Sample records for analysis molecular investigation

  1. Evolution & Phylogenetic Analysis: Classroom Activities for Investigating Molecular & Morphological Concepts (United States)

    Franklin, Wilfred A.


    In a flexible multisession laboratory, students investigate concepts of phylogenetic analysis at both the molecular and the morphological level. Students finish by conducting their own analysis on a collection of skeletons representing the major phyla of vertebrates, a collection of primate skulls, or a collection of hominid skulls.

  2. 3D-QSAR Investigation of Synthetic Antioxidant Chromone Derivatives by Molecular Field Analysis

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    Jiraporn Ungwitayatorn


    Full Text Available A series of 7-hydroxy, 8-hydroxy and 7,8-dihydroxy synthetic chromone derivatives was evaluated for their DPPH free radical scavenging activities. A training set of 30 synthetic chromone derivatives was subject to three-dimensional quantitative structure-activity relationship (3D-QSAR studies using molecular field analysis (MFA. The substitutional requirements for favorable antioxidant activity were investigated and a predictive model that could be used for the design of novel antioxidants was derived. Regression analysis was carried out using genetic partial least squares (G/PLS method. A highly predictive and statistically significant model was generated. The predictive ability of the developed model was assessed using a test set of 5 compounds (r2pred = 0.924. The analyzed MFA model demonstrated a good fit, having r2 value of 0.868 and crossvalidated coefficient r2cv value of 0.771.

  3. Investigating Molecular Interactions

    DEFF Research Database (Denmark)

    Clausen, Henrik Fanø


    give various crystal structures, which emphasizes that the synthetic control of coordination polymer systems is challenging. Furthermore, the metastable nature of one of the products demonstrates that kinetic factors can play an important role in the selfassembly of coordination polymers. The analysis...... of the experimentally determined charge density distribution of a cobalt coordination polymer at 15K is presented in Chapter 4. The study exemplifies the immense advances in experimental charge density analysis made possible by utilization of intense third generation synchrotrons, as even the single crystal structural...

  4. Investigation of the interaction of naringin palmitate with bovine serum albumin: spectroscopic analysis and molecular docking.

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    Xia Zhang

    Full Text Available BACKGROUND: Bovine serum albumin (BSA contains high affinity binding sites for several endogenous and exogenous compounds and has been used to replace human serum albumin (HSA, as these two compounds share a similar structure. Naringin palmitate is a modified product of naringin that is produced by an acylation reaction with palmitic acid, which is considered to be an effective substance for enhancing naringin lipophilicity. In this study, the interaction of naringin palmitate with BSA was characterised by spectroscopic and molecular docking techniques. METHODOLOGY/PRINCIPAL FINDINGS: The goal of this study was to investigate the interactions between naringin palmitate and BSA under physiological conditions, and differences in naringin and naringin palmitate affinities for BSA were further compared and analysed. The formation of naringin palmitate-BSA was revealed by fluorescence quenching, and the Stern-Volmer quenching constant (KSV was found to decrease with increasing temperature, suggesting that a static quenching mechanism was involved. The changes in enthalpy (ΔH and entropy (ΔS for the interaction were detected at -4.11 ± 0.18 kJ·mol(-1 and -76.59 ± 0.32 J·mol(-1·K(-1, respectively, which indicated that the naringin palmitate-BSA interaction occurred mainly through van der Waals forces and hydrogen bond formation. The negative free energy change (ΔG values of naringin palmitate at different temperatures suggested a spontaneous interaction. Circular dichroism studies revealed that the α-helical content of BSA decreased after interacting with naringin palmitate. Displacement studies suggested that naringin palmitate was partially bound to site I (subdomain IIA of the BSA, which was also substantiated by the molecular docking studies. CONCLUSIONS/SIGNIFICANCE: In conclusion, naringin palmitate was transported by BSA and was easily removed afterwards. As a consequence, an extension of naringin applications for use in food, cosmetic

  5. A Module Analysis Approach to Investigate Molecular Mechanism of TCM Formula: A Trial on Shu-feng-jie-du Formula

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    Jianglong Song


    Full Text Available At the molecular level, it is acknowledged that a TCM formula is often a complex system, which challenges researchers to fully understand its underlying pharmacological action. However, module detection technique developed from complex network provides new insight into systematic investigation of the mode of action of a TCM formula from the molecule perspective. We here proposed a computational approach integrating the module detection technique into a 2-class heterogeneous network (2-HN which models the complex pharmacological system of a TCM formula. This approach takes three steps: construction of a 2-HN, identification of primary pharmacological units, and pathway analysis. We employed this approach to study Shu-feng-jie-du (SHU formula, which aimed at discovering its molecular mechanism in defending against influenza infection. Actually, four primary pharmacological units were identified from the 2-HN for SHU formula and further analysis revealed numbers of biological pathways modulated by the four pharmacological units. 24 out of 40 enriched pathways that were ranked in top 10 corresponding to each of the four pharmacological units were found to be involved in the process of influenza infection. Therefore, this approach is capable of uncovering the mode of action underlying a TCM formula via module analysis.

  6. Investigation of the use of spectral clustering for the analysis of molecular data. (United States)

    Gan, Sonny; Cosgrove, David A; Gardiner, Eleanor J; Gillet, Valerie J


    Spectral clustering involves placing objects into clusters based on the eigenvectors and eigenvalues of an associated matrix. The technique was first applied to molecular data by Brewer [J. Chem. Inf. Model. 2007, 47, 1727-1733] who demonstrated its use on a very small dataset of 125 COX-2 inhibitors. We have determined suitable parameters for spectral clustering using a wide variety of molecular descriptors and several datasets of a few thousand compounds and compared the results of clustering using a nonoverlapping version of Brewer's use of Sarker and Boyer's algorithm with that of Ward's and k-means clustering. We then replaced the exact eigendecomposition method with two different approximate methods and concluded that Singular Value Decomposition is the most appropriate method for clustering larger compound collections of up to 100,000 compounds. We have also used spectral clustering with the Tversky coefficient to generate two sets of clusters linked by a common set of eigenvalues and have used this novel approach to cluster sets of fragments such as those used in fragment-based drug design.

  7. Molecular investigation of mental retardation locus gene PRSS12 by linkage analysis

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    Zafar Ali


    Full Text Available The present study was carried out to determine the prevalence of families having mental retardation in Pakistani population. We enrolled seven mentally retarded (MR families with two or more affected individuals. Family history was taken to minimize the chances of other abnormalities. Pedigrees were drawn using the Cyrillic software (version 2.1. The structure of pedigrees shows that all the marriages are consanguineous and the families have recessive mode of inheritance. All the families were studied by linkage analysis to mental retardation locus (MRT1/gene PRSS12. Three STR markers (D4S191, D4S2392, and D4S3024 in vicinity of mental retardation (MR locus (MRT1/gene PRSS12 were amplified on all the sample of each family by PCR. The PCR products were then genotyped on non denaturing polyacrylamide gel electrophoresis (PAGE. The Haplotype were constructed to determine the pattern of inheritance and also to determine that a family was linked or unlinked to gene PRSS12. One out of the seven families was potentially linked to gene PRSS12, while the other six families remain unlinked.

  8. Techniques for Investigating Molecular Toxicology of Nanomaterials. (United States)

    Wang, Yanli; Li, Chenchen; Yao, Chenjie; Ding, Lin; Lei, Zhendong; Wu, Minghong


    Nanotechnology has been a rapidly developing field in the past few decades, resulting in the more and more exposure of nanomaterials to human. The increased applications of nanomaterials for industrial, commercial and life purposes, such as fillers, catalysts, semiconductors, paints, cosmetic additives and drug carriers, have caused both obvious and potential impacts on human health and environment. Nanotoxicology is used to study the safety of nanomaterials and has grown at the historic moment. Molecular toxicology is a new subdiscipline to study the interactions and impacts of materials at the molecular level. To better understand the relationship between the molecular toxicology and nanomaterials, this review summarizes the typical techniques and methods in molecular toxicology which are applied when investigating the toxicology of nanomaterials and include six categories: namely; genetic mutation detection, gene expression analysis, DNA damage detection, chromosomal aberration analysis, proteomics, and metabolomics. Each category involves several experimental techniques and methods.

  9. Investigation of allosteric modulation mechanism of metabotropic glutamate receptor 1 by molecular dynamics simulations, free energy and weak interaction analysis (United States)

    Bai, Qifeng; Yao, Xiaojun


    Metabotropic glutamate receptor 1 (mGlu1), which belongs to class C G protein-coupled receptors (GPCRs), can be coupled with G protein to transfer extracellular signal by dimerization and allosteric regulation. Unraveling the dimer packing and allosteric mechanism can be of great help for understanding specific regulatory mechanism and designing more potential negative allosteric modulator (NAM). Here, we report molecular dynamics simulation studies of the modulation mechanism of FITM on the wild type, T815M and Y805A mutants of mGlu1 through weak interaction analysis and free energy calculation. The weak interaction analysis demonstrates that van der Waals (vdW) and hydrogen bonding play an important role on the dimer packing between six cholesterol molecules and mGlu1 as well as the interaction between allosteric sites T815, Y805 and FITM in wild type, T815M and Y805A mutants of mGlu1. Besides, the results of free energy calculations indicate that secondary binding pocket is mainly formed by the residues Thr748, Cys746, Lys811 and Ser735 except for FITM-bound pocket in crystal structure. Our results can not only reveal the dimer packing and allosteric regulation mechanism, but also can supply useful information for the design of potential NAM of mGlu1.

  10. Investigation of torsional potentials, molecular structure, vibrational properties, molecular characteristics and NBO analysis of some bipyridines using experimental and theoretical tools (United States)

    Prashanth, J.; Reddy, B. Venkatram; Rao, G. Ramana


    The Fourier Transform Infrared (FTIR) and Fourier Transform Raman (FT-Raman) spectra of 2,2‧-bipyridine (2BPE); 4,4‧-bipyridine (4BPE); and 2,4‧-bipyridine (24BPE) were measured in the range 4000-450 cm-1 and 4000-50 cm-1, respectively. Torsional potentials were evaluated at various angles of rotation around the C-C inter-ring bond for the three molecules in order to arrive at the molecular conformation of lowest energy. This conformation was further optimized to get ground state geometry. Vibrational frequencies along with infrared and Raman intensities were computed. In the above calculations, DFT employing B3LYP functional with 6311++G(d,p) basis set was used. The rms error between observed and calculated frequencies was 10.0, 10.9 and 10.2 cm-1 for 2BPE, 4BPE and 24BPE, respectively. A 54-parameter modified valence force field was derived by solving inverse vibrational problem using Wilson's GF matrix method. The force constants were refined using 117 experimental frequencies of the three molecules in overlay least-squares technique. The average error between observed and computed frequencies was 12.44 cm-1. PED and eigen vectors calculated in the process were used to make unambiguous vibrational assignments of all the fundamental vibrations. The values of dipole moment, polarizability and hyperpolarizability were computed to determine the NLO behaviour of these molecules. The HOMO and LUMO energies, thermodynamic parameters and molecular electrostatic surface potentials (MESP) were also evaluated. Stability of the molecules arising from hyper conjugative interactions, charge delocalization have been analyzed using natural bond orbital (NBO) analysis.

  11. Spectroscopic investigation, vibrational assignments, HOMO-LUMO, NBO, MEP analysis and molecular docking studies of oxoaporphine alkaloid liriodenine (United States)

    Costa, Renyer A.; Pitt, Priscilla Olliveira; Pinheiro, Maria Lucia B.; Oliveira, Kelson M. T.; Salomé, Kahlil Schwanka; Barison, Andersson; Costa, Emmanoel Vilaça


    A combined experimental and theoretical DFT study of the structural, vibrational and electronic properties of liriodenine is presented using B3LYP function with 6-311G (2d, p) basis set. The theoretical geometry optimization data were compared with the X-ray data for a similar structure in the associated literature, showing similar values. In addition, natural bond orbitals (NBOs), HOMO-LUMO energy gap, mapped molecular Electrostatic Potential (MEP) surface calculation, first and second order hyperpolarizabilities were also performed with the same calculation level. Theoretical UV spectrum agreed well with the measured experimental data, with transitions assigned. The molecular electrostatic potential map shows opposite potentials regions that forms hydrogen bonds that stabilize the dimeric form, which were confirmed by the close values related to the C dbnd O bond stretching between the dimeric form and the experimental IR spectra (1654 cm- 1 for the experimental, 1700 cm- 1 for the dimer form). Calculated HOMO/LUMO gaps shows the excitation energy for Liriodenine, justifying its stability and kinetics reaction. Molecular docking studies with Candida albicans dihydrofolate reductase (DHFR) and Candida albicans secreted aspartic protease (SAP) showed binding free energies values of - 8.5 and - 8.3 kcal/mol, suggesting good affinity between the liriodenine and the target macromolecules.

  12. Investigation of chemical modifiers for sulfur determination in diesel fuel samples by high-resolution continuum source graphite furnace molecular absorption spectrometry using direct analysis

    Energy Technology Data Exchange (ETDEWEB)

    Huber, Charles S. [Instituto Federal Sul-rio-grandense, Câmpus Pelotas, Pelotas, RS (Brazil); Universidade Federal do Rio Grande do Sul, Instituto de Química, Porto Alegre, RS (Brazil); Vale, Maria Goreti R. [Universidade Federal do Rio Grande do Sul, Instituto de Química, Porto Alegre, RS (Brazil); Instituto Nacional de Ciência e Tecnologia do CNPq, INCT de Energia e Ambiente, Universidade Federal da Bahia, Salvador, BA (Brazil); Welz, Bernhard [Instituto Nacional de Ciência e Tecnologia do CNPq, INCT de Energia e Ambiente, Universidade Federal da Bahia, Salvador, BA (Brazil); Universidade Federal de Santa Catarina, Departamento de Química, Florianópolis, SC (Brazil); Andrade, Jailson B. [Instituto Nacional de Ciência e Tecnologia do CNPq, INCT de Energia e Ambiente, Universidade Federal da Bahia, Salvador, BA (Brazil); Dessuy, Morgana B., E-mail: [Universidade Federal do Rio Grande do Sul, Instituto de Química, Porto Alegre, RS (Brazil); Instituto Nacional de Ciência e Tecnologia do CNPq, INCT de Energia e Ambiente, Universidade Federal da Bahia, Salvador, BA (Brazil)


    High-resolution continuum source graphite furnace molecular absorption spectrometry has been applied for sulfur determination in diesel fuel. The sharp rotational lines of the carbon monosulfide molecule (formed during the vaporization step) were used to measure the absorbance. The analytical line at 258.056 nm was monitored using the sum of three pixels. Different chemical modifiers were investigated and the mixture of palladium and magnesium was used as chemical modifier in combination with iridium as permanent modifier. L-Cysteine was chosen as sulfur standard and the calibration was done against aqueous standard solutions. The proposed method was applied for the analyses of four diesel samples: two S10 samples and two S500 samples. The trueness of the method was checked with a certified reference material (CRM) of sulfur in diesel fuel (NIST 2724b). Accurate results, for samples and CRM, were achieved after a dilution with propan-1-ol. The following figures of merit were obtained: characteristic mass of 17 ± 3 ng, limit of detection and limit of quantification of 1.4 mg kg{sup −1} and 4.7 mg kg{sup −1}, respectively. - Highlights: • Ir, Ru and Zr were investigated as permanent modifiers. • Ca, Mg, Pd and Pd/Mg were investigated as modifiers in solution. • Indirect determination of sulfur monitoring the molecular absorbance of the CS • Direct analysis of diesel samples using a dilution in propan-1-ol.

  13. Synthesis, crystal structure analysis, spectral investigations, DFT computations and molecular dynamics and docking study of 4-benzyl-5-oxomorpholine-3-carbamide, a potential bioactive agent (United States)

    Murthy, P. Krishna; Sheena Mary, Y.; Shyma Mary, Y.; Panicker, C. Yohannan; Suneetha, V.; Armaković, Stevan; Armaković, Sanja J.; Van Alsenoy, C.; Suchetan, P. A.


    4-benzyl-5-oxomorpholine-3-carbamide has been synthesized; single crystals were grown by slow evaporation solution growth technique at room temperature and characterized by single crystal X-ray diffraction, FT-IR, FT-Raman and 1H-NMR. The compound crystallizes in the monoclinic space group P21/n. The molecular geometry of the compound was optimized by using Density Functional Theory (DFT/B3LYP) method with 6-311++G(d,p) basis set in the ground state and geometric parameters are in agreement with the X-ray analysis results of the structure. The experimental vibrational spectra were compared with the calculated spectra and each vibrational wave number was assigned on the basis of potential energy distribution (PED). The electronic and charge transfer properties have been explained on the basis of highest occupied molecular orbital's (HOMOs) and lowest unoccupied molecular orbital's (LUMOs). Besides molecular electrostatic potential (MEP), frontier molecular orbital's (FMOs), some global reactivity descriptors, thermodynamic properties, non-linear optical (NLO) behavior and Mullikan charge analysis of the title compound were computed with the same method in gas phase, theoretically. Potential reactive sites of the title compound have been identified by average local ionization energy and Fukui functions, both mapped to the electron density surface. Bond dissociation energies for all single acyclic bonds have been calculated in order to investigate autoxidation and degradation properties of the title compound. Atoms with pronounced interactions with water molecules have been detected by calculations of radial distribution functions after molecular dynamics simulations. The experimental results are compared with the theoretical calculations using DFT methods for the fortification of the paper. Further the docking studies revealed that the title compound as a docked ligand forms a stable complex with pyrrole inhibitor with a binding affinity value of -7.5 kcal/mol. This

  14. A comprehensive investigation on iron cycling in a freshwater seep including microscopy, cultivation and molecular community analysis

    DEFF Research Database (Denmark)

    Bruun, Anne-Mette; Finster, Kai; Gunnlaugsson, Haraldur Pall


    Iron reduction and oxidation, as well as the microbial community involved in these processes, were investigated in a small pond that is continuously fed by slightly acidic, hypoxic, iron rich ground water. The seep area is located in a beech forest in central Jutland (Denmark), and beech litter...... is the dominant source of organic matter, carbon and energy for the microbial community. The pond is 30 to 50 cm deep with a water column depth ranging from 15 to 20 cm. Oxygen could only be detected down to 7 cm depth of the water column. Fe(II) concentrations increased with depth from about 30 μM close...

  15. [Molecular genetic investigations in muscular diseases]. (United States)

    Burgunder, J M


    The last couple of years have witnessed a rapid development in discoveries of the genetic background in myopathies. It is therefore timely to review the impact they have on clinical work. The recognition of a myopathy remains a clinical activity, and biopsy retains a major role. Molecular genetic investigation can be contemplated early in cases with certain typical clinical presentation. In others, the correct indication to such an investigation can only be made based on findings at biopsy. The information of precise mutation can be used for genetic counselling of the family. Knowledge of genes, whose mutations are sufficient to cause certain myopathies, have provided a great amount of knowledge about pathophysiological mechanisms involved. Some are arguably rare diseases, however, this knowledge also helps understand more frequent myopathies, as it has been the case in neurodegenerative disorders.

  16. Preparation, physicochemical analysis and molecular modeling investigation of 2,2‧-Bipyridine: β-Cyclodextrin inclusion complex in solution and solid state (United States)

    Periasamy, R.; Kothainayaki, S.; Sivakumar, K.


    Supramolecular interaction between 2,2‧-Bipyridine (BPY) and β-Cyclodextrin (β-CD) has been investigated in solution and solid state. Non-covalent interaction between BPY and β-CD was studied in solution using absorption and fluorescence spectroscopy. Inclusion complex of BPY and β-CD was prepared in solid state by co-precipitation method and it was characterized using Fourier Transform Infra-red spectroscopy (FT-IR), Thermal analysis, Scanning Electron Microscopy (SEM), Powder X-ray diffractometry (XRD) and Atomic Force Microscopy (AFM). Binding constant values and 1:1 stoichiometry of the inclusion complex were calculated using Benesi-Hildebrand plots at 303 K. Using continuous variation method the 1:1 stoichiometry has been confirmed for BPY: β-CD complex. Thermodynamic parameter, ΔG of inclusion complex formation was determined and the negative value indicated that the inclusion process was an exergonic and spontaneous process. The most probable model of BPY: β-CD inclusion complex suggested by molecular docking studies was in good agreement with the results obtained by experimental methods.

  17. "Mini-Array" Transcriptional Analysis of the "Listeria Monocytogenes" Lecithinase Operon as a Class Project: A Student Investigative Molecular Biology Laboratory Experience (United States)

    Christensen, Douglas; Jovic, Marko


    This report describes a molecular biotechnology-based laboratory curriculum developed to accompany an undergraduate genetics course. During the course of a semester, students researched the pathogen, developed a research question, designed experiments, and performed transcriptional analysis of a set of genes that confer virulence to the food-borne…

  18. Vibrational spectroscopic analysis of cyanopyrazine-2-carboxamide derivatives and investigation of their reactive properties by DFT calculations and molecular dynamics simulations (United States)

    Beegum, Shargina; Mary, Y. Sheena; Varghese, Hema Tresa; Panicker, C. Yohannan; Armaković, Stevan; Armaković, Sanja J.; Zitko, Jan; Dolezal, Martin; Van Alsenoy, C.


    Using density functional theory technique in the B3LYP approximation and cc-pVDZ (5D, 7F) basis set, the molecular structural parameters and vibrational wave numbers of two cyanopyrazine-2-carboxamide derivatives have been investigated. On the basis of potential energy distribution detailed vibrational assignments of observed FT-IR and FT-Raman bands have been proposed. Using molecular electrostatic potential map relative reactivities towards electrophilic and nucleophilic attack are predicted. The first and second hyperpolarizabilities are calculated and the first hyperpolarizability of the title compounds are greater than that of the standard NLO material urea. Molecular studies reveal that the predicted binding affinities of the best poses were -8.7 kcal/mol for BACPC, -9.0 kcal/mol for CBACPC, and -8.8 kcal/mol for the original inhibitor. Efforts were made in order to investigate local reactivity properties of title compounds as well. In order to do so we have calculated average local ionization energy (ALIE) surfaces, Fukui functions, bond dissociation energies (BDE) (within the framework of DFT calculations) and radial distribution functions (RDF) (within the molecular dynamics simulations). ALIE surfaces and Fukui functions gave us initial information on the site reactivity towards electrophilic and nucleophilic attacks. BDE indicated locations that might be prone to autoxidation mechanism, while RDF indicated which atoms of title molecules are having pronounced interactions with water.

  19. Binding affinities of Schiff base Fe(II) complex with BSA and calf-thymus DNA: Spectroscopic investigations and molecular docking analysis. (United States)

    Rudra, Suparna; Dasmandal, Somnath; Patra, Chiranjit; Kundu, Arjama; Mahapatra, Ambikesh


    The binding interaction of a synthesized Schiff base Fe(II) complex with biological macromolecules viz., bovine serum albumin (BSA) and calf thymus(ct)-DNA have been investigated using different spectroscopic techniques coupled with viscosity measurements at physiological pH and 298K. Regular amendments in emission intensities of BSA upon the action of the complex indicate significant interaction between them, and the binding interaction have been characterized by Stern Volmer plots and thermodynamic binding parameters. On the basis of this quenching technique one binding site with binding constant (Kb=(7.6±0.21)×10(5)) between complex and protein have been obtained at 298K. Time-resolved fluorescence studies have also been encountered to understand the mechanism of quenching induced by the complex. Binding affinities of the complex to the fluorophores of BSA namely tryptophan (Trp) and tyrosine (Tyr) have been judged by synchronous fluorescence studies. Secondary structural changes of BSA rooted by the complex has been revealed by CD spectra. On the other hand, hypochromicity of absorption spectra of the complex with the addition of ct-DNA and the gradual reduction in emission intensities of ethidium bromide bound ct-DNA in presence of the complex indicate noticeable interaction between ct-DNA and the complex with the binding constant (4.2±0.11)×10(6)M(-1). Life-time measurements have been studied to determine the relative amplitude of binding of the complex to ct-DNA base pairs. Mode of binding interaction of the complex with ct-DNA has been deciphered by viscosity measurements. CD spectra have also been used to understand the changes in ct-DNA structure upon binding with the metal complex. Density functional theory (DFT) and molecular docking analysis have been employed in highlighting the interactive phenomenon and binding location of the complex with the macromolecules.

  20. Binding affinities of Schiff base Fe(II) complex with BSA and calf-thymus DNA: Spectroscopic investigations and molecular docking analysis (United States)

    Rudra, Suparna; Dasmandal, Somnath; Patra, Chiranjit; Kundu, Arjama; Mahapatra, Ambikesh


    The binding interaction of a synthesized Schiff base Fe(II) complex with biological macromolecules viz., bovine serum albumin (BSA) and calf thymus(ct)-DNA have been investigated using different spectroscopic techniques coupled with viscosity measurements at physiological pH and 298 K. Regular amendments in emission intensities of BSA upon the action of the complex indicate significant interaction between them, and the binding interaction have been characterized by Stern Volmer plots and thermodynamic binding parameters. On the basis of this quenching technique one binding site with binding constant (Kb = (7.6 ± 0.21) × 105) between complex and protein have been obtained at 298 K. Time-resolved fluorescence studies have also been encountered to understand the mechanism of quenching induced by the complex. Binding affinities of the complex to the fluorophores of BSA namely tryptophan (Trp) and tyrosine (Tyr) have been judged by synchronous fluorescence studies. Secondary structural changes of BSA rooted by the complex has been revealed by CD spectra. On the other hand, hypochromicity of absorption spectra of the complex with the addition of ct-DNA and the gradual reduction in emission intensities of ethidium bromide bound ct-DNA in presence of the complex indicate noticeable interaction between ct-DNA and the complex with the binding constant (4.2 ± 0.11) × 106 M- 1. Life-time measurements have been studied to determine the relative amplitude of binding of the complex to ct-DNA base pairs. Mode of binding interaction of the complex with ct-DNA has been deciphered by viscosity measurements. CD spectra have also been used to understand the changes in ct-DNA structure upon binding with the metal complex. Density functional theory (DFT) and molecular docking analysis have been employed in highlighting the interactive phenomenon and binding location of the complex with the macromolecules.

  1. Signal analysis of behavioral and molecular cycles

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    Dowse Harold B


    Full Text Available Abstract Background Circadian clocks are biological oscillators that regulate molecular, physiological, and behavioral rhythms in a wide variety of organisms. While behavioral rhythms are typically monitored over many cycles, a similar approach to molecular rhythms was not possible until recently; the advent of real-time analysis using transgenic reporters now permits the observations of molecular rhythms over many cycles as well. This development suggests that new details about the relationship between molecular and behavioral rhythms may be revealed. Even so, behavioral and molecular rhythmicity have been analyzed using different methods, making such comparisons difficult to achieve. To address this shortcoming, among others, we developed a set of integrated analytical tools to unify the analysis of biological rhythms across modalities. Results We demonstrate an adaptation of digital signal analysis that allows similar treatment of both behavioral and molecular data from our studies of Drosophila. For both types of data, we apply digital filters to extract and clarify details of interest; we employ methods of autocorrelation and spectral analysis to assess rhythmicity and estimate the period; we evaluate phase shifts using crosscorrelation; and we use circular statistics to extract information about phase. Conclusion Using data generated by our investigation of rhythms in Drosophila we demonstrate how a unique aggregation of analytical tools may be used to analyze and compare behavioral and molecular rhythms. These methods are shown to be versatile and will also be adaptable to further experiments, owing in part to the non-proprietary nature of the code we have developed.

  2. RFLP Analysis and Allelic Discrimination with Real-Time PCR Using the Human Lactase Persistence Trait: A Pair of Molecular Genetic Investigations (United States)

    Weinlander, Kenneth M.; Hall, David J.; De Stasio, Elizabeth A.


    We describe here two open-ended laboratory investigations for an undergraduate laboratory course that uses students' DNA as templates for quantitative real-time PCR and for traditional PCR followed by RFLP analysis. Students are captivated by the immediacy of the application and the relevance of the genotypes and traits, lactase persistence or…

  3. Accident investigation and analysis

    NARCIS (Netherlands)

    Kampen, J. van; Drupsteen, L.


    Many organisations and companies take extensive proactive measures to identify, evaluate and reduce occupational risks. However, despite these efforts things still go wrong and unintended events occur. After a major incident or accident, conducting an accident investigation is generally the next ste

  4. Conformational stability, molecular orbital studies (chemical hardness and potential), vibrational investigation and theoretical NBO analysis of 4-tert-butyl-3-methoxy-2,6-dinitrotoluene. (United States)

    Saravanan, S; Balachandran, V; Vishwanathan, K


    The FT-IR and FT-Raman spectra of 4-tert-butyl-3-methoxy-2,6-dinitrotoluene (musk ambrette) have been recorded in the regions 4000-400 cm(-1) and 3500-100 cm(-1), respectively. The total energy calculations of musk ambrette were tried for the possible conformers. The molecular structure, geometry optimization, vibrational frequencies were obtained by the density functional theory (DFT) using B3LYP and LSDA method with 6-311G(d,p) basis set for the most stable conformer "C1". The complete assignments were performed on the basis of the potential energy distribution (PED) of the vibrational modes, calculated and the scaled values were compared with experimental FT-IR and FT-Raman spectra. The observed and the calculated frequencies are found to be in good agreement. The stability of the molecule arising from hyper conjugate interactions and the charge delocalization has been analyzed using bond orbital (NBO) analysis. The HOMO and LUMO energy gap reveals that the energy gap reflects the chemical activity of the molecule. The dipole moment (μ), polarizability (α), anisotropy polarizability (Δα) and first hyperpolarizability (βtot) of the molecule have been reported. The thermodynamic functions (heat capacity, entropy and enthalpy) were obtained for the range of temperature 100-1000 K. Information about the size, shape, charge density distribution and site of chemical reactivity of the molecule has been obtained by mapping electron density isosurface with molecular electrostatic potential (MEP).

  5. Investigating Genetic Diversity of Foeniculum Vulgare Mill using Molecular Markers

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    Omid Jadidi


    Full Text Available Medicinal plants are considered valuable genetic resources in Iran. One of these medicinal as well as spice plants is Foeniculum Vulgare Mill from Umbellifetae family used in different industries such as food, medicine, and cosmetics. It seems that due to different climate conditions in Iran this plant represents a high and valuable genetic diversity; therefore, management of genetic resources protection and obtaining information about genetic diversity will help awareness of evolution processes as well as genetic erosion of this valuable plant. Genetic diversity in local masses of Foeniculum Vulgare Mill can be investigated using molecule markers such as AFLP, RAPD, ISSR, SRAP, RFLP, and so on. In investigation of over 30 ecotype of local Foeniculum Vulgare Mill, different markers have shown that mean polymorphic content (PIC is about 36% and mean genetic diversity is estimated about 40% in different samples. Data obtained from molecule software analyses help to categorize Foeniculum Vulgare Mill genotype in different groups based on climate and geographical conditions. Principle components analysis (PCOA has also confirmed the results of cluster analysis. Dendrogram obtained by cluster analysis based on similarity coefficient of simple matching (SM and UPGMA algorithm can also categorize population of Foeniculum Vulgare Mill in different groups. Results of molecular variance analysis (AMOVA have shown that most genetic variance between geographical groups can be seen in populations. In general, according to investigations, there is a significant genetic diversity regarding agronomic and molecular traits of Foeniculum Vulgare Mill masses in Iran and knowing this genetic diversity will help in breeding programs, complementary studies, categorization, and so on.

  6. Investigation of the Molecular Response of Belugas to Stressors (United States)


    described above were obtained from this related project. REFERENCES Denis, F., Archambault, D., 2001. Molecular cloning and characterization of...mRNA expression levels serve as indicators to assess stress? BMC Veterinary Research 9:145. St-Laurent, G. and Archambault, D., 2000. Molecular ... cloning , phylogenetic analysis and expression of beluga whale (Delphinapterus leucas) interleukin 6. Veterinary Immunology Immunopathology 73: 31-44

  7. Molecular orbital studies (hardness, chemical potential and electrophilicity), vibrational investigation and theoretical NBO analysis of 4-4'-(1H-1,2,4-triazol-1-yl methylene) dibenzonitrile based on abinitio and DFT methods. (United States)

    Sheela, N R; Muthu, S; Sampathkrishnan, S


    The Fourier transform infrared (FTIR) and FT Raman (FTR) of 4-4'-(1H-1, 2, 4-triazol-1-yl methylene) dibenzonitrile (4-HTMDBN) have been recorded and analyzed. The equilibrium geometry harmonic vibrational frequencies have been investigated with the help of standard HF and DFT methods with 6-31G(d,p) as basis set. The assignments of the vibrational spectra have been carried out with the help of normal co-ordinate analysis (NCA) following the scaled quantum mechanical force field methodology (SQMFF). Theoretical simulations of the FTIR and FTR spectra of the title compound have been calculated. The (1)H and (13)C Nuclear Magnetic Resonance (NMR) chemical shifts of the molecule were calculated by the Gauge including atomic orbital (GIAO) method. The stability of the molecule has been analyzed using natural bond orbital (NBO) analysis. The linear polarizability (α) and the first order hyperpolarizability (β) values of the investigated molecule have been computed using HF/DFT/6-31G(d,p) methods on the finite field approach. UV-Vis spectrum of the compound is recorded and the electronic properties such as HOMO and LUMO energies, are performed. The directly calculated ionization potential (IP), electron affinity (EA), electronegativity (χ), electrophilicity index (ω), hardness (η) and chemical potential (ρ) are all correlated with the HOMO and LUMO energies with their molecular properties. Mulliken population analysis on atomic charges, molecular electrostatic potential maps (MEP) and thermodynamical properties of title compound at different temperature have been calculated.

  8. Analysis of molecular interactions in solid dosage forms; challenge to molecular pharmaceutics. (United States)

    Yamamoto, Keiji; Limwikrant, Waree; Moribe, Kunikazu


    The molecular states of active pharmaceutical ingredients (APIs) in pharmaceutical dosage forms strongly affect the properties and quality of a drug. Various important fundamental physicochemical studies were reviewed from the standpoint of molecular pharmaceutics. Mechanochemical effects were evaluated in mixtures of APIs and pharmaceutical additives. Amorphization, complex formation and nanoparticle formation are observed after grinding process depending on the combination of APIs and pharmaceutical additives. Sealed-heating method and mesoporous materials have been used to investigate drug molecular interactions in dosage forms. Molecular states have been investigated using powder X-ray diffraction, thermal analysis, IR, solid state fluorometry, and NMR.

  9. One Pot Selective Arylation of 2-Bromo-5-Chloro Thiophene; Molecular Structure Investigation via Density Functional Theory (DFT), X-ray Analysis, and Their Biological Activities. (United States)

    Rasool, Nasir; Kanwal, Aqsa; Rasheed, Tehmina; Ain, Quratulain; Mahmood, Tariq; Ayub, Khurshid; Zubair, Muhammad; Khan, Khalid Mohammed; Arshad, Muhammad Nadeem; M Asiri, Abdullah; Zia-Ul-Haq, Muhammad; Jaafar, Hawa Z E


    Synthesis of 2,5-bisarylthiophenes was accomplished by sequential Suzuki cross coupling reaction of 2-bromo-5-chloro thiophenes. Density functional theory (DFT) studies were carried out at the B3LYP/6-31G(d, p) level of theory to compare the geometric parameters of 2,5-bisarylthiophenes with those from X-ray diffraction results. The synthesized compounds are screened for in vitro bacteria scavenging abilities. At the concentration of 50 and 100 μg/mL, compounds 2b, 2c, 2d, 3c, and 3f with IC50-values of 51.4, 52.10, 58.0, 56.2, and 56.5 μg/mL respectively, were found most potent against E. coli. Among all the synthesized compounds 2a, 2d, 3c, and 3e with the least values of IC50 77, 76.26, 79.13 μg/mL respectively showed significant antioxidant activities. Almost all of the compounds showed good antibacterial activity against Escherichia coli, whereas 2-chloro-5-(4-methoxyphenyl) thiophene (2b) was found most active among all synthesized compound with an IC50 value of 51.4 μg/mL. All of the synthesized compounds were screened for nitric oxide scavenging activity as well. Frontier molecular orbitals (FMOs) and molecular electrostatic potentials of the target compounds were also studied theoretically to account for their relative reactivity.

  10. Generalized analysis of molecular variance.

    Directory of Open Access Journals (Sweden)

    Caroline M Nievergelt


    Full Text Available Many studies in the fields of genetic epidemiology and applied population genetics are predicated on, or require, an assessment of the genetic background diversity of the individuals chosen for study. A number of strategies have been developed for assessing genetic background diversity. These strategies typically focus on genotype data collected on the individuals in the study, based on a panel of DNA markers. However, many of these strategies are either rooted in cluster analysis techniques, and hence suffer from problems inherent to the assignment of the biological and statistical meaning to resulting clusters, or have formulations that do not permit easy and intuitive extensions. We describe a very general approach to the problem of assessing genetic background diversity that extends the analysis of molecular variance (AMOVA strategy introduced by Excoffier and colleagues some time ago. As in the original AMOVA strategy, the proposed approach, termed generalized AMOVA (GAMOVA, requires a genetic similarity matrix constructed from the allelic profiles of individuals under study and/or allele frequency summaries of the populations from which the individuals have been sampled. The proposed strategy can be used to either estimate the fraction of genetic variation explained by grouping factors such as country of origin, race, or ethnicity, or to quantify the strength of the relationship of the observed genetic background variation to quantitative measures collected on the subjects, such as blood pressure levels or anthropometric measures. Since the formulation of our test statistic is rooted in multivariate linear models, sets of variables can be related to genetic background in multiple regression-like contexts. GAMOVA can also be used to complement graphical representations of genetic diversity such as tree diagrams (dendrograms or heatmaps. We examine features, advantages, and power of the proposed procedure and showcase its flexibility by

  11. Uncertainty analysis in acoustic investigations



    The problem of uncertainty assessment in acoustic investigations is presented in the hereby paper. The aspect of the uncertainty asymmetry in processing of data obtained in the measuring test of sound levels, determined in decibels, was sketched. On the basis of the analysis of data obtained in the continuous monitoring of road traffic noise in Krakow typical probability distributions for a day, evening and night were determined. The method of the uncertainty assessment based on the propagati...

  12. Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy (United States)


    AWARD NUMBER: W81XWH-14-1-0399 TITLE: Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy PRINCIPAL INVESTIGATOR: John F...information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and...maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other

  13. Investigations on the adsorbents for uremic middle molecular toxins (II)

    Institute of Scientific and Technical Information of China (English)

    WANG; Hong


    normal and uremic urine by high-performance liquid chromatography, J. Chromatogr., 1982, 233: 107.[15]Mabuchi, H., Nakahashi, H., Analysis of middle molecular peptides in normal and uremic body fluids by high-performance gel chromatography, J. Chromatogr,, 1981,224: 322.[16]Flanagan, R. W. J., Murphy, R. F., Buchanan, K. D., Circulating forms of glucagon and related peptides in normal subjects and uraemic patients, Biochem. Soc. Transt., 1980, 8: 426.[17]Matthaei, D., Ludwig-Krln, H., Kramer, P. et al., Changes of plasma hormone levels in hemofiltration, Int. J. Artif. Organs,1983, 6: 21.[18]Ehrlich, R. W., Holland, F., Turnham, T. et al., Osmotic concentration of polypeptides from hemofiltrate of uremic patients,Clin. Nephrol., 1980, 14: 31.[19]Menyhart, J., Grof, J., Many hitherto unknown peptides are principal constituents of uremic “middle molecules”, Clin.Chem., 1981, 27: 1712.[20]Wang, S. X., Wu, J. P., Nephrology, Beijing: People's Health Publishing House, 1987, 740.[21]Chu, J. G., Investigations on the separation, characterization and toxicity of middle molecular substances, Doctoral Dissertation, Nankai University, 2000, 108.

  14. Molecular dynamics investigation of radiation damage in semiconductors (United States)

    Good, Brian S.


    Results of a molecular dynamics investigation of the effects of radiation damage on the crystallographic structure of semiconductors are reported. Particular cosiderastion is given to the formation of point defects and small defect complexes in silicon at the end of a radiation-damage cascade. The calculations described make use of the equivalent crystal theory of Smith and Banerjea (1988). Results on the existence of an atomic displacement threshold, the defect formation energy, and some crystallographic information on the defects observed are reported.

  15. Adsorption of homopolypeptides on gold investigated using atomistic molecular dynamics


    Vila Verde, A.; Beltramo, Peter J.; Maranas, Janna K.


    We investigate the role of dynamics on adsorption of peptides to gold surfaces using all-atom molecular dynamics simulations in explicit solvent. We choose six homopolypeptides [Ala 10 , Ser 10 , Thr 10 , Arg 10 , Lys 10 , and Gln 10 ], for which experimental surface coverages are not correlated with amino acid level affinities for gold, with the idea that dynamic properties may also play a role. To assess dynamics we determine both conformational movemen...

  16. Investigation of glassy state molecular motions in thermoset polymers (United States)

    Tu, Jianwei

    This dissertation presents the investigation of the glassy state molecular motions in isomeric thermoset epoxies by means of solid-state deuterium (2H) NMR spectroscopy technique. The network structure of crosslinked epoxies was altered through monomer isomerism; specifically, diglycidyl ether of bisphenol A (DGEBA) was cured with isomeric amine curatives, i.e., the meta-substituted diaminodiphenylsulfone (33DDS) and para-substituted diaminodiphenylsulfone (44DDS). The use of structural isomerism provided a path way for altering macroscopic material properties while maintaining identical chemical composition within the crosslinked networks. The effects of structural isomerism on the glassy state molecular motions were studied using solid-state 2H NMR spectroscopy, which offers unrivaled power to monitor site-specific molecular motions. Three distinctive molecular groups on each isomeric network, i.e., the phenylene rings in the bisphenol A structure (BPA), the phenylene rings in the diaminodiphenylsulfone structure (DDS), and the hydroxypropoyl ether group (HPE) have been selectively deuterated for a comprehensive study of the structure-dynamics- property relationships in thermoset epoxies. Quadrupolar echo experiments and line shape simulations were employed as the main research approach to gain both qualitative and quantitative motional information of the epoxy networks in the glassy state. Quantitative information on the geometry and rate of the molecular motions allows the elucidation of the relationship between molecular motions and macro physical properties and the role of these motions in the mechanical relaxation. Specifically, it is revealed that both the BPA and HPE moieties in the isomeric networks have almost identical behaviors in the deep glassy state, which indicates that the molecular motions in the glassy state are localized, and the correlation length of the motions does not exceed the length of the DGEBA repeat unit. BPA ring motions contribute

  17. Comparative Investigation of Normal Modes and Molecular Dynamics of Hepatitis C NS5B Protein (United States)

    Asafi, M. S.; Yildirim, A.; Tekpinar, M.


    Understanding dynamics of proteins has many practical implications in terms of finding a cure for many protein related diseases. Normal mode analysis and molecular dynamics methods are widely used physics-based computational methods for investigating dynamics of proteins. In this work, we studied dynamics of Hepatitis C NS5B protein with molecular dynamics and normal mode analysis. Principal components obtained from a 100 nanoseconds molecular dynamics simulation show good overlaps with normal modes calculated with a coarse-grained elastic network model. Coarse-grained normal mode analysis takes at least an order of magnitude shorter time. Encouraged by this good overlaps and short computation times, we analyzed further low frequency normal modes of Hepatitis C NS5B. Motion directions and average spatial fluctuations have been analyzed in detail. Finally, biological implications of these motions in drug design efforts against Hepatitis C infections have been elaborated.

  18. A molecular phylogenetic investigation of zoothamnium (ciliophora, peritrichia, sessilida). (United States)

    Clamp, John C; Williams, Daniel


    The gene coding for 18S small subunit ribosomal RNA (ssu rRNA) was sequenced in seven free-living, marine species of the sessiline peritrich genus Zoothamnium. These were Zoothamnium niveum, Zoothamnium alternans, Zoothamnium pelagicum, and four unidentified species. The ssu rRNA gene also was sequenced in Vorticella convallaria, Vorticella microstoma, and in an unidentified, freshwater species of Vorticella. Phylogenetic trees were constructed using these new sequences to test a previously published phylogenetic association between Zoothamnium arbuscula, currently in the family Zoothamniidae, and peritrichs in the family Vorticellidae. Trees constructed by means of neighbor-joining, maximum parsimony, maximum likelihood, and Bayesian inference methods all had similar topologies. The seven new sequences of Zoothamnium species grouped into three well-supported clades, each of which contained a diversity of morphological types. The three clades formed a poorly supported, larger clade that was deeply divergent from Z. arbuscula, which remained more closely associated with vorticellid peritrichs. It is apparent that Zoothamnium is a richly diverse genus and that a much more intensive investigation, involving both morphological and molecular data and a wider selection of species, will be necessary to resolve its phylogeny. A greater amount of molecular diversity than is predicted by morphological data exists within all major clades of sessiline peritrichs that have been included in molecular phylogenies, indicating that characteristics of stalk and peristomial structure traditionally used to differentiate taxa at the generic level and above may not be uniformly reliable.

  19. Investigating Molecular Kinetics by Variationally Optimized Diffusion Maps. (United States)

    Boninsegna, Lorenzo; Gobbo, Gianpaolo; Noé, Frank; Clementi, Cecilia


    Identification of the collective coordinates that describe rare events in complex molecular transitions such as protein folding has been a key challenge in the theoretical molecular sciences. In the Diffusion Map approach, one assumes that the molecular configurations sampled have been generated by a diffusion process, and one uses the eigenfunctions of the corresponding diffusion operator as reaction coordinates. While diffusion coordinates (DCs) appear to provide a good approximation to the true dynamical reaction coordinates, they are not parametrized using dynamical information. Thus, their approximation quality could not, as yet, be validated, nor could the diffusion map eigenvalues be used to compute relaxation rate constants of the system. Here we combine the Diffusion Map approach with the recently proposed Variational Approach for Conformation Dynamics (VAC). Diffusion Map coordinates are used as a basis set, and their optimal linear combination is sought using the VAC, which employs time-correlation information on the molecular dynamics (MD) trajectories. We have applied this approach to ultra-long MD simulations of the Fip35 WW domain and found that the first DCs are indeed a good approximation to the true reaction coordinates of the system, but they could be further improved using the VAC. Using the Diffusion Map basis, excellent approximations to the relaxation rates of the system are obtained. Finally, we evaluate the quality of different metric spaces and find that pairwise minimal root-mean-square deviation performs poorly, while operating in the recently introduced kinetic maps based on the time-lagged independent component analysis gives the best performance.

  20. Molecular and Cellular Quantitative Microscopy: theoretical investigations, technological developments and applications to neurobiology (United States)

    Esposito, Alessandro


    This PhD project aims at the development and evaluation of microscopy techniques for the quantitative detection of molecular interactions and cellular features. The primarily investigated techniques are Fαrster Resonance Energy Transfer imaging and Fluorescence Lifetime Imaging Microscopy. These techniques have the capability to quantitatively probe the biochemical environment of fluorophores. An automated microscope capable of unsupervised operation has been developed that enables the investigation of molecular and cellular properties at high throughput levels and the analysis of cellular heterogeneity. State-of-the-art Förster Resonance Energy Transfer imaging, Fluorescence Lifetime Imaging Microscopy, Confocal Laser Scanning Microscopy and the newly developed tools have been combined with cellular and molecular biology techniques for the investigation of protein-protein interactions, oligomerization and post-translational modifications of α-Synuclein and Tau, two proteins involved in Parkinson’s and Alzheimer’s disease, respectively. The high inter-disciplinarity of this project required the merging of the expertise of both the Molecular Biophysics Group at the Debye Institute - Utrecht University and the Cell Biophysics Group at the European Neuroscience Institute - Gαttingen University. This project was conducted also with the support and the collaboration of the Center for the Molecular Physiology of the Brain (Göttingen), particularly with the groups associated with the Molecular Quantitative Microscopy and Parkinson’s Disease and Aggregopathies areas. This work demonstrates that molecular and cellular quantitative microscopy can be used in combination with high-throughput screening as a powerful tool for the investigation of the molecular mechanisms of complex biological phenomena like those occurring in neurodegenerative diseases.

  1. Fluorescence fluctuation microscopy: a diversified arsenal of methods to investigate molecular dynamics inside cells. (United States)

    Weidemann, Thomas; Mücksch, Jonas; Schwille, Petra


    Fluorescence microscopy provides insight into the subcellular organization of biological functions. However, images are snap shots averaging over a highly dynamic molecular system. Fluorescence fluctuation microscopy, employing similar detection technology, encompasses a powerful arsenal of analysis tools that investigate the molecular heterogeneity in space and time. Analyzing signal fluctuations from small ensembles (several hundred particles) reveals their concentration, the stoichiometry, the stochastic motion, as well as superimposed signatures of the environment such as spatial confinement and binding events. Thus, fluctuation analysis provides access to dynamic molecular properties that can be used to build physical models of cellular processes. In the last decade these methods experienced a remarkable diversification, which we revisit here with a particular focus on live cell applications.

  2. Thermal and molecular investigation of laser tissue welding

    Energy Technology Data Exchange (ETDEWEB)

    Small, W., IV


    Despite the growing number of successful animal and human trials, the exact mechanisms of laser tissue welding remain unknown. Furthermore, the effects of laser heating on tissue on the molecular scale are not fully understood. To address these issues, a multi-front attack oil both extrinsic (solder/patch mediated) and intrinsic (laser only) tissue welding was launched using two-color infrared thermometry, computer modeling, weld strength assessment, biochemical assays, and vibrational spectroscopy. The coupling of experimentally measured surface temperatures with the predictive numerical simulations provided insight into the sub-surface dynamics of the laser tissue welding process. Quantification of the acute strength of the welds following the welding procedure enabled comparison among trials during an experiment, with previous experiments, and with other studies in the literature. The acute weld integrity also provided an indication of tile probability of long-term success. Molecular effects induced In the tissue by laser irradiation were investigated by measuring tile concentrations of specific collagen covalent crosslinks and characterizing the Fourier-Transform infrared (FTIR) spectra before and after the laser exposure.

  3. Molecular Dynamics Investigation of Benzene in Supercritical Water

    Institute of Scientific and Technical Information of China (English)


    Microscopic structure and diffusion properties of benzene in ambient water (298 K, 0.1 MPa) and super critical water (673-773 K, 25-35 MPa) are investigated by molecular dynamics simulation with site-site models. It is found that at the ambient condition, the water molecules surrounding a benzene molecule form a hydrogen bond network. The hydrogen bond interaction between supercritical water molecules decreases dramatically under supercritical conditions. The diffusion coefficients of both the solute molecule and solvent molecule at supercritical conditions increase by 30-180 times than those at the ambient condition. With the temperature approaching the critical temperature, the change of diffusion coefficient with pressure becomes pronounced.

  4. Molecular-dynamics investigation of the desensitization of detonable material (United States)

    Rice, Betsy M.; Mattson, William; Trevino, Samuel F.


    A molecular-dynamics investigation of the effects of a diluent on the detonation of a model crystalline explosive is presented. The diluent, a heavy material that cannot exothermally react with any species of the system, is inserted into the crystalline explosive in two ways. The first series of simulations investigates the attenuation of the energy of a detonation wave in a pure explosive after it encounters a small layer of crystalline diluent that has been inserted into the lattice of the pure explosive. After the shock wave has traversed the diluent layer, it reenters the pure explosive. Unsupported detonation is not reestablished unless the energy of the detonation wave exceeds a threshold value. The second series of simulations investigates detonation of solid solutions of different concentrations of the explosive and diluent. For both types of simulations, the key to reestablishing or reaching unsupported detonation is the attainment of a critical number density behind the shock front. Once this critical density is reached, the explosive molecules make a transition to an atomic phase. This is the first step in the reaction mechanism that leads to the heat release that sustains the detonation. The reactive fragments formed from the atomization of the heteronuclear reactants subsequently combine with new partners, with homonuclear product formation exothermally favored. The results of detonation of the explosive-diluent crystals are consistent with those presented in an earlier study on detonation of pure explosive [B. M. Rice, W. Mattson, J. Grosh, and S. F. Trevino, Phys. Rev. E 53, 611 (1996)].


    Directory of Open Access Journals (Sweden)

    Massoud HOUSHMAND


    Full Text Available Glutaric Acidemia, Type I (GA I, was first described in 1975. The disease is caused by a genetic deficiency of the enzyme, Glutaryl-CoA Dehydrogenase (GCD, which leads to the buildup of Glutaric acid in the tissues and its excretion in the urine of affected patients. GCD is involved in the catabolism of the amino acids, Lysine, Hydroxylysine, and Tryptophan. Over 200 cases of GA I have been reported in the medical literature. GA I is one of the most common organic acidemias and has an estimated incidence of about 1 in 50,000 live births.Because of the initial slow progression of clinical symptoms, GA I is frequently undiagnosed until an acute metabolic crisis occurs. A total of 25 unrelated patients suspected to GA1 were investigated in our study. Genomic DNA was extracted from peripheral blood cells of the 25 probands whom were biochemically and/or clinically and/or neuro-radiologically suspected to GA1. 15 of them had elevated glutaric acid in the urine organic acid test.PCR and direct sequencing of all 11 exons and their flanking region of the GCDH gene were examined.Some of them were investigated for known mutation in the other their family members. Fifteen patients had homozygous mutations and 10 patients were normal for GCDH gene. Our Results Showed:• 60% Known mutation were found in our 15 patients• 80% can be detected by 4 exons sequencing so for molecular investigatins exon 6, 7, 8, 10 are good choice for beginning of analysis• 33% was mutation in exon 7, so because of the cost of genetic diagnosis we suggest that investigation begin with this exon.• Pro 348 Leu was most detected 20%.• 40% are new mutations wich will be investigated for phenotype Genotype Correlations.


    Directory of Open Access Journals (Sweden)

    Antonina Argo


    Full Text Available In the past few years, contributions of molecular biology assays to the investigation of sudden juvenile death have permitted to clarify some of the pathogenetic aspects of sudden arrhythmic death, opening the way to preventive action on victims’ relatives. We reviewed literature on the genetics of sudden juvenile death, and on molecular biology assays performed on autoptic samples. Biological investigation permits the detection of genetic mutations underlying the susceptibility to sudden cardiac death of individuals with rare inherited forms of arrhythmia (Long QT Syndrome, Brugada Syndrome, Lev’s disease etc. through the analysis of critical sequences codifying for ion channel subunits (HERG, KvLQT1, MinK, Mirp1, SCN5A, KCNQ1, KCNH2, KCNE1, KCNE2. The main objective of post-mortem investigation in sudden juvenile death is the detection of treatable monogenic inherited disorders, in order to prevent further deaths among the relatives of the deceased patient.

  7. Random Matrix Theory in molecular dynamics analysis. (United States)

    Palese, Luigi Leonardo


    It is well known that, in some situations, principal component analysis (PCA) carried out on molecular dynamics data results in the appearance of cosine-shaped low index projections. Because this is reminiscent of the results obtained by performing PCA on a multidimensional Brownian dynamics, it has been suggested that short-time protein dynamics is essentially nothing more than a noisy signal. Here we use Random Matrix Theory to analyze a series of short-time molecular dynamics experiments which are specifically designed to be simulations with high cosine content. We use as a model system the protein apoCox17, a mitochondrial copper chaperone. Spectral analysis on correlation matrices allows to easily differentiate random correlations, simply deriving from the finite length of the process, from non-random signals reflecting the intrinsic system properties. Our results clearly show that protein dynamics is not really Brownian also in presence of the cosine-shaped low index projections on principal axes.

  8. Structural Analysis of Molecular Clouds: Dendrograms

    CERN Document Server

    Rosolowsky, E W; Kauffmann, J; Goodman, A A


    We demonstrate the utility of dendrograms at representing the essential features of the hierarchical structure of the isosurfaces for molecular line data cubes. The dendrogram of a data cube is an abstraction of the changing topology of the isosurfaces as a function of contour level. The ability to track hierarchical structure over a range of scales makes this analysis philosophically different from local segmentation algorithms like CLUMPFIND. Points in the dendrogram structure correspond to specific volumes in data cubes defined by their bounding isosurfaces. We further refine the technique by measuring the properties associated with each isosurface in the analysis allowing for a multiscale calculation of molecular gas properties. Using COMPLETE 13CO(1-0) data from the L1448 region in Perseus and mock observations of a simulated data cube, we identify regions that have a significant contribution by self-gravity to their energetics on a range of scales. We find evidence for self-gravitation on all spatial sc...

  9. Dental diagnostics: molecular analysis of oral biofilms. (United States)

    Hiyari, Sarah; Bennett, Katie M


    Dental biofilms are complex, multi-species bacterial communities that colonize the mouth in the form of plaque and are known to cause dental caries and periodontal disease. Biofilms are unique from planktonic bacteria in that they are mutualistic communities with a 3-dimensional structure and complex nutritional and communication pathways. The homeostasis within the biofilm colony can be disrupted, causing a shift in the bacterial composition of the colony and resulting in proliferation of pathogenic species. Because of this dynamic lifestyle, traditional microbiological techniques are inadequate for the study of biofilms. Many of the bacteria present in the oral cavity are viable but not culturable, which severely limits laboratory analysis. However, with the advent of new molecular techniques, the microbial makeup of oral biofilms can be better identified. Some of these techniques include DNA-DNA hybridization, 16S rRNA gene sequencing, denaturing gradient gel electrophoresis, terminal restriction fragment length polymorphism, denaturing high-performance liquid chromatography and pyrosequencing. This review provides an overview of biofilm formation and examines the major molecular techniques currently used in oral biofilm analysis. Future applications of the molecular analysis of oral biofilms in the diagnosis and treatment of caries and periodontal disease are also discussed.

  10. Investigation of multilayer painting by means of molecular spectroscopy (United States)

    Kadikova, I. F.; Grigorieva, I. A.


    The study of paintings' layer structure under microscope was implemented in the early XX century; since that time method of cross-section preparation as well as composition of embedded materials changed and capabilities of optical microscopy broadened. Nevertheless, until recently cross-sections were prepared only for analysis of paintings' layer-specific structure, morphological and technological features, tracks of restoration treatments. Examination of chemical composition required additional sampling as well as division of these samples layer by layer in order to determine pigments and binding media; these procedures didn't always lead to proper results. Micro-Raman and micro-FTIR spectroscopy allow carrying out investigation of painting cross-sections without any additional preliminary sampling; this is shown on example of investigation of a number of paintings.

  11. Investigation of multilayer painting by means of molecular spectroscopy

    Directory of Open Access Journals (Sweden)

    Kadikova I.F.


    Full Text Available The study of paintings’ layer structure under microscope was implemented in the early XX century; since that time method of cross-section preparation as well as composition of embedded materials changed and capabilities of optical microscopy broadened. Nevertheless, until recently cross-sections were prepared only for analysis of paintings’ layer-specific structure, morphological and technological features, tracks of restoration treatments. Examination of chemical composition required additional sampling as well as division of these samples layer by layer in order to determine pigments and binding media; these procedures didn’t always lead to proper results. Micro-Raman and micro-FTIR spectroscopy allow carrying out investigation of painting cross-sections without any additional preliminary sampling; this is shown on example of investigation of a number of paintings.

  12. Spectroscopic investigation (FT-IR and FT-Raman), vibrational assignments, HOMO-LUMO analysis and molecular docking study of 2-(Adamantan-1-yl)-5-(4-nitrophenyl)-1,3,4-oxadiazole (United States)

    Haress, Nadia G.; Al-Omary, Fatmah; El-Emam, Ali A.; Mary, Y. Sheena; Panicker, C. Yohannan; Al-Saadi, Abdulaziz A.; War, Javeed Ahmad; Van Alsenoy, Christian


    FT-IR and FT-Raman spectra of 2-(Adamantan-1-yl)-5-(4-nitrophenyl)-1,3,4-oxadiazole were recorded and analyzed. The vibrational wavenumbers were computed using DFT quantum chemical calculations. The data obtained from wavenumber calculations are used to assign vibrational bands obtained experimentally. The energy barriers of the internal rotations about the Csbnd C bonds connecting the oxadiazole to the adamantane and benzene rings are reported. The geometrical parameters (DFT) of the title compound are in agreement with the XRD results. The calculated HOMO and LUMO energies allow the calculations of atomic and molecular properties and they also showed that charge transfer occurs in the molecule. A detailed molecular picture of the title compound and its interactions were obtained from NBO analysis. As can be seen from the MEP map of the title compound, which regions having the negative potential are over the electro negative atoms, the region having the positive potential are over the phenyl and adamantine rings and the remaining species are surrounded by zero potential. The molecular docking studies reveal that the adamantyl derivative may exhibit C-South African HIV-proteas inhibitory activity.

  13. Molecular identification of blow flies recovered from human cadavers during crime scene investigations in Malaysia. (United States)

    Kavitha, Rajagopal; Nazni, Wasi Ahmad; Tan, Tian Chye; Lee, Han Lim; Isa, Mohd Noor Mat; Azirun, Mohd Sofian


    Forensic entomology applies knowledge about insects associated with decedent in crime scene investigation. It is possible to calculate a minimum postmortem interval (PMI) by determining the age and species of the oldest blow fly larvae feeding on decedent. This study was conducted in Malaysia to identify maggot specimens collected during crime scene investigations. The usefulness of the molecular and morphological approach in species identifications was evaluated in 10 morphologically identified blow fly larvae sampled from 10 different crime scenes in Malaysia. The molecular identification method involved the sequencing of a total length of 2.2 kilo base pairs encompassing the 'barcode' fragments of the mitochondrial cytochrome oxidase I (COI), cytochrome oxidase II (COII) and t-RNA leucine genes. Phylogenetic analyses confirmed the presence of Chrysomya megacephala, Chrysomya rufifacies and Chrysomya nigripes. In addition, one unidentified blow fly species was found based on phylogenetic tree analysis.

  14. Oncological image analysis: medical and molecular image analysis (United States)

    Brady, Michael


    This paper summarises the work we have been doing on joint projects with GE Healthcare on colorectal and liver cancer, and with Siemens Molecular Imaging on dynamic PET. First, we recall the salient facts about cancer and oncological image analysis. Then we introduce some of the work that we have done on analysing clinical MRI images of colorectal and liver cancer, specifically the detection of lymph nodes and segmentation of the circumferential resection margin. In the second part of the paper, we shift attention to the complementary aspect of molecular image analysis, illustrating our approach with some recent work on: tumour acidosis, tumour hypoxia, and multiply drug resistant tumours.

  15. Visual verification and analysis of cluster detection for molecular dynamics. (United States)

    Grottel, Sebastian; Reina, Guido; Vrabec, Jadran; Ertl, Thomas


    A current research topic in molecular thermodynamics is the condensation of vapor to liquid and the investigation of this process at the molecular level. Condensation is found in many physical phenomena, e.g. the formation of atmospheric clouds or the processes inside steam turbines, where a detailed knowledge of the dynamics of condensation processes will help to optimize energy efficiency and avoid problems with droplets of macroscopic size. The key properties of these processes are the nucleation rate and the critical cluster size. For the calculation of these properties it is essential to make use of a meaningful definition of molecular clusters, which currently is a not completely resolved issue. In this paper a framework capable of interactively visualizing molecular datasets of such nucleation simulations is presented, with an emphasis on the detected molecular clusters. To check the quality of the results of the cluster detection, our framework introduces the concept of flow groups to highlight potential cluster evolution over time which is not detected by the employed algorithm. To confirm the findings of the visual analysis, we coupled the rendering view with a schematic view of the clusters' evolution. This allows to rapidly assess the quality of the molecular cluster detection algorithm and to identify locations in the simulation data in space as well as in time where the cluster detection fails. Thus, thermodynamics researchers can eliminate weaknesses in their cluster detection algorithms. Several examples for the effective and efficient usage of our tool are presented.

  16. Molecular mechanics conformational analysis of tylosin (United States)

    Ivanov, Petko M.


    The conformations of the 16-membered macrolide antibiotic tylosin were studied with molecular mechanics (AMBER∗ force field) including modelling of the effect of the solvent on the conformational preferences (GB/SA). A Monte Carlo conformational search procedure was used for finding the most probable low-energy conformations. The present study provides complementary data to recently reported analysis of the conformations of tylosin based on NMR techniques. A search for the low-energy conformations of protynolide, a 16-membered lactone containing the same aglycone as tylosin, was also carried out, and the results were compared with the observed conformation in the crystal as well as with the most probable conformations of the macrocyclic ring of tylosin. The dependence of the results on force field was also studied by utilizing the MM3 force field. Some particular conformations were computed with the semiempirical molecular orbital methods AM1 and PM3.

  17. Theoretical Analysis of Dynamic Processes for Interacting Molecular Motors. (United States)

    Teimouri, Hamid; Kolomeisky, Anatoly B; Mehrabiani, Kareem


    Biological transport is supported by collective dynamics of enzymatic molecules that are called motor proteins or molecular motors. Experiments suggest that motor proteins interact locally via short-range potentials. We investigate the fundamental role of these interactions by analyzing a new class of totally asymmetric exclusion processes where interactions are accounted for in a thermodynamically consistent fashion. It allows us to connect explicitly microscopic features of motor proteins with their collective dynamic properties. Theoretical analysis that combines various mean-field calculations and computer simulations suggests that dynamic properties of molecular motors strongly depend on interactions, and correlations are stronger for interacting motor proteins. Surprisingly, it is found that there is an optimal strength of interactions (weak repulsion) that leads to a maximal particle flux. It is also argued that molecular motors transport is more sensitive to attractive interactions. Applications of these results for kinesin motor proteins are discussed.

  18. GenomicScape: an easy-to-use web tool for gene expression data analysis. Application to investigate the molecular events in the differentiation of B cells into plasma cells. (United States)

    Kassambara, Alboukadel; Rème, Thierry; Jourdan, Michel; Fest, Thierry; Hose, Dirk; Tarte, Karin; Klein, Bernard


    DNA microarrays have considerably helped to improve the understanding of biological processes and diseases. Large amounts of publicly available microarray data are accumulating, but are poorly exploited due to a lack of easy-to-use bioinformatics resources. The aim of this study is to build a free and convenient data-mining web site ( GenomicScape allows mining dataset from various microarray platforms, identifying genes differentially expressed between populations, clustering populations, visualizing expression profiles of large sets of genes, and exporting results and figures. We show how easily GenomicScape makes it possible to construct a molecular atlas of the B cell differentiation using publicly available transcriptome data of naïve B cells, centroblasts, centrocytes, memory B cells, preplasmablasts, plasmablasts, early plasma cells and bone marrow plasma cells. Genes overexpressed in each population and the pathways encoded by these genes are provided as well as how the populations cluster together. All the analyses, tables and figures can be easily done and exported using GenomicScape and this B cell to plasma cell atlas is freely available online. Beyond this B cell to plasma cell atlas, the molecular characteristics of any biological process can be easily and freely investigated by uploading the corresponding transcriptome files into GenomicScape.

  19. Spectroscopic (FT-IR, FT-Raman and UV) investigation, NLO, NBO, molecular orbital and MESP analysis of 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid (United States)

    Govindasamy, P.; Gunasekaran, S.


    In this work, FT-IR and FT-Raman spectra of 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid (abbreviated as 2DCPAPAA) have been reported in the regions 4000-450 cm-1 and 4000-50 cm-1, respectively. The molecular structure, geometry optimization, intensities, vibrational frequencies were obtained by the ab initio and DFT levels of theory B3LYP with 6-311++G(d,p) standard basis set and a different scaling of the calculated wave numbers. The complete vibrational assignments were performed on the basis of the potential energy distribution (PED) of the vibrational modes calculated using vibrational energy distribution analysis (VEDA 4) program. The harmonic frequencies were calculated and the scaled values were compared with experimental FT-IR and FT-Raman data. The observed and the calculated frequencies are found to be in good agreement. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The thermodynamic properties of the title compound at different temperature reveal the correlations between standard heat capacities (C) standard entropies (S) standard enthalpy changes (ΔH). The important non-linear optical properties such as electric dipole momentum, polarizability and first hyperpolarizability of 2DCPAPAA have been computed using B3LYP/6-311++G(d,p) quantum chemical calculations. The Natural charges, HOMO, LUMO, chemical hardness (η), chemical potential (μ), Electro negativity (χ) and electrophilicity values (ω) are calculated and reported. The oscillator's strength, wave length, and energy calculated by TD-DFT and 2DCPAPAA is approach complement with the experimental findings. The molecular electrostatic potential (MESP) surfaces of the molecule were constructed.

  20. [Molecular genetic investigation of sugar beet (Beta vulgaris L.)]. (United States)

    Butorina, A K; Kornienko, A V


    Molecular genetic studies of sugar beet (Beta vulgaris L.) are reviewed as a basis for the development of genomics of this species. The methods used to study structural and functional genomics are considered. The results and their application to increase the efficiency of sugar beet breeding are discussed.

  1. Investigating Ceiling Effects in Longitudinal Data Analysis (United States)

    Wang, Lijuan; Zhang, Zhiyong; McArdle, John J.; Salthouse, Timothy A.


    Score limitation at the top of a scale is commonly termed "ceiling effect." Ceiling effects can lead to serious artifactual parameter estimates in most data analysis. This study examines the consequences of ceiling effects in longitudinal data analysis and investigates several methods of dealing with ceiling effects through Monte Carlo simulations…

  2. Synchrotron based mass spectrometry to investigate the molecular properties of mineral-organic associations

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Suet Yi; Kleber, Markus; Takahashi, Lynelle K.; Nico, Peter; Keiluweit, Marco; Ahmed, Musahid


    Soil organic matter (OM) is important because its decay drives life processes in the biosphere. Analysis of organic compounds in geological systems is difficult because of their intimate association with mineral surfaces. To date there is no procedure capable of quantitatively separating organic from mineral phases without creating artifacts or mass loss. Therefore, analytical techniques that can (a) generate information about both organic and mineral phases simultaneously and (b) allow the examination of predetermined high-interest regions of the sample as opposed to conventional bulk analytical techniques are valuable. Laser Desorption Synchrotron Postionization (synchrotron-LDPI) mass spectrometry is introduced as a novel analytical tool to characterize the molecular properties of organic compounds in mineral-organic samples from terrestrial systems, and it is demonstrated that when combined with Secondary Ion Mass Spectrometry (SIMS), can provide complementary information on mineral composition. Mass spectrometry along a decomposition gradient in density fractions, verifies the consistency of our results with bulk analytical techniques. We further demonstrate that by changing laser and photoionization energies, variations in molecular stability of organic compounds associated with mineral surfaces can be determined. The combination of synchrotron-LDPI and SIMS shows that the energetic conditions involved in desorption and ionization of organic matter may be a greater determinant of mass spectral signatures than the inherent molecular structure of the organic compounds investigated. The latter has implications for molecular models of natural organic matter that are based on mass spectrometric information.

  3. Molecular-level investigation on electrochemical interfaces by Raman spectroscopy

    Institute of Scientific and Technical Information of China (English)

    TIAN, Zhong-Qun; REN, Bin


    The structure and dynamics of electrode/liquid interfaces play an increasingly important role in electrochemistry. Raman spectroscopy is capable of providing detailed structural information at molecular level and new insight into the interfacial structure, adsorption, reaction, electrocatalysis and corrosion. In this account we will summarize some progresses of surface Raman spectroscopy in the study of electrochemical interfaces, mainly based on our group's work, laying emphasis on the detection sensitivity, spectral resolution, time resolution and spatial resolution as well as the hyphenated technique.

