Broad spectrum antibiotic compounds and use thereof

DOEpatents

Koglin, Alexander; Strieker, Matthias

2016-07-05

The discovery of a non-ribosomal peptide synthetase (NRPS) gene cluster in the genome of Clostridium thermocellum that produces a secondary metabolite that is assembled outside of the host membrane is described. Also described is the identification of homologous NRPS gene clusters from several additional microorganisms. The secondary metabolites produced by the NRPS gene clusters exhibit broad spectrum antibiotic activity. Thus, antibiotic compounds produced by the NRPS gene clusters, and analogs thereof, their use for inhibiting bacterial growth, and methods of making the antibiotic compounds are described.

antiSMASH 3.0—a comprehensive resource for the genome mining of biosynthetic gene clusters

PubMed Central

Blin, Kai; Duddela, Srikanth; Krug, Daniel; Kim, Hyun Uk; Bruccoleri, Robert; Lee, Sang Yup; Fischbach, Michael A; Müller, Rolf; Wohlleben, Wolfgang; Breitling, Rainer; Takano, Eriko

2015-01-01

Abstract Microbial secondary metabolism constitutes a rich source of antibiotics, chemotherapeutics, insecticides and other high-value chemicals. Genome mining of gene clusters that encode the biosynthetic pathways for these metabolites has become a key methodology for novel compound discovery. In 2011, we introduced antiSMASH, a web server and stand-alone tool for the automatic genomic identification and analysis of biosynthetic gene clusters, available at http://antismash.secondarymetabolites.org. Here, we present version 3.0 of antiSMASH, which has undergone major improvements. A full integration of the recently published ClusterFinder algorithm now allows using this probabilistic algorithm to detect putative gene clusters of unknown types. Also, a new dereplication variant of the ClusterBlast module now identifies similarities of identified clusters to any of 1172 clusters with known end products. At the enzyme level, active sites of key biosynthetic enzymes are now pinpointed through a curated pattern-matching procedure and Enzyme Commission numbers are assigned to functionally classify all enzyme-coding genes. Additionally, chemical structure prediction has been improved by incorporating polyketide reduction states. Finally, in order for users to be able to organize and analyze multiple antiSMASH outputs in a private setting, a new XML output module allows offline editing of antiSMASH annotations within the Geneious software. PMID:25948579

Elimination-Fusion Self-Assembly of a Nanometer-Scale 72-Nucleus Silver Cluster Caging a Pair of [EuW10 O36 ]9- Polyoxometalates.

PubMed

Zhang, Shan-Shan; Su, Hai-Feng; Wang, Zhi; Wang, Xing-Po; Chen, Wen-Xian; Zhao, Quan-Qin; Tung, Chen-Ho; Sun, Di; Zheng, Lan-Sun

2018-02-06

The largest known polyoxometalate (POM)-templated silver-alkynyl cluster, [(EuW 10 O 36 ) 2 @Ag 72 (tBuC≡C) 48 Cl 2 ⋅4 BF 4 ] (SD/Ag20), was isolated under solvothermal conditions and structurally characterized. It was confirmed by single-crystal X-ray diffraction (SCXRD) as a {EuW 10 } 2 -in-{Ag 72 } clusters-in-cluster rod-like compound. The high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) shows that such a double anion-templated cluster is assembled from a crucial single anion-templated Ag 42 intermediate in the solution. The crystallization of Ag 42 species (SD/Ag21), followed by SCXRD, gave an important clue about the assembly route of SD/Ag20 in solution: the Ag 42 cluster eliminates six silver atoms laterally, then fuses together at the vacant face to form the final Ag 72 cluster (elimination-fusion mechanism). The characteristic emission of [EuW 10 O 36 ] 9- is well maintained in SD/Ag20. This work not only provides a new method for the synthesis of larger silver clusters as well as the functional integration of the silver cluster and POMs, but also gives deep insights about the high-nuclear silver cluster assembly mechanism. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A detailed comparison of analysis processes for MCC-IMS data in disease classification—Automated methods can replace manual peak annotations

PubMed Central

Horsch, Salome; Kopczynski, Dominik; Kuthe, Elias; Baumbach, Jörg Ingo; Rahmann, Sven

2017-01-01

Motivation Disease classification from molecular measurements typically requires an analysis pipeline from raw noisy measurements to final classification results. Multi capillary column—ion mobility spectrometry (MCC-IMS) is a promising technology for the detection of volatile organic compounds in the air of exhaled breath. From raw measurements, the peak regions representing the compounds have to be identified, quantified, and clustered across different experiments. Currently, several steps of this analysis process require manual intervention of human experts. Our goal is to identify a fully automatic pipeline that yields competitive disease classification results compared to an established but subjective and tedious semi-manual process. Method We combine a large number of modern methods for peak detection, peak clustering, and multivariate classification into analysis pipelines for raw MCC-IMS data. We evaluate all combinations on three different real datasets in an unbiased cross-validation setting. We determine which specific algorithmic combinations lead to high AUC values in disease classifications across the different medical application scenarios. Results The best fully automated analysis process achieves even better classification results than the established manual process. The best algorithms for the three analysis steps are (i) SGLTR (Savitzky-Golay Laplace-operator filter thresholding regions) and LM (Local Maxima) for automated peak identification, (ii) EM clustering (Expectation Maximization) and DBSCAN (Density-Based Spatial Clustering of Applications with Noise) for the clustering step and (iii) RF (Random Forest) for multivariate classification. Thus, automated methods can replace the manual steps in the analysis process to enable an unbiased high throughput use of the technology. PMID:28910313

PRN 88-2: Clustering of Quaternary Ammonium Compounds

EPA Pesticide Factsheets

This Notice announces that EPA has clustered the Quaternary Ammonium Compounds into four groups for the purpose of testing chemicals to build a database that will support continued registration of the entire family of quaternary ammonium compounds

Endohedral gallide cluster superconductors and superconductivity in ReGa5.

PubMed

Xie, Weiwei; Luo, Huixia; Phelan, Brendan F; Klimczuk, Tomasz; Cevallos, Francois Alexandre; Cava, Robert Joseph

2015-12-22

We present transition metal-embedded (T@Gan) endohedral Ga-clusters as a favorable structural motif for superconductivity and develop empirical, molecule-based, electron counting rules that govern the hierarchical architectures that the clusters assume in binary phases. Among the binary T@Gan endohedral cluster systems, Mo8Ga41, Mo6Ga31, Rh2Ga9, and Ir2Ga9 are all previously known superconductors. The well-known exotic superconductor PuCoGa5 and related phases are also members of this endohedral gallide cluster family. We show that electron-deficient compounds like Mo8Ga41 prefer architectures with vertex-sharing gallium clusters, whereas electron-rich compounds, like PdGa5, prefer edge-sharing cluster architectures. The superconducting transition temperatures are highest for the electron-poor, corner-sharing architectures. Based on this analysis, the previously unknown endohedral cluster compound ReGa5 is postulated to exist at an intermediate electron count and a mix of corner sharing and edge sharing cluster architectures. The empirical prediction is shown to be correct and leads to the discovery of superconductivity in ReGa5. The Fermi levels for endohedral gallide cluster compounds are located in deep pseudogaps in the electronic densities of states, an important factor in determining their chemical stability, while at the same time limiting their superconducting transition temperatures.

Ge(14)[Ge(SiMe(3))(3)](5)Li(3)(THF)(6): the largest metalloid cluster compound of germanium: on the way to fullerene-like compounds?

PubMed

Schenk, Christian; Schnepf, Andreas

2008-10-14

The reaction of GeBr with LiGe(SiMe(3))(3) yields the largest metalloid cluster compound of germanium Ge(14)[Ge(SiMe(3))(3)](5)Li(3)(THF)(6), in which 14 germanium atoms are arranged as a hollow sphere in the cluster core, showing that in the case of germanium also fullerene-like compounds might be present in the borderland between the molecular and solid states.

Fusion of Potentiometric & Voltammetric Electronic Tongue for Classification of Black Tea Taste based on Theaflavins (TF) Content

NASA Astrophysics Data System (ADS)

Bhattacharyya, Nabarun; Legin, Andrey; Papieva, Irina; Sarkar, Subrata; Kirsanov, Dmitry; Kartsova, Anna; Ghosh, Arunangshu; Bandyopadhyay, Rajib

2011-09-01

Black tea is an extensively consumed beverage worldwide with an expanding market. The final quality of black tea depends upon number of chemical compounds present in the tea. Out of these compounds, theaflavins (TF), which is responsible for astringency in black tea, plays an important role in determining the final taste of the finished black tea. The present paper reports our effort to correlate the theaflavins contents with the voltammetric and potentiometric electronic tongue (e-tongue) data. Noble metal-based electrode array has been used for collecting data though voltammetric electronic tongue where as liquid filled membrane based electrodes have been used for potentiometric electronic tongue. Black tea samples with tea taster score and biochemical results have been collected from Tea Research Association, Tocklai, India for the analysis purpose. In this paper, voltammetric and potentiometric e-tongue responses are combined to demonstrate improvement of cluster formation among tea samples with different ranges of TF values.

Endohedral gallide cluster superconductors and superconductivity in ReGa5

PubMed Central

Xie, Weiwei; Luo, Huixia; Phelan, Brendan F.; Klimczuk, Tomasz; Cevallos, Francois Alexandre; Cava, Robert Joseph

2015-01-01

We present transition metal-embedded (T@Gan) endohedral Ga-clusters as a favorable structural motif for superconductivity and develop empirical, molecule-based, electron counting rules that govern the hierarchical architectures that the clusters assume in binary phases. Among the binary T@Gan endohedral cluster systems, Mo8Ga41, Mo6Ga31, Rh2Ga9, and Ir2Ga9 are all previously known superconductors. The well-known exotic superconductor PuCoGa5 and related phases are also members of this endohedral gallide cluster family. We show that electron-deficient compounds like Mo8Ga41 prefer architectures with vertex-sharing gallium clusters, whereas electron-rich compounds, like PdGa5, prefer edge-sharing cluster architectures. The superconducting transition temperatures are highest for the electron-poor, corner-sharing architectures. Based on this analysis, the previously unknown endohedral cluster compound ReGa5 is postulated to exist at an intermediate electron count and a mix of corner sharing and edge sharing cluster architectures. The empirical prediction is shown to be correct and leads to the discovery of superconductivity in ReGa5. The Fermi levels for endohedral gallide cluster compounds are located in deep pseudogaps in the electronic densities of states, an important factor in determining their chemical stability, while at the same time limiting their superconducting transition temperatures. PMID:26644566

antiSMASH 3.0-a comprehensive resource for the genome mining of biosynthetic gene clusters.

PubMed

Weber, Tilmann; Blin, Kai; Duddela, Srikanth; Krug, Daniel; Kim, Hyun Uk; Bruccoleri, Robert; Lee, Sang Yup; Fischbach, Michael A; Müller, Rolf; Wohlleben, Wolfgang; Breitling, Rainer; Takano, Eriko; Medema, Marnix H

2015-07-01

Microbial secondary metabolism constitutes a rich source of antibiotics, chemotherapeutics, insecticides and other high-value chemicals. Genome mining of gene clusters that encode the biosynthetic pathways for these metabolites has become a key methodology for novel compound discovery. In 2011, we introduced antiSMASH, a web server and stand-alone tool for the automatic genomic identification and analysis of biosynthetic gene clusters, available at http://antismash.secondarymetabolites.org. Here, we present version 3.0 of antiSMASH, which has undergone major improvements. A full integration of the recently published ClusterFinder algorithm now allows using this probabilistic algorithm to detect putative gene clusters of unknown types. Also, a new dereplication variant of the ClusterBlast module now identifies similarities of identified clusters to any of 1172 clusters with known end products. At the enzyme level, active sites of key biosynthetic enzymes are now pinpointed through a curated pattern-matching procedure and Enzyme Commission numbers are assigned to functionally classify all enzyme-coding genes. Additionally, chemical structure prediction has been improved by incorporating polyketide reduction states. Finally, in order for users to be able to organize and analyze multiple antiSMASH outputs in a private setting, a new XML output module allows offline editing of antiSMASH annotations within the Geneious software. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Sulfur in Cometary Dust

NASA Technical Reports Server (NTRS)

Fomenkova, M. N.

1997-01-01

The computer-intensive project consisted of the analysis and synthesis of existing data on composition of comet Halley dust particles. The main objective was to obtain a complete inventory of sulfur containing compounds in the comet Halley dust by building upon the existing classification of organic and inorganic compounds and applying a variety of statistical techniques for cluster and cross-correlational analyses. A student hired for this project wrote and tested the software to perform cluster analysis. The following tasks were carried out: (1) selecting the data from existing database for the proposed project; (2) finding access to a standard library of statistical routines for cluster analysis; (3) reformatting the data as necessary for input into the library routines; (4) performing cluster analysis and constructing hierarchical cluster trees using three methods to define the proximity of clusters; (5) presenting the output results in different formats to facilitate the interpretation of the obtained cluster trees; (6) selecting groups of data points common for all three trees as stable clusters. We have also considered the chemistry of sulfur in inorganic compounds.

Blocked inverted indices for exact clustering of large chemical spaces.

PubMed

Thiel, Philipp; Sach-Peltason, Lisa; Ottmann, Christian; Kohlbacher, Oliver

2014-09-22

The calculation of pairwise compound similarities based on fingerprints is one of the fundamental tasks in chemoinformatics. Methods for efficient calculation of compound similarities are of the utmost importance for various applications like similarity searching or library clustering. With the increasing size of public compound databases, exact clustering of these databases is desirable, but often computationally prohibitively expensive. We present an optimized inverted index algorithm for the calculation of all pairwise similarities on 2D fingerprints of a given data set. In contrast to other algorithms, it neither requires GPU computing nor yields a stochastic approximation of the clustering. The algorithm has been designed to work well with multicore architectures and shows excellent parallel speedup. As an application example of this algorithm, we implemented a deterministic clustering application, which has been designed to decompose virtual libraries comprising tens of millions of compounds in a short time on current hardware. Our results show that our implementation achieves more than 400 million Tanimoto similarity calculations per second on a common desktop CPU. Deterministic clustering of the available chemical space thus can be done on modern multicore machines within a few days.

Manganese-Chromium-Cyanide Clusters: Molecular MnCr 6(CN) 18 and Mn 3Cr 6(CN) 18 Species and a Related MnCr 3(CN) 9 Chain Compound

NASA Astrophysics Data System (ADS)

Heinrich, Julie L.; Sokol, Jennifer J.; Hee, Allan G.; Long, Jeffrey R.

2001-07-01

As part of an ongoing effort to design new single-molecule magnets, we are exploring synthetic routes to high-nuclearity metal-cyanide clusters. Here, we report the results of solution assembly reactions between [(Me3tacn)Cr(CN)3] (Me3tacn= N,N‧,N″-trimethyl-1,4,7-triazacyclononane) and selected manganese(II) salts. Reaction with the perchlorate salt in the presence of AClO4 (A=Na, K) gives A[(Me3tacn)6MnCr6(CN)18] (ClO4)3, featuring a heptanuclear cluster in which six [(Me3tacn)Cr(CN)3] units surround a central MnII ion. The Mn coordination geometry closely approaches a trigonal prism, with triangular faces twisted away from a fully eclipsed position by an angle of 12.8° and 11.3° for A=Na and K, respectively. The magnetic behavior of both compounds indicates weak antiferromagnetic coupling between neighboring MnII and CrIII centers (J=-3.0 and -3.1 cm-1, respectively) to give an S={13}/{2}; ground state. Alternatively, addition of sodium tetraphenylborate to the reaction solution yields [(Me3tacn)6(H2O)6Mn3Cr6(CN)18] (BPh4)6·12H2O, in which attachment of two MnII ions to the preceding cluster generates a new species with two trigonal bipyramids sharing a common vertex. This compound displays magnetic behavior consistent with weak antiferromagnetic coupling and an S={3}/{2} ground state. Finally, a reaction employing manganese(II) triflate is found to produce the one-dimensional solid [(Me3tacn)3MnCr3(CN)9](CF3SO3)2, exhibiting a closely related chain structure, and, again, weak antiferromagnetic coupling.

Predicting the points of interaction of small molecules in the NF-κB pathway

PubMed Central

2011-01-01

Background The similarity property principle has been used extensively in drug discovery to identify small compounds that interact with specific drug targets. Here we show it can be applied to identify the interactions of small molecules within the NF-κB signalling pathway. Results Clusters that contain compounds with a predominant interaction within the pathway were created, which were then used to predict the interaction of compounds not included in the clustering analysis. Conclusions The technique successfully predicted the points of interactions of compounds that are known to interact with the NF-κB pathway. The method was also shown to be successful when compounds for which the interaction points were unknown were included in the clustering analysis. PMID:21342508

Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis

PubMed Central

Wan, Minghui; Liao, Dongjiang; Peng, Guilin; Xu, Xin; Yin, Weiqiang; Guo, Guixin; Jiang, Funeng; Zhong, Weide

2017-01-01

Chloride intracellular channel 1 (CLIC1) is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM) database using structure-based virtual screening and molecular dynamics (MD) simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for CLIC1 inhibition. PMID:29147652

Insight into the time-resolved extraction of aroma compounds during espresso coffee preparation: online monitoring by PTR-ToF-MS.

PubMed

Sánchez-López, José A; Zimmermann, Ralf; Yeretzian, Chahan

2014-12-02

Using proton-transfer-reaction time-of-flight mass-spectrometry (PTR-ToF-MS), we investigated the extraction dynamic of 95 ion traces in real time (time resolution = 1 s) during espresso coffee preparation. Fifty-two of these ions were tentatively identified. This was achieved by online sampling of the volatile organic compounds (VOCs) in close vicinity to the coffee flow, at the exit of the extraction hose of the espresso machine (single serve capsules). Ten replicates of six different single serve coffee types were extracted to a final weight between 20-120 g, according to the recommended cup size of the respective coffee capsule (Ristretto, Espresso, and Lungo), and analyzed. The results revealed considerable differences in the extraction kinetics between compounds, which led to a fast evolution of the volatile profiles in the extract flow and consequently to an evolution of the final aroma balance in the cup. Besides exploring the time-resolved extraction dynamics of VOCs, the dynamic data also allowed the coffees types (capsules) to be distinguished from one another. Both hierarchical cluster analysis (HCA) and principal component analysis (PCA) showed full separation between the coffees types. The methodology developed provides a fast and simple means of studying the extraction dynamics of VOCs and differentiating between different coffee types.

Exploring the effect of oxygen-containing functional groups on the water-holding capacity of lignite.

PubMed

Liu, Jie; Jiang, Xiangang; Cao, Yu; Zhang, Chen; Zhao, Guangyao; Zhao, Maoshuang; Feng, Li

2018-05-07

Graphene oxide with different degrees of oxidation was prepared and selected as a model compound of lignite to study quantitatively, using both experiment and theoretical calculation methods, the effect on water-holding capacity of oxygen-containing functional groups. The experimental results showed that graphite can be oxidized, and forms epoxy groups most easily, followed by hydroxyl and carboxyl groups. The prepared graphene oxide forms a membrane-state as a single layer structure, with an irregular surface. The water-holding capacity of lignite increased with the content of oxygen-containing functional groups. The influence on the configuration of water molecule clusters and binding energy of water molecules of different oxygen-containing functional groups was calculated by density functional theory. The calculation results indicated that the configuration of water molecule clusters was totally changed by oxygen-containing functional groups. The order of binding energy produced by oxygen-containing functional groups and water molecules was as follows: carboxyl > edge phenol hydroxyl >epoxy group. Finally, it can be concluded that the potential to form more hydrogen bonds is the key factor influencing the interaction energy between model compounds and water molecules.

Composition Formulas of Inorganic Compounds in Terms of Cluster Plus Glue Atom Model.

PubMed

Ma, Yanping; Dong, Dandan; Wu, Aimin; Dong, Chuang

2018-01-16

The present paper attempts to identify the molecule-like structural units in inorganic compounds, by applying the so-called "cluster plus glue atom model". This model, originating from metallic glasses and quasi-crystals, describes any structure in terms of a nearest-neighbor cluster and a few outer-shell glue atoms, expressed in the cluster formula [cluster](glue atoms). Similar to the case for normal molecules where the charge transfer occurs within the molecule to meet the commonly known octet electron rule, the octet state is reached after matching the nearest-neighbor cluster with certain outer-shell glue atoms. These kinds of structural units contain information on local atomic configuration, chemical composition, and electron numbers, just as for normal molecules. It is shown that the formulas of typical inorganic compounds, such as fluorides, oxides, and nitrides, satisfy a similar octet electron rule, with the total number of valence electrons per unit formula being multiples of eight.

Genomic insights into the evolution of hybrid isoprenoid biosynthetic gene clusters in the MAR4 marine streptomycete clade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gallagher, Kelley A.; Jensen, Paul R.

Background: Considerable advances have been made in our understanding of the molecular genetics of secondary metabolite biosynthesis. Coupled with increased access to genome sequence data, new insight can be gained into the diversity and distributions of secondary metabolite biosynthetic gene clusters and the evolutionary processes that generate them. Here we examine the distribution of gene clusters predicted to encode the biosynthesis of a structurally diverse class of molecules called hybrid isoprenoids (HIs) in the genus Streptomyces. These compounds are derived from a mixed biosynthetic origin that is characterized by the incorporation of a terpene moiety onto a variety of chemicalmore » scaffolds and include many potent antibiotic and cytotoxic agents. Results: One hundred and twenty Streptomyces genomes were searched for HI biosynthetic gene clusters using ABBA prenyltransferases (PTases) as queries. These enzymes are responsible for a key step in HI biosynthesis. The strains included 12 that belong to the ‘MAR4’ clade, a largely marine-derived lineage linked to the production of diverse HI secondary metabolites. We found ABBA PTase homologs in all of the MAR4 genomes, which averaged five copies per strain, compared with 21 % of the non-MAR4 genomes, which averaged one copy per strain. Phylogenetic analyses suggest that MAR4 PTase diversity has arisen by a combination of horizontal gene transfer and gene duplication. Furthermore, there is evidence that HI gene cluster diversity is generated by the horizontal exchange of orthologous PTases among clusters. Many putative HI gene clusters have not been linked to their secondary metabolic products, suggesting that MAR4 strains will yield additional new compounds in this structure class. Finally, we confirm that the mevalonate pathway is not always present in genomes that contain HI gene clusters and thus is not a reliable query for identifying strains with the potential to produce HI secondary metabolites. In conclusion: We found that marine-derived MAR4 streptomycetes possess a relatively high genetic potential for HI biosynthesis. The combination of horizontal gene transfer, duplication, and rearrangement indicate that complex evolutionary processes account for the high level of HI gene cluster diversity in these bacteria, the products of which may provide a yet to be defined adaptation to the marine environment.« less

Genomic insights into the evolution of hybrid isoprenoid biosynthetic gene clusters in the MAR4 marine streptomycete clade

DOE PAGES

Gallagher, Kelley A.; Jensen, Paul R.

2015-11-17

Background: Considerable advances have been made in our understanding of the molecular genetics of secondary metabolite biosynthesis. Coupled with increased access to genome sequence data, new insight can be gained into the diversity and distributions of secondary metabolite biosynthetic gene clusters and the evolutionary processes that generate them. Here we examine the distribution of gene clusters predicted to encode the biosynthesis of a structurally diverse class of molecules called hybrid isoprenoids (HIs) in the genus Streptomyces. These compounds are derived from a mixed biosynthetic origin that is characterized by the incorporation of a terpene moiety onto a variety of chemicalmore » scaffolds and include many potent antibiotic and cytotoxic agents. Results: One hundred and twenty Streptomyces genomes were searched for HI biosynthetic gene clusters using ABBA prenyltransferases (PTases) as queries. These enzymes are responsible for a key step in HI biosynthesis. The strains included 12 that belong to the ‘MAR4’ clade, a largely marine-derived lineage linked to the production of diverse HI secondary metabolites. We found ABBA PTase homologs in all of the MAR4 genomes, which averaged five copies per strain, compared with 21 % of the non-MAR4 genomes, which averaged one copy per strain. Phylogenetic analyses suggest that MAR4 PTase diversity has arisen by a combination of horizontal gene transfer and gene duplication. Furthermore, there is evidence that HI gene cluster diversity is generated by the horizontal exchange of orthologous PTases among clusters. Many putative HI gene clusters have not been linked to their secondary metabolic products, suggesting that MAR4 strains will yield additional new compounds in this structure class. Finally, we confirm that the mevalonate pathway is not always present in genomes that contain HI gene clusters and thus is not a reliable query for identifying strains with the potential to produce HI secondary metabolites. In conclusion: We found that marine-derived MAR4 streptomycetes possess a relatively high genetic potential for HI biosynthesis. The combination of horizontal gene transfer, duplication, and rearrangement indicate that complex evolutionary processes account for the high level of HI gene cluster diversity in these bacteria, the products of which may provide a yet to be defined adaptation to the marine environment.« less

Matching between the light spots and lenslets of an artificial compound eye system

NASA Astrophysics Data System (ADS)

He, Jianzheng; Jian, Huijie; Zhu, Qitao; Ma, Mengchao; Wang, Keyi

2017-10-01

As the visual organ of many arthropods, the compound eye has attracted a lot of attention with the advantage of wide field-of-view, multi-channel imaging ability and high agility. Extended from this concept, a new kind of artificial compound eye device is developed. There are 141 lenslets which share one image sensor distributed evenly on a curved surface, thus it is difficult to distinguish the lenslets which the light spot belongs to during calibration and positioning process. Therefore, the matching algorithm is proposed based on the device structure and the principle of calibration and positioning. Region partition of lenslet array is performed at first. Each lenslet and its adjacent lenslets are defined as cluster eyes and constructed into an index table. In the calibration process, a polar coordinate system is established, and the matching can be accomplished by comparing the rotary table position in the polar coordinate system and the central light spot angle in the image. In the positioning process, the spot is paired to the correct region according to the spots distribution firstly, and the final results is determined by the dispersion of the distance from the target point to the incident ray in the region traversal matching. Finally, the experiment results show that the presented algorithms provide a feasible and efficient way to match the spot to the lenslet, and perfectly meet the needs in the practical application of the compound eye system.

Localization and orientation of heavy-atom cluster compounds in protein crystals using molecular replacement

PubMed Central

Dahms, Sven O.; Kuester, Miriam; Streb, Carsten; Roth, Christian; Sträter, Norbert; Than, Manuel E.

