-coagulant protein C pathway molecules, increased expression of pro-thrombotic PAR1 and reduced protein C activation capability by 15–27%. Histones nearly completely prevented the activated protein C protection of endothelial cells from thrombin-induced permeability. In mice, lethal Stx2 challenge elevated plasma HMGB1 (day 2, 321 ± 118%; p < 0.01) and extracellular histones (day 3, 158 ± 62%; p < 0.01). Mice colonized with Stx2-expressing Citrobacter rodentium developed increased HMGB1 (day 5, 155 ± 55%; p < 0.01) and histones (day 3, 378 ± 188%; p < 0.01). Anti-histone antibody reduced both DAMPs to baseline, but was not sufficient to improve survival outcome or kidney function. Together, these data suggest a potential role Stx to produce DAMPs, and DAMPs to produce endothelial injury and a pro-thrombotic environment. PMID:25904918

  8. Bacterial regulatory networks—from self-organizing molecules to cell shape and patterns in bacterial communities

    PubMed Central

    Hengge, Regine; Sourjik, Victor

    2013-01-01

    The ESF–EMBO Conference on ‘Bacterial Networks' (BacNet13) was held in March 2013, in Pultusk, Poland. It brought together 164 molecular microbiologists, bacterial systems biologists and synthetic biologists to discuss the architecture, function and dynamics of regulatory networks in bacteria. PMID:23846311

  9. Covalent Chemistry beyond Molecules.

    PubMed

    Jiang, Juncong; Zhao, Yingbo; Yaghi, Omar M

    2016-03-16

    Linking molecular building units by covalent bonds to make crystalline extended structures has given rise to metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), thus bringing the precision and versatility of covalent chemistry beyond discrete molecules to extended structures. The key advance in this regard has been the development of strategies to overcome the "crystallization problem", which is usually encountered when attempting to link molecular building units into covalent solids. Currently, numerous MOFs and COFs are made as crystalline materials in which the large size of the constituent units provides for open frameworks. The molecular units thus reticulated become part of a new environment where they have (a) lower degrees of freedom because they are fixed into position within the framework; (b) well-defined spatial arrangements where their properties are influenced by the intricacies of the pores; and (c) ordered patterns onto which functional groups can be covalently attached to produce chemical complexity. The notion of covalent chemistry beyond molecules is further strengthened by the fact that covalent reactions can be carried out on such frameworks, with full retention of their crystallinity and porosity. MOFs are exemplars of how this chemistry has led to porosity with designed metrics and functionality, chemically-rich sequences of information within their frameworks, and well-defined mesoscopic constructs in which nanoMOFs enclose inorganic nanocrystals and give them new levels of spatial definition, stability, and functionality.

  10. Molecular characterization and expression patterns of myogenin in compensatory growth of Megalobrama amblycephala.

    PubMed

    Zhu, Kecheng; Chen, Liping; Zhao, Jinkun; Wang, Huijuan; Wang, Weimin; Li, Zhong; Wang, Huanling

    2014-04-01

    Myogenin (myog) is a muscle-specific basic helix-loop-helix (bHLH) transcription factor that plays an essential role in regulating skeletal muscle development and growth. To investigate molecular characterization of myog and the effect of starvation/refeeding on the gene expression, we isolated the myog cDNA sequence and analyzed the expression patterns using quantitative real-time polymerase chain reaction in Megalobrama amblycephala. Sequence analysis indicated that M. amblycephala myog shared an analogous structure with the highly conserved His/Cys-rich, bHLH and C-terminal helix III domains with other vertebrates. Sequence alignment and phylogenetic tree showed that M. amblycephala myog had the highest identity with the homologues of Ctenopharyngodon idella and Cyprinus carpio. Spatio-temporal expression patterns revealed that myog mRNA levels at the segmentation period and 12 h post-hatching (hph) were significantly higher than at other development stages (P<0.05). Furthermore, the highest myog expression level was predominantly observed in white muscle compared with the other types of muscle. Fish body weight continuously decreased during 21-day starvation and then significantly increased after 7days of refeeding and reached the similar level to the control at 21days of refeeding, indicating that the pattern of complete compensatory growth possibly occurred in M. amblycephala; meanwhile, the relative somatic growth rate after refeeding was also dramatically higher than the control group. In addition, the myog expression decreased during 21days of starvation and then exhibited a strong rebound effect after 7days of refeeding and subsequently declined gradually to the control level by 21days of refeeding.