  4. Propagation Modeling and Analysis of Molecular Motors in Molecular Communication. (United States)

    Chahibi, Youssef; Akyildiz, Ian F; Balasingham, Ilangko


    Molecular motor networks (MMNs) are networks constructed from molecular motors to enable nanomachines to perform coordinated tasks of sensing, computing, and actuation at the nano- and micro- scales. Living cells are naturally enabled with this same mechanism to establish point-to-point communication between different locations inside the cell. Similar to a railway system, the cytoplasm contains an intricate infrastructure of tracks, named microtubules, interconnecting different internal components of the cell. Motor proteins, such as kinesin and dynein, are able to travel along these tracks directionally, carrying with them large molecules that would otherwise be unreliably transported across the cytoplasm using free diffusion. Molecular communication has been previously proposed for the design and study of MMNs. However, the topological aspects of MMNs, including the effects of branches, have been ignored in the existing studies. In this paper, a physical end-to-end model for MMNs is developed, considering the location of the transmitter node, the network topology, and the receiver nodes. The end-to-end gain and group delay are considered as the performance measures, and analytical expressions for them are derived. The analytical model is validated by Monte-Carlo simulations and the performance of MMNs is analyzed numerically. It is shown that, depending on their nature and position, MMN nodes create impedance effects that are critical for the overall performance. This model could be applied to assist the design of artificial MMNs and to study cargo transport in neurofilaments to elucidate brain diseases related to microtubule jamming.

  5. Investigation of deformation mechanisms of staggered nanocomposites using molecular dynamics (United States)

    Mathiazhagan, S.; Anup, S.


    Biological materials with nanostructure of regularly or stair-wise staggered arrangements of hard platelets reinforced in a soft protein matrix have superior mechanical properties. Applications of these nanostructures to ceramic matrix composites could enhance their toughness. Using molecular dynamics simulations, mechanical behaviour of the bio-inspired nanocomposites is studied. Regularly staggered model shows better flow behaviour compared to stair-wise staggered model due to the symmetrical crack propagation along the interface. Though higher stiffness and strength are obtained for stair-wise staggered models, rapid crack propagation reduces the toughness. Arresting this crack propagation could lead to superior mechanical properties in stair-wise staggered models.

  6. Interaction of collagen with carbon nanotube: a molecular dynamics investigation. (United States)

    Gopalakrishnan, R; Subramanian, V


    In variety of biological applications carbon nano materials interact with different biological macromolecules, such as proteins, carbohydrates and nucleic acids. In this study carbon nanotube (CNT) has been used as the model for carbon nanomaterials. Since, collagen is a large protein; model collagen like peptide (CPs) has been used to understand the interaction between CNT and collagen. Molecular dynamics (MD) simulation showed that the hydrophobic-hydrophobic interaction of the CNT-CPs play a crucial role in attracting the CPs towards the CNT. No structural aberrations occured in collagen upon interaction with CNT and hence CNT can be employed in the tissue engineering applications.

  7. Identification of a Conserved 8 aa Insert in the PIP5K Protein in the Saccharomycetaceae family of Fungi and the Molecular Dynamics Simulations and Structural Analysis to investigate its Potential Functional Role. (United States)

    Khadka, Bijendra; Gupta, Radhey S


    Homologs of the phosphatidylinositol-4-phosphate-5-kinase (PIP5K), which controls a multitude of essential cellular functions, contain a 8 aa insert in a conserved region that is specific for the Saccharomycetaceae family of fungi. Using structures of human PIP4K proteins as templates, structural models were generated of the Saccharomyces cerevisiae and human PIP5K proteins. In the modeled S. cerevisiae PIP5K, the 8 aa insert forms a surface exposed loop, present on the same face of the protein as the activation loop of the kinase domain. Electrostatic potential analysis indicates that the residues from 8 aa conserved loop form a highly-positively charged surface patch, which through electrostatic interaction with the anionic portions of phospholipid head groups, is expected to play a role in the membrane interaction of the yeast PIP5K. To unravel this prediction, molecular dynamics (MD) simulations were carried out to examine the binding interaction of PIP5K, either containing or lacking the conserved signature insert (CSI), with two different membrane lipid bilayers. The results from MD studies provide insights concerning the mechanistic of interaction of PIP5K with lipid bilayer, and support the contention that the identified 8 aa conserved insert in fungal PIP5K plays an important role in the binding of this protein with membrane surface. This article is protected by copyright. All rights reserved.

  8. Molecular orbital studies (hardness, chemical potential, electronegativity and electrophilicity), vibrational spectroscopic investigation and normal coordinate analysis of 5-{1-hydroxy-2-[(propan-2-yl)amino]ethyl}benzene-1,3-diol. (United States)

    Muthu, S; Renuga, S


    FT-IR and FT-Raman spectra of 5-{1-hydroxy-2-[(propan-2-yl) amino] ethyl} benzene-1,3-diol (abbrevi- 54 ated as HPAEBD) were recorded in the region 4000-450 cm(-1) and 4000-100 cm(-1) respectively. The structure of the molecule was optimized and the structural characteristics were determined by density functional theory (B3LYP) and HF method with 6-31 G(d,p) as basis set. The theoretical wave numbers were scaled and compared with experimental FT-IR and FT-Raman spectra. A detailed interpretation of the vibrational spectra of this compound has been made on the basis of the calculated Potential energy distribution (PED). Stability of the molecule arising from hyperconjugation and charge delocalization is confirmed by the natural bond orbital analysis (NBO). The results show that electron density (ED) in the σ antibonding orbitals and E (2) energies confirm the occurrence of intra molecular charge transfer (ICT) within the molecule. The molecule orbital contributions were studied by using the total (TDOS), sum of α and β electron (αβDOS) density of States. Mulliken population analysis of atomic charges is also calculated. The calculated HOMO and LUMO energy gap shows that charge transfer occurs within the molecule. The electron density-based local reactivity descriptors such as Fukui functions were calculated to explain the chemical selectivity or reactivity site in this compound. On the basis of vibrational analyses, the thermodynamic properties of title compound at different temperatures have been calculated.

  9. Investigation of molecular penetration depth variation with SMBI fluxes (United States)

    Zhou, Yu-Lin; Wang, Zhan-Hui; Xu, Min; Wang, Qi; Nie, Lin; Feng, Hao; Sun, Wei-Guo


    We study the molecular penetration depth variation with the SMBI fluxes. The molecular transport process and the penetration depth during SMBI with various injection velocities and densities are simulated and compared. It is found that the penetration depth of molecules strongly depends on the radial convective transport of SMBI and it increases with the increase of the injection velocity. The penetration depth does not vary much once the SMBI injection density is larger than a critical value due to the dramatic increase of the dissociation rate on the fueling path. An effective way to improve the SMBI penetration depth has been predicted, which is SMBI with a large radial injection velocity and a lower molecule injection density than the critical density. Project supported by the National Natural Science Foundation of China (Grant Nos. 11375053, 11575055, 11405022, and 11405112), the Chinese National Fusion Project for ITER (Grant Nos. 2013GB107001 and 2013GB112005), the International S&T Cooperation Program of China (Grant No. 2015DFA61760), and the Funds of the Youth Innovation Team of Science and Technology in Sichuan Province of China (Grant No. 2014TD0023).

  10. Investigation of the charge transport through disordered organic molecular heterojunctions (United States)

    Houili, H.; Tutiš, E.; Batistić, I.; Zuppiroli, L.


    We present a three-dimensional multiparticle Monte Carlo (3DMPMC) simulation of hopping transport in disordered organic molecular media. We used this approach in order to study the charge transport across an energetically disordered organic molecular heterojunction which is known to strongly influence the characteristics of the multilayer devices based on thin organic films. The role of the energetic disorder and its spatial correlations, which govern the transport in the bulk, are examined here for the bilayer homopolar system where the heterojunction represents the bottleneck for the transport. We study the effects of disorder on both sides of the heterojunction, including the effects of the spatial correlation within each material and among the layers. The 3DMPMC approach allowed us to correctly tackle the effects of the Coulomb interaction among carriers in the region where the charge accumulation in the device is particularly important and the Coulomb interaction most pronounced. The Coulomb interaction enhances the current by increasing the electric field at the heterojunction as well as by affecting the thermalization of the carriers in front of the barrier. In order to build a rather comprehensive picture of the hopping transport over the homopolar heterojunction, we supplemented the MC simulations by a master equation (ME) calculation.

  11. Molecular forensic science analysis of nuclear materials (United States)

    Reilly, Dallas David

    Concerns over the proliferation and instances of nuclear material in the environment have increased interest in the expansion of nuclear forensics analysis and attribution programs. A new related field, molecular forensic science (MFS) has helped meet this expansion by applying common scientific analyses to nuclear forensics scenarios. In this work, MFS was applied to three scenarios related to nuclear forensics analysis. In the first, uranium dioxide was synthesized and aged at four sets of static environmental conditions and studied for changes in chemical speciation. The second highlighted the importance of bulk versus particle characterizations by analyzing a heterogeneous industrially prepared sample with similar techniques. In the third, mixed uranium/plutonium hot particles were collected from the McGuire Air Force Base BOMARC Site and analyzed for chemical speciation and elemental surface composition. This work has identified new signatures and has indicated unexpected chemical behavior under various conditions. These findings have lead to an expansion of basic actinide understanding, proof of MFS as a tool for nuclear forensic science, and new areas for expansion in these fields.

  12. Molecular analysis of holoprosencephaly in South America

    Directory of Open Access Journals (Sweden)

    Clarice Pagani Savastano


    Full Text Available Holoprosencephaly (HPE is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC, and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases.

  13. Investigation of deformation mechanisms of staggered nanocomposites using molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Mathiazhagan, S., E-mail:; Anup, S., E-mail:


    Biological materials with nanostructure of regularly or stair-wise staggered arrangements of hard platelets reinforced in a soft protein matrix have superior mechanical properties. Applications of these nanostructures to ceramic matrix composites could enhance their toughness. Using molecular dynamics simulations, mechanical behaviour of the bio-inspired nanocomposites is studied. Regularly staggered model shows better flow behaviour compared to stair-wise staggered model due to the symmetrical crack propagation along the interface. Though higher stiffness and strength are obtained for stair-wise staggered models, rapid crack propagation reduces the toughness. Arresting this crack propagation could lead to superior mechanical properties in stair-wise staggered models. - Highlights: • The deformation behaviour of staggered nanocomposites is studied. • Stair-wise staggered model has high stiffness and strength, but low toughness. • Rapid crack growth in overlap region causes this low toughness. • Toughness could be enhanced by arresting interfacial crack in the overlap.

  14. A molecular dynamics investigation of surface reconstruction on magnetite (001) (United States)

    Rustad, J. R.; Wasserman, E.; Felmy, A. R.


    Molecular dynamics calculations using analytical potential functions with polarizable oxygen ions have been used to identify a novel mode of reconstruction on the half-occupied tetrahedral layer termination of the magnetite (Fe 3O 4) (001) surface. In the proposed reconstruction, the twofold coordinated iron ion in the top monolayer rotates downward to occupy a vacant half-octahedral site in the plane of the second-layer iron ions. At the same time, half of the tetrahedral iron ions in the third iron layer are pushed upward to occupy an adjacent octahedral vacancy at the level of the second-layer iron ions. The other half of the third-layer iron ions remain roughly in their original positions. The proposed reconstruction is consistent with recent low-energy electron diffraction and X-ray photoelectron spectroscopy results. It also provides a compelling interpretation for the arrangement of atoms suggested by high-resolution scanning-tunneling microscopy studies.

  15. Who Scared the Cat? A Molecular Crime Scene Investigation Laboratory Exercise† (United States)

    Ott, Laura E.; Carson, Susan D.


    This introductory laboratory exercise gives first-year life science majors or nonmajors an opportunity to gain knowledge and experience in basic bioinformatics and molecular biology laboratory techniques and analysis in the context of a mock crime scene investigation. In this laboratory, students determine if a human (Lady) or dog (Kona) committed the fictional crime of scaring a cat. Students begin by performing in silico PCR using provided dog- and human-specific PCR primers to determine the sequences to be amplified and predict PCR amplicon sizes. They then BLAST (Basic Local Alignment Search Tool) the in silico PCR results to confirm that the PCR primers are designed to amplify genomic fragments of the cardiac actin gene in both dogs and humans. Finally, they use DNA quantification techniques, PCR, and agarose gel electrophoresis to identify the culprit and they confirm results by analyzing Sanger sequencing. Student learning gains were demonstrated by successful execution of the lab and by analysis and interpretation of data in the completion of laboratory reports. The student learning gains were also demonstrated by increased performance on a post-laboratory assessment compared to the pre-assessment. A post-activity assessment also revealed that students perceived gains in the skills and conceptual knowledge associated with the student learning outcomes. Finally, assessment of this introductory molecular biology and bio-informatics activity reveals that it allows first-year students to develop higher-order data analysis and interpretation skills. PMID:28101273

  16. Who Scared the Cat? A Molecular Crime Scene Investigation Laboratory Exercise

    Directory of Open Access Journals (Sweden)

    Laura E. Ott


    Full Text Available This introductory laboratory exercise gives first-year life science majors or nonmajors an opportunity to gain knowledge and experience in basic bioinformatics and molecular biology laboratory techniques and analysis in the context of a mock crime scene investigation. In this laboratory, students determine if a human (Lady or dog (Kona committed the fictional crime of scaring a cat. Students begin by performing in silico PCR using provided dog- and human-specific PCR primers to determine the sequences to be amplified and predict PCR amplicon sizes. They then BLAST (Basic Local Alignment Search Tool the in silico PCR results to confirm that the PCR primers are designed to amplify genomic fragments of the cardiac actin gene in both dogs and humans. Finally, they use DNA quantification techniques, PCR, and agarose gel electrophoresis to identify the culprit and they confirm results by analyzing Sanger sequencing. Student learning gains were demonstrated by successful execution of the lab and by analysis and interpretation of data in the completion of laboratory reports. The student learning gains were also demonstrated by increased performance on a post-laboratory assessment compared to the pre-assessment. A post-activity assessment also revealed that students perceived gains in the skills and conceptual knowledge associated with the student learning outcomes. Finally, assessment of this introductory molecular biology and bioinformatics activity reveals that it allows first-year students to develop higher-order data analysis and interpretation skills.

  17. Who Scared the Cat? A Molecular Crime Scene Investigation Laboratory Exercise. (United States)

    Ott, Laura E; Carson, Susan D


    This introductory laboratory exercise gives first-year life science majors or nonmajors an opportunity to gain knowledge and experience in basic bioinformatics and molecular biology laboratory techniques and analysis in the context of a mock crime scene investigation. In this laboratory, students determine if a human (Lady) or dog (Kona) committed the fictional crime of scaring a cat. Students begin by performing in silico PCR using provided dog- and human-specific PCR primers to determine the sequences to be amplified and predict PCR amplicon sizes. They then BLAST (Basic Local Alignment Search Tool) the in silico PCR results to confirm that the PCR primers are designed to amplify genomic fragments of the cardiac actin gene in both dogs and humans. Finally, they use DNA quantification techniques, PCR, and agarose gel electrophoresis to identify the culprit and they confirm results by analyzing Sanger sequencing. Student learning gains were demonstrated by successful execution of the lab and by analysis and interpretation of data in the completion of laboratory reports. The student learning gains were also demonstrated by increased performance on a post-laboratory assessment compared to the pre-assessment. A post-activity assessment also revealed that students perceived gains in the skills and conceptual knowledge associated with the student learning outcomes. Finally, assessment of this introductory molecular biology and bio-informatics activity reveals that it allows first-year students to develop higher-order data analysis and interpretation skills.

  18. Polymer Molecular Weight Analysis by [Superscript 1]H NMR Spectroscopy (United States)

    Izunobi, Josephat U.; Higginbotham, Clement L.


    The measurement and analysis of molecular weight and molecular weight distribution remain matters of fundamental importance for the characterization and physical properties of polymers. Gel permeation chromatography (GPC) is the most routinely used method for the molecular weight determination of polymers whereas matrix-assisted laser…

  19. Alternative Radioligands for Investigating the Molecular Pharmacology of Melatonin Receptors. (United States)

    Legros, Céline; Brasseur, Chantal; Delagrange, Philippe; Ducrot, Pierre; Nosjean, Olivier; Boutin, Jean A


    Melatonin exerts a variety of physiologic activities that are mainly relayed through the melatonin receptors MT1 and MT2 Low expressions of these receptors in tissues have led to widespread experimental use of the agonist 2-[(125)I]-iodomelatonin as a substitute for melatonin. We describe three iodinated ligands: 2-(2-[(2-iodo-4,5-dimethoxyphenyl)methyl]-4,5-dimethoxy phenyl) (DIV880) and (2-iodo-N-2-[5-methoxy-2-(naphthalen-1-yl)-1H-pyrrolo[3,2-b]pyridine-3-yl])acetamide (S70254), which are specific ligands at MT2 receptors, and N-[2-(5-methoxy-1H-indol-3-yl)ethyl]iodoacetamide (SD6), an analog of 2-[(125)I]-iodomelatonin with slightly different characteristics. Here, we further characterized these new ligands with regards to their molecular pharmacology. We performed binding experiments, saturation assays, association/dissociation rate measurements, and autoradiography using sheep and rat tissues and recombinant cell lines. Our results showed that [(125)I]-S70254 is receptor, and can be used with both cells and tissue. This radioligand can be used in autoradiography. Similarly, DIV880, a partial agonist [43% of melatonin on guanosine 5'-3-O-(thio)triphosphate binding assay], selective for MT2, can be used as a tool to selectively describe the pharmacology of this receptor in tissue samples. The molecular pharmacology of both human melatonin receptors MT1 and MT2, using a series of 24 ligands at these receptors and the new radioligands, did not lead to noticeable variations in the profiles. For the first time, we described radiolabeled tools that are specific for one of the melatonin receptors (MT2). These tools are amenable to binding experiments and to autoradiography using sheep or rat tissues. These specific tools will permit better understanding of the role and implication in physiopathologic processes of the melatonin receptors.

  20. Juvenile neuronal ceroid-lipofuscinosis: clinical and molecular investigation in a large family in Brazil

    Directory of Open Access Journals (Sweden)

    Eugênia Ribeiro Valadares


    Full Text Available OBJECTIVE: Juvenile Neuronal Ceroid-Lipofuscinosis (JNCL, CLN 3, Batten Disease (OMIM #204200 belongs to the most common group of neurodegenerative disorders of childhood. We report the clinical data and molecular analysis of a large Brazilian family. METHOD: Family composed of two consanguineous couples and thirty-two children. Clinical data of ten JNCL patients and molecular analyses on 13 participants were obtained. RESULTS: The large 1.02 kb deletion was detected. The most severe phenotype, with autistic behavior, tics and parkinsonism was seen in a 12-year-old female and a milder phenotype in a 14-year-old male. Nyctalopia was the first symptom in one deceased child. The visual loss of six patients has been first observed in the school and not at home. CONCLUSION: The report highlights the phenotypical intrafamily variation in 10 affected children of this family. The molecular investigation of this large family in our metabolic center turned possible the diagnosis, right approach and genetic counseling.

  1. An experimental and theoretical investigation of Acenaphthene-5-boronic acid: conformational study, NBO and NLO analysis, molecular structure and FT-IR, FT-Raman, NMR and UV spectra. (United States)

    Karabacak, Mehmet; Sinha, Leena; Prasad, Onkar; Asiri, Abdullah M; Cinar, Mehmet


    The solid state Fourier transform infrared (FT-IR) and FT-Raman spectra of Acenaphthene-5-boronic acid (AN-5-BA), have been recorded in the range 4000-400cm(-1) and 4000-10cm(-1), respectively. Density functional theory (DFT), with the B3LYP functional was used for the optimization of the ground state geometry and simulation of the infrared and Raman spectra of the molecule. The vibrational wave numbers and their assignments were examined theoretically using the Gaussian 09 set of quantum chemistry codes and the normal modes were assigned by a scaled quantum mechanical (SQM) force field approach. Hydrogen-bonded dimer of AN-5-BA, optimized by counterpoise correction, has also been studied by B3LYP at the 6-311++G(d,p) level and the effects of molecular association through O-H⋯O hydrogen bonding have been discussed. The (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by Gauge-Including Atomic Orbital (GIAO) method. Natural bond orbital (NBO) analysis has been applied to study stability of the molecule arising from charge delocalization. UV spectrum of the title compound was also recorded and the electronic properties, such as frontier orbitals, and band gap energies were measured by TD-DFT approach. The first order hyperpolarizability 〈β〉, its components and associated properties such as average polarizability and anisotropy of the polarizability (α and Δα) of AN-5-BA was calculated using the finite-field approach.

  2. Investigation of the molecular relationship between breast cancer and obesity by candidate gene prioritization methods

    Directory of Open Access Journals (Sweden)

    Saba Garshasbi


    Full Text Available Background: Cancer and obesity are two major public health concerns. More than 12 million cases of cancer are reported annually. Many reports confirmed obesity as a risk factor for cancer. The molecular relationship between obesity and breast cancer has not been clear yet. The purpose of this study was to investigate priorities of effective genes in the molecular relationship between obesity and breast cancer. Methods: In this study, computer simulation method was used for prioritizing the genes that involved in the molecular links between obesity and breast cancer in laboratory of systems biology and bioinformatics (LBB, Tehran University, Tehran, Iran, from March to July 2014. In this study, ENDEAVOUR software was used for prioritizing the genes and integrating multiple data sources was used for data analysis. Training genes were selected from effective genes in obesity and/or breast cancer. Two groups of candidate genes were selected. The first group was included the existential genes in 5 common region chromosomes (between obesity and breast cancer and the second group was included the results of genes microarray data analysis of research Creighton, et al (In 2012 on patients with breast cancer. The microarray data were analyzed with GER2 software (R online software on GEO website. Finally, both training and candidate genes were entered in ENDEAVOUR software package. Results: The candidate genes were prioritized to four style and five genes in ten of the first priorities were repeated twice. In other word, the outcome of prioritizing of 72 genes (Product of microarray data analysis and genes of 5 common chromosome regions (Between obesity and breast cancer showed, 5 genes (TNFRSF10B, F2, IGFALS, NTRK3 and HSP90B1 were the priorities in the molecular connection between obesity and breast cancer. Conclusion: There are some common genes between breast cancer and obesity. So, molecular relationship is confirmed. In this study the possible effect

  3. Dynamic Wetting on Graphene-Coated Surface: Molecular Dynamics Investigation (United States)

    Hung, Shih-Wei; Shiomi, Junichiro


    Wettability of graphene-coated surface gained significant attention recently due to discussion on the ``transparency'' (whether the wetting characteristics follow that of graphene or the underlying surface) and practical applications of graphene. In terms of static contact angle, the wettability of graphene-coated surfaces have been widely studied by experiments, simulations, and theory in recent years. However, the studies of dynamic wetting on graphene-coated surfaces are limited. In the present study, molecular dynamics simulation was performed to study the dynamic wetting of water droplet on graphene-coated surfaces from a microscopic point of view. The results show that the degree of similarity between the spreading behavior on graphene-coated surface and that on pure graphene (or that on the underlying surface) depends on time, i.e. how nonequilibrium the interface dynamics is. We also found that this feature can be altered by introducing defects into graphene. The work is partially supported by Grant-in-Aid for JSPS Fellows 26-04364 and JST CREST.

  4. A First-principles Molecular Dynamics Investigation of Superionic Conductivity (United States)

    Wood, Brandon; Marzari, Nicola


    Superionic materials---solids with liquid-like transport properties---have found widespread use in a variety of applications in fuel cells, switches, sensors, and batteries. However, reasons for fast-ion conduction in such materials, as well as the specific atomistic mechanisms involved, remain ill understood. Our work uses first-principles molecular dynamics to illuminate the mechanisms, pathways, and motivations for superionic conductivity in two materials representing different classes of ion conductors: α-AgI, an archetypal Type-I superionic; and CsHSO4, an anhydrous solid-state electrolyte candidate for hydrogen fuel cells. For α-AgI, we trace common pathways for silver ion conduction and discuss how a chemical signature in the electronic structure relates to enhanced silver ion mobility. We also characterize the dynamical lattice structure in the superionic phase and present the likely motivations for its existence. For CsHSO4, we isolate the dominant atomistic mechanisms involved in superprotonic conduction and discuss the effect of correlated diffusive events in enhancing proton transport. We also offer a detailed description of the dynamics of the hydrogen bond network topology in the course of proton diffusion and discuss the relevance of atomistic processes with competing timescales in facilitating proton transport.

  5. Multilocus sequence analysis for Leishmania braziliensis outbreak investigation.

    Directory of Open Access Journals (Sweden)

    Mariel A Marlow


    Full Text Available With the emergence of leishmaniasis in new regions around the world, molecular epidemiological methods with adequate discriminatory power, reproducibility, high throughput and inter-laboratory comparability are needed for outbreak investigation of this complex parasitic disease. As multilocus sequence analysis (MLSA has been projected as the future gold standard technique for Leishmania species characterization, we propose a MLSA panel of six housekeeping gene loci (6pgd, mpi, icd, hsp70, mdhmt, mdhnc for investigating intraspecific genetic variation of L. (Viannia braziliensis strains and compare the resulting genetic clusters with several epidemiological factors relevant to outbreak investigation. The recent outbreak of cutaneous leishmaniasis caused by L. (V. braziliensis in the southern Brazilian state of Santa Catarina is used to demonstrate the applicability of this technique. Sequenced fragments from six genetic markers from 86 L. (V. braziliensis strains from twelve Brazilian states, including 33 strains from Santa Catarina, were used to determine clonal complexes, genetic structure, and phylogenic networks. Associations between genetic clusters and networks with epidemiological characteristics of patients were investigated. MLSA revealed epidemiological patterns among L. (V. braziliensis strains, even identifying strains from imported cases among the Santa Catarina strains that presented extensive homogeneity. Evidence presented here has demonstrated MLSA possesses adequate discriminatory power for outbreak investigation, as well as other potential uses in the molecular epidemiology of leishmaniasis.

  6. Molecular self-assembly for biological investigations and nanoscale lithography (United States)

    Cheunkar, Sarawut

    Small, diffusible molecules when recognized by their binding partners, such as proteins and antibodies, trigger enzymatic activity, cell communication, and immune response. Progress in analytical methods enabling detection, characterization, and visualization of biological dynamics at the molecular level will advance our exploration of complex biological systems. In this dissertation, analytical platforms were fabricated to capture membrane-associated receptors, which are essential proteins in cell signaling pathways. The neurotransmitter serotonin and its biological precursor were immobilized on gold substrates coated with self-assembled monolayers (SAMs) of oligo(ethylene glycol)alkanethiols and their reactive derivatives. The SAM-coated substrates present the biologically selective affinity of immobilized molecules to target native membrane-associated receptors. These substrates were also tested for biospecificity using antibodies. In addition, small-molecule-functionalized platforms, expressing neurotransmitter pharmacophores, were employed to examine kinetic interactions between G-protein-coupled receptors and their associated neurotransmitters. The binding interactions were monitored using a quartz crystal microbalance equipped with liquid-flow injection. The interaction kinetics of G-protein-coupled serotonin 1A receptor and 5-hydroxytyptophan-functionalized surfaces were studied in a real-time, label-free environment. Key binding parameters, such as equilibrium dissociation constants, binding rate constants, and dissociative half-life, were extracted. These parameters are critical for understanding and comparing biomolecular interactions in modern biomedical research. By integrating self-assembly, surface functionalization, and nanofabrication, small-molecule microarrays were created for high-throughput screening. A hybrid soft-lithography, called microcontact insertion printing, was used to pattern small molecules at the dilute scales necessary for highly

  7. Molecular investigation of tularemia outbreaks, Spain, 1997-2008. (United States)

    Ariza-Miguel, Jaime; Johansson, Anders; Fernández-Natal, María Isabel; Martínez-Nistal, Carmen; Orduña, Antonio; Rodríguez-Ferri, Elías F; Hernández, Marta; Rodríguez-Lázaro, David


    Tularemia outbreaks occurred in northwestern Spain in 1997-1998 and 2007-2008 and affected >1,000 persons. We assessed isolates involved in these outbreaks by using pulsed-field gel electrophoresis with 2 restriction enzymes and multilocus variable number tandem repeat analysis of 16 genomic loci of Francisella tularensis, the cause of this disease. Isolates were divided into 3 pulsotypes by pulsed-field gel electrophoresis and 8 allelic profiles by multilocus variable number tandem repeat analysis. Isolates obtained from the second tularemia outbreak had the same genotypes as isolates obtained from the first outbreak. Both outbreaks were caused by genotypes of genetic subclade B.Br:FTNF002-00, which is widely distributed in countries in central and western Europe. Thus, reemergence of tularemia in Spain was not caused by the reintroduction of exotic strains, but probably by persistence of local reservoirs of infection.

  8. Molecular genetic investigations on Austria's patron saint Leopold III (United States)

    Bauer, Christiane Maria; Bodner, Martin; Niederstätter, Harald; Niederwieser, Daniela; Huber, Gabriela; Hatzer-Grubwieser, Petra; Holubar, Karl; Parson, Walther


    The successful marriage policy of margrave Leopold III increased the importance of the House of Babenberg in late medieval Austria (12th century). Historical documentation is inconclusive in providing evidence whether or not his eldest son Adalbert derived from an earlier relationship or from the marriage with King Henry IV's daughter Agnes of Waiblingen, with whom Leopold is considered to have had 17 children. As a matter of fact Adalbert was ignored in the line of succession in favor of a younger brother, Leopold IV, which has led to long term historical discussions. Human remains attributed to these individuals were subjected to DNA analysis. Autosomal, Y-chromosomal and mitochondrial DNA analyses brought successful results, which suggested that Leopold III, Agnes and Adalbert were related in parent–son constellation, in contrast to historical considerations. A possible mix-up of Adalbert's remains with those of his younger brother Ernst could not be confirmed by DNA analysis. PMID:23142176

  9. Cloning Yeast Actin cDNA Leads to an Investigative Approach for the Molecular Biology Laboratory (United States)

    Black, Michael W.; Tuan, Alice; Jonasson, Erin


    The emergence of molecular tools in multiple disciplines has elevated the importance of undergraduate laboratory courses that train students in molecular biology techniques. Although it would also be desirable to provide students with opportunities to apply these techniques in an investigative manner, this is generally not possible in the…

  10. Molecular tools for investigating ANME community structure and function

    Energy Technology Data Exchange (ETDEWEB)

    Hallam, Steven J.; Page, Antoine P.; Constan, Lea; Song, Young C.; Norbeck, Angela D.; Brewer, Heather M.; Pasa-Tolic, Ljiljana


    Methane production and consumption in anaerobic marine sediments 1 is catalyzed by a series of reversible tetramethanopterin (H4MPT)-linked C1 transfer reactions. Although many of these reactions are conserved between one-carbon compound utilizing microorganisms, two remain diagnostic for archaeal methane metabolism. These include reactions catalyzed by N5-methyltetrahydromethanopterin: coenzyme M methyltransferase and methyl coenzyme M reductase. The latter enzyme is central to C-H bond formation and cleavage underlying methanogenic and reverse methanogenic phenotypes. Here we describe a set of novel tools for the detection and functional analysis of H4MPT-linked C1 transfer reactions mediated by uncultivated anaerobic methane oxidizing archaea (ANME). These tools include polymerase chain reaction primers targeting ANME methyl coenzyme M reductase subunit A subgroups and protein extraction methods from marine sediments compatible with high-resolution mass spectrometry for profiling population structure and functional dynamics. [910, 1,043

  11. Delineation of Chondroid Lipoma: An Immunohistochemical and Molecular Biological Analysis

    Directory of Open Access Journals (Sweden)

    Ronald S. A. de Vreeze


    Full Text Available Aims. Chondroid lipoma (CL is a benign tumor that mimics a variety of soft tissue tumors and is characterized by translocation t(11;16. Here, we analyze CL and its histological mimics. Methods. CL (n=4 was compared to a variety of histological mimics (n=83 for morphological aspects and immunohistochemical features including cyclinD1(CCND1. Using FISH analysis, CCND1 and FUS were investigated as potential translocation partners. Results. All CLs were strongly positive for CCND1. One of 4 myoepitheliomas, CCND1, was positive. In well-differentiated lipomatous tumors and in chondrosarcomas, CCND1 was frequently expressed, but all myxoid liposarcomas were negative. FISH analysis did not give support for direct involvement of CCND1 and FUS as translocation partners. Conclusions. Chondroid lipoma is extremely rare and has several and more prevalent histological mimics. The differential diagnosis of chondroid lipomas can be unraveled using immunohistochemical and molecular support.

  12. Instant Replay: Investigating statistical Analysis in Sports

    CERN Document Server

    Sidhu, Gagan


    Technology has had an unquestionable impact on the way people watch sports. As technology has evolved, so too has the knowledge of a casual sports fan. A direct result of this evolution is the amount of statistical analysis in sport. The goal of statistical analysis in sports is a simple one: to eliminate subjective analysis. Over the past four decades, statistics have slowly pervaded the viewing experience of sports. In this paper, we analyze previous work that proposed metrics and models that seek to evaluate various aspects of sports. The unifying goal of these works is an accurate representation of either the player or sport. We also look at work that investigates certain situations and their impact on the outcome a game. We conclude this paper with the discussion of potential future work in certain areas of sport..

  13. Conformational analysis of methylphenidate: comparison of molecular orbital and molecular mechanics methods (United States)

    Gilbert, Kathleen M.; Skawinski, William J.; Misra, Milind; Paris, Kristina A.; Naik, Neelam H.; Buono, Ronald A.; Deutsch, Howard M.; Venanzi, Carol A.


    Methylphenidate (MP) binds to the cocaine binding site on the dopamine transporter and inhibits reuptake of dopamine, but does not appear to have the same abuse potential as cocaine. This study, part of a comprehensive effort to identify a drug treatment for cocaine abuse, investigates the effect of choice of calculation technique and of solvent model on the conformational potential energy surface (PES) of MP and a rigid methylphenidate (RMP) analogue which exhibits the same dopamine transporter binding affinity as MP. Conformational analysis was carried out by the AM1 and AM1/SM5.4 semiempirical molecular orbital methods, a molecular mechanics method (Tripos force field with the dielectric set equal to that of vacuum or water) and the HF/6-31G* molecular orbital method in vacuum phase. Although all three methods differ somewhat in the local details of the PES, the general trends are the same for neutral and protonated MP. In vacuum phase, protonation has a distinctive effect in decreasing the regions of space available to the local conformational minima. Solvent has little effect on the PES of the neutral molecule and tends to stabilize the protonated species. The random search (RS) conformational analysis technique using the Tripos force field was found to be capable of locating the minima found by the molecular orbital methods using systematic grid search. This suggests that the RS/Tripos force field/vacuum phase protocol is a reasonable choice for locating the local minima of MP. However, the Tripos force field gave significantly larger phenyl ring rotational barriers than the molecular orbital methods for MP and RMP. For both the neutral and protonated cases, all three methods found the phenyl ring rotational barriers for the RMP conformers/invertamers (denoted as cte, tte, and cta) to be: cte, tte> MP > cta. Solvation has negligible effect on the phenyl ring rotational barrier of RMP. The B3LYP/6-31G* density functional method was used to calculate the phenyl

  14. Molecular structure and spectral investigations of 3,5-Di-tert-butyl-o-benzoquinone (United States)

    Yilmaz, M.; Aydin, B.; Dogan, O.; Dereli, O.


    Conformational analysis of 3,5-Di-tert-butyl-o-benzoquinone molecule was performed and two stable conformers were determined by B3LYP/6-311++G(d,p). Using the most stable one, molecular structural parameters, vibrational frequencies were calculated by B3LYP/6-311++G(d,p), B3LYP/6-31G(d) and BLYP/6-31G(d,p) levels of theory. The FT-IR spectrum of the compound was recorded in the region 4000-550 cm-1. The Raman spectrum was also recorded in the region 3500-100 cm-1. Calculated results were compared with experimental counterparts. The best results were obtained from B3LYP/6-311++G(d,p) calculations. Experimental 13C and 1H NMR data of tittle compound were taken from literature and the calculated results compared with these data. Vibrational and NMR band assignments were performed. HOMO-LUMO energies, molecular electrostatic potentials and thermodynamic properties were also given for further investigations of our structure.

  15. Statistical analysis of molecular signal recording.

    Directory of Open Access Journals (Sweden)

    Joshua I Glaser

    Full Text Available A molecular device that records time-varying signals would enable new approaches in neuroscience. We have recently proposed such a device, termed a "molecular ticker tape", in which an engineered DNA polymerase (DNAP writes time-varying signals into DNA in the form of nucleotide misincorporation patterns. Here, we define a theoretical framework quantifying the expected capabilities of molecular ticker tapes as a function of experimental parameters. We present a decoding algorithm for estimating time-dependent input signals, and DNAP kinetic parameters, directly from misincorporation rates as determined by sequencing. We explore the requirements for accurate signal decoding, particularly the constraints on (1 the polymerase biochemical parameters, and (2 the amplitude, temporal resolution, and duration of the time-varying input signals. Our results suggest that molecular recording devices with kinetic properties similar to natural polymerases could be used to perform experiments in which neural activity is compared across several experimental conditions, and that devices engineered by combining favorable biochemical properties from multiple known polymerases could potentially measure faster phenomena such as slow synchronization of neuronal oscillations. Sophisticated engineering of DNAPs is likely required to achieve molecular recording of neuronal activity with single-spike temporal resolution over experimentally relevant timescales.

  16. Molecular and structural analysis of viscoelastic properties (United States)

    Yapp, Rebecca D.; Kalyanam, Sureshkumar; Insana, Michael F.


    Elasticity imaging is emerging as an important tool for breast cancer detection and monitoring of treatment. Viscoelastic image contrast in breast lesions is generated by disease specific processes that modify the molecular structure of connective tissues. We showed previously that gelatin hydrogels exhibit mechanical behavior similar to native collagen found in breast tissue and therefore are suitable as phantoms for elasticity imaging. This paper summarizes our study of the viscoelastic properties of hydrogels designed to discover molecular-scale sources of elasticity image contrast.

  17. Molecular cytogenetics and its applications to soft tissue tumor analysis. (United States)

    D'Amato, L


    Cytogenetic analyses have demonstrated the association of specific chromosomal changes with particular types of soft tissue tumors. This work describes the molecular cytogenetic approaches to genetic analysis of these tumors. It illustrates how molecular cytogenetics may provide a rapid and sensitive method of diagnosis and can contribute to identify specific genes implied in the aetiology of soft tissue tumors.

  18. Isotope effects in water as investigated by neutron diffraction and path integral molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Zeidler, Anita [University of Bath; Salmon, Phil [University of Bath; Fischer, Henry E [Institut Laue-Langevin (ILL); Neuefeind, Joerg C [ORNL; Simonson, J Michael {Mike} [ORNL; Markland, Thomas [Columbia University


    The structure of heavy and light water at 300 K was investigated by using a joint approach in which the method of neutron di raction with oxygen isotope substitution was combined with path integral molecular dynamics simulations. The di raction results, which give intra-molecular O-D and O-H bond distances of 0.985(5) and 0.990(5) A, were found to be in best agreement with those obtained by using the exible anharmonic TTM3-F water model. Both techniques show a di erence of '0.5% between the O-D and O-H intra-molecular bond lengths and the results support a competing quantum e ects model for water in which its structural and dynamical properties are governed by an o set between intra-molecular and inter-molecular quantum contributions. Further consideration of the O-O correlations is needed in order to improve agreement with experiment.

  19. Isotope effects in water as investigated by neutron diffraction and path integral molecular dynamics (United States)

    Zeidler, Anita; Salmon, Philip S.; Fischer, Henry E.; Neuefeind, Jörg C.; Simonson, J. Mike; Markland, Thomas E.


    The structures of heavy and light water at 300 K were investigated by using a joint approach in which the method of neutron diffraction with oxygen isotope substitution was complemented by path integral molecular dynamics simulations. The diffraction results, which give intra-molecular O-D and O-H bond distances of 0.985(5) and 0.990(5) Å, were found to be in best agreement with those obtained by using the flexible anharmonic TTM3-F water model. Both techniques show a difference of ≃ 0.5% between the O-D and O-H intra-molecular bond lengths, and the results support a competing quantum effects model for water in which its structural and dynamical properties are governed by an offset between intra-molecular and inter-molecular quantum contributions. Further consideration of the O-O correlations is needed in order to improve agreement with experiment.

  20. First principle and ReaxFF molecular dynamics investigations of formaldehyde dissociation on Fe(100) surface. (United States)

    Yamada, Takahiro; Phelps, Donald K; van Duin, Adri C T


    Detailed formaldehyde adsorption and dissociation reactions on Fe(100) surface were studied using first principle calculations and molecular dynamics (MD) simulations, and results were compared with available experimental data. The study includes formaldehyde, formyl radical (HCO), and CO adsorption and dissociation energy calculations on the surface, adsorbate vibrational frequency calculations, density of states analysis of clean and adsorbed surfaces, complete potential energy diagram construction from formaldehyde to atomic carbon (C), hydrogen (H), and oxygen (O), simulation of formaldehyde adsorption and dissociation reaction on the surface using reactive force field, ReaxFF MD, and reaction rate calculations of adsorbates using transition state theory (TST). Formaldehyde and HCO were adsorbed most strongly at the hollow (fourfold) site. Adsorption energies ranged from -22.9 to -33.9 kcal/mol for formaldehyde, and from -44.3 to -66.3 kcal/mol for HCO, depending on adsorption sites and molecular direction. The dissociation energies were investigated for the dissociation paths: formaldehyde → HCO + H, HCO → H + CO, and CO → C + O, and the calculated energies were 11.0, 4.1, and 26.3 kcal/mol, respectively. ReaxFF MD simulation results were compared with experimental surface analysis using high resolution electron energy loss spectrometry (HREELS) and TST based reaction rates. ReaxFF simulation showed less reactivity than HREELS observation at 310 and 523 K. ReaxFF simulation showed more reactivity than the TST based rate for formaldehyde dissociation and less reactivity than TST based rate for HCO dissociation at 523 K. TST-based rates are consistent with HREELS observation.


    Gordon Research Conference: Mammalian Gametogenesis and Embryogenesis New London, CT, July 1-6, 2000Molecular Analysis of Human Spermatozoa: Potential for Infertility ResearchDavid Miller 1, David Dix2, Robert Reid 3, Stephen A Krawetz 3 1Reproductive ...

  2. Molecular and genetics approaches for investigation of phospholipase D role in plant cells

    Directory of Open Access Journals (Sweden)

    Volotovsky I. D.


    Full Text Available The review is devoted to the analysis of publications ñoncerning the role of phospholipase D (PLD in regulation of metabolism in plant cells. Analysis of molecular and genetic studies suggest that PLD is an important component of various hormonal and stress signaling pathways

  3. Adaptive Molecular Resolution Approach in Hamiltonian Form: An Asymptotic Analysis

    CERN Document Server

    Zhu, Jinglong; Site, Luigi Delle


    Adaptive Molecular Resolution approaches in Molecular Dynamics are becoming relevant tools for the analysis of molecular liquids characterized by the interplay of different physical scales. The essential difference among these methods is in the way the change of molecular resolution is made in a buffer/transition region. In particular a central question concerns the possibility of the existence of a global Hamiltonian which, by describing the change of resolution, is at the same time physically consistent, mathematically well defined and numerically accurate. In this paper we present an asymptotic analysis of the adaptive process complemented by numerical results and show that under certain mathematical conditions a Hamiltonian, which is physically consistent and numerically accurate, may exist. \\blue{Such conditions show that molecular simulations in the current computational implementation require systems of large size and thus a Hamiltonian approach as the one proposed, at this stage, would not be practica...

  4. Investigation of naproxen drug using mass spectrometry, thermal analyses and semi-empirical molecular orbital calculation

    Directory of Open Access Journals (Sweden)

    M.A. Zayed


    Full Text Available Naproxen (C14H14O3 is a non-steroidal anti-inflammatory drug (NSAID. It is important to investigate its structure to know the active groups and weak bonds responsible for medical activity. In the present study, naproxen was investigated by mass spectrometry (MS, thermal analysis (TA measurements (TG/DTG and DTA and confirmed by semi empirical molecular orbital (MO calculation, using PM3 procedure. These calculations included, bond length, bond order, bond strain, partial charge distribution, ionization energy and heat of formation (ΔHf. The mass spectra and thermal analysis fragmentation pathways were proposed and compared to select the most suitable scheme representing the correct fragmentation pathway of the drug in both techniques. The PM3 procedure reveals that the primary cleavage site of the charged molecule is the rupture of the COOH group (lowest bond order and high strain which followed by CH3 loss of the methoxy group. Thermal analysis of the neutral drug reveals a high response to the temperature variation with very fast rate. It decomposed in several sequential steps in the temperature range 80–400 °C. These mass losses appear as two endothermic and one exothermic peaks which required energy values of 255.42, 10.67 and 371.49 J g−1 respectively. The initial thermal ruptures are similar to that obtained by mass spectral fragmentation (COOH rupture. It was followed by the loss of the methyl group and finally by ethylene loss. Therefore, comparison between MS and TA helps in selection of the proper pathway representing its fragmentation. This comparison is successfully confirmed by MO-calculation.

  5. Molecular dynamics investigation on the deviation from stoichiometry in martensitic transformation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Tetsuro, E-mail: [National Institute for Materials Science (Japan); Shimno, Masato; Otsuka, Kazuhiro; Ren, Xiaobing [National Institute for Materials Science (Japan); Saxena, Avadh [National Institute for Materials Science (Japan); Los Alamos National Laboratory (United States)


    Highlights: ► We have studied the martensitic transformation in Ti–Ni alloy near 50:50 stoichiometry. ► The atomistic process of the martensitic transformation is simulated by use of the molecular dynamics based on the 8-4 Lennard–Jones potential. ► The molecular dynamics provide atomistic picture when the formation of the martensite is suppressed for the deviation from 50:50 stoichiometry. -- Abstract: How the martensitic transformation in Ti–Ni alloy depends on the deviation from the stoichiometry is investigated by use of the molecular dynamics based on a simple model potential.

  6. Molecular analysis of the glucocerebrosidase gene locus

    Energy Technology Data Exchange (ETDEWEB)

    Winfield, S.L.; Martin, B.M.; Fandino, A. [Clinical Neuroscience Branch, Bethesda, MD (United States)] [and others


    Gaucher disease is due to a deficiency in the activity of the lysosomal enzyme glucocerebrosidase. Both the functional gene for this enzyme and a pseudogene are located in close proximity on chromosome 1q21. Analysis of the mutations present in patient samples has suggested interaction between the functional gene and the pseudogene in the origin of mutant genotypes. To investigate the involvement of regions flanking the functional gene and pseudogene in the origin of mutations found in Gaucher disease, a YAC clone containing DNA from this locus has been subcloned and characterized. The original YAC containing {approximately}360 kb was truncated with the use of fragmentation plasmids to about 85 kb. A lambda library derived from this YAC was screened to obtain clones containing glucocerebrosidase sequences. PCR amplification was used to identify subclones containing 5{prime}, central, or 3{prime} sequences of the functional gene or of the pseudogene. Clones spanning the entire distance from the last exon of the functional gene to intron 1 of the pseudogene, the 5{prime} end of the functional gene and 16 kb of 5{prime} flanking region and approximately 15 kb of 3{prime} flanking region of the pseudogene were sequenced. Sequence data from 48 kb of intergenic and flanking regions of the glucocerebrosidase gene and its pseudogene has been generated. A large number of Alu sequences and several simple repeats have been found. Two of these repeats exhibit fragment length polymorphism. There is almost 100% homology between the 3{prime} flanking regions of the functional gene and the pseudogene, extending to about 4 kb past the termination codons. A much lower degree of homology is observed in the 5{prime} flanking region. Patient samples are currently being screened for polymorphisms in these flanking regions.

  7. Formalizing the definition of meta-analysis in Molecular Ecology. (United States)

    ArchMiller, Althea A; Bauer, Eric F; Koch, Rebecca E; Wijayawardena, Bhagya K; Anil, Ammu; Kottwitz, Jack J; Munsterman, Amelia S; Wilson, Alan E


    Meta-analysis, the statistical synthesis of pertinent literature to develop evidence-based conclusions, is relatively new to the field of molecular ecology, with the first meta-analysis published in the journal Molecular Ecology in 2003 (Slate & Phua 2003). The goal of this article is to formalize the definition of meta-analysis for the authors, editors, reviewers and readers of Molecular Ecology by completing a review of the meta-analyses previously published in this journal. We also provide a brief overview of the many components required for meta-analysis with a more specific discussion of the issues related to the field of molecular ecology, including the use and statistical considerations of Wright's FST and its related analogues as effect sizes in meta-analysis. We performed a literature review to identify articles published as 'meta-analyses' in Molecular Ecology, which were then evaluated by at least two reviewers. We specifically targeted Molecular Ecology publications because as a flagship journal in this field, meta-analyses published in Molecular Ecology have the potential to set the standard for meta-analyses in other journals. We found that while many of these reviewed articles were strong meta-analyses, others failed to follow standard meta-analytical techniques. One of these unsatisfactory meta-analyses was in fact a secondary analysis. Other studies attempted meta-analyses but lacked the fundamental statistics that are considered necessary for an effective and powerful meta-analysis. By drawing attention to the inconsistency of studies labelled as meta-analyses, we emphasize the importance of understanding the components of traditional meta-analyses to fully embrace the strengths of quantitative data synthesis in the field of molecular ecology.

  8. Molecular structure activity on pharmaceutical applications of Phenacetin using spectroscopic investigation (United States)

    Madanagopal, A.; Periandy, S.; Gayathri, P.; Ramalingam, S.; Xavier, S.


    The pharmaceutical compound; Phenacetin was investigated by analyzing FT-IR, FT-Raman and 1H &13C NMR spectra. The hybrid efficient computational calculations performed for computing physical and chemical parameters. The cause of pharmaceutical activity due to the substitutions; carboxylic, methyl and amine groups in appropriate positions on the pedestal compound was deeply investigated. Moreover, 13C NMR and 1H NMR chemical shifts correlated with TMS standard to explain the truth of compositional ratio of base and ligand groups. The bathochromic shift due to chromophores over the energy levels in UV-Visible region was strongly emphasized the Anti-inflammatory chemical properties. The chemical stability was pronounced by the strong kubo gap which showed the occurring of charge transformation within the molecule. The occurrence of the chemical reaction was feasibly interpreted by Gibbs free energy profile. The standard vibrational analysis stressed the active participation of composed ligand groups for the existence of the analgesic as well as antipyretic properties of the Phenacetin compound. The strong dipole interaction energy utilization for the transition among non-vanishing donor and acceptor for composition of the molecular structure was interpreted.

  9. Molecular identification of python species: development and validation of a novel assay for forensic investigations. (United States)

    Ciavaglia, Sherryn A; Tobe, Shanan S; Donnellan, Stephen C; Henry, Julianne M; Linacre, Adrian M T


    Python snake species are often encountered in illegal activities and the question of species identity can be pertinent to such criminal investigations. Morphological identification of species of pythons can be confounded by many issues and molecular examination by DNA analysis can provide an alternative and objective means of identification. Our paper reports on the development and validation of a PCR primer pair that amplifies a segment of the mitochondrial cytochrome b gene that has been suggested previously as a good candidate locus for differentiating python species. We used this DNA region to perform species identification of pythons, even when the template DNA was of poor quality, as might be the case with forensic evidentiary items. Validation tests are presented to demonstrate the characteristics of the assay. Tests involved the cross-species amplification of this marker in non-target species, minimum amount of DNA template required, effects of degradation on product amplification and a blind trial to simulate a casework scenario that provided 100% correct identity. Our results demonstrate that this assay performs reliably and robustly on pythons and can be applied directly to forensic investigations where the presence of a species of python is in question.

  10. Synthesis, crystal structure analysis, spectral (NMR, FT-IR, FT-Raman and UV-Vis) investigations, molecular docking studies, antimicrobial studies and quantum chemical calculations of a novel 4-chloro-8-methoxyquinoline-2(1H)-one: An effective antimicrobial agent and an inhibition of DNA gyrase and lanosterol-14α-demethylase enzymes (United States)

    Murugavel, S.; Sundramoorthy, S.; Lakshmanan, D.; Subashini, R.; Pavan Kumar, P.


    The novel title compound 4-chloro-8-methoxyquinoline-2(1H)-one (4CMOQ) has been synthesized by slow evaporation solution growth technique at room temperature. The synthesized 4CMOQ molecule was characterized experimentally by FT-IR, FT-Raman, UV-Vis, NMR and single crystal diffraction (XRD) and theoretically by quantum chemical calculations. The molecular geometry was also optimized using density functional theory (DFT/B3LYP) method with the 6-311++G (d,p) basis set in ground state and compared with the experimental data. The entire vibrational assignments of wave numbers were made on the basis of potential energy distribution (PED) by VEDA 4 programme. The nuclear magnetic resonance spectra (1H and 13C NMR) are obtained by using the gauge-invariant atomic orbital (GIAO) method. The change in electron density (ED) in the antibonding orbital's and stabilization energies E(2) of the molecule have been evaluated by natural bond orbital (NBO) analysis to give clear evidence of stabilization. Moreover, electronic characteristics such as HOMO and LUMO energies, Mulliken atomic charges and molecular electrostatic potential surface are investigated. Absorption spectrum analysis, nonlinear optical properties, chemical reactivity descriptors and thermodynamic features are also outlined theoretically. Molecular docking studies were executed to understand the inhibitory activity of 4CMOQ against DNA gyrase and Lanosterol 14 α-demethylase. The antimicrobial activity of 4CMOQ was determined against bacterial strains such as Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and fungal strains such as Aspergillus niger, Monascus purpureus and Penicillium citrinum. The obtained results show that the compound exhibited good to moderate antimicrobial activity.

  11. Mathematical analysis and calculation of molecular surfaces (United States)

    Quan, Chaoyu; Stamm, Benjamin


    In this article we derive a complete characterization of the Solvent Excluded Surface (SES) for molecular systems including a complete characterization of singularities of the surface. The theory is based on an implicit representation of the SES, which, in turn, is based on the signed distance function to the Solvent Accessible Surface (SAS). All proofs are constructive so that the theory allows for efficient algorithms in order to compute the area of the SES and the volume of the SES-cavity, or to visualize the surface. Further, we propose to refine the notion of SAS and SES in order to take inner holes in a solute molecule into account or not.

  12. Molecular analysis of Ku redox regulation

    Directory of Open Access Journals (Sweden)

    Shatilla Andrea


    Full Text Available Abstract Background DNA double-strand breaks (DSBs can occur in response to ionizing radiation (IR, radiomimetic agents and from endogenous DNA-damaging reactive oxygen metabolites. Unrepaired or improperly repaired DSBs are potentially the most lethal form of DNA damage and can result in chromosomal translocations and contribute to the development of cancer. The principal mechanism for the repair of DSBs in humans is non-homologous end-joining (NHEJ. Ku is a key member of the NHEJ pathway and plays an important role in the recognition step when it binds to free DNA termini. Ku then stimulates the assembly and activation of other NHEJ components. DNA binding of Ku is regulated by redox conditions and evidence from our laboratory has demonstrated that Ku undergoes structural changes when oxidized that results in a reduction in DNA binding activity. The C-terminal domain and cysteine 493 of Ku80 were investigated for their contribution to redox regulation of Ku. Results We effectively removed the C-terminal domain of Ku80 generating a truncation mutant and co-expressed this variant with wild type Ku70 in an insect cell system to create a Ku70/80ΔC heterodimer. We also generated two single amino acid variants of Cys493, replacing this amino acid with either an alanine (C493A or a serine (C493S, and over-expressed the variant proteins in SF9 insect cells in complex with wild type Ku70. Neither the truncation nor the amino acid substitutions alters protein expression or stability as determined by SDS-PAGE and Western blot analysis. We show that the C493 mutations do not alter the ability of Ku to bind duplex DNA in vitro under reduced conditions while truncation of the Ku80 C-terminus slightly reduced DNA binding affinity. Diamide oxidation of cysteines was shown to inhibit DNA binding similarly for both the wild-type and all variant proteins. Interestingly, differential DNA binding activity following re-reduction was observed for the Ku70/80

  13. Dynamical analysis of highly excited molecular spectra

    Energy Technology Data Exchange (ETDEWEB)

    Kellman, M.E. [Univ. of Oregon, Eugene (United States)


    The goal of this program is new methods for analysis of spectra and dynamics of highly excited vibrational states of molecules. In these systems, strong mode coupling and anharmonicity give rise to complicated classical dynamics, and make the simple normal modes analysis unsatisfactory. New methods of spectral analysis, pattern recognition, and assignment are sought using techniques of nonlinear dynamics including bifurcation theory, phase space classification, and quantization of phase space structures. The emphasis is chaotic systems and systems with many degrees of freedom.

  14. Molecular dynamics analysis on impact behavior of carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Seifoori, Sajjad, E-mail:


    Graphical abstract: - Highlights: • We present an analytical solution of impact based on two degree of freedom model. • The accuracy is verified by Molecular dynamics simulations. • The effects of the small-size effects on the dynamic deflections are investigated. • The relative motion is also accounted that is due to local indentation. - Abstract: Dynamic analysis of impact of a nanoparticle on carbon nanotubes is investigated based on two degree of freedom model. The accuracy and stability of the present methods are verified by molecular dynamics (MD) simulations. The effect of different types of boundary condition on the maximum dynamic deflections is studied for zigzag and armchair SWCNTs with various aspect ratios (length/diameter). Besides, the influences of velocity of impactor on the dynamic deflections are studied. It is shown that the dynamic behavior on the armchair and zigzag single-walled carbon nanotubes are almost similar. Finally, by making use of the above MD simulation and theoretical results some insight has been obtained about the dynamic characteristics of the impact problems of nanobeam structures. Nonlocal Timoshenko beam models TBT2 should be employed for an accurate prediction of the dynamic deflection rather than nonlocal Euler–Bernoulli beam models EBT2 which ignores the effects of transverse shear deformation and rotary inertia that is especially significant for short beams. The results from nonlocal EBT2 and TBT2 models demonstrated good agreement with MD simulation. The EBT2 and TBT2 models also account for the relative motion between the nanoparticle and the nanobeam that is due to local indentation as can be seen in MD simulation.

  15. Solid-State Spectroscopic Investigation of Molecular Interactions between Clofazimine and Hypromellose Phthalate in Amorphous Solid Dispersions. (United States)

    Nie, Haichen; Su, Yongchao; Zhang, Mingtao; Song, Yang; Leone, Anthony; Taylor, Lynne S; Marsac, Patrick J; Li, Tonglei; Byrn, Stephen R


    It has been technically challenging to specify the detailed molecular interactions and binding motif between drugs and polymeric inhibitors in the solid state. To further investigate drug-polymer interactions from a molecular perspective, a solid dispersion of clofazimine (CLF) and hypromellose phthalate (HPMCP), with reported superior amorphous drug loading capacity and physical stability, was selected as a model system. The CLF-HPMCP interactions in solid dispersions were investigated by various solid state spectroscopic methods including ultraviolet-visible (UV-vis), infrared (IR), and solid-state NMR (ssNMR) spectroscopy. Significant spectral changes suggest that protonated CLF is ionically bonded to the carboxylate from the phthalyl substituents of HPMCP. In addition, multivariate analysis of spectra was applied to optimize the concentration of polymeric inhibitor used to formulate the amorphous solid dispersions. Most interestingly, proton transfer between CLF and carboxylic acid was experimentally investigated from 2D (1)H-(1)H homonuclear double quantum NMR spectra by utilizing the ultrafast magic-angle spinning (MAS) technique. The molecular interaction pattern and the critical bonding structure in CLF-HPMCP dispersions were further delineated by successfully correlating ssNMR findings with quantum chemistry calculations. These high-resolution investigations provide critical structural information on active pharmaceutical ingredient-polymer interaction, which can be useful for rational selection of appropriate polymeric carriers, which are effective crystallization inhibitors for amorphous drugs.

  16. Quantum Phase Analysis of Field-Free Molecular Alignment

    CERN Document Server

    Yun, Sang Jae; Lee, Jongmin; Nam, Chang Hee


    We present quantum mechanical explanations for unresolved phenomena observed in field-free molecular alignment by a femtosecond laser pulse. Quantum phase analysis of molecular rotational states reveals the physical origin of the following phenomena: strong alignment peaks appear periodically, and the temporal shape of each alignment peak changes in an orderly fashion depending on molecular species; the strongest alignment is not achieved at the first peak; the transition between aligned and anti-aligned states is very fast compared to the time scale of rotational dynamics. These features are understood in a unified way analogous to that describing a carrier-envelope-phase-stabilized mode-locked laser.

  17. Molecular and Cellular Quantitative Microscopy: theoretical investigations, technological developments and applications to neurobiology

    NARCIS (Netherlands)

    Esposito, Alessandro


    This PhD project aims at the development and evaluation of microscopy techniques for the quantitative detection of molecular interactions and cellular features. The primarily investigated techniques are Fαrster Resonance Energy Transfer imaging and Fluorescence Lifetime Imaging Microscopy. These tec

  18. Investigations of prebiotics and of inter- and intra-molecular glycan-protein interactions

    NARCIS (Netherlands)

    Beccati, D.


    Carbohydrate chains play key roles in living organisms. Novel techniques have been developed in recent years to investigate the structure/function of carbohydrates. 2D nuclear magnetic resonance (NMR) and molecular dynamics (MD) simulation in conjunction with NMR refinement, as well as surface plasm

  19. Molecular investigations of food-borne Cladosporium and Fusarium species from Nigeria (United States)

    A sampling of contaminated foodstuffs throughout southwest Nigeria yielded three fungal isolates belonging to the genus Fusarium and two fungal isolates belonging to the genus Cladosporium. In this study we subjected these isolates to various molecular investigations. We were able to confirm or refi...

  20. Investigation of imprinting parameters and their recognition nature for quinine-molecularly imprinted polymers (United States)

    He, Jian-feng; Zhu, Quan-hong; Deng, Qin-ying


    A series of molecularly imprinted polymers (MIPs) was prepared using quinine as the template molecules by bulk polymerization. The presence of monomer-template solution complexes in non-covalent MIPs systems has been verified by both fluorescence and UV-vis spectrometric detection. The influence of different synthetic conditions (porogen, functional monomer, cross-linkers, initiation methods, monomer-template ratio, etc.) on recognition properties of the polymers was investigated. Scatchard analysis revealed that two classes of binding sites were formed in the imprinted polymer. The corresponding dissociation constants were estimated to be 45.00 μmol l -1 and 1.42 mmol l -1, respectively, by utilizing a multi-site recognition model. The binding characteristics of the imprinted polymers were explored in various solvents using equilibrium binding experiments. In the organic media, results suggested that polar interactions (hydrogen bonding, ionic interactions, etc.) between acidic monomer/polymer and template molecules were mainly responsible for the recognition, whereas in aqueous media, hydrophobic interactions had a remarkable non-specific contribution to the overall binding. The specificity of MIP was evaluated by rebinding the other structurally similar compounds. The results indicated that the imprinted polymers exhibited an excellent stereo-selectivity toward quinine.

  1. Investigations on Binding Pattern of Kinase Inhibitors with PPARγ: Molecular Docking, Molecular Dynamic Simulations, and Free Energy Calculation Studies (United States)

    Mazumder, Mohit; Das, Umashankar; Gourinath, Samudrala


    Peroxisome proliferator-activated receptor gamma (PPARγ) is a potential target for the treatment of several disorders. In view of several FDA approved kinase inhibitors, in the current study, we have investigated the interaction of selected kinase inhibitors with PPARγ using computational modeling, docking, and molecular dynamics simulations (MDS). The docked conformations and MDS studies suggest that the selected KIs interact with PPARγ in the ligand binding domain (LBD) with high positive predictive values. Hence, we have for the first time shown the plausible binding of KIs in the PPARγ ligand binding site. The results obtained from these in silico investigations warrant further evaluation of kinase inhibitors as PPARγ ligands in vitro and in vivo.

  2. Molecular analysis of cytoplasmic male sterility

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, M.R.


    The ultimate aims of the project are to understand the molecular mechanism of the disruption in pollen development which occurs in cytoplasmic male sterile plants and to understand the control of respiratory energy flow in the higher plant cell. A mitochondrial locus termed S-pcf segregates with sterility and with an alteration in respiration in Petunia. This cloned locus contains three genes, an abnormal fused gene termed pcf, a gene for a subunit of an NADH dehydrogenase complex, and a small ribosomal subunit protein. The pcf gene is comprised of partial sequences of ATPase subunit 9, cytochrome oxidase subunit II, and an unidentified reading frame. Components of the S-Pcf locus will be introduced into the nuclear of a fertile genotype under the control of appropriate regulatory signals, and polypeptide products of introduced genes will be directed to the mitochondrion with a transit peptide. By examining transgenic plants, we can determine what elements of the locus are critical for altered respiration or sterility. Such knowledge could explain how mitochondrial DNA affects pollen development in the large number of plant species which exhibit the agronomically important trait of male sterility. 10 refs., 3 figs.

  3. Molecular road ecology: exploring the potential of genetics for investigating transportation impacts on wildlife. (United States)

    Balkenhol, Niko; Waits, Lisette P


    Transportation infrastructures such as roads, railroads and canals can have major environmental impacts. Ecological road effects include the destruction and fragmentation of habitat, the interruption of ecological processes and increased erosion and pollution. Growing concern about these ecological road effects has led to the emergence of a new scientific discipline called road ecology. The goal of road ecology is to provide planners with scientific advice on how to avoid, minimize or mitigate negative environmental impacts of transportation. In this review, we explore the potential of molecular genetics to contribute to road ecology. First, we summarize general findings from road ecology and review studies that investigate road effects using genetic data. These studies generally focus only on barrier effects of roads on local genetic diversity and structure and only use a fraction of available molecular approaches. Thus, we propose additional molecular applications that can be used to evaluate road effects across multiple scales and dimensions of the biodiversity hierarchy. Finally, we make recommendations for future research questions and study designs that would advance molecular road ecology. Our review demonstrates that molecular approaches can substantially contribute to road ecology research and that interdisciplinary, long-term collaborations will be particularly important for realizing the full potential of molecular road ecology.

  4. Investigation of a metal-organic interface. Realization and understanding of a molecular switch

    Energy Technology Data Exchange (ETDEWEB)

    Neucheva, Olga [Forschungszentrum Juelich (DE). Institute of Bio- and Nanosystems (IBN), Functional Nanostructures at Surfaces (IBN-3)


    The field of molecular organic electronics is an emerging and very dynamic area. The continued trend to miniaturisation, combined with increasing complexity and cost of production in conventional semiconductor electronics, forces companies to turn their attention to alternatives that promise the next levels of scale at significantly lower cost. After consumer electronic devices based on organic transistors, such as TVs and book readers, have already been presented, molecular electronics is expected to offer the next breakthrough in feature size. Unfortunately, most of the organic/metal interfaces contain intrinsic defects that break the homogeneity of the interface properties. In this thesis, the electronic and structural properties of such defects were examined in order to understand the influence of the inhomogeneities on the quality of the interface layer. However, the main focus of this work was the investigation of the local properties of a single molecule. Taking advantage of the Scanning Tunnelling Microscope's (STM's) ability to act as a local probe, a single molecular switch was realized and studied. Moreover, in close collaboration with theory groups, the underlying mechanism driving the switching process was identified and described. Besides the investigation of the switching process, the ability of the STM to build nanostructures of different shapes from large organic molecules was shown. Knowing the parameters for realization and control of the switching process and for building the molecular corrals, the results of this investigation enable the reconstruction of the studied molecular ensemble and its deployment in electric molecular circuits, constituting a next step towards further miniaturization of electronic devices. (orig.)

  5. Molecular Probe Analysis of Mammalian Brain Acetylcholinesterase (United States)


    Project and Degrees Awarded During this Reporting Period: Judith K. Marquis, Principal Investigator Thomas Biagioni , Senior Research Technician Robert...binding sites in nerve membrane vesicles. Comp. Biochem. Physiol. 80C: 203-205 (1985). 5. Volpe, L.S., T.M. Biagioni & J.K. Marquis: In vitro modulation of...Saxena, Vol. 6(1988Y.8 11. Marquis, J.K. & T.M. Biagioni : Selective inhibition of acetylcholinesterase and butyrylcholinesterase in human plasma

  6. Genetic and Molecular Network Analysis of Behavior


    Williams, Robert W.; Mulligan, Megan K.


    This chapter provides an introduction into the genetic control and analysis of behavioral variation using powerful online resources. We introduce you to the new field of systems genetics using "case studies" drawn from the world of behavioral genetics that exploit populations of genetically diverse lines of mice. These lines differ very widely in patterns of gene and protein expression in the brain and in patterns of behavior. In this chapter we address the following set of related questions:...

  7. Quasi- and inelastic neutron scattering to investigate the molecular dynamics of discotic molecules in the bulk

    Directory of Open Access Journals (Sweden)

    Krause Christina


    Full Text Available In- and quasielastic neutron scattering is employed to investigate both the vibrational density of states and the molecular dynamics of two homologous discotic liquid crystals (DLC with different length of the alkyl side chain based on a triphenylene derivate. For both compounds characteristic low frequency excess contributions to the vibrational density of states are found. Therefore it is concluded that these liquid crystals show a glass-like behaviour. Elastic scans further show that in these materials a rich molecular dynamics takes place.

  8. Investigation of the Interaction between Adenosine and Human Serum Albumin by Fluorescent Spectroscopy and Molecular Modeling

    Institute of Scientific and Technical Information of China (English)

    CUI Feng-Ling; WANG Jun-Li; LI Fang; FAN Jing; QU Gui-Rong; YAO Xiao-Jun; LEI Bei-Lei


    The binding interaction of adenosine with human serum albumin (HSA) was investigated under simulative physiological conditions by fluorescence spectroscopy in combination with a molecular modeling method. A strong fluorescence quenching reaction of adenosine to HSA was observed and the quenching mechanism was suggested as static quenching according to the Stern-Volmer equation. The binding constants (K) at different temperatures as well as thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS), were calculated according to relevant fluorescent data and Vant'Hoff equation. The hydrophobic interaction was a predominant intermolecular force in order to stabilize the complex, which was in agreement with the results of molecular modeling study.

  9. Adaptive molecular resolution approach in Hamiltonian form: An asymptotic analysis (United States)

    Zhu, Jinglong; Klein, Rupert; Delle Site, Luigi


    Adaptive molecular resolution approaches in molecular dynamics are becoming relevant tools for the analysis of molecular liquids characterized by the interplay of different physical scales. The essential difference among these methods is in the way the change of molecular resolution is made in a buffer (transition) region. In particular a central question concerns the possibility of the existence of a global Hamiltonian which, by describing the change of resolution, is at the same time physically consistent, mathematically well defined, and numerically accurate. In this paper we present an asymptotic analysis of the adaptive process complemented by numerical results and show that under certain mathematical conditions a Hamiltonian, which is physically consistent and numerically accurate, may exist. Such conditions show that molecular simulations in the current computational implementation require systems of large size, and thus a Hamiltonian approach such as the one proposed, at this stage, would not be practical from the numerical point of view. However, the Hamiltonian proposed provides the basis for a simplification and generalization of the numerical implementation of adaptive resolution algorithms to other molecular dynamics codes.

  10. Molecular Eigensolution Symmetry Analysis and Fine Structure

    Directory of Open Access Journals (Sweden)

    William G. Harter


    Full Text Available Spectra of high-symmetry molecules contain fine and superfine level cluster structure related to J-tunneling between hills and valleys on rovibronic energy surfaces (RES. Such graphic visualizations help disentangle multi-level dynamics, selection rules, and state mixing effects including widespread violation of nuclear spin symmetry species. A review of RES analysis compares it to that of potential energy surfaces (PES used in Born-Oppenheimer approximations. Both take advantage of adiabatic coupling in order to visualize Hamiltonian eigensolutions. RES of symmetric and D2 asymmetric top rank-2-tensor Hamiltonians are compared with Oh spherical top rank-4-tensor fine-structure clusters of 6-fold and 8-fold tunneling multiplets. Then extreme 12-fold and 24-fold multiplets are analyzed by RES plots of higher rank tensor Hamiltonians. Such extreme clustering is rare in fundamental bands but prevalent in hot bands, and analysis of its superfine structure requires more efficient labeling and a more powerful group theory. This is introduced using elementary examples involving two groups of order-6 (C6 and D3~C3v, then applied to families of Oh clusters in SF6 spectra and to extreme clusters.