2013-01-01

Heavy-atom clusters (HA clusters) containing a large number of specifically arranged electron-dense scatterers are especially useful for experimental phase determination of large complex structures, weakly diffracting crystals or structures with large unit cells. Often, the determination of the exact orientation of the HA cluster and hence of the individual heavy-atom positions proves to be the critical step in successful phasing and subsequent structure solution. Here, it is demonstrated that molecular replacement (MR) with either anomalous or isomorphous differences is a useful strategy for the correct placement of HA cluster compounds. The polyoxometallate cluster hexasodium α-metatungstate (HMT) was applied in phasing the structure of death receptor 6. Even though the HA cluster is bound in alternate partially occupied orientations and is located at a special position, its correct localization and orientation could be determined at resolutions as low as 4.9 Å. The broad applicability of this approach was demonstrated for five different derivative crystals that included the compounds tantalum tetradeca­bromide and trisodium phosphotungstate in addition to HMT. The correct placement of the HA cluster depends on the length of the intramolecular vectors chosen for MR, such that both a larger cluster size and the optimal choice of the wavelength used for anomalous data collection strongly affect the outcome. PMID:23385464

Two Zn coordination polymers with meso-helical chains based on mononuclear or dinuclear cluster units

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Ling, E-mail: qinling@hfut.edu.cn; Jiangsu Engineering Technology Research Center of Environmental Cleaning Materials; State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing National Laboratory of Microstructures, Nanjing University, Nanjing 210093

2016-07-15

Two zinc coordination polymers {[Zn_2(TPPBDA)(oba)_2]·DMF·1.5H_2O}{sub n} (1), {[Zn(TPPBDA)_1_/_2(tpdc)]·DMF}{sub n} (2) have been synthesized by zinc metal salt, nanosized tetradentate pyridine ligand with flexible or rigid V-shaped carboxylate co-ligands. These complexes were characterized by elemental analyses and X-ray single-crystal diffraction analyses. Compound 1 is a 2-fold interpenetrated 3D framework with [Zn{sub 2}(CO{sub 2}){sub 4}] clusters. Compound 2 can be defined as a five folded interpenetrating bbf topology with mononuclear Zn{sup 2+}. These mononuclear or dinuclear cluster units are linked by mix-ligands, resulting in various degrees of interpenetration. In addition, the photoluminescent properties for TPPBDA ligand under different state and coordination polymersmore » have been investigated in detail. - Graphical abstract: Two zinc coordination polymers have been synthesized by zinc metal salt, nanosized tetradentate pyridine ligand with flexible or rigid V-shaped carboxylate co-ligands. Compound 1 is a 2-fold interpenetrated 3D framework with [Zn{sub 2}(CO{sub 2}){sub 4}] clusters. Compound 2 can be defined as a five folded interpenetrating bbf topology with mononuclear Zn{sup 2+}. In addition, the photoluminescent properties for TPPBDA ligand under different status and coordination polymers have been investigated in detail. Display Omitted - Highlights: • Two Zn coordination polymers based on mononuclear or dinuclear cluster units have been synthesized. • Compound 1 is a 2-fold interpenetrated 3D framework with [Zn{sub 2}(CO{sub 2}){sub 4}] clusters. • Compound 2 is a five folded interpenetrating bbf topology with mononuclear Zn{sup 2+}. • The photoluminescent properties for TPPBDA with different state and two coordination polymers have been investigated.« less

The biosynthetic gene cluster for the cyanogenic glucoside dhurrin in Sorghum bicolor contains its co-expressed vacuolar MATE transporter

PubMed Central

Darbani, Behrooz; Motawia, Mohammed Saddik; Olsen, Carl Erik; Nour-Eldin, Hussam H.; Møller, Birger Lindberg; Rook, Fred

2016-01-01

Genomic gene clusters for the biosynthesis of chemical defence compounds are increasingly identified in plant genomes. We previously reported the independent evolution of biosynthetic gene clusters for cyanogenic glucoside biosynthesis in three plant lineages. Here we report that the gene cluster for the cyanogenic glucoside dhurrin in Sorghum bicolor additionally contains a gene, SbMATE2, encoding a transporter of the multidrug and toxic compound extrusion (MATE) family, which is co-expressed with the biosynthetic genes. The predicted localisation of SbMATE2 to the vacuolar membrane was demonstrated experimentally by transient expression of a SbMATE2-YFP fusion protein and confocal microscopy. Transport studies in Xenopus laevis oocytes demonstrate that SbMATE2 is able to transport dhurrin. In addition, SbMATE2 was able to transport non-endogenous cyanogenic glucosides, but not the anthocyanin cyanidin 3-O-glucoside or the glucosinolate indol-3-yl-methyl glucosinolate. The genomic co-localisation of a transporter gene with the biosynthetic genes producing the transported compound is discussed in relation to the role self-toxicity of chemical defence compounds may play in the formation of gene clusters. PMID:27841372

Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species.

PubMed

Adamek, Martina; Alanjary, Mohammad; Sales-Ortells, Helena; Goodfellow, Michael; Bull, Alan T; Winkler, Anika; Wibberg, Daniel; Kalinowski, Jörn; Ziemert, Nadine

2018-06-01

Genome mining tools have enabled us to predict biosynthetic gene clusters that might encode compounds with valuable functions for industrial and medical applications. With the continuously increasing number of genomes sequenced, we are confronted with an overwhelming number of predicted clusters. In order to guide the effective prioritization of biosynthetic gene clusters towards finding the most promising compounds, knowledge about diversity, phylogenetic relationships and distribution patterns of biosynthetic gene clusters is necessary. Here, we provide a comprehensive analysis of the model actinobacterial genus Amycolatopsis and its potential for the production of secondary metabolites. A phylogenetic characterization, together with a pan-genome analysis showed that within this highly diverse genus, four major lineages could be distinguished which differed in their potential to produce secondary metabolites. Furthermore, we were able to distinguish gene cluster families whose distribution correlated with phylogeny, indicating that vertical gene transfer plays a major role in the evolution of secondary metabolite gene clusters. Still, the vast majority of the diverse biosynthetic gene clusters were derived from clusters unique to the genus, and also unique in comparison to a database of known compounds. Our study on the locations of biosynthetic gene clusters in the genomes of Amycolatopsis' strains showed that clusters acquired by horizontal gene transfer tend to be incorporated into non-conserved regions of the genome thereby allowing us to distinguish core and hypervariable regions in Amycolatopsis genomes. Using a comparative genomics approach, it was possible to determine the potential of the genus Amycolatopsis to produce a huge diversity of secondary metabolites. Furthermore, the analysis demonstrates that horizontal and vertical gene transfer play an important role in the acquisition and maintenance of valuable secondary metabolites. Our results cast light on the interconnections between secondary metabolite gene clusters and provide a way to prioritize biosynthetic pathways in the search and discovery of novel compounds.

Grape cluster microclimate influences the aroma composition of Sauvignon blanc wine.

PubMed

Martin, Damian; Grose, Claire; Fedrizzi, Bruno; Stuart, Lily; Albright, Abby; McLachlan, Andrew

2016-11-01

New Zealand Sauvignon blanc (SB) wines are characterised by a distinctive combination of tropical-fruity and green-herbaceous aromatic compounds. The influence of sunlight exposure of grape clusters on juice and wine composition was investigated, with the aim of manipulating aromatic compounds in SB wine. In the absence of basal leaf removal SB clusters naturally exposed to sunlight were riper than shaded clusters, evidenced by higher total soluble solids (TSS) and proline, and lower malic acid, 3-isobutyl-2-methoxypyrazine (IBMP) and arginine. Volatile thiols in wines did not differ between shaded and exposed clusters. At equivalent TSS, cluster exposure had little or no effect on malic acid concentration. Conversely, wine from shaded clusters had almost double the IBMP concentration of wine from exposed clusters at equivalent TSS. The effects on SB juice and wine composition of natural variations in cluster microclimate are not comparable with the effects of cluster exposure created through leaf removal. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aromatic Borozene

PubMed Central

2009-01-01

Based on our comprehensive theoretical investigation and known experimental results for small boron clusters, we predict the existence of a novel aromatic inorganic molecule, B12H6. This molecule, which we refer to as borozene, has remarkably similar properties to the well-known benzene. Borozene is planar, possesses a large first excitation energy, D3hsymmetry, and more importantly is aromatic. Furthermore, the calculated anisotropy of the magnetic susceptibility of borozene is three times larger in absolute value than for benzene. Finally, we show that borozene molecules may be fused together to give larger aromatic compounds with even larger anisotropic susceptibilities. PMID:20596438

Spatial event cluster detection using an approximate normal distribution.

PubMed

Torabi, Mahmoud; Rosychuk, Rhonda J

2008-12-12

In geographic surveillance of disease, areas with large numbers of disease cases are to be identified so that investigations of the causes of high disease rates can be pursued. Areas with high rates are called disease clusters and statistical cluster detection tests are used to identify geographic areas with higher disease rates than expected by chance alone. Typically cluster detection tests are applied to incident or prevalent cases of disease, but surveillance of disease-related events, where an individual may have multiple events, may also be of interest. Previously, a compound Poisson approach that detects clusters of events by testing individual areas that may be combined with their neighbours has been proposed. However, the relevant probabilities from the compound Poisson distribution are obtained from a recursion relation that can be cumbersome if the number of events are large or analyses by strata are performed. We propose a simpler approach that uses an approximate normal distribution. This method is very easy to implement and is applicable to situations where the population sizes are large and the population distribution by important strata may differ by area. We demonstrate the approach on pediatric self-inflicted injury presentations to emergency departments and compare the results for probabilities based on the recursion and the normal approach. We also implement a Monte Carlo simulation to study the performance of the proposed approach. In a self-inflicted injury data example, the normal approach identifies twelve out of thirteen of the same clusters as the compound Poisson approach, noting that the compound Poisson method detects twelve significant clusters in total. Through simulation studies, the normal approach well approximates the compound Poisson approach for a variety of different population sizes and case and event thresholds. A drawback of the compound Poisson approach is that the relevant probabilities must be determined through a recursion relation and such calculations can be computationally intensive if the cluster size is relatively large or if analyses are conducted with strata variables. On the other hand, the normal approach is very flexible, easily implemented, and hence, more appealing for users. Moreover, the concepts may be more easily conveyed to non-statisticians interested in understanding the methodology associated with cluster detection test results.

Molecular Networking and Pattern-Based Genome Mining Improves discovery of biosynthetic gene clusters and their products from Salinispora species

PubMed Central

Duncan, Katherine R.; Crüsemann, Max; Lechner, Anna; Sarkar, Anindita; Li, Jie; Ziemert, Nadine; Wang, Mingxun; Bandeira, Nuno; Moore, Bradley S.; Dorrestein, Pieter C.; Jensen, Paul R.

2015-01-01

Summary Genome sequencing has revealed that bacteria contain many more biosynthetic gene clusters than predicted based on the number of secondary metabolites discovered to date. While this biosynthetic reservoir has fostered interest in new tools for natural product discovery, there remains a gap between gene cluster detection and compound discovery. Here we apply molecular networking and the new concept of pattern-based genome mining to 35 Salinispora strains including 30 for which draft genome sequences were either available or obtained for this study. The results provide a method to simultaneously compare large numbers of complex microbial extracts, which facilitated the identification of media components, known compounds and their derivatives, and new compounds that could be prioritized for structure elucidation. These efforts revealed considerable metabolite diversity and led to several molecular family-gene cluster pairings, of which the quinomycin-type depsipeptide retimycin A was characterized and linked to gene cluster NRPS40 using pattern-based bioinformatic approaches. PMID:25865308

A discrete Cu cluster and a 3D MnII-CuII framework based on assembly of Mn2Cu4 clusters: synthesis, structure and magnetic properties.

PubMed

Chakraborty, Anindita; Escuer, Albert; Ribas, Joan; Maji, Tapas Kumar

2016-10-04

The synthesis, single-crystal structure characterization and detailed magnetic study of a homometallic hexanuclear Cu II cluster [Cu 6 (μ 3 -OH) 2 (ppk) 6 (H 2 O) 2 (NO 3 ) 4 ] (1) and a three-dimensional (3D) compound [{MnCu 2 (dpkO 2 H) 2 (dpkO 2 )N 3 }·(NO 3 )·H 2 O] n (2) (ppk = phenyl-2-pyridyl ketoxime; dpk = di-2-pyridyl ketone) consisting of heterometallic Mn II -Cu II hexanuclear cores as secondary building units are reported in this paper. In compound 1, two symmetry-related Cu 3 triangles consisting of a hydroxido-bridged trinuclear unit, [Cu 3 (μ 3 -OH)(ppk) 3 (H 2 O)(NO 3 )] + , are assembled through nitrate bridging giving rise to the homometallic Cu 6 cluster. Compound 2 contains heterometallic {MnCu} cores, which are further connected to each other through an azido bridging ligand in all the crystallographic directions, resulting in a 3D metal-organic framework. Construction of such a heterometallic 3D framework from {MnCu} units is until now, unknown. Magnetic studies of both 1 and 2 were performed in detail and both compounds show dominant antiferromagnetic interaction in the respective clusters. Compound 1 reveals significant spin frustration and anti-symmetric exchange interaction in the trinuclear cores, with a significantly high value of J av (-655 cm -1 ). Furthermore, compound 2 exhibits a dominant antiferromagnetic interaction, which is also supported by an extensive magneto-structural correlation which considers the different magnetic pathways.

Uncovering production of specialized metabolites by Streptomyces argillaceus: Activation of cryptic biosynthesis gene clusters using nutritional and genetic approaches.

PubMed

Becerril, Adriana; Álvarez, Susana; Braña, Alfredo F; Rico, Sergio; Díaz, Margarita; Santamaría, Ramón I; Salas, José A; Méndez, Carmen

2018-01-01

Sequencing of Streptomyces genomes has revealed they harbor a high number of biosynthesis gene cluster (BGC), which uncovered their enormous potentiality to encode specialized metabolites. However, these metabolites are not usually produced under standard laboratory conditions. In this manuscript we report the activation of BGCs for antimycins, carotenoids, germicidins and desferrioxamine compounds in Streptomyces argillaceus, and the identification of the encoded compounds. This was achieved by following different strategies, including changing the growth conditions, heterologous expression of the cluster and inactivating the adpAa or overexpressing the abrC3 global regulatory genes. In addition, three new carotenoid compounds have been identified.

Semiconductor nanocrystals covalently bound to solid inorganic surfaces using self-assembled monolayers

DOEpatents

Alivisatos, A. Paul; Colvin, Vicki L.

1998-01-01

Methods are described for attaching semiconductor nanocrystals to solid inorganic surfaces, using self-assembled bifunctional organic monolayers as bridge compounds. Two different techniques are presented. One relies on the formation of self-assembled monolayers on these surfaces. When exposed to solutions of nanocrystals, these bridge compounds bind the crystals and anchor them to the surface. The second technique attaches nanocrystals already coated with bridge compounds to the surfaces. Analyses indicate the presence of quantum confined clusters on the surfaces at the nanolayer level. These materials allow electron spectroscopies to be completed on condensed phase clusters, and represent a first step towards synthesis of an organized assembly of clusters. These new products are also disclosed.

A hierarchical clustering methodology for the estimation of toxicity.

PubMed

Martin, Todd M; Harten, Paul; Venkatapathy, Raghuraman; Das, Shashikala; Young, Douglas M

2008-01-01

ABSTRACT A quantitative structure-activity relationship (QSAR) methodology based on hierarchical clustering was developed to predict toxicological endpoints. This methodology utilizes Ward's method to divide a training set into a series of structurally similar clusters. The structural similarity is defined in terms of 2-D physicochemical descriptors (such as connectivity and E-state indices). A genetic algorithm-based technique is used to generate statistically valid QSAR models for each cluster (using the pool of descriptors described above). The toxicity for a given query compound is estimated using the weighted average of the predictions from the closest cluster from each step in the hierarchical clustering assuming that the compound is within the domain of applicability of the cluster. The hierarchical clustering methodology was tested using a Tetrahymena pyriformis acute toxicity data set containing 644 chemicals in the training set and with two prediction sets containing 339 and 110 chemicals. The results from the hierarchical clustering methodology were compared to the results from several different QSAR methodologies.

Chassis optimization as a cornerstone for the application of synthetic biology based strategies in microbial secondary metabolism.

PubMed

Beites, Tiago; Mendes, Marta V

2015-01-01

The increased number of bacterial genome sequencing projects has generated over the last years a large reservoir of genomic information. In silico analysis of this genomic data has renewed the interest in bacterial bioprospecting for bioactive compounds by unveiling novel biosynthetic gene clusters of unknown or uncharacterized metabolites. However, only a small fraction of those metabolites is produced under laboratory-controlled conditions; the remaining clusters represent a pool of novel metabolites that are waiting to be "awaken". Activation of the biosynthetic gene clusters that present reduced or no expression (known as cryptic or silent clusters) by heterologous expression has emerged as a strategy for the identification and production of novel bioactive molecules. Synthetic biology, with engineering principles at its core, provides an excellent framework for the development of efficient heterologous systems for the expression of biosynthetic gene clusters. However, a common problem in its application is the host-interference problem, i.e., the unpredictable interactions between the device and the host that can hamper the desired output. Although an effort has been made to develop orthogonal devices, the most proficient way to overcome the host-interference problem is through genome simplification. In this review we present an overview on the strategies and tools used in the development of hosts/chassis for the heterologous expression of specialized metabolites biosynthetic gene clusters. Finally, we introduce the concept of specialized host as the next step of development of expression hosts.

Silencing of a second dimethylallyltryptophan synthase of Penicillium roqueforti reveals a novel clavine alkaloid gene cluster.

PubMed

Fernández-Bodega, Ángeles; Álvarez-Álvarez, Rubén; Liras, Paloma; Martín, Juan F

2017-08-01

Penicillium roqueforti produces several prenylated indole alkaloids, including roquefortine C and clavine alkaloids. The first step in the biosynthesis of roquefortine C is the prenylation of tryptophan-derived dipeptides by a dimethylallyltryptophan synthase, specific for roquefortine biosynthesis (roquefortine prenyltransferase). A second dimethylallyltryptophan synthase, DmaW2, different from the roquefortine prenyltransferase, has been studied in this article. Silencing the gene encoding this second dimethylallyltryptophan synthase, dmaW2, proved that inactivation of this gene does not prevent the production of roquefortine C, but suppresses the formation of other indole alkaloids. Mass spectrometry studies have identified these compounds as isofumigaclavine A, the pathway final product and prenylated intermediates. The silencing does not affect the production of mycophenolic acid and andrastin A. A bioinformatic study of the genome of P. roqueforti revealed that DmaW2 (renamed IfgA) is a prenyltransferase involved in isofumigaclavine A biosynthesis encoded by a gene located in a six genes cluster (cluster A). A second three genes cluster (cluster B) encodes the so-called yellow enzyme and enzymes for the late steps for the conversion of festuclavine to isofumigaclavine A. The yellow enzyme contains a tyrosine-181 at its active center, as occurs in Neosartorya fumigata, but in contrast to the Clavicipitaceae fungi. A complete isofumigaclavines A and B biosynthetic pathway is proposed based on the finding of these studies on the biosynthesis of clavine alkaloids.

Ionothermal synthesis of discrete supertetrahedral Tn (n = 4, 5) clusters with tunable components, band gaps, and fluorescence properties.

PubMed

Yang, Dan-Dan; Li, Wei; Xiong, Wei-Wei; Li, Jian-Rong; Huang, Xiao-Ying

2018-05-01

The preparation of crystalline molecularly supertetrahedral Tn clusters with variable sizes and components is of vital importance for the fundamental study of their physicochemical properties. However, setting up an efficient method to stabilize large discrete Tn clusters is a challenge due to their high negative charges and polymerization nature. In this work, we report on the ionothermal synthesis of three discrete T4 cluster compounds, namely [Bmmim]5[(CH3)2NH2]4[NH4][M4In16S31(SH)4]·6H2O (M = Mn (1), Zn (2), Cd (3), Bmmim = 1-buty-2,3-dimethyl-imidazolium), and four discrete T5 cluster compounds, namely [Bmmim]10[NH4]3[Cu5Ga30-xInxS52(SH)4] (x = 6.6 (5), 14.5 (6), 23.8 (7), and 30 (8)). The compound [Bmmim]10[NH4]3[Cu5Ga30S52(SH)4] (4) previously reported by us features a discrete T5 cluster. The steep UV-Vis absorption edges indicate band gaps of 2.20 eV for 1, 2.64 eV for 2, 2.69 eV for 3, 3.04 eV for 4, 2.65 eV for 5, 2.48 eV for 6, 2.32 eV for 7, and 2.30 eV for 8. The compositions of T5 clusters could be varied with the ratios of Ga : In in the starting reagents, providing an opportunity to systematically control the band gaps and fluorescence performances of T5 cluster-based compounds. This research might advance the understanding of the ionothermal preparation and functionality tuning of crystalline chalcogenides.

Metabolic Clustering Analysis as a Strategy for Compound Selection in the Drug Discovery Pipeline for Leishmaniasis.

PubMed

Armitage, Emily G; Godzien, Joanna; Peña, Imanol; López-Gonzálvez, Ángeles; Angulo, Santiago; Gradillas, Ana; Alonso-Herranz, Vanesa; Martín, Julio; Fiandor, Jose M; Barrett, Michael P; Gabarro, Raquel; Barbas, Coral

2018-05-18

A lack of viable hits, increasing resistance, and limited knowledge on mode of action is hindering drug discovery for many diseases. To optimize prioritization and accelerate the discovery process, a strategy to cluster compounds based on more than chemical structure is required. We show the power of metabolomics in comparing effects on metabolism of 28 different candidate treatments for Leishmaniasis (25 from the GSK Leishmania box, two analogues of Leishmania box series, and amphotericin B as a gold standard treatment), tested in the axenic amastigote form of Leishmania donovani. Capillary electrophoresis-mass spectrometry was applied to identify the metabolic profile of Leishmania donovani, and principal components analysis was used to cluster compounds on potential mode of action, offering a medium throughput screening approach in drug selection/prioritization. The comprehensive and sensitive nature of the data has also made detailed effects of each compound obtainable, providing a resource to assist in further mechanistic studies and prioritization of these compounds for the development of new antileishmanial drugs.

Aromaticity and Antiaromaticity in Zintl Clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Zhong -Ming; Liu, Chao; Popov, Ivan Aleksandrovich

Originally, the concepts of aromaticity and antiaromaticity were introduced to explain the stability and reactivity of unsaturated organic compounds. Since then, they have been extended to other species with delocalized electrons including various saturated systems, organometallic compounds, and even inorganic clusters and molecules. In this study, we focus on the most recent progress of using these concepts to guide experimental synthesis and rationalize geometrical and electronic structures of a particular family of polyanions composed of Group 14 and 15 elements, namely Zintl clusters.

Aromaticity and Antiaromaticity in Zintl Clusters

DOE PAGES

Sun, Zhong -Ming; Liu, Chao; Popov, Ivan Aleksandrovich; ...

2018-05-18

Originally, the concepts of aromaticity and antiaromaticity were introduced to explain the stability and reactivity of unsaturated organic compounds. Since then, they have been extended to other species with delocalized electrons including various saturated systems, organometallic compounds, and even inorganic clusters and molecules. In this study, we focus on the most recent progress of using these concepts to guide experimental synthesis and rationalize geometrical and electronic structures of a particular family of polyanions composed of Group 14 and 15 elements, namely Zintl clusters.

Rapid identification of herbal compounds derived metabolites using zebrafish larvae as the biotransformation system.

PubMed

Wang, Chen; Yin, Ying-Hao; Wei, Ying-Jie; Shi, Zi-Qi; Liu, Jian-Qun; Liu, Li-Fang; Xin, Gui-Zhong

2017-09-15

Metabolites derived from herbal compounds are becoming promising sources for discovering new drugs. However, the rapid identification of metabolites from biological matrixes is limited by massive endogenous interference and low abundance of metabolites. Thus, by using zebrafish larvae as the biotransformation system, we herein proposed and validated an integrated strategy for rapid identification of metabolites derived from herbal compounds. Two pivotal steps involved in this strategy are to differentiate metabolites from herbal compounds and match metabolites with their parent compounds. The differentiation step was achieved by cross orthogonal partial least-squares discriminant analysis. Automatic matching analysis was performed on R Project based on a self-developed program, of which the number of matched ionic clusters and its corresponding percentage between metabolite and parent compound were taken into account to assess their similarity. Using this strategy, 46 metabolites screened from incubation water samples of zebrafish treated with total Epimedium flavonoids (EFs) could be matched with their corresponding parent compounds, 37 of them were identified and validated by the known metabolic pathways and fragmentation patterns. Finally, 75% of the identified EFs metabolites were successfully detected in urine samples of rats treated with EFs. These experimental results indicate that the proposed strategy using zebrafish larvae as the biotransformation system will facilitate the rapid identification of metabolites derived from herbal compounds, which shows promising perspectives in providing additional resources for pharmaceutical developments from natural products. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of Compounds That Prolong Type I Interferon Signaling as Potential Vaccine Adjuvants.

PubMed

Shukla, Nikunj M; Arimoto, Kei-Ichiro; Yao, Shiyin; Fan, Jun-Bao; Zhang, Yue; Sato-Kaneko, Fumi; Lao, Fitzgerald S; Hosoya, Tadashi; Messer, Karen; Pu, Minya; Cottam, Howard B; Carson, Dennis A; Hayashi, Tomoko; Zhang, Dong-Er; Corr, Maripat

2018-05-01

Vaccines are reliant on adjuvants to enhance the immune stimulus, and type I interferons (IFNs) have been shown to be beneficial in augmenting this response. We were interested in identifying compounds that would sustain activation of an endogenous type I IFN response as a co-adjuvant. We began with generation of a human monocytic THP-1 cell line with an IFN-stimulated response element (ISRE)-β-lactamase reporter construct for high-throughput screening. Pilot studies were performed to optimize the parameters and conditions for this cell-based Förster resonance energy transfer (FRET) reporter assay for sustaining an IFN-α-induced ISRE activation signal. These conditions were confirmed in an initial pilot screen, followed by the main screen for evaluating prolongation of an IFN-α-induced ISRE activation signal at 16 h. Hit compounds were identified using a structure enrichment strategy based on chemoinformatic clustering and a naïve "Top X" approach. A select list of confirmed hits was then evaluated for toxicity and the ability to sustain IFN activity by gene and protein expression. Finally, for proof of concept, a panel of compounds was used to immunize mice as co-adjuvant with a model antigen and an IFN-inducing Toll-like receptor 4 agonist, lipopolysaccharide, as an adjuvant. Selected compounds significantly augmented antigen-specific immunoglobulin responses.

Solid-state NMR/NQR and first-principles study of two niobium halide cluster compounds.

PubMed

Perić, Berislav; Gautier, Régis; Pickard, Chris J; Bosiočić, Marko; Grbić, Mihael S; Požek, Miroslav

2014-01-01

Two hexanuclear niobium halide cluster compounds with a [Nb6X12](2+) (X=Cl, Br) diamagnetic cluster core, have been studied by a combination of experimental solid-state NMR/NQR techniques and PAW/GIPAW calculations. For niobium sites the NMR parameters were determined by using variable Bo field static broadband NMR measurements and additional NQR measurements. It was found that they possess large positive chemical shifts, contrary to majority of niobium compounds studied so far by solid-state NMR, but in accordance with chemical shifts of (95)Mo nuclei in structurally related compounds containing [Mo6Br8](4+) cluster cores. Experimentally determined δiso((93)Nb) values are in the range from 2,400 to 3,000 ppm. A detailed analysis of geometrical relations between computed electric field gradient (EFG) and chemical shift (CS) tensors with respect to structural features of cluster units was carried out. These tensors on niobium sites are almost axially symmetric with parallel orientation of the largest EFG and the smallest CS principal axes (Vzz and δ33) coinciding with the molecular four-fold axis of the [Nb6X12](2+) unit. Bridging halogen sites are characterized by large asymmetry of EFG and CS tensors, the largest EFG principal axis (Vzz) is perpendicular to the X-Nb bonds, while intermediate EFG principal axis (Vyy) and the largest CS principal axis (δ11) are oriented in the radial direction with respect to the center of the cluster unit. For more symmetrical bromide compound the PAW predictions for EFG parameters are in better correspondence with the NMR/NQR measurements than in the less symmetrical chlorine compound. Theoretically predicted NMR parameters of bridging halogen sites were checked by (79/81)Br NQR and (35)Cl solid-state NMR measurements. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of regulated deficit irrigation on quality parameters, carotenoids and phenolics of diverse tomato varieties (Solanum lycopersicum L.).

PubMed

Coyago-Cruz, Elena; Corell, Mireia; Stinco, Carla M; Hernanz, Dolores; Moriana, Alfonso; Meléndez-Martínez, Antonio J

2017-06-01

This study aims to evaluate the effects of regulated deficit irrigation (RDI) and of cluster position (CI: first and second cluster; CII: third and fourth cluster; CIII: fifth and sixth cluster) on fruit quality parameters, carotenoids and phenolics in tomatoes. Three common ('Tigerella', 'Palamós' and 'Byelsa') and two cherry varieties ('Lazarino' and 'Summerbrix') were studied. The results showed that the regulated deficit irrigation with reduction of 40 and 50% in the leaf water potential in common and cherry tomatoes did not affect greatly the organoleptic quality of common tomatoes and 'Summerbrix', while cherry varieties were significantly affected with the cluster position. In most case, significant changes in the levels of carotenoids were observed depending on the treatment and the cluster position in all varieties. Significant changes with the treatment and no change with the cluster position were observed in phenolic compounds. Thus, in general, increased total carotenoid levels and reduced the content of phenolic compounds were observed. Considering the significance of changes in the levels of these groups of compounds it was concluded that 'Lazarino' was more susceptible to water deficit, whereas 'Summerbrix' and 'Palamós' were more resistant. On the other hand, the organoleptic and functional quality changed with the variety. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phase stability and electronic structure of UMo2Al20: A first-principles study

NASA Astrophysics Data System (ADS)

Liu, Peng-Chuang; Xian, Ya-Jiang; Wang, Xin; Zhang, Yu-Ting; Zhang, Peng-Cheng

2017-09-01

In this paper, the phase stability of UMo2Al20 was explored using cluster formula in combination with first-principles calculations. Cluster formula analysis uncovered that the compound was composed of two principal clusters, i.e. [Mo-Al12] and [U-Al16]. The electronic interactions between U, Mo and Al atoms in this compound were discussed using elastic property, Bader charges and energy-resolved local bonding analysis, as well as the electronic interactions between Mo and Al atoms in [Mo-Al12] cluster and between U and Al atoms in [U-Al16] cluster. It revealed that UMo2Al20 satisfied the mechanical stability criterion for cubic system, and exhibited near ionic bonding character with weak bonding directionality. The calculations within both standard DFT and HSE frameworks demonstrated that U and Al atoms acted as an electron donor while Mo atoms acted as electron acceptor. The intrinsic stability of UMo2Al20 mainly stemmed from the bonding states of Mo-Al bonds and Al-Al bonds in [Mo-Al12] cluster. These calculations provide a further insight on the CeCr2Al20-type ternary compounds.