  11. Delta-like 1 homolog in Capra hircus: molecular characteristics, expression pattern and phylogeny.

    PubMed

    Hu, Jiangtao; Zhao, Wei; Zhan, Siyuan; Xiao, Ping; Zhou, Jingxuan; Wang, Linjie; Li, Li; Zhang, Hongping; Niu, Lili; Zhong, Tao

    2016-06-01

    To research the molecular characteristics, expression pattern and phylogeny of the Delta-like 1 homolog gene (Dlk1) in goats. Dlk1 transcripts were identified in the Jianyang Da'er goats by reverse-transcription polymerase chain reaction (RT-PCR). Phylogenetic trees were constructed by Bayesian inference and neighbor-joining methods. Quantitative real-time PCR (qPCR), western blotting and in situ hybridization were performed to analyze the expression pattern of Dlk1. Five alternatively transcripts were identified in different tissues and designated as Dlk1-AS1, 2, 3, 4 and 5. Compared with the normal transcript Dlk1-AS1, Dlk1-AS4 and Dlk1-AS5 retained the identical open reading frame (ORF) and encoded proteins with truncated epidermal-growth-factor like repeats of 121 and 83 amino acids, respectively. Using the Bayesian inference method, the consensus phylogenetic tree indicated that caprine Dlk1 had a closer relationship with bovine Dlk1 than with Dlk1 from pigs, humans and mice. qPCR revealed high expression levels of Dlk1 in the kidney (P < 0.01). However, mRNA and protein levels presented an inconsistent correlation, possibly because of post-transcriptional regulation. RNA in situ hybridization indicated that Dlk1 mRNA was localized in the interlobular bile duct and alongside the hepatocyte nuclei, in the epithelial cells of proximal and distal convoluted tubules and in the connective region between the mesothelium and myocardium in the heart. The Dlk1 gene in goats produces alternatively spliced transcripts, with specific expression and cellular localization patterns. These findings would lay the foundation for further study.

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

    PubMed

    Cossairt, Brandi M; Cummins, Christopher C

    2009-10-28

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

  13. Joint Measurements of Terahertz Wave Generation and High-Harmonic Generation from Aligned Nitrogen Molecules Reveal Angle-Resolved Molecular Structures

    NASA Astrophysics Data System (ADS)

    Huang, Yindong; Meng, Chao; Wang, Xiaowei; Lü, Zhihui; Zhang, Dongwen; Chen, Wenbo; Zhao, Jing; Yuan, Jianmin; Zhao, Zengxiu

    2015-09-01

    We report the synchronized measurements of terahertz wave generation and high-harmonic generation from aligned nitrogen molecules in dual-color laser fields. Both yields are found to be alignment dependent, showing the importance of molecular structures in the generation processes. By calibrating the angular ionization rates with the terahertz yields, we present a new way of retrieving the angular differential photoionization cross section (PICS) from the harmonic signals which avoids specific model calculations or separate measurements of the alignment-dependent ionization rates. The measured PICS is found to be consistent with theoretical predications, although some discrepancies exist. This all-optical method provides a new alternative for investigating molecular structures.

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  16. Multiscale modeling of cellular epigenetic states: stochasticity in molecular networks, chromatin folding in cell nuclei, and tissue pattern formation of cells

    PubMed Central

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

    2016-01-01

    Genome sequences provide the overall genetic blueprint of cells, but cells possessing the same genome can exhibit diverse phenotypes. There is a multitude of mechanisms controlling cellular epigenetic states and that dictate the behavior of cells. Among these, networks of interacting molecules, often under stochastic control, depending on the specific wirings of molecular components and the physiological conditions, can have a different landscape of cellular states. In addition, chromosome folding in three-dimensional space provides another important control mechanism for selective activation and repression of gene expression. Fully differentiated cells with different properties grow, divide, and interact through mechanical forces and communicate through signal transduction, resulting in the formation of complex tissue patterns. Developing quantitative models to study these multi-scale phenomena and to identify opportunities for improving human health requires development of theoretical models, algorithms, and computational tools. Here we review recent progress made in these important directions. PMID:27480462

  17. Positron-attachment to small molecules: Vibrational enhancement of positron affinities with configuration interaction level of multi-component molecular orbital approach

    SciTech Connect

    Tachikawa, Masanori

    2015-12-31

    To theoretically demonstrate the binding of a positron to small polarized molecules, we have calculated the vibrational averaged positron affinity (PA) values along the local vibrational contribution with the configuration interaction level of multi-component molecular orbital method. This method can take the electron-positron correlation contribution into account through single electronic - single positronic excitation configurations. The PA values are enhanced by including the local vibrational contribution from vertical PA values due to the anharmonicity of the potential.