  11. Molecular structure and spectral (FT-IR, Raman) investigations of 3-aminocoumarin (United States)

    Dereli, Ömer


    The molecular structure of 3-Aminocoumarin was determined by conformational analysis. Conformational space was scanned by conformer distribution option of Spartan 08 program package using Merck Molecular Force Field (MMFF) method. Then obtained conformers were optimized by B3LYP/6-311++ G( d, p) and B3LYP/6-311 G( d, p) levels of Density Functional Theory. As a result of these calculations, only one conformer was determined. Vibrational frequencies of this conformer were calculated by Gaussian 03 program package using the same levels of geometry optimizations. The FT-IR and Raman spectra of 3-Aminocoumarin were recorded and compared with the calculated values. Consequently, a good agreement between experimental and the calculated values were founded. Molecular electrostatic potentials (MEPs), HOMO-LUMO energies, thermodynamic properties and Mulliken atomic charges were also covered in this study.

  12. Investigation of molecular diagnosis in Chinese patients with myotonic dystrophy type 1

    Institute of Scientific and Technical Information of China (English)

    Li Mao; Wang Zhanjun; Cui Fang; Yang Fei; Chen Zhaohui; Ling Li; Pu Chuanqiang


    Background Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disease caused by abnormal expansion of cytosine-thymine-guanine (CTG) repeats in the myotonic dystrophy protein kinase gene.The clinical manifestations of DM1 are multisystemic and highly variable,and the unstable nature of CTG expansion causes wide genotypic and phenotypic presentations,which make molecular methods essential for the diagnosis.So far,very few studies about molecular diagnosis in Chinese patients with DM1 have been reported.Therefore,we carried out a study using two different methods in molecular diagnosis to verify the validity in detecting CTG expansion in Chinese patients showing DM signs.Methods A total of 97 Chinese individuals were referred for molecular diagnosis of DM1 using conventional polymerase chain reaction (PCR) accompanied by Southern blotting and triplet primed PCR (TP-PCR).We evaluated the sensitivity and limitation of each method using percentage.Results By conventional PCR 65 samples showed only one fragment corresponding to the normal allele and 62 out of them were correctly diagnosed as DM1 by TP-PCR and three homologous non-DM1 samples were ruled out; Southern blotting analysis successfully made 13 out of 16 correct diagnoses with a more sensitivity using α-32P-labeled probes than dig-labeled probes.Conclusion Molecular analysis is necessary for the diagnosis of DM1 and TP-PCR is a reliable,sensitive,and easily performed method in molecular diagnosis which is worthy to be popularized.

  13. Investigation of the molecular conformations of ethanol using electron momentum spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Ning, C G; Luo, Z H; Huang, Y R; Liu, K; Zhang, S F; Deng, J K [Department of Physics and Key Laboratory of Atomic and Molecular NanoSciences of MOE, Tsinghua University, Beijing 100084 (China); Hajgato, B; Morini, F; Deleuze, M S [Research Group of Theoretical Chemistry, Department SBG, Hasselt University, Agoralaan Gebouw D, B-3590 Diepenbeek (Belgium)], E-mail:, E-mail:, E-mail:


    The valence electronic structure and momentum-space electron density distributions of ethanol have been investigated with our newly constructed high-resolution electron momentum spectrometer. The measurements are compared to thermally averaged simulations based on Kohn-Sham (B3LYP) orbital densities as well as one-particle Green's function calculations of ionization spectra and Dyson orbital densities, assuming Boltzmann's statistical distribution of the molecular structure over the two energy minima defining the anti and gauche conformers. One-electron ionization energies and momentum distributions in the outer-valence region were found to be highly dependent upon the molecular conformation. Calculated momentum distributions indeed very sensitively reflect the distortions and topological changes that molecular orbitals undergo due to the internal rotation of the hydroxyl group, and thereby exhibit variations which can be traced experimentally. The B3LYP model Kohn-Sham orbital densities are overall in good agreement with the experimental distributions, and closely resemble benchmark ADC(3) Dyson orbital densities. Both approaches fail to quantitatively reproduce the experimental momentum distributions characterizing the highest occupied molecular orbital. Since electron momentum spectroscopy measurements at various electron impact energies indicate that the plane wave impulse approximation is valid, this discrepancy between theory and experiment is tentatively ascribed to thermal disorder, i.e. large-amplitude and thermally induced dynamical distortions of the molecular structure in the gas phase.

  14. Protein analysis based on molecular beacon probes and biofunctionalized nanoparticles

    Institute of Scientific and Technical Information of China (English)


    With the completion of the human genome-sequencing project, there has been a resulting change in the focus of studies from genomics to proteomics. By utilizing the inherent advantages of molecular beacon probes and biofunctionalized nanoparticles, a series of novel principles, methods and techniques have been exploited for bioanalytical and biomedical studies. This review mainly discusses the applications of molecular beacon probes and biofunctionalized nanoparticles-based technologies for realtime, in-situ, highly sensitive and highly selective protein analysis, including the nonspecific or specific protein detection and separation, protein/DNA interaction studies, cell surface protein recognition, and antigen-antibody binding process-based bacteria assays. The introduction of molecular beacon probes and biofunctionalized nanoparticles into the protein analysis area would necessarily advance the proteomics research.

  15. Investigation of the Polyaniline Nanoparticles as the Substrate of Molecular Imprinted Polymer

    Directory of Open Access Journals (Sweden)

    Mina Mobram


    Full Text Available The current research work deals with investigation of the polyaniline nanoparticles as the substrate of the molecular imprinted polymer. Molecular imprinting is an interesting way to emulate the natural molecular identification that will be realized by preparing artificial identification sites with preset election for different target analyses. In this method, the target analyte acts as a template and will be connected to functional monomers through covalent or non-covalent bonding during the process of polymerization. Among all the conducting polymers, polyaniline is known for its unique electrical conductivity which can be controlled by the degree of oxidation of the main chain and protonation. Also, it shows different color changes with respect to the degree of oxidation and the surrounding ph. The results and investigations conducted in this study suggest that molecular imprinted polymers can be successfully developed by using aniline as monomer and preparation of linear polymer, and by using method of conductometry, the presence or absence of imprinted substances can be observed in the polymer according to the changes in conductivity caused by these phenomena.

  16. Investigating thermal evolution of the self-gravitating one dimensional molecular cloud by smoothed particle hydrodynamics

    CERN Document Server

    Nejad-Asghar, Mohsen


    The heating of the ion-neutral (or ambipolar) diffusion may affect the thermal phases of the molecular clouds. We present an investigation on the effect of this heating mechanism in the thermal instability of the molecular clouds. A weakly ionized one dimensional slab geometry, which is allowed for self-gravity and ambipolar diffusion, is chosen to study its thermal phases. We use the thermodynamic evolution of the slab to obtain the regions where slab cloud becomes thermally unstable. We investigate this evolution using the model of ambipolar diffusion with two-fluid smoothed particle hydrodynamics, as outlined by Hosking & Whitworth. Firstly, some parts of the technique are improved to test the pioneer works on behavior of the ambipolar diffusion in an isothermal self-gravitating slab. Afterwards, the improved two-fluid technique is used for thermal evolution of the slab. The results show that the thermal instability may persist inhomogeneities with a large density contrast at the intermediate parts of ...

  17. Dynamic Water Networks in Cytochrome c Oxidase from Paracoccus denitrificans Investigated by Molecular Dynamics Simulations


    Olkhova, Elena; Hutter, Michael C; Lill, Markus A.; Helms, Volkhard; Michel, Hartmut


    We present a molecular dynamics study of cytochrome c oxidase from Paracoccus denitrificans in the fully oxidized state, embedded in a fully hydrated dimyristoylphosphatidylcholine lipid bilayer membrane. Parallel simulations with different levels of protein hydration, 1.125 ns each in length, were carried out under conditions of constant temperature and pressure using three-dimensional periodic boundary conditions and full electrostatics to investigate the distribution and dynamics of water ...

  18. Photometric investigation of the MBM 12 molecular cloud area in Aries. I. Photoelectric photometry

    CERN Document Server

    Kazlauskas, A; Laugalys, V; Straizys, V


    The results of photoelectric photometry in the Vilnius seven-color system are given for 152 stars down to 12.2 mag in the area of the molecular cloud MBM 12 and the dust clouds L1454 and L1457 in Aries. The results of photometric classification of stars are also given. The investigation of interstellar extinction in the area is described in the next paper.

  19. Molecular dynamics of spider dragline silk fiber investigated by 2H MAS NMR. (United States)

    Shi, Xiangyan; Holland, Gregory P; Yarger, Jeffery L


    The molecular dynamics of the proteins that comprise spider dragline silk were investigated with solid-state (2)H magic angle spinning (MAS) NMR line shape and spin-lattice relaxation time (T1) analysis. The experiments were performed on (2)H/(13)C/(15)N-enriched N. clavipes dragline silk fibers. The silk protein side-chain and backbone dynamics were probed for Ala-rich regions (β-sheet and 31-helical domains) in both native (dry) and supercontracted (wet) spider silk. In native (dry) silk fibers, the side chains in all Ala containing regions undergo similar fast methyl rotations (>10(9) s(-1)), while the backbone remains essentially static (silk is wet and supercontracted, the presence of water initiates fast side-chain and backbone motions for a fraction of the β-sheet region and 31-helicies. β-Sheet subregion 1 ascribed to the poly(Ala) core exhibits slower dynamics, while β-sheet subregion 2 present in the interfacial, primarily poly(Gly-Ala) region that links the β-sheets to disordered 31-helical motifs, exhibits faster motions when the silk is supercontracted. Particularly notable is the observation of microsecond backbone motions for β-sheet subregion 2 and 31-helicies. It is proposed that these microsecond backbone motions lead to hydrogen-bond disruption in β-sheet subregion 2 and helps to explain the decrease in silk stiffness when the silk is wet and supercontracted. In addition, water mobilizes and softens 31-helical motifs, contributing to the increased extensibility observed when the silk is in a supercontracted state. The present study provides critical insight into the supercontraction mechanism and corresponding changes in mechanical properties observed for spider dragline silks.

  20. A portable molecular beam epitaxy system for in situ x-ray investigations at synchrotron beamlines. (United States)

    Slobodskyy, T; Schroth, P; Grigoriev, D; Minkevich, A A; Hu, D Z; Schaadt, D M; Baumbach, T


    A portable synchrotron molecular beam epitaxy (MBE) system is designed and applied for in situ investigations. The growth chamber is equipped with all the standard MBE components such as effusion cells with shutters, main shutter, cooling shroud, manipulator, reflection high energy electron diffraction setup, and pressure gauges. The characteristic feature of the system is the beryllium windows which are used for in situ x-ray measurements. An UHV sample transfer case allows in vacuo transfer of samples prepared elsewhere. We describe the system design and demonstrate its performance by investigating the annealing process of buried InGaAs self-organized quantum dots.

  1. An investigation of the preparation of high molecular weight perfluorocarbon polyethers (United States)

    Watts, R. O.; Tarrant, P.


    High molecular weight perfluorocarbon polyether gums were obtained by photolysis of perfluorodienes and discyl fluorides containing a perfluorocarbon polyether backbond. The materials obtained are represented by chemical formulas. A method was developed whereby reactive acyl fluoride and trifluorovinyl end groups are converted into inert structures. In order to investigate the possible preparation of difunctional molecules which may be useful in polymer synthesis, the reactions of hexafluoropropene oxide (HFPO) with Grignard and organolithium reagents have been studied. Reactions of various nucleophilic reagents with HFPO were also investigated.

  2. Analysis and computational dissection of molecular signature multiplicity.

    Directory of Open Access Journals (Sweden)

    Alexander Statnikov


    Full Text Available Molecular signatures are computational or mathematical models created to diagnose disease and other phenotypes and to predict clinical outcomes and response to treatment. It is widely recognized that molecular signatures constitute one of the most important translational and basic science developments enabled by recent high-throughput molecular assays. A perplexing phenomenon that characterizes high-throughput data analysis is the ubiquitous multiplicity of molecular signatures. Multiplicity is a special form of data analysis instability in which different analysis methods used on the same data, or different samples from the same population lead to different but apparently maximally predictive signatures. This phenomenon has far-reaching implications for biological discovery and development of next generation patient diagnostics and personalized treatments. Currently the causes and interpretation of signature multiplicity are unknown, and several, often contradictory, conjectures have been made to explain it. We present a formal characterization of signature multiplicity and a new efficient algorithm that offers theoretical guarantees for extracting the set of maximally predictive and non-redundant signatures independent of distribution. The new algorithm identifies exactly the set of optimal signatures in controlled experiments and yields signatures with significantly better predictivity and reproducibility than previous algorithms in human microarray gene expression datasets. Our results shed light on the causes of signature multiplicity, provide computational tools for studying it empirically and introduce a framework for in silico bioequivalence of this important new class of diagnostic and personalized medicine modalities.

  3. Investigation of multiaxial molecular dynamics by 2H MAS NMR spectroscopy. (United States)

    Kristensen, J H; Hoatson, G L; Vold, R L


    The technique of 2H MAS NMR spectroscopy is presented for the investigation of multiaxial molecular dynamics. To evaluate the effects of discrete random reorientation a Lie algebraic formalism based on the stochastic Liouville-von Neumann equation is developed. The solution to the stochastic Liouville-von Neumann equation is obtained both in the presence and absence of rf irradiation. This allows effects of molecular dynamics to be evaluated during rf pulses and extends the applicability of the formalism to arbitrary multiple pulse experiments. Theoretical methods are presented for the description of multiaxial dynamics with particular emphasis on the application of vector parameters to represent molecular rotations. Numerical time and powder integration algorithms are presented that are both efficient and easy to implement computationally. The applicability of 2H MAS NMR spectroscopy for investigating molecular dynamics is evaluated from theoretical spectra. To demonstrate the potential of the technique the dynamics of thiourea-2H4 is investigated experimentally. From a series of variable temperature MAS and quadrupole echo spectra it has been found that the dynamics can be described by composite rotation about the CS and CN bonds. Both experiments are sensitive to the fast CS rotation which is shown to be described by the Arrhenius parameters E(CS) = 46.4 +/- 2.3 kJ mol(-1) and ln(A(CS))= 32.6 +/- 0.9. The MAS experiment represents a significant improvement by simultaneously allowing the dynamics of the slow CN rotation to be fully characterized in terms of E(CN) = 56.3 +/- 3.4 kJ mol(-1) and ln(A(CN)) = 25.3 +/- 1.1.

  4. Investigation of Terminal Group Effect on Electron Transport Through Open Molecular Structures

    Institute of Scientific and Technical Information of China (English)

    C.Preferencial Kala; P.Aruna Priya; D.John Thiruvadigal


    The effect of terminal groups on the electron transport through metal-molecule-metal system has been investigated using nonequilibrium Green's function (NEGF) formalism combined with extended Huckel theory (EHT).Au-molecule-Au junctions are constructed with borazine and BCN unit structure as core molecule and sulphur (S),oxygen (O),selenium (Se) and cyano-group (CN) as terminal groups.The electron transport characteristics of the borazine and BCN molecular systems are analyzed through the transmission spectra and the current-voltage curve.The results demonstrate that the terminal groups modifying the transport behaviors of these systems in a controlled way.Our result shows that,selenium is the best linker to couple borazine to Au electrode and oxygen is the best one to couple BCN to Au electrode.Furthermore,the results of borazine systems are compared with that of BCN molecular systems and are discussed.Simulation results show that the conductance through BCN molecular systems is four times larger than the borazine molecular systems.Negative differential resistance behavior is observed with borazine-CN system and the saturation feature appears in BCN systems.

  5. New Diethyl Ammonium Salt of Thiobarbituric Acid Derivative: Synthesis, Molecular Structure Investigations and Docking Studies

    Directory of Open Access Journals (Sweden)

    Assem Barakat


    Full Text Available The synthesis of the new diethyl ammonium salt of diethylammonium(E-5-(1,5-bis(4-fluorophenyl-3-oxopent-4-en-1-yl-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized by the strong intramolecular electron delocalization with the adjacent carbonyl groups and so the reaction proceeds without any cyclization. The molecular structure investigations of 3 were determined by single-crystal X-ray diffraction as well as DFT computations. The theoretically calculated (DFT/B3LYP geometry agrees well with the crystallographic data. The effect of fluorine replacement by chlorine atoms on the molecular structure aspects were investigated using DFT methods. Calculated electronic spectra showed a bathochromic shift of the π-π* transition when fluorine is replaced by chlorine. Charge decomposition analyses were performed to study possible interaction between the different fragments in the studied systems. Molecular docking simulations examining the inhibitory nature of the compound show an anti-diabetic activity with Pa (probability of activity value of 0.229.

  6. Software reliability experiments data analysis and investigation (United States)

    Walker, J. Leslie; Caglayan, Alper K.


    The objectives are to investigate the fundamental reasons which cause independently developed software programs to fail dependently, and to examine fault tolerant software structures which maximize reliability gain in the presence of such dependent failure behavior. The authors used 20 redundant programs from a software reliability experiment to analyze the software errors causing coincident failures, to compare the reliability of N-version and recovery block structures composed of these programs, and to examine the impact of diversity on software reliability using subpopulations of these programs. The results indicate that both conceptually related and unrelated errors can cause coincident failures and that recovery block structures offer more reliability gain than N-version structures if acceptance checks that fail independently from the software components are available. The authors present a theory of general program checkers that have potential application for acceptance tests.

  7. Investigation of Y/SBA Composite Molecular Sieves Morphology Control and Catalytic Performance for n-Pentane Aromatization (United States)

    Shi, Chun-Wei; Wu, Wen-Yuan; Li, Shuai; Bian, Xue; Zhao, Shan-Lin; Pei, Ming-Yuan


    Using Y molecular sieve as the core, Y/SBA-15 composite molecular sieves were prepared by different crystallization methods in the paper. The growth process and morphologies of the composite molecular sieves were controlled by adjusting the synthesis factors. The structures and acidity of two kinds of composite molecular sieves were characterized by X-ray diffraction (XRD), N2 adsorption/desorption, transmission electron microscopy (TEM), and NH3-TPD. The catalysis performances of the composite molecular sieves were investigated in the aromatization reaction of n-pentane. The results indicated that the desired core-shell composite molecular sieves were obtained when the crystallization conditions were 36 hours, 100 °C and secondary crystallization. The aromatization results showed that core-shell composite molecular sieves had better selectivity for producing high application value xylenes compared to mixed-crystal composite molecular sieves.

  8. Yield and Failure Behavior Investigated for Cross-Linked Phenolic Resins Using Molecular Dynamics (United States)

    Monk, Joshua D.; Lawson, John W.


    Molecular dynamics simulations were conducted to fundamentally evaluate the yield and failure behavior of cross-linked phenolic resins at temperatures below the glass transition. Yield stress was investigated at various temperatures, strain rates, and degrees of cross-linking. The onset of non-linear behavior in the cross-linked phenolic structures was caused by localized irreversible molecular rearrangements through the rotation of methylene linkers followed by the formation or annihilation of neighboring hydrogen bonds. The yield stress results, with respect to temperature and strain rate, could be fit by existing models used to describe yield behavior of amorphous glasses. The degree of cross-linking only indirectly influences the maximum yield stress through its influence on glass transition temperature (Tg), however there is a strong relationship between the degree of cross-linking and the failure mechanism. Low cross-linked samples were able to separate through void formation, whereas the highly cross-linked structures exhibited bond scission.

  9. Spectroscopic investigations on the interactions between isopropanol and trypsin at molecular level. (United States)

    Hu, Xinxin; Yu, Zehua; Liu, Rutao


    The toxicity of hydroxyl group of isopropanol to trypsin in aqueous solution was investigated by techniques including UV-visible absorption spectroscopy, fluorescence spectroscopy, circular dichroism (CD) spectroscopy, enzyme activity assay and molecular docking technology. The results of UV-visible absorption spectroscopy and CD spectra indicate that isopropanol could change the secondary structure of trypsin by increasing the content of α-helix and decreasing the content of β-sheet. The tertiary structure of trypsin was also changed owing to the loss of environmental asymmetry of amino acid residues. Isopropanol bound into a hydrophobic cavity on the surface of trypsin by a hydrogen bond located between the hydrogen atom on the hydroxyl of isopropanol and the oxygen atoms on SER 214 and hydrophobic interaction, as the molecular docking results showed. In addition, isopropanol could affect the function of trypsin by increasing its catalytic activity.

  10. Investigations of bisacodyl with modified β-cyclodextrins: Characterization, molecular modeling, and effect of PEG. (United States)

    Li, Shanshan; Wang, Lili; Jiang, Jian; Tang, Peixiao; Wang, Qing; Wu, Di; Li, Hui


    Bisacodyl inclusion into hydroxypropyl-β-cyclodextrin and 2,6-di-O-methyl-β-cyclodextrin cavities was experimentally and theoretically investigated, and the effect of PEG 4000 on these inclusions was studied. Isothermal calorimetry titration curves indicated that the binary inclusion processes are enthalpy- and entropy-driven. The solid-state complexes were fully characterized by FT-IR, XRPD, DSC and SEM analyses. FT-IR, (1)H NMR, and ROESY studies provided the most favorable encapsulation modes of binary complexes, and results were further confirmed by molecular docking and molecular dynamics studies. The presence of PEG 4000 slightly enhanced encapsulation efficiency, solubility and dissolution rates of the binary complexes. In vivo studies showed that complexes with CDs markedly accelerated gastrointestinal transit time compared with pure bisacodyl, whereas addition of PEG 4000 showed no further significant improvement of the bioavailability.

  11. Molecular Investigation of Leber’s Hereditary Optic Neuropathy Common Mutations in Suspected Patients

    Directory of Open Access Journals (Sweden)

    HR Soleimanpour


    Full Text Available LHON is a mitochondrial neurodegenerative disorder often manifesting itself in the second or third decade of life, and hence resulting in progressive central vision loss usually in a short period of 2-8 weeks within which different degrees of blindness may occur. Etiologically, more than twenty missense mutations have been reported for LHON, amongst which the three mutations of G11778A, G3460A and T14484C, affecting NADH dehydrogenase complex activity, are recognized as primary mutations. The three primary mutations account for 90% of LHON patients, emphasizing the importance of molecular investigation of these mutations for differential diagnosis of LHON. Using PCR-RFLP, this research resulted in the detection of two LHON families carrying the G11778A mutation in homoplasmy and described the clinical and molecular features of the disease in the patients.

  12. Investigating the Life Cycle of Molecular Clouds in the Andromeda Galaxy (United States)

    Beerman, Lori; Dalcanton, Julianne; Schruba, Andreas; Leroy, Adam K.; Johnson, Lent C.; Weisz, Daniel R.; Fouesneau, Morgan; PHAT Collaboration


    There is currently a great divide between high resolution studies of stellar clusters and molecular clouds in the Milky Way, and those done in extragalactic systems, where individual stars and clouds cannot usually be resolved. For my thesis work, I combined several astronomical data sets to investigate the life cycle of molecular clouds in the Andromeda Galaxy. The primary data sets I used are the Panchromatic Hubble Andromeda Treasury (PHAT), which catalogued over 200 million stars, and a molecular cloud catalogue that is constructed from new high spatial/spectral resolution (20 pc, 1 km/s) CARMA observations. Several ancillary data sets, including H-alpha and Spitzer IR emission maps were also used, taking advantage of broad wavelength coverage to search for indicators of star formation with different timescales. Comparisons were also made with the PHAT cluster sample, and the youngest (star formation indicator. The ages and masses of these clusters were determined by fitting the color-magnitude diagrams (CMDs) of their resolved stars to theoretical isochrones. The distribution of the youngest clusters shows a strong correlation with the molecular cloud distribution, while no correlation is evident for clusters greater than 30 Myr. Each molecular cloud in the sample was then classified as a star-forming cloud or a non-star forming cloud, based on the presence of any one of several star formation indicators. About 60% of the clouds in the sample were found to be associated with massive star formation. Based on the comparison between these observations and the results from a Monte Carlo simulation, I will also demonstrate how we can constrain the timescales for the relative phases in a cloud's life.

  13. Investigation of hybrid molecular material prepared by ionic liquid and polyoxometalate anion

    Indian Academy of Sciences (India)

    T Rajkumar; G Ranga Rao


    A solid hybrid molecular material containing 1-butyl 3-methyl imidazolium cations and Keggin anions of phosphotungstic acid has been synthesized. It is fully characterized by CHN analysis, FTIR, XRD, UV-Vis-NIR DRS, 31P MAS NMR, TGA and SEM. The FTIR spectrum of the compound shows the fingerprint vibrational bands of both Keggin molecular anions and imidazolium cations. The aromatic C-H stretch region (2700-3250 cm-1) of imidazolium cation is split due to the interaction between the ring C-H and bulky Keggin anion. The red-shift in the UV-Vis spectra and the downfield 31P MAS NMR chemical shift also confirm the electrostatic interaction between the ions in the compound. Near IR spectral region (1000-2500 nm) shows the elimination of water in the compound which is hydrophobic.

  14. Investigation of hydrogen bonded molecular solids by diffraction, spectroscopy, and computational chemistry (United States)

    Hudson, Matthew R.

    The nature of hydrogen-bonding interactions in the solid state is examined through the investigation of molecular crystals by incoherent inelastic neutron scattering (INS) spectroscopy, Raman spectroscopy, X-ray and neutron diffraction, and computational chemistry. The molecular solids studied range from small organic molecules to larger inorganic acid salts. Hydrogen bonding is the primary mode of interaction in the solid state for each of the systems studied. INS spectra were collected at 25 K for each molecular solid and the motions of the hydrogen atoms assigned. Raman spectra were collected at 78 and 298 K to aid in the molecular mode assignments of the INS spectra and to examine possible phase changes as a function of temperature. Neutron diffraction was employed, when possible, to accurately locate the hydrogen atom positions, and X-ray diffraction was performed to obtain accurate unit cell dimensions and to obtain initial characterizations of the samples. The diffraction structures served as the basis for solid-state density functional theory (DFT) calculations. DFT simulations were used to aid in the vibrational normal mode assignments, to investigate possible solid-phase transitions, and as a test of the limits of basis sets and the available DFT theory. Of the six molecular solids studied, several important observations were made: (1) the determination of a structural phase transition in L-alanine alaninium nitrate by both spectroscopic and theoretical methods, (2) the structure of picolinic acid was elucidated at 25 K and room-temperature by the combination of INS and theory, (3) glycine lithium sulfate was found to be a useful test of DFT to accurately optimize the structure and calculate the normal modes of a complex 3D network of hydrogen-bonding interactions, (4) nicotinic acid was found to be a useful test of one dimensional hydrogen-bonding interactions with pi-stacking interactions dominating the orthogonal directions, and (5) parabanic acid

  15. TREEFINDER: a powerful graphical analysis environment for molecular phylogenetics

    Directory of Open Access Journals (Sweden)

    von Haeseler Arndt


    Full Text Available Abstract Background Most analysis programs for inferring molecular phylogenies are difficult to use, in particular for researchers with little programming experience. Results TREEFINDER is an easy-to-use integrative platform-independent analysis environment for molecular phylogenetics. In this paper the main features of TREEFINDER (version of April 2004 are described. TREEFINDER is written in ANSI C and Java and implements powerful statistical approaches for inferring gene tree and related analyzes. In addition, it provides a user-friendly graphical interface and a phylogenetic programming language. Conclusions TREEFINDER is a versatile framework for analyzing phylogenetic data across different platforms that is suited both for exploratory as well as advanced studies.

  16. Molecular ions and protonated molecules observed in the atmospheric solids analysis probe analysis of steroids. (United States)

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


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

  17. A quantum mechanical/molecular mechanical approach to the investigation of particle-molecule interactions (United States)

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


    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)].

  18. Investigation of InN layers grown by molecular beam epitaxy on GaN templates

    Energy Technology Data Exchange (ETDEWEB)

    Vilalta-Clemente, A.; Mutta, G.R.; Chauvat, M.P.; Morales, M.; Doualan, J.L.; Ruterana, P. [CIMAP UMR 6252 CNRS-ENSICAEN-CEA-UCBN, Caen (France); Grandal, J.; Sanchez-Garcia, M.A.; Calle, F. [ISOM y Department de Ingenieria Electronica, E.T.S.I. Telecomunicacion, Universidad Politecnica de Madrid, Ciudad Universitaria (Spain); Valcheva, E.; Kirilov, K. [Faculty of Physics, Sofia University (Bulgaria)


    An investigation of InN layers grown on GaN templates by molecular beam epitaxy (MBE) has been carried out by X-ray diffraction (XRD), Raman spectroscopy (RS) and photoluminescence (PL). A good correlation is noticed between their crystalline quality and optical properties. The best samples exhibit a PL emission between 0.6 and 0.7 eV. The surface structure was quite different from one sample to the other, pointing out to a critical role of the growth conditions, which probably need to be tightly optimized for a good reproducibility. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  19. Investigations to improve carbon dioxide control with amine and molecular sieve type sorbers (United States)

    Bertrand, J. F.; Brose, H. F.; Kester, F. L.; Lunde, P. J.


    The optimization trends and operating parameters of an integral molecular sieve bed heat exchanger were investigated. The optimum combination of substrate and coating for the HS-B porous polymer was determined based on the CO2 dynamic capacity in the presence of water vapor. Full size HS-B canister performance was evaluated. An Amine CO2 Concentrator utilizing IR-45 sorber material and available Manned Orbiting Laboratory hardware was designed, fabricated and tested for use as an experiment in the NASA 90-day space simulator test of 1970. It supported four men in the simulator for 71 days out of the 90-day test duration.

  20. Diffusion and separation of CH4/N2 in pillared graphene nanomaterials: A molecular dynamics investigation (United States)

    Zhou, Sainan; Lu, Xiaoqing; Wu, Zhonghua; Jin, Dongliang; Guo, Chen; Wang, Maohuai; Wei, Shuxian


    Diffusion and separation of CH4/N2 in pillared graphene were investigated by molecular dynamics. The pillared graphene with (6, 6) carbon nanotube (CNT) exhibited the higher diffusion and selectivity of CH4 over N2 than that with (7, 7) CNT due to the cooperative effect of pore topological characteristics and interaction energy. The stronger interaction facilitated CH4 to enter CNT prior to N2, and higher pressure promoted CH4 to pass CNT more easily. The relative concentrations profiles showed that CH4 reached equilibrium state faster than N2 at low pressure. Our results highlight potential use of pillared graphene in gas purification and separation.

  1. Molecular-based investigation of Cryptosporidium and Giardia from animals in water catchments in southeastern Australia. (United States)

    Nolan, Matthew J; Jex, Aaron R; Koehler, Anson V; Haydon, Shane R; Stevens, Melita A; Gasser, Robin B


    There has been no large-scale systematic molecular epidemiological investigation of the waterborne protozoans, Cryptosporidium or Giardia, in southeastern Australia. Here, we explored, for the first time, the genetic composition of these genera in faecal samples from animals in nine Melbourne Water reservoir areas, collected over a period of two-years. We employed PCR-based single-strand conformation polymorphism (SSCP) and phylogenetic analyses of loci (pSSU and pgp60) in the small subunit (SSU) of ribosomal RNA and 60-kDa glycoprotein (gp60) genes to detect and characterise Cryptosporidium, and another locus (ptpi) in the triose-phosphate isomerase (tpi) gene to identify and characterise Giardia. Cryptosporidium was detected in 2.8% of the 2009 samples examined; the analysis of all amplicons defined 14 distinct sequence types for each of pSSU and pgp60, representing Cryptosporidium hominis (genotype Ib - subgenotype IbA10G2R2), Cryptosporidium parvum (genotype IIa - subgenotypes IIaA15G2R1, IIaA19G2R1, IIaA19G3R1, IIaA19G4R1, IIaA20G3R1, IIaA20G4R1, IIaA20G3R2 and IIaA21G3R1), Cryptosporidium cuniculus (genotype Vb - subgenotypes VbA22R4, VbA23R3, VbA24R3, VbA25R4 and VbA26R4), and Cryptosporidium canis, Cryptosporidium fayeri, Cryptosporidium macropodum and Cryptosporidium ubiquitum as well as six new pSSU sequence types. In addition, Giardia was identified in 3.4% of the samples; all 28 distinct ptpi sequence types defined were linked to assemblage A of Giardia duodenalis. Of all 56 sequence types characterised, eight and one have been recorded previously in Cryptosporidium and Giardia, respectively, from humans. In contrast, nothing is known about the zoonotic potential of 35 new genotypes of Cryptosporidium and Giardia recorded here for the first time. Future work aims to focus on estimating the prevalence of Cryptosporidium and Giardia genotypes in humans and a wide range of animals in Victoria and elsewhere in Australia. (Nucleotide sequences reported in

  2. Investigation of the torsional barrier of EDOT using molecular mechanics and DFT methods. (United States)

    Durães, Jussara A; da Silva Filho, Demétrio A; Ceschin, Artemis M; Sales, Maria J A; Martins, João B L


    When heterocyclic monomers are polymerized by electrochemical or chemical methods, they form fully conjugated polymers which have a wide range of applications due to their outstanding electronic properties. Among this class of compounds, thiophene derivatives are widely used due to their chemical stability and synthesis flexibility. With the goal to investigate the torsion barrier of polymer chains, a few units of 3,4-ethylenedioxythiophene (EDOT) were chosen and submitted to molecular mechanics (MM), density functional theory (DFT) and coupled cluster CCSD(T) calculations. This study helps to understand the performance and transferability of force fields used in molecular mechanics and molecular dynamics simulations often used to describe structure-property relationships of those systems. Determination of inter-ring torsion angle was performed in a comparative study using both force field, DFT and CCSD(T) methods. A good agreement was noticed between MM and QC results and highlights the importance of the description of the interactions involving the oxygen atoms present in the structure of EDOT. These observations are related to the α,α-coupling that occurs between the monomer units and yields a linear polymer. DFT HOMO and LUMO orbitals were also presented. Finally, UV-vis spectra of EDOT units were obtained using several levels of theory by means of time-dependent DFT calculations (TD-DFT).

  3. Theoretical studies on the molecular structure, conformational preferences, topological and vibrational analysis of allicin (United States)

    Durlak, Piotr; Berski, Sławomir; Latajka, Zdzisław


    The molecular structure, conformational preferences, topological and vibrational analysis of allicin has been investigated at two different approaches. Calculations have been carried out on static (DFT and MP2) levels with an assortment of Dunning's basis sets and dynamic CPMD simulations. In this both case within the isolated molecule approximation. The results point out that at least twenty different conformers coexist on the PES as confirmed by the flexible character of this molecule. The topological analysis of ELF showed very similar nature of the Ssbnd S and Ssbnd O bonds. The infrared spectrum has been calculated, and a comparative vibrational analysis has been performed.

  4. Investigation for Molecular Attraction Impact Between Contacting Surfaces in Micro-Gears (United States)

    Yang, Ping; Li, Xialong; Zhao, Yanfang; Yang, Haiying; Wang, Shuting; Yang, Jianming


    The aim of this research work is to provide a systematic method to perform molecular attraction impact between contacting surfaces in micro-gear train. This method is established by integrating involute profile analysis and molecular dynamics simulation. A mathematical computation of micro-gear involute is presented based on geometrical properties, Taylor expression and Hamaker assumption. In the meantime, Morse potential function and the cut-off radius are introduced with a molecular dynamics simulation. So a hybrid computational method for the Van Der Waals force between the contacting faces in micro-gear train is developed. An example is illustrated to show the performance of this method. The results show that the change of Van Der Waals force in micro-gear train has a nonlinear characteristic with parameters change such as the modulus of the gear and the tooth number of gear etc. The procedure implies a potential feasibility that we can control the Van Der Waals force by adjusting the manufacturing parameters for gear train design.

  5. A quantitative analysis of IRAS maps of molecular clouds (United States)

    Wiseman, Jennifer J.; Adams, Fred C.


    We present an analysis of IRAS maps of five molecular clouds: Orion, Ophiuchus, Perseus, Taurus, and Lupus. For the classification and description of these astrophysical maps, we use a newly developed technique which considers all maps of a given type to be elements of a pseudometric space. For each physical characteristic of interest, this formal system assigns a distance function (a pseudometric) to the space of all maps: this procedure allows us to measure quantitatively the difference between any two maps and to order the space of all maps. We thus obtain a quantitative classification scheme for molecular clouds. In this present study we use the IRAS continuum maps at 100 and 60 micrometer(s) to produce column density (or optical depth) maps for the five molecular cloud regions given above. For this sample of clouds, we compute the 'output' functions which measure the distribution of density, the distribution of topological components, the self-gravity, and the filamentary nature of the clouds. The results of this work provide a quantitative description of the structure in these molecular cloud regions. We then order the clouds according to the overall environmental 'complexity' of these star-forming regions. Finally, we compare our results with the observed populations of young stellar objects in these clouds and discuss the possible environmental effects on the star-formation process. Our results are consistent with the recently stated conjecture that more massive stars tend to form in more 'complex' environments.

  6. Incident investigation and analysis for E and P operations

    Energy Technology Data Exchange (ETDEWEB)

    Waterfall, K.W.; Willink, C.A.T.; Milne, D.J. (Shell International Petroleum Mij. B.V., The Hague (Netherlands))


    Incident investigation and analysis in Shell E and P operations is part of performance monitoring in health, safety, and environment (HSE) management systems. The focus is on identifying underlying causes. A step-wise approach is given from immediate response through determining the level of investigation, coverage of investigation aspects, analysis, recording, and follow-up. The means to analyze incidents by application of the Tripod system, which is directed toward understanding underlying causes of incidents, are reviewed.

  7. Cellular and molecular investigations of the adhesion and mechanics of Listeria monocytogenes (United States)

    Eskhan, Asma Omar

    Atomic force microscopy has been used to quantify the adherence and mechanical properties of an array of L. monocytogenes strains and their surface biopolymers. First, eight L. monocytogenes strains that represented the two major lineages of the species were compared for their adherence and mechanics at cellular and molecular levels. Our results indicated that strains of lineage' II were characterized by higher adhesion and Young's moduli, longer and more rigid surface biopolymers and lower specific and nonspecific forces when compared to lineage' I strains. Additionally, adherence and mechanical properties of eight L. monocytogenes epidemic and environmental strains were probed. Our results pointed to that environmental and epidemic strains representative of a given lineage were similar in their adherence and mechanical properties when investigated at a cellular level. However, when the molecular properties of the strains were considered, epidemic strains were characterized by higher specific and nonspecific forces, shorter, denser and more flexible biopolymers compared to environmental strains. Second, the role of environmental pH conditions of growth on the adhesion and mechanics of a pathogenic L. monocytogenes EGDe was investigated. Our results pointed to a transition in the adhesion energies for cells cultured at pH 7. In addition, when the types of molecular forces that govern the adhesion were quantified using Poisson statistical approach and using a new proposed method, specific hydrogen-bond energies dominated the bacterial adhesion process. Such a finding is instrumental to researchers designing methods to control bacterial adhesion. Similarly, bacterial cells underwent a transition in their mechanical properties. We have shown that cells cultured at pH 7 were the most rigid compared to those cultured in lower or higher pH conditions of growth. Due to transitions observed in adherence and mechanics when cells were cultured at pH 7, we hypothesized that

  8. Investigation of the inclusions of puerarin and daidzin with beta-cyclodextrin by molecular dynamics simulation. (United States)

    Zhang, Haiyang; Feng, Wei; Li, Cong; Tan, Tianwei


    Puerarin and daidzin, two major isoflavonoids of Radix puerariae , are widely adopted in traditional Chinese medicine. Foundational aspects related to separating the two compounds are essential to develop a more economical purification process. Inclusion models of the two compounds with beta-cyclodextrin (beta-CD) have been investigated by molecular dynamics simulation. Computational results reveal that both puerarin and daidzin can induce a conformational change of beta-CD, which is compressed in one direction and stretched in the other. The effect of solvent and media on the conformational change of beta-CD and the movement of guest molecules inside the cavity has been investigated. Furthermore, hydrogen bonding interactions have been analyzed, and the results have been utilized for the explanation of separating puerarin from daidzin.

  9. On the vibrational behavior of graphynes and its family: a molecular dynamics investigation

    Energy Technology Data Exchange (ETDEWEB)

    Rouhi, S.; Salmalian, K., E-mail: [Young Researchers Club, Langroud Branch, Islamic Azad University, Langroud, Guilan (Iran, Islamic Republic of); Ghasemi, A. [Young Researchers and Elite Club, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of)


    Molecular dynamics (MD) simulation is used to investigate the vibrational behavior of γ-graphyne and its family. Five different nanosheet types including graphyne, graphdiyne, 3-graphyne, 4-graphyne, and 5-graphyne are considered for investigation. The fundamental natural frequencies of armchair and zigzag nanosheets with different geometrical sizes under different boundary conditions are computed. It is shown that increasing the size of γ-graphyne results in decreasing the natural frequency. Comparing the vibrational behavior of armchair and zigzag nanosheets, it is shown that for large nanosheets, the effect of atomic structure on the fundamental natural frequency can be neglected. Besides, it is represented that increasing the number of acetylene links connecting neighboring hexagons in the structure of nanosheets leads to decreasing the frequency. (author)

  10. Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Bowsher, James, E-mail:; Giles, William; Yin, Fang-Fang [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 (United States); Yan, Susu [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 (United States); Roper, Justin [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States)


    Purpose: Onboard imaging—currently performed primarily by x-ray transmission modalities—is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. Methods: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. Results: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. Conclusions: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min

  11. Spectroscopic and molecular modeling investigation on the binding of a synthesized steroidal amide to protein

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hua-xin, E-mail:; Liu, E.


    Owing to the various valuable biological activities, steroidal amides have become a hot topic in steroidal pharmaceutical chemistry. In this paper, an anti-tumor steroid derivate (DAAO) was synthesized and identified. The interaction between DAAO and human serum albumin (HSA) was studied by fluorescence spectra, circular dichroism (CD) spectra, molecular modeling and molecular probe techniques. The results suggested that DAAO had reacted with HSA through hydrogen bonds and van der Waals power. The formation of DAAO–HSA complex at ground state led to static quenching of HSA's fluorescence. The number of binding sites, binding constants, enthalpy change (ΔH{sup θ}), Gibbs free energy change (ΔG{sup θ}) and entropy change (ΔS{sup θ}) were calculated at different temperatures based on fluorescence quenching theory and classic equation. Molecular modeling investigation indicated that DAAO was more inclined to absorb on Sudlow's site I in subdomain IIA of HSA molecule on grounds of the lowest energy principle and steric hindrance effect. The binding location was further confirmed by fluorescence probe experiment using warfarin (site I probe) for displacement. Furthermore, the conformational changes of HSA in presence of DAAO were investigated by CD spectra. The results could provide new evidence explaining the relationship between the chemical structure and biological activity and may be useful for understanding the anti-cancer mechanism of steroidal drug. - Highlights: • A designed steroidal amide compound (DAAO) was synthesized by introducing amido bonds into a steroid nucleus. • DAAO binds to Sudlow's site I in HSA through hydrogen bonds and van der Waals power. • The interaction was a spontaneous and exothermic process with modest degree of reversibility. • The secondary structure of HSA and the microenvironment of TRP214 altered. • Amido bond in steroid nucleus (–NH–CO–) plays important role in stabling the structure of

  12. Investigation of the influence factors of polyethylene molecule encapsulated into carbon nanotubes by molecular dynamics simulation (United States)

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


    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.

  13. Molecular phylogenetic analysis of an endangered Mexican sparrow: Spizella wortheni. (United States)

    Canales-del-Castillo, Ricardo; Klicka, John; Favela, Susana; González-Rojas, José I


    The Worthen's Sparrow (Spizella wortheni) is an endemic bird species of the Mexican Plateau that is protected by Mexican law. Considering its limited range (25 km(2)), small population size (100-120 individuals), and declining population, it is one of the most endangered avian species in North America. Although it has been assumed to be the sister taxon of the Field Sparrow (Spizella pusilla), the systematic and evolutionary relationships of Worthen's Sparrow have never been tested using modern molecular phylogenetic methods. We addressed the molecular phylogeny of S. wortheni analyzing six mitochondrial genes (3571 bp) from all of the natural members of the genus Spizella. Our maximum likelihood and Bayeasian analysis indicate that despite the superficial similarity, S. wortheni is not the sister taxon of S. pusilla, but is instead most closely related to the Brewer's Sparrow (Spizella breweri). Also new insights about the phylogenetics relationships of the Spizella genera are presented.

  14. Fetus in fetu: molecular analysis of a fetiform mass. (United States)

    Hing, A; Corteville, J; Foglia, R P; Bliss, D P; Donis-Keller, H; Dowton, S B


    Fetus-in-fetu is a rare condition presenting as a calcified intra-abdominal mass in the newborn infant. Over 50 cases of fetus-in-fetu have been reported since 1800. Karyotype analysis in 8 cases and protein polymorphisms in 4 documented identical findings in the host and fetiform mass. We report a case of fetus-in-fetu in a newborn female including cytogenetic and molecular studies of both the host and mass. Genotypic information from 7 polymerase chain reaction (PCR) assays representing 4 chromosomes demonstrates heterozygous and identical alleles in the infant and fetus-in-fetu at all loci studied. A review of the literature is provided including a discussion regarding the impact of molecular data on present hypotheses of fetus-in-fetu pathogenesis.

  15. Isolation, molecular characterization and phylogenetic analysis of canine parvovirus. (United States)

    Mohan Raj, J; Mukhopadhyay, H K; Thanislass, J; Antony, P X; Pillai, R M


    Canine parvovirus type 2 (CPV-2) causes acute haemorrhagic enteritis in dogs. Canine parvovirus is prone to genetic evolution and has undergone several mutations that produced different strains like CPV-2a, CPV-2b, New CPV-2a, New CPV-2b and CPV-2c in the past three decades. Mutations affecting the VP2 gene of CPV have been responsible for evolution of different antigenic variants. Sequence analysis of VP2 gene of the virus and subsequent characterization is important for molecular epidemiology. The present study was conducted to isolate and to characterize the virus by amplifying partial VP2 gene and further sequence analysis and also to estimate phylogenetic relationship of field virus with the reference strains. Out of 77 samples, 51 samples were found to be positive by PCR and all the 51 samples were subjected for virus isolation in CRFK cell line. Sixteen viruses could be isolated and 10 randomly selected isolates were subjected to sequence analysis along with four random clinical samples. All the 10 isolates and 4 clinical samples were characterized as New CPV-2a (CPV2a with 297-Ser→Ala). One of the field isolates was found to be phylogenetically closely related to New CPV-2a strains of Japan and India; another field isolates was found to share ancestral origins with New CPV-2a strains of Korea, USA, Italy, Brazil, Germany, Taiwan and Vietnam; rest other sequences had distinct lineage but shared molecular relationship with New CPV-2a reference strains.

  16. Investigation of polarization effects in the gramicidin A channel from ab initio molecular dynamics simulations. (United States)

    Timko, Jeff; Kuyucak, Serdar


    Polarization is an important component of molecular interactions and is expected to play a particularly significant role in inhomogeneous environments such as pores and interfaces. Here we investigate the effects of polarization in the gramicidin A ion channel by performing quantum mechanics/molecular mechanics molecular dynamics (MD) simulations and comparing the results with those obtained from classical MD simulations with non-polarizable force fields. We consider the dipole moments of backbone carbonyl groups and channel water molecules as well as a number of structural quantities of interest. The ab initio results show that the dipole moments of the carbonyl groups and water molecules are highly sensitive to the hydrogen bonds (H-bonds) they participate in. In the absence of a K(+) ion, water molecules in the channel are quite mobile, making the H-bond network highly dynamic. A central K(+) ion acts as an anchor for the channel waters, stabilizing the H-bond network and thereby increasing their average dipole moments. In contrast, the K(+) ion has little effect on the dipole moments of the neighboring carbonyl groups. The weakness of the ion-peptide interactions helps to explain the near diffusion-rate conductance of K(+) ions through the channel. We also address the sampling issue in relatively short ab initio MD simulations. Results obtained from a continuous 20 ps ab initio MD simulation are compared with those generated by sampling ten windows from a much longer classical MD simulation and running each window for 2 ps with ab initio MD. Both methods yield similar results for a number of quantities of interest, indicating that fluctuations are fast enough to justify the short ab initio MD simulations.

  17. Investigation of the silicon ion density during molecular beam epitaxy growth

    CERN Document Server

    Eifler, G; Ashurov, K; Morozov, S


    Ions impinging on a surface during molecular beam epitaxy influence the growth and the properties of the growing layer, for example, suppression of dopant segregation and the generation of crystal defects. The silicon electron gun in the molecular beam epitaxy (MBE) equipment is used as a source for silicon ions. To use the effect of ion bombardment the mechanism of generation and distribution of ions was investigated. A monitoring system was developed and attached at the substrate position in the MBE growth chamber to measure the ion and electron densities towards the substrate. A negative voltage was applied to the substrate to modify the ion energy and density. Furthermore the current caused by charge carriers impinging on the substrate was measured and compared with the results of the monitoring system. The electron and ion densities were measured by varying the emission current of the e-gun achieving silicon growth rates between 0.07 and 0.45 nm/s and by changing the voltage applied to the substrate betw...

  18. Raman investigation of GaP–Si interfaces grown by molecular beam epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Bondi, A.; Cornet, C.; Boyer, S.; Nguyen Thanh, T.; Létoublon, A.; Pedesseau, L.; Durand, O. [Université Européenne de Bretagne, INSA, FOTON, UMR CNRS 6082, 20 Avenue des Buttes de Coësmes, F-35708 Rennes (France); Moreac, A. [Institut de Physique de Rennes, UMR-CNRS n°6251, Université Rennes1, Campus de Beaulieu — 35042 Rennes cedex (France); Ponchet, A. [CEMES, UPR CNRS 8011, F-31055 Toulouse (France); Le Corre, A. [Université Européenne de Bretagne, INSA, FOTON, UMR CNRS 6082, 20 Avenue des Buttes de Coësmes, F-35708 Rennes (France); Even, J., E-mail: [Université Européenne de Bretagne, INSA, FOTON, UMR CNRS 6082, 20 Avenue des Buttes de Coësmes, F-35708 Rennes (France)


    Raman spectroscopy was used to investigate the residual strain in thin GaP layers deposited on Si substrates by molecular beam epitaxy. Different growth conditions were used to obtain a clean GaP–Si interface, including migration enhanced epitaxy. The strain induced Raman shifts of the longitudinal and the transverse optical GaP lattice modes were analyzed. The effects of crystalline defects are discussed, supported by high resolution transmission electron microscopy and X-ray scattering studies. Finally, Raman Spectroscopy reveals the presence of disorder (or surface)-activated optical phonons. This result is discussed in the light of surface morphology analyses. - Highlights: ► GaP thin layers grown by molecular beam epitaxy on Si substrates. ► Strain-induced Raman shifts of the optical GaP modes are analyzed. ► Simulation of optical GaP modes by density functional perturbation theory. ► Comparison with X-ray diffraction and electron and scanning probe microscopy data.

  19. The theoretical investigation of one of the derivatives of 1, 2-dithienylcyclopentene as a molecular switch. (United States)

    Safarpour, Mohammad Ali; Hashemianzadeh, Seyed Majid; Kasaeian, Azam


    The structural and electronic properties of a three-state molecular switch-an active device in a nano-electronic circuit-were studied using the B3LYP/6-31G* method. Due to its chemical stability, high conductivity upon doping, and non-linear optical properties, polythiophene is among the most widely studied conjugated organic polymers, both experimentally and theoretically. The aim of the present work was to theoretically study a very complex case: a three-state switch synthesized and experimentally investigated by Nishida et al. (Org Lett 6:2523-2526, 2004). An initial set of test calculations showed B3LYP level of theory and 6-31G* basis set to be the most appropriate for our purpose, i.e., the study of the structure, charge and spin distributions, as well as electrical characteristics such as electric polarizability, HOMO-LUMO gap (HLG) and electric dipole moment, for one of the 1,2-dithienylcyclopentene derivatives. Also, natural bond orbital analyses were performed to calculate local charges and charge transfers in order to study the capability of the molecule as a molecular switch. The results reported here are of general significance, and demonstrate that it is possible to use certain structural and electrical properties to understand and design electro-photochromic compounds showing a switching function in cases where stable forms can be exchanged by light or electron transfer. Figure Model of a thiophene wire incorporating a redox active unit.

  20. Molecular-orbital and structural descriptors in theoretical investigation of electroreduction of nitrodiazoles

    Directory of Open Access Journals (Sweden)



    Full Text Available It is shown how a simple theoretical approach can be used for the investigation of electro-organic reactions.Mononitroimidazoles and mononitropyrazoles were studied by the semiempirical MNDO-PM3 molecular orbital method. The electrochemical reduction potentials of diazoles have been correlated with the energy of the lowest unoccupied molecular orbital (LUMO. It was found that an admirable correlation could be obtained by the introduction of simple structural descriptors as a correction to the energy of the LUMO. The interaction of a molecule with its surrounding depends on electrostatic potential and on steric hindrance. Most of these steric effects are taken into account using two parameters having a very limited set of integer values. The first (b is the position of a ring substituent regarding ring nitrogens, which accounts for the different orientations of dipole moments and for the different shape of the electrostatic potential. The second (structural parameter (t is the type of the ring, which accounts mostly for different modes of electrode approach, and for different charge polarization patterns in two diazole rings. The extended correlation with ELUMO, b and t, is very good, having a regression coefficient r = 0.991. The intrinsic importance of b and t is exemplified by their high statistical weight.

  1. Investigations of Takeout proteins' ligand binding and release mechanism using molecular dynamics simulation. (United States)

    Zhang, Huijing; Yu, Hui; Zhao, Xi; Liu, Xiaoguang; Feng, Xianli; Huang, Xuri


    Takeout (To) proteins exist in a diverse range of insect species. They are involved in many important processes of insect physiology and behaviors. As the ligand carriers, To proteins can transport the small molecule to the target tissues. However, ligand release mechanism of To proteins is unclear so far. In this contribution, the process and pathway of the ligand binding and release are revealed by conventional molecular dynamics simulation, steered molecular dynamics simulation and umbrella sampling methods. Our results show that the α4-side of the protein is the unique gate for the ligand binding and release. The structural analysis confirms that the internal cavity of the protein has high rigidity, which is in accordance with the recent experimental results. By using the potential of mean force calculations in combination with residue cross correlation calculation, we concluded that the binding between the ligand and To proteins is a process of conformational selection. Furthermore, the conformational changes of To proteins and the hydrophobic interactions both are the key factors for ligand binding and release.

  2. Molecular investigations of mitochondrial deletions: evaluating the usefulness of different genetic tests. (United States)

    Tońska, Katarzyna; Piekutowska-Abramczuk, Dorota; Kaliszewska, Magdalena; Kowalski, Paweł; Tańska, Anna; Bartnik, Ewa; Pronicka, Ewa; Krajewska-Walasek, Małgorzata


    Deletions in mitochondrial DNA are a common cause of mitochondrial disorders. The molecular diagnosis of mtDNA deletions for years was based on Southern hybridization later replaced by PCR methods such as PCR with primers specific for a particular deletion (mainly the so-called common deletion of 4977 bp) and long PCR. In order to evaluate the usefulness of MLPA (Multiplex Ligation-dependent Probe Amplification) in molecular diagnosis of large scale mtDNA deletions we compare four diagnostic methods: Southern hybridization, PCR, long-PCR and MLPA in a group of 16 patients with suspected deletions. Analysis was performed on blood, muscle and in one case hepatic tissue DNA. The MLPA was not able to confirm all the deletions detected by PCR methods, but due to its relative ease of processing, minimal equipment, low costs and the additional possibility to detect frequent point mtDNA mutations in one assay it is worth considering as a screening method. We recommend to always confirm MLPA results by PCR methods.

  3. Chiral Analysis of Isopulegol by Fourier Transform Molecular Rotational Spectroscopy (United States)

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


    Chiral analysis on molecules with multiple chiral centers can be performed using pulsed-jet Fourier transform rotational spectroscopy. This analysis includes quantitative measurement of diastereomer products and, with the three wave mixing methods developed by Patterson, Schnell, and Doyle (Nature 497, 475-477 (2013)), quantitative determination of the enantiomeric excess of each diastereomer. The high resolution features enable to perform the analysis directly on complex samples without the need for chromatographic separation. Isopulegol has been chosen to show the capabilities of Fourier transform rotational spectroscopy for chiral analysis. Broadband rotational spectroscopy produces spectra with signal-to-noise ratio exceeding 1000:1. The ability to identify low-abundance (0.1-1%) diastereomers in the sample will be described. Methods to rapidly identify rotational spectra from isotopologues at natural abundance will be shown and the molecular structures obtained from this analysis will be compared to theory. The role that quantum chemistry calculations play in identifying structural minima and estimating their spectroscopic properties to aid spectral analysis will be described. Finally, the implementation of three wave mixing techniques to measure the enantiomeric excess of each diastereomer and determine the absolute configuration of the enantiomer in excess will be described.

  4. Electron microscopy investigation of interface between carbon fiber and ultra high molecular weight polyethylene

    Energy Technology Data Exchange (ETDEWEB)

    Stepashkin, A.A.; Chukov, D.I., E-mail:; Gorshenkov, M.V.; Tcherdyntsev, V.V.; Kaloshkin, S.D.


    Highlights: • Effect of the carbon fibers surface treatments on the adhesive interactions in UHMWPE composites was studied. • Air oxidation of carbon filler ensures most significant increase in adhesion interaction in UHMWPE based composites. • Nanosized UHMWPE fibers with 20–40 nm in diameter and with 6–10 μm in length, was observed on the surface of carbon fibers. -- Abstract: Scanning electron microscopy was used to investigate the surface of initial and modified high-strength and high-modulus carbon fibers as well as interfaces in the ultra high molecular weight polyethylene, filled with above-mentioned fibers. Effect of the fibers surface modifying method on the adhesive interactions in composites was studied. It was observed that interaction of matrix with a modified surface of fibers results in a formation of bonds with strength higher than the yield strength of the polymer. It results in a formation of long nanosized polymer wires at tensile fracture of composites.

  5. Molecular dynamics investigation of the grain boundary migration hysteresis of nanocrystalline Ni under cyclic shear loading (United States)

    Wang, Peng; Yang, Xinhua; Peng, Di


    The deformation behavior and grain boundary (GB) response of nanocrystalline Ni under cyclic shear loading are investigated by molecular dynamics simulations. The GB migration hysteresis phenomenon, in which the GB migration displacement lags behind the change in nominal shear strain, is observed in the symmetric tilt GBs for the first time. The elementary structure transformation occurring at the two end segments of the observed GB during GB migration produces a disordered and irreversible state, while the transformation in the middle segment is reversible. Both dislocation retraction and nucleation occur during unloading. Relatively large cyclic strain amplitudes lead to disordered GB segments of greater length, such that the residual GB migration displacement increases with increasing cyclic amplitude. GB migration hysteresis vanishes after the GB becomes immobile owing to a cyclic shear induced transition to a disordered state along its entire length.

  6. Photometric investigation of the MBM 12 molecular cloud area in Aries. II. Cloud distance

    CERN Document Server

    Straizys, V; Kazlauskas, A; Laugalys, V


    Photoelectric magnitudes and color indices in the Vilnius seven-color system for 152 stars are used to investigate the interstellar extinction in the area of the Aries molecular cloud MBM 12, coinciding with the L1454 and L1457 dust clouds. Spectral types, absolute magnitudes, color excesses, interstellar extinctions and distances of the stars are determined. The plot of interstellar extinction Av versus distance shows that the dust cloud is situated at a distance of 325 pc, at 180 pc from the Galactic plane, and its true diameter is about 11 pc. The interstellar extinction law in the area is found to be normal, typical for the diffuse dust. Ten peculiar or unresolved binary stars and some heavily reddened stars are detected.

  7. Investigating the influence of effective parameters on molecular characteristics of bovine serum albumin nanoparticles (United States)

    Rohiwal, S. S.; Satvekar, R. K.; Tiwari, A. P.; Raut, A. V.; Kumbhar, S. G.; Pawar, S. H.


    The protein nanoparticles formulation is a challenging task as they are prone to undergo conformational transitions while processing which may affect bioavailability for bioactive compounds. Herein, a modified desolvation method is employed to prepare Bovine Serum Albumin nanoparticles, with controllable particle size ranging from 100 to 300 nm and low polydispersity index. The factors influencing the size and structure of BSA NPs viz. protein concentration, pH and the conditions for purification are well investigated. The structure of BSA NPs is altered due to processing, and may affect the effective binding ability with drugs and bioactive compounds. With that aims, investigations of molecular characteristics of BSA NPs are carried out in detail by using spectroscopic techniques. UV-visible absorption and Fourier Transform Infrared demonstrate the alteration in protein structure of BSA NPs whereas the FT-Raman spectroscopy investigates changes in the secondary and tertiary structures of the protein. The conformational changes of BSA NPs are observed by change in fluorescence intensity and emission maximum wavelength of tryptophan residue by fluorescence spectroscopy. The field emission scanning electron and atomic force microscopy micrographs confirm the size and semi-spherical morphology of the BSA NPs. The effect of concentration and pH on particle size distribution is studied by particle size analyzer.

  8. Molecular dynamics investigation of the interaction of dislocations with carbides in BCC Fe (United States)

    Granberg, F.; Terentyev, D.; Nordlund, K.


    Different types of carbides are present in many steels used as structural materials. To safely use steel in demanding environments, like nuclear power plants, it is important to know how defects will affect the mechanical properties of the material. In this study, the effect of carbide precipitates on the edge dislocation movement is investigated. Three different types of carbides were investigated by means of molecular dynamics, with a Tersoff-like bond order interatomic potential by Henriksson et al. The obstacles were 4 nm in diameter and were of Fe3C- (cementite-), Fe23C6- and Cr23C6-type. The critical unpinning stress was calculated for each type at different temperatures, to get the temperature-dependent obstacle strength. The results showed a decreasing critical stress with increasing temperature, consistent with previous studies. The critical unpinning stress was seen to be dependent on the type of carbide, but the differences were small. A difference was also observed between the obstacles with the same structure, but with different composition. This study shows the relation between the existing Cr23C6 carbide and the experimentally non-existing Fe23C6 carbide, which needs to be used as a model system for investigations with interatomic potentials not able to describe the interaction of Cr in the Fe-C-system. We found the difference to be a between 7% and 10% higher critical unpinning stress for the chromium carbide, than for the iron carbide of the same type.

  9. Compressive characteristics of single walled carbon nanotube with water interactions investigated by using molecular dynamics simulation (United States)

    Wong, C. H.; Vijayaraghavan, V.


    The elastic properties of single walled carbon nanotube (SWCNT) with surrounding water interactions are studied using molecular dynamics simulation technique. The compressive loading characteristic of carbon nanotubes (CNTs) in a fluidic medium such as water is critical for its role in determining the lifetime and stability of CNT based nano-fluidic devices. In this paper, we conducted a comprehensive analysis on the effect of geometry, chirality and density of encapsulated water on the elastic properties of SWCNT. Our studies show that defect density and distribution can strongly impact the compressive resistance of SWCNTs in water. Further studies were conducted on capped SWCNTs with varying densities of encapsulated water, which is necessary to understand the strength of CNT as a potential drug carrier. The results obtained from this paper will help determining the potential applications of CNTs in the field of nano-electromechanical systems (NEMS) such as nano-biological and nano-fluidic devices.

  10. Compressive characteristics of single walled carbon nanotube with water interactions investigated by using molecular dynamics simulation

    Energy Technology Data Exchange (ETDEWEB)

    Wong, C.H., E-mail:; Vijayaraghavan, V.


    The elastic properties of single walled carbon nanotube (SWCNT) with surrounding water interactions are studied using molecular dynamics simulation technique. The compressive loading characteristic of carbon nanotubes (CNTs) in a fluidic medium such as water is critical for its role in determining the lifetime and stability of CNT based nano-fluidic devices. In this paper, we conducted a comprehensive analysis on the effect of geometry, chirality and density of encapsulated water on the elastic properties of SWCNT. Our studies show that defect density and distribution can strongly impact the compressive resistance of SWCNTs in water. Further studies were conducted on capped SWCNTs with varying densities of encapsulated water, which is necessary to understand the strength of CNT as a potential drug carrier. The results obtained from this paper will help determining the potential applications of CNTs in the field of nano-electromechanical systems (NEMS) such as nano-biological and nano-fluidic devices.

  11. Investigation of Localized States in GaAsSb Epilayers Grown by Molecular Beam Epitaxy. (United States)

    Gao, Xian; Wei, Zhipeng; Zhao, Fenghuan; Yang, Yahui; Chen, Rui; Fang, Xuan; Tang, Jilong; Fang, Dan; Wang, Dengkui; Li, Ruixue; Ge, Xiaotian; Ma, Xiaohui; Wang, Xiaohua


    We report the carrier dynamics in GaAsSb ternary alloy grown by molecular beam epitaxy through comprehensive spectroscopic characterization over a wide temperature range. A detailed analysis of the experimental data reveals a complex carrier relaxation process involving both localized and delocalized states. At low temperature, the localized degree shows linear relationship with the increase of Sb component. The existence of localized states is also confirmed by the temperature dependence of peak position and band width of the emission. At temperature higher than 60 K, emissions related to localized states are quenched while the band to band transition dominates the whole spectrum. This study indicates that the localized states are related to the Sb component in the GaAsSb alloy, while it leads to the poor crystal quality of the material, and the application of GaAsSb alloy would be limited by this deterioration.

  12. Identification of the Most Stable Sc2C80 Isomers: Structure, Electronic Property, and Molecular Spectra Investigations

    Institute of Scientific and Technical Information of China (English)

    吴静怡; 王太山; 舒春英; 吕鑫; 王春儒


    A systematic density functional theory investigation has been carried out to explore the possible structures of Sc2C80 at the BMK/6-31 G(d) level. The results clearly show that Sc2@C80-Ih, Sc2@Cso-Dsh, and Sc2C2@C78-C2v can be identified as three isomers of Sc2C80 metallofullerene with the lowest energy. Frontier molecular orbital analysis indicates that the two Sc2@C80 isomers have a charge state as (Sc〉)2@ C60 and the Sc2C2@C78 has a charge state of (Sc3+)2 C22- @ C784-. Moreover, the metal-cage covalent interactions have been studied to reveal the dynamics of endohedral moiety. The vertical electron affinity, vertical ionization potential, infrared spectra and 13C nuclear mag- netic resonance spectra have been also computed to further disclose the molecular structures and properties.

  13. Investigation of the behavior of HSA upon binding to amlodipine and propranolol: Spectroscopic and molecular modeling approaches (United States)

    Housaindokht, Mohammad Reza; Rouhbakhsh Zaeri, Zeinab; Bahrololoom, Mahmood; Chamani, Jamshid; Bozorgmehr, Mohammad Reza


    The interaction between human serum albumin (HSA) and two drugs - amlodipine and propranolol - was investigated using fluorescence, UV absorption and circular dichroism (CD) spectroscopy. In addition, the binding site was established by applying molecular modeling technique. Fluorescence data suggest that amlodipine will quench the intrinsic fluorescence of HSA; whereas propranolol enhances the fluorescence of HSA. The binding constants for the interaction of amlodipine and propranolol with HSA were found to be 3.63 × 10 5 M -1 and 2.29 × 10 4 M -1, respectively. The percentage of secondary structure feature of each one of the HSA-bound drugs, i.e. the α-helix content, was estimated empirically by circular dichroism. The results indicated that amlodipine causes an increase, and that propranolol leads to a decrease in α-helix content of HSA. The spectroscopic analysis indicates that the binding mechanisms of the two drugs are different from each other. The data obtained by the molecular modeling study indicated that these drugs bind, with different affinity, to different sites located in subdomain IIA and IIIA.

  14. Molecular genetic analysis of Dongzhou-period ancient human of Helingeer in Inner Mongolia, China

    Institute of Scientific and Technical Information of China (English)


    The mtDNA hypervariable region I (HVR-I) of 10 ancient individuals from Dongzhou-period ancient human populations in Helingeer county of Inner Mongolia were amplified and sequenced to investigate the genetic structure. The relationships between the ancient population and related extant populations, as well as its possible origin at the molecular level, were also studied. Moreover, phylogenetic analysis and multi-dimensional scaling analysis were also performed based on the mtDNA data of the ancient population in Helingeer and the related Eurasian population. The results showed that the ancient population in Helingeer were closer to the northern Asian populations than to the other compared populations in matrilineal lineage. Combining the research results of archaeology and anthropology as well as molecular biology, we inferred that they were nomads who migrated from Mongolia plateau and cis-Baikal region to Helingeer in Inner Mongolia, China.

  15. Molecular docking analysis of curcumin analogues as human neutrophil elastase inhibitors

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Narayanaswamy


    Full Text Available In the present study, we aimed to dock 17 different ligands of curcumin analogues with that of human neutrophil elastase. Molecular descriptors analysis using Molinspiration online tool was carried out including investigation on human neutrophil elastase putative binding sites using Discovery Studio. The molecular physicochemical analysis revealed that all of the curcumin analogues complied well with the five rules of thumb. With regard to bioact-ivity score, compound 17 has exhibited least score towards nuclear receptor ligand (0.05 and enzyme inhibitor (0.10 compared to all other ligands. Compounds 2, 4 and 13 exhibited the maximum interaction energy (-40 kcal/mol. Interestingly, seven compounds namely 3, 11-14, 16 and 17 interacted well with Arg147 amino acid residue. The present study outcomes therefore might provide new insight in understanding these 17 curcumin analogues as potential candidates for human neutrophil elastase inhibitory agents.

  16. Vibrational spectroscopic analysis, molecular dynamics simulations and molecular docking study of 5-nitro-2-phenoxymethyl benzimidazole (United States)

    Menon, Vidya V.; Foto, Egemen; Mary, Y. Sheena; Karatas, Esin; Panicker, C. Yohannan; Yalcin, Gözde; Armaković, Stevan; Armaković, Sanja J.; Van Alsenoy, C.; Yildiz, Ilkay


    FT-IR and FT-Raman spectra of 5-nitro-2-phenoxymethylbenzimidazole were recorded and analyzed theoretically and experimentally. The splitting of Nsbnd H stretching mode in the IR spectrum with a red shift from the calculated value indicates the weakening of the NH bond. The theoretical calculations give the phenyl ring breathing modes at 999 cm-1 for mono substituted benzene ring and at 1040 cm-1 for tri-substituted benzene ring. The theoretical NMR chemical shifts are in agreement with the experimental chemical shifts. The most reactive sites for electrophilic and nucleophilic attack are predicted from the MEP analysis. HOMO of π nature is delocalized over the entire molecule whereas the LUMO is located over the complete molecule except mono-substituted phenyl ring and oxygen atom. Reactive sites of the title molecule have been located with the help of ALIE surfaces and Fukui functions. In order to determine locations prone to autoxidation and locations interesting for starting of degradation, bond dissociation energies have been calculated for all single acyclic bonds. For the determination of atoms with pronounced interactions with water we have calculated radial distribution functions obtained after molecular dynamics simulations. The calculated first hyperpolarizability of the title compound is 58.03 times that of standard nonlinear optical material urea. The substrate binding site interactions of the title compound with Topo II enzyme is reported by using molecular docking study. Biological activity studies show that the title compound can be leaded for developing new anticancer agents.

  17. Investigating the Molecular Basis of Retinal Degeneration in a Familial Cohort of Pakistani Decent by Exome Sequencing.