Wide Distribution of Foxicin Biosynthetic Gene Clusters in Streptomyces Strains – An Unusual Secondary Metabolite with Various Properties

PubMed Central

Greule, Anja; Marolt, Marija; Deubel, Denise; Peintner, Iris; Zhang, Songya; Jessen-Trefzer, Claudia; De Ford, Christian; Burschel, Sabrina; Li, Shu-Ming; Friedrich, Thorsten; Merfort, Irmgard; Lüdeke, Steffen; Bisel, Philippe; Müller, Michael; Paululat, Thomas; Bechthold, Andreas

2017-01-01

Streptomyces diastatochromogenes Tü6028 is known to produce the polyketide antibiotic polyketomycin. The deletion of the pokOIV oxygenase gene led to a non-polyketomycin-producing mutant. Instead, novel compounds were produced by the mutant, which have not been detected before in the wild type strain. Four different compounds were identified and named foxicins A–D. Foxicin A was isolated and its structure was elucidated as an unusual nitrogen-containing quinone derivative using various spectroscopic methods. Through genome mining, the foxicin biosynthetic gene cluster was identified in the draft genome sequence of S. diastatochromogenes. The cluster spans 57 kb and encodes three PKS type I modules, one NRPS module and 41 additional enzymes. A foxBII gene-inactivated mutant of S. diastatochromogenes Tü6028 ΔpokOIV is unable to produce foxicins. Homologous fox biosynthetic gene clusters were found in more than 20 additional Streptomyces strains, overall in about 2.6% of all sequenced Streptomyces genomes. However, the production of foxicin-like compounds in these strains has never been described indicating that the clusters are expressed at a very low level or are silent under fermentation conditions. Foxicin A acts as a siderophore through interacting with ferric ions. Furthermore, it is a weak inhibitor of the Escherichia coli aerobic respiratory chain and shows moderate antibiotic activity. The wide distribution of the cluster and the various properties of the compound indicate a major role of foxicins in Streptomyces strains. PMID:28270798

Ligand combination strategy for the preparation of novel low-dimensional and open-framework metal cluster materials

NASA Astrophysics Data System (ADS)

Anokhina, Ekaterina V.

Low-dimensional and open-framework materials containing transition metals have a wide range of applications in redox catalysis, solid-state batteries, and electronic and magnetic devices. This dissertation reports on research carried out with the goal to develop a strategy for the preparation of low-dimensional and open-framework materials using octahedral metal clusters as building blocks. Our approach takes its roots from crystal engineering principles where the desired framework topologies are achieved through building block design. The key idea of this work is to induce directional bonding preferences in the cluster units using a combination of ligands with a large difference in charge density. This investigation led to the preparation and characterization of a new family of niobium oxychloride cluster compounds with original structure types exhibiting 1ow-dimensional or open-framework character. Most of these materials have framework topologies unprecedented in compounds containing octahedral clusters. Comparative analysis of their structural features indicates that the novel cluster connectivity patterns in these systems are the result of complex interplay between the effects of anisotropic ligand arrangement in the cluster unit and optimization of ligand-counterion electrostatic interactions. The important role played by these factors sets niobium oxychloride systems apart from cluster compounds with one ligand type or statistical ligand distribution where the main structure-determining factor is the total number of ligands. These results provide a blueprint for expanding the ligand combination strategy to other transition metal cluster systems and for the future rational design of cluster-based materials.

Semiconductor nanocrystals covalently bound to solid inorganic surfaces using self-assembled monolayers

DOEpatents

Alivisatos, A.P.; Colvin, V.L.

1998-05-12

Methods are described for attaching semiconductor nanocrystals to solid inorganic surfaces, using self-assembled bifunctional organic monolayers as bridge compounds. Two different techniques are presented. One relies on the formation of self-assembled monolayers on these surfaces. When exposed to solutions of nanocrystals, these bridge compounds bind the crystals and anchor them to the surface. The second technique attaches nanocrystals already coated with bridge compounds to the surfaces. Analyses indicate the presence of quantum confined clusters on the surfaces at the nanolayer level. These materials allow electron spectroscopies to be completed on condensed phase clusters, and represent a first step towards synthesis of an organized assembly of clusters. These new products are also disclosed. 10 figs.

A method for topological analysis of high nuclearity coordination clusters and its application to Mn coordination compounds.

PubMed

Kostakis, George E; Blatov, Vladislav A; Proserpio, Davide M

2012-04-21

A novel method for the topological description of high nuclearity coordination clusters (CCs) was improved and applied to all compounds containing only manganese as a metal center, the data on which are collected in the CCDC (CCDC 5.33 Nov. 2011). Using the TOPOS program package that supports this method, we identified 539 CCs with five or more Mn centers adopting 159 topologically different graphs. In the present database all the Mn CCs are collected and illustrated in such a way that can be searched by cluster topological symbol and nuclearity, compound name and Refcode. The main principles for such an analysis are described herein as well as useful applications of this method.

Polymer-coated nanoparticles: Carrier platforms for hydrophobic water- and air-sensitive metallo-organic compounds.

PubMed

Valdeperez, Daniel; Wang, Tianqiang; Eußner, Jens P; Weinert, Bastian; Hao, Jianyuan; Parak, Wolfgang J; Dehnen, Stefanie; Pelaz, Beatriz

2017-03-01

Many of the relevant compounds for anticancer therapy are metal-based compounds (metallodrugs), being platinum-based drugs such as cisplatin, carboplatin (Paraplatin ® ), and oxaliplatin (Eloxatin ® ) the most widely used. Despite this, their application is limited by issues such as cell-acquired platinum resistance and manifold side effects following systemic delivery. Thus, the development of new metal-based compounds is highly needed. The catalytic properties of a variety of metal-based compounds are nowadays very well known, which opens new opportunities to take advantage of them inside living cells or organisms. However, many of these compounds are hydrophobic and thus not soluble in aqueous solution, as they lack stability against water or oxygen presence. Thus, versatile platforms capable of enhancing the features of these compounds in aqueous solutions are of importance in the development of new drugs. Surface engineered nanoparticles may render metallodrugs with good colloidal stability in water and in complex media containing high salt concentration and/or proteins. Herein, polymer coated nanoparticles are proposed as a platform to link insoluble and water/oxygen sensitive drugs. The linkage of insoluble and oxygen sensitive tin clusters to nanoparticles is presented, aiming to enhance both, the solubility and the stability of these compounds in water, which may be an alternative approach in the development of metal-based drugs. The formation of the cluster-nanoparticle system was confirmed via inductively coupled plasma mass spectrometry experiments. The catalytic activity and the stability of the cluster in water were studied through the reduction of methylene blue. Results demonstrate that in fact the tin clusters could be transferred into aqueous solution and retained their catalytic activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti AIDS drug design with the help of neural networks

NASA Astrophysics Data System (ADS)

Tetko, I. V.; Tanchuk, V. Yu.; Luik, A. I.

1995-04-01

Artificial neural networks were used to analyze and predict the human immunodefiency virus type 1 reverse transcriptase inhibitors. Training and control set included 44 molecules (most of them are well-known substances such as AZT, TIBO, dde, etc.) The biological activities of molecules were taken from literature and rated for two classes: active and inactive compounds according to their values. We used topological indices as molecular parameters. Four most informative parameters (out of 46) were chosen using cluster analysis and original input parameters' estimation procedure and were used to predict activities of both control and new (synthesized in our institute) molecules. We applied pruning network algorithm and network ensembles to obtain the final classifier and avoid chance correlation. The increasing of neural network generalization of the data from the control set was observed, when using the aforementioned methods. The prognosis of new molecules revealed one molecule as possibly active. It was confirmed by further biological tests. The compound was as active as AZT and in order less toxic. The active compound is currently being evaluated in pre clinical trials as possible drug for anti-AIDS therapy.

Insertion of a single-molecule magnet inside a ferromagnetic lattice based on a 3D bimetallic oxalate network: towards molecular analogues of permanent magnets.

PubMed

Clemente-León, Miguel; Coronado, Eugenio; Gómez-García, Carlos J; López-Jordà, Maurici; Camón, Agustín; Repollés, Ana; Luis, Fernando

2014-02-03

The insertion of the single-molecule magnet (SMM) [Mn(III)(salen)(H2O)]2(2+) (salen(2-) = N,N'-ethylenebis-(salicylideneiminate)) into a ferromagnetic bimetallic oxalate network affords the hybrid compound [Mn(III)(salen)(H2O)]2[Mn(II)Cr(III)(ox)3]2⋅(CH3OH)⋅(CH3CN)2 (1). This cationic Mn2 cluster templates the growth of crystals formed by an unusual achiral 3D oxalate network. The magnetic properties of this hybrid magnet are compared with those of the analogous compounds [Mn(III)(salen)(H2O)]2[Zn(II)Cr(III)(ox)3]2⋅(CH3OH)⋅(CH3CN)2 (2) and [In(III)(sal2-trien)][Mn(II)Cr(III)(ox)3]⋅(H2O)0.25⋅(CH3OH)0.25⋅(CH3CN)0.25 (3), which are used as reference compounds. In 2 it has been shown that the magnetic isolation of the Mn2 clusters provided by their insertion into a paramagnetic oxalate network of Cr(III) affords a SMM behavior, albeit with blocking temperatures well below 500 mK even for frequencies as high as 160 kHz. In 3 the onset of ferromagnetism in the bimetallic Mn(II) Cr(III) network is observed at Tc = 5 K. Finally, in the hybrid compound 1 the interaction between the two magnetic networks leads to the antiparallel arrangement of their respective magnetizations, that is, to a ferrimagnetic phase. This coupling induces also important changes on the magnetic properties of 1 with respect to those of the reference compounds 2 and 3. In particular, compound 1 shows a large magnetization hysteresis below 1 K, which is in sharp contrast with the near-reversible magnetizations that the SMMs and the oxalate ferromagnetic lattice show under the same conditions. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spin-canting magnetization in an unusual Co4 cluster-based layer compound from a 2,3-dihydroxyquinoxaline ligand.

PubMed

Yang, Chen-I; Chuang, Po-Hsiang; Lee, Gene-Hsiang; Peng, Shie-Ming; Lu, Kuang-Lieh

2012-01-16

The self-assembly of Co(O(2)CPh)(2) with a 2,3-dihydroxyquinoxaline (H(2)dhq) linker has revealed a new two-dimensional cluster-based compound, [Co(4)(OMe)(2)(O(2)CPh)(2)(dhq)(2)(MeOH)(2)](n), which shows spin-canted magnetization and a definite magnetic hysteresis loop.

Multiple valence superatoms.

PubMed

Reveles, J U; Khanna, S N; Roach, P J; Castleman, A W

2006-12-05

We recently demonstrated that, in gas phase clusters containing aluminum and iodine atoms, an Al(13) cluster behaves like a halogen atom, whereas an Al(14) cluster exhibits properties analogous to an alkaline earth atom. These observations, together with our findings that Al(13)(-) is inert like a rare gas atom, have reinforced the idea that chosen clusters can exhibit chemical behaviors reminiscent of atoms in the periodic table, offering the exciting prospect of a new dimension of the periodic table formed by cluster elements, called superatoms. As the behavior of clusters can be controlled by size and composition, the superatoms offer the potential to create unique compounds with tailored properties. In this article, we provide evidence of an additional class of superatoms, namely Al(7)(-), that exhibit multiple valences, like some of the elements in the periodic table, and hence have the potential to form stable compounds when combined with other atoms. These findings support the contention that there should be no limitation in finding clusters, which mimic virtually all members of the periodic table.

Drug-likeness analysis of traditional Chinese medicines: 2. Characterization of scaffold architectures for drug-like compounds, non-drug-like compounds, and natural compounds from traditional Chinese medicines.

PubMed

Tian, Sheng; Li, Youyong; Wang, Junmei; Xu, Xiaojie; Xu, Lei; Wang, Xiaohong; Chen, Lei; Hou, Tingjun

2013-01-21

In order to better understand the structural features of natural compounds from traditional Chinese medicines, the scaffold architectures of drug-like compounds in MACCS-II Drug Data Report (MDDR), non-drug-like compounds in Available Chemical Directory (ACD), and natural compounds in Traditional Chinese Medicine Compound Database (TCMCD) were explored and compared. First, the different scaffolds were extracted from ACD, MDDR and TCMCD by using three scaffold representations, including Murcko frameworks, Scaffold Tree, and ring systems with different complexity and side chains. Then, by examining the accumulative frequency of the scaffolds in each dataset, we observed that the Level 1 scaffolds of the Scaffold Tree offer advantages over the other scaffold architectures to represent the scaffold diversity of the compound libraries. By comparing the similarity of the scaffold architectures presented in MDDR, ACD and TCMCD, structural overlaps were observed not only between MDDR and TCMCD but also between MDDR and ACD. Finally, Tree Maps were used to cluster the Level 1 scaffolds of the Scaffold Tree and visualize the scaffold space of the three datasets. The analysis of the scaffold architectures of MDDR, ACD and TCMCD shows that, on average, drug-like molecules in MDDR have the highest diversity while natural compounds in TCMCD have the highest complexity. According to the Tree Maps, it can be observed that the Level 1 scaffolds present in MDDR have higher diversity than those presented in TCMCD and ACD. However, some representative scaffolds in MDDR with high frequency show structural similarities to those in TCMCD and ACD, suggesting that some scaffolds in TCMCD and ACD may be potentially drug-like fragments for fragment-based and de novo drug design.

Drug-likeness analysis of traditional Chinese medicines: 2. Characterization of scaffold architectures for drug-like compounds, non-drug-like compounds, and natural compounds from traditional Chinese medicines

PubMed Central

2013-01-01

Background In order to better understand the structural features of natural compounds from traditional Chinese medicines, the scaffold architectures of drug-like compounds in MACCS-II Drug Data Report (MDDR), non-drug-like compounds in Available Chemical Directory (ACD), and natural compounds in Traditional Chinese Medicine Compound Database (TCMCD) were explored and compared. Results First, the different scaffolds were extracted from ACD, MDDR and TCMCD by using three scaffold representations, including Murcko frameworks, Scaffold Tree, and ring systems with different complexity and side chains. Then, by examining the accumulative frequency of the scaffolds in each dataset, we observed that the Level 1 scaffolds of the Scaffold Tree offer advantages over the other scaffold architectures to represent the scaffold diversity of the compound libraries. By comparing the similarity of the scaffold architectures presented in MDDR, ACD and TCMCD, structural overlaps were observed not only between MDDR and TCMCD but also between MDDR and ACD. Finally, Tree Maps were used to cluster the Level 1 scaffolds of the Scaffold Tree and visualize the scaffold space of the three datasets. Conclusion The analysis of the scaffold architectures of MDDR, ACD and TCMCD shows that, on average, drug-like molecules in MDDR have the highest diversity while natural compounds in TCMCD have the highest complexity. According to the Tree Maps, it can be observed that the Level 1 scaffolds present in MDDR have higher diversity than those presented in TCMCD and ACD. However, some representative scaffolds in MDDR with high frequency show structural similarities to those in TCMCD and ACD, suggesting that some scaffolds in TCMCD and ACD may be potentially drug-like fragments for fragment-based and de novo drug design. PMID:23336706

A spatial scan statistic for compound Poisson data.

PubMed

Rosychuk, Rhonda J; Chang, Hsing-Ming

2013-12-20

The topic of spatial cluster detection gained attention in statistics during the late 1980s and early 1990s. Effort has been devoted to the development of methods for detecting spatial clustering of cases and events in the biological sciences, astronomy and epidemiology. More recently, research has examined detecting clusters of correlated count data associated with health conditions of individuals. Such a method allows researchers to examine spatial relationships of disease-related events rather than just incident or prevalent cases. We introduce a spatial scan test that identifies clusters of events in a study region. Because an individual case may have multiple (repeated) events, we base the test on a compound Poisson model. We illustrate our method for cluster detection on emergency department visits, where individuals may make multiple disease-related visits. Copyright © 2013 John Wiley & Sons, Ltd.

Comparison of Metabolic Pathways in Escherichia coli by Using Genetic Algorithms.

PubMed

Ortegon, Patricia; Poot-Hernández, Augusto C; Perez-Rueda, Ernesto; Rodriguez-Vazquez, Katya

2015-01-01

In order to understand how cellular metabolism has taken its modern form, the conservation and variations between metabolic pathways were evaluated by using a genetic algorithm (GA). The GA approach considered information on the complete metabolism of the bacterium Escherichia coli K-12, as deposited in the KEGG database, and the enzymes belonging to a particular pathway were transformed into enzymatic step sequences by using the breadth-first search algorithm. These sequences represent contiguous enzymes linked to each other, based on their catalytic activities as they are encoded in the Enzyme Commission numbers. In a posterior step, these sequences were compared using a GA in an all-against-all (pairwise comparisons) approach. Individual reactions were chosen based on their measure of fitness to act as parents of offspring, which constitute the new generation. The sequences compared were used to construct a similarity matrix (of fitness values) that was then considered to be clustered by using a k-medoids algorithm. A total of 34 clusters of conserved reactions were obtained, and their sequences were finally aligned with a multiple-sequence alignment GA optimized to align all the reaction sequences included in each group or cluster. From these comparisons, maps associated with the metabolism of similar compounds also contained similar enzymatic step sequences, reinforcing the Patchwork Model for the evolution of metabolism in E. coli K-12, an observation that can be expanded to other organisms, for which there is metabolism information. Finally, our mapping of these reactions is discussed, with illustrations from a particular case.

Comparison of Metabolic Pathways in Escherichia coli by Using Genetic Algorithms

PubMed Central

Ortegon, Patricia; Poot-Hernández, Augusto C.; Perez-Rueda, Ernesto; Rodriguez-Vazquez, Katya

2015-01-01

In order to understand how cellular metabolism has taken its modern form, the conservation and variations between metabolic pathways were evaluated by using a genetic algorithm (GA). The GA approach considered information on the complete metabolism of the bacterium Escherichia coli K-12, as deposited in the KEGG database, and the enzymes belonging to a particular pathway were transformed into enzymatic step sequences by using the breadth-first search algorithm. These sequences represent contiguous enzymes linked to each other, based on their catalytic activities as they are encoded in the Enzyme Commission numbers. In a posterior step, these sequences were compared using a GA in an all-against-all (pairwise comparisons) approach. Individual reactions were chosen based on their measure of fitness to act as parents of offspring, which constitute the new generation. The sequences compared were used to construct a similarity matrix (of fitness values) that was then considered to be clustered by using a k-medoids algorithm. A total of 34 clusters of conserved reactions were obtained, and their sequences were finally aligned with a multiple-sequence alignment GA optimized to align all the reaction sequences included in each group or cluster. From these comparisons, maps associated with the metabolism of similar compounds also contained similar enzymatic step sequences, reinforcing the Patchwork Model for the evolution of metabolism in E. coli K-12, an observation that can be expanded to other organisms, for which there is metabolism information. Finally, our mapping of these reactions is discussed, with illustrations from a particular case. PMID:25973143

Microbial communities related to volatile organic compound emission in automobile air conditioning units.

PubMed

Diekmann, Nina; Burghartz, Melanie; Remus, Lars; Kaufholz, Anna-Lena; Nawrath, Thorben; Rohde, Manfred; Schulz, Stefan; Roselius, Louisa; Schaper, Jörg; Mamber, Oliver; Jahn, Dieter; Jahn, Martina

2013-10-01

During operation of mobile air conditioning (MAC) systems in automobiles, malodours can occur. We studied the microbial communities found on contaminated heat exchanger fins of 45 evaporators from car MAC systems which were operated in seven different regions of the world and identified corresponding volatile organic compounds. Collected biofilms were examined by scanning electron microscopy and fluorescent in situ hybridization. The detected bacteria were loosely attached to the metal surface. Further analyses of the bacteria using PCR-based single-strand conformation polymorphism and sequencing of isolated 16S rRNA gene fragments identified highly divergent microbial communities with multiple members of the Alphaproteobacteriales, Methylobacteria were the prevalent bacteria. In addition, Sphingomonadales, Burkholderiales, Bacillales, Alcanivorax spp. and Stenotrophomonas spp. were found among many others depending on the location the evaporators were operated. Interestingly, typical pathogenic bacteria related to air conditioning systems including Legionella spp. were not found. In order to determine the nature of the chemical compounds produced by the bacteria, the volatile organic compounds were examined by closed loop stripping analysis and identified by combined gas chromatography/mass spectrometry. Sulphur compounds, i.e. di-, tri- and multiple sulphides, acetylthiazole, aromatic compounds and diverse substituted pyrazines were detected. Mathematical clustering of the determined microbial community structures against their origin identified a European/American/Arabic cluster versus two mainly tropical Asian clusters. Interestingly, clustering of the determined volatiles against the origin of the corresponding MAC revealed a highly similar pattern. A close relationship of microbial community structure and resulting malodours to the climate and air quality at the location of MAC operation was concluded.

TOPICAL REVIEW: O- bound small polarons in oxide materials

NASA Astrophysics Data System (ADS)

Schirmer, O. F.

2006-11-01

Holes bound to acceptor defects in oxide crystals are often localized by lattice distortion at just one of the equivalent oxygen ligands of the defect. Such holes thus form small polarons in symmetric clusters of a few oxygen ions. An overview on mainly the optical manifestations of those clusters is given. The article is essentially divided into two parts: the first one covers the basic features of the phenomena and their explanations, exemplified by several paradigmatic defects; in the second part numerous oxide materials are presented which exhibit bound small polaron optical properties. The first part starts with summaries on the production of bound hole polarons and the identification of their structure. It is demonstrated why they show strong, wide absorption bands, usually visible, based on polaron stabilization energies of typically 1 eV. The basic absorption process is detailed with a fictitious two-well system. Clusters with four, six and twelve equivalent ions are realized in various oxide compounds. In these cases several degenerate optically excited polaron states occur, leading to characteristic final state resonance splittings. The peak energies of the absorption bands as well as the sign of the transfer energy depend on the topology of the clusters. A special section is devoted to the distinction between interpolaron and intrapolaron optical transitions. The latter are usually comparatively weak. The oxide compounds exhibiting bound hole small polaron absorptions include the alkaline earth oxides (e.g. MgO), BeO and ZnO, the perovskites BaTiO3 and KTaO3, quartz, the sillenites (e.g. Bi12TiO20), Al2O3, LiNbO3, topaz and various other materials. There are indications that the magnetic crystals NiO, doped with Li, and LaMnO3, doped with Sr, also show optical features caused by bound hole polarons. Beyond being elementary paradigms for the properties of small polarons in general, the defect species treated can be used to explain radiation and light induced absorption especially in laser and non-linear oxide materials, the role of some defects in photorefractive compounds, the coloration of various gemstones, the structure of certain catalytic surface centres, etc. The relation to further phenomena is discussed: free small polarons, similar distorted centres in the sulfides and selenides, acceptor defects trapping two holes.

X-ray attenuation coefficients of high-atomic-number, hexanuclear transition metal cluster compounds: a new paradigm for radiographic contrast agents.

PubMed

Mullan, B F; Madsen, M T; Messerle, L; Kolesnichenko, V; Kruger, J

2000-04-01

The purpose of this study was to examine the radiologic attenuation properties of the parent cluster compounds, particularly attenuation as a function of discrete photon energy, before investigating ligand substitutions, which are necessary to improve cluster biocompatibility and to impart desirable physicochemical properties. The linear attenuation coefficients for solutions of the cluster compounds Ta6Br14, K8Ta6O19, and (H3O)2W6Cl14 were determined at 60, 80, 103, 122, and 140 keV from gamma-ray transmission measurements with americium-241, xenon-133, gadolinium-153, cobalt-57, and technetium-99m radioactive sources. Transmission measurements were obtained for a fixed time interval that ensured a statistically accurate count distribution exceeding 20,000 counts through the sample for each trial. On a strictly mole per liter basis, a 0.075 mol/L aqueous solution of K8Ta6O19 showed 1.08 times the attenuation of 0.063 mol/L aqueous iohexol at 60 keV and 3.30 times the attenuation at 80 keV. Similarly, a 0.05 mol/L methanolic solution of (H3O)2W6Cl4 showed 0.96 times (96%) the attenuation of 0.063 mol/L aqueous iohexol at 60 keV but 3.09 times the attenuation of the iohexol solution at 80 keV. Attenuations of 0.063 mol/L aqueous iohexol and 0.0125 mol/L Ta6Br14 (ie, at approximately one-fifth the iohexol concentration) were comparable at greater than 60 keV. These results confirm the theoretic potential for use of early transition metal cluster compounds as radiographic contrast agents. At higher x-ray energies, cluster compounds demonstrate multiplied x-ray attenuation relative to iodinated contrast agents.

Identification of the Beer Component Hordenine as Food-Derived Dopamine D2 Receptor Agonist by Virtual Screening a 3D Compound Database

NASA Astrophysics Data System (ADS)

Sommer, Thomas; Hübner, Harald; El Kerdawy, Ahmed; Gmeiner, Peter; Pischetsrieder, Monika; Clark, Timothy

2017-03-01

The dopamine D2 receptor (D2R) is involved in food reward and compulsive food intake. The present study developed a virtual screening (VS) method to identify food components, which may modulate D2R signalling. In contrast to their common applications in drug discovery, VS methods are rarely applied for the discovery of bioactive food compounds. Here, databases were created that exclusively contain substances occurring in food and natural sources (about 13,000 different compounds in total) as the basis for combined pharmacophore searching, hit-list clustering and molecular docking into D2R homology models. From 17 compounds finally tested in radioligand assays to determine their binding affinities, seven were classified as hits (hit rate = 41%). Functional properties of the five most active compounds were further examined in β-arrestin recruitment and cAMP inhibition experiments. D2R-promoted G-protein activation was observed for hordenine, a constituent of barley and beer, with approximately identical ligand efficacy as dopamine (76%) and a Ki value of 13 μM. Moreover, hordenine antagonised D2-mediated β-arrestin recruitment indicating functional selectivity. Application of our databases provides new perspectives for the discovery of bioactive food constituents using VS methods. Based on its presence in beer, we suggest that hordenine significantly contributes to mood-elevating effects of beer.

Syntheses, structures and characterizations of three novel vanadium selenites with organically bonded copper/nickel complex

NASA Astrophysics Data System (ADS)

Qian, Cheng; Kong, Fang; Mao, Jiang-Gao

2016-06-01

A series of vanadium selenites covalently bonded with metal-organic complex, namely, Ni(2,2-bipy)2V2O4(SeO3)2 (1), Cu(2,2-bipy)V2O4(SeO3)2·0.5H2O (2) and Cu2(2,2-bipy)2V5O12(SeO3)2 (3) (2,2-bipy=2,2-bipyridine) have been hydrothermally synthesized and structurally characterized. They exhibit three different structural dimensions, from 0D cluster, 1D chain to 2D layer. Compound 1 features a 0D {Ni(2,2-bipy)2V2O4(SeO3)2}2 dimeric cluster composed of two {Ni(2,2-bipy)2}2+ moieties connected by the {V4O8(SeO3)4}4- cluster. Compound 2 shows a 1D {Cu(2,2-bipy)V2O4(SeO3)2}n chain in which the {Cu2(2,2-bipy)2}4+ moieties are bridged by the {V4O8(SeO3)4}4- clusters. Compound 3 displays a 2D structure consisted of mixed valence vanadium selenites layers {VIVVV4SeIV2O18}n4- and {Cu(2,2-bipy)}2+ complex moieties. The adjacent layers are further interconnected via π-π interactions between the 2,2-bipy ligands exhibiting an interesting 3D supramolecular architecture. Both compound 1 and 2 contain a new {V4O8(SeO3)4}4- cluster and compound 3 exhibits the first 2D vanadate polyhedral layer in vanadium selenites/tellurites with organic moieties.

Design of hydrophobic polyoxometalate hybrid assemblies beyond surfactant encapsulation.