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

    PubMed

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

    2013-01-01

    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.

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

    PubMed Central

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

    2007-01-01

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

  20. 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)

    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

    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.

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

    SciTech Connect

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

    2008-08-01

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

  2. Molecular modeling of the inhibition of protein-protein interactions with small molecules: The IL2-IL2Rα case

    NASA Astrophysics Data System (ADS)

    Pieraccini, Stefano; De Gonda, Riccardo; Sironi, Maurizio

    2011-12-01

    Developing drug like molecules targeting protein-protein interactions is one of the main goals of current medicinal chemistry. To drive the design process it is fundamental to locate those sites on the protein-protein contact surface that are more critical for protein binding, which are the most eligible targets to affect the protein complex formation. In this work we show how computational alanine scanning can be used to identify such critical sites and evaluate their interactions with small molecules designed to inhibit the complex formation. Complex of protein IL2 with IL2Rα and with some small molecule inhibitors are used as an example.

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

    PubMed

    Matta, Chérif F

    2010-04-30

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

  4. Pattern of Local Recurrence and Distant Metastasis in Breast Cancer By Molecular Subtype

    PubMed Central

    Wu, Xingrao; Baig, Ayesha; Kasymjanova, Goulnar; Kafi, Kamran; Holcroft, Christina; Mekouar, Hind; Carbonneau, Annie; Bahoric, Boris; Sultanem, Khalil

    2016-01-01

    Background and Purpose: No longer considered a single disease entity, breast cancer is being classified into several distinct molecular subtypes based on gene expression profiling. These subtypes appear to carry prognostic implications and have the potential to be incorporated into treatment decisions. In this study, we evaluated patterns of local recurrence (LR), distant metastasis (DM), and association of survival with molecular subtype in breast cancer patients in the post–adjuvant radiotherapy setting. Material and Methods: The medical records of 1,088 consecutive, non-metastatic breast cancer patients treated at a single institution between 2004 and 2012 were reviewed. Estrogen/progesterone receptors (ER/PR) and human epidermal growth factor receptor-2 (HER2) enrichment were evaluated by immunohistochemistry. Patients were categorized into one of four subtypes: luminal-A (LA; ER/PR+, HER2-, Grade 1-2), luminal-B (LB; ER/PR+, HER2-, Grade > 2), HER2 over-expression (HER2; ER/PR-, HER2+), and triple negative (TN; ER/PR-, HER2-).  Results: The median follow-up time was 6.9 years. During the follow-up, 16% (174/1,088) of patients failed initial treatment and developed either LR (48) or DM (126). The prevalence of LR was the highest in TN (12%) and the lowest in LA (2%). Breast or chest wall relapse was the most frequent site (≈80%) of recurrence in LA, LB, and HER2 subtypes, whereas the regional lymph nodes and chest wall were the common sites of relapse in the TN group (50.0%). DM rates were 6.4% in LA, 12.1% in LB, 19.2% in HER2, and 27.4% in TN subgroups. Five-year survival rates were 84%, 83%, 84%, and 77% in the LA, LB, HER2 and TN subgroups, respectively. There was a statistically significant association between survival and molecular subtypes in an univariate analysis. In the adjusted multivariate analysis, the following variables were independent prognostic factors for survival: T stage, N stage, and molecular subtype. Conclusions: Of the four

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

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

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

  6. Radiationless relaxation in “large” molecules: Experimental evidence for preparation of true molecular eigenstates and Born-Oppenheimer states by a coherent light source

    PubMed Central

    Zewail, A. H.; Orlowski, T. E.; Jones, K. E.