    Directory of Open Access Journals (Sweden)

    Bruno Maranhao

    Full Text Available To define the molecular basis of retinal degeneration in consanguineous Pakistani pedigrees with early onset retinal degeneration.A cohort of 277 individuals representing 26 pedigrees from the Punjab province of Pakistan was analyzed. Exomes were captured with commercial kits and sequenced on an Illumina HiSeq 2500. Candidate variants were identified using standard tools and analyzed using exomeSuite to detect all potentially pathogenic changes in genes implicated in retinal degeneration. Segregation analysis was performed by dideoxy sequencing and novel variants were additionally investigated for their presence in ethnicity-matched controls.We identified a total of nine causal mutations, including six novel variants in RPE65, LCA5, USH2A, CNGB1, FAM161A, CERKL and GUCY2D as the underlying cause of inherited retinal degenerations in 13 of 26 pedigrees. In addition to the causal variants, a total of 200 variants each observed in five or more unrelated pedigrees investigated in this study that were absent from the dbSNP, HapMap, 1000 Genomes, NHLBI ESP6500, and ExAC databases were identified, suggesting that they are common in, and unique to the Pakistani population.We identified causal mutations associated with retinal degeneration in nearly half of the pedigrees investigated in this study through next generation whole exome sequencing. All novel variants detected in this study through exome sequencing have been cataloged providing a reference database of variants common in, and unique to the Pakistani population.

  18. Nutritional Proteomics: Investigating molecular mechanisms underlying the health beneficial effect of functional foods

    Directory of Open Access Journals (Sweden)

    Yusuke Kawashima


    Full Text Available ABSTRACTObjective: We introduce a new technical and conceptual term “nutritional proteomics” by identifying and quantifying the proteins and their changes in a certain organ or tissue dependent on the food intake by utilizing a mass spectrometry-based proteomics technique.Purpose: Food intake is essentially important for every life on earth to sustain the physical as well as mental functions. The outcome of food intake will be manifested in the health state and its dysfunction. The molecular information about the protein expression change caused by diets will assist us to understand the significance of functional foods. We wish to develop nutritional proteomics to promote a new area in functional food studies for a better understanding of the role of functional foods in health and disease.Methods: We chose two classes of food ingredients to show the feasibility of nutritional proteomics, omega-3 polyunsaturated fatty acids and omega-6 polyunsaturated fatty acids both of which are involved in the inflammation/anti-inflammation axis. Each class of the polyunsaturated fatty acids was mixed in mouse chow respectively. The liver tissue of mice fed with omega-3 diet or omega-3 diet was analyzed by the state-of-the-art shotgun proteomics using nano-HPLC-ESI-MS/MS. The data were analyzed by the number of differentially expressed proteins that were guaranteed by 1% false discovery rate for protein identification and by the statistical significance of variance evaluated by p-value in two-tailed distribution analysis better than 0.05 (n=4. The differential pattern of protein expression was characterized with Gene Ontology designation.Results: The data analysis of the shotgun nutritional proteomics identified 2,810 proteins that are validated with 1% FDR. Among these 2,810 proteins, 125 were characterized with statistical significance of variance (p<0.05; n=4 between the omega-3 diet and the omega-6 diet by twotailed distribution analysis. The results

  19. Molecular cytogenetic analysis in the study of brain tumors: findings and applications. (United States)

    Bayani, Jane; Pandita, Ajay; Squire, Jeremy A


    Classic cytogenetics has evolved from black and white to technicolor images of chromosomes as a result of advances in fluorescence in situ hybridization (FISH) techniques, and is now called molecular cytogenetics. Improvements in the quality and diversity of probes suitable for FISH, coupled with advances in computerized image analysis, now permit the genome or tissue of interest to be analyzed in detail on a glass slide. It is evident that the growing list of options for cytogenetic analysis has improved the understanding of chromosomal changes in disease initiation, progression, and response to treatment. The contributions of classic and molecular cytogenetics to the study of brain tumors have provided scientists and clinicians alike with new avenues for investigation. In this review the authors summarize the contributions of molecular cytogenetics to the study of brain tumors, encompassing the findings of classic cytogenetics, interphase- and metaphase-based FISH studies, spectral karyotyping, and metaphase- and array-based comparative genomic hybridization. In addition, this review also details the role of molecular cytogenetic techniques in other aspects of understanding the pathogenesis of brain tumors, including xenograft, cancer stem cell, and telomere length studies.

  20. Molecular and Virological Investigation of a Focal Chikungunya Outbreak in Northern India

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    Manisha Soni


    Full Text Available Chikungunya (CHIK fever is one of the most important arboviral infections of medical significance. The objective of the present study is to identify and characterize the etiology of a focal febrile arthritis outbreak from Gwalior, northern India, during October-November 2010. A detailed virological (isolation and molecular (end-point RT-PCR, quantitative RT-PCR, and nucleotide sequencing investigation of this outbreak was carried out by collecting and studying 52 clinical samples and 15 mosquito pools from the affected region. The investigation revealed the presence of CHIK viral RNA in 29% of clinical samples and 13% mosquito pool by RT-PCR. The quantification of CHIK viral RNA in samples varied from 102.50 to 106.67 copies/mL, as demonstrated through quantitative RT-PCR. In addition, six CHIK viruses were isolated from RT-PCR positive samples. The nucleotide sequences of partial E1 gene of five representative CHIK viruses were deciphered, which revealed that all the viral strains from this outbreak belong to the recently emerging ECS African genotype. Identification of Chikungunya virus ECSA African genotype as the etiology of the present outbreak confirms the continued circulation of the novel genotype, since 2006, in India. The identification of CHIK virus in Aedes aegypti also confirmed it as the major vector in northern India.

  1. NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) Trial (United States)

    NCI's gateway for information about the NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) trial, in which patients with advanced cancer are assigned to treatment arms based on the molecular profiles of their disease.

  2. New AFM Techniques for Investigating Molecular Growth Mechanisms of Protein Crystals (United States)

    Li, Huayu; Nadarajah, Arunan; Konnert, John H.; Pusey, Marc L.


    Atomic Force Microscopy (AFM) has emerged as a powerful technique for investigating protein crystal growth. Earlier AFM studies were among the first to demonstrate that these crystals grew by dislocation and 2D nucleation growth mechanisms [1]. These investigations were restricted to the micron range where only surface features, such as dislocation hillocks and 2D islands are visible. Most AFM instruments can scan at higher resolutions and have the potential to resolve individual protein molecules at nanometer ranges. Such scans are essential for determining the molecular packing arrangements on crystal faces and for probing the growth process at the molecular level. However, at this resolution the AFM tip influences the image produced, with the resulting image being a convolution of the tip shape and the surface morphology [2]. In most studies this problem is resolved by deconvoluting the image to obtain the true surface morphology. Although deconvolution routines work reasonably well for simple one- dimensional shapes, for complex surfaces this approach does not produce accurate results. In this study we devised a new approach which takes advantage of the precise molecular order of crystal surfaces, combined with the knowledge of individual molecular shapes from the crystallographic data of the protein and the AFM tip shape. This information is used to construct expected theoretical AFM images by convoluting the tip shape with the constructed crystal surface shape for a given surface packing arrangement. By comparing the images from actual AFM scans with the constructed ones for different possible surface packing arrangements, the correct packing arrangement can be conclusively determined. This approach was used in this study to determine the correct one from two possible packing arrangements on (I 10) faces of tetragonal lysozyme crystals. Another novel AFM technique was also devised to measure the dimension of individual growth units of the crystal faces

  3. Linking healthcare associated norovirus outbreaks: a molecular epidemiologic method for investigating transmission

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    Andrews Nick


    Full Text Available Abstract Background Noroviruses are highly infectious pathogens that cause gastroenteritis in the community and in semi-closed institutions such as hospitals. During outbreaks, multiple units within a hospital are often affected, and a major question for control programs is: are the affected units part of the same outbreak or are they unrelated transmission events? In practice, investigators often assume a transmission link based on epidemiological observations, rather than a systematic approach to tracing transmission. Here, we present a combined molecular and statistical method for assessing: 1 whether observed clusters provide evidence of local transmission and 2 the probability that anecdotally|linked outbreaks truly shared a transmission event. Methods 76 healthcare associated outbreaks were observed in an active and prospective surveillance scheme of 15 hospitals in the county of Avon, England from April 2002 to March 2003. Viral RNA from 64 out of 76 specimens from distinct outbreaks was amplified by reverse transcription-PCR and was sequenced in the polymerase (ORF 1 and capsid (ORF 2 regions. The genetic diversity, at the nucleotide level, was analysed in relation to the epidemiological patterns. Results Two out of four genetic and epidemiological clusters of outbreaks were unlikely to have occurred by chance alone, thus suggesting local transmission. There was anecdotal epidemiological evidence of a transmission link among 5 outbreaks pairs. By combining this epidemiological observation with viral sequence data, the evidence of a link remained convincing in 3 of these pairs. These results are sensitive to prior beliefs of the strength of epidemiological evidence especially when the outbreak strains are common in the background population. Conclusion The evidence suggests that transmission between hospitals units does occur. Using the proposed criteria, certain hypothesized transmission links between outbreaks were supported while

  4. Investigation of the silicon ion density during molecular beam epitaxy growth (United States)

    Eifler, G.; Kasper, E.; Ashurov, Kh.; Morozov, S.


    Ions impinging on a surface during molecular beam epitaxy influence the growth and the properties of the growing layer, for example, suppression of dopant segregation and the generation of crystal defects. The silicon electron gun in the molecular beam epitaxy (MBE) equipment is used as a source for silicon ions. To use the effect of ion bombardment the mechanism of generation and distribution of ions was investigated. A monitoring system was developed and attached at the substrate position in the MBE growth chamber to measure the ion and electron densities towards the substrate. A negative voltage was applied to the substrate to modify the ion energy and density. Furthermore the current caused by charge carriers impinging on the substrate was measured and compared with the results of the monitoring system. The electron and ion densities were measured by varying the emission current of the e-gun achieving silicon growth rates between 0.07 and 0.45 nm/s and by changing the voltage applied to the substrate between 0 to -1000 V. The dependencies of ion and electron densities were shown and discussed within the framework of a simple model. The charged carrier densities measured with the monitoring system enable to separate the ion part of the substrate current and show its correlation to the generation rate. Comparing the ion density on the whole substrate and in the center gives a hint to the ion beam focusing effect. The maximum ion and electron current densities obtained were 0.40 and 0.61 μA/cm2, respectively.

  5. Phase-transition properties of glycerol-dipalmitate lipid bilayers investigated using molecular dynamics simulation. (United States)

    Laner, Monika; Hünenberger, Philippe H


    The phase- and phase-transition properties of glycerol-dipalmitate (GDP) bilayer patches are investigated using molecular dynamics simulations. This permits to characterize the influence of introducing a second aliphatic lipid tail by comparison to previously reported simulations of glycerol-1-monopalmitate (GMP). To this purpose, a set of 67 simulations (up to 300ns duration) of 2×8×8GDP bilayer patches are performed, considering the two GDP isomers glycerol-1,3-dipalmitate (13GDP) and glycerol-1,2-dipalmitate (12GDP; racemic), two hydration levels (12GDP only), and temperatures in the range 250-370K. In agreement with experiment, the GDP simulations reveal an increase in the main transition temperature by about 25K relative to GMP, and the occurrence of non-bilayer phases at high temperatures (inverted-cylinder or stacked phases). Structurally, the GDP system tends to evidence a tighter packing of the chains, a reduced extent of tilting, increased order parameters and a reduced fluidity. These differences are easily interpreted in terms of two key changes in molecular properties when going from GMP to GDP: (i) the reduction of the headgroup polarity and hydration (from two free hydroxyl groups to a single one); (ii) the increase in the effective tail cross-section relative to the (hydrated) headgroup cross-section, conferring to GDP a particular wedge shape. These two effects contribute to the relative instability of the liquid-crystalline phase, the stability being recovered in nature when the diglyceride headgroup is functionalized by a bulky or/and polar substituent.

  6. Investigating carbon dynamics in Siberian peat bogs using molecular-level analyses (United States)

    Kaiser, K.; Benner, R. H.


    Total hydrolysable carbohydrates, and lignin and cutin acid compounds were analyzed in peat cores collected 56.8 N (SIB04), 58.4 N (SIB06), 63.8 N (G137) and 66.5 N (E113) in the Western Siberian Lowland to investigate vegetation, chemical compositions and the stage of decomposition. Sphagnum mosses dominated peatland vegetation in all four cores. High-resolution molecular analyses revealed rapid vegetation changes on timescales of 50-200 years in the southern cores Sib4 and Sib6. Syringyl and vanillyl (S/V) ratios and cutin acids indicated these vegetation changes were due to varying inputs of angiosperm and gymnosperm and root material. In the G137 and E113 cores lichens briefly replaced sphagnum mosses and vascular plants. Molecular decomposition indicators used in this study tracked the decomposition of different organic constituents of peat organic matter. The carbohydrate decomposition index was sensitive to the polysaccharide component of all peat-forming plants, whereas acid/aldehyde ratios of S and V phenols (Ac/AlS,V) followed the lignin component of vascular plants. Low carbohydrate decomposition indices in peat layers corresponded well with elevated (Ad/Al)S,V ratios. This suggested both classes of biochemicals were simultaneously decomposed, and decomposition processes were associated with extensive total mass loss in these ombrotrophic systems. Selective decomposition or transformation of lignin was observed in the permafrost-influenced northern cores G137 and E113. Both cores exhibited the highest (Ad/Al)S,V ratios, almost four-fold higher than measured in peat-forming plants. The extent of decomposition in the four peat cores did not uniformly increase with age, but showed episodic extensive decomposition events. Variable decomposition events independent of climatic conditions and vegetation shifts highlight the complexity of peatland dynamics.

  7. Investigating the relative influences of molecular dimensions and binding energies on diffusivities of guest species inside nanoporous crystalline materials

    NARCIS (Netherlands)

    Krishna, R.; van Baten, J.M.


    The primary objective of this article is to investigate the relative influences of molecular dimensions and adsorption binding energies on unary diffusivities of guest species inside nanoporous crystalline materials such as zeolites and metal-organic frameworks (MOFs). The investigations are based o

  8. Investigations on the usefulness of CEACAMs as potential imaging targets for molecular imaging purposes.

    Directory of Open Access Journals (Sweden)

    Markus Heine

    Full Text Available Members of the carcinoembryonic antigen cell adhesion molecules (CEACAMs family are the prototype of tumour markers. Classically they are used as serum markers, however, CEACAMs could serve as targets for molecular imaging as well.In order to test the anti CEACAM monoclonal antibody T84.1 for imaging purposes, CEACAM expression was analysed using this antibody. Twelve human cancer cell lines from different entities were screened for their CEACAM expression using qPCR, Western Blot and FACS analysis. In addition, CEACAM expression was analyzed in primary tumour xenografts of these cells. Nine of 12 tumour cell lines expressed CEACAM mRNA and protein when grown in vitro. Pancreatic and colon cancer cell lines showed the highest expression levels with good correlation of mRNA and protein level. However, when grown in vivo, the CEACAM expression was generally downregulated except for the melanoma cell lines. As the CEACAM expression showed pronounced expression in FemX-1 primary tumours, this model system was used for further experiments. As the accessibility of the antibody after i.v. application is critical for its use in molecular imaging, the binding of the T84.1 monoclonal antibody was assessed after i.v. injection into SCID mice harbouring a FemX-1 primary tumour. When applied i.v., the CEACAM specific T84.1 antibody bound to tumour cells in the vicinity of blood vessels. This binding pattern was particularly pronounced in the periphery of the tumour xenograft, however, some antibody binding was also observed in the central areas of the tumour around blood vessels. Still, a general penetration of the tumour by i.v. application of the anti CEACAM antibody could not be achieved despite homogenous CEACAM expression of all melanoma cells when analysed in tissue sections. This lack of penetration is probably due to the increased interstitial fluid pressure in tumours caused by the absence of functional lymphatic vessels.

  9. Morphostructural investigation of the female reproductive system and molecular evidence for Wolbachia in Balclutha brevis Lindberg 1954 (Hemiptera, Cicadellidae). (United States)

    Pappalardo, A M; D'Urso, V; Viscuso, R; Ferrito, V; Giunta, M C; Cupani, S; Vitale, D G M


    Balclutha brevis Lindberg 1954 (Homoptera, Cicadellidae) is an allochthonous species that is rapidly spreading in Sicily and in mainland Europe due to the wide spread of its host plant and therefore could also compete with populations of native species. Considering these ecological implications, based on the lacking ultrastructural data about the reproductive systems of the Auchenorrhyncha and since previous investigations on the male reproductive system of B. brevis have shown some interesting features, we carried out morphostructural investigations on the female reproductive system of this alien leafhopper. Moreover, given the high interest in literature on Wolbachia entomoparasite and based on our previous studies, we provided a contribution to further investigations in applied sciences. For this aim we performed a molecular analysis on males and females of B. brevis to detect the possible presence of strains of the bacterium known to alter host reproductive biology. The female reproductive system has a morphological organization comparable to the general anatomical features of most of the Auchenorrhyncha species; however, comparing our data with the literature, some considerations are discussed. As for the histological and ultrastructural investigations, our results show a secretory activity of the various examined structures. In the spermatheca of B. brevis, in particular, the secretory activity is more marked in the sac-shaped tract, where histochemical investigations showed a lipid component of the secretion; possible origin of this component is discussed. Moreover, mainly free spermatozoa are found in the sac-shaped tract of the spermatheca and in the common oviduct. As for the latter, an interesting findings is the lack of cuticular intima on the epithelial surface of the common oviduct; furthermore, the observed features and the literature in this regards led us to review the significance of the structure called as spermatheca. The molecular screening

  10. Investigation of Sorption and Diffusion Mechanisms, and Preliminary Economic Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bhave, Ramesh R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jubin, Robert Thomas [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Spencer, Barry B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nair, Sankar [Georgia Inst. of Technology, Atlanta, GA (United States)


    This report describes the synthesis and evaluation of molecular sieve zeolite membranes to separate and concentrate tritiated water (HTO) from dilute HTO-bearing aqueous streams. Several monovalent and divalent cation exchanged silico alumino phosphate (SAPO-34) molecular sieve zeolite membranes were synthesized on disk supports and characterized with gas and vapor permeation measurements. The pervaporation process performance was evaluated for the separation and concentration of tritiated water. Experiments were performed using tritiated water feed solution containing tritium at the high end of the range (1 mCi/mL) anticipated in a nuclear fuel processing system that includes both acid and water streams recycling. The tritium concentration was about 0.1 ppm. The permeate was recovered under vacuum. The HTO/H2O selectivity and separation factor calculated from the measured tritium concentrations ranged from 0.99 to 1.23, and 0.83-0.98, respectively. Although the membrane performance for HTO separation was lower than expected, several encouraging observations including molecular sieving and high vapor permeance are reported. Additionally, several new approaches are proposed, such as tuning the sorption and diffusion properties offered by small pore LTA zeolite materials, and cation exchanged aluminosilicates with high metal loading. It is hypothesized that substantially improved preferential transport of tritium (HTO) resulting in a more concentrated permeate can be achieved. Preliminary economic analysis for the membrane-based process to concentrate tritiated water is also discussed.

  11. Molecular analysis of precursor lesions in familial pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Tatjana Crnogorac-Jurcevic

    Full Text Available BACKGROUND: With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical. METHODS AND FINDINGS: We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses. CONCLUSIONS: Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive

  12. Investigation of Weibull statistics in fracture analysis of cast aluminum (United States)

    Holland, F. A., Jr.; Zaretsky, E. V.


    The fracture strengths of two large batches of A357-T6 cast aluminum coupon specimens were compared by using two-parameter Weibull analysis. The minimum number of these specimens necessary to find the fracture strength of the material was determined. The applicability of three-parameter Weibull analysis was also investigated. A design methodolgy based on the combination of elementary stress analysis and Weibull statistical analysis is advanced and applied to the design of a spherical pressure vessel shell. The results from this design methodology are compared with results from the applicable ASME pressure vessel code.

  13. Investigating the influence of effective parameters on molecular characteristics of bovine serum albumin nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Rohiwal, S.S.; Satvekar, R.K.; Tiwari, A.P.; Raut, A.V.; Kumbhar, S.G.; Pawar, S.H., E-mail:


    Graphical abstract: The physiochemical properties of nanoparticles provide the basic aspects about the conformational transitions which could have a strong bearing on the bioavailability for bioactive molecules such as peptides and hormones. - Highlights: • Synthesis and surface and structural properties of Bovine Serum Albumin nanoparticles (BSANPs). • Study of conformational transitions of BSANPs by spectroscopic techniques. • Studies on the effect of pH and protein concentration on formulation of BSANPs. - Abstract: The protein nanoparticles formulation is a challenging task as they are prone to undergo conformational transitions while processing which may affect bioavailability for bioactive compounds. Herein, a modified desolvation method is employed to prepare Bovine Serum Albumin nanoparticles, with controllable particle size ranging from 100 to 300 nm and low polydispersity index. The factors influencing the size and structure of BSA NPs viz. protein concentration, pH and the conditions for purification are well investigated. The structure of BSA NPs is altered due to processing, and may affect the effective binding ability with drugs and bioactive compounds. With that aims, investigations of molecular characteristics of BSA NPs are carried out in detail by using spectroscopic techniques. UV–visible absorption and Fourier Transform Infrared demonstrate the alteration in protein structure of BSA NPs whereas the FT-Raman spectroscopy investigates changes in the secondary and tertiary structures of the protein. The conformational changes of BSA NPs are observed by change in fluorescence intensity and emission maximum wavelength of tryptophan residue by fluorescence spectroscopy. The field emission scanning electron and atomic force microscopy micrographs confirm the size and semi-spherical morphology of the BSA NPs. The effect of concentration and pH on particle size distribution is studied by particle size analyzer.


    Directory of Open Access Journals (Sweden)

    A. V. Demina


    Full Text Available The aim of this study was to investigate the outbreak of aseptic meningitis in theNovosibirskregion in 2008–2009. We studied genetic diversity and molecular-epidemiological characteristics of human enteroviruses that caused aseptic meningitis. Materials and metods. In the present study we investigated samples of cerebrospinal fluid from 199 patients with a diagnosis “aseptic meningitis”, based on the clinical characteristics of the disease (headache, stiff neck, fever, nausea, vomiting, and confirmed by laboratory tests of spinal fluid (lymphocyte cell count > 10 cells/ml.All samples were tested by PCR for RNA of Enterovirus and Flavivirus and DNA Myc. tuberculosis, Borrelia spp., Neisseria spp. In the samples there were not found RNA Flavivirus, DNA Myc. tuberculosis, Borrelia spp., Neisseria spp., but in 73 samples (37% was identified RNA enterovirus (EV. Determination of nucleotide sequences of 5’UTR and VP1-region of EV revealed that they belong to the following genotypes: the highest percentage was presented by genotype ECHO 30 (62%; another genotypes were Cox A2 (8%, Cox A4 (5%, Cox A14 (3%, Cox A16 (5%, Cox B5 (8%, ECHO 6 (3%, ECHO 9 (3% and ECHO 25 (3%. In 2008 most of the EV that caused the symptoms of aseptic meningitis belonged to genotype ECHO 30 (76%. In 2009 the clinical specimens containing genotype ECHO 30 were not found, but the largest percentage of EV belonged to genotypes Cox A2 (33% and Cox A4 (22%. Thus, in 2008 we recorded outbreak of aseptic meningitis, the major etiological factor was enterovirus ECHO 30. And the rise of the incidence of aseptic meningitis in 2009 is related to the circulation of new genotypes of EV. The investigated strains were deposited in an international database GenBank under accession numbers KP258231-KP258235, HM559584.

  15. Investigating the molecular mechanisms of organophosphate and pyrethroid resistance in the fall armyworm Spodoptera frugiperda. (United States)

    Carvalho, Renato A; Omoto, Celso; Field, Linda M; Williamson, Martin S; Bass, Chris


    The fall armyworm Spodoptera frugiperda is an economically important pest of small grain crops that occurs in all maize growing regions of the Americas. The intensive use of chemical pesticides for its control has led to the selection of resistant populations, however, to date, the molecular mechanisms underlying resistance have not been characterised. In this study the mechanisms involved in the resistance of two S. frugiperda strains collected in Brazil to chlorpyrifos (OP strain) or lambda-cyhalothrin (PYR strain) were investigated using molecular and genomic approaches. To examine the possible role of target-site insensitivity the genes encoding the organophosphate (acetylcholinesterase, AChE) and pyrethroid (voltage-gated sodium channel, VGSC) target-site proteins were PCR amplified. Sequencing of the S. frugiperda ace-1 gene identified several nucleotide changes in the OP strain when compared to a susceptible reference strain (SUS). These result in three amino acid substitutions, A201S, G227A and F290V, that have all been shown previously to confer organophosphate resistance in several other insect species. Sequencing of the gene encoding the VGSC in the PYR strain, identified mutations that result in three amino acid substitutions, T929I, L932F and L1014F, all of which have been shown previously to confer knockdown/super knockdown-type resistance in several arthropod species. To investigate the possible role of metabolic detoxification in the resistant phenotype of the OP and PYR stains all EST sequences available for S. frugiperda were used to design a gene-expression microarray. This was then used to compare gene expression in the resistant strains with the susceptible reference strain. Members of several gene families, previously implicated in metabolic resistance in other insects were found to be overexpressed in the resistant strains including glutathione S-transferases, cytochrome P450s and carboxylesterases. Taken together these results provide

  16. Investigating the molecular mechanisms of organophosphate and pyrethroid resistance in the fall armyworm Spodoptera frugiperda.

    Directory of Open Access Journals (Sweden)

    Renato A Carvalho

    Full Text Available The fall armyworm Spodoptera frugiperda is an economically important pest of small grain crops that occurs in all maize growing regions of the Americas. The intensive use of chemical pesticides for its control has led to the selection of resistant populations, however, to date, the molecular mechanisms underlying resistance have not been characterised. In this study the mechanisms involved in the resistance of two S. frugiperda strains collected in Brazil to chlorpyrifos (OP strain or lambda-cyhalothrin (PYR strain were investigated using molecular and genomic approaches. To examine the possible role of target-site insensitivity the genes encoding the organophosphate (acetylcholinesterase, AChE and pyrethroid (voltage-gated sodium channel, VGSC target-site proteins were PCR amplified. Sequencing of the S. frugiperda ace-1 gene identified several nucleotide changes in the OP strain when compared to a susceptible reference strain (SUS. These result in three amino acid substitutions, A201S, G227A and F290V, that have all been shown previously to confer organophosphate resistance in several other insect species. Sequencing of the gene encoding the VGSC in the PYR strain, identified mutations that result in three amino acid substitutions, T929I, L932F and L1014F, all of which have been shown previously to confer knockdown/super knockdown-type resistance in several arthropod species. To investigate the possible role of metabolic detoxification in the resistant phenotype of the OP and PYR stains all EST sequences available for S. frugiperda were used to design a gene-expression microarray. This was then used to compare gene expression in the resistant strains with the susceptible reference strain. Members of several gene families, previously implicated in metabolic resistance in other insects were found to be overexpressed in the resistant strains including glutathione S-transferases, cytochrome P450s and carboxylesterases. Taken together these results

  17. Investigating Molecular Inheritance of Carbon in Star-forming Regions along a Galactic Gradient

    KAUST Repository

    Smith, Rachel L.


    Observations of CO isotopologues taken at high spectral resolution toward young stellar objects (YSOs) are valuable tools for investigating protoplanetary chemical reservoirs, and enable robust comparisons between YSOs and solar system material (meteorites and the Sun). Investigating a range of YSO environments also helps parameterize variations in the distribution and evolution of carbon-based molecules, furthering an understanding of prebiotic chemistry. We have begun a wide survey of massive YSOs using Keck-NIRSPEC at high spectral resolution (R=25,000). Fundamental and first-overtone near-IR CO rovibrational absorption spectra have thus far been obtained toward 14 massive, luminous YSOs at Galactocentric radii (RGC) ranging from ~4.5 to 9.7 kpc. From these data we can obtain precise [12CO]/[13CO] gas-phase abundance ratios along a Galactic gradient, and [12CO]/[13CO]Gas can be further evaluated against published [12CO2]/[13CO2]Ice and [12CO]/[13CO]Ice because all observations are in absorption, a robust study of molecular inheritance is possible by virtue of comparing 12C/13C along the same lines-of-sight. Initial results for cold CO gas at RGC ~ 6.1 kpc and 9.4 kpc reveal [12C16O]/[13C16O] of 59+/‑8 and 74+/‑3, respectively, roughly following an expected 12C/13C Galactic gradient. Thus far, we find [12CO]/[13CO] in the cold CO gas to be lower than [12CO2]/[13CO2]Ice, suggesting that CO2 may not originate from CO reservoirs as often assumed. While very high-resolution observations of CO gas toward low-mass YSOs observed with VLT-CRIRES show significant heterogeneity in [12CO]/[13CO] at RGC ~ 8 kpc, this dispersion is not found for the massive YSOs. Both the low-mass and massive YSOs have higher [12CO]/[13CO] in warm vs. cold gas, and both show signatures suggesting possible interplay between CO ice and gas reservoirs. Overall, our results indicate that carbon isotopic evolution in massive YSO environments may follow different paths compared to low-mass YSOs

  18. Molecularly Imprinted Polymers for Ochratoxin A Extraction and Analysis

    Directory of Open Access Journals (Sweden)

    Jorn C. C. Yu


    Full Text Available Molecularly imprinted polymers (MIPs are considered as polymeric materials that mimic the functionality of antibodies. MIPs have been utilized for a wide variety of applications in chromatography, solid phase extraction, immunoassays, and sensor recognition. In this article, recent advances of MIPs for the extraction and analysis of ochratoxins are discussed. Selection of functional monomers to bind ochratoxin A (OTA with high affinities, optimization of extraction procedures, and limitations of MIPs are compared from different reports. The most relevant examples in the literature are described to clearly show how useful these materials are. Strategies on MIP preparation and schemes of analytical methods are also reviewed in order to suggest the next step that would make better use of MIPs in the field of ochratoxin research. The review ends by outlining the remaining issues and impediments.

  19. Genetic diversity analysis of common beans based on molecular markers. (United States)

    Gill-Langarica, Homar R; Muruaga-Martínez, José S; Vargas-Vázquez, M L Patricia; Rosales-Serna, Rigoberto; Mayek-Pérez, Netzahualcoyotl


    A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  20. Genetic diversity analysis of common beans based on molecular markers

    Directory of Open Access Journals (Sweden)

    Homar R. Gill-Langarica


    Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  1. Experimental and molecular docking investigation on metal-organic framework MIL-101(Cr) as a sorbent for vortex assisted dispersive micro-solid-phase extraction of trace 5-nitroimidazole residues in environmental water samples prior to UPLC-MS/MS analysis. (United States)

    Lu, Nan; Wang, Ting; Zhao, Pan; Zhang, Lianjun; Lun, Xiaowen; Zhang, Xueli; Hou, Xiaohong


    In the presented work, metal-organic framework (MOF) material MIL-101(Cr) (MIL, Matérial Institute Lavoisier) was used as a sorbent for vortex assisted dispersive micro-solid-phase extraction (VA-D-μ-SPE) of trace amount of metronidazole (MNZ), ronidazole (RNZ), secnidazole (SNZ), dimetridazole (DMZ), tinidazole (TNZ), and ornidazole (ONZ) in different environmental water samples. Ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was used to quantify the target analytes. The extraction conditions, including type of sorbents, amount of MIL-101(Cr), solution pH, extraction method, extraction time, effect of salt, and elution conditions were investigated. Upon the optimal conditions, the developed method showed an excellent extraction performance with the average recovery ranging from 75.2 to 98.8 %. Good sensitivity levels were achieved with the detection limits of 0.03∼0.06 μg/L and the quantitation limits of 0.09∼0.20 μg/L. The linear ranges were varied from 0.1 to 20 for SNZ and ONZ and from 0.2 to 40 μg/L for MNZ, RNZ, DMZ, and TNZ (r (2) > 0.992), and repeatability of the method was satisfactory with the relative standard deviations (RSD) extraction and determination of 5-nitroimidazoles (5-NDZs) in 12 real water samples, showing the positive findings of MNZ and TNZ ranging from 0.3 to 1.0 μg/L. Furthermore, molecular docking was applied to explain the molecular interactions and free binding energies between MIL-101(Cr) and 5-NDZs, providing a deep insight into the adsorption mechanism. The proposed method exhibited the advantages of simplicity, rapidly, less solvent consumption, ease of operation, higher sensitivity, and lower matrix effect. Graphical abstract Schematic diagram of the extraction process and molecular docking investigation.

  2. Alphavirus protease inhibitors from natural sources: A homology modeling and molecular docking investigation. (United States)

    Byler, Kendall G; Collins, Jasmine T; Ogungbe, Ifedayo Victor; Setzer, William N


    Alphaviruses such as Chikungunya virus (CHIKV), O'Nyong-Nyong virus (ONNV), Ross River virus (RRV), Eastern equine encephalitis virus (EEEV), Venezuelan equine encephalitis virus (VEEV), and Western equine encephalitis virus (WEEV), are mosquito-transmitted viruses that can cause fevers, rash, and rheumatic diseases (CHIKV, ONNV, RRV) or potentially fatal encephalitis (EEEV, VEEV, WEEV) in humans. These diseases are considered neglected tropical diseases for which there are no current antiviral therapies or vaccines available. The alphavirus non-structural protein 2 (nsP2) contains a papain-like protease, which is considered to be a promising target for antiviral drug discovery. In this work, molecular docking analyses have been carried out on a library of 2174 plant-derived natural products (290 alkaloids, 664 terpenoids, 1060 polyphenolics, and 160 miscellaneous phytochemicals) with the nsP2 proteases of CHIKV, ONNV, RRV, EEEV, VEEV, WEEV, as well as Aura virus (AURV), Barmah Forest Virus (BFV), Semliki Forest virus (SFV), and Sindbis virus (SINV) in order to identity structural scaffolds for inhibitor design or discovery. Of the 2174 phytochemicals examined, a total of 127 showed promising docking affinities and poses to one or more of the nsP2 proteases, and this knowledge can be used to guide experimental investigation of potential inhibitors.

  3. Investigation Into the Effects of Nucleotide Content on the Electrical Characteristics of DNA Plasmid Molecular Wires. (United States)

    Goshi, Noah; Narenji, Alaleh; Bui, Chris; Mokili, John L; Kassegne, Sam


    In this study, we investigate the effect of nucleotide content on the conductivity of plasmid length DNA molecular wires covalently bound to high aspect-ratio gold electrodes. The DNA wires were all between [Formula: see text] in length (>6000bp), and contained either 39%, 53%, or 64% GC base-pairs. We compared the current-voltage (I-V) and frequency-impedance characteristics of the DNA wires with varying GC content, and observed statistically significantly higher conductivity in DNA wires containing higher GC content in both AC and DC measurement methods. Additionally, we noted that the conductivity decreased as a function of time for all DNA wires, with the impedance at 100 Hz nearly doubling over a period of seven days. All readings were taken in humidity and temperature controlled environments on DNA wires suspended above an insulative substrate, thus minimizing the effect of experimental and environmental factors as well as potential for nonlinear alternate DNA confirmations. While other groups have studied the effect of GC content on the conductivity of nanoscale DNA molecules (DNA wires at scales that may be required during the fabrication of DNA-based electronics. Furthermore, our results provide further evidence that many of the charge transfer theories developed from experiments using nanoscale DNA molecules may still be applicable for DNA wires at the micro scale.

  4. Investigation of Effects of Nucleotide Content on Electrical Characteristics of DNA Plasmid Molecular Wires. (United States)

    Goshi, Noah; Narenji, Alaleh; Bui, Chris; Mokili, John L; Kassegne, Sam


    In this study, we investigate the effect of nucleotide content on the conductivity of plasmid length DNA molecular wires covalently bound to high aspect-ratio gold electrodes. The DNA wires were all between 2.20-2.35μm in length (>6000bp), and contained either 39%, 53%, or 64% GC base-pairs. We compared the current-voltage (I-V) and frequency-impedance characteristics of the DNA wires with varying GC content, and observed statistically significantly higher conductivity in DNA wires containing higher GC content in both AC and DC measurement methods. Additionally, we noted that the conductivity decreased as a function of time for all DNA wires, with the impedance at 100Hz nearly doubling over a period of seven days. All readings were taken in humidity and temperature controlled environments on DNA wires suspended above an insulative substrate, thus minimizing the effect of experimental and environmental factors as well as potential for nonlinear alternate DNA confirmations. While other groups have studied the effect of GC content on the conductivity of nano-scale DNA molecules (DNA wires at scales that may be required during the fabrication of DNA-based electronics. Furthermore, our results provide further evidence that many of the charge transfer theories developed from experiments using nano-scale DNA molecules may still be applicable for DNA wires at the micro-scale.

  5. Mechanistic investigations and molecular medicine applications of gold nanoparticle mediated (GNOME) laser transfection (United States)

    Schomaker, M.; Heinemann, D.; Kalies, S.; Willenbrock, S.; Murua Escobar, H.; Buch, A.; Sodeik, B.; Ripken, T.; Meyer, H.


    Alternative high throughput transfection methods are required to understand the molecular network of the cell, which is linked to the evaluation of target genes as therapeutic agents. Besides diagnostic purposes, the transfection of primary- and stem cells is of high interest for therapeutic use. Here, the cell release of trans- or exogene proteins is used to develop immune cancer therapies. The basic requirement to accomplish manipulation of cells is an efficient and gentle transfection method. Therefore, we developed an automatized cell manipulation platform providing high throughput by using GNOME laser transfection. Herein, the interaction of moderately focused laser pulses with gold nanoparticles in close vicinity to the cell membrane mediate transient membrane permeabilization. The exact nature of the involved permeabilization effects depends on the applied particles and laser parameters. Hereinafter, we describe investigations considering the parameter regime, the permeabilization mechanism and the safety profile of GNOME laser transfection. The experimental and calculated results imply a combined permeabilization mechanism consisting of both photochemical and photothermal effects. Furthermore, paramount spatial control achieved either by laser illumination with micrometer precision or targeted gold nanoparticle binding to the cells was demonstrated, allowing selective cell manipulation and destruction. Additionally, the possibility to manipulate difficult to transfect primary cells (neurons) is shown. These results give insights in the basic mechanisms involved in GNOME laser transfection and serve as a strong basis to deliver different molecules for therapeutic (e.g. proteins) and diagnostic (siRNA) use.

  6. Spectroscopic Parameter and Molecular Constant Investigations on Low-Lying States of BeF Radical

    Directory of Open Access Journals (Sweden)

    Jin Feng Sun


    Full Text Available The potential energy curves (PECs of X2Σ+, A2Πr and B2Σ+ states of BeF radical have been investigated using the complete active space self-consistent-field (CASSCF method, followed by the highly accurate valence internally contracted multireference configuration interaction (MRCI approach at the correlation-consistent basis sets, cc-pV5Z for Be and aug-cc-pV6Z for F. Based on the PECs of X2Σ+, A2Πr and B2Σ+ states, the spectroscopic parameters (De, Re, ωe, ωeχe, αe and Be have also been determined in the present work. With the PECs determined at the present level of theory, vibrational states have been predicted for each state when the rotational quantum number J equals zero (J = 0. The vibrational levels, inertial rotation and centrifugal distortion constants are determined for the three states, and the classical turning points are also calculated for the X2Σ+ state. Compared with the available experiments and other theories, it can be seen that the present spectroscopic parameter and molecular constant results are more fully in agreement with the experimental findings.

  7. Homogeneous nucleation and growth in supersaturated zinc vapor investigated by molecular dynamics simulation (United States)

    Römer, F.; Kraska, T.


    Homogeneous nucleation and growth of zinc from supersaturated vapor are investigated by nonequilibrium molecular dynamics simulations in the temperature range from 400to800K and for a supersaturation ranging from logS =2 to 11. Argon is added to the vapor phase as carrier gas to remove the latent heat from the forming zinc clusters. A new parametrization of the embedded atom method for zinc is employed for the interaction potential model. The simulation data are analyzed with respect to the nucleation rates and the critical cluster sizes by two different methods, namely, the threshold method of Yasuoka and Matsumoto [J. Chem. Phys. 109, 8451 (1998)] and the mean first passage time method for nucleation by Wedekind et al. [J. Chem. Phys. 126, 134103 (2007)]. The nucleation rates obtained by these methods differ approximately by one order of magnitude. Classical nucleation theory fails to describe the simulation data as well as the experimental data. The size of the critical cluster obtained by the mean first passage time method is significantly larger than that obtained from the nucleation theorem.

  8. Investigation of molecular heterogeneity of β-thalassemia disorder in District Charsadda of Pakistan (United States)

    Shakeel, Muhammad; Arif, Muhammad; Rehman, Shoaib Ur; Yaseen, Tabassum


    Objective: Thalassemia is blood related disease which arises from the reduced level of hemoglobin in red blood cells (RBC), a protein responsible for carrying oxygen inside the body. Considering its widespread occurrence in developing countries like Pakistan, this study aims to investigate the common molecular anomalies of the beta thalassemia disease in district Charsadda, Khyber Pakhtunkhwa. Methods: This work was done at Abdul Wali Khan University (AWKU) Mardan, Khyber Pakhtunkhwa, Pakistan. The work was performed on the blood samples collected from the patients and their families with beta thalassemia major (n = 13 families) belonged to District Charsadda. The collected blood samples were analyzed for presence of six known mutations with the help of polymerase cha in reaction technique i.e. amplification of refractory mutation system. Results: Our Study reports six known mutations (IVS-1-5, FSC 8/9, CD 41/42, IVS-1-1, CD 15 and FSC-5) accounting for about 90% of total beta thalassemia genes in this country. Among the reported mutations, IVS 1-5 was the most prevalent beta thalassemia gene in patients belonging to District Charsadda. Conclusion: The results and findings of the current study may help in accessing the frequency of these common mutations and in initiating pre-natal diagnosis programme in Pakistan. PMID:27182268

  9. Investigation into the Effect of Molds in Grasses on Their Content of Low Molecular Mass Thiols

    Directory of Open Access Journals (Sweden)

    Adam Nawrath


    Full Text Available The aim of this study was to investigate the effect of molds on levels of low molecular mass thiols in grasses. For this purpose, the three grass species Lolium perenne, Festulolium pabulare and Festulolium braunii were cultivated and sampled during four months, from June to September. The same species were also grown under controlled conditions. High-performance liquid chromatography with electrochemical detection was used for quantification of cysteine, reduced (GSH and oxidized (GSSG glutathione, and phytochelatins (PC2, PC3, PC4 and PC5. Data were statistically processed and analyzed. Thiols were present in all examined grass species. The effect of fungicide treatments applied under field conditions on the content of the evaluated thiols was shown to be insignificant. Species influenced (p < 0.05 PC3 and GSSG content. F. pabulare, an intergeneric hybrid of drought- and fungi-resistant Festuca arundinacea, was comparable in PC3 content with L. perenne and F. braunii under field conditions. Under controlled conditions, however, F. pabulare had higher (p < 0.05 PC3 content than did L. perenne and F. braunii. Under field conditions, differences between the evaluated species were recorded only in GSSG content, but only sampling in June was significant. F. pabulare had higher (p < 0.05 GSSG content in June than did L. perenne and F. braunii.

  10. A molecular dynamics investigation on the crizotinib resistance mechanism of C1156Y mutation in ALK

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Hui-Yong [Shandong University of Technology, Zibo 255049 (China); Ji, Feng-Qin, E-mail: [National Key Laboratory of Crop Genetic Improvement, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Center for Bioinformatics, Huazhong Agricultural University, Wuhan 430070 (China)


    Highlights: Black-Right-Pointing-Pointer The study revealed the detailed resistance mechanism of the non-active mutation C1156Y in ALK. Black-Right-Pointing-Pointer C1156Y leads to crizotinib displacement and conformational changes in the binding cavity. Black-Right-Pointing-Pointer The conformations cause a decline in the vdW and electrostatic energy between crizotinib and ALK. -- Abstract: Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that has recently been approved in the US for the treatment of non-small cell lung carcinoma (NSCLC). Despite its outstanding safety and efficacy, several resistant mutations against crizotinib have been detected in the treatment of NSCLC. However, in contrast to the widely accepted mechanism of steric hindrance by mutations at the active site, the mechanism by which the C1156Y non-active site mutation confers resistance against crizotinib remains unclear. In the present study, the resistance mechanism of C1156Y in ALK was investigated using molecular dynamics simulations. The results suggest that despite the non-active site mutation, C1156Y causes the dislocation of crizotinib as well as the indirect conformational changes in the binding cavity, which results in a marked decrease in the van der Waals and electrostatic interactions between crizotinib and ALK. The obtained results provide a detailed explanation of the resistance caused by C1156Y and may give a vital clue for the design of drugs to combat crizotinib resistance.

  11. Investigation of MWCNT Reinforcement on the Strain Hardening Behavior of Ultrahigh Molecular Weight Polyethylene

    Directory of Open Access Journals (Sweden)

    Hassan Mahfuz


    Full Text Available We have investigated strain hardening behavior of ultrahigh molecular weight polyethylene (UHMWPE reinforced with 2.0 wt% loading of multiwalled carbon nanotubes (MWCNTs. A solution spinning process was used to produce neat and MWCNT-reinforced filaments of UHMWPE. Tensile tests of filaments showed 62% and 114% improvement in strength and modulus, respectively. Strain hardening tests on filaments revealed spectacular contribution by MWCNTs in enhancing strength and modulus by more than one order of magnitude. SEM micrographs showed sufficient coating of nanotube surface with the polymer that promoted interface adhesion. This intimate interfacial interaction enforced alignment of nanotubes during repeated loading-unloading sequences and allowed effective load transfer to nanotubes. Close interaction between UHMWPE and nanotubes was further evidenced by Raman spectral distribution as a positive shift in the D-band suggesting compressive stress on nanotubes by lateral compression of polymer. Nanotubes thus deformed induced the desired strain hardening ability in the UHMWPE filament. Differential scanning calorimetry (DSC tests indicated around 15% increase in crystallinity after strain hardening—which together with nanotube alignment resulted in such dramatic improvement in properties.

  12. Raman spectroscopy based investigation of molecular changes associated with an early stage of dengue virus infection (United States)

    Bilal, Maria; Bilal, Muhammad; Saleem, Muhammad; Khurram, Muhammad; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, Mushtaq; Shahzada, Shaista; Ullah Khan, Ehsan


    Raman spectroscopy based investigations of the molecular changes associated with an early stage of dengue virus infection (DENV) using a partial least squares (PLS) regression model is presented. This study is based on non-structural protein 1 (NS1) which appears after three days of DENV infection. In total, 39 blood sera samples were collected and divided into two groups. The control group contained samples which were the negative for NS1 and antibodies and the positive group contained those samples in which NS1 is positive and antibodies were negative. Out of 39 samples, 29 Raman spectra were used for the model development while the remaining 10 were kept hidden for blind testing of the model. PLS regression yielded a vector of regression coefficients as a function of Raman shift, which were analyzed. Cytokines in the region 775–875 cm‑1, lectins at 1003, 1238, 1340, 1449 and 1672 cm‑1, DNA in the region 1040–1140 cm‑1 and alpha and beta structures of proteins in the region 933–967 cm‑1 have been identified in the regression vector for their role in an early stage of DENV infection. Validity of the model was established by its R-square value of 0.891. Sensitivity, specificity and accuracy were 100% each and the area under the receiver operator characteristic curve was found to be 1.

  13. Investigation of electron localization in harmonic emission from asymmetric molecular ion

    Institute of Scientific and Technical Information of China (English)

    张彩萍; 苗向阳


    We theoretically investigate the electron localization around two nuclei in harmonic emission from asymmetric molec-ular ion. The results show that the ionization process of electron localized around one nucleus competes with its transfer process to the other nucleus. By increasing the initial vibrational level, more electrons localized around the nucleus D+tend to transfer to the nucleus He2+so that the ionizations of electrons localized around the nucleus He2+increase. In this case, the difference in harmonic efficiency between HeH2+and HeD2+decreases while the difference in harmonic spectral structure increases. The evident minimum can be observed in the harmonic spectrum of HeH2+ compared with that in the spectral structure of HeD2+, which is due to the strong interference of multiple recombination channels originating from two nuclei. Time-dependent nuclear probability density, electron-nuclear probability density, double-well model, and time-frequency maps are presented to explain the underlying mechanisms.

  14. Molecular dynamics investigation of the effect of copper nanoparticle on the solid contact between friction surfaces (United States)

    Hu, Chengzhi; Bai, Minli; Lv, Jizu; Liu, Hao; Li, Xiaojie


    This study investigated the effect of copper (Cu) nanoparticles on the solid contact between friction surfaces by applying a molecular dynamics method to reveal the mechanisms responsible for the favorable friction properties of nanoparticles. Two models were built, which were named model A (without Cu) and model B (with Cu), respectively. The differences in the mechanical properties between these two models were compared. The simulation results demonstrated that the improvement in friction properties by Cu nanoparticles was more obvious at low velocity than at high velocity. At low velocity, a Cu nano-film was formed on the friction surface, which accommodated the velocity gradient and plastic deformation. Due to the good lubrication effect of the nano-film, the plastic deformation, defect structures and friction force of model B were improved compared with model A. Under high velocity conditions, a transfer layer appeared adjacent to the interface in both models. Because of this, the friction forces of the two models decreased with increased velocity. The fluid mechanics theory was used to explain why the friction force in model B was lower than that in model A at high velocity. The effect of the load on friction properties was also analyzed and the results showed that the mechanisms of anti-wear and friction reduction by Cu nanoparticles under a low load were the same as those under a high load.

  15. Serological and molecular investigation for brucellosis in swine in selected districts of Uganda. (United States)

    Erume, Joseph; Roesel, Kristina; Dione, Michel M; Ejobi, Francis; Mboowa, Gerald; Kungu, Joseph M; Akol, Joyce; Pezo, Danilo; El-Adawy, Hosny; Melzer, Falk; Elschner, Mandy; Neubauer, Heinrich; Grace, Delia


    Brucellosis is a notifiable zoonotic disease affecting livestock, humans, and wildlife in Uganda. Pigs can be infected with human pathogenic Brucella suis biovars 1 and 3 and can be a significant source of brucellosis for humans. Uganda has a rapidly growing pig population, and the pork consumption per capita is the highest in East Africa. The objective of this work was to determine the seroprevalence of brucellosis in Ugandan pigs. A cross-sectional serosurvey of pigs was conducted in three of the major pig-keeping districts in Uganda (Masaka (n = 381 samples), Mukono (n = 398), and Kamuli (n = 414)). In addition, pigs originating from these districts were sampled in the major pig abattoir in Kampala (n = 472). In total, 1665 serum samples were investigated by serological and molecular tests. Only three putative brucellosis-positive samples were detected serologically using indirect ELISA. These sera were found negative for Brucella antibodies by CFT; however, two had antibodies against Yersinia enterocolitica as determined by SAT. Presence of antibodies against Yersiniae was confirmed by Y. enterocolitica antibody-specific ELISA. The two Yersiniae ELISA-positive samples were brucellosis negative using real-time PCR. We tested additional 142 sera from the 1665 samples with real-time PCR. All tested negative. Under this type of production system, we expect a maximum B. suis prevalence of less than 1 % at 95 % confidence level, and therefore, the risk of acquiring brucellosis from the pigs or their products is negligible. However, pigs may harbor the zoonotic Y. enterocolitica. This is the first study to investigate the occurrence of brucellosis in pigs in Uganda and the first study to report Y. enterocolitica antibodies in swine in Uganda.

  16. Molecular mechanics and microcalorimetric investigations of the effects of molecular water on the aggregation of asphaltenes in solutions

    DEFF Research Database (Denmark)

    Murgich, J.; Lira-Galeana, C.; Garcia, Daniel Merino;


    by titration calorimetry. A simple dimer dissociation model was used to derive the information about the heat and the constant of dissociation from asphaltenes of Mexico and Alaska obtained from the calorimetric data. The association enthalpies calculated were found to be in excellent agreement with those......The interaction of two model asphaltene molecules from the Athabasca sand oil with a water molecule in a toluene solution was studied by means of molecular mechanics calculations. It was found that water forms bridging H bonds between the heteroatoms of asphaltenes with a considerable span...... in energies. The stronger H bond found has energies higher than those corresponding to the stacking of the aromatic areas of the same asphaltene molecules. This shows that the water molecule may generate additional mechanisms of aggregation of asphaltenes in toluene solution, as found experimentally. The H...

  17. Relationships of Campanian olive cultivars: comparative analysis of molecular and phenotypic data. (United States)

    Corrado, Giandomenico; La Mura, Maurizio; Ambrosino, Orsola; Pugliano, Giuseppe; Varricchio, Paola; Rao, Rosa


    Estimation of the genetic relatedness of traditional olive cultivars with genetic markers and phenotypic data enables progress in plant breeding, management of genetic resources, and protection of both breeders' rights and certified premium products. We used amplified fragment length polymorphisms (AFLPs), simple sequence repeats (SSRs), and quantitative and qualitative morphological traits, including characteristics recommended for variety registration, to study genetic diversity and relationships in the olive at different levels. The 14 varieties analyzed, which are used for the production of Protected Denomination of Origin extra-virgin olive oil, represent the most important cultivars in the Campania region of Italy and typify a regional diversity characteristic of traditional olive cultivation. The genetic distances obtained with the two DNA marker systems were significantly correlated, as were those obtained by quantitative and qualitative traits. A lower but significant correlation was also observed between distances based on molecular markers and quantitative traits, but qualitative traits, even if sampled in high numbers, failed to describe the pattern of molecular similarity. Our data imply that the type and the number of phenotypic traits scored can greatly influence the outcome of the analysis, and care should be taken when qualitative and quantitative data are combined. Furthermore, the data indicate that the two molecular marker systems are useful for investigating genetic relationships, but they may also be used to complement and assist the traditional registration of varieties. We propose that since the information provided by molecular and morphological marker systems in olive is different, they should serve different purposes.

  18. Neuroendocrine and squamous colonic composite carcinoma: Case report with molecular analysis

    Institute of Scientific and Technical Information of China (English)

    Sabrina C Wentz; Cindy Vnencak-Jones; William V Chopp


    Composite colorectal carcinomas are rare. There are a modest number of cases in the medical literature, with even fewer cases describing composite carcinoma with neuroendocrine and squamous components. There are to our knowledge no reports of composite carcinoma molecular alterations. We present a case of composite carcinoma of the splenic flexure in a 33 year-old Cau casian male to investigate the presence and prognos tic significance of molecular alterations in rare colonic carcinoma subtypes. Formalin-fixed paraffin-embedded (FFPE) tissue was hematoxylin and eosin- and mucicar-mine-stained according to protocol, and immuno-stained with cytokeratin (CK)7, CK20, CDX2, AE1/AE3, chromo-granin-A and synaptophysin. DNA was extracted from FFPE tissues and molecular analyses were performedaccording to lab-developed methods, followed by capil lary electrophoresis. Hematoxylin and eosin staining showed admixed neuroendocrine and keratinized squa mous cells. Positive nuclear CDX2 expression confirmed intestinal derivation. CK7 and CK20 were negative. Neuroendocrine cells stained positively for synaptophy sin and AE1/AE3 and negatively for chromogranin and mucicarmine. Hepatic metastases showed a similar im munohistochemical profile. Molecular analysis revealed a G13D KRAS mutation. BRAF mutational testing was negative and microsatellite instability was not detected. The patient had rapid disease progression on chemo therapy and died 60 d after presentation. Although the G13D KRAS mutation normally predicts an intermediate outcome, the aggressive tumor behavior suggests other modifying factors in rare types of colonic carcinomas.

  19. Application of Parallel Processing to the Investigation of Supercritical Droplet Evaporation and Combustion Using Molecular Dynamics (United States)


    Molecular dynamics (MD) implemented on parallel processors was used to model supercritical droplet phenomena occurring in combustion devices. The use...of molecular dynamics allows the modeling of supercritical phenomena without an a priori knowledge of the equation of state or transport properties

  20. Investigating Convergence Patterns for Numerical Methods Using Data Analysis (United States)

    Gordon, Sheldon P.


    The article investigates the patterns that arise in the convergence of numerical methods, particularly those in the errors involved in successive iterations, using data analysis and curve fitting methods. In particular, the results obtained are used to convey a deeper level of understanding of the concepts of linear, quadratic, and cubic…

  1. Investigations of the intermolecular forces between RDX and polyethylene by force-distance spectroscopy and molecular dynamics simulations. (United States)

    Taylor, D E; Strawhecker, K E; Shanholtz, E R; Sorescu, D C; Sausa, R C


    The development of novel nanoenergetic materials with enhanced bulk properties requires an understanding of the intermolecular interactions occurring between molecular components. We investigate the surface interactions between 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) and polyethylene (PE) crystals on the basis of combined use of molecular dynamics (MD) simulations and force-distance spectroscopy, in conjunction with Lifshitz macroscopic theory of van der Waals forces between continuous materials. The binding energy in the RDX-PE system depends both on the degree of PE crystallinity and on the RDX crystal face. Our MD simulations yield binding energies of approximately 132 and 120 mJ/m(2) for 100% amorphous and 100% crystalline PE on RDX (210), respectively. The average value is about 36% greater than our experimental value of 81 ± 15 mJ/m(2) for PE (∼48% amorphous) on RDX (210). By comparison, Liftshitz theory predicts a value of about 79 mJ/m(2) for PE interacting with RDX. Our MD simulations also predict larger binding energies for both amorphous and crystalline PE on RDX (210) compared to the RDX (001) surface. Analysis of the interaction potential indicates that about 60% of the binding energy in the PE-RDX system is due to attractive interactions between HPE-ORDX and CPE-NRDX pairs of atoms. Further, amorphous PE shows a much longer interaction distance than crystalline PE with the (210) and (001) RDX surfaces due to the possibility of larger polymer elongations in the case of amorphous PE as strain is applied. Also, we report estimates of the binding energies of energetic materials RDX and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) with PE, propylene, polystyrene, and several fluorine-containing polymers using Lifshitz theory and compare these with reported MD calculations.

  2. MDAnalysis: a toolkit for the analysis of molecular dynamics simulations. (United States)

    Michaud-Agrawal, Naveen; Denning, Elizabeth J; Woolf, Thomas B; Beckstein, Oliver


    MDAnalysis is an object-oriented library for structural and temporal analysis of molecular dynamics (MD) simulation trajectories and individual protein structures. It is written in the Python language with some performance-critical code in C. It uses the powerful NumPy package to expose trajectory data as fast and efficient NumPy arrays. It has been tested on systems of millions of particles. Many common file formats of simulation packages including CHARMM, Gromacs, Amber, and NAMD and the Protein Data Bank format can be read and written. Atoms can be selected with a syntax similar to CHARMM's powerful selection commands. MDAnalysis enables both novice and experienced programmers to rapidly write their own analytical tools and access data stored in trajectories in an easily accessible manner that facilitates interactive explorative analysis. MDAnalysis has been tested on and works for most Unix-based platforms such as Linux and Mac OS X. It is freely available under the GNU General Public License from


    Directory of Open Access Journals (Sweden)

    Dainerys Infante-Santana


    Full Text Available

    El artículo describe el Programa de calidad para las investigaciones del Centro de Inmunología Molecular. Este programa incorpora el cumplimiento de las Buenas Prácticas de Laboratorio con una gestión basada en el comportamiento, el análisis de los riesgos, el enfoque a procesos y la evaluación a través de indicadores. La aplicación del nuevo programa de calidad en el proceso de la actividad científica, permitió disminuir los incumplimientos de las mencionadas prácticas, mejorar los indicadores de productividad científica y lograr una mayor cultura de calidad en el área de investigaciones del Centro de Inmunología Molecular.


    The paper describes the Program of quality for the investigations of the Center of Molecular Immunology. This program incorporates the execution of the Good Practices of Laboratory with a behaviour-based management, the analysis of the risks, the process approach and the assessment through indicators. The application of the new quality program in the process of the scientific activity, allowed to decrease the nonfulfillments of the above mentioned practices, to improve the scientific productivity indicators and to achieve a greater quality culture in the area of investigations of the Center of Molecular Immunology.

  4. Molecular analysis of microbial communities in endotracheal tube biofilms.

    Directory of Open Access Journals (Sweden)

    Scott Cairns

    Full Text Available BACKGROUND: Ventilator-associated pneumonia is the most prevalent acquired infection of patients on intensive care units and is associated with considerable morbidity and mortality. Evidence suggests that an improved understanding of the composition of the biofilm communities that form on endotracheal tubes may result in the development of improved preventative strategies for ventilator-associated pneumonia. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was to characterise microbial biofilms on the inner luminal surface of extubated endotracheal tubes from ICU patients using PCR and molecular profiling. Twenty-four endotracheal tubes were obtained from twenty mechanically ventilated patients. Denaturing gradient gel electrophoresis (DGGE profiling of 16S rRNA gene amplicons was used to assess the diversity of the bacterial population, together with species specific PCR of key marker oral microorganisms and a quantitative assessment of culturable aerobic bacteria. Analysis of culturable aerobic bacteria revealed a range of colonisation from no growth to 2.1×10(8 colony forming units (cfu/cm(2 of endotracheal tube (mean 1.4×10(7 cfu/cm(2. PCR targeting of specific bacterial species detected the oral bacteria Streptococcus mutans (n = 5 and Porphyromonas gingivalis (n = 5. DGGE profiling of the endotracheal biofilms revealed complex banding patterns containing between 3 and 22 (mean 6 bands per tube, thus demonstrating the marked complexity of the constituent biofilms. Significant inter-patient diversity was evident. The number of DGGE bands detected was not related to total viable microbial counts or the duration of intubation. CONCLUSIONS/SIGNIFICANCE: Molecular profiling using DGGE demonstrated considerable biofilm compositional complexity and inter-patient diversity and provides a rapid method for the further study of biofilm composition in longitudinal and interventional studies. The presence of oral microorganisms in

  5. Can molecular projected density of states (PDOS be systematically used in electronic conductance analysis?

    Directory of Open Access Journals (Sweden)

    Tonatiuh Rangel


    Full Text Available Using benzenediamine and benzenedithiol molecular junctions as benchmarks, we investigate the widespread analysis of the quantum transport conductance in terms of the projected density of states (PDOS onto molecular orbitals (MOs. We first consider two different methods for identifying the relevant MOs: (1 diagonalization of the Hamiltonian of the isolated molecule and (2 diagonalization of a submatrix of the junction Hamiltonian constructed by considering only basis elements localized on the molecule. We find that these two methods can lead to substantially different MOs and hence PDOS. Furthermore, within Method 1, the PDOS can differ depending on the isolated molecule chosen to represent the molecular junction (e.g., with or without dangling bonds; within Method 2, the PDOS depends on the chosen basis set. We show that these differences can be critical when the PDOS is used to provide a physical interpretation of the conductance (especially when its value is small, as it happens typically at zero bias. In this work, we propose a new approach in an attempt to reconcile the two traditional methods. Although some improvements were achieved, the main problems remain unsolved. Our results raise more general questions and doubts on a PDOS-based analysis of the conductance.

  6. Molecular dynamics investigation of structure and high-temperature mechanical properties of SiBCO ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Ningbo, E-mail:; Xue, Wei, E-mail:; Zhou, Hongming; Zhang, Miao


    Highlights: • The nano-domain structure of SiBCO is reproduced by large-scale atomistic simulations. • Calculated pair and angular distribution functions consist with experiments and DFT calculation. • Silicon atoms form mixed bonds tetrahedron with carbon and oxygen at domains interfaces. • Change in slope of temperature-dependent Young’s moduli indicates glass transition temperature. - Abstract: SiCO ceramics present excellent properties at high temperatures, the addition of boron for SiCO leads to enhanced performance on thermal stability and creep temperature. Investigating atomic structure and its influence on material property are essential for further study. In this study, large-scale molecular dynamics simulations were used to study amorphous SiBCO structures with different carbon contents. Phase separation and free carbon structures were successfully reproduced by melt-quench simulation. The calculated pair distribution functions of SiBCO are comparable to those of SiCO in experiments, the C–C–C angular distribution indicates strong sp{sup 2} carbon character together with a sp{sup 3} character. Si-centered tetrahedrons present in amorphous SiBCO and the most popular case is Si–C/O tetrahedron. Si{sub 3}BC{sub 7}O{sub 3} presents the largest Young’s modulus for all the temperatures due to the network structure of free carbon. A change in the slope of temperature-dependent Young’s moduli at 1300 K–1700 K for Si{sub 3}BC{sub 3}O{sub 3} indicates the glass transition temperature.

  7. 2D IR spectra of cyanide in water investigated by molecular dynamics simulations (United States)

    Lee, Myung Won; Carr, Joshua K.; Göllner, Michael; Hamm, Peter; Meuwly, Markus


    Using classical molecular dynamics simulations, the 2D infrared (IR) spectroscopy of CN− solvated in D2O is investigated. Depending on the force field parametrizations, most of which are based on multipolar interactions for the CN− molecule, the frequency-frequency correlation function and observables computed from it differ. Most notably, models based on multipoles for CN− and TIP3P for water yield quantitatively correct results when compared with experiments. Furthermore, the recent finding that T 1 times are sensitive to the van der Waals ranges on the CN− is confirmed in the present study. For the linear IR spectrum, the best model reproduces the full widths at half maximum almost quantitatively (13.0 cm−1 vs. 14.9 cm−1) if the rotational contribution to the linewidth is included. Without the rotational contribution, the lines are too narrow by about a factor of two, which agrees with Raman and IR experiments. The computed and experimental tilt angles (or nodal slopes) α as a function of the 2D IR waiting time compare favorably with the measured ones and the frequency fluctuation correlation function is invariably found to contain three time scales: a sub-ps, 1 ps, and one on the 10-ps time scale. These time scales are discussed in terms of the structural dynamics of the surrounding solvent and it is found that the longest time scale (≈10 ps) most likely corresponds to solvent exchange between the first and second solvation shell, in agreement with interpretations from nuclear magnetic resonance measurements.

  8. Combustion of butanol isomers - A detailed molecular beam mass spectrometry investigation of their flame chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Osswald, Patrick; Gueldenberg, Hanna; Kohse-Hoeinghaus, Katharina [Department of Chemistry, Bielefeld University (Germany); Yang, Bin [National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, Anhui (China); Department of Aerospace and Mechanical Engineering, University of Southern California, Los Angeles, CA (United States); Yuan, Tao; Qi, Fei [National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, Anhui (China)


    The combustion chemistry of the four butanol isomers, 1-, 2-, iso- and tert-butanol was studied in flat, premixed, laminar low-pressure (40 mbar) flames of the respective alcohols. Fuel-rich ({phi} = 1.7) butanol-oxygen-(25%)argon flames were investigated using different molecular beam mass spectrometry (MBMS) techniques. Quantitative mole fraction profiles are reported as a function of burner distance. In total, 57 chemical compounds, including radical and isomeric species, have been unambiguously assigned and detected quantitatively in each flame using a combination of vacuum ultraviolet (VUV) photoionization (PI) and electron ionization (EI) MBMS. Synchrotron-based PI-MBMS allowed to separate isomeric combustion intermediates according to their different ionization thresholds. Complementary measurements in the same flames with a high mass-resolution EI-MBMS system provided the exact elementary composition of the involved species. Resulting mole fraction profiles from both instruments are generally in good quantitative agreement. In these flames of the four butanol isomers, temperature, measured by laser-induced fluorescence (LIF) of seeded nitric oxide, and major species profiles are strikingly similar, indicating seemingly analog global combustion behavior. However, significant variations in the intermediate species pool are observed between the fuels and discussed with respect to fuel-specific destruction pathways. As a consequence, different, fuel-specific pollutant emissions may be expected, by both their chemical nature and concentrations. The results reported here are the first of their kind from premixed isomeric butanol flames and are thought to be valuable for improving existing kinetic combustion models. (author)

  9. Molecular polymorphism: microwave spectra, equilibrium structures, and an astronomical investigation of the HNCS isomeric family. (United States)

    McGuire, Brett A; Martin-Drumel, Marie-Aline; Thorwirth, Sven; Brünken, Sandra; Lattanzi, Valerio; Neill, Justin L; Spezzano, Silvia; Yu, Zhenhong; Zaleski, Daniel P; Remijan, Anthony J; Pate, Brooks H; McCarthy, Michael C


    The rotational spectra of thioisocyanic acid (HNCS), and its three energetic isomers (HSCN, HCNS, and HSNC) have been observed at high spectral resolution by a combination of chirped-pulse and Fabry-Pérot Fourier-transform microwave spectroscopy between 6 and 40 GHz in a pulsed-jet discharge expansion. Two isomers, thiofulminic acid (HCNS) and isothiofulminic acid (HSNC), calculated here to be 35-37 kcal mol(-1) less stable than the ground state isomer HNCS, have been detected for the first time. Precise rotational, centrifugal distortion, and nitrogen hyperfine coupling constants have been determined for the normal and rare isotopic species of both molecules; all are in good agreement with theoretical predictions obtained at the coupled cluster level of theory. On the basis of isotopic spectroscopy, precise molecular structures have been derived for all four isomers by correcting experimental rotational constants for the effects of rotation-vibration interaction calculated theoretically. Formation and isomerization pathways have also been investigated; the high abundance of HSCN relative to ground state HNCS, and the detection of strong lines of SH using CH3CN and H2S, suggest that HSCN is preferentially produced by the radical-radical reaction HS + CN. A radio astronomical search for HSCN and its isomers has been undertaken toward the high-mass star-forming region Sgr B2(N) in the Galactic Center with the 100 m Green Bank Telescope. While we find clear evidence for HSCN, only a tentative detection of HNCS is proposed, and there is no indication of HCNS or HSNC at the same rms noise level. HSCN, and tentatively HNCS, displays clear deviations from a single-excitation temperature model, suggesting weak masing may be occurring in some transitions in this source.

  10. Visualization of molecular interactions using bimolecular fluorescence complementation analysis: characteristics of protein fragment complementation. (United States)

    Kerppola, Tom K


    Investigations of the molecular processes that sustain life must include studies of these processes in their normal cellular environment. The bimolecular fluorescence complementation (BiFC) assay provides an approach for the visualization of protein interactions and modifications in living cells. This assay is based on the facilitated association of complementary fragments of a fluorescent protein that are fused to interaction partners. Complex formation by the interaction partners tethers the fluorescent protein fragments in proximity to each other, which can facilitate their association. The BiFC assay enables sensitive visualization of protein complexes with high spatial resolution. The temporal resolution of BiFC analysis is limited by the time required for fluorophore formation, as well as the stabilization of complexes by association of the fluorescent protein fragments. Many modifications and enhancements to the BiFC assay have been developed. The multicolor BiFC assay enables simultaneous visualization of multiple protein complexes in the same cell, and can be used to investigate competition among mutually exclusive interaction partners for complex formation in cells. The ubiquitin-mediated fluorescence complementation (UbFC) assay enables visualization of covalent ubiquitin family peptide conjugation to substrate proteins in cells. The BiFC assay can also be used to visualize protein binding to specific chromatin domains, as well as other molecular scaffolds in cells. BiFC analysis therefore provides a powerful approach for the visualization of a variety of processes that affect molecular proximity in living cells. The visualization of macromolecular interactions and modifications is of great importance owing to the central roles of proteins, nucleic acids and other macromolecular complexes in the regulation of cellular functions. This tutorial review describes the BiFC assay, and discusses the advantages and disadvantages of this experimental approach

  11. Adsorption and diffusion of alkanes in CuBTC crystals investigated using infra-red microscopy and molecular simulations

    NARCIS (Netherlands)

    Chmelik, C.; Kärger, J.; Wiebcke, M.; Caro, J.; van Baten, J.M.; Krishna, R.