PubMed

Song, Yu-Fei; McMillan, Nicola; Long, De-Liang; Thiel, Johannes; Ding, Yulong; Chen, Haisheng; Gadegaard, Nikolaj; Cronin, Leroy

2008-01-01

Grafting of C-6, C-16 and C-18 alkyl chains onto the hydrophilic Mn-Anderson clusters (compounds 2-4) has been achieved. Exchange of the tetrabutyl ammonium (TBA) with dimethyldioctadecyl ammonium (DMDOA) results in the formation of new polyoxometalate (POM) assemblies (compounds 5-6), in which the POM cores are covalently functionalized by hydrophilic alkyl-chains and enclosed by surfactant of DMDOABr. As a result, we have been able to design and synthesize POM-containing hydrophobic materials beyond surfactant encapsulation. In solid state, scanning electron and transmission electron microscopy (SEM and TEM) studies of the TBA salts of compounds 3 and 4 show highly ordered, uniform, reproducible assemblies with unique segmented rodlike morphology. SEM and TEM studies of the DMDOA salts of compounds 5 and 6 show that they form spherical and sea urchin 3D objects in different solvent systems. In solution, the physical properties of compound 5 and 6 (combination of surfactant-encapsulated cluster (SEC) and surface-grafted cluster (SGC)) show a liquid-to-gel phase transition in pure chloroform below 0 degrees C, which are much lower than other reported SECs. By utilizing light scattering measurements, the nanoparticle size for compounds 5 and 6 were measured at 5 degrees C and 30 degrees C, respectively. Other physical properties including differential scanning calorimetry have been reported.

Characterization of anticancer agents by their growth inhibitory activity and relationships to mechanism of action and structure.

PubMed

Keskin, O; Bahar, I; Jernigan, R L; Beutler, J A; Shoemaker, R H; Sausville, E A; Covell, D G

2000-04-01

An analysis of the growth inhibitory potency of 122 anticancer agents available from the National Cancer Institute anticancer drug screen is presented. Methods of singular value decomposition (SVD) were applied to determine the matrix of distances between all compounds. These SVD-derived dissimilarity distances were used to cluster compounds that exhibit similar tumor growth inhibitory activity patterns against 60 human cancer cell lines. Cluster analysis divides the 122 standard agents into 25 statistically distinct groups. The first eight groups include structurally diverse compounds with reactive functionalities that act as DNA-damaging agents while the remaining 17 groups include compounds that inhibit nucleic acid biosynthesis and mitosis. Examination of the average activity patterns across the 60 tumor cell lines reveals unique 'fingerprints' associated with each group. A diverse set of structural features are observed for compounds within these groups, with frequent occurrences of strong within-group structural similarities. Clustering of cell types by their response to the 122 anticancer agents divides the 60 cell types into 21 groups. The strongest within-panel groupings were found for the renal, leukemia and ovarian cell panels. These results contribute to the basis for comparisons between log(GI(50)) screening patterns of the 122 anticancer agents and additional tested compounds.

A bronze matryoshka: the discrete intermetalloid cluster [Sn@Cu12@Sn20](12-) in the ternary phases A12Cu12Sn21 (A = Na, K).

PubMed

Stegmaier, Saskia; Fässler, Thomas F

2011-12-14

The synthesis and crystal structure of the first ternary A-Cu-Sn intermetallic phases for the heavier alkali metals A = Na to Cs is reported. The title compounds A(12)Cu(12)Sn(21) show discrete 33-atom intermetalloid Cu-Sn clusters {Sn@Cu(12)@Sn(20)}, which are composed of {Sn(20)} pentagonal dodecahedra surrounding {Cu(12)} icosahedra with single Sn atoms at the center. Na(12)Cu(12)Sn(21) and K(12)Cu(12)Sn(21) were characterized by single-crystal XRD studies, and the successful synthesis of analogous A-Cu-Sn compounds with A = Rb and Cs is deduced from powder XRD data. The isotypic A(12)Cu(12)Sn(21) phases crystallize in the cubic space group Pn ̅3m (No. 224), with the Cu-Sn clusters adopting a face centered cubic arrangement. A formal charge of 12- can be assigned to the {Sn@Cu(12)@Sn(20)} cluster unit, and the interpretation of the title compounds as salt-like intermetallic phases featuring discrete anionic intermetalloid [Sn@Cu(12)@Sn(20)](12-) clusters separated by alkali metal cations is supported by electronic structure calculations. For both Na(12)Cu(12)Sn(21) and K(12)Cu(12)Sn(21), DFT band structure calculations (TB-LMTO-ASA) reveal a band gap. The discrete [Sn@Cu(12)@Sn(20)](12-) cluster is analyzed in consideration of the molecular orbitals obtained from hybrid DFT calculations (Gaussian 09) for the cluster anion. The [Sn@Cu(12)@Sn(20)](12-) cluster MOs can be classified with labels indicating the numbers of radial and angular nodes, in the style of spherical shell models of cluster bonding. © 2011 American Chemical Society

BioCompoundML: A General Biofuel Property Screening Tool for Biological Molecules Using Random Forest Classifiers

DOE PAGES

Whitmore, Leanne S.; Davis, Ryan W.; McCormick, Robert L.; ...

2016-09-15

Screening a large number of biologically derived molecules for potential fuel compounds without recourse to experimental testing is important in identifying understudied yet valuable molecules. Experimental testing, although a valuable standard for measuring fuel properties, has several major limitations, including the requirement of testably high quantities, considerable expense, and a large amount of time. This paper discusses the development of a general-purpose fuel property tool, using machine learning, whose outcome is to screen molecules for desirable fuel properties. BioCompoundML adopts a general methodology, requiring as input only a list of training compounds (with identifiers and measured values) and a listmore » of testing compounds (with identifiers). For the training data, BioCompoundML collects open data from the National Center for Biotechnology Information, incorporates user-provided features, imputes missing values, performs feature reduction, builds a classifier, and clusters compounds. BioCompoundML then collects data for the testing compounds, predicts class membership, and determines whether compounds are found in the range of variability of the training data set. We demonstrate this tool using three different fuel properties: research octane number (RON), threshold soot index (TSI), and melting point (MP). Here we provide measures of its success with these properties using randomized train/test measurements: average accuracy is 88% in RON, 85% in TSI, and 94% in MP; average precision is 88% in RON, 88% in TSI, and 95% in MP; and average recall is 88% in RON, 82% in TSI, and 97% in MP. The receiver operator characteristics (area under the curve) were estimated at 0.88 in RON, 0.86 in TSI, and 0.87 in MP. We also measured the success of BioCompoundML by sending 16 compounds for direct RON determination. Finally, we provide a screen of 1977 hydrocarbons/oxygenates within the 8696 compounds in MetaCyc, identifying compounds with high predictive strength for high or low RON.« less

Cooling rate dependence of simulated Cu{sub 64.5}Zr{sub 35.5} metallic glass structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryltsev, R. E.; Ural Federal University, 19 Mira Str., 620002 Ekaterinburg; L.D. Landau Institute for Theoretical Physics, Russian Academy of Sciences, 2 Kosygina Str., 119334 Moscow

Using molecular dynamics simulations with embedded atom model potential, we study structural evolution of Cu{sub 64.5}Zr{sub 35.5} alloy during the cooling in a wide range of cooling rates γ ∈ (1.5 ⋅ 10{sup 9}, 10{sup 13}) K/s. Investigating short- and medium-range orders, we show that the structure of Cu{sub 64.5}Zr{sub 35.5} metallic glass essentially depends on cooling rate. In particular, a decrease of the cooling rate leads to an increase of abundances of both the icosahedral-like clusters and Frank-Kasper Z16 polyhedra. The amounts of these clusters in the glassy state drastically increase at the γ{sub min} = 1.5 ⋅ 10{supmore » 9} K/s. Analysing the structure of the glass at γ{sub min}, we observe the formation of nano-sized crystalline grain of Cu{sub 2}Zr intermetallic compound with the structure of Cu{sub 2}Mg Laves phase. The structure of this compound is isomorphous with that for Cu{sub 5}Zr intermetallic compound. Both crystal lattices consist of two types of clusters: Cu-centered 13-atom icosahedral-like cluster and Zr-centered 17-atom Frank-Kasper polyhedron Z16. That suggests the same structural motifs for the metallic glass and intermetallic compounds of Cu–Zr system and explains the drastic increase of the abundances of these clusters observed at γ{sub min}.« less

A Systems Biology Approach for Identifying Hepatotoxicant Groups Based on Similarity in Mechanisms of Action and Chemical Structure.

PubMed

Hebels, Dennie G A J; Rasche, Axel; Herwig, Ralf; van Westen, Gerard J P; Jennen, Danyel G J; Kleinjans, Jos C S

2016-01-01

When evaluating compound similarity, addressing multiple sources of information to reach conclusions about common pharmaceutical and/or toxicological mechanisms of action is a crucial strategy. In this chapter, we describe a systems biology approach that incorporates analyses of hepatotoxicant data for 33 compounds from three different sources: a chemical structure similarity analysis based on the 3D Tanimoto coefficient, a chemical structure-based protein target prediction analysis, and a cross-study/cross-platform meta-analysis of in vitro and in vivo human and rat transcriptomics data derived from public resources (i.e., the diXa data warehouse). Hierarchical clustering of the outcome scores of the separate analyses did not result in a satisfactory grouping of compounds considering their known toxic mechanism as described in literature. However, a combined analysis of multiple data types may hypothetically compensate for missing or unreliable information in any of the single data types. We therefore performed an integrated clustering analysis of all three data sets using the R-based tool iClusterPlus. This indeed improved the grouping results. The compound clusters that were formed by means of iClusterPlus represent groups that show similar gene expression while simultaneously integrating a similarity in structure and protein targets, which corresponds much better with the known mechanism of action of these toxicants. Using an integrative systems biology approach may thus overcome the limitations of the separate analyses when grouping liver toxicants sharing a similar mechanism of toxicity.

Cellular internalization and morphological analysis after intravenous injection of a highly hydrophilic octahedral rhenium cluster complex - a new promising X-ray contrast agent.

PubMed

Krasilnikova, Anna A; Solovieva, Anastasiya O; Trifonova, Kristina E; Brylev, Konstantin A; Ivanov, Anton A; Kim, Sung-Jin; Shestopalov, Michael A; Fufaeva, Maria S; Shestopalov, Alexander M; Mironov, Yuri V; Poveshchenko, Alexander F; Shestopalova, Lidia V

2016-11-01

The octahedral cluster compound Na 2 H 8 [{Re 6 Se 8 }(P(C 2 H 4 CONH 2 )(C 2 H 4 COO) 2 ) 6 ] has been shown to be highly radio dense, thus becoming a promising X-ray contrast agent. It was also shown that this compound had low cytotoxic effect in vitro, low acute toxicity in vivo and was eliminated rapidly from the body through the urinary tract. The present contribution describes a more detailed cellular internalization assay and morphological analysis after intravenous injection of this hexarhenium cluster compound at different doses. The median lethal dose (LD 50 ) of intravenously administrated compound was calculated (4.67 ± 0.69 g/kg). Results of the study clearly indicated that the cluster complex H n [{Re 6 Se 8 }(P(C 2 H 4 CONH 2 )(C 2 H 4 COO) 2 ) 6 ] n-10 was not internalized into cells in vitro and induced only moderate morphological alterations of kidneys at high doses without any changes in morphology of liver, spleen, duodenum, or heart of mice. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Pep2Path: automated mass spectrometry-guided genome mining of peptidic natural products.

PubMed

Medema, Marnix H; Paalvast, Yared; Nguyen, Don D; Melnik, Alexey; Dorrestein, Pieter C; Takano, Eriko; Breitling, Rainer

2014-09-01

Nonribosomally and ribosomally synthesized bioactive peptides constitute a source of molecules of great biomedical importance, including antibiotics such as penicillin, immunosuppressants such as cyclosporine, and cytostatics such as bleomycin. Recently, an innovative mass-spectrometry-based strategy, peptidogenomics, has been pioneered to effectively mine microbial strains for novel peptidic metabolites. Even though mass-spectrometric peptide detection can be performed quite fast, true high-throughput natural product discovery approaches have still been limited by the inability to rapidly match the identified tandem mass spectra to the gene clusters responsible for the biosynthesis of the corresponding compounds. With Pep2Path, we introduce a software package to fully automate the peptidogenomics approach through the rapid Bayesian probabilistic matching of mass spectra to their corresponding biosynthetic gene clusters. Detailed benchmarking of the method shows that the approach is powerful enough to correctly identify gene clusters even in data sets that consist of hundreds of genomes, which also makes it possible to match compounds from unsequenced organisms to closely related biosynthetic gene clusters in other genomes. Applying Pep2Path to a data set of compounds without known biosynthesis routes, we were able to identify candidate gene clusters for the biosynthesis of five important compounds. Notably, one of these clusters was detected in a genome from a different subphylum of Proteobacteria than that in which the molecule had first been identified. All in all, our approach paves the way towards high-throughput discovery of novel peptidic natural products. Pep2Path is freely available from http://pep2path.sourceforge.net/, implemented in Python, licensed under the GNU General Public License v3 and supported on MS Windows, Linux and Mac OS X.

Footprinting of Inhibitor Interactions of In Silico Identified Inhibitors of Trypanothione Reductase of Leishmania Parasite

PubMed Central

Venkatesan, Santhosh K.; Dubey, Vikash Kumar

2012-01-01

Structure-based virtual screening of NCI Diversity set II compounds was performed to indentify novel inhibitor scaffolds of trypanothione reductase (TR) from Leishmania infantum. The top 50 ranked hits were clustered using the AuPoSOM tool. Majority of the top-ranked compounds were Tricyclic. Clustering of hits yielded four major clusters each comprising varying number of subclusters differing in their mode of binding and orientation in the active site. Moreover, for the first time, we report selected alkaloids and dibenzothiazepines as inhibitors of Leishmania infantum TR. The mode of binding observed among the clusters also potentiates the probable in vitro inhibition kinetics and aids in defining key interaction which might contribute to the inhibition of enzymatic reduction of T[S] 2. The method provides scope for automation and integration into the virtual screening process employing docking softwares, for clustering the small molecule inhibitors based upon protein-ligand interactions. PMID:22550471

Fast Metabolite Identification in Nuclear Magnetic Resonance Metabolomic Studies: Statistical Peak Sorting and Peak Overlap Detection for More Reliable Database Queries.

PubMed

Hoijemberg, Pablo A; Pelczer, István

2018-01-05

A lot of time is spent by researchers in the identification of metabolites in NMR-based metabolomic studies. The usual metabolite identification starts employing public or commercial databases to match chemical shifts thought to belong to a given compound. Statistical total correlation spectroscopy (STOCSY), in use for more than a decade, speeds the process by finding statistical correlations among peaks, being able to create a better peak list as input for the database query. However, the (normally not automated) analysis becomes challenging due to the intrinsic issue of peak overlap, where correlations of more than one compound appear in the STOCSY trace. Here we present a fully automated methodology that analyzes all STOCSY traces at once (every peak is chosen as driver peak) and overcomes the peak overlap obstacle. Peak overlap detection by clustering analysis and sorting of traces (POD-CAST) first creates an overlap matrix from the STOCSY traces, then clusters the overlap traces based on their similarity and finally calculates a cumulative overlap index (COI) to account for both strong and intermediate correlations. This information is gathered in one plot to help the user identify the groups of peaks that would belong to a single molecule and perform a more reliable database query. The simultaneous examination of all traces reduces the time of analysis, compared to viewing STOCSY traces by pairs or small groups, and condenses the redundant information in the 2D STOCSY matrix into bands containing similar traces. The COI helps in the detection of overlapping peaks, which can be added to the peak list from another cross-correlated band. POD-CAST overcomes the generally overlooked and underestimated presence of overlapping peaks and it detects them to include them in the search of all compounds contributing to the peak overlap, enabling the user to accelerate the metabolite identification process with more successful database queries and searching all tentative compounds in the sample set.

A cluster-based strategy for assessing the overlap between large chemical libraries and its application to a recent acquisition.

PubMed

Engels, Michael F M; Gibbs, Alan C; Jaeger, Edward P; Verbinnen, Danny; Lobanov, Victor S; Agrafiotis, Dimitris K

2006-01-01

We report on the structural comparison of the corporate collections of Johnson & Johnson Pharmaceutical Research & Development (JNJPRD) and 3-Dimensional Pharmaceuticals (3DP), performed in the context of the recent acquisition of 3DP by JNJPRD. The main objective of the study was to assess the druglikeness of the 3DP library and the extent to which it enriched the chemical diversity of the JNJPRD corporate collection. The two databases, at the time of acquisition, collectively contained more than 1.1 million compounds with a clearly defined structural description. The analysis was based on a clustering approach and aimed at providing an intuitive quantitative estimate and visual representation of this enrichment. A novel hierarchical clustering algorithm called divisive k-means was employed in combination with Kelley's cluster-level selection method to partition the combined data set into clusters, and the diversity contribution of each library was evaluated as a function of the relative occupancy of these clusters. Typical 3DP chemotypes enriching the diversity of the JNJPRD collection were catalogued and visualized using a modified maximum common substructure algorithm. The joint collection of JNJPRD and 3DP compounds was also compared to other databases of known medicinally active or druglike compounds. The potential of the methodology for the analysis of very large chemical databases is discussed.

Image-based compound profiling reveals a dual inhibitor of tyrosine kinase and microtubule polymerization.

PubMed

Tanabe, Kenji

2016-04-27

Small-molecule compounds are widely used as biological research tools and therapeutic drugs. Therefore, uncovering novel targets of these compounds should provide insights that are valuable in both basic and clinical studies. I developed a method for image-based compound profiling by quantitating the effects of compounds on signal transduction and vesicle trafficking of epidermal growth factor receptor (EGFR). Using six signal transduction molecules and two markers of vesicle trafficking, 570 image features were obtained and subjected to multivariate analysis. Fourteen compounds that affected EGFR or its pathways were classified into four clusters, based on their phenotypic features. Surprisingly, one EGFR inhibitor (CAS 879127-07-8) was classified into the same cluster as nocodazole, a microtubule depolymerizer. In fact, this compound directly depolymerized microtubules. These results indicate that CAS 879127-07-8 could be used as a chemical probe to investigate both the EGFR pathway and microtubule dynamics. The image-based multivariate analysis developed herein has potential as a powerful tool for discovering unexpected drug properties.

Robust Classification of Small-Molecule Mechanism of Action Using a Minimalist High-Content Microscopy Screen and Multidimensional Phenotypic Trajectory Analysis

PubMed Central

Twarog, Nathaniel R.; Low, Jonathan A.; Currier, Duane G.; Miller, Greg; Chen, Taosheng; Shelat, Anang A.

2016-01-01

Phenotypic screening through high-content automated microscopy is a powerful tool for evaluating the mechanism of action of candidate therapeutics. Despite more than a decade of development, however, high content assays have yielded mixed results, identifying robust phenotypes in only a small subset of compound classes. This has led to a combinatorial explosion of assay techniques, analyzing cellular phenotypes across dozens of assays with hundreds of measurements. Here, using a minimalist three-stain assay and only 23 basic cellular measurements, we developed an analytical approach that leverages informative dimensions extracted by linear discriminant analysis to evaluate similarity between the phenotypic trajectories of different compounds in response to a range of doses. This method enabled us to visualize biologically-interpretable phenotypic tracks populated by compounds of similar mechanism of action, cluster compounds according to phenotypic similarity, and classify novel compounds by comparing them to phenotypically active exemplars. Hierarchical clustering applied to 154 compounds from over a dozen different mechanistic classes demonstrated tight agreement with published compound mechanism classification. Using 11 phenotypically active mechanism classes, classification was performed on all 154 compounds: 78% were correctly identified as belonging to one of the 11 exemplar classes or to a different unspecified class, with accuracy increasing to 89% when less phenotypically active compounds were excluded. Importantly, several apparent clustering and classification failures, including rigosertib and 5-fluoro-2’-deoxycytidine, instead revealed more complex mechanisms or off-target effects verified by more recent publications. These results show that a simple, easily replicated, minimalist high-content assay can reveal subtle variations in the cellular phenotype induced by compounds and can correctly predict mechanism of action, as long as the appropriate analytical tools are used. PMID:26886014

Robust Classification of Small-Molecule Mechanism of Action Using a Minimalist High-Content Microscopy Screen and Multidimensional Phenotypic Trajectory Analysis.

PubMed

Twarog, Nathaniel R; Low, Jonathan A; Currier, Duane G; Miller, Greg; Chen, Taosheng; Shelat, Anang A

2016-01-01

Phenotypic screening through high-content automated microscopy is a powerful tool for evaluating the mechanism of action of candidate therapeutics. Despite more than a decade of development, however, high content assays have yielded mixed results, identifying robust phenotypes in only a small subset of compound classes. This has led to a combinatorial explosion of assay techniques, analyzing cellular phenotypes across dozens of assays with hundreds of measurements. Here, using a minimalist three-stain assay and only 23 basic cellular measurements, we developed an analytical approach that leverages informative dimensions extracted by linear discriminant analysis to evaluate similarity between the phenotypic trajectories of different compounds in response to a range of doses. This method enabled us to visualize biologically-interpretable phenotypic tracks populated by compounds of similar mechanism of action, cluster compounds according to phenotypic similarity, and classify novel compounds by comparing them to phenotypically active exemplars. Hierarchical clustering applied to 154 compounds from over a dozen different mechanistic classes demonstrated tight agreement with published compound mechanism classification. Using 11 phenotypically active mechanism classes, classification was performed on all 154 compounds: 78% were correctly identified as belonging to one of the 11 exemplar classes or to a different unspecified class, with accuracy increasing to 89% when less phenotypically active compounds were excluded. Importantly, several apparent clustering and classification failures, including rigosertib and 5-fluoro-2'-deoxycytidine, instead revealed more complex mechanisms or off-target effects verified by more recent publications. These results show that a simple, easily replicated, minimalist high-content assay can reveal subtle variations in the cellular phenotype induced by compounds and can correctly predict mechanism of action, as long as the appropriate analytical tools are used.

Metabolic syndrome: pathophysiology, management, and modulation by natural compounds

PubMed Central

Rochlani, Yogita; Pothineni, Naga Venkata; Kovelamudi, Swathi; Mehta, Jawahar L.

2017-01-01

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities that include hypertension, central obesity, insulin resistance, and atherogenic dyslipidemia, and is strongly associated with an increased risk for developing diabetes and atherosclerotic and nonatherosclerotic cardiovascular disease (CVD). The pathogenesis of MetS involves both genetic and acquired factors that contribute to the final pathway of inflammation that leads to CVD. MetS has gained significant importance recently due to the exponential increase in obesity worldwide. Early diagnosis is important in order to employ lifestyle and risk factor modification. Here, we review the epidemiology and pathogenesis of MetS, the role of inflammation in MetS, and summarize existing natural therapies for MetS. PMID:28639538

Lattice and Valence Electronic Structures of Crystalline Octahedral Molybdenum Halide Clusters-Based Compounds, Cs2[Mo6X14] (X = Cl, Br, I), Studied by Density Functional Theory Calculations.

PubMed

Saito, Norio; Cordier, Stéphane; Lemoine, Pierric; Ohsawa, Takeo; Wada, Yoshiki; Grasset, Fabien; Cross, Jeffrey S; Ohashi, Naoki

2017-06-05

The electronic and crystal structures of Cs 2 [Mo 6 X 14 ] (X = Cl, Br, I) cluster-based compounds were investigated by density functional theory (DFT) simulations and experimental methods such as powder X-ray diffraction, ultraviolet-visible spectroscopy, and X-ray photoemission spectroscopy (XPS). The experimentally determined lattice parameters were in good agreement with theoretically optimized ones, indicating the usefulness of DFT calculations for the structural investigation of these clusters. The calculated band gaps of these compounds reproduced those experimentally determined by UV-vis reflectance within an error of a few tenths of an eV. Core-level XPS and effective charge analyses indicated bonding states of the halogens changed according to their sites. The XPS valence spectra were fairly well reproduced by simulations based on the projected electron density of states weighted with cross sections of Al K α , suggesting that DFT calculations can predict the electronic properties of metal-cluster-based crystals with good accuracy.

Syntheses, structures and characterizations of three novel vanadium selenites with organically bonded copper/nickel complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qian, Cheng; State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002; Kong, Fang

2016-06-15

A series of vanadium selenites covalently bonded with metal-organic complex, namely, Ni(2,2-bipy){sub 2}V{sub 2}O{sub 4}(SeO{sub 3}){sub 2} (1), Cu(2,2-bipy)V{sub 2}O{sub 4}(SeO{sub 3}){sub 2}·0.5H{sub 2}O (2) and Cu{sub 2}(2,2-bipy){sub 2}V{sub 5}O{sub 12}(SeO{sub 3}){sub 2} (3) (2,2-bipy=2,2-bipyridine) have been hydrothermally synthesized and structurally characterized. They exhibit three different structural dimensions, from 0D cluster, 1D chain to 2D layer. Compound 1 features a 0D {Ni(2,2-bipy)_2V_2O_4(SeO_3)_2}{sub 2} dimeric cluster composed of two {Ni(2,2-bipy)_2}{sup 2+} moieties connected by the {V_4O_8(SeO_3)_4}{sup 4-} cluster. Compound 2 shows a 1D {Cu(2,2-bipy)V_2O_4(SeO_3)_2}{sub n} chain in which the {Cu_2(2,2-bipy)_2}{sup 4+} moieties are bridged by the {V_4O_8(SeO_3)_4}{sup 4−} clusters. Compound 3more » displays a 2D structure consisted of mixed valence vanadium selenites layers {V"I"VV"V_4Se"I"V_2O_1_8}{sub n}{sup 4−} and {Cu(2,2-bipy)}{sup 2+} complex moieties. The adjacent layers are further interconnected via π-π interactions between the 2,2-bipy ligands exhibiting an interesting 3D supramolecular architecture. Both compound 1 and 2 contain a new {V_4O_8(SeO_3)_4}{sup 4−} cluster and compound 3 exhibits the first 2D vanadate polyhedral layer in vanadium selenites/tellurites with organic moieties. - Graphical abstract: We got three new vanadium selenites with organically linked copper/nickel complex, namely, Ni(2,2-bipy){sub 2}V{sub 2}O{sub 4}(SeO{sub 3}){sub 2} (1), Cu(2,2-bipy)V{sub 2}O{sub 4}(SeO{sub 3}){sub 2}·0.5H{sub 2}O (2) and Cu{sub 2}(2,2-bipy){sub 2}V{sub 5}O{sub 12}(SeO{sub 3}){sub 2} (3) by hydrothermally syntheses. They display three different structural dimensions, from 0D cluster, to 1D chain and 2D layer. Display Omitted - Highlights: • Three new compounds display three different structural dimensions, from 0D cluster, to 1D chain and 2D layer. • The Tetranuclear {V_4O_8(SeO_3)_4}{sup 4−} cluster and the vanadate {V_5O_1_7}{sub n} 2D layer are observed firstly. • Optical Properties and Magnetic Properties of three compounds are reported.« less

Aroma profile and sensory characteristics of a sulfur dioxide-free mulberry (Morus nigra) wine subjected to non-thermal accelerating aging techniques.

PubMed

Tchabo, William; Ma, Yongkun; Kwaw, Emmanuel; Zhang, Haining; Xiao, Lulu; Tahir, Haroon Elrasheid

2017-10-01

The present study was undertaken to assess accelerating aging effects of high pressure, ultrasound and manosonication on the aromatic profile and sensorial attributes of aged mulberry wines (AMW). A total of 166 volatile compounds were found amongst the AMW. The outcomes of the investigation were presented by means of geometric mean (GM), cluster analysis (CA), principal component analysis (PCA), partial least squares regressions (PLSR) and principal component regression (PCR). GM highlighted 24 organoleptic attributes responsible for the sensorial profile of the AMW. Moreover, CA revealed that the volatile composition of the non-thermal accelerated aged wines differs from that of the conventional aged wines. Besides, PCA discriminated the AMW on the basis of their main sensorial characteristics. Furthermore, PLSR identified 75 aroma compounds which were mainly responsible for the olfactory notes of the AMW. Finally, the overall quality of the AMW was noted to be better predicted by PLSR than PCR. Copyright © 2017 Elsevier Ltd. All rights reserved.

TyPol - a new methodology for organic compounds clustering based on their molecular characteristics and environmental behavior.