    1977-01-01

    Photon absorption and emission by molecules that undergo radiationless transitions are examined using the single modes of lasers having well-defined coherence properties. Contrary to the usual beliefs, where it is assumed that the molecule is prepared in a Born-Oppenheimer singlet state and then “crosses-over” to other states (vibrationally “hot” singlets and/or triplets), it is shown experimentally that the true eigenstates of the molecule can be prepared, even in “large” molecules, if the laser correlation time is relatively long and the molecular relaxation is made slow. On the other hand, lasers with short (psec) correlation time have yielded effectively the singlet Born-Oppenheimer state, which has a much shorter lifetime than the true eigenstates. Effects of magnetic fields and temperature are also reported. The former changes the amount of mixing amongst the Born-Oppenheimer states. The latter, on the other hand, swings the molecule from being “small” (i.e., sparse vibronic structure with long lifetimes) to being “large” (i.e., dense statistical distribution of levels) since the relaxation between levels is very effective at high temperatures. Finally, the results of this work show that the words fluorescence and phosphorescence in their strict meaning are misleading if the true eigenstates, which may contain both singlet and triplet character, are prepared. Images PMID:16578747

  7. A Bayesian approach on molecules and behavior: reconsidering phylogenetic and evolutionary patterns of the Salamandridae with emphasis on Triturus newts.

    PubMed

    Steinfartz, Sebastian; Vicario, Saverio; Arntzen, J W; Caccone, Adalgisa

    2007-03-15

    The monophyly of European newts of the genus Triturus within the family Salamandridae has for decades rested on presumably homologous behavioral and morphological characters. Molecular data challenge this hypothesis, but the phylogenetic position of Triturus within the Salamandridae has not yet been convincingly resolved. We addressed this issue and the temporal divergence of Triturus within the Salamandridae with novel Bayesian approaches applied to DNA sequence data from three mitochondrial genes (12S, 16S and cytb). We included 38 salamandrid species comprising all 13 recognized species of Triturus and 16 out of 17 salamandrid genera. A clade comprising all the "Newts" can be separated from the "True Salamanders" and Salamandrina clades. Within the "Newts" well-supported clades are: Tylototriton-Pleurodeles, the "New World Newts" (Notophthalmus-Taricha), and the "Modern Eurasian Newts" (Cynops, Pachytriton, Paramesotriton=together the "Modern Asian Newts", Calotriton, Euproctus, Neurergus and Triturus species). We found that Triturus is a non-monophyletic species assemblage, which includes four groups that are themselves monophyletic: (i) the "Large-Bodied Triturus" (six species), (ii) the "Small-Bodied Triturus" (five species), (iii) T. alpestris and (iv) T. vittatus. We estimated that the last common ancestor of Triturus existed around 64 million years ago (mya) while the root of the Salamandridae dates back to 95 mya. This was estimated using a fossil-based molecular dating approach and an explicit framework to select calibration points that least underestimated their corresponding nodes. Using the molecular phylogeny we mapped the evolution of life history and courtship traits in Triturus and found that several Triturus-specific courtship traits evolved independently.

  8. Patterning and Fabrication of Conductive Nanowires as Interconnects for Nanoelectronic Circuits Using Nucleic Acid Molecules as Templates

    DTIC Science & Technology

    2005-12-31

    Localization. J. Am. Chem. Soc. 125, 8710-8711 (2003). Becerril , H.A.; Stoltenberg, R.M.; Monson, C.F.; Woolley, A.T. Ionic Surface Masking for Low Background...using a Gas Flow Cell. Nano Lett. 4, 1481-1484 (2004). Becerril , H.A.; Stoltenberg, R.M.; Wheeler, D.R.; Davis, R.C.; Harb, J.N.; Woolley, A.T. DNA...Imaging. Meth. Mol. Biol. 283, 305-319 (2004). Becerril , H.A.; Nelson, A.R.; Woolley, A.T. Micromachined Substrates for Molecular Follow-Up in DNA

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

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

    PubMed

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

    2013-08-01

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

  12. Evolutionary implications of morphogenesis and molecular patterning of the blind gut in the planarian Schmidtea polychroa.

    PubMed

    Martín-Durán, José María; Romero, Rafael

    2011-04-01

    The formation of a through-gut was a key innovation in the evolution of metazoans. There is still controversy regarding the origin of the anus and how it may have been either gained or lost during evolution in different bilaterian taxa. Thus, the study of groups with a blind gut is of great importance for understanding the evolution of this organ system. Here, we describe the morphogenesis and molecular patterning of the blind gut in the sexual triclad Schmidtea polychroa. We identify and analyze the expression of goosecoid, commonly associated with the foregut, and the GATA, ParaHox and T-box genes, members of which commonly are associated with gut regionalization. We show that GATA456a is expressed in the b