    The adsorption and intra-crystalline diffusion of n-butane (nC4), iso-butane (iC4), 2-methylbutane (2MB), and 2,2-dimethylpropane (neoP) in CuBTC (Cu-3(BTC)(2) where BTC = benzene-1,3,5-tricarboxylate) has been investigated using infrared microscopy (IRM), combined with molecular simulations. Both e

  12. Development of molecular methods for detection and epidemiological investigation of HIV-1, HIV-2, and HTLV-I/II infections

    NARCIS (Netherlands)

    Meijer A; Borleffs JCC; Roosendaal G; Loon AM van; VIR; AZU; Van Creveld Kliniek Utrecht


    The work presented here was initiated to determine the possibilities of molecular methods for the detection and epidemiological investigation of HIV and HTLV infections. We present the results of a literature research and describe the development and partial evaluation of a new PCR method for the am

  13. Structure of the antimicrobial beta-hairpin peptide protegrin-1 in a DLPC lipid bilayer investigated by molecular dynamics simulation

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Kaznessis, Yiannis N


    All atom molecular dynamics simulations of the 18-residue beta-hairpin antimicrobial peptide protegrin-1 (PG-1, RGGRLCYCRRRFCVCVGR-NH(2)) in a fully hydrated dilauroylphosphatidylcholine (DLPC) lipid bilayer have been implemented. The goal of the reported work is to investigate the structure of t...

  14. Symmetry-resolved spectroscopy by detection of a metastable hydrogen atom for investigating the doubly excited states of molecular hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Odagiri, Takeshi; Kumagai, Yoshiaki; Tanabe, Takehiko; Nakano, Motoyoshi; Kouchi, Noriyuki [Department of Chemistry, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8551 (Japan); Suzuki, Isao H, E-mail: [Photon Factory, IMSS, KEK, Tsukuba, Ibaraki 305-0801 (Japan)


    Symmetry-resolved spectroscopy for investigating the doubly excited states of molecular hydrogen has been newly developed, where a metastable hydrogen atom dissociating in a direction parallel and perpendicular to the electric vector of the linearly polarized incident light is detected.

  15. Molecular investigation of a fungemia outbreak due to Candida parapsilosis in an intensive care unit

    Directory of Open Access Journals (Sweden)

    Murat Dizbay


    Full Text Available We investigated a nosocomial cluster of four Candida parapsilosis fungemia episodes that occurred in a neurological intensive care unit over a two-week period. The four infected patients had received parenteral nutrition through central lines, and all four had catheter-related candidemia. All of the isolates were susceptible to all of the antifungals tested, including amphotericin B, fluconazole, voriconazole, and caspofungin. They had strictly related fingerprints, based on randomly amplified polymorphic DNA analysis. Additional DNA sequencing data revealed that they were same strain. Although no isolate of Candida parapsilosis was recovered from other clinical, surveillance, or environmental samples, nosocomial spread of this yeast ceased, following the reinforcement of infection-control measures. Candida parapsilosis may require an intravascular foreign body to cause fungemia, but this outbreak shows that it can be transmitted nosocomially and can cause epidemics.

  16. The origin of the cooperativity in the streptavidin-biotin system: A computational investigation through molecular dynamics simulations. (United States)

    Liu, Fengjiao; Zhang, John Z H; Mei, Ye


    Previous experimental study measuring the binding affinities of biotin to the wild type streptavidin (WT) and three mutants (S45A, D128A and S45A/D128A double mutant) has shown that the loss of binding affinity from the double mutation is larger than the direct sum of those from two single mutations. The origin of this cooperativity has been investigated in this work through molecular dynamics simulations and the end-state free energy method using the polarized protein-specific charge. The results show that this cooperativity comes from both the enthalpy and entropy contributions. The former contribution mainly comes from the alternations of solvation free energy. Decomposition analysis shows that the mutated residues nearly have no contributions to the cooperativity. Instead, N49 and S88, which are located at the entry of the binding pocket and interact with the carboxyl group of biotin, make the dominant contribution among all the residues in the first binding shell around biotin.

  17. Molecular characterization of two microalgal strains in Egypt and investigation of the antimicrobial activity of their extracts

    Directory of Open Access Journals (Sweden)

    El Semary, NA.


    Full Text Available The emergence of new pathogens and the increasing drug-resistance of recognized ones pose a difficult challenge. One way that this challenge is being addressed is through the discovery of new cost-effective drug resources in the form of bioactive compounds. Algae represent a promising source of bioactive compounds in this regard. In the present research, we used molecular and phylogenetic analysis to isolate and identify two microalgal strains. We found that one strain belonged to the phylum chrysophyta and the other to the cyanobacteria. We also investigated the antimicrobial activity of some of the lipophilic extracts of the two microalgal strains. Several fractions showed high individual antimicrobial bioactivity against multidrug-resistant Salmonella sp., Citrobacter sp., Aspergillus niger and Aspergillus flavus. Fraction III from Poterioochromonas malhamensis showed the highest level of activity against two multidrug-resistant bacterial pathogens. The inhibition zone diameter was 1.4 cm for Salmonella and 1.4 cm for Citrobacter. Meanwhile, another lipophilic fraction from the cyanobacterium Synechocystis salina showed broad-spectrum bioactivity (inhibition zone diameter of 0.9 cm for Aspergillus niger, 1 cm for Citrobacter and 0.9 cm for Salmonella. One lipophilic fraction from Aphanizomenon showed antifungal bioactivity against Aspergillus niger and Aspergillus flavus, where the inhibition zone diameter was 1.1 cm and 1.0 cm, respectively. The study highlights the antimicrobial bioactivity of extracts from local microalgae and emphasizes the importance of carrying out screening programs for those microorganisms.

  18. Synthesis, vibrational spectroscopic investigations, molecular docking, antibacterial and antimicrobial studies of 5-ethylsulphonyl-2-(p-aminophenyl)benzoxazole (United States)

    Parveen S, Shana; Al-Alshaikh, Monirah A.; Panicker, C. Yohannan; El-Emam, Ali A.; Arisoy, Mustafa; Temiz-Arpaci, Ozlem; Van Alsenoy, C.


    The optimized molecular structure, vibrational wavenumbers, corresponding vibrational assignments of 5-ethylsulphonyl-2-(p-aminophenyl)benzoxazole have been investigated experimentally and theoretically based on density functional theory. Synthesis and antibacterial and antimicrobial activities of the title compound were reported. The FT-IR and FT-Raman spectra were recorded in solid phase and the experimental bands were assigned and characterized on the basis of potential energy distribution. The HOMO and LUMO energies show that the charge transfer occur within the molecule. Stability arising from hyperconjugative interactions and charge delocalization were analysed using natural bond orbital analysis. Binding free energy of -9.8 kcal/mol as predicted by docking studies suggests good binding affinity and the inhibitor forms a stable complex with FAK as is evident from the ligand-receptor interactions. The title compound possesses lower activity against Candida albicans with MIC value of 64 μg/ml than the compared reference drugs as fluconazole and amphotericin B and possesses the same activity with value of 64 μg/ml against Candida krusei as the reference drug, fluconazole.

  19. Investigating the composition of organic aerosol resulting from cyclohexene ozonolysis: low molecular weight and heterogeneous reaction products

    Directory of Open Access Journals (Sweden)

    J. F. Hamilton


    Full Text Available The composition of organic aerosol formed from the gas phase ozonolysis of cyclohexene has been investigated in a smog chamber experiment. Comprehensive gas chromatography with time of flight mass spectrometric detection was used to determine that dicarboxylic acids and corresponding cyclic anhydrides dominated the small gas phase reaction products found in aerosol sampled during the first hour after initial aerosol formation. Structural analysis of larger more polar molecules was performed using liquid chromatography with ion trap tandem mass spectrometry. This indicated that the majority of identified organic mass was in dimer form, built up from combinations of the most abundant small acid molecules, with frequent indication of the inclusion of adipic acid. Trimers and tetramers potentially formed via similar acid combinations were also observed in lower abundances. Tandem mass spectral data indicated dimers with either acid anhydride or ester functionalities as the linkage between monomers. High-resolution mass spectrometry identified the molecular formulae of the most abundant dimer species to be C10H16O6, C11H18O6, C10H14O8 and C11H16O8 and could be used in some cases to reduce uncertainty in exact chemical structure determination by tandem MS.

  20. The origin of the cooperativity in the streptavidin-biotin system: A computational investigation through molecular dynamics simulations (United States)

    Liu, Fengjiao; Zhang, John Z. H.; Mei, Ye


    Previous experimental study measuring the binding affinities of biotin to the wild type streptavidin (WT) and three mutants (S45A, D128A and S45A/D128A double mutant) has shown that the loss of binding affinity from the double mutation is larger than the direct sum of those from two single mutations. The origin of this cooperativity has been investigated in this work through molecular dynamics simulations and the end-state free energy method using the polarized protein-specific charge. The results show that this cooperativity comes from both the enthalpy and entropy contributions. The former contribution mainly comes from the alternations of solvation free energy. Decomposition analysis shows that the mutated residues nearly have no contributions to the cooperativity. Instead, N49 and S88, which are located at the entry of the binding pocket and interact with the carboxyl group of biotin, make the dominant contribution among all the residues in the first binding shell around biotin.

  1. Molecular Modeling and Structural Analysis of Arylesterase of Ancylostoma Duodenale (United States)

    Panda, Subhamay; Panda, Santamay; Kumari, Leena


    Parasitic worm infection of humans is one of the most commonly prevalent helminth infection that has imposed great impact on society and public health in the developing world. The two species of hookworm, namely Ancylostoma duodenale and Necator americanus may be primarily responsible for causing parasitic infections in human beings. The highly prevalent areas for Ancylostoma duodenale infections are mainly India, Middle East, Australia, northern Africa and other parts of the world. The serum arylesterases/paraoxonases are family of enzymes that is involved in the hydrolysis of a number of organophosphorus insecticides to the nontoxic products. The participation of the enzymes in the breakdown of a variety of organophosphate substrates that is generally made up of paraoxon and numerous aromatic carboxylic acid esters (e.g., phenyl acetate), and hence combats the toxic effect of organophosphates. The aim of the present investigation is to evaluate the arylesterases of Ancylostoma duodenale giving special importance to structure generation, validation of the generated models, distribution of secondary structural elements and positive charge distribution over the structure. By the implementation of comparative modeling approach we propose the first molecular model structure of arylesterases of Ancylostoma duodenale. PMID:27642240

  2. Molecular dynamics analysis on buckling of defective carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Kulathunga, D D T K; Ang, K K [Department of Civil Engineering, National University of Singapore (Singapore); Reddy, J N, E-mail: [Department of Mechanical Engineering, Texas A and M University, College Station, TX 77843-3123 (United States)


    Owing to their remarkable mechanical properties, carbon nanotubes have been employed in many diverse areas of applications. However, similar to any of the many man-made materials used today, carbon nanotubes (CNTs) are also susceptible to various kinds of defects. Understanding the effect of defects on the mechanical properties and behavior of CNTs is essential in the design of nanotube-based devices and composites. It has been found in various past studies that these defects can considerably affect the tensile strength and fracture of CNTs. Comprehensive studies on the effect of defects on the buckling and vibration of nanotubes is however lacking in the literature. In this paper, the effects of various configurations of atomic vacancy defects, on axial buckling of single-walled carbon nanotubes (SWCNTs), in different thermal environments, is investigated using molecular dynamics simulations (MDS), based on a COMPASS force field. Our findings revealed that even a single missing atom can cause a significant reduction in the critical buckling strain and load of SWCNTs. In general, increasing the number of missing atoms, asymmetry of vacancy configurations and asymmetric distribution of vacancy clusters seemed to lead to higher deterioration in buckling properties. Further, SWCNTs with a single vacancy cluster, compared to SWCNTs with two or more vacancy clusters having the same number of missing atoms, appeared to cause higher deterioration of buckling properties. However, exceptions from the above mentioned trends could be expected due to chemical instabilities of defects. Temperature appeared to have less effect on defective CNTs compared to pristine CNTs.

  3. Investigation of mechanism and molecular epidemiology of linezolid-resistant Enterococcus faecalis in China. (United States)

    Wang, Lipeng; He, Yunyan; Xia, Yun; Wang, Huijuan; Liang, Shumei


    Enterococcus is a major cause of important nosocomial infections. Linezolid, the first member of an entirely new class of antibiotics (oxazolidinones), is effective against serious infections caused by Enterococcus. However, resistance to linezolid has been discovered throughout the world rapidly. From 2011 to 2013, nine linezolid-resistant E. faecalis isolates were collected and the possible mechanisms of linezolid resistance, including mutations in domain V of 23S rRNA genes and in ribosomal proteins L3 and L4, and the multiresistance gene cfr, were investigated. Furthermore, an epidemiological survey of the nine linezolid-resistant E. faecalis isolates was performed by pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and DiversiLab. The three methods were compared to evaluate their merits and demerits, respectively. We failed to find the resistance mechanisms that have been revealed in recent years by PCR and sequencing analysis in the linezolid-resistant E. faecalis. Epidemiological investigation suggested that a small-scale outbreak of linezolid-resistant E. faecalis emerged in neurosurgery ICU from March to May of 2013. DiversiLab was a reliable typing tool and a suitable alternative to PFGE because it was as discriminatory as PFGE and better than MLST.

  4. Sex Change in Clownfish: Molecular Insights from Transcriptome Analysis

    KAUST Repository

    Casas, Laura


    Sequential hermaphroditism is a unique reproductive strategy among teleosts that is displayed mainly in fish species living in the coral reef environment. The reproductive biology of hermaphrodites has long been intriguing; however, very little is known about the molecular pathways underlying their sex change. Here, we provide the first de novo transcriptome analyses of a hermaphrodite teleost´s undergoing sex change in its natural environment. Our study has examined relative gene expression across multiple groups—rather than just two contrasting conditions— and has allowed us to explore the differential expression patterns throughout the whole process. Our analysis has highlighted the rapid and complex genomic response of the brain associated with sex change, which is subsequently transmitted to the gonads, identifying a large number of candidate genes, some well-known and some novel, involved in the process. The present study provides strong evidence of the importance of the sex steroidogenic machinery during sex change in clownfish, with the aromatase gene playing a central role, both in the brain and the gonad. This work constitutes the first genome-wide study in a social sex-changing species and provides insights into the genetic mechanism governing social sex change and gonadal restructuring in protandrous hermaphrodites.

  5. [Phenotype analysis and the molecular mechanism of enamel hypoplasia]. (United States)

    Lv, Ping; Gao, Xue-jun


    Enamel hypoplasia is a surface defect of the tooth crown caused by a disturbance of enamel matrix secretion. Enamel hypoplasia may be inherited, or result from illness, malnutrition, trauma, or high concentrations of fluorides or strontium in the drinking water or food. Different types of enamel hypoplasia have been distinguished, such as pit-type, plane-type, and linear enamel hypoplasia. Hypoplasia has been related to the intensity and duration of stress events, the number of affected ameloblasts, and their position along the forming tooth crown. Amelogenesis imperfecta (AI) is a heterogeneous group of inherited defects in dental enamel formation, most teeth are affected in both the primary and permanent dentition. The malformed enamel can be unusually thin, soft, rough and stained. The strict definition of AI includes only those cases where enamel defects occur in the absence of other symptoms. Currently, there are seven candidate genes for AI: amelogenin, enamelin, ameloblastin, tuftelin, distal-less homeobox 3, enamelysin, and kallikrein 4. Since the enamel is formed according to a strict chronological sequence, and once formed, undergoes no repair or regeneration. Then the analysis the phenotype of enamel hypoplasia can provide insights of the severity of inherited or environmental stress and the molecular mechanism during the period of enamel formation.

  6. Molecular analysis of Korean isolate of barley yellow mosaic virus. (United States)

    Lee, Kui Jae; Choi, Min Kyung; Lee, Wang Hyu; Rajkumar, Mani


    The complete sequences of both RNAs of an isolate of barley yellow mosaic virus (BaYMV) from Haenam, Korea, were determined. RNA1 is 7639 nucleotides long [excluding the 3'-poly(A)], and codes for a 270 kDa polyprotein of 2411 amino acids which contains the capsid protein (CP) at the C terminus and seven putative non-structural proteins. RNA2 is 3582 nucleotides long and codes for a polyprotein of 890 amino acids, which contains a 28 kDa putative proteinase (P1) and a 73 kDa polypeptide (P2). The whole sequences of Korean isolate (BaYMV-K) closely resembled those of an isolate from Japan (BaYMV-J) (99.6 identical nucleotides for RNA1; 99.4 for RNA2) and china (BaYMV-C) (96.7 and 96.2%, respectively) than from Germany (BaYMV-G) (93.6 and 90.4%, respectively). The greatest differences between the BaYMV-K and BaYMV-J isolates were in the 3'-NCRs of RNA1 and 5' NCRs of RNA2 and there were also some other regions of difference in Nib Pro (RNA1) and P1 (RNA2). Further, the phylogenetic analysis of CP region showed that Asian and European isolates formed distinct clusters. However, molecular variations between isolates could not be linked to earlier results showing differences in cultivar response.

  7. Molecular analysis of mutants of the Neurospora adenylosuccinate synthetase locus

    Indian Academy of Sciences (India)

    A. Wiest; A. J. McCarthy; R. Schnittker; K. McCluskey


    The ad-8 gene of Neurospora crassa, in addition to being used for the study of purine biology, has been extensively studied as a model for gene structure, mutagenesis and intralocus recombination. Because of this there is an extensive collection of well-characterized N. crassa ad-8 mutants in the Fungal Genetics Stock Center collection. Among these are spontaneous mutants and mutants induced with X-ray, UV or chemical mutagens. The specific lesions in these mutants have been genetically mapped at high resolution. We have sequenced the ad-8 locus from 13 of these mutants and identified the molecular nature of the mutation in each strain. We compare the historical fine-structure map to the DNA and amino acid sequence of each allele. The placement of the individual lesions in the fine-structure map was more accurate at the 5′ end of the gene and no mutants were identified in the 3′ untranslated region of this gene. We additionally analysed ad-8+ alleles in 18 N. crassa strains subjected to whole-genome sequence analysis and describe the variability among Neurospora strains and among fungi and other organisms.

  8. Sex Change in Clownfish: Molecular Insights from Transcriptome Analysis (United States)

    Casas, Laura; Saborido-Rey, Fran; Ryu, Taewoo; Michell, Craig; Ravasi, Timothy; Irigoien, Xabier


    Sequential hermaphroditism is a unique reproductive strategy among teleosts that is displayed mainly in fish species living in the coral reef environment. The reproductive biology of hermaphrodites has long been intriguing; however, very little is known about the molecular pathways underlying their sex change. Here, we provide the first de novo transcriptome analyses of a hermaphrodite teleost´s undergoing sex change in its natural environment. Our study has examined relative gene expression across multiple groups—rather than just two contrasting conditions— and has allowed us to explore the differential expression patterns throughout the whole process. Our analysis has highlighted the rapid and complex genomic response of the brain associated with sex change, which is subsequently transmitted to the gonads, identifying a large number of candidate genes, some well-known and some novel, involved in the process. The present study provides strong evidence of the importance of the sex steroidogenic machinery during sex change in clownfish, with the aromatase gene playing a central role, both in the brain and the gonad. This work constitutes the first genome-wide study in a social sex-changing species and provides insights into the genetic mechanism governing social sex change and gonadal restructuring in protandrous hermaphrodites. PMID:27748421

  9. Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

    Directory of Open Access Journals (Sweden)

    Jose A Santiago

    Full Text Available BACKGROUND: Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. METHODS AND FINDINGS: Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP, previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS and the Prognostic Biomarker Study (PROBE, revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients. CONCLUSIONS: These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers

  10. HCN hyperfine ratio analysis of massive molecular clumps (United States)

    Schap, W. J.; Barnes, P. J.; Ordoñez, A.; Ginsburg, A.; Yonekura, Y.; Fukui, Y.


    We report a new analysis protocol for HCN hyperfine data, based on the PYSPECKIT package, and results of using this new protocol to analyse a sample area of seven massive molecular clumps from the Census of High- and Medium-mass Protostars (CHaMP) survey, in order to derive maps of column density for this species. There is a strong correlation between the HCN integrated intensity, IHCN, and previously reported I_HCO+ in the clumps, but I_N_{2H+} is not well correlated with either of these other two 'dense gas tracers'. The four fitted parameters from PYSPECKIT in this region fall in the range of VLSR = 8-10 km s-1, σV = 1.2-2.2 km s-1, Tex = 4-15 K, and τ = 0.2-2.5. These parameters allow us to derive a column density map of these clouds, without limiting assumptions about the excitation or opacity. A more traditional (linear) method of converting IHCN to total mass column gives much lower clump masses than our results based on the hyperfine analysis. This is primarily due to areas in the sample region of low I, low Tex, and high τ. We conclude that there may be more dense gas in these massive clumps not engaged in massive star formation than previously recognized. If this result holds for other clouds in the CHaMP sample, it would have dramatic consequences for the calibration of the Kennicutt-Schmidt star formation laws, including a large increase in the gas depletion time-scale in such regions.

  11. Molecular electrostatic potential analysis of non-covalent complexes

    Indian Academy of Sciences (India)



    Ab initio MP4/Aug-cc-pvDZ//MP2/6-311++g(d,p) level interaction energy (Eint) and molecular electrostatic potential analysis (MESP) of a large variety of non-covalent intermolecular complexes, viz. tetrel, chalcogen, pnicogen, halogen, hydrogen, dihydrogen and lithium bonded complexes have been reported. The electronic changes associated with the non-covalent complex formation is monitored in terms of MESP minimum (Vmin) in the free and complexed states of the donor and acceptor molecules as well as in terms ofMESP at the donor and acceptor atoms (Vn) of the free monomers and complexes. The change in Vmin or Vn on the donor molecule (ΔVmin(D) or ΔVn(D)) during complex formation is proportional to its electron donating ability while such a change on the acceptor molecule (ΔVmin(A) or ΔVn(A)) is proportional to its electron accepting ability. Further, the quantities ΔΔVmin = ΔVmin(D) −ΔVmin(A) and ΔΔVn = ΔVn(D) −ΔVn(A) have shown strong linear correlations with Eint of the complex (Eint values fall in the range 0.7 to 46.2 kcal/mol for 54 complexes) and suggest that the intermolecular non-covalent interactions in a wide variety of systems can be monitored and assessed in terms of change in MESP due to complex formation in the gas phase. With the incorporation of solvent effect in the calculation, charged systems showed significant deviations from the linear correlation. The MESP based analysis proposes that the large variety of intermolecular non-covalent complexes considered in this study can be grouped under the general category of electron donor-acceptor (eDA) complexes

  12. QTL Analysis for Plant Height with Molecular Markers in Maize

    Institute of Scientific and Technical Information of China (English)

    YAN Jian-bing; TANG Hua; HUANG Yi-qin; SHI Yong-gang; ZHENG Yong-lian; LI Jian-sheng


    Plant height has become one of important agronomic traits with the increase of planting densityrecently and the rapid developments of molecular markers have provided powerful tools to localize importantagronomic QTL at the genomic level. The purposes of this investigation are to map plant height QTL with mo-lecular markers and to analyze their genetic effects in maize. An F2:3 population from an elite combination(Zong3 × 87-1) was utilized for evaluating plant height in two locations, Wuhan and Xiangfan, with a ran-domized complete block design. The mapping population included 266 F2:3 family lines. A genetic linkagemap, containing 150 SSR and 24 RFLP markers, was constructed, spanning a total of 2 531.6 cm with an av-erage interval of 14.5 cm. Totally 10 QTL affecting plant height were mapped on six different chromosomeswith the composite interval mapping. Seven of 10 QTL were detected in two locations. The contributions tophenotypic variations for the single QTL varied between 5.3 and 17.1%. Additive, partial dominance, domi-nance, and overdominance actions existed among all detected QTL affecting plant heights. A large number ofdigenic interactions for plant height were detected by two-way analyses of variance. 107 and 98 two-locus com-binations were found to be significant at a 0.01 probability level in two locations respectively. 23 of them weresimultaneously detected in both locations. They accounted for phenotypic variations of 4.5 -11%. It was no-ticed that a locus, umc1122, had digenic interactive effects with other four different loci for plant height,which distributed on three chromosomes. A few of plant height QTL was involved in significant digenic inter-actions, but most significant interactions occurred between markers that are not adjacent to mapped QTL.These results demonstrated that epistatic interactions might play an equal importance role as the single-locuseffects in determining plant height of maize.

  13. Gene hunting : molecular analysis of the chicken genome

    NARCIS (Netherlands)

    Crooijmans, R.P.M.A.


    This dissertation describes the development of molecular tools to identify genes that are involved in production and health traits in poultry. To unravel the chicken genome, fluorescent molecular markers (microsatellite markers) were developed and optimized to perform high throughput screening of re

  14. Investigation of molecular interactions in the complex formation of tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid

    Institute of Scientific and Technical Information of China (English)


    The molecular interactions in the complex formation of two tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid are investigated. The complex formation with a 1:1 stoichiometry between tartaric acid derivatives and D2EHPA can be obtained through UV-Vis titration, NMR chemical shifts and molecular dynamic simulations. Furthermore, the differences of the two complexes on the binding constants and strength of hydrogen bonds can also be determined. Such research will ideally provide insight into ways of regulating the complex forming properties of tartaric acid derivatives for composing or syn- thesizing new chiral resolving agents.

  15. Investigation of molecular interactions in the complex formation of tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid

    Institute of Scientific and Technical Information of China (English)

    TAN Bin; ZHAI Zheng; LUO GuangSheng; WANG JiaDing


    The molecular interactions in the complex formation of two tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid are investigated. The complex formation with a 1:1 stoichiometry between tartaric acid derivatives and D2EHPA can be obtained through UV-Vis titration, NMR chemical shifts and molecular dynamic simulations. Furthermore, the differences of the two complexes on the binding constants and strength of hydrogen bonds can also be determined. Such research will ideally provide insight into ways of regulating the complex forming properties of tartaric acid derivatives for composing or syn-thesizing new chiral resolving agents.

  16. A systematic investigation of the preparation and properties of composite carbon molecular sieves containing inorganic oxides (United States)

    Foley, Henry C.


    The objective of this research is to define the methodology for the preparation and characterization of new carbon-based molecular sieves with composite structures. Carbon molecular sieves have found increasing application in the field of separation and purification of gases. These materials are relatively easy to prepare and their surfaces can be modified to some extent. It is expected that by combining inorganic oxides with the carbonaceous structure one can begin to design composite materials with a wider range of possible chemical and physical properties. In this way, the IOM-CMS materials may confer distinct advantages over pure carbon molecular sieves, not just for separation, but also for catalysis. The most recent results in the design and characterization of these IOM-CMS materials are reviewed and summarized. Directions for further research are also presented.

  17. Circulating tumor cells (CTCs) in breast cancer: a diagnostic tool for prognosis and molecular analysis

    Institute of Scientific and Technical Information of China (English)

    Xiaoshen Dong; R.Katherine Alpaugh; Massimo Cristofanilli


    Metastatic breast cancer (MBC) is characterized by a combination of tumor growth,proliferation and metastatic progression and is typically managed with palliative intent.The benefit of standard systemic therapies is relatively limited and the disease is considered incurable suggesting the need to investigate the biological drivers of the various phases of the metastatic process in order to improve the selection of molecularly driven therapies.The detection,enumeration and molecular analysis of circulating tumor cells (CTCs) provide an intriguing opportunity to advance this knowledge.CTCs enumerated by the Food and Drugs Administration-cleared CellSearchTM system are an independent prognostic factor of progression-free survival (PFS) and overall survival (OS) in MBC patients.Several published papers demonstrated the poor prognosis for MBC patients that presented basal CTC count ≥5 in 7.5 mL of blood.Therefore,the enumeration of CTCs during treatment for MBC provides a tool with the ability to predict progression of disease earlier than standard timing of anatomical assessment using conventional radiological tests.During the metastatic process cancer cells exhibit morphological and phenotypic plasticity undergoing epithelial-mesenchymal transition (EMT).This important phenomenon is associated with down regulation of epithelial marker (e.g.,EpCAM) with potential limitations in the applicability of current CTCs enrichment methods.Such observations translated in a number of investigations aimed at improving our capabilities to enumerate and perform molecular characterization of CTCs.Theoretically,the phenotypic analysis of CTCs can represent a "liquid" biopsy of breast tumor that is able to identify a new potential target against the metastatic disease and advance the development and monitoring of personalized therapies.

  18. First genome analysis and molecular characterization of Chickpea chlorotic dwarf virus Egyptian isolate infecting squash. (United States)

    Fahmy, Inas Farouk; Taha, Omnia; El-Ashry, Abdel Nasser


    This study aims to identifying and characterizing some molecular properties of geminiviruses co-infection in squash field crop cultivated in Egypt. Squash crops observed to be heavily infected with several insect vectors, also severe chlorosis and stunting was observed. Electron microscopic analysis has revealed geminate capsid particles which indicate the infection of Geminiviruses, especially SqLCV which represent an economic problem to squash filed crop in Egypt. We have investigated possible mixed infections with different plant viruses associated with chlorotic stunt diseases and or other genus groups of geminiviruses. The main objective of this study is to investigate the recombination events, possible recombinants and variants among these genera in the same family differing in vector transmission. This is the first report of the molecular characterization, phylogenetic analysis and putative recombination events of the full length genome of the Chickpea Chlorotic Dwarf Mastrevirus in Egypt. And the first report of co-infection with another begomovirus infecting squash plants. A full length clone of both viruses were isolated and characterized at the molecular level. The complete nucleotide sequence of DNA-A was determined (2,572 bp) and submitted to the genbank under accession no. KF692356. The isolate from Egypt has about 97.8 % homology with the Chickpea chlorotic dwarf virus (CpCDV) isolate from Syria DNA-A isolate FR687959, a 83.2 % homology with the Sudan isolate AM933134 and a 82.7 % homology with Pakistan isolate FR687960. To best of our knowledge this is the first report of complete genome of CpCDV that infect squash plants in Egypt and worldwide.

  19. Classical and quantum analysis of a hetero-triatomic molecular Bose-Einstein condensate model

    Energy Technology Data Exchange (ETDEWEB)

    Tonel, A.P. [CCET da Universidade Federal do Pampa/Unipampa, Bag´e, RS (Brazil); Kuhn, C.C.N.; Foerster, A. [Instituto de F´ısica da UFRGS, Porto Alegre, RS (Brazil); Santos, G. [Departamento de Físi a - UFS, São Cristóvão, SE (Brazil); Roditi, I.; Santos, Z.V.T. [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil)


    We investigate an integrable Hamiltonian modelling a hetero-triatomic-molecular Bose-Einstein condensate. This model describes a mixture of two species of atoms in different proportions, which can combine to form a triatomic molecule. Beginning with a classical analysis, we determine the fixed points of the system. Bifurcations of these points separate the parameter space into different regions. Three distinct scenarios are found, varying with the atomic population imbalance. This result suggests the ground state properties of the quantum model exhibits a sensitivity on the atomic population imbalance, which is confirmed by a quantum analysis using different approaches, such as the ground-state expectation values, the behaviour of the quantum dynamics, the energy gap and the ground state fidelity. (author)

  20. HMW glutenin subunits in multiploid Aegilops species: composition analysis and molecular cloning of coding sequences

    Institute of Scientific and Technical Information of China (English)


    The Aegilops genus contains species closely related to wheat. Incommon with wheat, Aegilops species accumulate high molecular weight (HMW) glutenin subunits in their endospermic tissue. In this study, we investigated the composition of HMW glutenin subunits in four multiploid Aegilops species using SDS-PAGE analysis. Furthermore, by working with Ae. ventricosa, we established an efficient genomic PCR condition for simultaneous amplification of DNA sequences coding for either x-ory-type HMW glutenin subunits from polyploid Aegilops species. Using the genomic PCR condition, we amplified and subsequently cloned two DNA fragments that may code for HMW glutenin subunits in Ae. ventricosa. Based on an analysis of the deduced amino acid sequences, we concluded that the two cloned sequences encode one x- and one y-type of HMW glutenin subunit, respectively.

  1. Ampelographic Characteristics and Molecular Investigation of Azerbaijani Local Grape Varieties by Microsatellites

    Directory of Open Access Journals (Sweden)



    Full Text Available The article aims at introducing of some local grapevine varieties cultivated in different areas of Azerbaijan. The cultivars are grown in the ampelographic collection of the Azerbaijani Scientific Research Institute of Viticulture and Wine-making. The description of their ampelographic specifications was based on the OIV list. Comparing cultivars, it has been found that, although there are similarities in various descriptor traits, most of the characteristics are distinctive of specific cultivars. A considerable polymorphism was found concerning the botanical features of leaves, clusters, berries, as well as considering some biological and technological characteristics. In more details, these genotypes differ each other by the morphological features of leaves; the shape, size and structure of clusters; the shape, color and flavor of berries; the productivity indices; the resistance to pests and diseases; the duration of their vegetative period; the sugar and acid contents; and the number of seeds in the berry. This study was carried out on nine grape cultivars grown in region Garabagh, Nakhchyvan and Absheron in 2008- 2012. Analyses of the ampelographic features of the studied grape varieties showed that the genotypes considerably differ by their main morphological, biological and technological characteristics. 42 Azerbaijani grape varieties (including above mentioned have been investigated comparatively with Caucasian countries` and European grape varieties. Based on the descriptive statistics Azerbaijani samples appeared having the highest genetic diversity. The first two coordinates of the PCoA differentiated the samples into two main clusters, despite the presence of overlapping zones: i the group clusterizing the most part of cultivars from Azerbaijan; ii the other Caucasian and European varieties. STRUCTURE analysis revealed the optimal K value equal to 3, highlighting 3 groups: i Central European group; ii an admixed group, containing

  2. Genetic diversity in cultivated carioca common beans based on molecular marker analysis

    Directory of Open Access Journals (Sweden)

    Juliana Morini Küpper Cardoso Perseguini


    Full Text Available A wide array of molecular markers has been used to investigate the genetic diversity among common bean species. However, the best combination of markers for studying such diversity among common bean cultivars has yet to be determined. Few reports have examined the genetic diversity of the carioca bean, commercially one of the most important common beans in Brazil. In this study, we examined the usefulness of two molecular marker systems (simple sequence repeats - SSRs and amplified fragment length polymorphisms - AFLPs for assessing the genetic diversity of carioca beans. The amount of information provided by Roger's modified genetic distance was used to analyze SSR data and Jaccards similarity coefficient was used for AFLP data. Seventy SSRs were polymorphic and 20 AFLP primer combinations produced 635 polymorphic bands. Molecular analysis showed that carioca genotypes were quite diverse. AFLPs revealed greater genetic differentiation and variation within the carioca genotypes (Gst = 98% and Fst = 0.83, respectively than SSRs and provided better resolution for clustering the carioca genotypes. SSRs and AFLPs were both suitable for assessing the genetic diversity of Brazilian carioca genotypes since the number of markers used in each system provided a low coefficient of variation. However, fingerprint profiles were generated faster with AFLPs, making them a better choice for assessing genetic diversity in the carioca germplasm.

  3. Molecular analysis of skeletal tuberculosis in an ancient Egyptian population. (United States)

    Zink, A; Haas, C J; Reischl, U; Szeimies, U; Nerlich, A G


    A paleomicrobiological study was performed on 37 skeletal tissue specimens from cadavers in the necropolis of Thebes-West, Upper Egypt, (2120-500 BC) and four from the necropolis of Abydos (3000 BC). The subjects had typical macromorphological evidence of osseous tuberculosis (n = 3), morphological alterations that were not specific, but probably resulted from tuberculosis (n = 17), or were without morphological osseous changes (n = 21). DNA was extracted from these bone samples and amplified by PCR with a primer pair that recognised the Mycobacterium tuberculosis complex insertion sequence IS6110. To confirm specificity of the analysis, the amplification products of several samples were subjected to restriction enzyme digestion, or direct sequencing, or both. In 30 of the 41 cases analysed, ancient DNA was demonstrated by amplification by the presence of the human beta-actin or the amelogenin gene and nine of these cases were positive for M. tuberculosis DNA. The results were confirmed by restriction endonuclease digestion and sequencing. A positive result for M. tuberculosis DNA was seen in two of the three cases with typical morphological signs of tuberculosis and amplifiable DNA, in five of 13 non-specific, but probable cases (including two cases from c. 3000 BC), but also in two of 14 cases without pathological bone changes. These observations confirm that tuberculosis may be diagnosed unequivocally in skeletal material from ancient Egypt, even dating back to c. 3000 BC. As a positive molecular reaction was observed in most of the typical cases of skeletal tuberculosis, in about one-third of non-specific, but probable tuberculous osseous changes and, surprisingly, in about one-seventh of unremarkable samples, this suggests that infection with M. tuberculosis was relatively frequent in ancient Egypt.

  4. Molecular Investigation of the Aum Shinrikyo Anthrax Release in Kameido, Japan



    In 1993, the Aum Shinrikyo cult aerosolized Bacillus anthracis spores over Kameido, Japan. Spore samples were obtained from the release site, cultured, and characterized by molecular genetic typing. The isolates were consistent with strain Sterne 34F2, which is used in Japan for animal prophylaxis against anthrax.

  5. Investigation on the protein-binding properties of icotinib by spectroscopic and molecular modeling method (United States)

    Zhang, Hua-xin; Xiong, Hang-xing; Li, Li-wei


    Icotinib is a highly-selective epidermal growth factor receptor tyrosine kinase inhibitor with preclinical and clinical activity in non-small cell lung cancer, which has been developed as a new targeted anti-tumor drug in China. In this work, the interaction of icotinib and human serum albumin (HSA) were studied by three-dimensional fluorescence spectra, ultraviolet spectra, circular dichroism (CD) spectra, molecular probe and molecular modeling methods. The results showed that icotinib binds to Sudlow's site I in subdomain IIA of HSA molecule, resulting in icotinib-HSA complexes formed at ground state. The number of binding sites, equilibrium constants, and thermodynamic parameters of the reaction were calculated at different temperatures. The negative enthalpy change (ΔHθ) and entropy change (ΔSθ) indicated that the structure of new complexes was stabilized by hydrogen bonds and van der Waals power. The distance between donor and acceptor was calculated according to Förster's non-radiation resonance energy transfer theory. The structural changes of HSA caused by icotinib binding were detected by synchronous spectra and circular dichroism (CD) spectra. Molecular modeling method was employed to unfold full details of the interaction at molecular level, most of which could be supported by experimental results. The study analyzed the probability that serum albumins act as carriers for this new anticarcinogen and provided fundamental information on the process of delivering icotinib to its target tissues, which might be helpful in understanding the mechanism of icotinib in cancer therapy.

  6. Metal-amyloid-β peptide interactions: a preliminary investigation of molecular mechanisms for Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    JIAO Yong; YANG Pin


    Although humans have spent exactly 100 years combating Alzheimer's disease (AD), the molecular mechanisms of AD remain unclear. Owing to the rapid growth of the oldest age groups of the population and the continuous increase of the incidence of AD, it has become one of the crucial problems to modern sciences. It would be impossible to prevent or reverse AD at the root without elucidating its molecular mechanisms. From the point of view of metal-amyloid-β peptide (Aβ) interactions, we review the molecular mechanisms of AD, mainly including Cu2+ and Zn2+ inducing the aggregation of Aβ, catalysing the production of active oxygen species from Aβ, as well as interacting with the ion-channel-like structures of Aβ. Moreover, the development of therapeutic drugs on the basis of metal-Aβ interactions is also briefly introduced. With the increasingly rapid progress of the molecular mechanisms of AD, we are now entering a new dawn that promises the delivery of revolutionary developments for the control of dementias.

  7. Teaching Molecular Phylogenetics through Investigating a Real-World Phylogenetic Problem (United States)

    Zhang, Xiaorong


    A phylogenetics exercise is incorporated into the "Introduction to biocomputing" course, a junior-level course at Savannah State University. This exercise is designed to help students learn important concepts and practical skills in molecular phylogenetics through solving a real-world problem. In this application, students are required to identify…

  8. Structural investigation of bistrifluron using x-ray crystallography, NMR spectroscopy, and molecular modeling

    CERN Document Server

    Moon, J K; Rhee, S K; Kim, G B; Yun, H S; Chung, B J; Lee, S S; Lim, Y H


    A new insecticide, bistrifluron acts as an inhibitor of insect development and interferes with the cuticle formation of insects. Since it shows low acute oral and dermal toxicities, it can be one of potent insecticides. Based on X-ray crystallography, NMR spectroscopy and molecular modeling, the structural studies of bistrifluron have been carried out.

  9. In silico investigation of molecular effects caused by missense mutations in creatine transporter protein (United States)

    Zhang, Zhe; Schwatz, Charles; Alexov, Emil


    Creatine transporter (CT) protein, which is encoded by SLC6A8 gene, is essential for taking up the creatine in the cell, which in turn plays a key role in the spatial and temporal maintenance of energy in skeletal and cardiac muscle cells. It was shown that some missense mutations in CT cause mental retardation, while others are harmless non-synonymous single nucleoside polymorphism (nsSNP). Currently fifteen missense mutations in CT are known, among which twelve are disease-causing. Sequence analysis reveals that there is no clear trend distinguishing disease-causing from harmless missense mutations. Because of that, we built 3D model of the CT using highly homologous template and use the model to investigate the effects of mutations of CT stability and hydrogen bond network. It is demonstrated that disease-causing mutations affect the folding free energy and ionization states of titratable group in much greater extend as compared with harmless mutations. Supported by grants from NLM, NIH, grant numbers 1R03LM009748 and 1R03LM009748-S1.

  10. Genome wide molecular analysis of minimally differentiated acute myeloid leukemia

    NARCIS (Netherlands)

    Silva, Fernando P. G.; Almeida, Ines; Morolli, Bruno; Brouwer-Mandema, Geeske; Wessels, Hans; Vossen, Rolf; Vrieling, Harry; Marijt, Erik W. A.; Valk, Peter J. M.; Kluin-Nelemans, Hanneke C.; Sperr, Wolfgang R.; Ludwig, Wolf-Dieter; Giphart-Gassler, Micheline


    Background Minimally differentiated acute myeloid leukemia is heterogeneous in karyotype and is defined by immature morphological and molecular characteristics. This originally French-American-British classification is still used in the new World Health Organization classification when other criteri

  11. Investigation and correlation of drug polymer miscibility and molecular interactions by various approaches for the preparation of amorphous solid dispersions. (United States)

    Meng, Fan; Trivino, Anne; Prasad, Dev; Chauhan, Harsh


    Curcumin (CUR) was used as a poorly soluble drug whereas polyvinyl pyrrolidone K90 (PVP), Eudragit EPO (EPO), hydroxypropyl methylcellulose E5 (HPMC) and polyethylene glycol 8000 (PEG) were used as hydrophilic polymers. CUR polymer miscibility was evaluated by solubility parameter, melting point depression and glass transition temperature (Tg) measurements. Molecular interactions between CUR and polymers were determined by Fourier-transform infrared spectroscopy (FTIR) and Raman. Amorphous solid dispersions were prepared with CUR-polymer ratio of 70:30 (w/w) by solvent evaporation technique and were evaluated for dissolution enhancement using USP II method. Physical states of solid dispersions were characterized by X-ray diffraction (XRD) whereas thermal behaviors were investigated using modulated differential scanning calorimetry (MDSC). CUR-EPO system showed good miscibility through all the approaches, whereas immiscibility was found in other CUR-polymer systems. CUR-EPO and CUR-HPMC systems showed significant molecular interactions whereas CUR-PVP and CUR-PEG showed no molecular interactions. All solid dispersions showed significant dissolution enhancement with CUR-EPO showing highest dissolution rate during first 1h whereas CUR-HPMC was effective in maintaining high CUR concentrations for 6h. The study highlights the importance of investigating and correlating drug polymer miscibility and molecular interactions by various approaches for successful formulation of amorphous solid dispersions.

  12. Molecular investigation of a dicentric 13;17 chromosome found in a 21-week gestation fetus with multiple congenital abnormalities. (United States)

    Cockwell, A E; Maloney, V K; Thomas, N S; Smith, E L; Gonda, P; Bass, P; Crolla, J A


    We report a 21-week gestation fetus terminated because of multiple congenital abnormalities seen on ultrasound scan, including ventriculomegaly, possible clefting of the hard palate, cervical hemivertebrae, micrognathia, abnormal heart, horseshoe kidney and a 2-vessel umbilical cord. On cytogenetic examination, the fetus was found to have a male karyotype with 45 chromosomes with a dicentric chromosome, which appeared to consist of the long arms of chromosomes 13 and 17. Molecular genetic investigations and fluorescence in situ hybridization (FISH) unexpectedly showed that the derivative chromosome contained two interstitial blocks of chromosome 17 short arm sequences, totalling approximately 7 Mb, between the two centromeres. This effectively made the fetus monosomic for approximately 15 Mb of 17p without the concurrent trisomy for another chromosome normally seen following malsegregation of reciprocal translocations. It also illustrates the complexity involved in the formation of some structurally abnormal chromosomes, which can only be resolved by detailed molecular investigations.

  13. Molecular analysis of the Salmonella typhimurium tdc operon regulation. (United States)

    Kim, Min-Jeong; Lim, Sangyong; Ryu, Sangryeol


    Efficient expression of the Salmonella Typhimurium tdcABCDEG operon involved in the degradation of Lserine and L-threonine requires TdcA, the transcriptional activator of the tdc operon. We found that the tdcA gene was transiently activated when bacterial growth condition was changed from aerobic to anaerobic, but this was not observed if Salmonella was grown anaerobically from the beginning of the culture. Expression kinetics of six tdc genes after anaerobic shock demonstrated by a real-time PCR assay showed that the tdcCDEG genes were not induced in tdcA mutant but tdcB maintained its inducibility by anaerobic shock even in the absence of tdcA, suggesting that an additional unknown transcriptional regulation may work for the tdcB expression. We also investigated the effects of nucleoid-associated proteins by primer extension analysis and found that H-NS repressed tdcA under anaerobic shock conditions and fis mutation delayed the peak expression time of the tdc operon. DNA microarray analysis of genes regulated by TdcA revealed that the genes involved in Nacetylmannosamine, maltose, and propanediol utilization were significantly induced in a tdcA mutant. These findings suggest that Tdc enzymes may play a pivotal role in energy metabolism under a sudden change of oxygen tension.

  14. Molecular-Level Computational Investigation of Mechanical Transverse Behavior of p-Phenylene Terephthalamide (PPTA) Fibers (United States)


    Structures Vol. 9 No. 4, 2013 pp. 462-498 q Emerald Group Publishing Limited 1573-6105 DOI 10.1108/MMMS-11-2012-0018 MMMS 9,4 462 1. Introduction The...provide insight into the behavior of PPTA fibers when subjected to transverse loading; and . to reveal the role of various microstructural and...molecular-level computational methods have been employed in the present work in order to obtain additional insight into the PPTA fiber transverse behavior





    Molecular dynamics simulation of nanostructure behavior under impulse heating is carried out. These structures are formed by self-rolling of nano-thickness bilayer crystal films. The interatomic interactions are described by potentials obtained by the embedded atom method. The calculation data are shown that simulated nanostructures can transform the supplied thermal energy into the mechanical oscillations of its free edges. The influence of heating rate and its duration, medium viscosity pro...

  16. Investigation of Combining Plant Genotypic Values and Molecular Marker Information for Constructing Core Subsets

    Institute of Scientific and Technical Information of China (English)

    Jian-Cheng Wang; Jin Hu; Ning-Ning Liu; Hai-Ming Xu; Sheng Zhang


    In the present study, a strategy was proposed for constructing plant core subsets by clusters based on the combination of continuous data for genotypic values and discrete data for molecular marker information. A mixed linear model approach was used to predict genotypic values for eliminating the environment effect.The "mixed genetic distance" was designed to solve the difficult problem of combining continuous and discrete data to construct a core subset by cluster. Four commonly used genetic distances for continuous data (Euclidean distance, standardized Euclidean distance, city block distance, and Mahalanobis distance)were used to assess the validity of the continuous data part of the mixed genetic distance; three commonly used genetic distances for discrete data (cosine distance, correlation distance, and Jaccard distance) were used to assess the validity of the discrete data part of the mixed genetic distance. A rice germplasm group with eight quantitative traits and information for 60 molecular markers was used to evaluate the validity of the new strategy. The results suggest that the validity of both parts of the mixed genetic distance are equal to or higher than the common genetic distance. The core subset constructed on the basis of a combination of data for genotypic values and molecular marker information was more representative than that constructed on the basis of data from genotypic values or molecular marker information alone. Moreover, the strategy of using combined data was able to treat dominant marker information and could combine any other continuous data and discrete data together to perform cluster to construct a plant core subset.

  17. Adsorption mechanisms of microcystin variant conformations at water-mineral interfaces: A molecular modeling investigation. (United States)

    Pochodylo, Amy L; Aoki, Thalia G; Aristilde, Ludmilla


    Microcystins (MCs) are potent toxins released during cyanobacterial blooms. Clay minerals are implicated in trapping MCs within soil particles in surface waters and sediments. In the absence of molecular characterization, the relevance of previously proposed adsorption mechanisms is lacking. Towards obtaining this characterization, we conducted Monte Carlo simulations combined with molecular dynamics relaxation of two MC variants, MC-leucine-arginine (MC-LR) and MC-leucine-alanine (MC-LA), adsorbed on hydrated montmorillonite with different electrolytes. The resulting adsorbate structures revealed how MC conformations and aqueous conditions dictate binding interactions at the mineral surface. Electrostatic coupling between the arginine residue and a carboxylate in MC-LR excluded the participation of arginine in mediating adsorption on montmorillonite in a NaCl solution. However, in a CaCl2 solution, the complexation of Ca by two carboxylate moieties in MC-LR changed the MC conformation, which allowed arginine to mediate electrostatic interaction with the mineral. By contrast, due to the lack of arginine in MC-LA, complexation of Ca by only one carboxylate in MC-LA was required to favor Ca-bridging interaction with the mineral. Multiple water-bridged H-bonding interactions were also important in anchoring MCs at the mineral surface. Our modeling results offer molecular insights into the structural and chemical factors that can control the fate of MCs at water-mineral interfaces.

  18. Molecular investigations of protriptyline as a multi-target directed ligand in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Sneha B Bansode

    Full Text Available Alzheimer's disease (AD is a complex neurodegenerative disorder involving multiple cellular and molecular processes. The discovery of drug molecules capable of targeting multiple factors involved in AD pathogenesis would greatly facilitate in improving therapeutic strategies. The repositioning of existing non-toxic drugs could dramatically reduce the time and costs involved in developmental and clinical trial stages. In this study, preliminary screening of 140 FDA approved nervous system drugs by docking suggested the viability of the tricyclic group of antidepressants against three major AD targets, viz. Acetylcholinesterase (AChE, β-secretase (BACE-1, and amyloid β (Aβ aggregation, with one member, protriptyline, showing highest inhibitory activity. Detailed biophysical assays, together with isothermal calorimetry, fluorescence quenching experiments, kinetic studies and atomic force microscopy established the strong inhibitory activity of protriptyline against all three major targets. The molecular basis of inhibition was supported with comprehensive molecular dynamics simulations. Further, the drug inhibited glycation induced amyloid aggregation, another important causal factor in AD progression. This study has led to the discovery of protriptyline as a potent multi target directed ligand and established its viability as a promising candidate for AD treatment.

  19. Molecular dynamics investigation of dynamical heterogeneity and local structure in the supercooled liquid and glass states of Al

    Energy Technology Data Exchange (ETDEWEB)

    Li, M.; Wang, C. Z.; Mandelev, M.; Ho, K. M.


    Molecular dynamics simulations are performed to study the structure and dynamical heterogeneity in the liquid and glass states of Al using a frequently employed embedded atom potential. While the pair correlation function of the glass and liquid states displays only minor differences, the icosahedral short-range order (ISRO) and the dynamics of the two states are very different. The ISRO is much stronger in the glass than in the liquid. It is also found that both the most mobile and the most immobile atoms in the glass state tend to form clusters, and the clusters formed by the immobile atoms are more compact. In order to investigate the local environment of each atom in the liquid and glass states, a local density is defined to characterize the local atomic packing. There is a strong correlation between the local packing density and the mobility of the atoms. These results indicate that dynamical heterogeneity in glasses is directly correlated to the local structure. We also analyze the diffusion mechanisms of atoms in the liquid and glass states. It is found that for the mobile atoms in the glass state, initially they are confined in the cages formed by their nearest neighbors and vibrating. On the time scale of {beta} relaxation, the mobile atoms try to break up the cage confinement and hop into new cages. In the supercooled liquid states, however, atoms continuously diffuse. Furthermore, it is found that on the time scale of {beta} relaxation, some of the mobile atoms in the glass state cooperatively hop, which is facilitated by the stringlike cluster structures. On the longer time scale, it is found that a certain fraction of atoms can simultaneously hop, although they are not nearest neighbors. Further analysis shows that these hopping atoms form big and more compact clusters than the characterized most mobile atoms. The cooperative rearrangement of these big compact clusters might facilitate the simultaneous hopping of atoms in the glass states on the long

  20. Molecular structure and DFT investigations on new cobalt(II) chloride complex with superbase guanidine type ligand

    Indian Academy of Sciences (India)

    Saied M Soliman; Morsy A M Abu-Youssef; Jörg Albering; Ayman El-Faham


    The new [Co(btmgn)Cl2] complex and the 1,8-bis(tetramethylguanidino)naphthalene (btmgn) ligand were synthesized and characterized. The X-ray single crystal investigation showed distorted tetrahedral geometry around the Co(II) ion. The geometry of the btmgn and [Co(btmgn)Cl2] complex was optimized using the B3LYP/6–311G(d,p) method. The calculated geometric parameters at the optimized structure of the [Co(btmgn)Cl2] complex showed good agreement with our reported X-ray structure. The two tetramethylguanidino groups are in a cis-type position to the naphthalene ring plane both in the free and coordinated btmgn. The large red shift of the C=N mode upon coordination indicates the strong ligand–metal interactions. The calculated natural charges using natural bond orbital (NBO) analysis at the two coordinated Cl-atoms are not equivalent. Also the two LP(4)Cl → LP*(3)Co intramolecular charge transfer interaction energies (E(2)) are 29.00 and 39.17 kcal/mol, respectively. The two Co-Cl bonds are not equivalent where the longer Co-Cl bond has more electronegative chlorine atom than the shorter one. Molecular electrostatic potential (MEP) study of the btmgn ligand showed that the N4 and N7 atoms are the most reactive nucleophilic centers for the coordination with the Co2+ ion. The [Co(btmgn)Cl2] complex has higher polarizability (0), first hyperpolarizability (0) and lower energy gap (E) than the free ligand. The TD-DFT calculations predicted the transition bands at 337.2 nm (f=0.2299, H→L) and 342.6 nm (f=0.1465, H-2/H→L) for the btmgn and [Co(btmgn)Cl2], respectively.

  1. Investigation of the interaction between isomeric derivatives and human serum albumin by fluorescence spectroscopy and molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ruiyong, E-mail:; Dou, Huanjing; Yin, Yujing; Xie, Yuanzhe; Sun, Li; Liu, Chunmei; Dong, Jingjing; Huang, Gang; Zhu, Yanyan; Song, Chuanjun, E-mail:; Chang, Junbiao, E-mail:


    In this paper, we have synthesized 9H-pyrrolo[1,2-a]indol-9-ones and the isomeric indeno[2,1-b]pyrrol-8-ones. The interactions of human serum albumin with series of isomeric derivatives have been studied by spectrophotometric methods. Results show the intrinsic fluorescence is quenched by the derivatives with a static quenching procedure. The thermodynamics parameters indicate that van der Waals forces and hydrogen bonds play a major role in the interactions. The results of synchronous fluorescence spectra demonstrate that the microenvironments of Trp residue of human serum albumin are disturbed by most derivatives. Thermodynamic results showed that the 9H-pyrrolo[1,2-a]indol-9-ones are stronger quenchers and bind to human serum albumin with the higher affinity than isomeric indeno[2,1-b]pyrrol-8-ones. The influence of molecular structure on the binding aspects has been investigated. - Highlights: • The interactions between isomeric derivatives and HSA have been investigated. • Results reveal that 9H-pyrrolo[1,2-a]indol-9-ones are stronger quenchers for HSA. • Hydrogen bonds and van der Waals forces play major role in the binding process. • The influence of molecular structure on the binding aspects has been investigated. • The binding study was also modeled by molecular docking.

  2. Simulated, Emulated, and Physical Investigative Analysis (SEPIA) of networked systems.

    Energy Technology Data Exchange (ETDEWEB)

    Burton, David P.; Van Leeuwen, Brian P.; McDonald, Michael James; Onunkwo, Uzoma A.; Tarman, Thomas David; Urias, Vincent E.


    This report describes recent progress made in developing and utilizing hybrid Simulated, Emulated, and Physical Investigative Analysis (SEPIA) environments. Many organizations require advanced tools to analyze their information system's security, reliability, and resilience against cyber attack. Today's security analysis utilize real systems such as computers, network routers and other network equipment, computer emulations (e.g., virtual machines) and simulation models separately to analyze interplay between threats and safeguards. In contrast, this work developed new methods to combine these three approaches to provide integrated hybrid SEPIA environments. Our SEPIA environments enable an analyst to rapidly configure hybrid environments to pass network traffic and perform, from the outside, like real networks. This provides higher fidelity representations of key network nodes while still leveraging the scalability and cost advantages of simulation tools. The result is to rapidly produce large yet relatively low-cost multi-fidelity SEPIA networks of computers and routers that let analysts quickly investigate threats and test protection approaches.

  3. Investigating product development strategy in beverage industry using factor analysis

    Directory of Open Access Journals (Sweden)

    Naser Azad


    Full Text Available Selecting a product development strategy that is associated with the company's current service or product innovation, based on customers’ needs and changing environment, plays an important role in increasing demand, increasing market share, increasing sales and profits. Therefore, it is important to extract effective variables associated with product development to improve performance measurement of firms. This paper investigates important factors influencing product development strategies using factor analysis. The proposed model of this paper investigates 36 factors and, using factor analysis, we extract six most influential factors including information sharing, intelligence information, exposure strategy, differentiation, research and development strategy and market survey. The first strategy, partnership, includes five sub-factor including product development partnership, partnership with foreign firms, customers’ perception from competitors’ products, Customer involvement in product development, inter-agency coordination, customer-oriented approach to innovation and transmission of product development change where inter-agency coordination has been considered the most important factor. Internal strengths are the most influential factors impacting the second strategy, intelligence information. The third factor, introducing strategy, introducing strategy, includes four sub criteria and consumer buying behavior is the most influencing factor. Differentiation is the next important factor with five components where knowledge and expertise in product innovation is the most important one. Research and development strategy with four sub-criteria where reducing product development cycle plays the most influential factor and finally, market survey strategy is the last important factor with three factors and finding new market plays the most important role.

  4. Molecular typing of Treponema pallidum: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Rui-Rui Peng


    Full Text Available BACKGROUND: Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum with three objectives: (1 to determine specimen types most suitable for molecular typing; (2 to determine T. pallidum subtype distribution across geographic areas; and (3 to summarize available information on subtypes associated with neurosyphilis and macrolide resistance. METHODOLOGY/PRINCIPAL FINDINGS: Two researchers independently searched five databases from 1998 through 2010, assessed for eligibility and study quality, and extracted data. Search terms included "Treponema pallidum," or "syphilis," combined with the subject headings "molecular," "subtyping," "typing," "genotype," and "epidemiology." Sixteen eligible studies were included. Publication bias was not statistically significant by the Begg rank correlation test. Medians, inter-quartile ranges, and 95% confidence intervals were determined for DNA extraction and full typing efficiency. A random-effects model was used to perform subgroup analyses to reduce obvious between-study heterogeneity. Primary and secondary lesions and ear lobe blood specimens had an average higher yield of T. pallidum DNA (83.0% vs. 28.2%, χ(2 = 247.6, p<0.001 and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, χ(2 = 102.3, p<0.001 compared to plasma, whole blood, and cerebrospinal fluid. A pooled analysis of subtype distribution based on country location showed that 14d was the most common subtype, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited. CONCLUSIONS/SIGNIFICANCE: Primary lesion was a better specimen for obtaining T. pallidum DNA than blood. There was wide geographic variation in T. pallidum subtypes. More research is needed on the

  5. Ancestry analysis in the 11-M Madrid bomb attack investigation.

    Directory of Open Access Journals (Sweden)

    Christopher Phillips

    Full Text Available The 11-M Madrid commuter train bombings of 2004 constituted the second biggest terrorist attack to occur in Europe after Lockerbie, while the subsequent investigation became the most complex and wide-ranging forensic case in Spain. Standard short tandem repeat (STR profiling of 600 exhibits left certain key incriminatory samples unmatched to any of the apprehended suspects. A judicial order to perform analyses of unmatched samples to differentiate European and North African ancestry became a critical part of the investigation and was instigated to help refine the search for further suspects. Although mitochondrial DNA (mtDNA and Y-chromosome markers routinely demonstrate informative geographic differentiation, the populations compared in this analysis were known to show a proportion of shared mtDNA and Y haplotypes as a result of recent gene-flow across the western Mediterranean, while any two loci can be unrepresentative of the ancestry of an individual as a whole. We based our principal analysis on a validated 34plex autosomal ancestry-informative-marker single nucleotide polymorphism (AIM-SNP assay to make an assignment of ancestry for DNA from seven unmatched case samples including a handprint from a bag containing undetonated explosives together with personal items recovered from various locations in Madrid associated with the suspects. To assess marker informativeness before genotyping, we predicted the probable classification success for the 34plex assay with standard error estimators for a naïve Bayesian classifier using Moroccan and Spanish training sets (each n = 48. Once misclassification error was found to be sufficiently low, genotyping yielded seven near-complete profiles (33 of 34 AIM-SNPs that in four cases gave probabilities providing a clear assignment of ancestry. One of the suspects predicted to be North African by AIM-SNP analysis of DNA from a toothbrush was identified late in the investigation as Algerian in origin. The

  6. Accurate molecular structure and spectroscopic properties for nucleobases: A combined computational - microwave investigation of 2-thiouracil as a case study (United States)

    Puzzarini, Cristina; Biczysko, Malgorzata; Barone, Vincenzo; Peña, Isabel; Cabezas, Carlos; Alonso, José L.


    The computational composite scheme purposely set up for accurately describing the electronic structure and spectroscopic properties of small biomolecules has been applied to the first study of the rotational spectrum of 2-thiouracil. The experimental investigation was made possible thanks to the combination of the laser ablation technique with Fourier Transform Microwave spectrometers. The joint experimental – computational study allowed us to determine accurate molecular structure and spectroscopic properties for the title molecule, but more important, it demonstrates a reliable approach for the accurate investigation of isolated small biomolecules. PMID:24002739

  7. Molecular rheological analysis on binary blends of perfluoropolyether lubricants (United States)

    Seung Chung, Pil; Hari Vemuri, Sesha; Park, Sejoon; Jhon, Myung S.


    The molecular rheology of PFPE becomes critically important in designing optimal lubricants that control the friction/wear and air-bearing by tuning elastic or viscous shear/elongation deformations, which affect the performance and reliability of the hard disk drive. In this paper, we examine the rheological responses of nano blended PFPEs including storage (elastic) and loss (viscous) moduli (G' and G″), by monitoring the time-dependent-stress-strain relationship via non-equilibrium molecular dynamics simulations. By introducing binary blend of nonfunctional and functional PFPEs, we control the degree of liquid/solid-like behavior using the rheology as a complementary tool for design criteria by tuning molecular conformation and diffusion with nano blend ratio.

  8. The Silica-Water Interface from the Analysis of Molecular Dynamic Simulations

    KAUST Repository

    Lardhi, Sheikha F.


    Surface chemistry is an emerging field that can give detailed insight about the elec- tronic properties and the interaction of complex material surfaces with their neigh- bors. This is for both solid-solid and solid-liquid interfaces. Among the latter class, the silica-water interface plays a major role in nature. Silica is among the most abundant materials on earth, as well in advanced technological applications such as catalysis and nanotechnology. This immediately indicates the relevance of a detailed understanding of the silica-water interface. In this study, we investigate the details of this interaction at microscopic level by analyzing trajectories obtained with ab initio molecular dynamic simulations. The system we consider consists of bulk liquid water confined between two β-cristobalite silica surfaces. The molecular dynamics were generated with the CP2K, an ab initio molecular dynamic simulation tool. The simulations are 25 picoseconds long, and the CP2K program was run on 64 cores on a supercomputer cluster. During the simulations the program integrates Newton’s equations of motion for the system and generates the trajectory for analysis. For analysis, we focused on the following properties that characterize the silica water interface. We calculated the density profile of the water layers from the silica surface, and we also calculated the radial distribution function (RDF) of the hydrogen bond at the silanols on the silica surface. The main focus of this thesis is to write the programs for calculating the atom density profile and the RDF from the generated MD trajectories. The atomic probability density profile shows that water is strongly adsorbed on the (001) cristobalite surface, while the RDF indicates differently ad- sorbed water molecules in the first adsorption layer. As final remark, the protocol and the tools developed in this thesis can be applied to the study of basically any crystal-water interface.

  9. Molecular dynamics simulation and NMR investigation of the association of the β-blockers atenolol and propranolol with a chiral molecular micelle (United States)

    Morris, Kevin F.; Billiot, Eugene J.; Billiot, Fereshteh H.; Hoffman, Charlene B.; Gladis, Ashley A.; Lipkowitz, Kenny B.; Southerland, William M.; Fang, Yayin


    Molecular dynamics simulations and NMR spectroscopy were used to compare the binding of two β-blocker drugs to the chiral molecular micelle poly-(sodium undecyl-(L)-leucine-valine). The molecular micelle is used as a chiral selector in capillary electrophoresis. This study is part of a larger effort to understand the mechanism of chiral recognition in capillary electrophoresis by characterizing the molecular micelle binding of chiral compounds with different geometries and charges. Propranolol and atenolol were chosen because their structures are similar, but their chiral interactions with the molecular micelle are different. Molecular dynamics simulations showed both propranolol enantiomers inserted their aromatic rings into the molecular micelle core and that (S)-propranolol associated more strongly with the molecular micelle than (R)-propranolol. This difference was attributed to stronger molecular micelle hydrogen bonding interactions experienced by (S)-propranolol. Atenolol enantiomers were found to bind near the molecular micelle surface and to have similar molecular micelle binding free energies.

  10. Investigations on the antiretroviral activity of carbon nanotubes using computational molecular approach. (United States)

    Krishnaraj, R Navanietha; Chandran, Saravanan; Pal, Parimal; Berchmans, Sheela


    Carbon nanotubes are the interesting class of materials with wide range of applications. They have excellent physical, chemical and electrical properties. Numerous reports were made on the antiviral activities of carbon nanotubes. However the mechanism of antiviral action is still in infancy. Herein we report, our recent novel findings on the molecular interactions of carbon nanotubes with the three key target proteins of HIV using computational chemistry approach. Armchair, chiral and zigzag CNTs were modeled and used as ligands for the interaction studies. The structure of the key proteins involved in HIV mediated infection namely HIV- Vpr, Nef and Gag proteins were collected from the PDB database. The docking studies were performed to quantify the interaction of the CNT with the three different disease targets. Results showed that the carbon nanotubes had high binding affinity to these proteins which confirms the antagonistic molecular interaction of carbon nanotubes to the disease targets. The modeled armchair carbon nanotubes had the binding affinities of -12.4 Kcal/mole, -20 Kcal/mole and -11.7 Kcal/mole with the Vpr, Nef and Gag proteins of HIV. Chiral CNTs also had the maximum affinity of -16.4 Kcal/mole to Nef. The binding affinity of chiral CNTs to Vpr and Gag was found to be -10.9 Kcal/mole and -10.3 Kcal/mole respectively. The zigzag CNTs had the binding affinity of -11.1 Kcal/mole with Vpr, -18.3 Kcal/mole with Nef and -10.9 with Gag respectively. The strong molecular interactions suggest the efficacy of CNTs for targeting the HIV mediated retroviral infections.

  11. Synthesis, spectroscopic investigations (X-ray, NMR and TD-DFT), antimicrobial activity and molecular docking of 2,6-bis(hydroxy(phenyl)methyl)cyclohexanone. (United States)

    Barakat, Assem; Ghabbour, Hazem A; Al-Majid, Abdullah Mohammed; Soliman, Saied M; Ali, M; Mabkhot, Yahia Nasser; Shaik, Mohammed Rafi; Fun, Hoong-Kun


    The synthesis of 2,6-bis(hydroxy(phenyl)methyl)cyclohexanone 1 is described. The molecular structure of the title compound 1 was confirmed by NMR, FT-IR, MS, CHN microanalysis, and X-ray crystallography. The molecular structure was also investigated by a set of computational studies and found to be in good agreement with the experimental data obtained from the various spectrophotometric techniques. The antimicrobial activity and molecular docking of the synthesized compound was investigated.

  12. Ultrasonic Investigations of Molecular Interaction in Binary Mixtures of Benzyl Benzoate with Acetonitrile and Benzonitrile

    Directory of Open Access Journals (Sweden)

    N. Jaya Madhuri


    Full Text Available Ultrasonic velocity, density and viscosity have been measured in the binary mixtures of benzyl benzoate with acetonitrile, benzonitrile at three temperatures 30, 40 and 50 °C. From the experimental data, thermodynamic parameters like adiabatic compressibility, internal pressure, enthalpy, activation energy etc., were computed and the molecular interactions were predicted based on the variation of excess parameters in the mixture. Also theoretical evaluation of velocities was made employing the standard theories. CFT and NOMOTO were found to have an edge. All the three mixtures have shown out strong intermolecular interactions between the unlike molecules and endothermic type of chemical reaction.

  13. Wetting and evaporation of salt-water nanodroplets: A molecular dynamics investigation


    Zhang, Jun; Borg, Matthew; Sefiane, Khellil; Reese, Jason


    We employ molecular dynamics simulations to study the wetting and evaporation of salt-water nanodroplets on platinum surfaces. Our results show that the contact angle of the droplets increases with the salt concentration. To verify this, a second simulation system of a thin salt-water film on a platinum surface is used to calculate the various surface tensions. We find that both the solid-liquid and liquid-vapor surface tensions increase with salt concentration and as a result these cause an ...

  14. Theoretical investigation on functional monomer and solvent selection for molecular imprinting of tramadol (United States)

    Fonseca, Matheus C.; Nascimento, Clebio S.; Borges, Keyller B.


    The purpose of this Letter was to study for the first time the interaction process of tramadol (TRM) with distinct functional monomers (FM) in the formation of molecular imprinted polymer (MIP), using density functional theory (DFT) calculations at B3LYP/6-31G(d,p). As result we were able to establish that the best MIP synthesis conditions are obtained with acrylic acid as FM in 1:3 molar ratio and with chloroform as solvent. This condition presented the lowest stabilization energy for the pre-polymerization complexes. Besides, the intermolecular hydrogen bonds found between the template molecule and functional monomers play a primary role to the complex stability.

  15. New Diethyl Ammonium Salt of Thiobarbituric Acid Derivative: Synthesis, Molecular Structure Investigations and Docking Studies


    Assem Barakat; Abdullah Mohammed Al-Majid; Saied M. Soliman; Gehad Lotfy; Ghabbour, Hazem A; Hoong-Kun Fun; Abdul Wadood; Ismail Warad; Joseph C. Sloop


    The synthesis of the new diethyl ammonium salt of diethylammonium(E)-5-(1,5-bis(4-fluorophenyl)-3-oxopent-4-en-1-yl)-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized by the strong intramolecular electron delocalization with the adjacent carbonyl groups and so the reaction proceeds without any cyclization. The molecular stru...

  16. Methodologies and Application of New Target Identification, Drug Action Mechanism Investigation and New Molecular Entity Discovery

    Institute of Scientific and Technical Information of China (English)


    @@ The group, headed by Prof.JIANG Hualiang with the CAS Shanghai Institute of Materia Medica, has been centering on the basic research of pharmaceutical science, including identifying new targets, studying new drug action mechanisms and discovering new drug candidates.On the basis of new methodology development, an effective multi-disciplinary research platform for drug research and discovery has been established through the integration of different disciplines of computational chemistry, organic synthesis, molecular and cellular biology.A bunch of creative results have been achieved in these areas.

  17. Molecular analysis of myophosphorylase deficiency in Dutch patients with McArdle's disease.

    NARCIS (Netherlands)

    Martin, M.A.; Rubio, J.C.; Wevers, R.A.; Engelen, B.G.M. van; Steenbergen-Spanjers, G.C.H.; Diggelen, O.P. van; Visser, M. de; Die-Smulders, C.E.M. de; Blazquez, A.; Andreu, A.L.; Arenas, J.