PubMed

Servien, Rémi; Mamy, Laure; Li, Ziang; Rossard, Virginie; Latrille, Eric; Bessac, Fabienne; Patureau, Dominique; Benoit, Pierre

2014-09-01

Following legislation, the assessment of the environmental risks of 30000-100000 chemical substances is required for their registration dossiers. However, their behavior in the environment and their transfer to environmental components such as water or atmosphere are studied for only a very small proportion of the chemical in laboratory tests or monitoring studies because it is time-consuming and/or cost prohibitive. Therefore, the objective of this work was to develop a new methodology, TyPol, to classify organic compounds, and their degradation products, according to both their behavior in the environment and their molecular properties. The strategy relies on partial least squares analysis and hierarchical clustering. The calculation of molecular descriptors is based on an in silico approach, and the environmental endpoints (i.e. environmental parameters) are extracted from several available databases and literature. The classification of 215 organic compounds inputted in TyPol for this proof-of-concept study showed that the combination of some specific molecular descriptors could be related to a particular behavior in the environment. TyPol also provided an analysis of similarities (or dissimilarities) between organic compounds and their degradation products. Among the 24 degradation products that were inputted, 58% were found in the same cluster as their parents. The robustness of the method was tested and shown to be good. TyPol could help to predict the environmental behavior of a "new" compound (parent compound or degradation product) from its affiliation to one cluster, but also to select representative substances from a large data set in order to answer some specific questions regarding their behavior in the environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effective virtual screening strategy focusing on the identification of novel Bruton's tyrosine kinase inhibitors.

PubMed

Xiao, Jianhu; Zhang, Shengping; Luo, Minghao; Zou, Yi; Zhang, Yihua; Lai, Yisheng

2015-07-01

Dysregulation of the B-cell receptor (BCR) signaling pathway plays a vital role in the pathogenesis and development of B-cell malignancies. Bruton's tyrosine kinase (BTK), a key component in the BCR signaling, has been validated as a valuable target for the treatment of B-cell malignancies. In an attempt to find novel and potent BTK inhibitors, both ligand- and structure-based pharmacophore models were generated using Discovery Studio 2.5 and Ligandscout 3.11 with the aim of screening the ChemBridge database. The resulting hits were then subjected to sequential docking experiments using two independent docking programs, CDOCKER and Glide. Molecules displaying high glide scores and H-bond interactions with the key residue Met477 in both of the docking programs were retained. Drug-like criteria including Lipinski's rule of five and ADMET properties filters were employed for further refinement of the retrieved hits. By clustering, eight promising compounds with novel chemical scaffolds were finally selected and the top two ranking compounds were evaluated by molecular dynamics simulation. We believe that these compounds are of great potential in BTK inhibition and will be used for further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites.

PubMed

Omura, S; Ikeda, H; Ishikawa, J; Hanamoto, A; Takahashi, C; Shinose, M; Takahashi, Y; Horikawa, H; Nakazawa, H; Osonoe, T; Kikuchi, H; Shiba, T; Sakaki, Y; Hattori, M

2001-10-09

Streptomyces avermitilis is a soil bacterium that carries out not only a complex morphological differentiation but also the production of secondary metabolites, one of which, avermectin, is commercially important in human and veterinary medicine. The major interest in this genus Streptomyces is the diversity of its production of secondary metabolites as an industrial microorganism. A major factor in its prominence as a producer of the variety of secondary metabolites is its possession of several metabolic pathways for biosynthesis. Here we report sequence analysis of S. avermitilis, covering 99% of its genome. At least 8.7 million base pairs exist in the linear chromosome; this is the largest bacterial genome sequence, and it provides insights into the intrinsic diversity of the production of the secondary metabolites of Streptomyces. Twenty-five kinds of secondary metabolite gene clusters were found in the genome of S. avermitilis. Four of them are concerned with the biosyntheses of melanin pigments, in which two clusters encode tyrosinase and its cofactor, another two encode an ochronotic pigment derived from homogentiginic acid, and another polyketide-derived melanin. The gene clusters for carotenoid and siderophore biosyntheses are composed of seven and five genes, respectively. There are eight kinds of gene clusters for type-I polyketide compound biosyntheses, and two clusters are involved in the biosyntheses of type-II polyketide-derived compounds. Furthermore, a polyketide synthase that resembles phloroglucinol synthase was detected. Eight clusters are involved in the biosyntheses of peptide compounds that are synthesized by nonribosomal peptide synthetases. These secondary metabolite clusters are widely located in the genome but half of them are near both ends of the genome. The total length of these clusters occupies about 6.4% of the genome.

Boronated tartrolon antibiotic produced by symbiotic cellulose-degrading bacteria in shipworm gills.

PubMed

Elshahawi, Sherif I; Trindade-Silva, Amaro E; Hanora, Amro; Han, Andrew W; Flores, Malem S; Vizzoni, Vinicius; Schrago, Carlos G; Soares, Carlos A; Concepcion, Gisela P; Distel, Dan L; Schmidt, Eric W; Haygood, Margo G

2013-01-22

Shipworms are marine wood-boring bivalve mollusks (family Teredinidae) that harbor a community of closely related Gammaproteobacteria as intracellular endosymbionts in their gills. These symbionts have been proposed to assist the shipworm host in cellulose digestion and have been shown to play a role in nitrogen fixation. The genome of one strain of Teredinibacter turnerae, the first shipworm symbiont to be cultivated, was sequenced, revealing potential as a rich source of polyketides and nonribosomal peptides. Bioassay-guided fractionation led to the isolation and identification of two macrodioloide polyketides belonging to the tartrolon class. Both compounds were found to possess antibacterial properties, and the major compound was found to inhibit other shipworm symbiont strains and various pathogenic bacteria. The gene cluster responsible for the synthesis of these compounds was identified and characterized, and the ketosynthase domains were analyzed phylogenetically. Reverse-transcription PCR in addition to liquid chromatography and high-resolution mass spectrometry and tandem mass spectrometry revealed the transcription of these genes and the presence of the compounds in the shipworm, suggesting that the gene cluster is expressed in vivo and that the compounds may fulfill a specific function for the shipworm host. This study reports tartrolon polyketides from a shipworm symbiont and unveils the biosynthetic gene cluster of a member of this class of compounds, which might reveal the mechanism by which these bioactive metabolites are biosynthesized.

A Constraint-Based Approach to Acquisition of Word-Final Consonant Clusters in Turkish Children

ERIC Educational Resources Information Center

Gokgoz-Kurt, Burcu

2017-01-01

The current study provides a constraint-based analysis of L1 word-final consonant cluster acquisition in Turkish child language, based on the data originally presented by Topbas and Kopkalli-Yavuz (2008). The present analysis was done using [?]+obstruent consonant cluster acquisition. A comparison of Gradual Learning Algorithm (GLA) under…

Ion-neutral Clustering of Bile Acids in Electrospray Ionization Across UPLC Flow Regimes

NASA Astrophysics Data System (ADS)

Brophy, Patrick; Broeckling, Corey D.; Murphy, James; Prenni, Jessica E.

2018-02-01

Bile acid authentic standards were used as model compounds to quantitatively evaluate complex in-source phenomenon on a UPLC-ESI-TOF-MS operated in the negative mode. Three different diameter columns and a ceramic-based microfluidic separation device were utilized, allowing for detailed descriptions of bile acid behavior across a wide range of flow regimes and instantaneous concentrations. A custom processing algorithm based on correlation analysis was developed to group together all ion signals arising from a single compound; these grouped signals produce verified compound spectra for each bile acid at each on-column mass loading. Significant adduction was observed for all bile acids investigated under all flow regimes and across a wide range of bile acid concentrations. The distribution of bile acid containing clusters was found to depend on the specific bile acid species, solvent flow rate, and bile acid concentration. Relative abundancies of each cluster changed non-linearly with concentration. It was found that summing all MS level (low collisional energy) ions and ion-neutral adducts arising from a single compound improves linearity across the concentration range (0.125-5 ng on column) and increases the sensitivity of MS level quantification. The behavior of each cluster roughly follows simple equilibrium processes consistent with our understanding of electrospray ionization mechanisms and ion transport processes occurring in atmospheric pressure interfaces. [Figure not available: see fulltext.

Peak clustering in two-dimensional gas chromatography with mass spectrometric detection based on theoretical calculation of two-dimensional peak shapes: the 2DAid approach.

PubMed

van Stee, Leo L P; Brinkman, Udo A Th

2011-10-28

A method is presented to facilitate the non-target analysis of data obtained in temperature-programmed comprehensive two-dimensional (2D) gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-ToF-MS). One main difficulty of GC×GC data analysis is that each peak is usually modulated several times and therefore appears as a series of peaks (or peaklets) in the one-dimensionally recorded data. The proposed method, 2DAid, uses basic chromatographic laws to calculate the theoretical shape of a 2D peak (a cluster of peaklets originating from the same analyte) in order to define the area in which the peaklets of each individual compound can be expected to show up. Based on analyte-identity information obtained by means of mass spectral library searching, the individual peaklets are then combined into a single 2D peak. The method is applied, amongst others, to a complex mixture containing 362 analytes. It is demonstrated that the 2D peak shapes can be accurately predicted and that clustering and further processing can reduce the final peak list to a manageable size. Copyright © 2011 Elsevier B.V. All rights reserved.

IDENTIFICATION OF UNANTICIPATED COMPOUNDS BY HIGH RESOLUTION MASS SPECTROMETRY

EPA Science Inventory

Localized outbreaks of acute illness could result from deliberate addition of unanticipated
compounds into water, air, or food. Cancer clusters resulting from long-term exposure to trace-
levels of compounds are more difficult to detect, but can be revealed by epidemiolog...

Classification of clouds sampled at the puy de Dôme (France) based on 10 yr of monitoring of their physicochemical properties

NASA Astrophysics Data System (ADS)

Deguillaume, L.; Charbouillot, T.; Joly, M.; Vaïtilingom, M.; Parazols, M.; Marinoni, A.; Amato, P.; Delort, A.-M.; Vinatier, V.; Flossmann, A.; Chaumerliac, N.; Pichon, J. M.; Houdier, S.; Laj, P.; Sellegri, K.; Colomb, A.; Brigante, M.; Mailhot, G.

2014-02-01

Long-term monitoring of the chemical composition of clouds (73 cloud events representing 199 individual samples) sampled at the puy de Dôme (pdD) station (France) was performed between 2001 and 2011. Physicochemical parameters, as well as the concentrations of the major organic and inorganic constituents, were measured and analyzed by multicomponent statistical analysis. Along with the corresponding back-trajectory plots, this allowed for distinguishing four different categories of air masses reaching the summit of the pdD: polluted, continental, marine and highly marine. The statistical analysis led to the determination of criteria (concentrations of inorganic compounds, pH) that differentiate each category of air masses. Highly marine clouds exhibited high concentrations of Na+ and Cl-; the marine category presented lower concentration of ions but more elevated pH. Finally, the two remaining clusters were classified as "continental" and "polluted"; these clusters had the second-highest and highest levels of NH4+, NO3-, and SO24-, respectively. This unique data set of cloud chemical composition is then discussed as a function of this classification. Total organic carbon (TOC) is significantly higher in polluted air masses than in the other categories, which suggests additional anthropogenic sources. Concentrations of carboxylic acids and carbonyls represent around 10% of the organic matter in all categories of air masses and are studied for their relative importance. Iron concentrations are significantly higher for polluted air masses and iron is mainly present in its oxidation state (+II) in all categories of air masses. Finally, H2O2 concentrations are much more varied in marine and highly marine clouds than in polluted clouds, which are characterized by the lowest average concentration of H2O2. This data set provides concentration ranges of main inorganic and organic compounds for modeling purposes on multiphase cloud chemistry.

Revisiting benzene cluster cations for the chemical ionization of dimethyl sulfide and select volatile organic compounds

DOE PAGES

Kim, Michelle J.; Zoerb, Matthew C.; Campbell, Nicole R.; ...

2016-04-05

Here, benzene cluster cations were revisited as a sensitive and selective reagent ion for the chemical ionization of dimethyl sulfide (DMS) and a select group of volatile organic compounds (VOCs). Laboratory characterization was performed using both a new set of compounds (i.e., DMS, β-caryophyllene) as well as previously studied VOCs (i.e., isoprene, α-pinene). Using a field deployable chemical-ionization time-of-flight mass spectrometer (CI-ToFMS), benzene cluster cations demonstrated high sensitivity (> 1 ncps ppt −1) to DMS, isoprene, and α-pinene standards. Parallel measurements conducted using a chemical-ionization quadrupole mass spectrometer, with a much weaker electric field, demonstrated that ion–molecule reactions likely proceed through amore » combination of ligand-switching and direct charge transfer mechanisms. Laboratory tests suggest that benzene cluster cations may be suitable for the selective ionization of sesquiterpenes, where minimal fragmentation (< 25 %) was observed for the detection of β-caryophyllene, a bicyclic sesquiterpene. The in-field stability of benzene cluster cations using CI-ToFMS was examined in the marine boundary layer during the High Wind Gas Exchange Study (HiWinGS). The use of benzene cluster cation chemistry for the selective detection of DMS was validated against an atmospheric pressure ionization mass spectrometer, where measurements from the two instruments were highly correlated ( R 2 > 0.95, 10 s averages) over a wide range of sampling conditions.« less

The Draft Genome Sequence of Actinokineospora bangkokensis 44EHWT Reveals the Biosynthetic Pathway of the Antifungal Thailandin Compounds with Unusual Butylmalonyl-CoA Extender Units.

PubMed

Greule, Anja; Intra, Bungonsiri; Flemming, Stephan; Rommel, Marcel G E; Panbangred, Watanalai; Bechthold, Andreas

2016-11-23

We report the draft genome sequence of Actinokineospora bangkokensis 44EHW T , the producer of the antifungal polyene compounds, thailandins A and B. The sequence contains 7.45 Mb, 74.1% GC content and 35 putative gene clusters for the biosynthesis of secondary metabolites. There are three gene clusters encoding large polyketide synthases of type I. Annotation of the ORF functions and targeted gene disruption enabled us to identify the cluster for thailandin biosynthesis. We propose a plausible biosynthetic pathway for thailandin, where the unusual butylmalonyl-CoA extender unit is incorporated and results in an untypical side chain.

Strategies, linkers and coordination polymers for high-performance sorbents

DOEpatents

Matzger, Adam J.; Wong-Foy, Antek G.; Lebel, Oliver

2015-09-15

A linking ligand compound includes three bidentate chemical moieties distributed about a central chemical moiety. Another linking ligand compound includes a bidentate linking ligand and a monodentate chemical moiety. Coordination polymers include a plurality of metal clusters linked together by residues of the linking ligand compounds.

Influence of lanthanides on spin-relaxation and spin-structure in a family of Fe 7Ln 4 single molecule magnets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prodius, Denis; Mereacre, Valeriu; Singh, Prashant

A family of isostructural undecanuclear 3d–4f coordination clusters of formula [Fe III 7Ln III 4O 4(OH) 3(tea) 2(Htea) 3(Piv) 7(H 2O) 2(NO 3) 3], where Ln = Y (1), Gd (2), Tb (3), Dy (4); PivH ≡ pivalic acid and H 3tea ≡ triethanolamine, was synthesised in this paper. The central Fe7 core of the coordination cluster can be described in terms of two {Fe 4O 2} butterfly motifs sharing a common body Fe atom. The two Fe 4 mean-planes subtend a dihedral angle of ca. 72°. The Tb (3) and Dy (4) compounds show Single Molecule Magnet (SMM) behaviourmore » as confirmed by ac-susceptibility and μ-SQUID measurements. Furthermore, 57Fe Mössbauer spectra of 1–4 confirm the presence of high-spin Fe III sites. The spectra of all complexes in the high temperature range (30–300 K) show broad overlapping doublets which were assigned to the body and wing-tip pairs of metal ions within the Fe 7 core. The low temperature Mössbauer spectra show dependence on the nature of the rare-earth metal as a result of its interaction with the iron sites. Finally, we observed a transition from fast (2), to intermediate (1) and very slow (frozen) (3, 4) spin fluctuation phenomena in these compounds.« less

Influence of lanthanides on spin-relaxation and spin-structure in a family of Fe 7Ln 4 single molecule magnets

DOE PAGES

Prodius, Denis; Mereacre, Valeriu; Singh, Prashant; ...

2018-03-01

A family of isostructural undecanuclear 3d–4f coordination clusters of formula [Fe III 7Ln III 4O 4(OH) 3(tea) 2(Htea) 3(Piv) 7(H 2O) 2(NO 3) 3], where Ln = Y (1), Gd (2), Tb (3), Dy (4); PivH ≡ pivalic acid and H 3tea ≡ triethanolamine, was synthesised in this paper. The central Fe7 core of the coordination cluster can be described in terms of two {Fe 4O 2} butterfly motifs sharing a common body Fe atom. The two Fe 4 mean-planes subtend a dihedral angle of ca. 72°. The Tb (3) and Dy (4) compounds show Single Molecule Magnet (SMM) behaviourmore » as confirmed by ac-susceptibility and μ-SQUID measurements. Furthermore, 57Fe Mössbauer spectra of 1–4 confirm the presence of high-spin Fe III sites. The spectra of all complexes in the high temperature range (30–300 K) show broad overlapping doublets which were assigned to the body and wing-tip pairs of metal ions within the Fe 7 core. The low temperature Mössbauer spectra show dependence on the nature of the rare-earth metal as a result of its interaction with the iron sites. Finally, we observed a transition from fast (2), to intermediate (1) and very slow (frozen) (3, 4) spin fluctuation phenomena in these compounds.« less

Photoemission and Auger-electron spectroscopic study of the Chevrel-phase compound FexMo6S8

NASA Astrophysics Data System (ADS)

Fujimori, A.; Sekita, M.; Wada, H.

1986-05-01

The electronic structure of the Chevrel-phase compound FexMo6S8 has been studied by photoemission and Auger-electron spectroscopy. Core-level shifts suggest a large charge transfer from the Fe atoms to the Mo6S8 clusters and a small Mo-to-S charge transfer within the cluster. Line-shape asymmetry in the core levels indicates that the density of states (DOS) at the Fermi level has a finite S 3p component as well as the dominant Mo 3d character. Satellite structure and exchange splitting in the Fe core levels point to weak Fe 3d-S 3p hybridization in spite of the short Fe-S distances comparable to that in FeS. The x-ray and ultraviolet valence-band photoemission spectra and the Mo 4d partial DOS obtained by deconvoluting the Mo M4,5VV Auger spectrum are compared with existing band-structure calculations, and the Mo 4d-S 3p bonding character, the structure of the Mo 4d-derived conduction band etc., are discussed. In particular, it is shown that the conduction-band structure is sensitive to the noncubic distortion of the crystal through changes in the intercluster Mo 4d-S 3p hybridization. A pronounced final-state effect is found in the Mo M4,5N2,3V Auger spectrum and is attributed to strong 4p-4d intershell coupling.

Gap junctions contribute to anchorage-independent clustering of breast cancer cells.

PubMed

Gava, Fabien; Rigal, Lise; Mondesert, Odile; Pesce, Elise; Ducommun, Bernard; Lobjois, Valérie

2018-02-27

Cancer cell aggregation is a key process involved in the formation of clusters of circulating tumor cells. We previously reported that cell-cell adhesion proteins, such as E-cadherin, and desmosomal proteins are involved in cell aggregation to form clusters independently of cell migration or matrix adhesion. Here, we investigated the involvement of gap junction intercellular communication (GJIC) during anchorage-independent clustering of MCF7 breast adenocarcinoma cells. We used live cell image acquisition and analysis to monitor the kinetics of MCF7 cell clustering in the presence/absence of GJIC pharmacological inhibitors and to screen a LOPAC® bioactive compound library. We also used a calcein transfer assay and flow cytometry to evaluate GJIC involvement in cancer cell clustering. We first demonstrated that functional GJIC are established in the early phase of cancer cell aggregation. We then showed that pharmacological inhibition of GJIC using tonabersat and meclofenamate delayed MCF7 cell clustering and reduced calcein transfer. We also found that brefeldin A, an inhibitor of vesicular trafficking, which we identified by screening a small compound library, and latrunculin A, an actin cytoskeleton-disrupting agent, both impaired MCF7 cell clustering and calcein transfer. Our results demonstrate that GJIC are involved from the earliest stages of anchorage-independent cancer cell aggregation. They also give insights into the regulatory mechanisms that could modulate the formation of clusters of circulating tumor cells.

Synthesis and characterization of new fluorescent styrene-containing carborane derivatives: the singular quenching role of a phenyl substituent.

PubMed

Ferrer-Ugalde, Albert; Juárez-Pérez, Emilio José; Teixidor, Francesc; Viñas, Clara; Sillanpää, Reijo; Pérez-Inestrosa, Ezequiel; Núñez, Rosario

2012-01-09

A set of neutral and anionic carborane derivatives in which the styrenyl fragment is introduced as a fluorophore group has been successfully synthesized and characterized. The reaction of the monolithium salts of 1-Ph-1,2-C(2)B(10)H(11), 1-Me-1,2-C(2)B(10)H(11) and 1,2-C(2)B(10)H(12) with one equivalent of 4-vinylbenzyl chloride leads to the formation of compounds 1-3, whereas the reaction of the dilithium salt of 1,2-C(2)B(10)H(12) with two equivalents of 4-vinylbenzyl chloride gives disubstituted compound 4. The closo clusters were degraded using the classical method, KOH in EtOH, to afford the corresponding nido species, which were isolated as tetramethylammonium salts. The crystal structure of the four closo compounds 1-4 were analyzed by X-ray diffraction. All compounds, except 1, display emission properties, with quantum yields dependent on the nature of the cluster (closo or nido) and the substituent on the second C(cluster) atom. In general, closo compounds 2-4 exhibit high fluorescence emission, whereas the presence of a nido cluster produces a decrease of the emission intensity. The presence of a phenyl group bonded to the C(cluster) results in an excellent electron-acceptor unit that produces a quenching of the fluorescence. DFT calculations have confirmed the charge-separation state in 1 to explain the quenching of the fluorescence and the key role of the carboranyl fragment in this luminescent process. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pineapple [Ananas comosus (L.) Merr].

PubMed

Yabor, Lourdes; Espinosa, Patricia; Arencibia, Ariel D; Lorenzo, José C

2006-01-01

A procedure for pineapple [Ananas comosus (L.) Merr.] genetic transformation is described, which involves temporary immersion bioreactors (TIB) for selection of transgenic plants. Success in the production of transgenic pineapple plants combines tissue culture factors. Firstly, the use of regenerable pineapple callus as starting material for transformation whose cells shown to be competent for Agrobacterium infection. Secondly, the used of filtered callus, resulting in homogeneously sized clusters, thereby increasing the contact between the cell surfaces and A. tumefaciens and releasing phenolic compounds which induce Agrobacterium virulence. Thirdly, regeneration of primary plants without selection pressure, that allowing a massive production of putative transgenic pineapples. Finally, we support that TIB technology is a powerful system to recover nonchimera transgenic plants by micropropagation with the use of an adequate selection agent.

Electronic structure and properties of magnetic defects in Co(1+x)Al(1-x) and Fe(1+x)Al(1-x) alloys. Ph.D. Thesis - Paris Univ.

NASA Technical Reports Server (NTRS)

Abbe, D.

1984-01-01

CoAl and FeAl compounds are developed along two directions. Magnetic susceptibility and specific heat at low temperature on (NiCo)Al and (CoFe)Al ternary alloys are in good agreement with band calculations. Results on magnetization and specific heat under field at low temperature on nonstoichiometric compounds show clearly the importance of the nearest neighbor effects. In the case of CoAl, the isolated cobalt atoms substituting aluminum are characterized by a Kondo behavior, and, for FeAl, the isolated extra iron atoms are magnetic and polarize the matrix. Moreover, for the two compounds, clusters of higher order play a considerable part in the magnetic properties for CoAl, these clusters also seem to be characterized by a Kondo behavior, for FeAl, these clusters whose moment is higher than in the case of isolated atoms, could be constituted of excess parts of iron atoms.

[Antioxidant properties of cluster rhenium compounds and their effect on erythropoiesis of rats with guerin carcinoma].

PubMed

Voronkova, Y S; Babiy, S O; Ivans'kar, L V; Shtemenko, O V; Shtemenko, N I

2015-01-01

Biochemical characteristics of kidneys, pe- ripheral blood and bone marrow of rats in model of tumor growth under introduction of cisplatin and cis-tetrachlorodi-μ-isobutyratodirhenium(III), cis-Re2(i-C3H7COO)2Cl4 (I) have been investigated. It was shown that introduction of I alone and together with cisplatin led to decrease of biochemical markers of oxidation of lipids and proteins in tissue homogenates of the kidneys, change of enzyme activity in the urea and tissue homogenates of the kidneys, by a decrease of filtration function of kidneys. Introduction of nanoliposomal forms of the rhenium cluster compound led to a practically normal morphological picture of bone marrow and increase of the RBC (by 60%) with normalization of hematocrit counts, and decrease of quantities of destructed RBC (3.2 times) in comparison with the tumor-bearing animals. A tentative scheme of influence of cluster rhenium compound on erythropoiesis through regulation of synthesis of erythropoietin in kidneys has been proposed.

Structural diversities induced by cation sizes in a series of fluorogermanophosphates: A2[GeF2(HPO4)2] (A = Na, K, Rb, NH4, and Cs).

PubMed

Chen, Zhang-Gai; Huang, Xia; Zhuang, Rong-Chuan; Zhang, Yu; Liu, Xin; Shi, Tao; Wang, Shuai-Hua; Wu, Shao-Fan; Mi, Jin-Xiao; Huang, Ya-Xi

2017-09-12

Germanophosphates, in comparison with other metal phosphates, have been less studied but potentially exhibit more diverse structural chemistry with wide applications. Herein we applied a hydro-/solvo-fluorothermal route to make use of both the "tailor effect" of fluoride for the formation of low dimensional anionic clusters and the presence of alkali cations of different sizes to align the anionic clusters to control the overall crystal symmetries of germanophosphates. The synergetic effects of fluoride and alkali cations led to structural changes from chain-like structures to layered structures in a series of five novel fluorogermanophosphates: A 2 [GeF 2 (HPO 4 ) 2 ] (A = Na, K, Rb, NH 4 , and Cs, denoted as Na, K, Rb, NH4, and Cs). Although these fluorogermanophosphates have stoichiometrically equivalent formulas, they feature different anionic clusters, diverse structural dimensionalities, and contrasting crystal symmetries. Chain-like structures were observed for the compounds with the smaller sized alkali ions (Na + , K + , and Rb + ), whereas layered structures were found for those containing the larger sized cations ((NH 4 ) + and Cs + ). Specifically, monoclinic space groups were observed for the Na, K, Rb, and NH4 compounds, whereas a tetragonal space group P4/mbm was found for the Cs compound. These compounds provide new insights into the effects of cation sizes on the anionic clusters built from GeO 4 F 2 octahedra and HPO 4 tetrahedra as well as their influences on the overall structural symmetries in germanophosphates. Further characterization including IR spectroscopy and thermal analyses for all five compounds is also presented.

Identification of the Main Regulator Responsible for Synthesis of the Typical Yellow Pigment Produced by Trichoderma reesei

PubMed Central

Derntl, Christian; Rassinger, Alice; Srebotnik, Ewald; Mach, Robert L.

2016-01-01

ABSTRACT The industrially used ascomycete Trichoderma reesei secretes a typical yellow pigment during cultivation, while other Trichoderma species do not. A comparative genomic analysis suggested that a putative secondary metabolism cluster, containing two polyketide-synthase encoding genes, is responsible for the yellow pigment synthesis. This cluster is conserved in a set of rather distantly related fungi, including Acremonium chrysogenum and Penicillium chrysogenum. In an attempt to silence the cluster in T. reesei, two genes of the cluster encoding transcription factors were individually deleted. For a complete genetic proof-of-function, the genes were reinserted into the genomes of the respective deletion strains. The deletion of the first transcription factor (termed yellow pigment regulator 1 [Ypr1]) resulted in the full abolishment of the yellow pigment formation and the expression of most genes of this cluster. A comparative high-pressure liquid chromatography (HPLC) analysis of supernatants of the ypr1 deletion and its parent strain suggested the presence of several yellow compounds in T. reesei that are all derived from the same cluster. A subsequent gas chromatography/mass spectrometry analysis strongly indicated the presence of sorbicillin in the major HPLC peak. The presence of the second transcription factor, termed yellow pigment regulator 2 (Ypr2), reduces the yellow pigment formation and the expression of most cluster genes, including the gene encoding the activator Ypr1. IMPORTANCE Trichoderma reesei is used for industry-scale production of carbohydrate-active enzymes. During growth, it secretes a typical yellow pigment. This is not favorable for industrial enzyme production because it makes the downstream process more complicated and thus increases operating costs. In this study, we demonstrate which regulators influence the synthesis of the yellow pigment. Based on these data, we also provide indication as to which genes are under the control of these regulators and are finally responsible for the biosynthesis of the yellow pigment. These genes are organized in a cluster that is also found in other industrially relevant fungi, such as the two antibiotic producers Penicillium chrysogenum and Acremonium chrysogenum. The targeted manipulation of a secondary metabolism cluster is an important option for any biotechnologically applied microorganism. PMID:27520818

The influence of volatile semiochemicals from stink bug eggs and oviposition-damaged plants on the foraging behaviour of the egg parasitoid Telenomus podisi.

PubMed

Michereff, M F F; Borges, M; Aquino, M F S; Laumann, R A; Mendes Gomes, A C M; Blassioli-Moraes, M C

2016-10-01

During host selection, physical and chemical stimuli provide important cues that modify search behaviours of natural enemies. We evaluated the influence of volatiles released by eggs and egg extracts of the stink bug Euschistus heros and by soybean plants treated with the eggs and egg extracts on Telenomus podisi foraging behaviour. Responses to volatiles were evaluated in Y-tube olfactometers after exposure to (1) one egg cluster for 24 h; (2) plants with eggs laid by the stink bug, tested at 24, 48, and 72 h after treatment; (3) plants with eggs laid artificially, tested at 24, 48, and 72 h after treatment; and (4) plants treated with acetone or hexane extracts of eggs. Telenomus podisi was attracted to volatiles emitted by one egg cluster and to acetone extracts of one egg cluster, but not to air or acetone controls. There were no responses to odours of plants treated with eggs or egg extracts. Analysis of acetone extracts of egg clusters by gas chromatography revealed the major components were saturated and unsaturated fatty acids, including hexadecanoic acid, linoleic acid, and (Z)-9-octadecenoic acid. Our results suggest that one egg cluster and the acetone extract of one egg cluster contain volatile compounds that can modify T. podisi foraging behaviour, and that the amounts of these compounds, probably together with some minor compounds, are important for host recognition by T. podisi. Also, the oviposition damage or egg extracts on the plant did not elicit indirect defences that attracted Telenomus podisi.

Structure of transition-metal cluster compounds: Use of an additional orbital resulting from the f, g character of spd bond orbitals*

PubMed Central

Pauling, Linus

1977-01-01

A general theory of the structure of complexes of the transition metals is developed on the basis of the enneacovalence of the metals and the requirements of the electroneutrality principle. An extra orbital may be provided through the small but not negligible amount of f and g character of spd bond orbitals, and an extra electron or electron pair may be accepted in this orbital for a single metal or a cluster to neutralize the positive electric charge resulting from the partial ionic character of the bonds with ligands, such as the carbonyl group. Examples of cluster compounds of cobalt, ruthenium, rhodium, osmium, and gold are discussed. PMID:16592470

Structure of transition-metal cluster compounds: Use of an additional orbital resulting from the f, g character of spd bond orbitals.

PubMed

Pauling, L

1977-12-01

A general theory of the structure of complexes of the transition metals is developed on the basis of the enneacovalence of the metals and the requirements of the electroneutrality principle. An extra orbital may be provided through the small but not negligible amount of f and g character of spd bond orbitals, and an extra electron or electron pair may be accepted in this orbital for a single metal or a cluster to neutralize the positive electric charge resulting from the partial ionic character of the bonds with ligands, such as the carbonyl group. Examples of cluster compounds of cobalt, ruthenium, rhodium, osmium, and gold are discussed.

Employing linear tetranuclear [Zn4(COO)4(OH)2] clusters as building subunits to construct a new Zn(II) coordination polymer with tunable luminescent properties

NASA Astrophysics Data System (ADS)

Li, Wu-Wu; Zhang, Zun-Ting

2016-02-01

A new Zn(II) coordination polymer, [Zn2(btc) (biimpy) (OH)]n (1 H3btc = 1,3,5-benzenetricarboxylic acid, biimpy = 2,6-bis(1-imdazoly)pyridine) has been successfully synthesized and characterized by elemental analysis, powder single crystal X-ray diffraction analyses. Compound 1 features a 3D framework employing linear tetranuclear [Zn4(COO)4(OH)2] cluster as building subunits. Topological analysis reveals it represents a (3,10)-connected structural topology by viewing btc3-, linear tetranuclear clusters and biimpy as 3-connected nodes, 10-connected nodes, linear linkers, respectively. Moreover, the thermal stability and luminescent property of compound 1 have been well investigated.

α-cluster versus non-α-cluster decay of the excited compound nucleus Ce124* using the dynamical cluster-decay model

NASA Astrophysics Data System (ADS)

Kaur, Arshdeep; Chopra, Sahila; Gupta, Raj K.

2014-03-01

The dynamical cluster-decay model (DCM), an extended version of the preformed cluster model (PCM) for ground-state (T =0) decays, is applied to study the decay of the proton-rich compound nucleus Ce124* formed in the S32 + Mo92 reaction at an above-barrier beam energy of 150 MeV. Application of the statistical code pace4 to experimental data shows large deviations in all cases of proton clusters' (2p, 3p, and 4p) evaporation residue (ER) and the non-α nucleus Be6 intermediate mass fragment (IMF). Furthermore, the α-nucleus Be8 decay is not observed in this experiment (not even the upper limit is given). Using the DCM, with effects of deformations up to hexadecapole and "compact" orientations included, for the best-fitted cross sections of 2p and 3p ERs and of Li5 and Be6 IMFs, the relative cross section of Be8 is found to be more than that of Be6, possibly due to the α-nucleus structure of Be8. The same is shown to be true for C12 versus C10, i.e., α-nuclei clusters are populated strongly relative to non-α clusters, similar to what was predicted by one of us (R.K.G.) et al. [S. Kumar, D. Bir, and R. K. Gupta, Phys. Rev. C 51, 1762 (1995), 10.1103/PhysRevC.51.1762] for ground-state decays of such nuclei and the decay of Ba116* formed in the Ni58 + Ni58 reaction at various compound nucleus excitation energies [R. K. Gupta et al., J. Phys. G: Nucl. Part. Phys. 32, 345 (2006), 10.1088/0954-3899/32/3/009]. The only parameter of the DCM is the neck-length ΔR, related to the "barrier-lowering" parameter. The compound nucleus formation probability and "barrier-lowering/-modification" effects are analyzed, and the role of varying the deformations of Be6 and/or Be8 nuclei on relative cross sections is studied, since the measured deformations are not available. The ones used here are from relativistic mean-field calculations [β2(6Be )=-0.087 and β2(8Be)=-0.094]. Calculations are also presented for a beam energy of 140 MeV, supporting the above result.

Classification via Clustering for Predicting Final Marks Based on Student Participation in Forums

ERIC Educational Resources Information Center

Lopez, M. I.; Luna, J. M.; Romero, C.; Ventura, S.

2012-01-01

This paper proposes a classification via clustering approach to predict the final marks in a university course on the basis of forum data. The objective is twofold: to determine if student participation in the course forum can be a good predictor of the final marks for the course and to examine whether the proposed classification via clustering…

Similarities among receptor pockets and among compounds: analysis and application to in silico ligand screening.

PubMed

Fukunishi, Yoshifumi; Mikami, Yoshiaki; Nakamura, Haruki

2005-09-01

We developed a new method to evaluate the distances and similarities between receptor pockets or chemical compounds based on a multi-receptor versus multi-ligand docking affinity matrix. The receptors were classified by a cluster analysis based on calculations of the distance between receptor pockets. A set of low homologous receptors that bind a similar compound could be classified into one cluster. Based on this line of reasoning, we proposed a new in silico screening method. According to this method, compounds in a database were docked to multiple targets. The new docking score was a slightly modified version of the multiple active site correction (MASC) score. Receptors that were at a set distance from the target receptor were not included in the analysis, and the modified MASC scores were calculated for the selected receptors. The choice of the receptors is important to achieve a good screening result, and our clustering of receptors is useful to this purpose. This method was applied to the analysis of a set of 132 receptors and 132 compounds, and the results demonstrated that this method achieves a high hit ratio, as compared to that of a uniform sampling, using a receptor-ligand docking program, Sievgene, which was newly developed with a good docking performance yielding 50.8% of the reconstructed complexes at a distance of less than 2 A RMSD.

Water-Soluble Phosphine-Protected Au₁₁ Clusters: Synthesis, Electronic Structure, and Chiral Phase Transfer in a Synergistic Fashion.

PubMed

Yao, Hiroshi; Iwatsu, Mana

2016-04-05

Synthesis of atomically precise, water-soluble phosphine-protected gold clusters is still currently limited probably due to a stability issue. We here present the synthesis, magic-number isolation, and exploration of the electronic structures as well as the asymmetric conversion of triphenylphosphine monosulfonate (TPPS)-protected gold clusters. Electrospray ionization mass spectrometry and elemental analysis result in the primary formation of Au11(TPPS)9Cl undecagold cluster compound. Magnetic circular dichroism (MCD) spectroscopy clarifies that extremely weak transitions are present in the low-energy region unresolved in the UV-vis absorption, which can be due to the Faraday B-terms based on the magnetically allowed transitions in the cluster. Asymmetric conversion without changing the nuclearity is remarkable by the chiral phase transfer in a synergistic fashion, which yields a rather small anisotropy factor (g-factor) of at most (2.5-7.0) × 10(-5). Quantum chemical calculations for model undecagold cluster compounds are then used to evaluate the optical and chiroptical responses induced by the chiral phase transfer. On this basis, we find that the Au core distortion is ignorable, and the chiral ion-pairing causes a slight increase in the CD response of the Au11 cluster.

The effect of antioxidant concentration of N-isopropyl-N-phenyl-p-phenylenediamine, and 2,2,4-trimethyl-1,2-dihydroquinoline and mixing time of physical properties, thermal properties, mechanical properties and microstructure on natural rubber compound

NASA Astrophysics Data System (ADS)

Budiarto

2017-03-01

Study the influence of high concentrations of antioxidants N-isopropyl-N-phenyl-p-phenylenediamine (IPPD) and 2,2,4-trimethyl-1,2-dihydroquinoline (TMQ) and the mixing time of the vulcanization physical properties, thermal properties, mechanical properties and structure micro on natural rubber compound has been done. The purpose of this study is to compare the effect of anti-oxidants types IPPD and TMQ and mixing time of vulcanization of the physical properties, mechanical properties, microstructure and elemental composition of the synthesis of natural rubber compound. Processes of vulcanization with variations in the concentration of antioxidant IPPD and TMQ: 2, 3, and 4 grams and mixing time: 20, 30, and 40 minutes. Analysis characterization of physical properties and mechanical properties of natural rubber compound showed that the maturity value 0,499Nm (TMQ) and 0.489 Nm (IPPD), Mooney viscosity value of 26.7 (TMQ) and 20.8 (IPPD), the value of the elongation at break 583.75 % (IPPD), and 552.63% (TMQ) as well as the value of tensile strength of 28.108 M.Pa (TMQ), and 27.986 M.Pa (IPPD). Analysis of thermal properties of natural rubber compound antioxidant IPPD with DTA shows there are three endothermic peak on the curve that is temperature 405°C, 550°C and 660°C and tested by TGA showed that the curve of the total reduction in the sample are 81.745% and compound rubber antioxidant TMQ with the analysis of DTA also contained 3 endothermic peak at a temperature 397,21°C, 514,02°C, and 610,27°C and TGA analysis shows the curve of the total sample of 82.356% reduction. Gsi fun group analysis rubber-antioxidant compound IPPD / TMQ with FTIR spectrophotometer shows some typical infrared absorption peak at the wave number (1 / λ) 833-895 cm-1 for cluster / CH bonds, 1,313 cm-1 for group / single bond Si-O, 1368 cm-1 to g ugus / single bond CC, 1507 cm-1, for cluster / bond C = C, 1665 cm-1For cluster / bond-C = O, 2128 cm-1 is the group / bond CN single, 3371cm-1 for group-OH, 3506 cm-1 for cluster / CH3 bond and 3585 cm-1 showed the presence of vibration in the cluster / bond-NH. The results of morphological observation with SEM produces uneven surface (homogeneous) and are compatible at 2000 times magnification, as well as the test composition by EDX spectroscopy showed that the biggest element in the rubber compound is carbon and Zn, S, Ca, Si, Mg, Al, N. This shows that the natural rubber compound antioxidant IPPD / TMQ meet the standard of "Mechanical Properties of Industrial Tyre rubber Compounds".

Selected Plant Metabolites Involved in Oxidation-Reduction Processes during Bud Dormancy and Ontogenetic Development in Sweet Cherry Buds (Prunus avium L.).

PubMed

Baldermann, Susanne; Homann, Thomas; Neugart, Susanne; Chmielewski, Frank-M; Götz, Klaus-Peter; Gödeke, Kristin; Huschek, Gerd; Morlock, Getrud E; Rawel, Harshadrai M

2018-05-17

Many biochemical processes are involved in regulating the consecutive transition of different phases of dormancy in sweet cherry buds. An evaluation based on a metabolic approach has, as yet, only been partly addressed. The aim of this work, therefore, was to determine which plant metabolites could serve as biomarkers for the different transitions in sweet cherry buds. The focus here was on those metabolites involved in oxidation-reduction processes during bud dormancy, as determined by targeted and untargeted mass spectrometry-based methods. The metabolites addressed included phenolic compounds, ascorbate/dehydroascorbate, reducing sugars, carotenoids and chlorophylls. The results demonstrate that the content of phenolic compounds decrease until the end of endodormancy. After a long period of constancy until the end of ecodormancy, a final phase of further decrease followed up to the phenophase open cluster. The main phenolic compounds were caffeoylquinic acids, coumaroylquinic acids and catechins, as well as quercetin and kaempferol derivatives. The data also support the protective role of ascorbate and glutathione in the para- and endodormancy phases. Consistent trends in the content of reducing sugars can be elucidated for the different phenophases of dormancy, too. The untargeted approach with principle component analysis (PCA) clearly differentiates the different timings of dormancy giving further valuable information.

Influence of sticking vs non-sticking limits of moment of inertia and higher order deformations in the decay of 214,216Rn* compound systems

NASA Astrophysics Data System (ADS)

Mittal, Rajni; Jain, Deepika; Sharma, Manoj K.

2017-12-01

The dynamical cluster decay model (DCM) is employed to explore the relative effect of sticking (IS) and non-sticking (INS) limits of moment of inertia (MOI) in the decay of hot and rotating 214,216Rn* compound nuclei, formed in 16,18O + 198Pt reactions. Beside this, the nuclear deformation effects i.e. quadrupole β2 (static and dynamic) and higher order static deformations up to hexadecapole (β4) are duly incorporated and studied within DCM. The influence of both 'INS/IS' addressing rotational energy component and 'deformations' is gauged through the barrier characteristics, preformation factor and barrier lowering effects. The experimentally given ER and ff data is addressed by optimizing the neck-length ΔR, that strongly depends on the limiting angular momentum, which in turn depends on the sticking or non-sticking limits of interaction. In addition to this, the influence of increase in energy and neutron number is probed in reference to ER survival probability of Rn compound nucleus. Finally, the ff cross-sections of 214,216Rn* nuclei are predicted within sticking limit of moment of inertia as the same seems to be more suitable for such decay paths.

A Novel Coordination Polymer Based on Trinuclear Cobalt Building Blocks Cluster: Synthesis, Crystal Structure, and Properties

NASA Astrophysics Data System (ADS)

Lu, J. F.; Tang, Z. H.; Shi, J.; Ge, H. G.; Jiang, M.; Song, J.; Jin, L. X.

2017-12-01

The title compound {[Co3(μ3-OH)(μ2-H2O)2(H2O)5(BTC)2] · 6H2O} n (H3BTC is a 1,3,5-benzenetricarboxylic acid) was prepared and characterized by single crystal and powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric and elemental analyses. The single crystal X-ray diffraction reveals that the title compound consists of 1D infinite zigzag chains which were constructed by trinuclear cobalt cluster and BTC3- ligand. Neighbouring above-mentioned 1D infinite zigzag chains are further linked by intermolecular hydrogen bonding to form a 3D supermolecular structure. In addition, the luminescent properties of the title compound were investigated.

Dietary Strategies Implicated in the Prevention and Treatment of Metabolic Syndrome

PubMed Central

de la Iglesia, Rocio; Loria-Kohen, Viviana; Zulet, Maria Angeles; Martinez, Jose Alfredo; Reglero, Guillermo; Ramirez de Molina, Ana

2016-01-01

Metabolic syndrome (MetS) is established as the combination of central obesity and different metabolic disturbances, such as insulin resistance, hypertension and dyslipidemia. This cluster of factors affects approximately 10%–50% of adults worldwide and the prevalence has been increasing in epidemic proportions over the last years. Thus, dietary strategies to treat this heterogenic disease are under continuous study. In this sense, diets based on negative-energy-balance, the Mediterranean dietary pattern, n-3 fatty acids, total antioxidant capacity and meal frequency have been suggested as effective approaches to treat MetS. Furthermore, the type and percentage of carbohydrates, the glycemic index or glycemic load, and dietary fiber content are some of the most relevant aspects related to insulin resistance and impaired glucose tolerance, which are important co-morbidities of MetS. Finally, new studies focused on the molecular action of specific nutritional bioactive compounds with positive effects on the MetS are currently an objective of scientific research worldwide. The present review summarizes some of the most relevant dietary approaches and bioactive compounds employed in the treatment of the MetS to date. PMID:27834920

CheS-Mapper - Chemical Space Mapping and Visualization in 3D.

PubMed

Gütlein, Martin; Karwath, Andreas; Kramer, Stefan

2012-03-17

Analyzing chemical datasets is a challenging task for scientific researchers in the field of chemoinformatics. It is important, yet difficult to understand the relationship between the structure of chemical compounds, their physico-chemical properties, and biological or toxic effects. To that respect, visualization tools can help to better comprehend the underlying correlations. Our recently developed 3D molecular viewer CheS-Mapper (Chemical Space Mapper) divides large datasets into clusters of similar compounds and consequently arranges them in 3D space, such that their spatial proximity reflects their similarity. The user can indirectly determine similarity, by selecting which features to employ in the process. The tool can use and calculate different kind of features, like structural fragments as well as quantitative chemical descriptors. These features can be highlighted within CheS-Mapper, which aids the chemist to better understand patterns and regularities and relate the observations to established scientific knowledge. As a final function, the tool can also be used to select and export specific subsets of a given dataset for further analysis.

CheS-Mapper - Chemical Space Mapping and Visualization in 3D

PubMed Central

2012-01-01

Analyzing chemical datasets is a challenging task for scientific researchers in the field of chemoinformatics. It is important, yet difficult to understand the relationship between the structure of chemical compounds, their physico-chemical properties, and biological or toxic effects. To that respect, visualization tools can help to better comprehend the underlying correlations. Our recently developed 3D molecular viewer CheS-Mapper (Chemical Space Mapper) divides large datasets into clusters of similar compounds and consequently arranges them in 3D space, such that their spatial proximity reflects their similarity. The user can indirectly determine similarity, by selecting which features to employ in the process. The tool can use and calculate different kind of features, like structural fragments as well as quantitative chemical descriptors. These features can be highlighted within CheS-Mapper, which aids the chemist to better understand patterns and regularities and relate the observations to established scientific knowledge. As a final function, the tool can also be used to select and export specific subsets of a given dataset for further analysis. PMID:22424447

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allendorf, M.D.; Arsenlis, A.; Bastasz, R.

Titanium nitride (TiN) films deposited by chemical vapor deposition (CVD) techniques are of interest for a wide range of commercial applications. In this report, the authors describe a mechanism that predicts Tin film growth rates from TiCl{sub 4}/NH{sub 3} mixtures as a function of process parameters, including inlet reactant concentrations, substrate temperatures, reactor pressures, and total gas flow rates. Model predictions were verified by comparison with the results of TiN deposition experiments in the literature and with measurements made in a new stagnation-flow reactor developed for the purpose of testing deposition mechanisms such as this. In addition, they describe abmore » initio calculations that predict thermodynamic properties for titanium-containing compounds. The results of calculations using Moeller-Plesset perturbation theory, density functional theory, and coupled cluster theory are encouraging and suggest that these methods can be used to estimate thermodynamic data that are essential for the development of CVD models involving transition-metal compounds. Finally, measurements of the adsorption and desorption kinetics of NH{sub 3} on TiN films using temperature-programmed desorption are described and their relevance to TiN CVD and mechanism development are discussed.« less

Efficient Agent-Based Cluster Ensembles

NASA Technical Reports Server (NTRS)

Agogino, Adrian; Tumer, Kagan

2006-01-01

Numerous domains ranging from distributed data acquisition to knowledge reuse need to solve the cluster ensemble problem of combining multiple clusterings into a single unified clustering. Unfortunately current non-agent-based cluster combining methods do not work in a distributed environment, are not robust to corrupted clusterings and require centralized access to all original clusterings. Overcoming these issues will allow cluster ensembles to be used in fundamentally distributed and failure-prone domains such as data acquisition from satellite constellations, in addition to domains demanding confidentiality such as combining clusterings of user profiles. This paper proposes an efficient, distributed, agent-based clustering ensemble method that addresses these issues. In this approach each agent is assigned a small subset of the data and votes on which final cluster its data points should belong to. The final clustering is then evaluated by a global utility, computed in a distributed way. This clustering is also evaluated using an agent-specific utility that is shown to be easier for the agents to maximize. Results show that agents using the agent-specific utility can achieve better performance than traditional non-agent based methods and are effective even when up to 50% of the agents fail.

Phylum-wide comparative genomics unravel the diversity of secondary metabolism in Cyanobacteria

DOE PAGES

Calteau, Alexandra; Fewer, David P.; Latifi, Amel; ...

2014-11-18

Cyanobacteria are an ancient lineage of photosynthetic bacteria from which hundreds of natural products have been described, including many notorious toxins but also potent natural products of interest to the pharmaceutical and biotechnological industries. Many of these compounds are the products of non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) pathways. However, current understanding of the diversification of these pathways is largely based on the chemical structure of the bioactive compounds, while the evolutionary forces driving their remarkable chemical diversity are poorly understood. We carried out a phylum-wide investigation of genetic diversification of the cyanobacterial NRPS and PKS pathways formore » the production of bioactive compounds. 452 NRPS and PKS gene clusters were identified from 89 cyanobacterial genomes, revealing a clear burst in late-branching lineages. Our genomic analysis further grouped the clusters into 286 highly diversified cluster families (CF) of pathways. Some CFs appeared vertically inherited, while others presented a more complex evolutionary history. Only a few horizontal gene transfers were evidenced amongst strongly conserved CFs in the phylum, while several others have undergone drastic gene shuffling events, which could result in the observed diversification of the pathways. In addition to toxin production, several NRPS and PKS gene clusters are devoted to important cellular processes of these bacteria such as nitrogen fixation and iron uptake. The majority of the biosynthetic clusters identified here have unknown end products, highlighting the power of genome mining for the discovery of new natural products.« less

Phylum-wide comparative genomics unravel the diversity of secondary metabolism in Cyanobacteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calteau, Alexandra; Fewer, David P.; Latifi, Amel

Cyanobacteria are an ancient lineage of photosynthetic bacteria from which hundreds of natural products have been described, including many notorious toxins but also potent natural products of interest to the pharmaceutical and biotechnological industries. Many of these compounds are the products of non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) pathways. However, current understanding of the diversification of these pathways is largely based on the chemical structure of the bioactive compounds, while the evolutionary forces driving their remarkable chemical diversity are poorly understood. We carried out a phylum-wide investigation of genetic diversification of the cyanobacterial NRPS and PKS pathways formore » the production of bioactive compounds. 452 NRPS and PKS gene clusters were identified from 89 cyanobacterial genomes, revealing a clear burst in late-branching lineages. Our genomic analysis further grouped the clusters into 286 highly diversified cluster families (CF) of pathways. Some CFs appeared vertically inherited, while others presented a more complex evolutionary history. Only a few horizontal gene transfers were evidenced amongst strongly conserved CFs in the phylum, while several others have undergone drastic gene shuffling events, which could result in the observed diversification of the pathways. In addition to toxin production, several NRPS and PKS gene clusters are devoted to important cellular processes of these bacteria such as nitrogen fixation and iron uptake. The majority of the biosynthetic clusters identified here have unknown end products, highlighting the power of genome mining for the discovery of new natural products.« less

Pharmacophore modeling, molecular docking and molecular dynamics studies on natural products database to discover novel skeleton as non-purine xanthine oxidase inhibitors.

PubMed

Peng, Jiale; Li, Yaping; Zhou, Yeheng; Zhang, Li; Liu, Xingyong; Zuo, Zhili

2018-05-29

Gout is a common inflammatory arthritis caused by the deposition of urate crystals within joints. It is increasingly in prevalence during the past few decades as shown by the epidemiological survey results. Xanthine oxidase (XO) is a key enzyme to transfer hypoxanthine and xanthine to uric acid, whose overproduction leads to gout. Therefore, inhibiting the activity of xanthine oxidase is an important way to reduce the production of urate. In the study, in order to identify the potential natural products targeting XO, pharmacophore modeling was employed to filter databases. Here, two methods, pharmacophore based on ligand and pharmacophore based on receptor-ligand, were constructed by Discovery Studio. Then GOLD was used to refine the potential compounds with higher fitness scores. Finally, molecular docking and dynamics simulations were employed to analyze the interactions between compounds and protein. The best hypothesis was set as a 3D query to screen database, returning 785 and 297 compounds respectively. A merged set of the above 1082 molecules was subjected to molecular docking, which returned 144 hits with high-fitness scores. These molecules were clustered in four main kinds depending on different backbones. What is more, molecular docking showed that the representative compounds established key interactions with the amino acid residues in the protein, and the RMSD and RMSF of molecular dynamics results showed that these compounds can stabilize the protein. The information represented in the study confirmed previous reports. And it may assist to discover and design new backbones as potential XO inhibitors based on natural products.

A comparative bear model for immobility-induced osteopenia

NASA Technical Reports Server (NTRS)

Milbury, P. E.; Vaughan, M. R.; Farley, S.; Matula, G. J. Jr; Convertino, V. A.; Matson, W. R.

1998-01-01

The National Institutes of Health (NIH) and the National Aeronautics and Space Administration (NASA) are seeking solutions to the human problem of osteopenia, or immobility-induced bone loss. Bears, during winter dormancy, appear uniquely exempted from the debilitating effects of immobility osteopenia. NIH and ESA, Inc. are creating a large database of metabolic information on human ambulatory and bedrest plasma samples for comparison with metabolic data obtained from bear plasma samples collected in different seasons. The database generated from NASA's HR113 human bedrest study showed a clear difference between plasma samples of ambulatory and immobile subjects through cluster analysis using compounds determined by high performance liquid chromatography with coulometric electrochemical array detection (HPLC-EC). We collected plasma samples from black bears (Ursus americanus) across 4 seasons and from 3 areas and subjected them to similar analysis, with particular attention to compounds that changed significantly in the NASA human study. We found seasonal differences in 28 known compounds and 33 unknown compounds. A final database contained 40 known and 120 unknown peaks that were reliably assayed in all bear and human samples; these were the primary data set for interspecies comparison. Six unidentified compounds changed significantly but differentially in wintering bears and immobile humans. The data are discussed in light of current theories regarding dormancy, starvation, and anabolic metabolism. Work is in progress by ESA Laboratories on a larger database to confirm these findings prior to a chemical isolation and identification effort. This research could lead to new pharmaceuticals or dietary interventions for the treatment of immobility osteopenia.