    We report on 8 Dutch patients with McArdle's disease from 6 unrelated families. Molecular analysis revealed the presence of four previously described mutations: the common R49X mutation, the IVS14+1G>A mutation and the recently reported R269X and Y84X nonsense mutations; and two new molecular def

  18. Investigating molecular interactions and surface morphology of wax-doped asphaltenes. (United States)

    Pahlavan, Farideh; Mousavi, Masoumeh; Hung, Albert; Fini, Ellie H


    The nature and origin of bee-like microstructures (bees) in asphalt binders and their impact on asphalt oxidation have been the subject of extensive discussions in recent years. While several studies refer to the bees as solely surface features, some others consider them to be bulk microcrystalline components that are formed due to co-precipitation of wax and asphaltene molecules. In this study, we use a rigorous theoretical and experimental approach to investigate the interplay of asphalt components (mainly asphaltene and wax) and their impact on bee formation. In the theoretical section, quantum-mechanical calculations using density functional theory (DFT) are used to evaluate the strength of interactions between asphaltene unit sheets in the presence and absence of a wax component, as well as the mutual interactions between asphaltene molecules (monomers and dimers) and paraffin wax. The results of this section reveal that paraffin waxes not only do not reinforce the interaction between the asphaltene unit sheets, they destabilize asphaltene assembly and dimerization. AIM (Atom in Molecules) analysis shows the destabilizing effect of wax on asphaltene assembly as a reduction in the number of cage and bond critical points between asphaltenes. This destabilization effect among interacting systems (asphaltene-asphaltene and wax-asphaltene) does not support the hypothesis that interaction between paraffin waxes and non-wax components, such as asphaltene, is responsible for their co-precipitation and bee formation. To further examine the effect of wax component on asphalt microstructure experimentally, we used atomic force microscopy (AFM) to study the surface morphology of an asphalt sample doped with 1% to 25% paraffin wax. In agreement with the conclusions drawn from the DFT approach, our experiments indicate that paraffin wax tends to crystallize separately and form lamellar paraffin wax crystal inclusions with 10 nm thickness. Moreover, the addition of 3% wax

  19. Radioprotective cerium oxide nanoparticles: Molecular imaging investigations of conps' pharmacokinetics, efficacy, and mechanisms of action (United States)

    McDonagh, Philip Reed Wills, III

    Cerium oxide nanoparticles (CONPs) are being investigated for several anti-oxidant applications in medicine. One of their most promising applications is as a radioprotective drug, an area of research in need due to the severe side effects from radiation therapy. In this work, the potential of CONPs as a radioprotective drug is examined using four criteria: favorable biodistribution/pharmacokinetics, low toxicity, ability to protect normal tissue from radiation damage, and lack of protection of tumor. The mechanisms of action of CONPs are also studied. Biodistribution was determined in radiolabeled CONPs with surface coatings including citrate, dextran T10-amine (DT10-NH2), dextran T10-polyethylene glycol (DT10-PEG), dextran T10-sulfobetaine (DT10-SB) and poly(acrylic acid) (PAA), and compared to uncoated. 89Zr was incorporated into CONPs for positron emission tomography (PET) imaging and ex vivo tissue analysis in tumor bearing mice. Compared to uncoated [ 89Zr]CONPs, coated [89Zr]CONPs showed improved biodistribution, including significantly enhanced renal clearance of PAA- [89Zr]CONPs. The toxicity of CONPs was evaluated in vitro and in vivo, with low toxicity at therapeutic doses. After clinically mimetic radiation therapy, pre-treatment of mice with coated and uncoated CONPs showed greater than 50% reduction of cell death in normal colon tissue, comparable to the clinically available radioprotective drug amifostine. Tumor control after irradiation of spontaneous colon tumors was unchanged with PAA-CONP pre-treatment, while citrate, DT10-PEG, and uncoated CONP pre-treatment had slightly less tumor control. Xenograft tumors were irradiated after pH normalizing treatment with sodium bicarbonate and PAA-CONP pre-treatment. Treatment of these tumors showed slightly less tumor control than irradiation alone or PAA-CONP plus irradiation, demonstrating that the acidic pH of the tumor microenvironment may be the basis of preventing CONPs' radioprotective properties in

  20. High-molecular products analysis of VOC destruction in atmospheric pressure discharge (United States)

    Grossmannova, Hana; Ciganek, Miroslav; Krcma, Frantisek


    We investigate the issue of applicability of the solid phase microextraction (SPME) in the analysis of volatile organic compounds (VOCs) destruction products in the gliding arc discharge. Our research is focused on the measurements with the simple one stage gliding arc reactor, applied voltage was varied in the range of 3.5-4 kV. As a carrier gas, the dry air and its mixtures with nitrogen and oxygen, enriched by toluene, with flow rate of 1000-3500 ml/min was used. Total decomposition of toluene of 97 % was achieved at the oxygen content in carrier gas of 60 %. For measurements with air as a carrier gas, the highest efficiency was 95 %. We also tested the SPME technique suitability for the quantitative analysis of exhausts gases and if this technique can be used efficiently in the field to extract byproducts. Carbowax/divinylbenzene and Carboxen/polydimethylsiloxane/divinylbenzene fibres were chosen for sampling. Tens of various high-molecular substances were observed, especially a large number of oxygenous compounds and further several nitrogenous and CxHy compounds. The concentrations of various generated compounds strongly depend on the oxygen content in gas mixture composition. The results showed that the fiber coated by Carbowax/divinylbenzene can extract more products independently on the used VOC compound. The Carboxen/polydimethylsiloxane/divinylbenzene fiber is useful for the analysis of oxygenous compounds and its use will be recommended especially when the destruction is done in the oxygen rich atmosphere. With the higher ratio of oxygen in the carrier gas a distinctive decline of CxHy compounds amount have been observed. We also tried to describe the significant production of some compounds like benzyl alcohol, benzeneacetaldehyde, even in oxygen content is proximate 0 %. Experimental data demonstrated that it is necessary to use several SPME fibres for full-scale high-molecular products analysis.

  1. Solvation of uranium hexachloro complexes in room-temperature ionic liquids. A molecular dynamics investigation in two liquids. (United States)

    Schurhammer, Rachel; Wipff, Georges


    We report a molecular dynamics study of the solvation of UCl(6)(-), UCl(6)(2-), and UCl(6)(3-) complexes in the [BMI][Tf(2)N] and [MeBu(3)N][Tf(2)N] ionic liquid cations based on the same anion (bis(trifluoromethylsulfonyl)imide (Tf(2)N-)) and the butyl-3-methyl-imidazolium+ (BMI+) or methyl-tri-n-butyl-ammonium (MeBu(3)N+) cation, respectively. The comparison of two electrostatic models of the complexes (ionic model with -1 charged halides versus quantum mechanically derived charges) yields similar solvation features of a given solute. In the two liquids, the first solvation shell of the complexes is positively charged and evolves from purely cationic in the case of UCl(6)(3-) to a mixture of cations and anions in the case of UCl(6)(-). UCl(6)(3-) is exclusively "coordinated" to BMI+ or MeBu(3)N+ solvent cations that mainly interact via their CH aromatic protons or their N-Me group, respectively. Around the less charged UCl(6)(-) complex, the cations interact via the less polar moieties (butyl chains of BMI+ or MeBu(3)N+) and the anions display nonspecific interactions. In no case does the uranium atom further coordinate solvent ions. According to an energy components analysis, UCl(6)(3-) interacts more attractively with the [BMI][Tf(2)N] liquid than with [MeBu(3)N][Tf(2)N], while UCl(6)(-) does not show any preference, suggesting a significant solvation effect of the redox properties of uranium, also supported by free energy perturbation simulations. The effect of ionic liquid (IL) humidity is investigated by simulating the three complexes in 1:8 water/IL mixtures. In contrast to the case of "naked" ions (e.g., lanthanide(3+), UO2(2+), alkali, or halides), water has little influence on the solvation of the UCl(6)(n-) complexes in the two simulated ILs, as indicated by structural and energy analysis. This is in full agreement with the experimental observations (Nikitenko, S. I.; et al. Inorg. Chem. 2005, 44, 9497).

  2. Investigation of ligand selectivity in CYP3A7 by molecular dynamics simulations. (United States)

    Fan, Jing-Rong; Zheng, Qing-Chuan; Cui, Ying-Lu; Li, Wei-Kang; Zhang, Hong-Xing


    Cytochrome P450 (CYP) 3A7 plays a crucial role in the biotransformation of the metabolized endogenous and exogenous steroids. To compare the metabolic capabilities of CYP3A7-ligands complexes, three endogenous ligands were selected, namely dehydroepiandrosterone (DHEA), estrone, and estradiol. In this study, a three-dimensional model of CYP3A7 was constructed by homology modeling using the crystal structure of CYP3A4 as the template and refined by molecular dynamics simulation (MD). The docking method was adopted, combined with MD simulation and the molecular mechanics generalized born surface area method, to probe the ligand selectivity of CYP3A7. These results demonstrate that DHEA has the highest binding affinity, and the results of the binding free energy were in accordance with the experimental conclusion that estrone is better than estradiol. Moreover, several key residues responsible for substrate specificity were identified on the enzyme. Arg372 may be the most important residue due to the low interaction energies and the existence of hydrogen bond with DHEA throughout simulation. In addition, a cluster of Phe residues provides a hydrophobic environment to stabilize ligands. This study provides insights into the structural features of CYP3A7, which could contribute to further understanding of related protein structures and dynamics.

  3. Experimental Investigation of Molecular Species Formation in Metal Plasmas During Laser Ablation (United States)

    Radousky, H.; Crowhurst, J.; Rose, T.; Armstrong, M.; Stavrou, E.; Zaug, J.; Weisz, D.; Azer, M.; Finko, M.; Curreli, D.


    Atomic and molecular spectra on metal plasmas generated by laser ablation have been measured using single, nominally 6-7 ns pulses at 1064 nm, and with energies less than 50 mJ. The primary goal for these studies is to constrain the physical and chemical mechanisms that control the distribution of radionuclides in fallout after a nuclear detonation. In this work, laser emission spectroscopy was used to obtain in situdata for vapor phase molecular species as they form in a controlled oxygen atmosphere for a variety of metals such as Fe, Al, as well as preliminary results for U. In particular, the ablation plumes created from these metals have been imaged with a resolution of 10 ns, and it is possible to observe the expansion of the plume out to 0.5 us. These data serve as one set of inputs for a semi-empirical model to describe the chemical fractionation of uranium during fallout formation. Prepared by LLNL under Contract DE-AC52-07NA27344. This project was sponsored by the Department of the Defense, Defense Threat Reduction Agency, under Grant Number HDTRA1-16-1-0020.

  4. Molecular mobility in dense protein systems: an investigation through 1H NMR relaxometry and diffusometry. (United States)

    Bouchoux, Antoine; Schorr, Diane; Daffé, Awa; Cambert, Mireille; Gésan-Guiziou, Geneviève; Mariette, François


    Understanding how proteins behave in highly concentrated systems is a major issue in many fields of research, including biology, biophysics, and chemical engineering. In this paper, we provide a comprehensive (1)H NMR study of molecular mobility in dilute to highly concentrated dispersions of the exact same protein (casein) but organized in two distinct supramolecular forms: spongelike casein micelles or soft casein aggregates. Both relaxometry and diffusometry experiments were performed, so that three different parameters are reported: spin-spin relaxation rates of non-water protons (1/T(2,ne)), spin-spin relaxation rates of water protons (1/T(2,e+w)), and water self-diffusion coefficients (D(w)). The results are discussed in an effort to understand the respective effects of protein crowding and protein supramolecular organization on each mobility indicator. We also examine if connections exist between the observed changes in molecular mobility and the already documented changes in rheological and osmotic properties of casein dispersions as concentration is increased.

  5. Molecular Dynamics Simulation to Investigate the Interaction of Asphaltene and Oxide in Aggregate

    Directory of Open Access Journals (Sweden)

    Rui Li


    Full Text Available The asphalt-aggregate interface interaction (AAI plays a significant role in the overall performances of asphalt mixture, which is caused due to the complicated physicochemical processes and is influenced by various factors, including the acid-base property of aggregates. In order to analyze the effects of the chemical constitution of aggregate on the AAI, the average structure C65H74N2S2 is selected to represent the asphaltene in asphalt and magnesium oxide (MgO, calcium oxide (CaO, aluminium sesquioxide (Al2O3, and silicon dioxide (SiO2 are selected to represent the major oxides in aggregate. The molecular models are established for asphaltene and the four oxides, respectively, and the molecular dynamics (MD simulation was conducted for the four kinds of asphaltene-oxide system at different temperatures. The interfacial energy in MD simulation is calculated to evaluate the AAI, and higher value means better interaction. The results show that interfacial energy between asphaltene and oxide reaches the maximum value at 25°C and 80°C and the minimum value at 40°C. In addition, the interfacial energy between asphaltene and MgO was found to be the greatest, followed by CaO, Al2O3, and SiO2, which demonstrates that the AAI between asphalt and alkaline aggregates is better than acidic aggregates.

  6. Continuous distribution model for the investigation of complex molecular architectures near interfaces with scattering techniques. (United States)

    Shekhar, Prabhanshu; Nanda, Hirsh; Lösche, Mathias; Heinrich, Frank


    Biological membranes are composed of a thermally disordered lipid matrix and therefore require non-crystallographic scattering approaches for structural characterization with x-rays or neutrons. Here we develop a continuous distribution (CD) model to refine neutron or x-ray reflectivity data from complex architectures of organic molecules. The new model is a flexible implementation of the composition-space refinement of interfacial structures to constrain the resulting scattering length density profiles. We show this model increases the precision with which molecular components may be localized within a sample, with a minimal use of free model parameters. We validate the new model by parameterizing all-atom molecular dynamics (MD) simulations of bilayers and by evaluating the neutron reflectivity of a phospholipid bilayer physisorbed to a solid support. The determination of the structural arrangement of a sparsely-tethered bilayer lipid membrane (stBLM) comprised of a multi-component phospholipid bilayer anchored to a gold substrate by a thiolated oligo(ethylene oxide) linker is also demonstrated. From the model we extract the bilayer composition and density of tether points, information which was previously inaccessible for stBLM systems. The new modeling strategy has been implemented into the ga_refl reflectivity data evaluation suite, available through the National Institute of Standards and Technology (NIST) Center for Neutron Research (NCNR).

  7. Molecular Analysis of AFP and HSA Interactions with PTEN Protein. (United States)

    Zhu, Mingyue; Lin, Bo; Zhou, Peng; Li, Mengsen


    Human cytoplasmic alpha-fetoprotein (AFP) has been classified as a member of the albuminoid gene family. The protein sequence of AFP has significant homology to that of human serum albumin (HSA), but its biological characteristics are vastly different from HSA. The AFP functions as a regulator in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway, but HSA plays a key role as a transport protein. To probe their molecular mechanisms, we have applied colocalization, coimmunoprecipitation (co-IP), and molecular docking approaches to analyze the differences between AFP and HSA. The data from colocalization and co-IP displayed a strong interaction between AFP and PTEN (phosphatase and tensin homolog), demonstrating that AFP did bind to PTEN, but HSA did not. The molecular docking study further showed that the AFP domains I and III could contact with PTEN. In silicon substitutions of AFP binding site residues at position 490M/K and 105L/R corresponding to residues K490 and R105 in HSA resulted in steric clashes with PTEN residues R150 and K46, respectively. These steric clashes may explain the reason why HSA cannot bind to PTEN. Ultimately, the experimental results and the molecular modeling data from the interactions of AFP and HSA with PTEN will help us to identify targets for designing drugs and vaccines against human hepatocellular carcinoma.

  8. Analysis of Molecular Genetics Content in Spanish Secondary School Textbooks (United States)

    Martinez-Gracia, M. V.; Gil-Quilez, M. J.; Osada, J.


    The treatment of molecular biology in thirty-four Spanish high school biology textbooks has been analysed using a check-list made up of twenty-three items. The study showed a tendency to confuse the genetic code with genetic information. The treatment of DNA transcription, regulation of gene expression and translation were presented as masses of…

  9. Molecular analysis of candidate probiotic effector molecules of Lactobacillus plantarum

    NARCIS (Netherlands)

    Remus, D.M.


    Probiotics are health-promoting microorganisms that exert their beneficial effects in several ways. While it is known that probiotic bacteria interact with cells of the host gastrointestinal tractand modulate cell-signaling responses by which they might promote health, the underlying molecular mecha

  10. Synthesis, Crystal Structure, and Hirshfeld Surface Analysis of Ciprofloxacin-Salicylic Acid Molecular Salt

    Directory of Open Access Journals (Sweden)

    Ravikumar Nagalapalli


    Full Text Available In the present study, ciprofloxacin-salicylic acid molecular salt has been synthesized and preliminarily characterized by FT-IR spectroscopy. The single crystal X-ray diffraction (SCXRD reveals the proton transfer from carboxylic acid group of salicylic acid to piperazine moiety in ciprofloxacin confirming the formation of new molecular salt. The molecular packing of the molecular salt is mainly supported by N+–H⋯O−, O–H⋯O, C–H⋯F, C–H⋯π, and π-π interactions. The 3D Hirshfeld surfaces and the associated 2D fingerprint plots were investigated for intermolecular hydrogen bonding interactions.

  11. Molecular Analysis of Bacterial Microbiota on Brazilian Currency Note Surfaces. (United States)

    Pereira da Fonseca, Tairacan Augusto; Pessôa, Rodrigo; Sanabani, Sabri Saeed


    Currency notes have been implicated as a vehicle for transmitting community-acquired bacterial infections. However, the overall diversity of the bacterial population residing on banknotes is still unknown in Brazil. In this study, we aimed to investigate the overall bacterial population from 150 different Brazilian Rial (R$) notes in circulation using a culture-independent Illumina massively parallel sequencing approach of the 16S rRNA genes. Samples were randomly collected from three different street markets or "feiras" in the metropolitan region of São Paulo. Taxonomical composition revealed the abundance of Proteobacteria phyla, followed by Firmicutes and Streptophyta, with a total of 1193 bacterial families and 3310 bacterial genera. Most of these bacterial genera are of human, animal, and environmental origins. Also, our analysis revealed the presence of some potential pathogenic bacterial genera including Salmonella, Staphylococcus, and Klebsiella. The results demonstrate that there is a tremendous diversity of bacterial contamination on currency notes, including organisms known to be opportunistic pathogens. One of the factors that may contribute to the richness of bacterial diversity in currency notes is personal hygiene. Thus, our results underscore the need to increase public awareness of the importance of personal hygiene of money handlers who also handle food.

  12. Molecular Analysis of Bacterial Microbiota on Brazilian Currency Note Surfaces

    Directory of Open Access Journals (Sweden)

    Tairacan Augusto Pereira da Fonseca


    Full Text Available Currency notes have been implicated as a vehicle for transmitting community-acquired bacterial infections. However, the overall diversity of the bacterial population residing on banknotes is still unknown in Brazil. In this study, we aimed to investigate the overall bacterial population from 150 different Brazilian Rial (R$ notes in circulation using a culture-independent Illumina massively parallel sequencing approach of the 16S rRNA genes. Samples were randomly collected from three different street markets or “feiras” in the metropolitan region of São Paulo. Taxonomical composition revealed the abundance of Proteobacteria phyla, followed by Firmicutes and Streptophyta, with a total of 1193 bacterial families and 3310 bacterial genera. Most of these bacterial genera are of human, animal, and environmental origins. Also, our analysis revealed the presence of some potential pathogenic bacterial genera including Salmonella, Staphylococcus, and Klebsiella. The results demonstrate that there is a tremendous diversity of bacterial contamination on currency notes, including organisms known to be opportunistic pathogens. One of the factors that may contribute to the richness of bacterial diversity in currency notes is personal hygiene. Thus, our results underscore the need to increase public awareness of the importance of personal hygiene of money handlers who also handle food.

  13. Molecular Investigation of Francisella-Like Endosymbiont in Ticks and Francisella tularensis in Ixodid Ticks and Mosquitoes in Turkey. (United States)

    Duzlu, Onder; Yildirim, Alparslan; Inci, Abdullah; Gumussoy, Kadir Semih; Ciloglu, Arif; Onder, Zuhal


    This study was carried out to investigate the molecular prevalence of Francisella-like endosymbionts (FLEs) and Francisella tularensis in ticks (Acari: Ixodidae) and mosquitoes in Turkey. Genomic DNA pools were constructed from a total of 1477 adult hard ticks of Rhipicephalus (Rh.) annulatus, Rh. turanicus, Rh. sanguineus, Rh. bursa, Haemaphysalis (Hae.) parva, Hae. sulcata, Hyalomma marginatum marginatum, H. anatolicum anatolicum, H. anatolicum excavatum, H. detritum detritum, H. dromedarii, Dermacentor marginatus, and Ixodes ricinus species, which were collected from several barns, cattle, and people. Genomic DNA was also extracted from pools consisting of 6203 adult female mosquito species belonging to Aedes vexans, Culex (Cx.) pipiens, Cx. hortensis, Cx. theileri, Culiseta annulata, and Anopheles maculipennis species. Conventional PCR and TaqMan probe-based real- time PCR targeting the 16S rRNA gene for FLEs and the lpnA gene for F. tularensis, respectively, were performed on the DNA isolates obtained. FLEs and F. tularensis were not found in any genomic DNA pools constructed from ixodid ticks and mosquitos. This study represents the first investigation of F. tularensis and FLEs in potential vector ticks and mosquitoes by molecular methods in Turkey. The present study provides useful insights into the molecular epidemiology of F. tularensis and FLEs. One of the major conclusions of the study is that tularemia outbreaks may be essentially due to direct transmission from the environment (especially from water) in Turkey and not to vector-borne transmission.

  14. Molecular-Cytological Identification and Chromosome Behavior Analysis of Telotetrasomic in Rice

    Institute of Scientific and Technical Information of China (English)

    GONG Zhi-yun; GAO Qing-song; YU Heng-xiu; YI Chuan-deng; GU Ming-hong


    From the progenies of a telotrisomic of chromosome 9 short arm of an indica rice variety, Zhongxian 3037, a phenotypical variant was selected. The variant plant had rolled leaves, dispersed plant type, as well as a low seed-setting rate. Cytological and molecular cytological investigations revealed two extra chromosomes, which were the shortest in somatic cells of the variant. Fluorescent in situ hybridization (FISH) analysis using a rice centromere specific DNA (RCS2) and a DNA sequence specific for chromosome 9 on premetaphase and pachytene chromosomes showed that these two chromosomes were the short arms of chromosome 9. That is to say, the variant was a telotetrasomic of chromosome 9. Among the 25 pachytene cells, the two telosomic chromosomes paired each other to form a bivalent and didn't pair with other normal chromosome 9 as multivalents in 96% cells. However, the bivalent was easy to disassociate in advance.

  15. Concentration transient analysis of antimony surface segregation during Si(100) molecular beam epitaxy (United States)

    Markert, L. C.; Greene, J. E.; Ni, W.-X.; Hansson, G. V.; Sundgren, J.-E.


    Antimony surface segregation during Si(100) molecular beam epitaxy (MBE) was investigated at temperatures T(sub s) = 515 - 800 C using concentration transient analysis (CTA). The dopant surface coverage Theta, bulk fraction gamma, and incorporation probability sigma during MBE were determined from secondary-ion mass spectrometry depth profiles of modulation-doped films. Programmed T(sub s) changes during growth were used to trap the surface-segregated dopant overlayer, producing concentration spikes whose integrated area corresponds to Theta. Thermal antimony doping by coevaporation was found to result in segregation strongly dependent on T(sub s) with Theta(sub Sb) values up to 0.9 monolayers (ML): in films doped with Sb(+) ions accelerated by 100 V, Theta(sub Sb) was less than or equal to 4 x 10(exp -3) ML. Surface segregation of coevaporated antimony was kinematically limited for the film growth conditions in these experiments.

  16. Molecular Structural Studies of Captopril Drug, Using Thermal Analysis, mass Spectral Fragmentation and Semi- empirical MO- Calculations

    Directory of Open Access Journals (Sweden)

    H. M. Arafa


    Full Text Available In this work captopril an antihypertensive (KPL drug, was investigated using thermal analysis (TA measurements (TG-DTA in comparison with electron impact (EI mass spectral (MS fragmentation at 70 eV. Semi-empirical molecular (MO calculations, using PM3 method in the neutral and positively charged forms of the drug. These include molecular geometry, bond order, charge distribution, heats of formation and ionization energy. The behavior of the drug under drug TA decomposition, reveal a moderate stability up to 160Co before a completely decomposition in the range 160-240 Co. The initial decomposition is due to COOH + CH3 loss, followed by SH loss. On the other hand, the molecular ion can easily fragmented by CO2 loss followed by SH loss. This is the best-selected pathway comparable with decomposition using TA. MO-Calculation is used to declare these observations.

  17. Probing the interaction of a therapeutic flavonoid, pinostrobin with human serum albumin: multiple spectroscopic and molecular modeling investigations.

    Directory of Open Access Journals (Sweden)

    Shevin R Feroz

    Full Text Available Interaction of a pharmacologically important flavonoid, pinostrobin (PS with the major transport protein of human blood circulation, human serum albumin (HSA has been examined using a multitude of spectroscopic techniques and molecular docking studies. Analysis of the fluorescence quenching data showed a moderate binding affinity (1.03 × 10(5 M(-1 at 25°C between PS and HSA with a 1∶1 stoichiometry. Thermodynamic analysis of the binding data (ΔS = +44.06 J mol(-1 K(-1 and ΔH = -15.48 kJ mol(-1 and molecular simulation results suggested the involvement of hydrophobic and van der Waals forces, as well as hydrogen bonding in the complex formation. Both secondary and tertiary structural perturbations in HSA were observed upon PS binding, as revealed by intrinsic, synchronous, and three-dimensional fluorescence results. Far-UV circular dichroism data revealed increased thermal stability of the protein upon complexation with PS. Competitive drug displacement results suggested the binding site of PS on HSA as Sudlow's site I, located at subdomain IIA, and was well supported by the molecular modelling data.

  18. Synthesis, vibrational spectroscopic investigations, molecular docking, antibacterial studies and molecular dynamics study of 5-[(4-nitrophenyl)acetamido]-2-(4-tert-butylphenyl)benzoxazole (United States)

    Sheena Mary, Y.; Al-Shehri, Mona M.; Jalaja, K.; Al-Omary, Fatmah A. M.; El-Emam, Ali A.; Yohannan Panicker, C.; Armaković, Stevan; Armaković, Sanja J.; Temiz-Arpaci, Ozlem; Van Alsenoy, C.


    Antimicrobial active 5-[(4-nitrophenyl)acetamido]-2-(4-tert-butylphenyl)benzoxazole (NATPB) was synthesized and observed IR, Raman bands are compared with the theoretically predicted wave numbers. In the IR spectrum the NH stretching wave number splits into a doublet with a noted difference and is red shifted from the computed value, which indicates the weakening of NH bond resulting in proton transfer to the neighbouring oxygen atom. The HOMO-LUMO plots reveal the charge transfer in the molecular system through the conjugated paths. The electrophilic and nucleophilic reactive sites are identified from the MEP plot. Mapping of average local ionization energy (ALIE) values to the electron density surface served us as a tool for prediction of molecule sites possibly prone to electrophilic attacks. Other important reactive centres of the title molecule were detected by calculations of Fukui functions. Calculations of bond dissociation energies (BDE) for hydrogen abstraction were used in order to assess whether the NATPB molecules is prone to autoxidation mechanism or not, while BDE of the remaining single acyclic bonds were used in order to determine the weakest bond. Interaction properties with water were investigated by molecular dynamics (MD) simulations and calculations of radial distribution functions (RDFs). The compound possessed broad spectrum activity against all of the tested Gram-positive and Gram-negative bacteria and yeasts, their minimum inhibitory concentrations (MICs) ranging between 32 and 128 μg/ml. The compound exhibited significant antibacterial activity (32 μg/ml) against an antibiotic resistant E. faecalis isolate, at same potency with the compared standard drugs vancomycin and gentamycin sulfate. The molecular docking studies show that the compound might exhibit inhibitory activity against CDK inhibitors.

  19. Molecular Investigations of Bacteroides as Microbial Source Tracking Tools in Southeast Louisiana Watersheds (United States)

    Schulz, C. J.; Childers, G. W.; Engel, A. S.


    Microbial Source Tracking (MST) is a developing field that is gaining increased attention. MST refers to a host of techniques that discriminates among the origins of fecal material found in natural waters from different sources (e.g. human, livestock, and wildlife) by using microbial indicator species with specificity to only certain host organisms. The development of species-specific molecular markers would allow for better evaluation of public health risks and tracking of nutrient sources impacting a watershed. Although several MST methods have been reported with varying levels of success, few offer general applicability for natural waters due to spatial and temporal constraints associated with these methods. One group of molecular MST markers that show promise for broad environmental applications are molecular 16S rDNA probes for Bacteroides. This method is based on 16S rDNA detection directly from environmental samples without the need for a preliminary cultivation step. In this study we have expanded previous sampling efforts to compile a database of over 1000 partial 16S rRNA Bacteroides genes retrieved from the fecal material of 15 different host species (human, cat, dog, pig, kangaroo). To characterize survival of Bacteroides outside of the host, survival time of the Bacteroides marker was compared to that of E.coli under varying natural environmental conditions (temperature and salinity). Bacteroides displayed a survival curve with shouldering and tailing similar to that of E.coli, but log reduction times differed with treatment. In summary, MST marker stability was identified within host species and the overall Bacteroides community structure correlated to host diet, suggesting that detection of a Bacteroides community could confidently identify fecal contamination point sources. Natural water samples from southeast Louisiana were collected for MST including the Tangipahoa River watershed where the source of fecal contamination has been hotly debated. The

  20. Investigating the Inhibitory Effect of Wortmannin in the Hotspot Mutation at Codon 1047 of PIK3CA Kinase Domain: A Molecular Docking and Molecular Dynamics Approach. (United States)

    Kumar, D Thirumal; Doss, C George Priya


    Oncogenic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) are the most frequently reported in association with various forms of cancer. Several studies have reported the significance of hotspot mutations in a catalytic subunit of PIK3CA in association with breast cancer. Mutations are frequently observed in the highly conserved region of the kinase domain (797-1068 amino acids) of PIK3CA are activating or gain-of-function mutations. Mutation in codon 1047 occurs in the C-terminal region of the kinase domain with histidine (H) replaced by arginine (R), lysine (L), and tyrosine (Y). Pathogenicity and protein stability predictors PhD-SNP, Align GVGD, HANSA, iStable, and MUpro classified H1047R as highly deleterious when compared to H1047L and H1047Y. To explore the inhibitory activity of Wortmannin toward PIK3CA, the three-dimensional structure of the mutant protein was determined using homology modeling followed by molecular docking and molecular dynamics analysis. Docking studies were performed for the three mutants and native with Wortmannin to measure the differences in their binding pattern. Comparative docking study revealed that H1047R-Wortmannin complex has a higher number of hydrogen bonds as well as the best binding affinity next to the native protein. Furthermore, 100 ns molecular dynamics simulation was initiated with the docked complexes to understand the various changes induced by the mutation. Though Wortmannin was found to nullify the effect of H1047R over the protein, further studies are required for designing a better compound. As SNPs are major genetic variations observed in disease condition, personalized medicine would provide enhanced drug therapy.

  1. Computer System for Analysis of Molecular Evolution Modes (SAMEM): analysis of molecular evolution modes at deep inner branches of the phylogenetic tree. (United States)

    Gunbin, Konstantin V; Suslov, Valentin V; Genaev, Mikhail A; Afonnikov, Dmitry A

    SAMEM (System for Analysis of Molecular Evolution Modes), a web-based pipeline system for inferring modes of molecular evolution in genes and proteins (, is presented. Pipeline 1 performs analyses of protein-coding gene evolution; pipeline 2 performs analyses of protein evolution; pipeline 3 prepares datasets of genes and/or proteins, performs their primary analysis, and builds BLOSUM matrices; pipeline 4 checks if these genes really are protein-coding. Pipeline 1 has an all-new feature, which allows the user to obtain K(R)/K(C) estimates using several different methods. An important feature of pipeline 2 is an original method for analyzing the rates of amino acid substitutions at the branches of a phylogenetic tree. The method is based on Markov modeling and a non-parametric permutation test, which compares expected and observed frequencies of amino acid substitutions, and infers the modes of molecular evolution at deep inner branches.

  2. Binding of molecular oxygen by an artificial heme analogue: investigation on the formation of an Fe–tetracarbene superoxo complex

    KAUST Repository

    Anneser, Markus R.


    The dioxygen reactivity of a cyclic iron(II) tetra–NHC-complex (NHC: N-heterocyclic carbene) is investigated. Divergent oxidation behavior is observed depending on the choice of the solvent (acetonitrile or acetone). In the first case, exposure to molecular oxygen leads to an oxygen free Fe(III) whereas in the latter case an oxide bridged Fe(III) dimer is formed. In acetone, an Fe(III)-superoxide can be trapped, isolated and characterized as intermediate at low temperatures. An Fe(III)–O–Fe(III) dimer is formed from the Fe(III) superoxide in acetone upon warming and the molecular structure has been revealed by single crystal X-ray diffraction. It is shown that the oxidation of the Fe(II) complex in both solvents is a reversible process. For the regeneration of the initial Fe(II) complex both organic and inorganic reducing agents can be used.

  3. The Sample Analysis at Mars Investigation and Instrument Suite (United States)

    Mahaffy, Paul; Webster, Christopher R.; Conrad, Pamela G.; Arvey, Robert; Bleacher, Lora; Brinckerhoff, William B.; Eigenbrode, Jennifer L.; Chalmers, Robert A.; Dworkin, Jason P.; Errigo, Therese; Farley, Rodger; Feng, Steven; Frazier, Gregory; Glavin, Daniel P.; Harpold, Daniel N.; Jordan, Partick; Kellogg, James; Lewis, Jesse; Martin, David K.; Maurer, John; McAdam, Amy C.; McLennan, Douglas; Pavlov, Alexander A.; Raaen, Eric; Schinman, Oren


    The Sample Analysis at Mars (SAM) investigation of the Mars Science Laboratory (MSL) addresses the chemical and isotopic composition of the atmosphere and volatiles extracted from solid samples. The SAM investigation is designed to contribute substantially to the mission goal of quantitatively assessing the habitability of Mars as an essential step in the search for past or present life on Mars. SAM is a 40 kg instrument suite located in the interior of MSL's Curiosity rover. The SAM instruments are a quadrupole mass spectrometer, a tunable laser spectrometer, and a 6-column gas chromatograph all coupled through solid and gas processing systems to provide complementary information on the same samples. The SAM suite is able to measure a suite of light isotopes and to analyze volatiles directly from the atmosphere or thermally released from solid samples. In addition to measurements of simple inorganic compounds and noble gases SAM will conduct a sensitive search for organic compounds with either thermal or chemical extraction from sieved samples delivered by the sample processing system on the Curiosity rover's robotic arm,

  4. The Sample Analysis at Mars Investigation and Instrument Suite (United States)

    Mahaffy, Paul; Webster, Chris R.; Cabane, M.; Conrad, Pamela G.; Coll, Patrice; Atreya, Sushil K.; Arvey, Robert; Barciniak, Michael; Benna, Mehdi; Bleacher, L.; Brinckerhoff, William B.; Eigenbrode, Jennifer L.; Carignan, Daniel; Cascia, Mark; Chalmers, Robert A.; Dworkin, Jason P.; Errigo, Therese; Everson, Paula; Franz, Heather; Farley, Rodger; Feng, Steven; Frazier, Gregory; Freissinet, Caroline; Glavin, Daniel P.; Harpold, Daniel N.


    The Sample Analysis at Mars (SAM) investigation of the Mars Science Laboratory(MSL) addresses the chemical and isotopic composition of the atmosphere and volatilesextracted from solid samples. The SAM investigation is designed to contribute substantiallyto the mission goal of quantitatively assessing the habitability of Mars as an essentialstep in the search for past or present life on Mars. SAM is a 40 kg instrument suite locatedin the interior of MSLs Curiosity rover. The SAM instruments are a quadrupole massspectrometer, a tunable laser spectrometer, and a 6-column gas chromatograph all coupledthrough solid and gas processing systems to provide complementary information on thesame samples. The SAM suite is able to measure a suite of light isotopes and to analyzevolatiles directly from the atmosphere or thermally released from solid samples. In additionto measurements of simple inorganic compounds and noble gases SAM will conducta sensitive search for organic compounds with either thermal or chemical extraction fromsieved samples delivered by the sample processing system on the Curiosity rovers roboticarm.

  5. The Sample Analysis at Mars Investigation and Instrument Suite (United States)

    Mahaffy, Paul R.; Webster, Christopher R.; Cabane, Michel; Conrad, Pamela G.; Coll, Patrice; Atreya, Sushil K.; Arvey, Robert; Barciniak, Michael; Benna, Mehdi; Bleacher, Lora; Brinckerhoff, William B.; Eigenbrode, Jennifer L.; Carignan, Daniel; Cascia, Mark; Chalmers, Robert A.; Dworkin, Jason P.; Errigo, Therese; Everson, Paula; Franz, Heather; Farley, Rodger; Feng, Steven; Frazier, Gregory; Freissinet, Caroline; Glavin, Daniel P.; Harpold, Daniel N.; Hawk, Douglas; Holmes, Vincent; Johnson, Christopher S.; Jones, Andrea; Jordan, Patrick; Kellogg, James; Lewis, Jesse; Lyness, Eric; Malespin, Charles A.; Martin, David K.; Maurer, John; McAdam, Amy C.; McLennan, Douglas; Nolan, Thomas J.; Noriega, Marvin; Pavlov, Alexander A.; Prats, Benito; Raaen, Eric; Sheinman, Oren; Sheppard, David; Smith, James; Stern, Jennifer C.; Tan, Florence; Trainer, Melissa; Ming, Douglas W.; Morris, Richard V.; Jones, John; Gundersen, Cindy; Steele, Andrew; Wray, James; Botta, Oliver; Leshin, Laurie A.; Owen, Tobias; Battel, Steve; Jakosky, Bruce M.; Manning, Heidi; Squyres, Steven; Navarro-González, Rafael; McKay, Christopher P.; Raulin, Francois; Sternberg, Robert; Buch, Arnaud; Sorensen, Paul; Kline-Schoder, Robert; Coscia, David; Szopa, Cyril; Teinturier, Samuel; Baffes, Curt; Feldman, Jason; Flesch, Greg; Forouhar, Siamak; Garcia, Ray; Keymeulen, Didier; Woodward, Steve; Block, Bruce P.; Arnett, Ken; Miller, Ryan; Edmonson, Charles; Gorevan, Stephen; Mumm, Erik


    The Sample Analysis at Mars (SAM) investigation of the Mars Science Laboratory (MSL) addresses the chemical and isotopic composition of the atmosphere and volatiles extracted from solid samples. The SAM investigation is designed to contribute substantially to the mission goal of quantitatively assessing the habitability of Mars as an essential step in the search for past or present life on Mars. SAM is a 40 kg instrument suite located in the interior of MSL's Curiosity rover. The SAM instruments are a quadrupole mass spectrometer, a tunable laser spectrometer, and a 6-column gas chromatograph all coupled through solid and gas processing systems to provide complementary information on the same samples. The SAM suite is able to measure a suite of light isotopes and to analyze volatiles directly from the atmosphere or thermally released from solid samples. In addition to measurements of simple inorganic compounds and noble gases SAM will conduct a sensitive search for organic compounds with either thermal or chemical extraction from sieved samples delivered by the sample processing system on the Curiosity rover's robotic arm.

  6. Sustained effects of acupuncture stimulation investigated with centrality mapping analysis

    Directory of Open Access Journals (Sweden)

    Xiangyu Long


    Full Text Available Acupuncture can have instant and sustained effects, however its mechanisms of action are still unclear. Here we investigated the sustained effect of acupuncture by evaluating centrality changes in resting-state functional magnetic resonance imaging after manually stimulating the acupuncture point ST36 at the lower leg or two control point locations (CP1 same dermatome, CP2 different dermatome. Data from a previously published experiment evaluating instant BOLD effects and S2-seed-based resting state connectivity was re-analyzed using eigenvector centrality mapping (ECM and degree centrality mapping (DCM. These data-driven methods might add new insights into sustained acupuncture effects on both global and local inter-region connectivity (centrality by evaluating the summary of connections of every voxel. We found higher centrality in parahippocampal gyrus and middle temporal gyrus after ST36 stimulation in comparison to the two control points. These regions are positively correlated to major hubs of the default mode network, which might be the primary network affected by chronic pain. The stronger integration of both regions within the whole-brain connectome after stimulation of ST36 might be a potential contributor to pain modulation by acupuncture. These findings highlight centrality mapping as a valuable analysis for future imaging studies investigating clinically-relevant outcomes associated with physiological response to acupuncture stimulation.

  7. Investigation of Plasma Eects in Ultra High Molecular Weight Polyethylene (UHMWPE) Cords

    DEFF Research Database (Denmark)

    Teodoru, Steluta; Kusano, Yukihiro; Rozlosnik, Noemi

    modication for improved wetting and/or adhesion with other polymeric materials. Atmospheric pressure plasma treatment is promising for this purpose due to its environmental compatibility, high treatment eects without aecting the textural characteristics of the bulk material, its applicability to a variety......Ultra-high-molecular-weight polyethylene (UHMWPE) has been widely used because of its high chemical stabil- ity, high impact strength, exibility and low cost. Its eld of applications includes use in composites, packing for microelectronic components and biomaterials, usually requiring its surface...... of shapes, and easy up-scaling and construction of in-line production processes. An atmospheric pressure dielectric barrier discharge (DBD) plasma is used to study surface modication eect on UHMWPE cords, operated at a frequency of ca. 40 kHz in He, He/O2, O2 and N2 gases. The cords were continuously...

  8. Molecular Dynamics Investigation of the Products of Alkoxysilane Condensation: Bulk Gels and Surface Coatings (United States)

    Faller, Roland; Deetz, Joshua

    We characterize silica gels and organo-silicon surface coatings using reactive molecular dynamics simulations. To model the chemical reactions, we use a reactive force field (ReaxFF) which we have optimized in a novel parallelized semi-automatic way to model hydrolysis and condensation reactions. The morphologies of silica gels obtained from tetra- and tri-alkoxysilanes are determined by allowing the system to condense while simultaneously removing water and replacing it with precursor solution. It is found that the gels obtained from trialkoxysilanes are more loosely bonded, and that the chemistry of the headgroup is important to the gel morphology. We furthermore simulated the chemisorption of alkoxysilanes with organic headgroups to hydroxylated silica surfaces. We observe a competition between alkoxysilanes condensing with themselves or with the silica surface.

  9. Structural Effects of Small Molecules on Phospholipid Bilayers Investigated by Molecular Simulations

    CERN Document Server

    Lee, B W; Sum, A K; Vattulainen, I; Patra, M; Karttunen, M; Lee, Bryan W; Faller, Roland; Sum, Amadeu K; Vattulainen, Ilpo; Patra, Michael; Karttunen, Mikko


    We summarize and compare recent Molecular Dynamics simulations on the interactions of dipalmitoylphosphatidylcholine (DPPC) bilayers in the liquid crystalline phase with a number of small molecules including trehalose, a disaccharide of glucose, alcohols, and dimethylsulfoxide (DMSO). The sugar molecules tend to stabilize the structure of the bilayer as they bridge adjacent lipid headgroups. They do not strongly change the structure of the bilayer. Alcohols and DMSO destabilize the bilayer as they increase its area per molecule in the bilayer plane and decrease the order parameter. Alcohols have a stronger detrimental effect than DMSO. The observables which we compare are the area per molecule in the plane of the bilayer, the membrane thickness, and the NMR order parameter of DPPC hydrocarbon tails. The area per molecule and the order parameter are very well correlated whereas the bilayer thickness is not necessarily correlated with them.

  10. Molecular Polymorphism: Microwave Spectra, Equilibrium Structures, and an Astronomical Investigation of the HNCS Isomeric Family

    CERN Document Server

    McGuire, Brett A; Thorwirth, Sven; Brünken, Sandra; Lattanzi, Valerio; Neill, Justin L; Spezzano, Silvia; Yu, Zhenhong; Zaleski, Daniel P; Remijan, Anthony J; Pate, Brooks H; McCarthy, Michael C


    The rotational spectra of thioisocyanic acid (HNCS), and its three energetic isomers (HSCN, HCNS, and HSNC) have been observed at high spectral resolution by a combination of chirped-pulse and Fabry-P\\'{e}rot Fourier-transform microwave spectroscopy between 6 and 40~GHz in a pulsed-jet discharge expansion. Two isomers, thiofulminic acid (HCNS) and isothiofulminic acid (HSNC), calculated here to be 35-37~kcal/mol less stable than the ground state isomer HNCS, have been detected for the first time. Precise rotational, centrifugal distortion, and nitrogen hyperfine coupling constants have been determined for the normal and rare isotopic species of both molecules; all are in good agreement with theoretical predictions obtained at the coupled cluster level of theory. On the basis of isotopic spectroscopy, precise molecular structures have been derived for all four isomers by correcting experimental rotational constants for the effects of rotation-vibration calculated theoretically. Formation and isomerization path...

  11. Investigations into the role of oxacarbenium ions in glycosylation reactions by ab initio molecular dynamics. (United States)

    Ionescu, Andrei R; Whitfield, Dennis M; Zgierski, Marek Z; Nukada, Tomoo


    We present a constrained ab initio molecular dynamics method that allows the modeling of the conformational interconversions of glycopyranosyl oxacarbenium ions. The model was successfully tested by estimating the barriers to ring inversion for two 4-substituted tetrahydropyranosyl oxacarbenium ions. The model was further extended to predict the pathways that connect the (4)H(3) half-chair conformation of 2,3,4,6-tetra-O-methyl-d-glucopyranosyl cation to its inverted (5)S(1) conformation and the (4)H(3) half-chair conformation of 2,3,4,6-tetra-O-methyl-d-mannopyranosyl cation to its inverted (3)E conformation. The modeled interconversion pathways reconcile a large body of experimental work on the acid-catalyzed hydrolysis of glycosides and the mechanisms of a number of glucosidases and mannosidases.

  12. Molecular dynamics investigation of carbon nanotube junctions in non-aqueous solutions

    KAUST Repository

    Gkionis, Konstantinos


    The properties of liquids in a confined environment are known to differ from those in the bulk. Extending this knowledge to geometries defined by two metallic layers in contact with the ends of a carbon nanotube is important for describing a large class of nanodevices that operate in non-aqueous environments. Here we report a series of classical molecular dynamics simulations for gold-electrode junctions in acetone, cyclohexane and N,N-dimethylformamide solutions and analyze the structure and the dynamics of the solvents in different regions of the nanojunction. The presence of the nanotube has little effect on the ordering of the solvents along its axis, while in the transversal direction deviations are observed. Importantly, the orientational dynamics of the solvents at the electrode-nanotube interface differ dramatically from that found when only the electrodes are present.

  13. Way toward "dietary pesticides": molecular investigation of insecticidal action of caffeic acid against Helicoverpa armigera. (United States)

    Joshi, R S; Wagh, T P; Sharma, N; Mulani, F A; Sonavane, U; Thulasiram, H V; Joshi, R; Gupta, V S; Giri, A P


    Bioprospecting of natural molecules is essential to overcome serious environmental issues and pesticide resistance in insects. Here we are reporting insights into insecticidal activity of a plant natural phenol. In silico and in vitro screening of multiple molecules supported by in vivo validations suggested that caffeic acid (CA) is a potent inhibitor of Helicoverpa armigera gut proteases. Protease activity and gene expression were altered in CA-fed larvae. The structure-activity relationship of CA highlighted that all the functional groups are crucial for inhibition of protease activity. Biophysical studies and molecular dynamic simulations revealed that sequential binding of multiple CA molecules induces conformational changes in the protease(s) and thus lead to a significant decline in their activity. CA treatment significantly inhibits the insect's detoxification enzymes, thus intensifying the insecticidal effect. Our findings suggest that CA can be implicated as a potent insecticidal molecule and explored for the development of effective dietary pesticides.

  14. Molecular genetic analysis of hereditary non-polyposis colorectal cancer syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Froggatt, N.J. [Cambridge Univ. (United Kingdom)]|[Addenbrooke`s Hospital, Cambridge (United Kingdom); Koch, D.J.; Barton, D.E. [Addenbrooke`s Hospital, Cambridge (United Kingdom)] [and others


    HNPCC is estimated to account for 5-10% of all cases of colorectal cancer. Recently genes for HNPCC have been mapped to chromosomes 2p and 3p and candidate genes (hMSH2 and hMLH1) have been identified. We have investigated the molecular pathology of HNPCC by linkage analysis and direct mutation analysis. 14 HNPCC families were investigated for linkage to hMSH2 and hMLH1 with microsatellite markers at D2S119, D2S123, D2S136, D2S391, D2S378 and D3S1007, D3S1029, D3S1076, D3S1298, D3S1611, respectively. Overall the only significant linkage was obtained with D2S123 (Zmax=3.77 at {theta}=0.0), but locus heterogeneity was confirmed: linkage to hMSH2 and hMLH1 was excluded in 6 and 5 families, respectively. 3 families were uniformative for linkage/exclusion to either candidate gene, but no evidence for a third HNPCC locus could be detected. There was no correlation between clinical phenotype (Lynch type I or II) and the results of linkage analysis. No individual family gave a lod score of >3 with any marker, and only a minority of our HNPCC families have been suitable for genetic linkage analysis. We therefore screened affected individuals from 37 unrelated kindreds for mutations in hMSH2 and exons 3 and 4 of the APC gene. Mutation screening was performed using exon specific primers and SSCP analysis. No abnormalities were found in the APC exons suggesting that mutations in these APC 5{prime} exons are not a common cause of HNPCC. hMSH2 screening is continuing, and one missense mutation in a highly conserved codon 322 in exon 6 has been identified.

  15. Scaling analysis for the investigation of slip mechanisms in nanofluids (United States)

    Savithiri, S.; Pattamatta, Arvind; Das, Sarit K.


    The primary objective of this study is to investigate the effect of slip mechanisms in nanofluids through scaling analysis. The role of nanoparticle slip mechanisms in both water- and ethylene glycol-based nanofluids is analyzed by considering shape, size, concentration, and temperature of the nanoparticles. From the scaling analysis, it is found that all of the slip mechanisms are dominant in particles of cylindrical shape as compared to that of spherical and sheet particles. The magnitudes of slip mechanisms are found to be higher for particles of size between 10 and 80 nm. The Brownian force is found to dominate in smaller particles below 10 nm and also at smaller volume fraction. However, the drag force is found to dominate in smaller particles below 10 nm and at higher volume fraction. The effect of thermophoresis and Magnus forces is found to increase with the particle size and concentration. In terms of time scales, the Brownian and gravity forces act considerably over a longer duration than the other forces. For copper-water-based nanofluid, the effective contribution of slip mechanisms leads to a heat transfer augmentation which is approximately 36% over that of the base fluid. The drag and gravity forces tend to reduce the Nusselt number of the nanofluid while the other forces tend to enhance it.

  16. Investigating echo state networks dynamics by means of recurrence analysis

    CERN Document Server

    Bianchi, Filippo Maria; Alippi, Cesare


    In this paper, we elaborate over the well-known interpretability issue in echo state networks. The idea is to investigate the dynamics of reservoir neurons with time-series analysis techniques taken from research on complex systems. Notably, we analyze time-series of neuron activations with Recurrence Plots (RPs) and Recurrence Quantification Analysis (RQA), which permit to visualize and characterize high-dimensional dynamical systems. We show that this approach is useful in a number of ways. First, the two-dimensional representation offered by RPs provides a way for visualizing the high-dimensional dynamics of a reservoir. Our results suggest that, if the network is stable, reservoir and input denote similar line patterns in the respective RPs. Conversely, the more unstable the ESN, the more the RP of the reservoir presents instability patterns. As a second result, we show that the $\\mathrm{L_{max}}$ measure is highly correlated with the well-established maximal local Lyapunov exponent. This suggests that co...

  17. Scaling analysis for the investigation of slip mechanisms in nanofluids

    Directory of Open Access Journals (Sweden)

    Savithiri S


    Full Text Available Abstract The primary objective of this study is to investigate the effect of slip mechanisms in nanofluids through scaling analysis. The role of nanoparticle slip mechanisms in both water- and ethylene glycol-based nanofluids is analyzed by considering shape, size, concentration, and temperature of the nanoparticles. From the scaling analysis, it is found that all of the slip mechanisms are dominant in particles of cylindrical shape as compared to that of spherical and sheet particles. The magnitudes of slip mechanisms are found to be higher for particles of size between 10 and 80 nm. The Brownian force is found to dominate in smaller particles below 10 nm and also at smaller volume fraction. However, the drag force is found to dominate in smaller particles below 10 nm and at higher volume fraction. The effect of thermophoresis and Magnus forces is found to increase with the particle size and concentration. In terms of time scales, the Brownian and gravity forces act considerably over a longer duration than the other forces. For copper-water-based nanofluid, the effective contribution of slip mechanisms leads to a heat transfer augmentation which is approximately 36% over that of the base fluid. The drag and gravity forces tend to reduce the Nusselt number of the nanofluid while the other forces tend to enhance it.

  18. Real-space investigation of energy transfer in heterogeneous molecular dimers. (United States)

    Imada, Hiroshi; Miwa, Kuniyuki; Imai-Imada, Miyabi; Kawahara, Shota; Kimura, Kensuke; Kim, Yousoo


    Given its central role in photosynthesis and artificial energy-harvesting devices, energy transfer has been widely studied using optical spectroscopy to monitor excitation dynamics and probe the molecular-level control of energy transfer between coupled molecules. However, the spatial resolution of conventional optical spectroscopy is limited to a few hundred nanometres and thus cannot reveal the nanoscale spatial features associated with such processes. In contrast, scanning tunnelling luminescence spectroscopy has revealed the energy dynamics associated with phenomena ranging from single-molecule electroluminescence, absorption of localized plasmons and quantum interference effects to energy delocalization and intervalley electron scattering with submolecular spatial resolution in real space. Here we apply this technique to individual molecular dimers that comprise a magnesium phthalocyanine and a free-base phthalocyanine (MgPc and H2Pc) and find that locally exciting MgPc with the tunnelling current of the scanning tunnelling microscope generates a luminescence signal from a nearby H2Pc molecule as a result of resonance energy transfer from the former to the latter. A reciprocating resonance energy transfer is observed when exciting the second singlet state (S2) of H2Pc, which results in energy transfer to the first singlet state (S1) of MgPc and final funnelling to the S1 state of H2Pc. We also show that tautomerization of H2Pc changes the energy transfer characteristics within the dimer system, which essentially makes H2Pc a single-molecule energy transfer valve device that manifests itself by blinking resonance energy transfer behaviour.

  19. Real-space investigation of energy transfer in heterogeneous molecular dimers (United States)

    Imada, Hiroshi; Miwa, Kuniyuki; Imai-Imada, Miyabi; Kawahara, Shota; Kimura, Kensuke; Kim, Yousoo


    Given its central role in photosynthesis and artificial energy-harvesting devices, energy transfer has been widely studied using optical spectroscopy to monitor excitation dynamics and probe the molecular-level control of energy transfer between coupled molecules. However, the spatial resolution of conventional optical spectroscopy is limited to a few hundred nanometres and thus cannot reveal the nanoscale spatial features associated with such processes. In contrast, scanning tunnelling luminescence spectroscopy has revealed the energy dynamics associated with phenomena ranging from single-molecule electroluminescence, absorption of localized plasmons and quantum interference effects to energy delocalization and intervalley electron scattering with submolecular spatial resolution in real space. Here we apply this technique to individual molecular dimers that comprise a magnesium phthalocyanine and a free-base phthalocyanine (MgPc and H2Pc) and find that locally exciting MgPc with the tunnelling current of the scanning tunnelling microscope generates a luminescence signal from a nearby H2Pc molecule as a result of resonance energy transfer from the former to the latter. A reciprocating resonance energy transfer is observed when exciting the second singlet state (S2) of H2Pc, which results in energy transfer to the first singlet state (S1) of MgPc and final funnelling to the S1 state of H2Pc. We also show that tautomerization of H2Pc changes the energy transfer characteristics within the dimer system, which essentially makes H2Pc a single-molecule energy transfer valve device that manifests itself by blinking resonance energy transfer behaviour.

  20. In vitro and in vivo models for analysis of resistance to anticancer molecular therapies. (United States)

    Rosa, Roberta; Monteleone, Francesca; Zambrano, Nicola; Bianco, Roberto


    The efficacy of classical and molecular therapies in cancer is hampered by the occurrence of primary (intrinsic) and secondary (acquired) refractoriness of tumours to selected therapeutic regimens. Nevertheless, the increased knowledge of the genetic, molecular and metabolic mechanisms underlying cancer results in the generation of a correspondingly increasing number of druggable targets and molecular drugs. Thus, a current challenge in molecular oncology and medicinal chemistry is to cope with the increased need for modelling, both in cellular and animal systems, the genetic assets associated to cancer resistance to drugs. In this review, we summarize the current strategies for generation and analysis of in vitro and in vivo models, which may reveal useful to extract information on the molecular basis of intrinsic and acquired resistance to anticancer molecular agents.

  1. A Theoretical Investigation of the Structure and Reactivity of the Molecular Constituents of Oil Sand and Oil Shale

    Energy Technology Data Exchange (ETDEWEB)

    Parish, Carol A. [Univ. of Richmond, VA (United States)


    2 reaction at three different sites on the 2-thienylmethyl radical. The addition is exothermic by 37 ~ 55 kcal mol-1 relative to the entrance channel. These excess energies are available to promote further decomposition or rearrangement of the adducts that lead to nascent products such as H, OH, H2O and CH2O. The reaction surfaces are characterized by relatively low barriers (most are lower than 10 kcal mol-1). Based upon a careful analysis of the overall barrier heights and reaction exothermicities, the formation of O2, OH and H2O is likely to be an important pathway in the radical recombination reactions of 2-thienylmethyl + HO2. This work was published in the Journal of Physical Chemistry A, 2011, 115, 14546-14557. REACTION OF THIOPHENE AND METHYLTHIOPHENE WITH SINGLET AND TRIPLET MOLECULAR OXYGEN Mechanisms for the reaction of thiophene and 2-methylthiophene with molecular oxygen on both the triplet and singlet potential energy surfaces (PESs) were investigated using ab initio methods. Thiophene and 2-methylthiophene where shown to react with O2 via two types of mechanisms; namely, direct hydrogen abstraction and addition/elimination. The barriers for reaction with triplet oxygen are all significantly large (i.e., > 30 kcal mol-1), which indicates that the direct oxidation of thiophene by ground state oxygen might be important only in high temperature processes. Reaction of thiophene with singlet oxygen via a 2+4 cycloaddition leading to endoperoxides is the most favorable channel. Moreover, it was found that alkylation of the thiophene ring (i.e., methyl-substituted thiophene) is capable of lowering the barrier height for the addition pathway. The implication of the current theoretical results may shed new light on the initiation mechanisms for combustion of asphaltenes. This work was published in the Journal of Physical Chemistry A, 2012 116, 4934-4946. JAHN-TELLER STABILIZATION IN POSS CATIONS We have a long

  2. Investigation of the local environment of Eu3+ in a silicophosphate glass using site-selective spectroscopy and Molecular Dynamics simulations (United States)

    Ben Slimen, F.; Haouari, M.; Ben Ouada, H.; Guichaoua, D.; Raso, P.; Bidault, X.; Turlier, J.; Gaumer, N.; Chaussedent, S.


    Silicophosphate glasses (SiO2-P2O5) doped with Eu3+ ions were synthesized by the sol-gel process. Optical properties of these glasses were investigated by means of emission spectra and lifetime measurements. The Fluorescence Line Narrowing (FLN) technique was also used to explore the local structure around the Eu3+ ions in this host and to understand the role of phosphate as a codopant. As it is the case for aluminum, the ability of phosphate to avoid the rare earth clustering was investigated, and the role of this codopant in modifying the local order around the rare earth ion was evidenced. The analysis of the FLN spectra and lifetime measurements is consistent with this interpretation. Molecular Dynamics simulations were performed to evaluate and confirm these structural features. Two classes of europium sites were distinguished in agreement with the experimental characterization.

  3. Morphological and molecular investigations of a microsporidium infecting the European grape vine moth, Lobesia botrana Den. et Schiff., and its taxonomic determination as Cystosporogenes legeri nov. comb. (United States)

    Kleespies, Regina G; Vossbrinck, Charles R; Lange, Martin; Jehle, Johannes A


    We have isolated a microsporidium from a laboratory stock of the European grape vine moth, Lobesia botrana Den. et Schiff. (Lepidoptera, Tortricidae). Screening of this stock showed an infection rate of more than 90%, whereas field collected larvae from three different locations in Rhineland-Palatinate (Germany) did not demonstrate any signs of infection. Light and electron microscopic investigations of infected insects showed that gross pathology, morphology, and ultrastructure of the microsporidium are similar to those described earlier for Pleistophora legeri. Comparative phylogenetic analysis of the small subunit rDNA using maximum likelihood, maximum parsimony, and neighbour joining distance methods showed that our isolate was closely related to Cystosporogenes operophterae. Based on our morphological and molecular investigations we propose to rename this species Cystosporogenes legeri nov. comb.

  4. A molecular propeller effect for chiral separation and analysis (United States)

    Clemens, Jonathon B.; Kibar, Osman; Chachisvilis, Mirianas


    Enantiomers share nearly identical physical properties but have different chiral geometries, making their identification and separation difficult. Here we show that when exposed to a rotating electric field, the left- and right-handed chiral molecules rotate with the field and act as microscopic propellers; moreover, owing to their opposite handedness, they propel along the axis of field rotation in opposite directions. We introduce a new molecular parameter called hydrodynamic chirality to characterize the coupling of rotational motion of a chiral molecule into its translational motion and quantify the direction and velocity of such motion. We demonstrate >80% enrichment level of counterpart enantiomers in solution without using chiral selectors or circularly polarized light. We expect our results to have an impact on multiple applications in drug discovery, analytical and chiral chemistry, including determination of absolute configuration, as well as in influencing the understanding of artificial and natural molecular systems where rotational motion of the molecules is involved.

  5. Quantum information analysis of electronic states at different molecular structures

    CERN Document Server

    Barcza, G; Marti, K H; Reiher, M


    We have studied transition metal clusters from a quantum information theory perspective using the density-matrix renormalization group (DMRG) method. We demonstrate the competition between entanglement and interaction localization. We also discuss the application of the configuration interaction based dynamically extended active space procedure which significantly reduces the effective system size and accelerates the speed of convergence for complicated molecular electronic structures to a great extent. Our results indicate the importance of taking entanglement among molecular orbitals into account in order to devise an optimal orbital ordering and carry out efficient calculations on transition metal clusters. We propose a recipe to perform DMRG calculations in a black-box fashion and we point out the connections of our work to other tensor network state approaches.

  6. A Modiifed Molecular Structure Mechanics Method for Analysis of Graphene

    Institute of Scientific and Technical Information of China (English)

    HUA Jun; LI Dongbo; ZHAO Dong; LIANG Shengwei; LIU Qinlong; JIA Ruiyan


    Based on molecular mechanics and the deformation characteristics of the atomic lattice structure of graphene, a modiifed molecular structure mechanics method was developed to improve the original one, that is, the semi-rigid connections were used to model the bond angle variations between the C-C bonds in graphene. The simulated results show that the equivalent space frame model with semi-rigid connections for graphene proposed in this article is a simple, efifcient, and accurate model to evaluate the equivalent elastic properties of graphene. Though the present computational model of the semi-rigid connected space frame is only applied to characterize the mechanical behaviors of the space lattices of graphene, it has more potential applications in the static and dynamic analyses of graphene and other nanomaterials.

  7. [DNA extraction methods of compost for molecular ecology analysis]. (United States)

    Yang, Zhao-Hui; Xiao, Yong; Zeng, Guang-Ming; Liu, Yun-Guo; Deng, Jiu-Hua


    Molecular ecology provides new techniques for studying compost microbes, and the DNA extraction is the basis of molecular techniques. Because of the contamination of humic acids, it turns to be more difficult for compost microbial DNA extraction. Three different approaches, named as lysozyme lysis, ultrasonic lysis and proteinase K lysis with CTAB, were used to extract the total DNA from compost. The detection performed on a nucleic acids and protein analyzer showed that all the three approaches produced high DNA yields. The agarose gel electrophoresis showed that the DNA fragments extracted from compost had a length of about 23 kb. A eubacterial 16S rRNA gene targeted primer pair (27F and 1 495R) was used for PCR amplification, and all the samples got almost the full length 16S rDNA sequence (about 1.5 kb). After digested by restriction endonucleases (Hae Ill and Alu I), the restriction map showed relatively identical microbial diversity in the DNA, which was extracted by the three different approaches. All the compost microbial DNA extracted by the three different approaches could be used for molecular ecological study, and researchers should choose the right approach for extracting microbial DNA from compost based on the facts.

  8. Radiogenomics of glioblastoma: a pilot multi-institutional study to investigate a relationship between tumor shape features and tumor molecular subtype (United States)

    Czarnek, Nicholas M.; Clark, Kal; Peters, Katherine B.; Collins, Leslie M.; Mazurowski, Maciej A.


    Genomic subtype has been shown to be an important predictor of therapy response for patients with glioblastomas. Unfortunately, obtaining the genomic subtype is an expensive process that is not typically included in the standard of care. It is therefore of interest to investigate potential surrogates of molecular subtypes that use standard diagnostic data such as magnetic resonance (MR) imaging. In this study, we analyze the relationship between tumor genomic subtypes, proposed by Verhaak et al, 2010, and novel features that capture the shape of abnormalities as seen in fluid attenuated inversion recovery (FLAIR) MR images. In our study, we used data from 54 patients with glioblastomas from four institutions provided by The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA). We explore five shape features calculated by computer algorithms implemented in our laboratory that assess shape both in individual slices and in rendered three-dimensional tumor volumes. The association between each feature and molecular subtype was assessed using area under the receiver operating characteristic curve analysis. We show that the two dimensional measures of edge complexity are significant discriminators between mesenchymal and classical tumors. These preliminary findings show promise for an imaging-based surrogate of molecular subtype and contribute to the understanding of the relationship between tumor biology and its radiology phenotype.

  9. Binding of mitomycin C to blood proteins: A spectroscopic analysis and molecular docking (United States)

    Jang, Jongchol; Liu, Hui; Chen, Wei; Zou, Guolin


    Mitomycin C (MMC) was the first recognized bioreductive alkylating agent, and has been widely used clinically for antitumor therapy. The binding of MMC to two human blood proteins, human serum albumin (HSA) and human hemoglobin (HHb), have been investigated by fluorescence quenching, synchronous fluorescence, circular dichroism (CD) spectroscopy and molecular docking methods. The fluorescence data showed that binding of MMC to proteins caused strong fluorescence quenching of proteins through a static quenching way, and each protein had only one binding site for the drug. The binding constants of MMC to HSA and HHb at 298 K were 2.71 × 10 4 and 2.56 × 10 4 L mol -1, respectively. Thermodynamic analysis suggested that both hydrophobic interaction and hydrogen bonding played major roles in the binding of MMC to HSA or HHb. The CD spectroscopy indicated that the secondary structures of the two proteins were not changed in the presence of MMC. The study of molecular docking showed that MMC was located in the entrance of site I of HSA, and in the central cavity of HHb.

  10. Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Ruifen Dong


    Full Text Available Abstract Background Patient derived xenografts (PDX are generated by transplanting the original patient’s tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma (HGSC is a deadly form of ovarian/fallopian tube cancer whose response to current chemotherapies varies widely due to patient variability. Therefore, a PDX model can provide a valuable tool to study and test treatment options for each individual patient. Methods In this study, over 200 PDX tumors from nine HGSC were analyzed to investigate the nature and behavior of PDX tumors originating from HGSC. PDX tumors were serially passaged (from P0 to P4 and tumors were grafted orthotopically under the ovarian bursa or subcutaneously. Results Comparative analysis of the histology and molecular markers of tumors from over 200 PDX tumor-bearing mice, revealed that the tumors maintained similar histologies, stem cell populations, and expression for the majority of the tested oncogenic markers, compared to the primary tumors. However, a significant loss of steroid hormone receptors and altered expression of immunoresponsive genes in PDX tumors were also noted. Conclusion Our findings provide substantial new information about PDX tumor characteristics from HGSC which will be valuable towards the development of personalized therapy and new drug development for HGSC.

  11. Molecular tools for epidemiological investigations into Legionella pneumophila environmental diffusion: applications for the prevention

    Directory of Open Access Journals (Sweden)

    Stefania Boccia


    Full Text Available

    Microbiological typing is a useful tool in the epidemiological investigations of infectious diseases, given that it allows for the identification of specific clones among a set of isolates.

     In the last ten years several studies have demonstrated how genotyping methods can be useful in Legionella spp investigations in hospital setting (e.g., epidemic events. Pulsed field gel electrophoresis and amplified fragment length polymorphisms are the current typing methods of choice, even though multilocus sequence typing will probably be the gold standard of the future.