Deciphering the underlying mechanisms of Diesun Miaofang in traumatic injury from a systems pharmacology perspective

PubMed Central

ZHENG, CHUN-SONG; FU, CHANG-LONG; PAN, CAI-BIN; BAO, HONG-JUAN; CHEN, XING-QIANG; YE, HONG-ZHI; YE, JIN-XIA; WU, GUANG-WEN; LI, XI-HAI; XU, HUI-FENG; XU, XIAO-JIE; LIU, XIAN-XIANG

2015-01-01

Diesun Miaofang (DSMF) is a traditional herbal formula, which has been reported to activate blood, remove stasis, promote qi circulation and relieve pain. DSMF holds a great promise for the treatment of traumatic injury in an integrative and holistic manner. However, its underlying mechanisms remain to be elucidated. In the present study, a systems pharmacology model, which integrated cluster ligands, human intestinal absorption and aqueous solution prediction, chemical space mapping, molecular docking and network pharmacology techniques were used. The compounds from DSMF were diverse in the clusters and chemical space. The majority of the compounds exhibited drug-like properties. A total of 59 compounds were identified to interact with 16 potential targets. In the herb-compound-target network, the majority of compounds acted on only one target; however, a small number of compounds acted on a large number of targets, up to a maximum of 12. The comparison of key topological properties in compound-target networks associated with the above efficacy intuitively demonstrated that potential active compounds possessed diverse functions. These results successfully explained the polypharmcological mechanism underlying the efficiency of DSMF for the treatment of traumatic injury as well as provided insight into potential novel therapeutic strategies for traumatic injury from herbal medicine. PMID:25891262

Comparative genomic analysis of secondary metabolite biosynthetic gene clusters in 207 isolates of Fusarium

USDA-ARS?s Scientific Manuscript database

Fusarium species are known for their ability to produce secondary metabolites (SMs), including plant hormones, pigments, mycotoxins, and other compounds with potential agricultural, pharmaceutical, and biotechnological impact. Understanding the distribution of SM biosynthetic gene clusters across th...

Fe-Cluster Compounds of Chalcogenides: Candidates for Rare-Earth-Free Permanent Magnet and Magnetic Nodal-Line Topological Material.

PubMed

Zhao, Xin; Wang, Cai-Zhuang; Kim, Minsung; Ho, Kai-Ming

2017-12-04

Fe-cluster-based crystal structures are predicted for chalcogenides Fe 3 X 4 (X = S, Se, Te) using an adaptive genetic algorithm. Topologically different from the well-studied layered structures of iron chalcogenides, the newly predicted structures consist of Fe clusters that are either separated by the chalcogen atoms or connected via sharing of the vertex Fe atoms. Using first-principles calculations, we demonstrate that these structures have competitive or even lower formation energies than the experimentally synthesized Fe 3 X 4 compounds and exhibit interesting magnetic and electronic properties. In particular, we show that Fe 3 Te 4 can be a good candidate as a rare-earth-free permanent magnet and Fe 3 S 4 can be a magnetic nodal-line topological material.

Supramolecular clusters between carbohydrates and concave pyridines. Detection in the gas phase by resonance-enhanced multi-photon ionization reflectron time-of-flight mass spectrometer.

PubMed

Liebig, Timo; Lüning, Ulrich; Grotemeyer, Jürgen

2006-01-01

For the first time the formation of supramolecular clusters between concave pyridines and different carbohydrates could be observed in the gas phase. The different clusters have been investigated by means of laser desorption into a supersonic beam followed by resonant multi photon excitation yielding mass spectra with high intensity of the different cluster. These preliminary results open a way for the investigations of the hydrogen bonds in these compounds.

Spectroscopic and computational studies of ionic clusters as models of solvation and atmospheric reactions

NASA Astrophysics Data System (ADS)

Kuwata, Keith T.

Ionic clusters are useful as model systems for the study of fundamental processes in solution and in the atmosphere. Their structure and reactivity can be studied in detail using vibrational predissociation spectroscopy, in conjunction with high level ab initio calculations. This thesis presents the applications of infrared spectroscopy and computation to a variety of gas-phase cluster systems. A crucial component of the process of stratospheric ozone depletion is the action of polar stratospheric clouds (PSCs) to convert the reservoir species HCl and chlorine nitrate (ClONO2) to photochemically labile compounds. Quantum chemistry was used to explore one possible mechanism by which this activation is effected: Cl- + ClONO2 /to Cl2 + NO3- eqno(1)Correlated ab initio calculations predicted that the direct reaction of chloride ion with ClONO2 is facile, which was confirmed in an experimental kinetics study. In the reaction a weakly bound intermediate Cl2-NO3- is formed, with ~70% of the charge localized on the nitrate moiety. This enables the Cl2-NO3- cluster to be well solvated even in bulk solution, allowing (1) to be facile on PSCs. Quantum chemistry was also applied to the hydration of nitrosonium ion (NO+), an important process in the ionosphere. The calculations, in conjunction with an infrared spectroscopy experiment, revealed the structure of the gas-phase clusters NO+(H2O)n. The large degree of covalent interaction between NO+ and the lone pairs of the H2O ligands is contrasted with the weak electrostatic bonding between iodide ion and H2O. Finally, the competition between ion solvation and solvent self-association is explored for the gas-phase clusters Cl/-(H2O)n and Cl-(NH3)n. For the case of water, vibrational predissociation spectroscopy reveals less hydrogen bonding among H2O ligands than predicted by ab initio calculations. Nevertheless, for n /ge 5, cluster structure is dominated by water-water interactions, with Cl- only partially solvated by the water cluster. Preliminary infrared spectra and computations on Cl- (NH3)n indicate that NH3 preferentially binds to Cl- ion instead of forming inter-solvent networks.

Fungal secondary metabolites - strategies to activate silent gene clusters.

PubMed

Brakhage, Axel A; Schroeckh, Volker

2011-01-01

Filamentous fungi produce a multitude of low molecular weight bioactive compounds. The increasing number of fungal genome sequences impressively demonstrated that their biosynthetic potential is far from being exploited. In fungi, the genes required for the biosynthesis of a secondary metabolite are clustered. Many of these bioinformatically newly discovered secondary metabolism gene clusters are silent under standard laboratory conditions. Consequently, no product can be found. This review summarizes the current strategies that have been successfully applied during the last years to activate these silent gene clusters in filamentous fungi, especially in the genus Aspergillus. The techniques take advantage of genome mining, vary from the simple search for compounds with bioinformatically predicted physicochemical properties up to methods that exploit a probable interaction of microorganisms. Until now, the majority of successful approaches have been based on molecular biology like the generation of gene "knock outs", promoter exchange, overexpression of transcription factors or other pleiotropic regulators. Moreover, strategies based on epigenetics opened a new avenue for the elucidation of the regulation of secondary metabolite formation and will certainly continue to play a significant role for the elucidation of cryptic natural products. The conditions under which a given gene cluster is naturally expressed are largely unknown. One technique is to attempt to simulate the natural habitat by co-cultivation of microorganisms from the same ecosystem. This has already led to the activation of silent gene clusters and the identification of novel compounds in Aspergillus nidulans. These simulation strategies will help discover new natural products in the future, and may also provide fundamental new insights into microbial communication. Copyright © 2010 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2013-01-01

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

Organotin Selenide Clusters and Hybrid Capsules.

PubMed

Dehnen, Stefanie; Hanau, Katharina; Rinn, Niklas; Argentari, Mario

2018-05-22

Several compounds with unique structural motifs that have already been known from organotin sulfide chemistry, but remained unprecedented in organotin selenide chemistry so far, have been synthesized. The reaction of [(R1Sn)4Se6] (R1 = CMe2CH2C(O)Me) with N2H4·H2O/(SiMe3)2Se and with PhN2H3/(SiMe3)2Se led to the formation of [{(R2Sn)2SnSe4}2(µ-Se)2] (1) and [{(R3Sn)2SnSe4}2(µ-Se)2] (2) (R2 = CMe2CH2C(Me)NNH2, R3 = CMe2CH2C(Me)NNPhH), respectively. Addition of o-phthalaldehyde to [(R2Sn)4Se6] yielded a cluster with intramolecular bridging of the organic groups, [(R4Sn2)2Se6] (3, R4 = (CMe2CH2C(Me)NNCH)2C6H4). The introduction of organic ligands with longer chains finally allowed the isolation of inorganic-organic capsules of the type [(µ-R)3(Sn3Se4)2]X2, with R = (CMe2CH2C(Me)NNHC(O))2(CH2)4, X = [SnC3], Cl (4a, 4b) or R = CMe2CH2C(Me)NNH)2, X = [SnCl3] (5). The capsules enclose solvent molecules and/or anions as guests. All compounds were characterized via single-crystal X-ray diffraction, NMR spectroscopy and mass spectrometry. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of high explosive particles using cluster secondary ion mass spectrometry.

PubMed

Gillen, Greg; Mahoney, Christine; Wight, Scott; Lareau, Richard

2006-01-01

The use of secondary ion mass spectrometry (SIMS) for the detection and spatially resolved analysis of individual high explosive particles is described. A C(8) (-) carbon cluster primary ion beam was used in a commercial SIMS instrument to analyze samples of high explosives dispersed as particles on silicon substrates. In comparison with monatomic primary ion bombardment, the carbon cluster primary ion beam was found to greatly enhance characteristic secondary ion signals from the explosive compounds while causing minimal beam-induced degradation. The resistance of these compounds to degradation under ion bombardment allows explosive particles to be analyzed under high primary ion dose bombardment (dynamic SIMS) conditions, facilitating the rapid acquisition of spatially resolved molecular information. The use of cluster SIMS combined with computer control of the sample stage position allows for the automated identification and counting of explosive particle distributions on silicon surfaces. This will be useful for characterizing the efficiency of transfer of particulates in trace explosive detection portal collectors and/or swipes utilized for ion mobility spectrometry applications.

Li3Ge3Se6: the first ternary lithium germanium selenide with interesting ∞[Ge6Se12]n chains constructed by ethane-like [Ge2Se6]6- clusters.

PubMed

Li, Guangmao; Zhen, Ni; Chu, Yu; Zhou, Zhongxiang

2017-12-21

Li 3 Ge 3 Se 6 , the first compound of the ternary Li/Ge/Se system, has been synthesized. Note that interesting 1D ∞ [Ge 6 Se 12 ] n chains constructed by ethane-like [Ge 2 Se 6 ] 6- clusters were discovered in its structure. Investigations on the structures of all the [Ge 2 Se 6 ] 6- cluster-containing compounds have shown that only in Li 3 Ge 3 Se 6 are there 1D chains composed of [Ge 2 Se 6 ] 6- clusters, which result from the space limitation within the tunnels surrounded by LiSe 6 octahedra. Raman spectrum was obtained to demonstrate the existence of Ge-Ge bonds. UV-visible-NIR diffuse reflection spectrum showed an optical bandgap of 2.08 eV. Theoretical calculations based on first principles have also been performed for its band structure and density of states to analyze its structure-property relationship.

Ternary alloy material prediction using genetic algorithm and cluster expansion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Chong

2015-12-01

This thesis summarizes our study on the crystal structures prediction of Fe-V-Si system using genetic algorithm and cluster expansion. Our goal is to explore and look for new stable compounds. We started from the current ten known experimental phases, and calculated formation energies of those compounds using density functional theory (DFT) package, namely, VASP. The convex hull was generated based on the DFT calculations of the experimental known phases. Then we did random search on some metal rich (Fe and V) compositions and found that the lowest energy structures were body centered cube (bcc) underlying lattice, under which we didmore » our computational systematic searches using genetic algorithm and cluster expansion. Among hundreds of the searched compositions, thirteen were selected and DFT formation energies were obtained by VASP. The stability checking of those thirteen compounds was done in reference to the experimental convex hull. We found that the composition, 24-8-16, i.e., Fe 3VSi 2 is a new stable phase and it can be very inspiring to the future experiments.« less

Toward An Understanding of Cluster Evolution: A Deep X-Ray Selected Cluster Catalog from ROSAT

NASA Technical Reports Server (NTRS)

Jones, Christine; Oliversen, Ronald (Technical Monitor)

2002-01-01

In the past year, we have focussed on studying individual clusters found in this sample with Chandra, as well as using Chandra to measure the luminosity-temperature relation for a sample of distant clusters identified through the ROSAT study, and finally we are continuing our study of fossil groups. For the luminosity-temperature study, we compared a sample of nearby clusters with a sample of distant clusters and, for the first time, measured a significant change in the relation as a function of redshift (Vikhlinin et al. in final preparation for submission to Cape). We also used our ROSAT analysis to select and propose for Chandra observations of individual clusters. We are now analyzing the Chandra observations of the distant cluster A520, which appears to have undergone a recent merger. Finally, we have completed the analysis of the fossil groups identified in ROM observations. In the past few months, we have derived X-ray fluxes and luminosities as well as X-ray extents for an initial sample of 89 objects. Based on the X-ray extents and the lack of bright galaxies, we have identified 16 fossil groups. We are comparing their X-ray and optical properties with those of optically rich groups. A paper is being readied for submission (Jones, Forman, and Vikhlinin in preparation).

Discovery of the New Plant Growth-Regulating Compound LYXLF2 Based on Manipulating the Halogenase in Amycolatopsis orientalis.

PubMed

Xu, Li; Han, Ting; Ge, Mei; Zhu, Li; Qian, XiuPing

2016-09-01

Analysis of the Amycolatopsis orientalis HCCB10007 genome revealed new gene clusters involved in natural product biosynthesis that were not associated with the production of known compounds. Halogenases are a type of tailoring enzymes that are usually found within these secondary gene clusters. In this study, we identified an indole-type halometabolite 6-chrolo-1H-indole-3-carboxamide, named LYXLF2, by whole genome mining and metabolic profiling of a flavin-dependent halogenase mutant. LYXLF2 is a new plant growth-regulating compound that promotes root elongation. The results of this study demonstrated that the special gene knock-out/comparative metabolic profiling approach provides a powerful tool for the discovery of novel natural products by genome mining.

Accurate prediction of secondary metabolite gene clusters in filamentous fungi.

PubMed

Andersen, Mikael R; Nielsen, Jakob B; Klitgaard, Andreas; Petersen, Lene M; Zachariasen, Mia; Hansen, Tilde J; Blicher, Lene H; Gotfredsen, Charlotte H; Larsen, Thomas O; Nielsen, Kristian F; Mortensen, Uffe H

2013-01-02

Biosynthetic pathways of secondary metabolites from fungi are currently subject to an intense effort to elucidate the genetic basis for these compounds due to their large potential within pharmaceutics and synthetic biochemistry. The preferred method is methodical gene deletions to identify supporting enzymes for key synthases one cluster at a time. In this study, we design and apply a DNA expression array for Aspergillus nidulans in combination with legacy data to form a comprehensive gene expression compendium. We apply a guilt-by-association-based analysis to predict the extent of the biosynthetic clusters for the 58 synthases active in our set of experimental conditions. A comparison with legacy data shows the method to be accurate in 13 of 16 known clusters and nearly accurate for the remaining 3 clusters. Furthermore, we apply a data clustering approach, which identifies cross-chemistry between physically separate gene clusters (superclusters), and validate this both with legacy data and experimentally by prediction and verification of a supercluster consisting of the synthase AN1242 and the prenyltransferase AN11080, as well as identification of the product compound nidulanin A. We have used A. nidulans for our method development and validation due to the wealth of available biochemical data, but the method can be applied to any fungus with a sequenced and assembled genome, thus supporting further secondary metabolite pathway elucidation in the fungal kingdom.

Reexamining cluster radioactivity in trans-lead nuclei with consideration of specific density distributions in daughter nuclei and clusters

NASA Astrophysics Data System (ADS)

Qian, Yibin; Ren, Zhongzhou; Ni, Dongdong

2016-08-01

We further investigate the cluster emission from heavy nuclei beyond the lead region in the framework of the preformed cluster model. The refined cluster-core potential is constructed by the double-folding integral of the density distributions of the daughter nucleus and the emitted cluster, where the radius or the diffuseness parameter in the Fermi density distribution formula is determined according to the available experimental data on the charge radii and the neutron skin thickness. The Schrödinger equation of the cluster-daughter relative motion is then solved within the outgoing Coulomb wave-function boundary conditions to obtain the decay width. It is found that the present decay width of cluster emitters is clearly enhanced as compared to that in the previous case, which involved the fixed parametrization for the density distributions of daughter nuclei and clusters. Among the whole procedure, the nuclear deformation of clusters is also introduced into the calculations, and the degree of its influence on the final decay half-life is checked to some extent. Moreover, the effect from the bubble density distribution of clusters on the final decay width is carefully discussed by using the central depressed distribution.

In vitro motility evaluation of aggregated cancer cells by means of automatic image processing.

PubMed

De Hauwer, C; Darro, F; Camby, I; Kiss, R; Van Ham, P; Decaesteker, C

1999-05-01

Set up of an automatic image processing based method that enables the motility of in vitro aggregated cells to be evaluated for a number of hours. Our biological model included the PC-3 human prostate cancer cell line growing as a monolayer on the bottom of Falcon plastic dishes containing conventional culture media. Our equipment consisted of an incubator, an inverted phase contrast microscope, a Charge Coupled Device (CCD) video camera, and a computer equipped with an image processing software developed in our laboratory. This computer-assisted microscope analysis of aggregated cells enables global cluster motility to be evaluated. This analysis also enables the trajectory of each cell to be isolated and parametrized within a given cluster or, indeed, the trajectories of individual cells outside a cluster. The results show that motility inside a PC-3 cluster is not restricted to slight motion due to cluster expansion, but rather consists of a marked cell movement within the cluster. The proposed equipment enables in vitro aggregated cell motility to be studied. This method can, therefore, be used in pharmacological studies in order to select anti-motility related compounds. The compounds selected by the equipment described could then be tested in vivo as potential anti-metastatic.

Understanding the polypharmacological anticancer effects of Xiao Chai Hu Tang via a computational pharmacological model

PubMed Central

ZHENG, CHUN-SONG; WU, YIN-SHENG; BAO, HONG-JUAN; XU, XIAO-JIE; CHEN, XING-QIANG; YE, HONG-ZHI; WU, GUANG-WEN; XU, HUI-FENG; LI, XI-HAI; CHEN, JIA-SHOU; LIU, XIAN-XIANG

2014-01-01

Xiao Chai Hu Tang (XCHT), a traditional herbal formula, is widely administered as a cancer treatment. However, the underlying molecular mechanisms of its anticancer effects are not fully understood. In the present study, a computational pharmacological model that combined chemical space mapping, molecular docking and network analysis was employed to predict which chemical compounds in XCHT are potential inhibitors of cancer-associated targets, and to establish a compound-target (C-T) network and compound-compound (C-C) association network. The identified compounds from XCHT demonstrated diversity in chemical space. Furthermore, they occupied regions of chemical space that were the same, or close to, those occupied by drug or drug-like compounds that are associated with cancer, according to the Therapeutic Targets Database. The analysis of the molecular docking and the C-T network demonstrated that the potential inhibitors possessed the properties of promiscuous drugs and combination therapies. The C-C network was classified into four clusters and the different clusters contained various multi-compound combinations that acted on different targets. The study indicated that XCHT has a polypharmacological role in treating cancer and the potential inhibitory components of XCHT require further investigation as potential therapeutic strategies for cancer patients. PMID:24926384

Fe-Cluster Compounds of Chalcogenides: Candidates for Rare-Earth-Free Permanent Magnet and Magnetic Nodal-Line Topological Material

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Xin; Wang, Cai-Zhuang; Kim, Minsung

Here, Fe-cluster-based crystal structures are predicted for chalcogenides Fe 3X 4 (X = S, Se, Te) using an adaptive genetic algorithm. Topologically different from the well-studied layered structures of iron chalcogenides, the newly predicted structures consist of Fe clusters that are either separated by the chalcogen atoms or connected via sharing of the vertex Fe atoms. Additionally, using first-principles calculations, we demonstrate that these structures have competitive or even lower formation energies than the experimentally synthesized Fe 3X 4 compounds and exhibit interesting magnetic and electronic properties. In particular, we show that Fe 3X 4 can be a good candidatemore » as a rare-earth-free permanent magnet and Fe 3X 4 can be a magnetic nodal-line topological material.« less

Fe-Cluster Compounds of Chalcogenides: Candidates for Rare-Earth-Free Permanent Magnet and Magnetic Nodal-Line Topological Material

DOE PAGES

Zhao, Xin; Wang, Cai-Zhuang; Kim, Minsung; ...

2017-11-13

Here, Fe-cluster-based crystal structures are predicted for chalcogenides Fe 3X 4 (X = S, Se, Te) using an adaptive genetic algorithm. Topologically different from the well-studied layered structures of iron chalcogenides, the newly predicted structures consist of Fe clusters that are either separated by the chalcogen atoms or connected via sharing of the vertex Fe atoms. Additionally, using first-principles calculations, we demonstrate that these structures have competitive or even lower formation energies than the experimentally synthesized Fe 3X 4 compounds and exhibit interesting magnetic and electronic properties. In particular, we show that Fe 3X 4 can be a good candidatemore » as a rare-earth-free permanent magnet and Fe 3X 4 can be a magnetic nodal-line topological material.« less

Synthesis, Characterization, and Reactivity of Functionalized Trinuclear Iron–Sulfur Clusters – A New Class of Bioinspired Hydrogenase Models

PubMed Central

Kaiser, Manuel; Knör, Günther

2015-01-01

The air- and moisture-stable iron–sulfur carbonyl clusters Fe3S2(CO)7(dppm) (1) and Fe3S2(CO)7(dppf) (2) carrying the bisphosphine ligands bis(diphenylphosphanyl)methane (dppm) and 1,1′-bis(diphenylphosphanyl)ferrocene (dppf) were prepared and fully characterized. Two alternative synthetic routes based on different thionation reactions of triiron dodecacarbonyl were tested. The molecular structures of the methylene-bridged compound 1 and the ferrocene-functionalized derivative 2 were determined by single-crystal X-ray diffraction. The catalytic reactivity of the trinuclear iron–sulfur cluster core for proton reduction in solution at low overpotential was demonstrated. These deeply colored bisphosphine-bridged sulfur-capped iron carbonyl systems are discussed as promising candidates for the development of new bioinspired model compounds of iron-based hydrogenases. PMID:26512211

Chiral Silver-Lanthanide Metal-Organic Frameworks Comprised of One-Dimensional Triple Right-Handed Helical Chains Based on [Ln7(μ3-OH)8]13+ Clusters.

PubMed

Guo, Yan; Zhang, Lijuan; Muhammad, Nadeem; Xu, Yan; Zhou, Yunshan; Tang, Fang; Yang, Shaowei

2018-02-05

Three new isostructural chiral silver-lanthanide heterometal-organic frameworks [Ag 3 Ln 7 (μ 3 -OH) 8 (bpdc) 6 (NO 3 ) 3 (H 2 O) 6 ](NO 3 )·2H 2 O [Ln = Eu (1), Tb (2, Sm (3); H 2 bpdc = 2,2'-bipyridine-3,3'-dicarboxylic acid] based on heptanuclear lanthanide clusters [Ln 7 (μ 3 -OH) 8 ] 13+ comprised of one-dimensional triple right-handed helical chains were hydrothermally synthesized. Various means such as UV-vis spectroscopy, IR spectroscopy, elemental analysis, powder X-ray diffraction, and thermogravimetric/differential thermal analysis were used to characterize the compounds, wherein compound 3 was crystallographically characterized. In the structure of compound 3, eight μ 3 -OH - groups link seven Sm 3+ ions, forming a heptanuclear cluster, [Sm 7 (μ 3 -OH) 8 ] 13+ , and the adjacent [Sm 7 (μ 3 -OH) 8 ] 13+ clusters are linked by the carboxylic groups of bpdc 2- ligands, leading to the formation of a one-dimensional triple right-handed helical chain. The adjacent triple right-handed helical chains are further joined together by coordinating the pyridyl N atoms of the bpdc 2- ligands with Ag + , resulting in a chiral three-dimensional silver(I)-lanthanide(III) heterometal-organic framework with one-dimensional channels wherein NO 3 - anions and crystal lattice H 2 O molecules are trapped. The compounds were studied systematically with respect to their photoluminescence properties and energy-transfer mechanism, and it was found that H 2 bpdc (the energy level for the triplet states of the ligand H 2 bpdc is 21505 cm -1 ) can sensitize Eu 3+ luminescence more effectively than Tb 3+ and Sm 3+ luminescence because of effective energy transfer from bpdc 2- to Eu 3+ under excitation in compound 1.

Structural, stability, and vibrational properties of BinPm clusters

NASA Astrophysics Data System (ADS)

Shen, Wanting; Han, Lihong; Liang, Dan; Zhang, Chunfang; Ruge, Quhe; Wang, Shumin; Lu, Pengfei

2018-04-01

An in-depth investigation is performed on stability mechanisms, electronic and optical properties of III-V semiconductor vapor phases clusters. First principles electronic structure calculations of CAM-B3LYP are performed on neutral BinPm (n + m ≤ 14) clusters. The geometrical evolution of all stable structures remains amorphous as the clusters size increases. Binding energies (BEs), energy gains and highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO-LUMO) gaps confirm that all four-atom structures of BinPm clusters have more stable optical properties. Orbitals composition and vibrational spectra of stable clusters are analyzed. Our calculations will contribute to the study of diluted bismuth alloys and compounds.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi

Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H{sub 2}ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H{sub 2}hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd{sub 2}(2,6-ndc){sub 2}(bpp)(DMF)]·2DMF (1) and [Cd{sub 3}(hmdb){sub 3}(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations inmore » 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.« less

Bootstrap Percolation on Homogeneous Trees Has 2 Phase Transitions

NASA Astrophysics Data System (ADS)

Fontes, L. R. G.; Schonmann, R. H.

2008-09-01

We study the threshold θ bootstrap percolation model on the homogeneous tree with degree b+1, 2≤ θ≤ b, and initial density p. It is known that there exists a nontrivial critical value for p, which we call p f , such that a) for p> p f , the final bootstrapped configuration is fully occupied for almost every initial configuration, and b) if p< p f , then for almost every initial configuration, the final bootstrapped configuration has density of occupied vertices less than 1. In this paper, we establish the existence of a distinct critical value for p, p c , such that 0< p c < p f , with the following properties: 1) if p≤ p c , then for almost every initial configuration there is no infinite cluster of occupied vertices in the final bootstrapped configuration; 2) if p> p c , then for almost every initial configuration there are infinite clusters of occupied vertices in the final bootstrapped configuration. Moreover, we show that 3) for p< p c , the distribution of the occupied cluster size in the final bootstrapped configuration has an exponential tail; 4) at p= p c , the expected occupied cluster size in the final bootstrapped configuration is infinite; 5) the probability of percolation of occupied vertices in the final bootstrapped configuration is continuous on [0, p f ] and analytic on ( p c , p f ), admitting an analytic continuation from the right at p c and, only in the case θ= b, also from the left at p f .

Fragmentation analysis of α-induced reactions using clusterization approach

NASA Astrophysics Data System (ADS)

Kaur, Amandeep; Sharma, Manoj K.

2018-01-01

The dynamics of α-induced reactions are worked out over an incident beam energy Eα ∼ 10- 15 MeV using targets of different masses. The decay patterns of odd mass compound systems 117Sb*, 145Pm* and 191Ir* formed in α +113In, α +141Pr and α +187Re reactions are investigated in view of n-evaporation data. The methodology of collective clusterization is applied by optimizing the neck-length parameter ΔR and the DCM calculated cross-sections find nice agreement with the experimental data. The resulting compound systems with ACN = 117- 191 cover a wide range of compound nucleus mass, and hence give an opportunity to explore various aspects related to the dynamics involved. Moreover the neutron-proton asymmetry dependence is explored in terms of the Bulk constant (α) (in the liquid drop binding energy expression) and radius term Ri and its consequent influence on the fragmentation structure of these compound systems is investigated.

A systematic study of mitochondrial toxicity of environmental chemicals using quantitative high throughput screening

PubMed Central

Attene-Ramos, Matias S.; Huang, Ruili; Sakamuru, Srilatha; Witt, Kristine L.; Beeson, Gyda C.; Shou, Louie; Schnellmann, Rick G.; Beeson, Craig C.; Tice, Raymond R.; Austin, Christopher P.; Xia, Menghang

2014-01-01

A goal of the Tox21 program is to transit toxicity testing from traditional in vivo models to in vitro assays that assess how chemicals affect cellular responses and toxicity pathways. A critical contribution of the NIH Chemical Genomics center (NCGC) to the Tox21 program is the implementation of a quantitative high throughput screening (qHTS) approach, using cell- and biochemical-based assays to generate toxicological profiles for thousands of environmental compounds. Here, we evaluated the effect of chemical compounds on mitochondrial membrane potential in HepG2 cells by screening a library of 1,408 compounds provided by the National Toxicology Program (NTP) in a qHTS platform. Compounds were screened over 14 concentrations, and results showed that 91 and 88 compounds disrupted mitochondrial membrane potential after treatment for one or five h, respectively. Seventy-six compounds active at both time points were clustered by structural similarity, producing 11 clusters and 23 singletons. Thirty-eight compounds covering most of the active chemical space were more extensively evaluated. Thirty-six of the 38 compounds were confirmed to disrupt mitochondrial membrane potential using a fluorescence plate reader and 35 were confirmed using a high content imaging approach. Among the 38 compounds, 4 and 6 induced LDH release, a measure of cytotoxicity, at 1 or 5 h, respectively. Compounds were further assessed for mechanism of action (MOA) by measuring changes in oxygen consumption rate, which enabled identification of 20 compounds as uncouplers. This comprehensive approach allows for evaluation of thousands of environmental chemicals for mitochondrial toxicity and identification of possible MOAs. PMID:23895456

Targeted Single-Site MOF Node Modification: Trivalent Metal Loading via Atomic Layer Deposition

DOE PAGES

Kim, In Soo; Borycz, Joshua; Platero-Prats, Ana E.; ...