  12. Reactive Molecular Dynamics Investigations of Alkoxysilane Sol-Gel and Surface Coating Processes (United States)

    Deetz, Joshua David

    The ability to generate nanostructured materials with tailored morphology or chemistry is of great technological interest. One proven method of generating metal-oxide materials, and chemically modifying metal-oxide surfaces is through the reactions of molecular building blocks known as alkoxysilanes. Alkoxysilanes are a class of chemicals which contain one or more organic alkoxy groups bonded to silicon atoms. Alkoxysilane (Si-O-R) chemical groups can undergo reactions to form bridges (Si-O-M) with metal oxides. Due to their ability to "attach" to metal-oxides through condensation reactions, alkoxysilanes have a number of interesting applications, such as: the generation of synthetic siloxane materials through the sol-gel process, and the formation of functionalized surface coatings on metal-oxide surfaces. Despite widespread study of sol-gel and surface coatings processes, it is difficult to predict the morphology of the final products due to the large number of process variables involved, such as precursor molecule structure, solvent effects, solution composition, temperature, and pH. To determine the influence of these variables on the products of sol-gel and coatings processes reactive molecular dynamics simulations are used. A reactive force field was used (ReaxFF) to allow the chemical bonds in simulation to dynamically form and break. The force field parameters were optimized using a parallel optimization scheme with a combination of experimental information, and density functional theory calculations. Polycondensation of alkoxysilanes in mixtures of alcohol and water were studied. Steric effects were observed to influence the rates of hydrolysis and condensation in solutions containing different precursor monomers. By restricting the access of nucleophiles to the central silicon atom, the nucleation rate of siloxanes can be controlled. The influence of solution precursor, water, and methanol composition on reaction rates was explored. It was determined that

  13. Investigating the Molecular Mechanism of TSO1 Function in Arabidopsis cell division and meristem development

    Energy Technology Data Exchange (ETDEWEB)

    Zhongchi Liu


    Unlike animals, plants are constantly exposed to environmental mutagens including ultraviolet light and reactive oxygen species. Further, plant cells are totipotent with highly plastic developmental programs. An understanding of molecular mechanisms underlying the ability of plants to monitor and repair its DNA and to eliminate damaged cells are of great importance. Previously we have identified two genes, TSO1 and TSO2, from a flowering plant Arabidopsis thaliana. Mutations in these two genes cause callus-like flowers, fasciated shoot apical meristems, and abnormal cell division, indicating that TSO1 and TSO2 may encode important cell cycle regulators. Previous funding from DOE led to the molecular cloning of TSO1, which was shown to encode a novel nuclear protein with two CXC domains suspected to bind DNA. This DOE grant has allowed us to characterize and isolate TSO2 that encodes the small subunit of the ribonucleotide reductase (RNR). RNR comprises two large subunits (R1) an d two small subunits (R2), catalyzes a rate-limiting step in the production of deoxyribonucleotides needed for DNA replication and repair. Previous studies in yeast and mammals indicated that defective RNR often led to cell cycle arrest, growth retardation and p53-dependent apoptosis while abnormally elevated RNR activities led to higher mutation rates. Subsequently, we identified two additional R2 genes, R2A and R2B in the Arabidopsis genome. Using reverse genetics, mutations in R2A and R2B were isolated, and double and triple mutants among the three R2 genes (TSO2, R2A and R2B) were constructed and analyzed. We showed that Arabidopsis tso2 mutants, with reduced dNTP levels, were more sensitive to UV-C. While r2a or r2b single mutants did not exhibit any phenotypes, tso2 r2b double mutants were embryonic lethal and tso2 r2a double mutants were seedling lethal indicating redundant functions among the three R2 genes. Furthermore, tso2 r2a double mutants exhibited increased DNA dam age

  14. Pteros: fast and easy to use open-source C++ library for molecular analysis. (United States)

    Yesylevskyy, Semen O


    An open-source Pteros library for molecular modeling and analysis of molecular dynamics trajectories for C++ programming language is introduced. Pteros provides a number of routine analysis operations ranging from reading and writing trajectory files and geometry transformations to structural alignment and computation of nonbonded interaction energies. The library features asynchronous trajectory reading and parallel execution of several analysis routines, which greatly simplifies development of computationally intensive trajectory analysis algorithms. Pteros programming interface is very simple and intuitive while the source code is well documented and easily extendible. Pteros is available for free under open-source Artistic License from

  15. Direct investigation of viscosity of an atypical inner membrane of Bacillus spores: a molecular rotor/FLIM study. (United States)

    Loison, Pauline; Hosny, Neveen A; Gervais, Patrick; Champion, Dominique; Kuimova, Marina K; Perrier-Cornet, Jean-Marie


    We utilize the fluorescent molecular rotor Bodipy-C12 to investigate the viscoelastic properties of hydrophobic layers of bacterial spores Bacillus subtilis. The molecular rotor shows a marked increase in fluorescence lifetime, from 0.3 to 4ns, upon viscosity increase from 1 to 1500cP and can be incorporated into the hydrophobic layers within the spores from dormant state through to germination. We use fluorescence lifetime imaging microscopy to visualize the viscosity inside different compartments of the bacterial spore in order to investigate the inner membrane and relate its compaction to the extreme resistance observed during exposure of spores to toxic chemicals. We demonstrate that the bacterial spores possess an inner membrane that is characterized by a very high viscosity, exceeding 1000cP, where the lipid bilayer is likely in a gel state. We also show that this membrane evolves during germination to reach a viscosity value close to that of a vegetative cell membrane, ca. 600cP. The present study demonstrates quantitative imaging of the microscopic viscosity in hydrophobic layers of bacterial spores Bacillus subtilis and shows the potential for further investigation of spore membranes under environmental stress.

  16. Radiomic analysis reveals DCE-MRI features for prediction of molecular subtypes of breast cancer (United States)

    Fan, Ming; Li, Hui; Wang, Shijian; Zheng, Bin; Zhang, Juan; Li, Lihua


    The purpose of this study was to investigate the role of features derived from breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and to incorporated clinical information to predict the molecular subtypes of breast cancer. In particular, 60 breast cancers with the following four molecular subtypes were analyzed: luminal A, luminal B, human epidermal growth factor receptor-2 (HER2)-over-expressing and basal-like. The breast region was segmented and the suspicious tumor was depicted on sequentially scanned MR images from each case. In total, 90 features were obtained, including 88 imaging features related to morphology and texture as well as dynamic features from tumor and background parenchymal enhancement (BPE) and 2 clinical information-based parameters, namely, age and menopausal status. An evolutionary algorithm was used to select an optimal subset of features for classification. Using these features, we trained a multi-class logistic regression classifier that calculated the area under the receiver operating characteristic curve (AUC). The results of a prediction model using 24 selected features showed high overall classification performance, with an AUC value of 0.869. The predictive model discriminated among the luminal A, luminal B, HER2 and basal-like subtypes, with AUC values of 0.867, 0.786, 0.888 and 0.923, respectively. An additional independent dataset with 36 patients was utilized to validate the results. A similar classification analysis of the validation dataset showed an AUC of 0.872 using 15 image features, 10 of which were identical to those from the first cohort. We identified clinical information and 3D imaging features from DCE-MRI as candidate biomarkers for discriminating among four molecular subtypes of breast cancer. PMID:28166261

  17. Application of Molecular Genetics to the Investigation of Inherited Bleeding Disorders

    DEFF Research Database (Denmark)

    Lethagen, Stefan Rune; Dunø, Morten; Nielsen, Lars Bo


    Hemophilia is an inherited bleeding disorder primarily caused by deficiency of coagulation factor (F)VIII (hemophilia A) or FIX (hemophilia B). Both conditions are X-linked. More than 2100 different F8 mutations have been described, the most common being a 500 kb inversion involving exon 1 to exon...... 22. In hemophilia B, more than 1100 unique F9 mutations have been described scattered all over the gene. Carrier analysis, genetic counseling, prenatal and pre-implantation genetic diagnosis are all based on correct identifying the disease-causing mutation. Linkage analysis can be considered when...

  18. Serological and Molecular Investigation of Swine Hepatitis E Virus in Pigs Raised in Southern Italy. (United States)

    Costanzo, Nicola; Sarno, Eleonora; Peretti, Vincenzo; Ciambrone, Lucia; Casalinuovo, Francesco; Santoro, Adriano


    Hepatitis E virus (HEV) infection is a common acute hepatitis transmitted by the fecal-oral route. In developed countries, the virus has a zoonotic potential, and domestic pigs and wild boars are considered main reservoirs. To assess the prevalence of HEV-positive animals in the Calabria region (southern Italy) on a serological and molecular level, a total of 216 autochthonous healthy pigs (Apulo-Calabrese breed) were sampled. Both sera and feces were collected. Pigs were grouped based on age: 117 pigs pigs >6 months. By using a commercial enzyme-linked immunosorbent assay system, a total of 173 (80%) of the 216 pigs tested seropositive. In all sampled farms (n = 8), pigs with antibodies (immunoglobulin G) against HEV were detected at a level higher than 60%, with a significant difference among age groups (P pigs were found to be nested reverse transcription PCR positive and thus to shed viral genomes in their feces. These positive findings resulted in a prevalence of 48.4% on the farm level (16 of 35 pigs) and an overall prevalence of 7.4% at the animal level (16 of 216 pigs). Based on the present study, HEV seems to circulate among the autochthonous domestic pig population of southern Italy with a low sharing rate. Further studies exploring the origin of infection are needed to minimize the risk of human exposure and to reduce consequences for public health.

  19. Multiscale scattering investigations of asphaltene cluster breakup, nanoaggregate dissociation, and molecular ordering. (United States)

    Hoepfner, Michael P; Fogler, H Scott


    Small-angle X-ray and neutron scattering (SAXS/SANS) by asphaltenes in various solvents (toluene, tetrahydrofuran, and 1-methylnaphthalene) at dilute concentrations of asphaltenes are presented and discussed. As asphaltenes are diluted, it was found that the cluster size decreases and follows a fractal scaling law. This observation reveals that asphaltene clusters persist to dilute concentrations and maintain fractal characteristics, regardless of concentration. For the first time, the fraction of asphaltenes that exist in nanoaggregates compared to those molecularly dispersed was estimated from the scattering intensity. Significant dissociation was detected at concentrations similar to the previously reported critical nanoaggregate concentration (CNAC); however, the dissociation was observed to occur gradually as the asphaltene concentration was lowered. Complete dissociation was not detected, and aggregates persisted down to asphaltene concentrations as low as 15 mg/L (0.00125 vol. %). A simplified thermodynamic aggregation model was applied to the measurements, and the free energy change of association per asphaltene-asphaltene interaction was calculated to be approximately -31 kJ/mol. Finally, novel solvent-corrected WAXS results of asphaltene in a liquid environment are presented and reveal three distinct separation distances, in contrast to the two separation distances observed in diffraction studies of solid phase asphaltenes. Significant differences in the WAXS peak positions and shapes between aromatic and nonaromatic solvents suggests that there may be large differences between the solvation shell or conformation of the asphaltene alkyl shell depending on the surrounding liquid environment.

  20. Environmental surveillance and molecular investigation of Legionella spp. in Apulia, in the years 2008-2011. (United States)

    Iatta, R; Cuna, T; Napoli, C; De Giglio, O; Montagna, M T


    Legionella spp. is considered an emerging microorganism involved in aquatic environments contamination and cause of Legionnaires' disease. The aims of the study are to evaluate the level of contamination of Legionella spp. in the water system of the largest Hospital of Apulia region during a 4-year surveillance and to establish, by molecular method, the presence of a predominant genotype of L. pn. sg 1. The results showed that Legionella spp. was present in 36% of water samples with Legionella pneumophila serogroup 1 (L. pn. sg 1) the most prevalent species and serogroup and the wards most contaminated are the high risk units. In addition, despite four main clones of L. pn. sg 1 were identified, a predominant genotype existed. In conclusion the study demonstrates the necessity for periodic evaluation on hospitals water system to assess the potential contamination of Legionella spp., performing decontamination in the presence of bacterial contamination, even low, in particular in high risk wards. Moreover, the switching of the disinfection methods may be suggested in order to prevent resistance phenomenon by some L. pn. sg 1 clones.

  1. MDM2-MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance. (United States)

    Moscetti, Ilaria; Teveroni, Emanuela; Moretti, Fabiola; Bizzarri, Anna Rita; Cannistraro, Salvatore

    Murine double minute 2 (MDM2) and 4 (MDM4) are known as the main negative regulators of p53, a tumor suppressor. They are able to form heterodimers that are much more effective in the downregulation of p53. Therefore, the MDM2-MDM4 complex could be a target for promising therapeutic restoration of p53 function. To this aim, a deeper understanding of the molecular mechanisms underlining the heterodimerization is needed. The kinetic and thermodynamic characterization of the MDM2-MDM4 complex was performed with two complementary approaches: atomic force spectroscopy and surface plasmon resonance. Both techniques revealed an equilibrium dissociation constant (KD ) in the micromolar range for the MDM2-MDM4 heterodimer, similar to related complexes involved in the p53 network. Furthermore, the MDM2-MDM4 complex is characterized by a relatively high free energy, through a single energy barrier, and by a lifetime in the order of tens of seconds. New insights into the MDM2-MDM4 interaction could be highly important for developing innovative anticancer drugs focused on p53 reactivation.

  2. Molecular Dynamics Investigations of the Ablator/Fuel Interface during Early Stages of Inertial Confinement Fusion (United States)

    Stanton, Liam; Glosli, James; Murillo, Michael


    At the National Ignition Facility, high-powered laser beams are used to compress a small target to generate fusion reactions. A critical issue in achieving this is the understanding of mix at the ablator/fuel interface. Mixing occurs at various length scales, ranging from atomic inter-species diffusion to hydrodynamic instabilities. Because the interface is preheated by energy from the incoming shock, it is important to understand the dynamics before the shock arrives. The interface is in the warm dense matter phase with a deuterium/tritium fuel mixture on one side and a plastic mixture on the other. We would like to understand various aspects of the evolution, including the state of the interface when the main shock arrives, the role of electric field generation at the interface, and the character and time scales for diffusion. We present a multiscale approach to model these processes, which combines molecular dynamics to simulate the ionic degrees of freedom with orbital-free density functional theory to calculate the electronic structure. Simulation results are presented and connections to hydrodynamic models are discussed. This work is performed under the auspices of the U. S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  3. Wetting and evaporation of salt-water nanodroplets: A molecular dynamics investigation. (United States)

    Zhang, Jun; Borg, Matthew K; Sefiane, Khellil; Reese, Jason M


    We employ molecular dynamics simulations to study the wetting and evaporation of salt-water nanodroplets on platinum surfaces. Our results show that the contact angle of the droplets increases with the salt concentration. To verify this, a second simulation system of a thin salt-water film on a platinum surface is used to calculate the various surface tensions. We find that both the solid-liquid and liquid-vapor surface tensions increase with salt concentration and as a result these cause an increase in the contact angle. However, the evaporation rate of salt-water droplets decreases as the salt concentration increases, due to the hydration of salt ions. When the water molecules have all evaporated from the droplet, two forms of salt crystals are deposited, clump and ringlike, depending on the solid-liquid interaction strength and the evaporation rate. To form salt crystals in a ring, it is crucial that there is a pinned stage in the evaporation process, during which salt ions can move from the center to the rim of the droplets. With a stronger solid-liquid interaction strength, a slower evaporation rate, and a higher salt concentration, a complete salt crystal ring can be deposited on the surface.

  4. Investigation of molecular mechanism of CNS symptoms induced by DDVP poisoning

    Institute of Scientific and Technical Information of China (English)

    ZHAOZanmei; WANGHanbin


    Objective To Screen differentially expressed genes related to dichlorphos(DDVP) poisoning from rat's hippocampus using oligonucleotide microarray technology in order to elucidate the mechanism of DDVP poisoning. Methods We composed probes of 40 genes of our interest. The probes were retrotranscribed on plata glass and oligonucleotide microarray was formed. 0.5 ml DDVP was given to the rats in experimental group and 0.Sml-pumping brine was given to the rats in control group by hypodermic injection, twenty minutes after convulsion, all hippocampus were collected for total RNA extraction, cDNAs were marked with Cy3 and Cy5 for control group and experiment group respectively, and hybridized with loligonucleotide microarray. Hybridization signals were collected and analyzed following scanning by laser co-focal scanner. Results There were 8 differentially expressed genes identified. Conclusion Many genes expressing changed by DDVP poisoning could be analyzed in a time period by using oligonucleotide microarray, which provides a powerful method for further studies on the molecular mechanism of DDVP poisoning.

  5. Size effect on local magnetic moments in ferrimagnetic molecular complexes: an XMCD investigation

    CERN Document Server

    Champion, G; Cartier-Dit-Moulin, C; Arrio, M A; Sainctavit, P; Zacchigna, M; Zangrando, M; Finazzi, M; Parmigiani, F; Mathoniere, C


    Molecular chemistry allows to synthesize new magnetic systems with controlled properties such as size, magnetization or anisotropy. The theoretical study of the magnetic properties of small molecules (from 2 to 10 metallic cations per molecule) predicts that the magnetization at saturation of each ion does not reach the expected value for uncoupled ions when the magnetic interaction is antiferromagnetic. The quantum origin of this effect is due to the linear combination of several spin states building the wave function of the ground state and clusters of finite size and of finite spin value exhibit this property. When single crystals are available, spin densities on each atom can be experimentally given by polarized neutron diffraction (PND) experiments. In the case of bimetallic MnCu powdered samples, we will show that x-ray magnetic circular dichroism (XMCD) spectroscopy can be used to follow the evolution of the spin distribution on the Mn sup I sup I and Cu sup I sup I sites when passing from a dinuclear ...

  6. Synthesis, structural investigations, hydrogen-deuterium exchange studies, and molecular modeling of conformationally stablilized aromatic oligoamides. (United States)

    Yan, Yan; Qin, Bo; Ren, Changliang; Chen, Xiuying; Yip, Yeow Kwan; Ye, Ruijuan; Zhang, Dawei; Su, Haibin; Zeng, Huaqiang


    Biasing the conformational preferences of aromatic oligoamides by internally placing intramolecular hydrogen bonds has led to a series of stably folded molecular strands. This article presents the results from extensive solid-state, solution, and computational studies on these folding oligomers. Depending on its backbone length, an oligoamide adopts a crescent or helical conformation. Surprisingly, despite the highly repetitive nature of the backbone, the internally placed, otherwise very similar intramolecular hydrogen bonds showed significantly different stabilities as demonstrated by hydrogen-deuterium exchange data. It was also observed that the hydrogen-bonding strength can be tuned by adjusting the substituents attached to the exterior of the aromatic backbones. Examining the amide hydrogen-deuterium exchange rates of trimers revealed that a six-membered hydrogen bond nearing the ester end is the weakest among all the four intramolecular hydrogen bonds of a molecule. This observation was verified by ab initio quantum mechanical calculations at the level of B3LYP/6-31G*. Such a "weak point" creates the "battle of the bulge" where backbone twisting is centered, which is consistently observed in the solid-state structures of the four trimer molecules studied. In the solid state, the oligomers assemble into interesting one-dimensional structures. A pronounced columnar packing of short oligomers (i.e., dimers, trimers, and tetramer) and channel-like, potentially ion-conducting stacks of longer oligomers (i.e., tetramer, pentamer, and hexamer) were observed.

  7. Adsorption of collagen onto single walled carbon nanotubes: a molecular dynamics investigation. (United States)

    Gopalakrishnan, Ravimohan; Balamurugan, Kanagasabai; Singam, Ettayapuram Ramaprasad Azhagiya; Sundaraman, Subramanian; Subramanian, Venkatesan


    Classical molecular dynamics (MD) simulation has been carried out to understand the adsorption of collagen like peptides onto single walled carbon nanotubes (CNT) in an aqueous environment. It is observed that the triple helical structure of all the model collagen like peptides (CPs) has been unaltered upon adsorption onto CNT. The model CPs do not wrap around the CNT, however, the axis of the triple helix subtends a cross angle with respect to the axis of the CNT. The interaction between the CPs and CNT as well as that between the CPs and water molecules was observed by MD simulation snapshots. The inherent nature of the interaction of CPs with CNT facilitates the penetration of CPs into the water/CNT interface. During this process, water molecules trapped between the CPs and CNT are appreciably displaced. Although, hydrophobic-hydrophobic interaction is crucial for the interaction, the role of πR (R = OH and NH(2)) interactions are also observed from the geometrical parameters. The sequence specific interaction of CPs with CNT is evident from the results. It is found that the length of the CNT, curvature of the CNT and length of the CPs do not significantly influence interaction between the two systems. Overall the findings provide important information for the development of nanocomposite materials from collagen and CNT.

  8. Synthesis of focused library of novel aryloxyacids and pyrazoline derivatives: Molecular docking studies and antimicrobial investigation

    Directory of Open Access Journals (Sweden)



    Full Text Available Infectious diseases are on the rise due to development of multidrug-resistant strains, and this renders the search for newer antimicrobials. Hybrid compounds of different scaffolds are expected to enhance the bioactivity by improved affinity to target proteins while retaining the biological efficacy of each of the components. In view of this, a series of pyrazolines with aryloxy acid in the side chain are synthesized and evaluated for their antimicrobial potential. Pyrazoline-substituted aryloxy acids were synthesized in very good yields, starting from chalcones. Synthetic method is adopted in such a way that the use of any solvents is avoided. The structures of these compounds were confirmed using FTIR, NMR, and Mass spectrometry. The potential of these molecules as antimicrobial agents was predicted using molecular docking studies. The activities were also assessed using zone of inhibition and minimum inhibitory concentration (MIC measurement against tuberculosis variant bacteria, Mycobacterium smegmatis; Gram-positive pathogen, Staphylococcus aureus; Gram-negative Escherichia coli; and fungi, Candida albicans. The positional isomers with the electron-withdrawing group farthest from the acid function showed the best activity in both chalcone acids as well as pyrazoline acids. Many of the compounds exhibited zones of inhibition comparable with the standard drugs, ciprofloxacin and fluconazole, considered for the study. Although many compounds exhibited significant zones of inhibition, their minimum inhibitory concentrations established by broth assay were higher, suggesting these molecules are not potent at lower concentrations.

  9. Investigation of Inhibition Mechanism of Chemokine Receptor CCR5 by Micro-second Molecular Dynamics Simulations. (United States)

    Salmas, Ramin Ekhteiari; Yurtsever, Mine; Durdagi, Serdar


    Chemokine receptor 5 (CCR5) belongs to G protein coupled receptors (GPCRs) and plays an important role in treatment of human immunodeficiency virus (HIV) infection since HIV uses CCR5 protein as a co-receptor. Recently, the crystal structure of CCR5-bound complex with an approved anti-retroviral drug (maroviroc) was resolved. During the crystallization procedure, amino acid residues (i.e., Cys224, Arg225, Asn226 and Glu227) at the third intra-cellular loop were replaced by the rubredoxin for stability reasons. In the current study, we aimed to understand the impact of the incorporated rubredoxin on the conformations of TM domains of the target protein. For this reason, rubredoxin was deleted from the crystal structure and the missing amino acids were engineered. The resultant structure was subjected to long (μs) molecular dynamics (MD) simulations to shed light into the inhibitory mechanism. The derived model structure displayed a significant deviation in the cytoplasmic domain of TM5 and IC3 in the absence of rubredoxin. The principal component analyses (PCA) and MD trajectory analyses revealed important structural and dynamical differences at apo and holo forms of the CCR5.

  10. Wetting and evaporation of salt-water nanodroplets: A molecular dynamics investigation (United States)

    Zhang, Jun; Borg, Matthew K.; Sefiane, Khellil; Reese, Jason M.


    We employ molecular dynamics simulations to study the wetting and evaporation of salt-water nanodroplets on platinum surfaces. Our results show that the contact angle of the droplets increases with the salt concentration. To verify this, a second simulation system of a thin salt-water film on a platinum surface is used to calculate the various surface tensions. We find that both the solid-liquid and liquid-vapor surface tensions increase with salt concentration and as a result these cause an increase in the contact angle. However, the evaporation rate of salt-water droplets decreases as the salt concentration increases, due to the hydration of salt ions. When the water molecules have all evaporated from the droplet, two forms of salt crystals are deposited, clump and ringlike, depending on the solid-liquid interaction strength and the evaporation rate. To form salt crystals in a ring, it is crucial that there is a pinned stage in the evaporation process, during which salt ions can move from the center to the rim of the droplets. With a stronger solid-liquid interaction strength, a slower evaporation rate, and a higher salt concentration, a complete salt crystal ring can be deposited on the surface.

  11. Investigating the allosteric reverse signalling of PARP inhibitors with microsecond molecular dynamic simulations and fluorescence anisotropy. (United States)

    Marchand, Jean-Rémy; Carotti, Andrea; Passeri, Daniela; Filipponi, Paolo; Liscio, Paride; Camaioni, Emidio; Pellicciari, Roberto; Gioiello, Antimo; Macchiarulo, Antonio


    The inhibition of the poly(ADP-ribose) polymerase (PARP) family members is a strategy pursued for the development of novel therapeutic agents in a range of diseases, including stroke, cardiac ischemia, cancer, inflammation and diabetes. Even though some PARP-1 inhibitors have advanced to clinical setting for cancer therapy, a great deal of attention is being devoted to understand the polypharmacology of current PARP inhibitors. Besides blocking the catalytic activity, recent works have shown that some PARP inhibitors exhibit a poisoning activity, by trapping the enzyme at damaged sites of DNA and forming cytotoxic complexes. In this study we have used microsecond molecular dynamics to study the allosteric reverse signalling that is at the basis of such an effect. We show that Olaparib, but not Veliparib and HYDAMTIQ, is able to induce a specific conformational drift of the WGR domain of PARP-1, which stabilizes PARP-1/DNA complex through the locking of several salt bridge interactions. Fluorescence anisotropy assays support such a mechanism, providing the first experimental evidence that HYDAMTIQ, a potent PARP inhibitor with neuroprotective properties, is less potent than Olaparib to trap PARP-1/DNA complex.

  12. Investigating very extended objects with HAWC: from Molecular Clouds to Fermi Bubbles (United States)

    Ayala, Hugo; Coel, Matthew; Hüntemeyer, Petra; Casanova, Sabrina; HAWC Collaboration


    The observation of large gamma-ray emission structures is useful for tracing the propagation and distribution of cosmic rays throughout our Galaxy. For example, the search for gamma-ray emission from Giant Molecular Clouds may allow us to probe the flux of cosmic rays in distant galactic regions and compare it with the flux measured at Earth. Also, by observing at the gamma-ray signal, the composition of the cosmic rays can be measured by studying the emission from hadronic or leptonic processes. In the case of emission from the Fermi Bubbles specifically, constraining the mechanism of gamma-ray production can point to their origin. The High Altitude Water Cherenkov (HAWC) Observatory is located at 4100m above sea level in Mexico. It is designed to measure high-energy gamma rays between 300GeV to 100TeV. HAWC possesses a large field of view and good sensitivity to spatially extended sources, which currently makes it the best suited ground-based observatory to detect extended regions. NSF; DoE; Michigan Technological University; Los Alamos National Lab; CONACyT; UNAM; BUAP; others.

  13. Photometric Investigation of the MBM 12 Molecular Cloud Area in ARIES. III. CCD Photometry (United States)

    Straižys, V.; Zdanavičius, J.; Zdanavičius, K.; Kazlauskas, A.; Černis, K.; Laugalys, V.; Boyle, R. P.; Corbally, C. J.; Philip, A. G. D.

    Magnitudes and color indices of 138 stars down to l V = 15 mag in the seven-color Vilnius photometric system are determined in the area of the Aries molecular cloud MBM 12. Spectral types, color excesses, interstellar extinctions and distances of stars are determined from the photometric data. For some stars classification is verified from spectrograms. The plot of extinction vs. distance exhibits a steep rise of the extinction up to 4 mag at 300 pc which corresponds to the distance of the dust cloud at 375 pc. However, this distance may be overestimated if the heavily reddened stars found in the present study are not inside the cloud, but behind it. Additionally, a small bump of the extinction is present at 100--140 pc which can be related to the extension of the Taurus-Auriga dark cloud complex. Four known T Tauri type stars were measured and classified, and their variability confirmed. Two new T Tauri stars are suspected. More young objects may be present among the stars with peculiar color indices. Some of them can also be unresolved binaries. Some new heavily reddened stars are identified and discussed.

  14. Pure and Modified Co-Poly(amide-12-b-ethylene oxide Membranes for Gas Separation Studied by Molecular Investigations

    Directory of Open Access Journals (Sweden)

    Luana De Lorenzo


    Full Text Available This paper deals with a theoretical investigation of gas transport properties in a pure and modified PEBAX block copolymer membrane with N-ethyl-o/p-toluene sulfonamide (KET as additive molecules. Molecular dynamics simulations using COMPASS force field, Gusev-Suter Transition State Theory (TST and Monte Carlo methods were used. Bulk models of PEBAX and PEBAX/KET in different copolymer/additive compositions were assembled and analyzed to evaluate gas permeability and morphology to characterize structure-performance relationships.

  15. The origin of the cooperativity in the streptavidin-biotin system: A computational investigation through molecular dynamics simulations


    Fengjiao Liu; Zhang, John Z. H.; Ye Mei


    Previous experimental study measuring the binding affinities of biotin to the wild type streptavidin (WT) and three mutants (S45A, D128A and S45A/D128A double mutant) has shown that the loss of binding affinity from the double mutation is larger than the direct sum of those from two single mutations. The origin of this cooperativity has been investigated in this work through molecular dynamics simulations and the end-state free energy method using the polarized protein-specific charge. The re...


    Physicochemical and analytical studies of the fibrous protein and other constituents of the axoplasm of the giant fibers of the large squid Dosidicus ... gigas were made. Axon material was dissected from a large number of squid and stock piled for future analysis. Initial experiments were made in an

  17. Analysis of the Offspring Sex Ratio of Chicken by Using Molecular Sexing

    Institute of Scientific and Technical Information of China (English)

    FENG Yan-ping; GONG Yan-zhang; Nabeel Ahmed Affara; PENG Xiu-li; YUAN Jin-feng; ZHAO Rui-xia; Mohammed Yusuf; Osman Jeffer; ZHANG Shu-jun


    The overall sex ratio of offspring (dead embryos and hatch chicks) from all the fertilized eggs of 140 hens collected for30 days was studied using duplex PCR of certain fragments of sex chromosomes. Additional 894 dead embryos over a period of 21 days of incubation were also investigated to verify the sex ratio of the dead embryos. The sex of the early dead embryos was identified using this molecular sexing technique. The sex ratio of the hatch chicks and the total offspring of the hens investigated in this experiment did not differ from the expected sex ratio (i.e., 1:1). However, the number of female dead embryos was significantly more than that of males. The data indicated that the different physiologic function of males and females contributed to female-biased mortality during incubation. It was also found by further analysis that the sex ratios of the offspring of some hens were significantly biased to female or male over the period investigated, which suggested that the sex ratio of offspring might be influenced by the maternal condition to some degrees.

  18. Numerical methodologies for investigation of moderate-velocity flow using a hybrid computational fluid dynamics - molecular dynamics simulation approach

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Soon Heum [Linkoeping University, Linkoeping (Sweden); Kim, Na Yong; Nikitopoulos, Dimitris E.; Moldovan, Dorel [Louisiana State University, Baton Rouge (United States); Jha, Shantenu [Rutgers University, Piscataway (United States)


    Numerical approaches are presented to minimize the statistical errors inherently present due to finite sampling and the presence of thermal fluctuations in the molecular region of a hybrid computational fluid dynamics (CFD) - molecular dynamics (MD) flow solution. Near the fluid-solid interface the hybrid CFD-MD simulation approach provides a more accurate solution, especially in the presence of significant molecular-level phenomena, than the traditional continuum-based simulation techniques. It also involves less computational cost than the pure particle-based MD. Despite these advantages the hybrid CFD-MD methodology has been applied mostly in flow studies at high velocities, mainly because of the higher statistical errors associated with low velocities. As an alternative to the costly increase of the size of the MD region to decrease statistical errors, we investigate a few numerical approaches that reduce sampling noise of the solution at moderate-velocities. These methods are based on sampling of multiple simulation replicas and linear regression of multiple spatial/temporal samples. We discuss the advantages and disadvantages of each technique in the perspective of solution accuracy and computational cost.

  19. O6-methylguanine-DNA methyltransferase in equine sarcoids: molecular and epigenetic analysis

    Directory of Open Access Journals (Sweden)

    Altamura Gennaro


    Full Text Available Abstract Background Bovine papillomaviruses (BPVs types 1 and 2 are the only known papillomaviruses able to jump the species. In fact, BPVs 1/2 induce neoplasia in their natural bovine host but infection is also associated to neoplastic skin lesions in equids termed sarcoids. The equine sarcoid is considered to be the most common equine cutaneous tumour worldwide for which no effective therapy is available. Very little is known about the molecular mechanisms underlying tumourigenesis, although genes contributing to sarcoid development have been identified. Several studies associate the development of cancer to the loss of function of a number of oncosuppressor genes. In this study the putative role of O6-methylguanine-DNA methyltrasferase (MGMT was investigated for sarcoids. The expression of the oncosuppressor protein was assessed in normal and sarcoid cells and tissues. In addition, the DNA methylation profile was analysed to assess the role of epigenetic mechanism in regulation of MGMT expression. Results A group of 15 equine sarcoids and two primary sarcoid cell lines (fibroblasts were analyzed for the expression of MGMT protein by immunohistochemistry, immunofluorescence and Western blotting techniques. The sarcoid cell line EqSO4b and the tumour samples showed a reduction or absence of MGMT expression. To investigate the causes of deregulated MGMT expression, ten samples were analyzed for the DNA methylation profile of the CpG island associated to the MGMT promoter. The analysis of 73 CpGs encompassing the region of interest showed in 1 out of 10 (10% sarcoids a pronouncedly altered methylation profile when compared to the control epidermal sample. Similarily the EqSO4b cell line showed an altered MGMT methylation pattern in comparison to normal fibroblasts. Conclusion As previously demonstrated for the oncosuppressor gene FHIT, analysis of MGMT expression in sarcoid tissues and a sarcoid-derived fibroblast cell line further suggests that

  20. Wavelet Analysis for Investigation of Precise Gnss Solutions' Credibility (United States)

    Bogusz, Janusz; Klos, Anna


    This publication presents the results of searching short-term oscillations of the ASG network sites using wavelet transform. Polish Active Geodetic Network (ASG-EUPOS) is the multifunctional precise satellite positioning system established by the Head Office of Geodesy and Cartography in 2008. The adjusted network consisted of over 130 stations from Poland and neighbouring countries. The period covered observations gathered from June 2008 to July 2010. The method of processing elaborated in the CAG (Centre of Applied Geomatics, Warsaw Military University of Technology), which is one of the 17 EPN LAC (EUREF Permanent Network Local Analysis Centre) acting now in Europe, established at the end of 2009, is similar with the official one used in EPN. It is based on the Bernese 5.0 software, but the difference to the EPN's solutions lies in the resolution of resulting coordinates. In the presented research the 1-hour sampling rate with 3-hour windowing (66% of correlation) is applied. This allows us to make the interpretations concerning short period information in GNSS (Global Navigation Satellite System) coordinates series. Analyses using FFT and least squares (tidal) gave very coherent results and confirmed several millimetres diurnal and sub-diurnal oscillations. Wavelet analysis is aimed at the investigation of credibility of the precise GNSS solutions in terms of changes of the amplitude of oscillations in time. As a result of this study the changes in the amplitude of oscillations at diurnal and sub-diurnal frequency bands were obtained. These could be caused by the artificial modulations of the near-by frequencies, but also some geophysical signals could be clearly distinguished. Additionally the comparison of Continuous Wavelet Transforms of near stations (three pairs from ASG-EUPOS network) was performed. This comparison showed different behaviour of oscillations of residual coordinates, mainly due to the different thermal response or artefacts related to the

  1. Productivity Analysis of Public and Private Airports: A Causal Investigation (United States)

    Vasigh, Bijan; Gorjidooz, Javad


    Around the world, airports are being viewed as enterprises, rather than public services, which are expected to be managed efficiently and provide passengers with courteous customer services. Governments are, increasingly, turning to the private sectors for their efficiency in managing the operation, financing, and development, as well as providing security for airports. Operational and financial performance evaluation has become increasingly important to airport operators due to recent trends in airport privatization. Assessing performance allows the airport operators to plan for human resources and capital investment as efficiently as possible. Productivity measurements may be used as comparisons and guidelines in strategic planning, in the internal analysis of operational efficiency and effectiveness, and in assessing the competitive position of an airport in transportation industry. The primary purpose of this paper is to investigate the operational and financial efficiencies of 22 major airports in the United States and Europe. These airports are divided into three groups based on private ownership (7 British Airport Authority airports), public ownership (8 major United States airports), and a mix of private and public ownership (7 major European Union airports. The detail ownership structures of these airports are presented in Appendix A. Total factor productivity (TFP) model was utilized to measure airport performance in terms of financial and operational efficiencies and to develop a benchmarking tool to identify the areas of strength and weakness. A regression model was then employed to measure the relationship between TFP and ownership structure. Finally a Granger causality test was performed to determine whether ownership structure is a Granger cause of TFP. The results of the analysis presented in this paper demonstrate that there is not a significant relationship between airport TFP and ownership structure. Airport productivity and efficiency is

  2. Molecular Dynamics Simulations to Investigate the Binding Mode of the Natural Product Liphagal with Phosphoinositide 3-Kinase α

    Directory of Open Access Journals (Sweden)

    Yanjuan Gao


    Full Text Available Phosphatidylinositol 3-kinase α (PI3Kα is an attractive target for anticancer drug design. Liphagal, isolated from the marine sponge Aka coralliphaga, possesses the special “liphagane” meroterpenoid carbon skeleton and has been demonstrated as a PI3Kα inhibitor. Molecular docking and molecular dynamics simulations were performed to explore the dynamic behaviors of PI3Kα binding with liphagal, and free energy calculations and energy decomposition analysis were carried out by use of molecular mechanics/Poisson-Boltzmann (generalized Born surface area (MM/PB(GBSA methods. The results reveal that the heteroatom rich aromatic D-ring of liphagal extends towards the polar region of the binding site, and the D-ring 15-hydroxyl and 16-hydroxyl form three hydrogen bonds with Asp810 and Tyr836. The cyclohexyl A-ring projects up into the upper pocket of the lipophilic region, and the hydrophobic/van der Waals interactions with the residues Met772, Trp780, Ile800, Ile848, Val850, Met922, Phe930, Ile932 could be the key interactions for the affinity of liphagal to PI3Kα. Thus, a new strategy for the rational design of more potent analogs of liphagal against PI3Kα is provided. Our proposed PI3Kα/liphagal binding mode would be beneficial for the discovery of new active analogs of liphagal against PI3Kα.

  3. Investigating the link between molecular subtypes of glioblastoma, epithelial-mesenchymal transition, and CD133 cell surface protein.

    Directory of Open Access Journals (Sweden)

    Hadi Zarkoob

    Full Text Available In this manuscript, we use genetic data to provide a three-faceted analysis on the links between molecular subclasses of glioblastoma, epithelial-to-mesenchymal transition (EMT and CD133 cell surface protein. The contribution of this paper is three-fold: First, we use a newly identified signature for epithelial-to-mesenchymal transition in human mammary epithelial cells, and demonstrate that genes in this signature have significant overlap with genes differentially expressed in all known GBM subtypes. However, the overlap between genes up regulated in the mesenchymal subtype of GBM and in the EMT signature was more significant than other GBM subtypes. Second, we provide evidence that there is a negative correlation between the genetic signature of EMT and that of CD133 cell surface protein, a putative marker for neural stem cells. Third, we study the correlation between GBM molecular subtypes and the genetic signature of CD133 cell surface protein. We demonstrate that the mesenchymal and neural subtypes of GBM have the strongest correlations with the CD133 genetic signature. While the mesenchymal subtype of GBM displays similarity with the signatures of both EMT and CD133, it also exhibits some differences with each of these signatures that are partly due to the fact that the signatures of EMT and CD133 are inversely related to each other. Taken together these data shed light on the role of the mesenchymal transition and neural stem cells, and their mutual interaction, in molecular subtypes of glioblastoma multiforme.

  4. Molecular Laser Spectroscopy as a Tool for Gas Analysis Applications

    Directory of Open Access Journals (Sweden)

    Javis Anyangwe Nwaboh


    Full Text Available We have used the traceable infrared laser spectrometric amount fraction measurement (TILSAM method to perform absolute concentration measurements of molecular species using three laser spectroscopic techniques. We report results performed by tunable diode laser absorption spectroscopy (TDLAS, quantum cascade laser absorption spectroscopy (QCLAS, and cavity ring down spectroscopy (CRDS, all based on the TILSAM methodology. The measured results of the different spectroscopic techniques are in agreement with respective gravimetric values, showing that the TILSAM method is feasible with all different techniques. We emphasize the data quality objectives given by traceability issues and uncertainty analyses.

  5. On the accurate molecular dynamics analysis of biological molecules (United States)

    Yamashita, Takefumi


    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.

  6. Thermodynamic Models from Fluctuation Solution Theory Analysis of Molecular Simulations

    DEFF Research Database (Denmark)

    Christensen, Steen; Peters, Günther H.j.; Hansen, Flemming Yssing


    Fluctuation solution theory (FST) is employed to analyze results of molecular dynamics (MD) simulations of liquid mixtures. The objective is to generate parameters for macroscopic GE-models, here the modified Margules model. We present a strategy for choosing the number of parameters included......, Mol. Simul. 33 (4–5) (2007) 449–457.]. The new one has advantages for systems with data points at dilute conditions. Prediction of bubble point pressures using parameters from the two objective functions are compared with experimental data for the binary mixtures methyl acetate–n-pentane and methyl...

  7. Molecular analysis of immunoglobulin genes in multiple myeloma. (United States)

    Kosmas, C; Stamatopoulos, K; Stavroyianni, N; Belessi, C; Viniou, N; Yataganas, X


    The study of immunoglobulin genes in multiple myeloma over the last five years has provided important information regarding biology, ontogenetic location, disease evolution, pathogenic consequences and tumor-specific therapeutic intervention with idiotypic vaccination. Detailed analysis of V(H) genes has revealed clonal relationship between switch variants expressed by the bone marrow plasma cell and myeloma progenitors in the marrow and peripheral blood. V(H) gene usage is biased against V4-34 (encoding antibodies with cold agglutinin specificity; anti-l/i) explaining the absence of autoimmune phenomena in myeloma compared to other B-cell lymphoproliferative disorders. V(H) genes accumulate somatic hypermutations following a distribution compatible with antigen selection, but with no intraclonal heterogeneity. V(L) genes indicate a bias in usage of VkappaI family members and somatic hypermutation, in line with antigen selection, of the expressed Vkappa genes is higher than any other B-cell lymphoid disorder. A complementary imprint of antigen selection as evidenced by somatic hypermutation of either the V(H) or V(L) clonogenic genes has been observed. The absence of ongoing somatic mutations in either V(H) or V(L) genes gives rise to the notion that the cell of origin in myeloma is a post-germinal center memory B-cell. Clinical application of sensitive PCR methods in order to detect clonal immunoglobulin gene rearrangements has made relevant the monitoring and follow-up of minimal residual disease in stem cell autografts and after myeloablative therapy. The fact that surface immunoglobulin V(H) and V(L) sequences constitute unique tumor-specific antigenic determinants has stimulated investigators to devise strategies aiming to generate active specific immunity against the idiotype of malignant B-cells in myeloma by constructing vaccines based on expressed single-chain Fv fragments, DNA plasmids carrying V(H)+V(L) clonogenic genes for naked DNA vaccination, or

  8. Compound-Specific Isotope Analysis of Diesel Fuels in a Forensic Investigation (United States)

    Muhammad, Syahidah; Frew, Russell; Hayman, Alan


    Compound-specific isotope analysis (CSIA) offers great potential as a tool to provide chemical evidence in a forensic investigation. Many attempts to trace environmental oil spills were successful where isotopic values were particularly distinct. However, difficulties arise when a large data set is analyzed and the isotopic differences between samples are subtle. In the present study, discrimination of diesel oils involved in a diesel theft case was carried out to infer the relatedness of the samples to potential source samples. This discriminatory analysis used a suite of hydrocarbon diagnostic indices, alkanes, to generate carbon and hydrogen isotopic data of the compositions of the compounds which were then processed using multivariate statistical analyses to infer the relatedness of the data set. The results from this analysis were put into context by comparing the data with the δ13C and δ2H of alkanes in commercial diesel samples obtained from various locations in the South Island of New Zealand. Based on the isotopic character of the alkanes, it is suggested that diesel fuels involved in the diesel theft case were distinguishable. This manuscript shows that CSIA when used in tandem with multivariate statistical analysis provide a defensible means to differentiate and source-apportion qualitatively similar oils at the molecular level. This approach was able to overcome confounding challenges posed by the near single-point source of origin i.e. the very subtle differences in isotopic values between the samples.

  9. Investigation of cellular and molecular responses to pulsed focused ultrasound in a mouse model.

    Directory of Open Access Journals (Sweden)

    Scott R Burks

    Full Text Available Continuous focused ultrasound (cFUS has been widely used for thermal ablation of tissues, relying on continuous exposures to generate temperatures necessary to induce coagulative necrosis. Pulsed FUS (pFUS employs non-continuous exposures that lower the rate of energy deposition and allow cooling to occur between pulses, thereby minimizing thermal effects and emphasizing effects created by non-thermal mechanisms of FUS (i.e., acoustic radiation forces and acoustic cavitation. pFUS has shown promise for a variety of applications including drug and nanoparticle delivery; however, little is understood about the effects these exposures have on tissue, especially with regard to cellular pro-homing factors (growth factors, cytokines, and cell adhesion molecules. We examined changes in murine hamstring muscle following pFUS or cFUS and demonstrate that pFUS, unlike cFUS, has little effect on the histological integrity of muscle and does not induce cell death. Infiltration of macrophages was observed 3 and 8 days following pFUS or cFUS exposures. pFUS increased expression of several cytokines (e.g., IL-1α, IL-1β, TNFα, INFγ, MIP-1α, MCP-1, and GMCSF creating a local cytokine gradient on days 0 and 1 post-pFUS that returns to baseline levels by day 3 post-pFUS. pFUS exposures induced upregulation of other signaling molecules (e.g., VEGF, FGF, PlGF, HGF, and SDF-1α and cell adhesion molecules (e.g., ICAM-1 and VCAM-1 on muscle vasculature. The observed molecular changes in muscle following pFUS may be utilized to target cellular therapies by increasing homing to areas of pathology.

  10. Structural basis of type 2A von Willebrand disease investigated by molecular dynamics simulations and experiments.

    Directory of Open Access Journals (Sweden)

    Gianluca Interlandi

    Full Text Available The hemostatic function of von Willebrand factor is downregulated by the metalloprotease ADAMTS13, which cleaves at a unique site normally buried in the A2 domain. Exposure of the proteolytic site is induced in the wild-type by shear stress as von Willebrand factor circulates in blood. Mutations in the A2 domain, which increase its susceptibility to cleavage, cause type 2A von Willebrand disease. In this study, molecular dynamics simulations suggest that the A2 domain unfolds under tensile force progressively through a series of steps. The simulation results also indicated that three type 2A mutations in the C-terminal half of the A2 domain, L1657I, I1628T and E1638K, destabilize the native state fold of the protein. Furthermore, all three type 2A mutations lowered in silico the tensile force necessary to undock the C-terminal helix α6 from the rest of the A2 domain, the first event in the unfolding pathway. The mutations F1520A, I1651A and A1661G were also predicted by simulations to destabilize the A2 domain and facilitate exposure of the cleavage site. Recombinant A2 domain proteins were expressed and cleavage assays were performed with the wild-type and single-point mutants. All three type 2A and two of the three predicted mutations exhibited increased rate of cleavage by ADAMTS13. These results confirm that destabilization of the helix α6 in the A2 domain facilitates exposure of the cleavage site and increases the rate of cleavage by ADAMTS13.

  11. Investigating the quartz (1010)/water interface using classical and ab initio molecular dynamics. (United States)

    Skelton, A A; Wesolowski, D J; Cummings, P T


    Two different terminations of the (1010) surface of quartz (α and β) interacting with water are simulated by classical (CMD) (using two different force fields) and ab initio molecular dynamics (AIMD) and compared with previously published X-ray reflectivity (XR) experiments. Radial distribution functions between hydroxyl and water show good agreement between AIMD and CMD using the ClayFF force field for both terminations. The Lopes et al. (Lopes, P. E. M.; Murashov, V.; Tazi, M.; Demchuk, E.; MacKerell, A. D. J. Phys. Chem. B2006, 110, 2782-2792) force field (LFF), however, underestimates the extent of hydroxyl-water hydrogen bonding. The β termination is found to contain hydroxyl-hydroxyl hydrogen bonds; the quartz surface hydroxyl hydrogens and oxygens that hydrogen bond with each other exhibit greatly reduced hydrogen bonding to water. Conversely, the hydroxyl hydrogen and oxygens that are not hydrogen bonded to other surface hydroxyls but are connected to those that are show a considerable amount of hydrogen bonding to water. The electron density distribution of an annealed surface of quartz (1010) obtained by XR is in qualitative agreement with electron densities calculated by CMD and AIMD. In all simulation methods, the interfacial water peak appears farther from the surface than observed by XR. Agreement among AIMD, LFF, and XR is observed for the relaxation of the near-surface atoms; however, ClayFF shows a larger discrepancy. Overall, results show that for both terminations of (1010), LFF treats the near-surface structure more accurately whereas ClayFF treats the interfacial water structure more accurately. It is shown that the number of hydroxyl and water hydrogen bonds to the bridging Si-O-Si oxygens connecting the surface silica groups to the rest of the crystal is much greater for the α than the β termination. It is suggested that this may play a role in the greater resistance to dissolution of the β termination than that of the α termination.

  12. Atomic force microscopy for the investigation of molecular and cellular behavior. (United States)

    Ozkan, Alper D; Topal, Ahmet E; Dana, Aykutlu; Guler, Mustafa O; Tekinay, Ayse B


    The present review details the methods used for the measurement of cells and their exudates using atomic force microscopy (AFM) and outlines the general conclusions drawn by the mechanical characterization of biological materials through this method. AFM is a material characterization technique that can be operated in liquid conditions, allowing its use for the investigation of the mechanical properties of biological materials in their native environments. AFM has been used for the mechanical investigation of proteins, nucleic acids, biofilms, secretions, membrane bilayers, tissues and bacterial or eukaryotic cells; however, comparison between studies is difficult due to variances between tip sizes and morphologies, sample fixation and immobilization strategies, conditions of measurement and the mechanical parameters used for the quantification of biomaterial response. Although standard protocols for the AFM investigation of biological materials are limited and minor differences in measurement conditions may create large discrepancies, the method is nonetheless highly effective for comparatively evaluating the mechanical integrity of biomaterials and can be used for the real-time acquisition of elasticity data following the introduction of a chemical or mechanical stimulus. While it is currently of limited diagnostic value, the technique is also useful for basic research in cancer biology and the characterization of disease progression and wound healing processes.

  13. Investigation and analysis on fatigue status of military pilots

    Directory of Open Access Journals (Sweden)

    Jian-sheng GUO


    Full Text Available Objective To investigate the fatigue status and its characteristics and influential factors of military pilots. Methods Questionnaire survey was conducted on 924 military pilots by using Fatigue Assessment Instrument (FAI and Fatigue Scale (FS-14, χ2 test and Pearson correlation analysis were performed on the data results with SPSS 17.0 software. Results The findings of fatigue status indicated 343 subjects (37.1% with positive fatigue symptoms and 581 subjects (62.9% with negative fatigue symptoms. FAI factor 1 (severity of fatigue, factor 2 (mental fatigue factor, factor 3 (consequence of fatique and the total score, FS-14 factor 1 (physical fatigue factor and the total score in fatigue-positive group were all higher than those in fatiguenegative group, and the differences were all statistically significant (P 0.05 in the possibility of developing fatigue symptoms between subjects with different aircraft types. Age and flight time were positively correlated with factor 1 and total score in FAI and factor 1, factor 2 and total score in FS-14. However, the aircraft type was associated with neither the individual factors and total score in FAI nor the individual factors and total score in FS-14. Conclusion It is common for military pilots to develop fatigue symptoms, characterized by obvious manifestations of severity, environmental specificity, consequences of fatigue and physical fatigue, and the possibilities of developing fatigue symptoms for different ages and flight time were different.

  14. Pharmacognostical Investigation and Physicochemical Analysis of Celastrus paniculatus Willd. Leaves

    Institute of Scientific and Technical Information of China (English)

    Kalaskar Mohan G.; Saner Sachin Y.; Pawar Manohar V.; Rokade Dipak L; Surana Sanjay J


    Objective: Celastrus paniculatus Willd. is an important Indian medicinal plant and widely used in the treatment of the verity of disease and well explored scientifically for their pharmacological properties. The current study was therefore carried out to provide requisite pharmacognostic details about the plant. Methods: Pharmacognostic investigation of the fresh, powdered and anatomical sections of the leaves of Celastrus paniculatus Willd. was carried out to determine its morphological, anatomical, and phytochemical diagnostic features. Quantitative diagnostic characteristics, physicochemical properties and quantitative phytochemical measures were established. Results: The morphology of leave reveled, leaves are alternate, acute, acuminate or obtuse, rounded with cuncate base,; margin is finely crenate, venation is reticulate. The microscopy reveals the dorsiventral type of leave, with anomocytic stomata, covering (lower epidermis) and glandular (upper epidermis) trichomes. The collateral vascular bundle crowned with sclerenchymatous fiber, ideoblast of calcium oxalate. The Quantitative diagnostic characteristics such as leaf constant were measured. Physicochemical properties such as ash, extractive values and fluorescence analysis were established. Quantitative phytochemical revealed presence of carbohydrates, fixed oil, glycosides, cumarines, tannins, flavonoids, saponins, steroids and triterpenoids. Conclusion: The results of the study could be useful in setting some diagnostic indices for the identification and preparation of a monograph of the plant.

  15. Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase). (United States)

    Bonthron, D T; Brady, N; Donaldson, I A; Steinmann, B


    Essential fructosuria is one of the oldest known inborn errors of metabolism. It is a benign condition which is believed to result from deficiency of hepatic fructokinase (ketohexokinase, KHK, E.C. This enzyme catalyses the first step of metabolism of dietary fructose, conversion of fructose to fructose-1-phosphate. Despite the early recognition of this disorder, the primary structure of human KHK and the molecular basis of essential fructosuria have not been previously defined. In this report, the isolation and sequencing of full-length cDNA clones encoding human ketohexokinase are described. Alternative mRNA species and alternative KHK isozymes are produced by alternative polyadenylation and splicing of the KHK gene. The KHK proteins show a high level of sequence conservation relative to rat KHK. Direct evidence that mutation of the KHK structural gene is the cause of essential fructosuria was also obtained. In a well-characterized family, in which three of eight siblings have fructosuria, all affected individuals are compound heterozygotes for two mutations Gly40Arg and Ala43Thr. Both mutations result from G-->A transitions, and each alters the same conserved region of the KHK protein. Neither mutation was seen in a sample of 52 unrelated control individuals. An additional conservative amino acid change (Val49IIe) was present on the KHK allele bearing Ala43Thr.

  16. Real time spectroscopic ellipsometry investigation of homoepitaxial GaN grown by plasma assisted molecular beam epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tong-Ho; Choi, Soojeong; Wu, Pae; Brown, April [Department of Electrical and Computer Engineering, Duke University, 128 Hudson Hall, Durham, NC (United States); Losurdo, Maria; Giangregorio, Maria M.; Bruno, Giovanni [Institute of Inorganic Methodologies and of Plasmas, IMIP-CNR and INSTM UdR Bari, via Orabona, 4, 70126 Bari (Italy); Moto, Akihiro [Innovation Core SEI, Inc., 3235 Kifer Road, Santa Clara, CA 95051 (United States)


    The growth of GaN by plasma assisted molecular beam epitaxy on GaN template substrates (GaN on sapphire) is investigated with in-situ multi-channel spectroscopic ellipsometry. Growth is performed under various Ga/N flux ratios at growth temperatures in the range 710-780 C. The thermal roughening of the GaN template caused by decomposition of the surface is investigated through the temporal variation of the GaN pseudodielectric function over the temperature range of 650 C to 850 C. The structural, morphological, and optical properties are also discussed. (copyright 2006 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  17. Induction of autoimmune disease by radiation exposure. Analysis of molecular structure of myeloperoxidase in neutrophil

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Kazuo; Okawara, Akiko; Ohashi, Yuko; Hashimoto, Yuki [National Inst. of Infectious Diseases, Tokyo (Japan)


    Recently, antineutrophil cytoplasmic antibody (ANCA) that is one of autoimmune antibodies has been paid attention since the antibody was found in patients with articular rheumatism. Molecular structure of myeloperoxidase (MPO), which has been regarded as the antigen of ANCA was investigated in this study. Peripheral neutrophil was exposed to {gamma}-ray at 10 and 30 Gy followed by addition of cytochalasin B. The extracellular and intracellular activities of MPO were determined to estimate the effects of the radiation. Moreover, MPO released to the culture medium was purified from the crude extract of the medium and investigated by Western blot analysis to confirm the occurrence of molecular cleavage in MPO. The releasing activity of MPO was decreased by {gamma}-ray exposure at a dose ranging from 0.1 to 1.0 Gy and it tended to increase with 10 or 30 Gy. On the other hand, the activity of the released enzyme was increased by exposure at 0.1-3.0 Gy and became the normal level with 10 or 30 Gy. There were no changes in the SDS-PAGE pattern for the proteins from neutrophils. Western blotting revealed that 30 kDa fragment was included in the proteins released from neutrophils exposed to 0.1-0.3 Gy. The evidence that a low dose exposure induced such fragmentation of MPO molecule would be utilized to evaluate the effects of low-dose radiation. These results suggested that the MPO molecule fragmented by radiation exposure is highly reactive with the autoantibody in neutrophils, but correlation between MPO and its ANCA- related autoimmune disease has not yet demonstrated. (M.N.)

  18. Molecular and epigenetic analysis of the fragile histidine triad tumour suppressor gene in equine sarcoids

    Directory of Open Access Journals (Sweden)

    Strazzullo Maria


    Full Text Available Abstract Background Sarcoids are peculiar equine benign tumours. Their onset is associated with Bovine Papillomavirus type -1 or -2 (BPV-1/2 infection. Little is known about the molecular interplay between viral infection and neoplastic transformation. The data regarding papillomavirus infections in human species show the inactivation of a number of tumour suppressor genes as basic mechanism of transformation. In this study the putative role of the tumour suppressor gene Fragile Histidine Triad (FHIT in sarcoid tumour was investigated in different experimental models. The expression of the oncosuppressor protein was assessed in normal and sarcoid cells and tissue. Results Nine paraffin embedded sarcoids and sarcoid derived cell lines were analysed for the expression of FHIT protein by immunohistochemistry, immunofluorescence techniques and western blotting. These analyses revealed the absence of signal in seven out of nine sarcoids. The two sarcoid derived cell lines too showed a reduced signal of the protein. To investigate the causes of the altered protein expression, the samples were analysed for the DNA methylation profile of the CpG island associated with the FHIT promoter. The analysis of the 32 CpGs encompassing the region of interest showed no significative differential methylation profile between pathological tissues and cell lines and their normal counterparts. Conclusion This study represent a further evidence of the role of a tumour suppressor gene in equine sarcoids and approaches the epigenetic regulation in this well known equine neoplasm. The data obtained in sarcoid tissues and sarcoid derived cell lines suggest that also in horse, as in humans, there is a possible involvement of the tumour suppressor FHIT gene in BPV induced tumours. DNA methylation seems not to be involved in the gene expression alteration. Further studies are needed to understand the basic molecular mechanisms involved in reduced FHIT expression.

  19. The IMAGE project: methodological issues for the molecular genetic analysis of ADHD

    Directory of Open Access Journals (Sweden)

    Faraone Stephen V


    Full Text Available Abstract The genetic mechanisms involved in attention deficit hyperactivity disorder (ADHD are being studied with considerable success by several centres worldwide. These studies confirm prior hypotheses about the role of genetic variation within genes involved in the regulation of dopamine, norepinephrine and serotonin neurotransmission in susceptibility to ADHD. Despite the importance of these findings, uncertainties remain due to the very small effects sizes that are observed. We discuss possible reasons for why the true strength of the associations may have been underestimated in research to date, considering the effects of linkage disequilibrium, allelic heterogeneity, population differences and gene by environment interactions. With the identification of genes associated with ADHD, the goal of ADHD genetics is now shifting from gene discovery towards gene functionality – the study of intermediate phenotypes ('endophenotypes'. We discuss methodological issues relating to quantitative genetic data from twin and family studies on candidate endophenotypes and how such data can inform attempts to link molecular genetic data to cognitive, affective and motivational processes in ADHD. The International Multi-centre ADHD Gene (IMAGE project exemplifies current collaborative research efforts on the genetics of ADHD. This European multi-site project is well placed to take advantage of the resources that are emerging following the sequencing of the human genome and the development of international resources for whole genome association analysis. As a result of IMAGE and other molecular genetic investigations of ADHD, we envisage a rapid increase in the number of identified genetic variants and the promise of identifying novel gene systems that we are not currently investigating, opening further doors in the study of gene functionality.

  20. A hardware investigation of robotic SPECT for functional and molecular imaging onboard radiation therapy systems

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Susu, E-mail:; Tough, MengHeng [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 (United States); Bowsher, James; Yin, Fang-Fang [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 and Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Cheng, Lin [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States)


    Purpose: To construct a robotic SPECT system and to demonstrate its capability to image a thorax phantom on a radiation therapy flat-top couch, as a step toward onboard functional and molecular imaging in radiation therapy. Methods: A robotic SPECT imaging system was constructed utilizing a gamma camera detector (Digirad 2020tc) and a robot (KUKA KR150 L110 robot). An imaging study was performed with a phantom (PET CT Phantom{sup TM}), which includes five spheres of 10, 13, 17, 22, and 28 mm diameters. The phantom was placed on a flat-top couch. SPECT projections were acquired either with a parallel-hole collimator or a single-pinhole collimator, both without background in the phantom and with background at 1/10th the sphere activity concentration. The imaging trajectories of parallel-hole and pinhole collimated detectors spanned 180° and 228°, respectively. The pinhole detector viewed an off-centered spherical common volume which encompassed the 28 and 22 mm spheres. The common volume for parallel-hole system was centered at the phantom which encompassed all five spheres in the phantom. The maneuverability of the robotic system was tested by navigating the detector to trace the phantom and flat-top table while avoiding collision and maintaining the closest possible proximity to the common volume. The robot base and tool coordinates were used for image reconstruction. Results: The robotic SPECT system was able to maneuver parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector radius of rotation. Without background, all five spheres were visible in the reconstructed parallel-hole image, while four spheres, all except the smallest one, were visible in the reconstructed pinhole image. With background, three spheres of 17, 22, and 28 mm diameters were readily observed with the parallel-hole imaging, and the targeted spheres (22 and 28 mm diameters) were readily observed in the

  1. Conformational and functional analysis of molecular dynamics trajectories by Self-Organising Maps

    Directory of Open Access Journals (Sweden)

    Stella Fabio


    Full Text Available Abstract Background Molecular dynamics (MD simulations are powerful tools to investigate the conformational dynamics of proteins that is often a critical element of their function. Identification of functionally relevant conformations is generally done clustering the large ensemble of structures that are generated. Recently, Self-Organising Maps (SOMs were reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data mining problems. We present a novel strategy to analyse and compare conformational ensembles of protein domains using a two-level approach that combines SOMs and hierarchical clustering. Results The conformational dynamics of the α-spectrin SH3 protein domain and six single mutants were analysed by MD simulations. The Cα's Cartesian coordinates of conformations sampled in the essential space were used as input data vectors for SOM training, then complete linkage clustering was performed on the SOM prototype vectors. A specific protocol to optimize a SOM for structural ensembles was proposed: the optimal SOM was selected by means of a Taguchi experimental design plan applied to different data sets, and the optimal sampling rate of the MD trajectory was selected. The proposed two-level approach was applied to single trajectories of the SH3 domain independently as well as to groups of them at the same time. The results demonstrated the potential of this approach in the analysis of large ensembles of molecular structures: the possibility of producing a topological mapping of the conformational space in a simple 2D visualisation, as well as of effectively highlighting differences in the conformational dynamics directly related to biological functions. Conclusions The use of a two-level approach combining SOMs and hierarchical clustering for conformational analysis of structural ensembles of proteins was proposed. It can easily be extended to other study cases and to

  2. Investigation of interphase effects in silica-polystyrene nanocomposites based on a hybrid molecular-dynamics-finite-element simulation framework (United States)

    Pfaller, Sebastian; Possart, Gunnar; Steinmann, Paul; Rahimi, Mohammad; Müller-Plathe, Florian; Böhm, Michael C.


    A recently developed hybrid method is employed to study the mechanical behavior of silica-polystyrene nanocomposites (NCs) under uniaxial elongation. The hybrid method couples a particle domain to a continuum domain. The region of physical interest, i.e., the interphase around a nanoparticle (NP), is treated at molecular resolution, while the surrounding elastic continuum is handled with a finite-element approach. In the present paper we analyze the polymer behavior in the neighborhood of one or two nanoparticle(s) at molecular resolution. The coarse-grained hybrid method allows us to simulate a large polymer matrix region surrounding the nanoparticles. We consider NCs with dilute concentration of NPs embedded in an atactic polystyrene matrix formed by 300 chains with 200 monomer beads. The overall orientation of polymer segments relative to the deformation direction is determined in the neighborhood of the nanoparticle to investigate the polymer response to this perturbation. Calculations of strainlike quantities give insight into the deformation behavior of a system with two NPs and show that the applied strain and the nanoparticle distance have significant influence on the deformation behavior. Finally, we investigate to what extent a continuum-based description may account for the specific effects occurring in the interphase between the polymer matrix and the NPs.

  3. Clinical, biochemical and molecular investigations of three Taiwanese children with Laron syndrome. (United States)

    Yang, Chen; Chen, Julia Yi-Ru; Lai, Chien-Cherng; Lin, Hsiu-Chen; Yeh, Geng-Chang; Hsu, Hsun-Hui


    Three children of two Taiwanese families were diagnosed with Laron syndrome, two sisters and one boy. Both sets of parents were consanguineous. Clinically, all three presented with the typical craniofacies of Laron syndrome, consisting of prominent forehead and hypoplastic nasal bridge, high-pitched voice, short stature, and central obesity. Biochemically, their levels of serum IGF-I were less than 5 microg/ml before and after an IGF-I generation test, and levels of IGFBP-3 were reduced in all three patients. Sequence analysis of the growth hormone receptor gene revealed that all three carried a homozygous missense D152G mutation in exon 6.

  4. Virological and molecular biological investigations into equine herpes virus type 2 (EHV-2) experimental infections. (United States)

    Borchers, K; Wolfinger, U; Ludwig, H; Thein, P; Baxi, S; Field, H J; Slater, J D


    Two 18-month-old naturally reared ponies were used to investigate the pathogenicity of EHV-2. After dexamethasone treatment, pony 1 was inoculated intranasally with EHV-2 strain T16, which has been isolated from a foal with keratoconjunctivitis superficialis and pony 2 was similarly inoculated with strain LK4 which was originally isolated from a horse with upper respiratory tract disease. Following virus inoculation, pyrexia was not detected in either pony but both developed conjunctivitis, lymphadenopathy, and coughing. EHV-2 was detected in nasal mucus samples up to day 12 post infection (p.i.), in eye swabs up to day 10 p.i., and in buffy coat cells throughout the investigation in both animals. EHV-2-specific antibody titres were raised significantly 18 days p.i. Following the administration of dexamethasone, 3 months p.i., infectious virus was again detected in nasal mucus and conjunctival swabs from both ponies for 7 days. The tissue distribution of EHV-2 genome was studied post mortem, by means of a nested PCR. EHV-2 was detected in lymphoid tissues, lung, conjunctiva, trigeminal ganglia and olfactory lobes of pony 2, whereas in pony 1 only the conjunctiva of the left eye was PCR positive.

  5. Ultrasonic Investigations of Molecular Interaction in Binary Mixtures of Cyclohexanone with Isomers of Butanol

    Directory of Open Access Journals (Sweden)

    Sk. Md Nayeem


    Full Text Available Ultrasonic speed, u, and density, ρ, have been measured in binary liquid mixtures of cyclohexanone with the isomers of butanol (n-butanol, sec-butanol, and tert-butanol at 308.15 K over the entire range of composition. Molar volume (Vm, adiabatic compressibility (ks, intermolecular free length (Lf, acoustic impedance (z, and their excess/deviation along with Δu have been calculated from the experimental data. These values have been fitted to Redlich-Kister type polynomial equation. Positive values of VmE, Δks, LfE and negative values of zE, Δu have been observed for all the liquid mixtures indicating the existence of weak interactions between components. Rupture of H-bond or reduction in H-bond strength of isomers of butanol or breaking of the structure of one or both of the components in a solution causes the existence of dispersions in the present investigated binary mixtures. The data obtained from V-m,1, V-m,2, and excess partial molar volumes V-m, 1E, V-m, 2E, reflects the inferences drawn from VmE. Furthermore, FTIR spectra support the conclusions drawn from excess/deviation properties. The measured values of ultrasonic speed for all the investigated mixtures have been compared with the theoretically estimated values using empirical relations such as, Nomoto, Van Dael and Vangeels, Impedance and Rao specific sound speed.

  6. A Comprehensive Theoretical Investigation of the Molecular Properties of Methyl Bromide (CH3Br) (United States)

    Yu, Ang-Yang; Efil, Kürşat; Yang, Rui; Hu, Qing-Miao


    The properties of the ground and the lowest excited state of methyl bromide (CH3Br) have been studied with and without inclusion of the solvent effects in this work. The geometric parameters, energies, and frequencies of the ground state and the triplet state are calculated by using the MP2(full)/6-311++G** level of theory. The vertical excitation for the singlet state is also investigated. It is found that the theoretical results performed by the TDDFT/B3P86/6-311++G** method are in the best agreement with the experimental results. In addition, the dissociation energy of CH3Br molecule is computed at MP2(full)/6-311++G** level of theory for the gas phase and in water. The ionisation potential (IP), electron affinity (EA), electronegativity (χ), electrophilicity index (ω), hardness (η), softness (S), and chemical potential (μ) values are calculated from HOMO-LUMO energies both in the gas phase and in solvent (water). These theoretical results could serve as a guide for future experimental investigations.

  7. The flexibility of hydrated bovine serum albumin investigated by THz spectroscopy and molecular modeling (United States)

    Mernea, Maria; Calborean, Octavian; Petrescu, Livia; Dinca, Mihai P.; Leca, Aurel; Apostol, Dan; Dascalu, Traian; Mihailescu, Dan


    The native cellular environment represents a crowded system comprising high concentrations of soluble molecules that interact mostly in a nonspecific manner. Some of the macromolecular crowding effects occurring in biological media are conformational changes and macromolecular associations. Most of our knowledge on protein folding and protein-protein interactions was acquired from experiments on proteins in dilute solutions or from theoretical models of isolated proteins in either explicit or implicit solvent. Here we present a 50% w/w bovine serum albumin (BSA) solution model that comprises two solute molecules included in a single water box. We determined the vibration spectrum of the 50% w/w BSA solution using THz spectroscopy and we calculated the theoretical THz spectrum. We observed a good correlation between the experimental and theoretical spectra for the frequency range of 0.3 - 1.5 THz. We also investigated the contribution of each BSA molecule to the solution THz spectrum by simulating THz spectra of the two BSA molecules from the solution model and water, each accounting for a 50% w/w BSA solution. The spectra appear to be similar. As the two molecules in our solution model have different conformations, we investigated the importance of the apparently insignificant differences between simulated THz spectra of the two proteins. We found that the differences should be considered significant, as they reflect differences between the flexibility of the two BSA molecules.

  8. Molecular mobility in Medicago truncatula seed during early stage of germination: Neutron scattering and NMR investigations

    Energy Technology Data Exchange (ETDEWEB)

    Falourd, Xavier [UR1268 Biopolymères Interactions Assemblages, INRA, F-44316 Nantes (France); Natali, Francesca [CNR-IOM-OGG, c/o Institut Laue-Langevin, 6 rue Jules Horowitz, BP 156, 38042 Grenoble Cedex 9 (France); Institut Laue-Langevin, 6 rue Jules Horowitz, BP 156, 38042 Grenoble Cedex 9 (France); Peters, Judith [Institut Laue-Langevin, 6 rue Jules Horowitz, BP 156, 38042 Grenoble Cedex 9 (France); Université Joseph Fourier UFR PhITEM, BP 53, 38041 Grenoble Cedex 9 (France); Institut de Biologie Structurale, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1 (France); Foucat, Loïc, E-mail: [UR1268 Biopolymères Interactions Assemblages, INRA, F-44316 Nantes (France)


    Highlights: • Neutron scattering and NMR approaches were used to characterize seed germination. • A parallel between macromolecular motions and water dynamics was established. • Freezing/thawing cycle revealed a hysteresis connected to the seed hydration level. - Abstract: First hours of Medicago truncatula (MT) seeds germination were investigated using elastic incoherent neutron scattering (EINS) and nuclear magnetic resonance (NMR), to follow respectively how macromolecular motions and water mobility evolve when water permeates into the seed. From EINS results, it was shown that there is an increase in macromolecular mobility with the water uptake. Changes in NMR relaxation parameters reflected microstructural changes associated with the recovery of the metabolic processes. The EINS investigation of the effect of temperature on macromolecular motions showed that there is a relationship between the amount of water in the seeds and the effect of freezing–thawing cycle. The NMR relaxometry results obtained at 253 K allowed establishing possible link between the freezing of water molecules tightly bound to macromolecules and their drastic motion restriction around 250 K, as observed with EINS at the highest water content.

  9. Hybrid molecular dynamics simulation for plasma induced damage analysis (United States)

    Matsukuma, Masaaki


    In order to enable further device size reduction (also known as Moore's law) and improved power performance, the semiconductor industry is introducing new materials and device structures into the semiconductor fabrication process. Materials now include III-V compounds, germanium, cobalt, ruthenium, hafnium, and others. The device structure in both memory and logic has been evolving from planar to three dimensional (3D). One such device is the FinFET, where the transistor gate is a vertical fin made either of silicon, silicon-germanium or germanium. These changes have brought renewed interests in the structural damages caused by energetic ion bombardment of the fin sidewalls which are exposed to the ion flux from the plasma during the fin-strip off step. Better control of the physical damage of the 3D devices requires a better understanding of the damage formation mechanisms on such new materials and structures. In this study, the damage formation processes by ion bombardment have been simulated for Si and Ge substrate by Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid simulations and compared to the results from the classical molecular dynamics (MD) simulations. In our QM/MM simulations, the highly reactive region in which the structural damage is created is simulated with the Density Functional based Tight Binding (DFTB) method and the region remote from the primary region is simulated using classical MD with the Stillinger-Weber and Moliere potentials. The learn on the fly method is also used to reduce the computational load. Hence our QM/MM simulation is much faster than the full QC-MD simulations and the original QM/MM simulations. The amorphous layers profile simulated with QM/MM have obvious differences in their thickness for silicon and germanium substrate. The profile of damaged structure in the germanium substrate is characterized by a deeper tail then in silicon. These traits are also observed in the results from the mass selected ion beam

  10. A critical analysis of the models connecting molecular mass distribution and shear viscosity functions

    Directory of Open Access Journals (Sweden)


    Full Text Available Thermoplastics having various short and long-chain branches, characterized by the melt index measured at the processing temperature – according to their average molecular mass – can be processed using universal principles, independently of their chemical composition. The average molecular mass is the result of a molecular mass distribution, being the fingerprint of the chemical synthetic technology. The actual shape of the shear viscosity function aiming at the quantitative characterization of viscous flow, containing material-dependent parameters, depends on the ratio of high and low molecular mass fractions, the width of the molecular mass distribution function and on the number of short and long chain branches. This publication deals with the critical analysis of the mathematical methods of transforming these two curves of basic importance into each other.

  11. Factorized molecular wave functions: Analysis of the nuclear factor

    Energy Technology Data Exchange (ETDEWEB)

    Lefebvre, R., E-mail: [Institut des Sciences Moléculaires d’ Orsay, Bâtiment 350, UMR8214, CNRS- Université. Paris-Sud, 91405 Orsay, France and Sorbonne Universités, UPMC Univ Paris 06, UFR925, F-75005 Paris (France)


    The exact factorization of molecular wave functions leads to nuclear factors which should be nodeless functions. We reconsider the case of vibrational perturbations in a diatomic species, a situation usually treated by combining Born-Oppenheimer products. It was shown [R. Lefebvre, J. Chem. Phys. 142, 074106 (2015)] that it is possible to derive, from the solutions of coupled equations, the form of the factorized function. By increasing artificially the interstate coupling in the usual approach, the adiabatic regime can be reached, whereby the wave function can be reduced to a single product. The nuclear factor of this product is determined by the lowest of the two potentials obtained by diagonalization of the potential matrix. By comparison with the nuclear wave function of the factorized scheme, it is shown that by a simple rectification, an agreement is obtained between the modified nodeless function and that of the adiabatic scheme.

  12. [Clinical and molecular genetic analysis of hereditary optic neuropathies]. (United States)

    Avetisov, S É; Sheremet, N L; Vorob'eva, O K; Eliseeva, É G; Chukhrova, A L; Loginova, A N; Khanakova, N A; Poliakov, A V


    DNA samples of 50 patients with optic neuropathy (ON) associated with congenital cataract were studied to find 3 major mt-DNA mutations (m.11778G>A, m.3460G>A, m.14484T>C), mutations in "hot" regions of OPA 1 gene (exons 8, 14, 15, 16, 18, 27, 28) and in the entire coding sequence of OPA3 gene for molecular genetic confirmation of diagnosis of hereditary Leber and autosomal dominant ON. Primary mutations of mtDNA responsible for hereditary Leber ON were found in 16 patients (32%). Pathogenic mutations of OPAl gene (c.869G>A and c. 2850delT) were identified in 2 patients (4%), these mutations were not found in the literature. OPA3 gene mutations were not revealed.

  13. Using Molecular Modeling in Teaching Group Theory Analysis of the Infrared Spectra of Organometallic Compounds (United States)

    Wang, Lihua


    A new method is introduced for teaching group theory analysis of the infrared spectra of organometallic compounds using molecular modeling. The main focus of this method is to enhance student understanding of the symmetry properties of vibrational modes and of the group theory analysis of infrared (IR) spectra by using visual aids provided by…

  14. Monte Carlo analysis: error of extrapolated thermal conductivity from molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiang-Yang [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Andersson, Anders David [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    In this short report, we give an analysis of the extrapolated thermal conductivity of UO2 from earlier molecular dynamics (MD) simulations [1]. Because almost all material properties are functions of temperature, e.g. fission gas release, the fuel thermal conductivity is the most important parameter from a model sensitivity perspective [2]. Thus, it is useful to perform such analysis.

  15. Investigation of spectral analysis techniques for randomly sampled velocimetry data (United States)

    Sree, Dave


    It is well known that velocimetry (LV) generates individual realization velocity data that are randomly or unevenly sampled in time. Spectral analysis of such data to obtain the turbulence spectra, and hence turbulence scales information, requires special techniques. The 'slotting' technique of Mayo et al, also described by Roberts and Ajmani, and the 'Direct Transform' method of Gaster and Roberts are well known in the LV community. The slotting technique is faster than the direct transform method in computation. There are practical limitations, however, as to how a high frequency and accurate estimate can be made for a given mean sampling rate. These high frequency estimates are important in obtaining the microscale information of turbulence structure. It was found from previous studies that reliable spectral estimates can be made up to about the mean sampling frequency (mean data rate) or less. If the data were evenly samples, the frequency range would be half the sampling frequency (i.e. up to Nyquist frequency); otherwise, aliasing problem would occur. The mean data rate and the sample size (total number of points) basically limit the frequency range. Also, there are large variabilities or errors associated with the high frequency estimates from randomly sampled signals. Roberts and Ajmani proposed certain pre-filtering techniques to reduce these variabilities, but at the cost of low frequency estimates. The prefiltering acts as a high-pass filter. Further, Shapiro and Silverman showed theoretically that, for Poisson sampled signals, it is possible to obtain alias-free spectral estimates far beyond the mean sampling frequency. But the question is, how far? During his tenure under 1993 NASA-ASEE Summer Faculty Fellowship Program, the author investigated from his studies on the spectral analysis techniques for randomly sampled signals that the spectral estimates can be enhanced or improved up to about 4-5 times the mean sampling frequency by using a suitable

  16. Fourier transformed infrared spectral investigations of molecular interactions in propionic acid-2-propanol binary system. (United States)

    Umadevi, M; Thomas, Ammu Elizabeth


    FTIR spectra of propionic acid (PA), 2-propanol (PROH) and its binary mixtures with varying molefraction of the PA were recorded in the region 500-3500 cm(-1), to investigate the formation of hydrogen bonded complexes in a mixed system. The observed features in nu(CO), nu(CO) and delta(COH) of PA, nu(CO) of PROH and delta(COH) of PA+PROH have been explained in terms of the hydrogen bonding interactions between PROH and PA and dipole-dipole interaction. The dipole moment derivative for the above mentioned vibrational modes have also been predicted from the integrated absorbance. The intrinsic linewidth for the vibrational modes nu(CO) and delta(COH) of PA has been elucidated using Bondarev and Mardaeva model.

  17. Studies on the synthesis, spectroscopic analysis, molecular docking and DFT calculations on 1-hydroxy-2-(4-hydroxyphenyl)-4,5-dimethyl-imidazol 3-oxide (United States)

    Benzon, K. B.; Sheena, Mary Y.; Panicker, C. Yohannan; Armaković, Stevan; Armaković, Sanja J.; Pradhan, Kiran; Nanda, Ashis Kumar; Van Alsenoy, C.


    In this work we have investigated in details the spectroscopic and reactive properties of newly synthesized imidazole derivative, namely the 1-hydroxy-2-(4-hydroxyphenyl)-4,5-dimethyl-imidazole 3-oxide (HHPDI). FT-IR and NMR spectra were measured and compared with theoretically obtained data provided by calculations of potential energy distribution and chemical shifts, respectively. Insight into the global reactivity properties has been obtained by analysis of frontier molecular orbitals, while local reactivity properties have been investigated by analysis of charge distribution, ionization energies and Fukui functions. NBO analysis was also employed to understand the stability of molecule, while hyperpolarizability has been calculated in order to assess the nonlinear optical properties of title molecule. Sensitivity towards autoxidation and hydrolysis mechanisms has been investigated by calculations of bond dissociation energies and radial distribution functions, respectively. Molecular docking study was also performed, in order to determine the pharmaceutical potential of the investigated molecule.

  18. Plant and fungal diversity in gut microbiota as revealed by molecular and culture investigations.

    Directory of Open Access Journals (Sweden)

    Nina Gouba

    Full Text Available BACKGROUND: Few studies describing eukaryotic communities in the human gut microbiota have been published. The objective of this study was to investigate comprehensively the repertoire of plant and fungal species in the gut microbiota of an obese patient. METHODOLOGY/PRINCIPAL FINDINGS: A stool specimen was collected from a 27-year-old Caucasian woman with a body mass index of 48.9 who was living in Marseille, France. Plant and fungal species were identified using a PCR-based method incorporating 25 primer pairs specific for each eukaryotic phylum and universal eukaryotic primers targeting 18S rRNA, internal transcribed spacer (ITS and a chloroplast gene. The PCR products amplified using these primers were cloned and sequenced. Three different culture media were used to isolate fungi, and these cultured fungi were further identified by ITS sequencing. A total of 37 eukaryotic species were identified, including a Diatoms (Blastocystis sp. species, 18 plant species from the Streptophyta phylum and 18 fungal species from the Ascomycota, Basidiomycota and Chytridiocomycota phyla. Cultures yielded 16 fungal species, while PCR-sequencing identified 7 fungal species. Of these 7 species of fungi, 5 were also identified by culture. Twenty-one eukaryotic species were discovered for the first time in human gut microbiota, including 8 fungi (Aspergillus flavipes, Beauveria bassiana, Isaria farinosa, Penicillium brevicompactum, Penicillium dipodomyicola, Penicillium camemberti, Climacocystis sp. and Malassezia restricta. Many fungal species apparently originated from food, as did 11 plant species. However, four plant species (Atractylodes japonica, Fibraurea tinctoria, Angelica anomala, Mitella nuda are used as medicinal plants. CONCLUSIONS/SIGNIFICANCE: Investigating the eukaryotic components of gut microbiota may help us to understand their role in human health.

  19. Pairing preferences of the model mono-valence mono-atomic ions investigated by molecular simulation. (United States)

    Zhang, Qiang; Zhang, Ruiting; Zhao, Ying; Li, HuanHuan; Gao, Yi Qin; Zhuang, Wei


    We carried out a series of potential of mean force calculations to study the pairing preferences of a series of model mono-atomic 1:1 ions with evenly varied sizes. The probabilities of forming the contact ion pair (CIP) and the single water separate ion pair (SIP) were presented in the two-dimensional plots with respect to the ion sizes. The pairing preferences reflected in these plots largely agree with the empirical rule of matching ion sizes in the small and big size regions. In the region that the ion sizes are close to the size of the water molecule; however, a significant deviation from this conventional rule is observed. Our further analysis indicated that this deviation originates from the competition between CIP and the water bridging SIP state. The competition is mainly an enthalpy modulated phenomenon in which the existing of the water bridging plays a significant role.

  20. Experimental and modelling investigation of surface EMG spike analysis. (United States)

    Gabriel, David A; Christie, Anita; Inglis, J Greig; Kamen, Gary


    A pattern classification method based on five measures extracted from the surface electromyographic (sEMG) signal is used to provide a unique characterization of the interference pattern for different motor unit behaviours. This study investigated the sensitivity of the five sEMG measures during the force gradation process. Tissue and electrode filtering effects were further evaluated using a sEMG model. Subjects (N=8) performed isometric elbow flexion contractions from 0 to 100% MVC. The sEMG signals from the biceps brachii were recorded simultaneously with force. The basic building block of the sEMG model was the detection of single fibre action potentials (SFAPs) through a homogeneous, equivalent isotropic, infinite volume conduction medium. The SFAPs were summed to generate single motor unit action potentials. The physiologic properties from a well-known muscle model and motor unit recruitment and firing rate schemes were combined to generate synthetic sEMG signals. The following pattern classification measures were calculated: mean spike amplitude, mean spike frequency, mean spike slope, mean spike duration, and the mean number of peaks per spike. Root-mean-square amplitude and mean power frequency were also calculated. Taken together, the experimental data and modelling analysis showed that below 50% MVC, the pattern classification measures were more sensitive to changes in force than traditional time and frequency measures. However, there are additional limitations associated with electrode distance from the source that must be explored further. Future experimental work should ensure that the inter-electrode distance is no greater than 1cm to mitigate the effects of tissue filtering.

  1. Origins of the amphiploid species Brassica napus L. investigated by chloroplast and nuclear molecular markers

    Directory of Open Access Journals (Sweden)

    Allender Charlotte J


    Full Text Available Abstract Background The amphiploid species Brassica napus (oilseed rape, Canola is a globally important oil crop yielding food, biofuels and industrial compounds such as lubricants and surfactants. Identification of the likely ancestors of each of the two genomes (designated A and C found in B. napus would facilitate incorporation of novel alleles from the wider Brassica genepool in oilseed rape crop genetic improvement programmes. Knowledge of the closest extant relatives of the genotypes involved in the initial formation of B. napus would also allow further investigation of the genetic factors required for the formation of a stable amphiploid and permit the more efficient creation of fully fertile re-synthesised B. napus. We have used a combination of chloroplast and nuclear genetic markers to investigate the closest extant relatives of the original maternal progenitors of B. napus. This was based on a comprehensive sampling of the relevant genepools, including 83 accessions of A genome B. rapa L. (both wild and cultivated types, 94 accessions of B. napus and 181 accessions of C genome wild and cultivated B. oleracea L. and related species. Results Three chloroplast haplotypes occurred in B. napus. The most prevalent haplotype (found in 79% of accessions was not present within the C genome accessions but was found at low frequencies in B. rapa. Chloroplast haplotypes characteristic of B. napus were found in a small number of wild and weedy B. rapa populations, and also in two accessions of cultivated B. rapa 'brocoletto'. Whilst introgression of the B. napus chloroplast type in the wild and weedy B. rapa populations has been proposed by other studies, the presence of this haplotype within the two brocoletto accessions is unexplained. Conclusions The distribution of chloroplast haplotypes eliminate any of the C genome species as being the maternal ancestor of the majority of the B. napus accessions. The presence of multiple chloroplast

  2. HIV-1 integrase strand-transfer inhibitors: design, synthesis and molecular modeling investigation. (United States)

    De Luca, Laura; De Grazia, Sara; Ferro, Stefania; Gitto, Rosaria; Christ, Frauke; Debyser, Zeger; Chimirri, Alba


    This study is focused on a new series of benzylindole derivatives with various substituents at the benzene-fused ring, suggested by our 3D pharmacophore model developed for HIV-1 integrase inhibitors (INIs). All synthesized compounds proved to be active in the nanomolar range (6-35 nM) on the strand-transfer step (ST). In particular, derivative 4-[1-(4-fluorobenzyl)-5,7-dimethoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (8e), presenting the highest best-fit value on pharmacophore model, showed a potency comparable to that of clinical INSTIs GS 9137 (1) and MK-0518 (2). The binding mode of our molecules has been investigated using the recently published crystal structure of the complex of full-length integrase from the prototype foamy virus in complex with its cognate DNA (PFV-IN/DNA). The results highlighted the ability of derivative 8e to assume the same binding mode of MK-0518 and GS 9137.

  3. Investigations of Protostellar Outflow Launching and Gas Entrainment: Hydrodynamic Simulations and Molecular Emission

    CERN Document Server

    Offner, S S R


    We investigate protostellar outflow evolution, gas entrainment, and star formation efficiency using radiation-hydrodynamic simulations of isolated, turbulent low-mass cores. We adopt an X-wind launching model, in which the outflow rate is coupled to the instantaneous protostellar accretion rate and evolution. We vary the outflow collimation angle from $\\theta$=0.01-0.1 and find that even well collimated outflows effectively sweep up and entrain significant core mass. The Stage 0 lifetime ranges from 0.14-0.19 Myr, which is similar to the observed Class 0 lifetime. The star formation efficiency of the cores spans 0.41-0.51. In all cases, the outflows drive strong turbulence in the surrounding material. Although the initial core turbulence is purely solenoidal by construction, the simulations converge to approximate equipartition between solenoidal and compressive motions due to a combination of outflow driving and collapse. When compared to a simulation of a cluster of protostars, which is not gravitationally ...

  4. Growth, physiological and molecular traits in Salicaceae trees investigated for phytoremediation of heavy metals and organics. (United States)

    Marmiroli, Marta; Pietrini, Fabrizio; Maestri, Elena; Zacchini, Massimo; Marmiroli, Nelson; Massacci, Angelo


    Worldwide, there are many large areas moderately contaminated with heavy metals and/or organics that have not been remediated due to the high cost and technical drawbacks of currently available technologies. Methods with a good potential for coping with these limitations are emerging from phytoremediation techniques, using, for example, specific amendments and/or plants selected from various candidates proven in several investigations to be reasonably efficient in extracting heavy metals from soil or water, or in co-metabolizing organics with bacteria flourishing or inoculated in their rhizospheres. Populus and Salix spp., two genera belonging to the Salicaceae family, include genotypes that can be considered among the candidates for this phytoremediation approach. This review shows the recent improvements in analytical tools based on the identification of useful genetic diversity associated with classical growth, physiological and biochemical traits, and the importance of plant genotype selection for enhancing phytoremediation efficiency. Particularly interesting are studies on the application of the phytoremediation of heavy metals and of chlorinated organics, in which microorganisms selected for their degradation capabilities were bioaugmented in the rhizosphere of Salicaceae planted at a high density for biomass and bioenergy production.

  5. Molecular investigation of Cryptosporidium in small caged pets in northeast China: host specificity and zoonotic implications. (United States)

    Li, Qiao; Li, Lu; Tao, Wei; Jiang, Yanxue; Wan, Qiang; Lin, Yongchao; Li, Wei


    This study screened 151 pet-derived fecal specimens randomly collected from four commercial markets in northeast China for the presence of Cryptosporidium by genus-specific nested PCRs of the small subunit rRNA gene. Of these, 14 specimens (9.3 %) from nine species of birds, two types of rodents, and a hedgehog were positive for Cryptosporidium. Sequence analysis on the PCR-positive isolates facilitated identification of three Cryptosporidium species (C. baileyi, C. galli, and C. ubiquitum) and two Cryptosporidium genotypes (ferret genotype and avian genotype V). The study birds were affected predominantly with bird-specific C. baileyi (Atlantic canary, budgerigar, crested myna, rock dove, and silky fowl), C. galli (Chinese hwamei), and Cryptosporidium avian genotype V (Fischer's lovebird and rosy-faced lovebird). Cryptosporidium ferret genotype previously considered rodent-adapted was identified in three specimens from budgerigar, chipmunk, and red squirrel. Two specimens collected from common hill myna and hedgehog were positive for C. ubiquitum. The species of birds that can be colonized by Cryptosporidium were extended. Moreover, the data expanded the host range of Cryptosporidium ferret genotype and C. ubiquitum, especially the birds. The carriage of zoonotic C. ubiquitum in small caged pets is of public health importance.

  6. Interaction of human chymase with ginkgolides, terpene trilactones of Ginkgo biloba investigated by molecular docking simulations. (United States)

    Dubey, Amit; Marabotti, Anna; Ramteke, Pramod W; Facchiano, Angelo


    The search for natural chymase inhibitors has a good potential to provide a novel therapeutic approach against the cardiovascular diseases and other heart ailments. We selected from literature 20 promising Ginkgo biloba compounds, and tested them for their potential ability to bind chymase enzyme using docking and a deep analysis of surface pocket features. Docking results indicated that the compounds may interact with the active site of human chymase, with favorable distinct interactions with important residues Lys40, His57, Lys192, Phe191, Val146, Ser218, Gly216, and Ser195. In particular, proanthocyanidin is the one with the best-predicted binding energy, with seven hydrogen bonds. Interestingly, all active G. biloba compounds have formed the hydrogen bond interactions with the positively charged Lys192 residue at the active site, involved in the mechanism of pH enhancement for the cleavage of angiotensin I site. Ginkgolic acid and proanthocyanidin have better predicted binding energy towards chymase than other serine proteases, i.e kallikrein, tryptase and elastase, suggesting specificity for chymase inhibition. Our study suggests these G. biloba compounds are a promising starting point for developing chymase inhibitors for the potential development of future drugs.

  7. Investigation of TNB/NNAP cocrystal synthesis, molecular interaction and formation process (United States)

    Chen, Peng-Yuan; Zhang, Lin; Zhu, Shun-Guan; Cheng, Guang-Bin; Li, Ning-Rui


    A novel cocrystal of 1,3,5-trinitrobenzene (TNB) and 1-nitronaphthalene (NNAP) was synthesized by solution and mechanochemical method, respectively. The crystal structure was characterized by single crystal X-ray diffraction (SXRD). Then the intermolecular interaction was illustrated quantitatively by Hirshfeld surface analysis accordingly. Two other isostructural cocrystals, TNT (2,4,6-trinitrotoluene)/NNAP and TNP (2,4,6-trinitrophenol)/NNAP were also calculated for comparison. Among the three cocrystals, TNB/NNAP cocrystal has the largest proportion of π-π stacking interaction (12.7%). While TNP/NNAP cocrystal has a greater percentage of hydrogen bonding than the other two cocrystals, which is 43.2% of the total interactions. These results indicate electronic effect has an influence on the intermolecular interaction in the cocrystal. The IR spectra of the intermediate products provide more information about the formation process of hydrogen bonding and π-π stacking. We can tell from the differential scanning calorimetry (DSC) thermograms that a eutectic mixture was generated first after TNB and NNAP were physically mixed without grinding, and then turned into the cocrystal and finally transformed completely.

  8. Large scale molecular analysis of traditional European maize populations. Relationships with morphological variation. (United States)

    Rebourg, C; Gouesnard, B; Charcosset, A


    A representative sample of 130 European traditional maize populations was analysed for both their morphological and molecular variation. The morphological analysis of 19 variables revealed a significant variability. Correlation analysis allowed us to distinguish between traits affected by earliness (plant and ear height) and structural traits (plant architecture, grain structure). Two main morphological types could be distinguished. Molecular analyses were performed for 29 RFLP loci on DNA bulks. The number of alleles detected was high when compared to previous studies (9.59 alleles per locus). Genetic diversity was also high (0.55), with a strong differentiation between populations (GST value of 35.6%). A clear relationship between the genetic diversity of the populations and their agronomic performances was highlighted. Morphological and molecular distances showed a tendency towards a triangular relationship. We therefore considered a two-phase process to be the most efficient approach for the classification of genetic resources: firstly, a molecular study to define groups of genetically close populations, and secondly a morphological description of populations from each group. In our European collection, this approach allowed us to separate the populations from Northern and Southern Europe and to define six groups of genetically close populations, comparable to European races. This study opens new prospects concerning the molecular analysis of very large collections of genetic resources, hitherto limited by the necessity of individual analyses, and proposes a first molecular classification of European maize germplasm.

  9. Molecular genetic analysis of X-linked hypogammaglobulinemia and isolated growth hormone deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, D.M.; Kurman, C.C.; Staudt, L.M. [Univ. of Brescia (Italy)] [and others


    In 1980 the clinical syndrome of X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA/GHD) was described. XLA/GHD patients have reduced serum levels of Ig and normal cell-mediated immunity, and thus resemble patients with Bruton`s X-linked agammaglobulinemia (XLA). However, XLA/GHD patients also have isolated GHD. Mutations and deletions in the Bruton`s tyrosine kinase gene (BTK) are responsible for Bruton`s XLA. We investigated BTK gene expression in an XLA/GHD patient from the family originally described by Northern analysis, cDNA sequencing, and Western analysis of protein production using mAb to BTK. BTK mRNA was normal in size and abundance, and the mRNA sequence was normal over the coding region, except for a single silent mutation. BTK protein was present in normal amounts in PBMC of this patient. Thus, at the molecular level, XLA/GHD is a different disease entity from Bruton`s XLA. These results suggest that undescribed genes critical for B cell development and growth hormone production exist on the X chromosome. 17 refs., 4 figs.

  10. Molecular modeling, spectroscopic signature and NBO analysis of some building blocks of organic conductors. (United States)

    Mukherjee, V


    Vibrational spectra with IR and Raman intensities in optimum state have been calculated for 2,2'-Bi-1,3-diselenole (commonly known as tetraselenafulvalene) and its halogen derivatives. All these calculations have been done by employing density functional theory (DFT) and second order Moller-Plesset perturbation theory (MP2) methods incorporated with suitable functionals and basis sets. Normal coordinate analysis has also been performed to calculate potential energy distributions (PEDs) to make a conspicuous assignment. The vibrational frequencies of all the four molecules have been assigned using PEDs and the results are compared with available values for the most similar molecules like tetrathiafulvalene. The molecular stability and bond strength have investigated by applying the Natural Bond Orbital (NBO) analysis. The energy gap between HOMO and LUMO is 2.041 eV for tetraselenafulvalene and it is slightly less than 2eV for halogen derivatives which implies that these molecules fall in the wide band gap semiconductor groups.

  11. Transcriptome analysis in Concholepas concholepas (Gastropoda, Muricidae): mining and characterization of new genomic and molecular markers. (United States)

    Cárdenas, Leyla; Sánchez, Roland; Gomez, Daniela; Fuenzalida, Gonzalo; Gallardo-Escárate, Cristián; Tanguy, Arnaud


    The marine gastropod Concholepas concholepas, locally known as the "loco", is the main target species of the benthonic Chilean fisheries. Genetic and genomic tools are necessary to study the genome of this species in order to understand the molecular basis of its development, growth, and other key traits to improve the management strategies and to identify local adaptation to prevent loss of biodiversity. Here, we use pyrosequencing technologies to generate the first transcriptomic database from adult specimens of the loco. After trimming, a total of 140,756 Expressed Sequence Tag sequences were achieved. Clustering and assembly analysis identified 19,219 contigs and 105,435 singleton sequences. BlastN analysis showed a significant identity with Expressed Sequence Tags of different gastropod species available in public databases. Similarly, BlastX results showed that only 895 out of the total 124,654 had significant hits and may represent novel genes for marine gastropods. From this database, simple sequence repeat motifs were also identified and a total of 38 primer pairs were designed and tested to assess their potential as informative markers and to investigate their cross-species amplification in different related gastropod species. This dataset represents the first publicly available 454 data for a marine gastropod endemic to the southeastern Pacific coast, providing a valuable transcriptomic resource for future efforts of gene discovery and development of functional markers in other marine gastropods.

  12. Molecular cytogenetic analysis of human blastocysts andcytotrophoblasts by multi-color FISH and Spectra Imaging analyses

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Jingly F.; Ferlatte, Christy; Baumgartner, Adolf; Jung,Christine J.; Nguyen, Ha-Nam; Chu, Lisa W.; Pedersen, Roger A.; Fisher,Susan J.; Weier, Heinz-Ulrich G.


    Numerical chromosome aberrations in gametes typically lead to failed fertilization, spontaneous abortion or a chromosomally abnormal fetus. By means of preimplantation genetic diagnosis (PGD), we now can screen human embryos in vitro for aneuploidy before transferring the embryos to the uterus. PGD allows us to select unaffected embryos for transfer and increases the implantation rate in in vitro fertilization programs. Molecular cytogenetic analyses using multi-color fluorescence in situ hybridization (FISH) of blastomeres have become the major tool for preimplantation genetic screening of aneuploidy. However, current FISH technology can test for only a small number of chromosome abnormalities and hitherto failed to increase the pregnancy rates as expected. We are in the process of developing technologies to score all 24 chromosomes in single cells within a 3 day time limit, which we believe is vital to the clinical setting. Also, human placental cytotrophoblasts (CTBs) at the fetal-maternal interface acquire aneuploidies as they differentiate to an invasive phenotype. About 20-50% of invasive CTB cells from uncomplicated pregnancies were found aneuploidy, suggesting that the acquisition of aneuploidy is an important component of normal placentation, perhaps limiting the proliferative and invasive potential of CTBs. Since most invasive CTBs are interphase cells and possess extreme heterogeneity, we applied multi-color FISH and repeated hybridizations to investigate individual CTBs. In summary, this study demonstrates the strength of Spectral Imaging analysis and repeated hybridizations, which provides a basis for full karyotype analysis of single interphase cells.

  13. Synthesis, molecular structure investigations and antimicrobial activity of 2-thioxothiazolidin-4-one derivatives (United States)

    Barakat, Assem; Al-Najjar, Hany J.; Al-Majid, Abdullah Mohammed; Soliman, Saied M.; Mabkhot, Yahia Nasser; Al-Agamy, Mohamed H. M.; Ghabbour, Hazem A.; Fun, Hoong-Kun


    A variety of 2-thioxothiazolidin-4-one derivatives were prepared and their in vitro antimicrobial activities were studied. Most of these compounds showed significant antibacterial activity specifically against Gram-positive bacteria, among which compounds 4a,e,g, 5b,e,g,h and 6f exhibit high levels of antimicrobial activity against Bacillus subtilis ATCC 10400 with Minimum Inhibitory Concentration (MIC) value of 16 μg/mL. All compounds have antifungal activity against Candida albicans. Unfortunately, however, none of the compounds were active against Gram-negative bacteria. The chemical structure of 3 was confirmed by X-ray single crystal diffraction technique. DFT calculations of 3 have been performed on the free C10H7Cl2NO2S2, 3a and the H-bonded complex, C10H7Cl2NO2S2·H2O, 3b to explore the effect of the H-bonding interactions on the geometric and electronic properties of the studied systems. A small increase in bond length was observed in the C12-O6 due to the H-bonding interactions between 3a and water molecule. MEP study has been used to recognize the most reactive sites towards electrophilic and nucleophilic attacks as well as the possible sites for the H-bonding interactions. The TD-DFT calculations have been used to predict theoretically the electronic spectra of the studied compound. The most intense transition band is predicted at 283.9 nm due to the HOMO-2/HOMO-1 to LUMO transitions. NBO analyses were carried out to investigate the stabilization energy of the various intramolecular charge transfer interactions within the studied molecules.

  14. Molecular epidemiology of a hepatitis C virus epidemic in a haemodialysis unit: outbreak investigation and infection outcome

    Directory of Open Access Journals (Sweden)

    Lanini Simone


    Full Text Available Abstract Background HCV is a leading cause of liver chronic diseases all over the world. In developed countries the highest prevalence of infection is reported among intravenous drug users and haemodialysis (HD patients. The present report is to identify the pathway of HCV transmission during an outbreak of HCV infection in a privately run haemodialysis (HD unit in Italy in 2005. Methods Dynamics of the outbreak and infection clinical outcomes were defined through an ambi-directional cohort study. Molecular epidemiology techniques were used to define the relationships between the viral variants infecting the patients and confirm the outbreak. Risk analysis and auditing procedures were carried out to define the transmission pathway(s. Results Of the 50 patients treated in the HD unit 5 were already anti-HCV positive and 13 became positive during the study period (AR = 28.9%. Phylogenic analysis identified that, all the molecularly characterized incident cases (10 out of 13, were infected with the same viral variant of one of the prevalent cases. The multivariate analysis and the auditing procedure disclosed a single event of multi-dose vials heparin contamination as the cause of transmission of the infection in 11 out of the 13 incident cases; 2 additional incident cases occurred possibly as a result of inappropriate risk management. Discussion More than 30% of all HCV infections in developed countries results from poor application of standard precautions during percutaneous procedures. Comprehensive strategy which included: educational programmes, periodical auditing on standard precaution, use of single-dose vials whenever possible, prospective surveillance for blood-borne infections (including a system of prompt notification and risk assessment/management dedicated staff are the cornerstone to contain and prevent outbreaks in HD Conclusions The outbreak described should serve as a reminder to HD providers that patients undergoing dialysis are

  15. Low-molecular weight plasma proteome analysis using centrifugal ultrafiltration. (United States)

    Greening, David W; Simpson, Richard J


    The low-molecular weight fraction (LMF) of the human plasma proteome is an invaluable source of biological information, especially in the context of identifying plasma-based biomarkers of disease. This protocol outlines a standardized procedure for the rapid/reproducible LMF profiling of human plasma samples using centrifugal ultrafiltration fractionation, followed by 1D-SDS-PAGE separation and nano-LC-MS/MS. Ultrafiltration is a convective process that uses anisotropic semipermeable membranes to separate macromolecular species on the basis of size. We have optimized centrifugal ultrafiltration for plasma fractionation with respect to buffer and solvent composition, centrifugal force, duration and temperature to facilitate >95% recovery, and enrichment of low-M (r) components from human plasma. Using this protocol, >260 unique peptides can be identified from a single plasma profiling experiment using 100 μL of plasma (Greening and Simpson, J Proteomics 73:637-648, 2010). The efficacy of this method is demonstrated by the identification, for the first time, of several plasma proteins (e.g., protein KIAA0649 (Q9Y4D3), rheumatoid factor D5, serine protease inhibitor A3, and transmembrane adapter protein PAG) previously not reported in extant high-confidence Human Proteome Organization Plasma Proteome Project datasets.

  16. Molecular cytogenetic analysis of dicentric chromosomes in acute myeloid leukemia. (United States)

    Sarova, Iveta; Brezinova, Jana; Zemanova, Zuzana; Ransdorfova, Sarka; Izakova, Silvia; Svobodova, Karla; Pavlistova, Lenka; Berkova, Adela; Cermak, Jaroslav; Jonasova, Anna; Siskova, Magda; Michalova, Kyra


    Dicentric chromosomes (DCs) have been described in many hematological diseases, including acute myeloid leukemia (AML). They are markers of cancer and induce chromosomal instability, leading to the formation of other chromosomal aberrations and the clonal evolution of pathological cells. Our knowledge of the roles and behavior of human DCs is often derived from studies of induced DCs and cell lines. It is difficult to identify all the DCs in the karyotypes of patients because of the limitations of metaphase cytogenetic methods. The aim of this study was to revise the karyotypes of 20 AML patients in whom DCs were found with conventional G-banding or multicolor fluorescence in situ hybridization (mFISH) with (multi)centromeric probes and to characterize the DCs at the molecular cytogenetic level. FISH analyses confirmed 23 of the 29 expected DCs in 18 of 20 patients and identified 13 others that had not been detected cytogenetically. Fourteen DCs were altered by other chromosomal changes. In conclusion, karyotypes with DCs are usually very complex, and we have shown that they often contain more than one DC, which can be missed with conventional or mFISH methods. Our study indicates an association between number of DCs in karyotype and very short survival of patients.

  17. Molecular cytogenetic applications in analysis of the cancer genome. (United States)

    Rao, Pulivarthi H; Nandula, Subhadra V; Murty, Vundavalli V


    Cancer cells exhibit nonrandom and complex chromosome abnormalities. The role of genomic changes in cancer is well established. However, the identification of complex and cryptic chromosomal changes is beyond the resolution of conventional banding methods. The fluorescence microscopy afforded by imaging technologies, developed recently, facilitates a precise identification of these chromosome alterations in cancer. The three most commonly utilized molecular cytogenetics methods comparative genomic hybridization, spectral karyotype, and fluorescence in situ hybridization, that have already become benchmark tools in cancer cytogenetics, are described in this chapter. Comparative genomic hybridization is a powerful tool for screening copy-number changes in tumor genomes without the need for preparation of metaphases from tumor cells. Multicolor spectral karyotype permits visualization of all chromosomes in one experiment permitting identification of precise chromosomal changes on metaphases derived from tumor cells. The uses of fluorescence in situ hybridization are diverse, including mapping of alteration in single copy genes, chromosomal regions, or entire chromosomes. The opportunities to detect genetic alterations in cancer cells continue to evolve with the use of these methodologies both in diagnosis and research.

  18. Investigation of the Interaction between Patulin and Human Serum Albumin by a Spectroscopic Method, Atomic Force Microscopy, and Molecular Modeling

    Directory of Open Access Journals (Sweden)

    Li Yuqin


    Full Text Available The interaction of patulin with human serum albumin (HSA was studied in vitro under normal physiological conditions. The study was performed using fluorescence, ultraviolet-visible spectroscopy (UV-Vis, circular dichroism (CD, atomic force microscopy (AFM, and molecular modeling techniques. The quenching mechanism was investigated using the association constants, the number of binding sites, and basic thermodynamic parameters. A dynamic quenching mechanism occurred between HSA and patulin, and the binding constants (K were 2.60 × 104, 4.59 × 104, and 7.01 × 104 M−1 at 288, 300, and 310 K, respectively. Based on fluorescence resonance energy transfer, the distance between the HSA and patulin was determined to be 2.847 nm. The ΔG0, ΔH0, and ΔS0 values across various temperatures indicated that hydrophobic interaction was the predominant binding force. The UV-Vis and CD results confirmed that the secondary structure of HSA was altered in the presence of patulin. The AFM results revealed that the individual HSA molecule dimensions were larger after interaction with patulin. In addition, molecular modeling showed that the patulin-HSA complex was stabilized by hydrophobic and hydrogen bond forces. The study results suggested that a weak intermolecular interaction occurred between patulin and HSA. Overall, the results are potentially useful for elucidating the toxigenicity of patulin when it is combined with the biomolecular function effect, transmembrane transport, toxicological, testing and other experiments.

  19. Dethreading of a Photoactive Azobenzene-Containing Molecular Axle from a Crown Ether Ring: A Computational Investigation. (United States)

    Tabacchi, Gloria; Silvi, Serena; Venturi, Margherita; Credi, Alberto; Fois, Ettore


    Pseudorotaxanes formed by a dibenzo[24]crown-8 ring (R) and a dialkylammonium axle bearing either two E- or two Z-azobenzene units (EE-A or ZZ-A) revealed useful for the construction of light-powered molecular machines and motors, as they provide the opportunity of photocontrolling self-assembly/disassembly processes. The potential energies profiles for the dethreading of these complexes have been investigated by adopting a combination of first-principles molecular dynamics, metadynamics and quantum-chemical geometry optimization approaches. While the dethreading of the EE-A axle is associated with a monotonic energy increase, for that of the ZZ-A axle a transition state and an intermediate structure, in which the components are still threaded together, are found. The rate determining step for the dethreading of the ZZ axle has a higher energy barrier than that of the EE axle, in agreement with the experimental kinetic data. Moreover, the results suggest that the elliptic shape of the ring cavity is important for discriminating between the E and Z terminal azobenzene during dethreading.

  20. Molecular docking study investigating the possible mode of binding of C.I. Acid Red 73 with DNA. (United States)

    Guo, Yumei; Yue, Qinyan; Gao, Baoyu


    C.I. Acid Red 73 is a reactive azo dye with a variable potential carcinogenicity. The mechanism mediating interactions that occur between the dye and DNA have not been completely understood thus far. In this study, molecular docking techniques were applied to describe the most probable mode of DNA binding as well as the sequence selectivity of the C.I. Acid Red 73 dye. These docking experiments revealed that the dye is capable of interacting with the minor groove of the DNA on the basis of its curved shape, which fits well with the topology of double-stranded DNA. In addition, the dye can bind selectively to the minor groove of the DNA by applying CGT sequence selectivity. Further, the minor groove can be recognized although DNA targets present intercalation gaps. However, intercalative binding can also occur when the DNA target possesses an appropriate intercalation gap. Compared with the other eight DNA sequences that were studied, the DNA dodecamer d(CGCGATATCGCG)(2) (PDB ID: 1DNE) presents a very favorable target for the binding of C.I. Acid Red 73 to the minor groove, with the lowest binding free energy -9.19 kcal/mol. Results reported from this study are expected to provide useful information for research involving further simulations of molecular dynamics and toxicology investigations of the dye.

  1. Molecular cloning and expression analysis on LPL of Coilia nasus. (United States)

    Wang, Meiyao; Xu, Dongpo; Liu, Kai; Yang, Jian; Xu, Pao


    Coilia nasus is one important commercial anadromous species which mainly distributed in the Yangtze River in China. At present, it has been on the "National Key Protective Species List" because of its severe resource damage. Lipid metabolism is very important during its long-distance migration. To make further research on lipid metabolism of C. nasus, we cloned lipoprotein lipase gene with homologous cloning method. A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. The deduced amino acids had high similarity with the reported LPL sequence of other species. It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. LPL expressed in all the detected tissues. The highest expression was in mesenteric adipose, and followed by liver, muscle, stomach. Lipid expressed lowly in spleen, heart, head kidney, trunk kidney, gill and brain. The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus.

  2. Synthesis, molecular spectroscopy and thermal analysis of some cefepime complexes (United States)

    Masoud, Mamdouh S.; Ali, Alaa E.; Ghareeb, Doaa A.; Nasr, Nessma M.


    The metal complexes of cefepime with Cr (III), Mn (II), Fe (III), Co (II), Cu (II), Zn (II), Cd (II), Hg (II) and mixed metals (Fe, Ni) or (Cu, Fe) were synthesized, the suggested structures of the complexes are based on the results of the elemental analysis, infrared, UV-visible, mass and HNMR spectra, effective magnetic moment as well as the thermal analysis (DTA, TGA & DSC) and characterized by energy dispersive x-ray (EDX) and scanning electron microscopy (SEM). The results obtained suggested that cefepime reacted with metal ions as bidentate ligand through the nitrogen of the β-lactone thiozolidine ring and carboxylate ion forming a five membered ring. The kinetic thermodynamic parameters were estimated from the DTA curves.

  3. Employing Power Graph Analysis to Facilitate Modeling Molecular Interaction Networks

    Directory of Open Access Journals (Sweden)

    Momchil Nenov


    Full Text Available Mathematical modeling is used to explore and understand complex systems ranging from weather patterns to social networks to gene-expression regulatory mechanisms. There is an upper limit to the amount of details that can be reflected in a model imposed by finite computational resources. Thus, there are methods to reduce the complexity of the modeled system to its most significant parameters. We discuss the suitability of clustering techniques, in particular Power Graph Analysis as an intermediate step of modeling.

  4. Molecular diagnostic analysis for Huntington's disease: a prospective evaluation.


    MacMillan, J C; Davies, P.; Harper, P S


    The availability of mutation analysis for the CAG repeat expansion associated with Huntington's disease has prompted clinicians in various specialties to request testing of samples from patients displaying clinical features that might be attributable to Huntington's disease. A series of 38 cases presenting with clinical features thought possibly to be due to Huntington's disease were analysed prospectively. In 53% of such cases presenting initially with chorea and 62.5% with psychiatric sympt...

  5. First-Principles Molecular Dynamics Investigation of the Atomic-Scale Energy Transport: From Heat Conduction to Thermal Radiation

    CERN Document Server

    Ji, Pengfei


    First-principles molecular dynamics simulation based on a plane wave/pseudopotential implementation of density functional theory is adopted to investigate atomic scale energy transport for semiconductors (silicon and germanium). By imposing thermostats to keep constant temperatures of the nanoscale thin layers, initial thermal non-equilibrium between the neighboring layers is established under the vacuum condition. Models with variable gap distances with an interval of lattice constant increment of the simulated materials are set up and statistical comparisons of temperature evolution curves are made. Moreover, the equilibration time from non-equilibrium state to thermal equilibrium state of different silicon or/and germanium layers combinations are calculated. The results show significant distinctions of heat transfer under different materials and temperatures combinations. Further discussions on the equilibrium time are made to explain the simulation results. As the first work of the atomic scale energy tra...

  6. A molecular dynamics investigation of the deformation mechanism and shape memory effect of epoxy shape memory polymers (United States)

    Yang, Hua; Wang, ZhengDao; Guo, YaFang; Shi, XingHua


    Following deformation, thermally induced shape memory polymers (SMPs) have the ability to recover their original shape with a change in temperature. In this work, the thermomechanical properties and shape memory behaviors of three types of epoxy SMPs with varying curing agent contents were investigated using a molecular dynamics (MD) method. The mechanical properties under uniaxial tension at different temperatures were obtained, and the simulation results compared reasonably with experimental data. In addition, in a thermomechanical cycle, ideal shape memory effects for the three types of SMPs were revealed through the shape frozen and shape recovery responses at low and high temperatures, respectively, indicating that the recovery time is strongly influenced by the ratio of E-51 to 4,4'-Methylenedianiline.

  7. Investigation on Molecular Non-covalent Interaction in the Sodium Dodecyl Benzene Sulfonatepolychrome Blue B-protein Replacement Reaction

    Institute of Scientific and Technical Information of China (English)

    GAO,Hong-Wen(郜洪文); WU,Ji-Rong(邬继荣); SHEN,Rong(沈荣)


    The molecular non-covalent interaction often originates from the electrostatic attraction and accords with the Langmuir isothermal adsorption. The sodium dodecyl benzene sulfonate (SDBS)-polychrome blue B (PCB)-protein [bovine serum albumin (BSA), ovalbumin (OVA) and myoglobin (MB)] ternary reaction has been investigated at Ph 3.88. Protein to replace PCB from the PCB-SDBS binding product was used to characterize the assembly of an invisible-spectral compound, SDBS, on proteins by measuring the variation of PCB light-absorption by the microsurface adsorption-spectral correction (MSASC) technique. The effect of ionic strength and temperature on the aggregation was studied. Results showed that the aggregates SDBS92·BSA, SDBS58·OVA and SDBS15·MB at 30 ℃ and SDBS83·BSA, SDBS39·OVA and SDBS10·MB at 50 ℃ are formed.

  8. Importance of molecular cell biology investigations in human medicine in the story of the Hutchinson-Gilford progeria syndrome. (United States)

    Raška, Ivan


    Ranged among laminopathies, Hutchinson-Gilford progeria syndrome is a syndrome that involves premature aging, leading usually to death at the age between 10 to 14 years predominatly due to a myocardial infarction or a stroke. In the lecture I shall overview the importance of molecular cell biology investigations that led to the discovery of the basic mechanism standing behind this rare syndrome. The genetic basis in most cases is a mutation at the nucleotide position 1824 of the lamin A gene. At this position, cytosine is substituted for thymine so that a cryptic splice site within the precursor mRNA for lamin A is generated. This results in a production of abnormal lamin A, termed progerin, its presence in cells having a deleterious dominant effect. Depending on the cell type and tissue, progerin induces a pleiotropy of defects that vary in different tissues. The present endeavour how to challenge this terrible disease will be also mentioned.

  9. Experimental and Molecular Dynamics Simulations for Investigating the Effect of Fatty Acid and Its Derivatives on Low Sulfur Diesel Lubricity

    Institute of Scientific and Technical Information of China (English)

    Luo Hui; Fan Weiyu; Li Yang; Zhao Pinhui; Nan Guozhi


    In this work, fatty acid and its derivatives were adopted as lubricity additives for low sulfur diesel. Tribological evaluation obtained from the High-Frequency Reciprocating Rig (HFRR) apparatus showed that the lubricating performance of the additives increased in the following order:stearic acid>glycol monopalmitate>stearyl alcohol>ethyl palmitate>cetyl ethyl ether. The adsorption behavior of the additives on Fe (110) surface and Fe2O3 (001) surface was investigated by mo-lecular dynamics (MD) simulations to verify their lubricity performance. The results suggested that adsorption energies of the additives on Fe (110) surface are determined by the van der Waals forces, while adsorptions on Fe2O3 (001) surface are signiifcantly attributed to the electrostatic attractive forces. Higher values of adsorption energy of the additives on Fe2O3 (001) surface indicate that the additive has more efifcient lubricity enhancing properties.

  10. Two-dimensional functional molecular nanoarchitectures - Complementary investigations with scanning tunneling microscopy and X-ray spectroscopy (United States)

    Klappenberger, Florian


    Functional molecular nanoarchitectures (FMNs) are highly relevant for the development of future nanotechnology devices. Profound knowledge about the atomically controlled construction of such nanoscale assemblies is an indispensable requirement to render the implementation of such components into a real product successful. For exploiting their full potential the architectures’ functionalities have to be characterized in detail including the ways to tailor them. In recent years a plethora of sophisticated constructs were fabricated touching a wide range of research topics. The present review summarizes important achievements of bottom-up fabricated, molecular nanostructures created on single crystal metal surfaces under ultra-high vacuum conditions. This selection focuses on examples where self-assembly mechanisms played a central role for their construction. Such systems, though typically quite complex, can be comprehensively understood by the STM+XS approach combining scanning tunneling microscopy (STM) with X-ray spectroscopy (XS) and being aided in the atomic interpretation by the appropriate theoretic analysis, often from density functional theory. The symbiosis of the techniques is especially fruitful because of the complementary character of the information accessed by the local microscopy and the space-averaging spectroscopy tools. STM delivers sub-molecular spatial-resolution, but suffers from limited sensitivity for the chemical and conformational states of the building-blocks. XS compensates these weaknesses with element- and moiety-specific data, which in turn would be hard to interpret with respect to structure formation without the topographic details revealed by STM. The united merit of this methodology allows detailed geometric information to be obtained and addresses both the electronic and chemical state of the complex organic species constituting such architectures. Thus, possible changes induced by the various processes such as surface

  11. Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population

    Directory of Open Access Journals (Sweden)

    Sameer A


    Full Text Available Abstract The development and progression of colorectal cancer (CRC is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (APC and β-catenin plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in the APC and β-catenin genes in the pathogenesis of CRC in the Kashmir valley, and to correlate it with various clinicopathological variables. We examined the paired tumour and normal-tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region (MCR of the APC gene and exon 3 of the β-catenin gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP and/or PCR-direct sequencing. Analysis of promoter hypermethylation of the APC gene was also carried out using methylation-specific PCR (MS-PCR. The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12.8 per cent (11 of 86. Promoter hypermethylation of APC was observed in 54.65 per cent (47 of 86 of cases. Furthermore, we found a significant association between tumour location, tumour grade and node status and the methylation status of the APC gene (p ≤ 0.05. Although the number of mutations in the APC and β-catenin genes in our CRC cases was very low, the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator, APC, of the Wnt pathway in the development of CRC in the Kashmiri population.

  12. Analysis of smoke PAHs from selected Taiwanese cigarettes by using molecular imprinting polymers. (United States)

    Ho, Wei L; Lin, Ta C; Liu, Yu Y; Chen, Jiun A


    Polycyclic aromatic hydrocarbons (PAHs) and their derivatives are common trace pollutants produced during incomplete combustion of organic substances, such as tobacco. After sampling cigarette smoke, PAH collators must undergo pretreatment processes such as extraction, cleanup and concentration before instrument analysis. This study combines molecular imprinted polymers (MIPs) and solid-phase extraction (SPE) to create a novel sample pretreatment technique. Experimental results demonstrate that MIPs have good selectivity for benz[a]pyrene (BaP) from a mixture of 16 PAH solvents. The MIPs were applied to a sample taken from mainstream smoke from a cigarette. Based on functional monomers and crosslinkers, this study investigated two groups of MIPs. After the template was removed, various tests, including capacity, selectivity, recovery, scanning electron microscope (SEM) observations and real environmental sample tests, were conducted. Experimental results show that MIP-1 is the best MIP, with a capacity of 20.78 +/- 1.7 (micro g/g), BaP selectivity and recovery exceeding 93%. In environmental sample tests, i.e., mainstream smoke from S and M brand cigarettes, 80% of BaP was absorbed by the MIP compared with absorbed by the filters. All experimental results suggest that MIPs effectively adsorbed BaP among 16 different PAHs, reduced background interference and increased signal resolution compared with traditional extraction techniques. Additionally, using MIPs for sample pretreatment is less time-consuming than traditional sample pretreatments and also reduces the amount of organic solvent used. Using molecular imprinted polymers solid extraction (MISPE) may separate target analytes from a complex sample more effectively than traditional Soxhlet extraction. Future toxicity tests should contribute to the understanding of toxic compounds emitted from specific pollution sources.

  13. Phylogenetic and Molecular Clock Analysis of Dengue Serotype 1 and 3 from New Delhi, India. (United States)

    Afreen, Nazia; Naqvi, Irshad H; Broor, Shobha; Ahmed, Anwar; Parveen, Shama


    Dengue fever is the most prevalent arboviral disease in the tropical and sub-tropical regions of the world. The present report describes molecular detection and serotyping of dengue viruses in acute phase blood samples collected from New Delhi, India. Phylogenetic and molecular clock analysis of dengue virus serotype 1 and 3 strains were also investigated. Dengue virus infection was detected in 68.87% out of 604 samples tested by RT-PCR between 2011 & 2014. Dengue serotype 1 was detected in 25.48% samples, dengue serotype 2 in 79.56% samples and dengue serotype 3 in 11.29% samples. Dengue serotype 4 was not detected. Co-infection by more than one dengue serotype was detected in 18.26% samples. Envelope gene of 29 DENV-1 and 14 DENV-3 strains were sequenced in the study. All the DENV-1 strains grouped with the American African genotype. All DENV-3 strains were found to belong to Genotype III. Nucleotide substitution rates of dengue 1 and 3 viruses were determined in the study. Time to the most recent common ancestor (TMRCA) of dengue 1 viruses was determined to be 132 years. TMRCA of DENV-3 viruses was estimated to be 149 years. Bayesian skyline plots were constructed for Indian DENV-1 and 3 strains which showed a decrease in population size since 2005 in case of DENV- 1 strains while no change was observed in recent years in case of DENV-3 strains. The study also revealed a change in the dominating serotype in Delhi, India in recent years. The study will be helpful in formulating control strategies for the outbreaks. In addition, it will also assist in tracking the movement and evolution of this emerging virus.

  14. Identification and in silico analysis of the Citrus HSP70 molecular chaperone gene family

    Directory of Open Access Journals (Sweden)

    Luciano G. Fietto


    Full Text Available The completion of the genome sequencing of the Arabidopsis thaliana model system provided a powerful molecular tool for comparative analysis of gene families present in the genome of economically relevant plant species. In this investigation, we used the sequences of the Arabidopsis Hsp70 gene family to identify and annotate the Citrus Hsp70 genes represented in the CitEST database. Based on sequence comparison analysis, we identified 18 clusters that were further divided into 5 subgroups encoding four mitochondrial mtHsp70s, three plastid csHsp70s, one ER luminal Hsp70 BiP, two HSP110/SSE-related proteins and eight cytosolic Hsp/Hsc70s. We also analyzed the expression profile by digital Northern of each Hsp70 transcript in different organs and in response to stress conditions. The EST database revealed a distinct population distribution of Hsp70 ESTs among isoforms and across the organs surveyed. The Hsp70-5 isoform was highly expressed in seeds, whereas BiP, mitochondrial and plastid HSp70 mRNAs displayed a similar expression profile in the organs analyzed, and were predominantly represented in flowers. Distinct Hsp70 mRNAs were also differentially expressed during Xylella infection and Citrus tristeza viral infection as well as during water deficit. This in silico study sets the groundwork for future investigations to fully characterize functionally the Citrus Hsp70 family and underscores the relevance of Hsp70s in response to abiotic and biotic stresses in Citrus.

  15. KEGG for representation and analysis of molecular networks involving diseases and drugs. (United States)

    Kanehisa, Minoru; Goto, Susumu; Furumichi, Miho; Tanabe, Mao; Hirakawa, Mika


    Most human diseases are complex multi-factorial diseases resulting from the combination of various genetic and environmental factors. In the KEGG database resource (, diseases are viewed as perturbed states of the molecular system, and drugs as perturbants to the molecular system. Disease information is computerized in two forms: pathway maps and gene/molecule lists. The KEGG PATHWAY database contains pathway maps for the molecular systems in both normal and perturbed states. In the KEGG DISEASE database, each disease is represented by a list of known disease genes, any known environmental factors at the molecular level, diagnostic markers and therapeutic drugs, which may reflect the underlying molecular system. The KEGG DRUG database contains chemical structures and/or chemical components of all drugs in Japan, including crude drugs and TCM (Traditional Chinese Medicine) formulas, and drugs in the USA and Europe. This database also captures knowledge about two types of molecular networks: the interaction network with target molecules, metabolizing enzymes, other drugs, etc. and the chemical structure transformation network in the history of drug development. The new disease/drug information resource named KEGG MEDICUS can be used as a reference knowledge base for computational analysis of molecular networks, especially, by integrating large-scale experimental datasets.

  16. Inhibition of MMP-9 by green tea catechins and prediction of their interaction by molecular docking analysis. (United States)

    Sarkar, Jaganmay; Nandy, Suman Kumar; Chowdhury, Animesh; Chakraborti, Tapati; Chakraborti, Sajal


    Green tea polyphenolic catechins have been shown to prevent various types of diseases such as pulmonary hypertension (PAH), cancer and cardiac and neurological disorders. Matrix metalloproteinases (MMPs) play an important role in the development of PAH. The present study demonstrated that among the four green tea catechins (EGCG, ECG, EC and EGC), EGCG and ECG inhibit pro-/active MMP-9 activities in pulmonary artery smooth muscle cell culture supernatant. Based on the above, we investigated the interactions of pro-/active MMP-9 with the green tea catechins by computational methods. In silico molecular docking analysis revealed a strong interaction between pro-/active MMP-9 and EGCG/ECG, and galloyl group appears to be responsible for this enhanced interaction. The molecular docking studies corroborate our experimental observation that EGCG and ECG are mainly active in preventing both the proMMP-9 and MMP-9 activities.

  17. Molecular Packing Structure of Mesogenic Octa-Hexyl Substituted Phthalocyanine Thin Film by X-ray Diffraction Analysis. (United States)

    Ohmori, Masashi; Higashi, Takuya; Fujii, Akihiko; Ozaki, Masanori


    The molecular packing structure in a thin film of the liquid crystalline phthalocyanine, 1,4,8,11,15,18,22,25-octahexylphthalocyanine (C6PcH2), which is a promising small-molecular material for solution-processable organic thin-film solar cells, has been investigated by X-ray diffraction (XRD) measurement. The crystal structure of C6PcH2 in the spin-coated film was determined to be a centered rectangular structure (a = 36.4 Å, b = 20.3 Å). The tilt angle of the phthalocyanine core normal vector was 34-39° from the column axis, and the shortest intermolecular distance was 3.9-4.0 A. The crystal structure determined by XRD analysis was ascertained to be consistent with that calculated by Fourier analvsis.

  18. Comparative molecular field analysis of quinoline derivatives as selective and noncompetitive mGluR1 antagonists. (United States)

    Sekhar, Y Nataraja; Nayana, M Ravi Shashi; Ravikumar, Muttineni; Mahmood, S K


    A 3D- QSAR model os Comparative Molecular Field Analysib (CoMFA) of 45 quinoline derivatives as metaborropic glutamate receptor subtype 1 (mGluR1) inhibitors wew investigated. The CoMFA analysis provided a model with q(2) value of 0.827 and r(2) value of 0.990, in which q(2) value of 0.827 and an r(2) value of 0.990, in which the good correlation between the inhibitory activities and the steric and electrostatic molecular field around the analoques was observed. The predictive ability of the models was validated using the set of 12 compounds that were not included in the training set of 33 compounds. These results provided further understanding of the relationship between the structural features of quinolone derivatives and its activities, which should be applicable to design and find new potential mGluR1 inhibitors.

  19. The role of internal node sequences and the molecular clock in the analysis of serially-sampled data. (United States)

    Buendia, Patricia; Collins, Timothy M; Narasimhan, Giri


    Algorithms that infer phylogenetic relationships between serially-sampled sequences have been developed in recent years to assist in the analysis of rapidly-evolving human pathogens. Our study consisted of evaluating seven relevant methods using empirical as well as simulated data sets. In particular, we investigated how the molecular clock hypothesis affected their relative performance, as three of the algorithms that accept serially-sampled data as input assume a molecular clock. Our results show that the standard phylogenetic methods and MinPD had a better overall performance. Surprisingly, when all internal node sequences were included in the data, the topological performance measure of all the methods, with the exception of MinPD, dropped significantly.

  20. Pteros 2.0: Evolution of the fast parallel molecular analysis library for C++ and python. (United States)

    Yesylevskyy, Semen O


    Pteros is the high-performance open-source library for molecular modeling and analysis of molecular dynamics trajectories. Starting from version 2.0 Pteros is available for C++ and Python programming languages with very similar interfaces. This makes it suitable for writing complex reusable programs in C++ and simple interactive scripts in Python alike. New version improves the facilities for asynchronous trajectory reading and parallel execution of analysis tasks by introducing analysis plugins which could be written in either C++ or Python in completely uniform way. The high level of abstraction provided by analysis plugins greatly simplifies prototyping and implementation of complex analysis algorithms. Pteros is available for free under Artistic License from

  1. Flurbiprofen–antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling

    Directory of Open Access Journals (Sweden)

    Ashraf Z


    prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2 proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities with reduced GI adverse effects than the parent drug. Keywords: flurbiprofen prodrugs, natural antioxidants, molecular docking, molecular dynamic simulation, pharmacological investigation, NSAIDs

  2. Molecular analysis of the emergence of pandemic Vibrio parahaemolyticus

    Directory of Open Access Journals (Sweden)

    Binnewies Tim T


    Full Text Available Abstract Background Vibrio parahaemolyticus is abundant in the aquatic environment particularly in warmer waters and is the leading cause of seafood borne gastroenteritis worldwide. Prior to 1995, numerous V. parahaemolyticus serogroups were associated with disease, however, in that year an O3:K6 serogroup emerged in Southeast Asia causing large outbreaks and rapid hospitalizations. This new highly virulent strain is now globally disseminated. Results We performed a four-way BLAST analysis on the genome sequence of V. parahaemolyticus RIMD2210633, an O3:K6 isolate from Japan recovered in 1996, versus the genomes of four published Vibrio species and constructed genome BLAST atlases. We identified 24 regions, gaps in the genome atlas, of greater than 10 kb that were unique to RIMD2210633. These 24 regions included an integron, f237 phage, 2 type III secretion systems (T3SS, a type VI secretion system (T6SS and 7 Vibrio parahaemolyticus genomic islands (VPaI-1 to VPaI-7. Comparative genomic analysis of our fifth genome, V. parahaemolyticus AQ3810, an O3:K6 isolate recovered in 1983, identified four regions unique to each V. parahaemolyticus strain. Interestingly, AQ3810 did not encode 8 of the 24 regions unique to RMID, including a T6SS, which suggests an additional virulence mechanism in RIMD2210633. The distribution of only the VPaI regions was highly variable among a collection of 42 isolates and phylogenetic analysis of these isolates show that these regions are confined to a pathogenic clade. Conclusion Our data show that there is considerable genomic flux in this species and that the new highly virulent clone arose from an O3:K6 isolate that acquired at least seven novel regions, which included both a T3SS and a T6SS.

  3. Molecular analysis of the emergence of pandemic Vibrio parahaemolyticus

    DEFF Research Database (Denmark)

    Boyd, EF; Cohen, AL; Naughton, LM


    emerged in Southeast Asia causing large outbreaks and rapid hospitalizations. This new highly virulent strain is now globally disseminated. Results We performed a four-way BLAST analysis on the genome sequence of V. parahaemolyticus RIMD2210633, an O3:K6 isolate from Japan recovered in 1996, versus....... Conclusion Our data show that there is considerable genomic flux in this species and that the new highly virulent clone arose from an O3:K6 isolate that acquired at least seven novel regions, which included both a T3SS and a T6SS....

  4. Molecular spectroscopic investigation on fractionation-induced changes on biomacromolecule of co-products from bioethanol processing to explore protein metabolism in ruminants (United States)

    Zhang, Xuewei; Yan, Xiaogang; Beltranena, Eduardo; Yu, Peiqiang


    Fractionation processing is an efficient technology which is capable to redesign/redevelop a new food or feed product with a specified chemical and nutrient profile. This processing technique was able to produce four different fractions (called "A", "B", "C", "D" fractions/treatments) with different nutrient profile form a co-product of bioethanol processing [wheat dried distillers grains with soluble (DDGS)]. To date, there is no study on the effect of fractionation processing on inherent molecular structure of different fractions and how the processing-induced structural change affect the metabolic characteristics of protein and nutrient availability. The objectives of this experiment were to: (1) investigate the effect of fractionation processing on changes of protein functional groups (amide I, amide II, and their ratio) and molecular structure (modeled α-helix, β-sheet, and their ratio), and (2) study the relationship between the fractionation processing-induced changes of protein molecular structure and nutrients availability as well as the metabolic characteristics of protein. The hypothesis of this study was that the fractionation processing changes the molecular structure and such changes affect the metabolic characteristics of protein. The protein molecular structure spectral profile of the fractions A, B, C and D were identified by Fourier-transform infrared attenuated total reflection spectroscopy (FT/IR-ATR). The results showed that the fractionation processing significantly affected the protein molecular spectral profiles. The differences in amide I to amide II peak area and height ratios were strongly significant (P < 0.01) among the treatment fractions, ranging from 4.98 to 6.33 and 3.28 to 4.00, respectively. The difference in the modeled protein α-helix to β-sheet ratio was also strongly significant (P < 0.01) among the treatment fractions. Multivariate molecular spectral analysis with cluster (CLA) and principal component analyses (PCA

  5. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

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    Farshad Farshidfar


    Full Text Available Cholangiocarcinoma (CCA is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

  6. Systems theoretic analysis of the central dogma of molecular biology: some recent results. (United States)

    Gao, Rui; Yu, Juanyi; Zhang, Mingjun; Tarn, Tzyh-Jong; Li, Jr-Shin


    This paper extends our early study on a mathematical formulation of the central dogma of molecular biology, and focuses discussions on recent insights obtained by employing advanced systems theoretic analysis. The goal of this paper is to mathematically represent and interpret the genetic information flow at the molecular level, and explore the fundamental principle of molecular biology at the system level. Specifically, group theory was employed to interpret concepts and properties of gene mutation, and predict backbone torsion angle along the peptide chain. Finite state machine theory was extensively applied to interpret key concepts and analyze the processes related to DNA hybridization. Using the proposed model, we have transferred the character-based model in molecular biology to a sophisticated mathematical model for calculation and interpretation.

  7. Modeling and analysis of Schistosoma Argonaute protein molecular spatial conformation

    Institute of Scientific and Technical Information of China (English)

    Jianhua Zhang; Zhigang Shang; Xiaohui Zhang; Yuntao Zhang


    Objective: To analyze the amino acid sequence composition, secondary structure, the spatial conformation of its domain and other characteristics of Argonaute protein. Methods:Bioinformatics tools and the internet server were used. Firstly, the amino acid sequence composition features of the Argonaute protein were analyzed, and the phylogenetic tree was constructed. Secondly, Argonaute protein’s distribution of secondary structure and its physicochemical properties were predicted. Lastly, the protein functional expression form of the domain group was established through the Phyre-based analysis on the spatial conformation of Argonaute protein domains. Results: 593 amino acids were encoded by Argonaute protein, the phylogenetic tree was constructed, and Argonaute protein’s distribution of secondary structure and its physicochemical properties were obtained through analysis. In addition, the functional expression form which comprised the N-terminal PAZ domain and C-terminal Piwi domain for the Argonaute protein was obtained with Phyre. Conclusions: The information relationship between the structure and function of the Argonaute protein can be initially established with bioinformatics tools and the internet server, and this provides the theoretical basis for further clarifying the function of Schistosoma Argonaute protein.

  8. Comparative molecular analysis of bacterial species associated with periodontal disease. (United States)

    De Iuliis, V; Ursi, S; Di Tommaso, L M; Caruso, M; Marino, A; D Ercole, S; Caputi, S; Sinjari, B; Festa, F; Macri, M; Martinotti, S; Vitullo, G; Toniato, E


    Periodontal disease is an inflammatory disorder affecting the supporting teeth structures, including gingiva, periodontal ligament and alveolar bone, causing loss of connective tissue, reabsorption of alveolar bone and formation of periodontal pockets. The aim of this study is to find a correlation between bacterial growth and periodontal disease. Fifty-seven patients aged between 21 and 65 years, median age 46 years, were enrolled. According to gingival pocket depth, ranging from 3 to 7 mm, patients were divided into two groups: the first (30 patients, 53%) with deep pockets ³ 5 mm and the second (27 patients, 47%) less than 5 mm. The samples taken were processed for microbiological analysis by absolute quantitative real-time Taq-Man technique. Patients affected by periodontal disease were 32 (56%) and patients with gingival bleeding were 35 (61%). This data showed that the presence, the type and the bacterial load in gingival pockets were strongly correlated with gingival depth, periodontal disease and gingival bleeding. Quantitative microbiological analysis is a key point to improve patient compliance, allowing to choose the specific antibiotic treatment. avoiding antibiotic resistance and ensuring the successful outcome of therapy for periodontal disease.

  9. Genetic and molecular analysis of wild-derived arrhythmic mice.

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Watanabe

    Full Text Available A new circadian variant was isolated by screening the intercross offspring of wild-caught mice (Mus musculus castaneus. This variant was characterized by an initial maintenance of damped oscillations and subsequent loss of rhythmicity after being transferred from light-dark (LD cycles to constant darkness (DD. To map the genes responsible for the persistence of rhythmicity (circadian ratio and the length of free-running period (tau, quantitative trait locus (QTL analysis was performed using F(2 mice obtained from an F(1 cross between the circadian variant and C57BL/6J mice. As a result, a significant QTL with a main effect for circadian ratio (Arrhythmicity; Arrh-1 was mapped on Chromosome (Chr 8. For tau, four significant QTLs, Short free-running period (Sfp-1 (Chr 1, Sfp-2 (Chr 6, Sfp-3 (Chr 8, Sfp-4 (Chr 11 were determined. An epistatic interaction was detected between Chr 3 (Arrh-2 and Chr 5 (Arrh-3. An in situ hybridization study of clock genes and mouse Period1::luciferase (mPer1::luc real-time monitoring analysis in the suprachiasmatic nucleus (SCN suggested that arrhythmicity in this variant might not be attributed to core circadian mechanisms in the SCN neurons. Our strategy using wild-derived variant mice may provide a novel opportunity to evaluate circadian and its related disorders in human that arise from the interaction between multiple variant genes.

  10. Investigating the benefits of transactional analysis in conflict management


    Donoghue, Amy


    This dissertation looks into the current literature on behaviour management in England’s secondary schools, from media coverage to policy to psychology. A focus on therapeutic education and Transactional Analysis then allows for small scale research with a year eight form group to find out if learning about and applying Transactional Analysis has any benefits or potential benefits for conflict management. The results show a small number of benefits, and few disadvantages, but gained a positiv...

  11. Molecular analysis of HBV genotypes and subgenotypes in the Central-East region of Tunisia

    Directory of Open Access Journals (Sweden)

    Gharbi Jawhar


    Full Text Available Abstract Background In Tunisia, country of intermediate endemicity for Hepatitis B virus (HBV infection, most molecular studies on the virus have been carried out in the North of the country and little is known about other regions. The aim of this study was to determine HBV genotype and subgenotypes in Central-East Tunisia. A total of 217 HBs antigen positive patients were enrolled and determination of genotype was investigated in 130 patients with detectable HBV DNA. HBV genotyping methods were: PCR-RFLP on the pre-S region, a PCR using type-specific primers in the S region (TSP-PCR and partial sequencing in the pre-S region. Results Three genotypes (D, B and A were detected by the PCR-RFLP method and two (D and A with the TSP-PCR method, the concordance between the two methods was 93%. Sequencing and phylogenetic analysis of 32 strains, retrieved the same genotype (D and A for samples with concordant results and genotype D for samples with discordant results. The sequences of discordant genotypes had a restriction site in the pre-S gene which led to erroneous result by the PCR-RFLP method. Thus, prevalence of genotype D and A was 96% and 4%, respectively. Phylogenetic analysis showed the predominance of two subgenotypes D1 (55% and D7 (41%. Only one strain clustered with D3 subgenotype (3%. Conclusions Predominance of subgenotype D7 appears to occur in northern regions of Africa with transition to subgenotype D1 in the East of the continent. HBV genetic variabi