2015-07-02

Postsynthetic functionalization of metal organic frameworks (MOFs) enables the controlled, high-density incorporation of new atoms on a crystallographically precise framework. Leveraging the broad palette of known atomic layer deposition (ALD) chemistries, ALD in MOFs (AIM) is one such targeted approach to construct diverse, highly functional, few-atom clusters. In this paper, we demonstrate the saturating reaction of trimethylindium (InMe 3) with the node hydroxyls and ligated water of NU-1000, which takes place without significant loss of MOF crystallinity or internal surface area. We computationally identify the elementary steps by which trimethylated trivalent metal compounds (ALD precursors) react with this Zr-based MOFmore » node to generate a uniform and well characterized new surface layer on the node itself, and we predict a final structure that is fully consistent with experimental X-ray pair distribution function (PDF) analysis. Finally, we further demonstrate tunable metal loading through controlled number density of the reactive handles (–OH and –OH 2) achieved through node dehydration at elevated temperatures.« less

Targeted Single-Site MOF Node Modification: Trivalent Metal Loading via Atomic Layer Deposition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, In Soo; Borycz, Joshua; Platero-Prats, Ana E.

Postsynthetic functionalization of metal organic frameworks (MOFs) enables the controlled, high-density incorporation of new atoms on a crystallographically precise framework. Leveraging the broad palette of known atomic layer deposition (ALD) chemistries, ALD in MOFs (AIM) is one such targeted approach to construct diverse, highly functional, few-atom clusters. In this paper, we demonstrate the saturating reaction of trimethylindium (InMe 3) with the node hydroxyls and ligated water of NU-1000, which takes place without significant loss of MOF crystallinity or internal surface area. We computationally identify the elementary steps by which trimethylated trivalent metal compounds (ALD precursors) react with this Zr-based MOFmore » node to generate a uniform and well characterized new surface layer on the node itself, and we predict a final structure that is fully consistent with experimental X-ray pair distribution function (PDF) analysis. Finally, we further demonstrate tunable metal loading through controlled number density of the reactive handles (–OH and –OH 2) achieved through node dehydration at elevated temperatures.« less

Properties of Prussian blue materials manifested in molecular complexes: observation of cyanide linkage isomerism and spin-crossover behavior in pentanuclear cyanide clusters.

PubMed

Shatruk, Mikhail; Dragulescu-Andrasi, Alina; Chambers, Kristen E; Stoian, Sebastian A; Bominaar, Emile L; Achim, Catalina; Dunbar, Kim R

2007-05-16

Pentanuclear, cyanide-bridged clusters [M(tmphen)2]3[M'(CN)6]2 (M/M' = Zn/Cr (1), Zn/Fe (2), Fe/Fe (3), Fe/Co (4), and Fe/Cr (5); tmphen = 3,4,7,8-tetramethyl-1,10-phenanthroline) were prepared by combining [M'III(CN)6]3- anions with mononuclear complexes of MII ions with two capping tmphen ligands. The clusters consist of a trigonal bipyramidal (TBP) core with three MII ions in the equatorial positions and two M'III ions in the axial positions. Compounds 1-4 are isostructural and crystallize in the monoclinic space group P21/c. Complex 5 crystallizes in the enantiomorphic space group P3221. The magnetic properties of compounds 1 and 2 reflect the contributions of the individual [CrIII(CN)6]3- and [FeIII(CN)6]3- ions. The FeII ions in compounds 3 and 4 exhibit a gradual, temperature-induced spin transition between high spin (HS) and low spin (LS), as determined by the combination of Mössbauer spectroscopy, magnetic measurements, and single-crystal X-ray studies. The investigation of compound 5 by these methods and by IR spectroscopy indicates that cyanide linkage isomerism occurs during cluster formation. The magnetic behavior of 5 is determined by weak ferromagnetic coupling between the axial CrIII centers mediated by the equatorial diamagnetic FeII ions. Mössbauer spectra collected in the presence of a high applied field have allowed, for the first time, the direct experimental observation of uncompensated spin density at diamagnetic metal ions that bridge paramagnetic metal ions.

Application of Time-Dependent Density Functional and Natural Bond Orbital Theories to the UV-vis Absorption Spectra of Some Phenolic Compounds.

PubMed

Marković, Svetlana; Tošović, Jelena

2015-09-03

The UV-vis properties of 22 natural phenolic compounds, comprising anthraquinones, neoflavonoids, and flavonoids were systematically examined. The time-dependent density functional theory (TDDFT) approach in combination with the B3LYP, B3LYP-D2, B3P86, and M06-2X functionals was used to simulate the UV-vis spectra of the investigated compounds. It was shown that all methods exhibit very good (B3LYP slightly better) performance in reproducing the examined UV-vis spectra. However, the shapes of the Kohn-Sham molecular orbitals (MOs) involved in electronic transitions were misleading in constructing the MO correlation diagrams. To provide better understanding of redistribution of electron density upon excitation, the natural bond orbital (NBO) analysis was applied. Bearing in mind the spatial and energetic separations, as well as the character of the π bonding, lone pair, and π* antibonding natural localized molecular orbitals (NLMOs), the "NLMO clusters" were constructed. NLMO cluster should be understood as a part of a molecule characterized with distinguished electron density. It was shown that all absorption bands including all electronic transitions need to be inspected to fully understand the UV-vis spectrum of a certain compound, and, thus, to learn more about its UV-vis light absorption. Our investigation showed that the TDDFT and NBO theories are complementary, as the results from the two approaches can be combined to interpret the UV-vis spectra. Agreement between the predictions of the TDDFT approach and those based on the NLMO clusters is excellent in the case of major electronic transitions and long wavelengths. It should be emphasized that the approach for investigation of UV-vis light absorption based on the NLMO clusters is applied for the first time.

Profiling of the Tox21 Chemical Collection for Mitochondrial Function to Identify Compounds that Acutely Decrease Mitochondrial Membrane Potential

PubMed Central

Attene-Ramos, Matias S.; Huang, Ruili; Michael, Sam; Witt, Kristine L.; Richard, Ann; Tice, Raymond R.; Simeonov, Anton; Austin, Christopher P.

2014-01-01

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding whether different environmental chemicals and druglike molecules impact mitochondrial function represents an initial step in predicting exposure-related toxicity and defining a possible role for such compounds in the onset of various diseases. Objectives: We sought to identify individual chemicals and general structural features associated with changes in mitochondrial membrane potential (MMP). Methods: We used a multiplexed [two end points in one screen; MMP and adenosine triphosphate (ATP) content] quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 library of 10,000 compounds (~ 8,300 unique chemicals) at 15 concentrations each in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells. Results: Approximately 11% of the compounds (913 unique compounds) decreased MMP after 1 hr of treatment without affecting cell viability (ATP content). In addition, 309 compounds decreased MMP over a concentration range that also produced measurable cytotoxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay ≤ 3; p < 0.05]. More than 11% of the structural clusters that constitute the Tox21 library (76 of 651 clusters) were significantly enriched for compounds that decreased the MMP. Conclusions: Our multiplexed qHTS approach allowed us to generate a robust and reliable data set to evaluate the ability of thousands of drugs and environmental compounds to decrease MMP. The use of structure-based clustering analysis allowed us to identify molecular features that are likely responsible for the observed activity. Citation: Attene-Ramos MS, Huang R, Michael S, Witt KL, Richard A, Tice RR, Simeonov A, Austin CP, Xia M. 2015. Profiling of the Tox21 chemical collection for mitochondrial function to identify compounds that acutely decrease mitochondrial membrane potential. Environ Health Perspect 123:49–56; http://dx.doi.org/10.1289/ehp.1408642 PMID:25302578

(Tl, Au)/Si(1 1 1){\\sqrt7 \\times \\sqrt7} 2D compound: an ordered array of identical Au clusters embedded in Tl matrix

NASA Astrophysics Data System (ADS)

Mihalyuk, A. N.; Hsing, C. R.; Wei, C. M.; Eremeev, S. V.; Bondarenko, L. V.; Tupchaya, A. Y.; Gruznev, D. V.; Zotov, A. V.; Saranin, A. A.

2018-01-01

Formation of the highly-ordered \\sqrt7 × \\sqrt7 -periodicity 2D compound has been detected in the (Tl, Au)/Si(1 1 1) system as a result of Au deposition onto the Tl/Si(1 1 1) surface, its composition, structure and electronic properties have been characterized using scanning tunneling microscopy, angle-resolved photoelectron spectroscopy and density-functional-theory calculations. On the basis of these data, the structural model of the Tl-Au compound has been proposed, which adopts 12 Tl atoms and 10 Au atoms (in total, 22 atoms) per \\sqrt7 × \\sqrt7 unit cell, i.e.  ˜1.71 ML of Tl and  ˜1.43 ML of Au (in total, ˜3.14 ML). Qualitatively, the model can be visualized as consisting of truncated-pyramid-like Au clusters with a Tl atom on top, while the other Tl atoms form a double layer around the Au clusters. The (Tl, Au)/Si(1 1 1)\\sqrt7 × \\sqrt7 compound has been found to exhibit pronounced metallic properties at least down to temperatures as low as  ˜25 K, which makes it a promising object for studying electrical transport phenomena in the 2D metallic systems.

Multiheteromacrocycles that Complex Metal Ions. Ninth Progress Report (includes results of last three years), 1 May 1980 -- 30 April 1983

DOE R&D Accomplishments Database

Cram, D. J.

1982-09-15

The overall objective of this research is to design, synthesize, and evaluate cyclic and polycyclic host organic compounds for the abilities to complex and lipophilize guest metal ions, their complexes, and their clusters. Host organic compounds consist of strategically placed solvating, coordinating, and ion-pairing sites tied together by covalent bonds through hydrocarbon units around cavities shaped to be occupied by guest metal ions, or by metal ions plus their ligands. Specificity in complexation is sought by matching the following properties of host and guest: cavity and metal ion sizes; geometric arrangements of binding sites; numbers of binding sites; characters of binding sites; and valences. The hope is to synthesize new classes of compounds useful in the separation of metal ions, their complexes, and their clusters.

Combining Computational Methods for Hit to Lead Optimization in Mycobacterium tuberculosis Drug Discovery

PubMed Central

Ekins, Sean; Freundlich, Joel S.; Hobrath, Judith V.; White, E. Lucile; Reynolds, Robert C

2013-01-01

Purpose Tuberculosis treatments need to be shorter and overcome drug resistance. Our previous large scale phenotypic high-throughput screening against Mycobacterium tuberculosis (Mtb) has identified 737 active compounds and thousands that are inactive. We have used this data for building computational models as an approach to minimize the number of compounds tested. Methods A cheminformatics clustering approach followed by Bayesian machine learning models (based on publicly available Mtb screening data) was used to illustrate that application of these models for screening set selections can enrich the hit rate. Results In order to explore chemical diversity around active cluster scaffolds of the dose-response hits obtained from our previous Mtb screens a set of 1924 commercially available molecules have been selected and evaluated for antitubercular activity and cytotoxicity using Vero, THP-1 and HepG2 cell lines with 4.3%, 4.2% and 2.7% hit rates, respectively. We demonstrate that models incorporating antitubercular and cytotoxicity data in Vero cells can significantly enrich the selection of non-toxic actives compared to random selection. Across all cell lines, the Molecular Libraries Small Molecule Repository (MLSMR) and cytotoxicity model identified ~10% of the hits in the top 1% screened (>10 fold enrichment). We also showed that seven out of nine Mtb active compounds from different academic published studies and eight out of eleven Mtb active compounds from a pharmaceutical screen (GSK) would have been identified by these Bayesian models. Conclusion Combining clustering and Bayesian models represents a useful strategy for compound prioritization and hit-to lead optimization of antitubercular agents. PMID:24132686

Rapid recognition of volatile organic compounds with colorimetric sensor arrays for lung cancer screening.

PubMed

Zhong, Xianhua; Li, Dan; Du, Wei; Yan, Mengqiu; Wang, You; Huo, Danqun; Hou, Changjun

2018-06-01

Volatile organic compounds (VOCs) in breath can be used as biomarkers to identify early stages of lung cancer. Herein, we report a disposable colorimetric array that has been constructed from diverse chemo-responsive colorants. Distinguishable difference maps were plotted within 4 min for specifically targeted VOCs. Through the consideration of various chemical interactions with VOCs, the arrays successfully discriminate between 20 different volatile organic compounds in breath that are related to lung cancer. VOCs were identified either with the visualized difference maps or through pattern recognition with an accuracy of at least 90%. No uncertainties or errors were observed in the hierarchical cluster analysis (HCA). Finally, good reproducibility and stability of the array was achieved against changes in humidity. Generally, this work provides fundamental support for construction of simple and rapid VOC sensors. More importantly, this approach provides a hypothesis-free array method for breath testing via VOC profiling. Therefore, this small, rapid, non-invasive, inexpensive, and visualized sensor array is a powerful and promising tool for early screening of lung cancer. Graphical abstract A disposable colorimetric array has been developed with broadly chemo-responsive dyes to incorporate various chemical interactions, through which the arrays successfully discriminate 20 VOCs that are related to lung cancer via difference maps alone or chemometrics within 4 min. The hydrophobic porous matrix provides good stability against changes in humidity.

IRIS Toxicological Review of Thallium and Compounds (Final Report)

EPA Science Inventory

EPA has finalized the Toxicological Review of Thallium and Compounds: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

Overproduction of Ristomycin A by Activation of a Silent Gene Cluster in Amycolatopsis japonicum MG417-CF17

PubMed Central

Spohn, Marius; Kirchner, Norbert; Kulik, Andreas; Jochim, Angelika; Wolf, Felix; Muenzer, Patrick; Borst, Oliver; Gross, Harald; Wohlleben, Wolfgang

2014-01-01

The emergence of antibiotic-resistant pathogenic bacteria within the last decades is one reason for the urgent need for new antibacterial agents. A strategy to discover new anti-infective compounds is the evaluation of the genetic capacity of secondary metabolite producers and the activation of cryptic gene clusters (genome mining). One genus known for its potential to synthesize medically important products is Amycolatopsis. However, Amycolatopsis japonicum does not produce an antibiotic under standard laboratory conditions. In contrast to most Amycolatopsis strains, A. japonicum is genetically tractable with different methods. In order to activate a possible silent glycopeptide cluster, we introduced a gene encoding the transcriptional activator of balhimycin biosynthesis, the bbr gene from Amycolatopsis balhimycina (bbrAba), into A. japonicum. This resulted in the production of an antibiotically active compound. Following whole-genome sequencing of A. japonicum, 29 cryptic gene clusters were identified by genome mining. One of these gene clusters is a putative glycopeptide biosynthesis gene cluster. Using bioinformatic tools, ristomycin (syn. ristocetin), a type III glycopeptide, which has antibacterial activity and which is used for the diagnosis of von Willebrand disease and Bernard-Soulier syndrome, was deduced as a possible product of the gene cluster. Chemical analyses by high-performance liquid chromatography and mass spectrometry (HPLC-MS), tandem mass spectrometry (MS/MS), and nuclear magnetic resonance (NMR) spectroscopy confirmed the in silico prediction that the recombinant A. japonicum/pRM4-bbrAba synthesizes ristomycin A. PMID:25114137

Discovery of Gene Cluster for Mycosporine-Like Amino Acid Biosynthesis from Actinomycetales Microorganisms and Production of a Novel Mycosporine-Like Amino Acid by Heterologous Expression

PubMed Central

Miyamoto, Kiyoko T.; Komatsu, Mamoru

2014-01-01

Mycosporines and mycosporine-like amino acids (MAAs), including shinorine (mycosporine-glycine-serine) and porphyra-334 (mycosporine-glycine-threonine), are UV-absorbing compounds produced by cyanobacteria, fungi, and marine micro- and macroalgae. These MAAs have the ability to protect these organisms from damage by environmental UV radiation. Although no reports have described the production of MAAs and the corresponding genes involved in MAA biosynthesis from Gram-positive bacteria to date, genome mining of the Gram-positive bacterial database revealed that two microorganisms belonging to the order Actinomycetales, Actinosynnema mirum DSM 43827 and Pseudonocardia sp. strain P1, possess a gene cluster homologous to the biosynthetic gene clusters identified from cyanobacteria. When the two strains were grown in liquid culture, Pseudonocardia sp. accumulated a very small amount of MAA-like compound in a medium-dependent manner, whereas A. mirum did not produce MAAs under any culture conditions, indicating that the biosynthetic gene cluster of A. mirum was in a cryptic state in this microorganism. In order to characterize these biosynthetic gene clusters, each biosynthetic gene cluster was heterologously expressed in an engineered host, Streptomyces avermitilis SUKA22. Since the resultant transformants carrying the entire biosynthetic gene cluster controlled by an alternative promoter produced mainly shinorine, this is the first confirmation of a biosynthetic gene cluster for MAA from Gram-positive bacteria. Furthermore, S. avermitilis SUKA22 transformants carrying the biosynthetic gene cluster for MAA of A. mirum accumulated not only shinorine and porphyra-334 but also a novel MAA. Structure elucidation revealed that the novel MAA is mycosporine-glycine-alanine, which substitutes l-alanine for the l-serine of shinorine. PMID:24907338

Discovery of gene cluster for mycosporine-like amino acid biosynthesis from Actinomycetales microorganisms and production of a novel mycosporine-like amino acid by heterologous expression.

PubMed

Miyamoto, Kiyoko T; Komatsu, Mamoru; Ikeda, Haruo

2014-08-01

Mycosporines and mycosporine-like amino acids (MAAs), including shinorine (mycosporine-glycine-serine) and porphyra-334 (mycosporine-glycine-threonine), are UV-absorbing compounds produced by cyanobacteria, fungi, and marine micro- and macroalgae. These MAAs have the ability to protect these organisms from damage by environmental UV radiation. Although no reports have described the production of MAAs and the corresponding genes involved in MAA biosynthesis from Gram-positive bacteria to date, genome mining of the Gram-positive bacterial database revealed that two microorganisms belonging to the order Actinomycetales, Actinosynnema mirum DSM 43827 and Pseudonocardia sp. strain P1, possess a gene cluster homologous to the biosynthetic gene clusters identified from cyanobacteria. When the two strains were grown in liquid culture, Pseudonocardia sp. accumulated a very small amount of MAA-like compound in a medium-dependent manner, whereas A. mirum did not produce MAAs under any culture conditions, indicating that the biosynthetic gene cluster of A. mirum was in a cryptic state in this microorganism. In order to characterize these biosynthetic gene clusters, each biosynthetic gene cluster was heterologously expressed in an engineered host, Streptomyces avermitilis SUKA22. Since the resultant transformants carrying the entire biosynthetic gene cluster controlled by an alternative promoter produced mainly shinorine, this is the first confirmation of a biosynthetic gene cluster for MAA from Gram-positive bacteria. Furthermore, S. avermitilis SUKA22 transformants carrying the biosynthetic gene cluster for MAA of A. mirum accumulated not only shinorine and porphyra-334 but also a novel MAA. Structure elucidation revealed that the novel MAA is mycosporine-glycine-alanine, which substitutes l-alanine for the l-serine of shinorine. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Information Theory and Voting Based Consensus Clustering for Combining Multiple Clusterings of Chemical Structures.

PubMed

Saeed, Faisal; Salim, Naomie; Abdo, Ammar

2013-07-01

Many consensus clustering methods have been applied in different areas such as pattern recognition, machine learning, information theory and bioinformatics. However, few methods have been used for chemical compounds clustering. In this paper, an information theory and voting based algorithm (Adaptive Cumulative Voting-based Aggregation Algorithm A-CVAA) was examined for combining multiple clusterings of chemical structures. The effectiveness of clusterings was evaluated based on the ability of the clustering method to separate active from inactive molecules in each cluster, and the results were compared with Ward's method. The chemical dataset MDL Drug Data Report (MDDR) and the Maximum Unbiased Validation (MUV) dataset were used. Experiments suggest that the adaptive cumulative voting-based consensus method can improve the effectiveness of combining multiple clusterings of chemical structures. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Periodic and Aperiodic Close Packing: A Spontaneous Hard-Sphere Model.

ERIC Educational Resources Information Center

van de Waal, B. W.

1985-01-01

Shows how to make close-packed models from balloons and table tennis balls to illustrate structural features of clusters and organometallic cluster-compounds (which are of great interest in the study of chemical reactions). These models provide a very inexpensive and tactile illustration of the organization of matter for concrete operational…

SOS System Induction Inhibits the Assembly of Chemoreceptor Signaling Clusters in Salmonella enterica

PubMed Central

Irazoki, Oihane; Mayola, Albert; Campoy, Susana; Barbé, Jordi

2016-01-01

Swarming, a flagellar-driven multicellular form of motility, is associated with bacterial virulence and increased antibiotic resistance. In this work we demonstrate that activation of the SOS response reversibly inhibits swarming motility by preventing the assembly of chemoreceptor-signaling polar arrays. We also show that an increase in the concentration of the RecA protein, generated by SOS system activation, rather than another function of this genetic network impairs chemoreceptor polar cluster formation. Our data provide evidence that the molecular balance between RecA and CheW proteins is crucial to allow polar cluster formation in Salmonella enterica cells. Thus, activation of the SOS response by the presence of a DNA-injuring compound increases the RecA concentration, thereby disturbing the equilibrium between RecA and CheW and resulting in the cessation of swarming. Nevertheless, when the DNA-damage decreases and the SOS response is no longer activated, basal RecA levels and thus polar cluster assembly are reestablished. These results clearly show that bacterial populations moving over surfaces make use of specific mechanisms to avoid contact with DNA-damaging compounds. PMID:26784887

SOS System Induction Inhibits the Assembly of Chemoreceptor Signaling Clusters in Salmonella enterica.

PubMed

Irazoki, Oihane; Mayola, Albert; Campoy, Susana; Barbé, Jordi

2016-01-01

Swarming, a flagellar-driven multicellular form of motility, is associated with bacterial virulence and increased antibiotic resistance. In this work we demonstrate that activation of the SOS response reversibly inhibits swarming motility by preventing the assembly of chemoreceptor-signaling polar arrays. We also show that an increase in the concentration of the RecA protein, generated by SOS system activation, rather than another function of this genetic network impairs chemoreceptor polar cluster formation. Our data provide evidence that the molecular balance between RecA and CheW proteins is crucial to allow polar cluster formation in Salmonella enterica cells. Thus, activation of the SOS response by the presence of a DNA-injuring compound increases the RecA concentration, thereby disturbing the equilibrium between RecA and CheW and resulting in the cessation of swarming. Nevertheless, when the DNA-damage decreases and the SOS response is no longer activated, basal RecA levels and thus polar cluster assembly are reestablished. These results clearly show that bacterial populations moving over surfaces make use of specific mechanisms to avoid contact with DNA-damaging compounds.

Two Horizontally Transferred Xenobiotic Resistance Gene Clusters Associated with Detoxification of Benzoxazolinones by Fusarium Species

PubMed Central

Glenn, Anthony E.; Davis, C. Britton; Gao, Minglu; Gold, Scott E.; Mitchell, Trevor R.; Proctor, Robert H.; Stewart, Jane E.; Snook, Maurice E.

2016-01-01

Microbes encounter a broad spectrum of antimicrobial compounds in their environments and often possess metabolic strategies to detoxify such xenobiotics. We have previously shown that Fusarium verticillioides, a fungal pathogen of maize known for its production of fumonisin mycotoxins, possesses two unlinked loci, FDB1 and FDB2, necessary for detoxification of antimicrobial compounds produced by maize, including the γ-lactam 2-benzoxazolinone (BOA). In support of these earlier studies, microarray analysis of F. verticillioides exposed to BOA identified the induction of multiple genes at FDB1 and FDB2, indicating the loci consist of gene clusters. One of the FDB1 cluster genes encoded a protein having domain homology to the metallo-β-lactamase (MBL) superfamily. Deletion of this gene (MBL1) rendered F. verticillioides incapable of metabolizing BOA and thus unable to grow on BOA-amended media. Deletion of other FDB1 cluster genes, in particular AMD1 and DLH1, did not affect BOA degradation. Phylogenetic analyses and topology testing of the FDB1 and FDB2 cluster genes suggested two horizontal transfer events among fungi, one being transfer of FDB1 from Fusarium to Colletotrichum, and the second being transfer of the FDB2 cluster from Fusarium to Aspergillus. Together, the results suggest that plant-derived xenobiotics have exerted evolutionary pressure on these fungi, leading to horizontal transfer of genes that enhance fitness or virulence. PMID:26808652

Water-soluble phosphine-protected Au9 clusters: Electronic structures and nuclearity conversion via phase transfer

NASA Astrophysics Data System (ADS)

Yao, Hiroshi; Tsubota, Shuhei

2017-08-01

In this article, isolation, exploration of electronic structures, and nuclearity conversion of water-soluble triphenylphosphine monosulfonate (TPPS)-protected nonagold (Au9) clusters are outlined. The Au9 clusters are obtained by the reduction of solutions containing TPPS and HAuCl4 and subsequent electrophoretic fractionation. Mass spectrometry and elemental analysis reveal the formation of [Au9(TPPS)8]5- nonagold cluster. UV-vis absorption and magnetic circular dichroism (MCD) spectra of aqueous [Au9(TPPS)8]5- are quite similar to those of [Au9(PPh3)8]3+ in organic solvent, so the solution-phase structures are likely similar for both systems. Simultaneous deconvolution analysis of absorption and MCD spectra demonstrates the presence of some weak electronic transitions that are essentially unresolved in the UV-vis absorption. Quantum chemical calculations for a model compound [Au9(pH3)8]3+ show that the possible (solution-phase) skeletal structure of the nonagold cluster has D2h core symmetry rather than C4-symmetrical centered crown conformation, which is known as the crystal form of the Au9 compound. Moreover, we find a new nuclearity conversion route from Au9 to Au8; that is, phase transfer of aqueous [Au9(TPPS)8]5- into chloroform using tetraoctylammonium bromide yields [Au8(TPPS)8]6- clusters in the absence of excess phosphine.

[Spectrophotometric study of the interaction between rhenium complexes and phosphatidylcholine during liposome formation].

PubMed

Shtemenko, O V; Zeleniuk, M A; Shtemenko, N I; Verbyts'ka, Ia S

2002-01-01

The electron absorption spectra of halogenides and halogencarboxylate complex compounds of rhenium (III) having cluster structure with phosphatydilcholine and their lyposome forms were investigated. Some results which evidence for the interaction of these compounds with phosphatydilcholine were obtained. The possible mechanism of this interaction is discussed.

Profiling of the Tox21 Chemical Collection for Mitochondrial ...

EPA Pesticide Factsheets

Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding how different environmental chemicals and drug-like molecules impact mitochondrial function represents an initial step in predicting exposure-related toxic effects and defining a possible role for such compounds in the onset of various diseases. OBJECTIVES: To identify individual chemicals and general structural features associated with the disruption of mitochondrial membrane potential (MMP). METHODS: We used a multiplexed quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 10,000 compound library (~8300 unique chemicals) at 15 concentrations in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells. RESULTS: In the primary screening, approximately 11% of the compounds (913 unique compounds) decreased the MMP after 1 h of treatment without affecting cell viability. Additionally, 309 compounds decreased MMP over a concentration range that also produced measurable cytotoxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay) ≤ 3, p<0.05]. Over 11% of the structural clusters that constitute the Tox21 library (76 of 651 clusters) were significantly enriched for compounds that decreased the MMP. CONCLUSIONS: Our multiplexed qHTS approach

The sensitivity of benzene cluster cation chemical ionization mass spectrometry to select biogenic terpenes

NASA Astrophysics Data System (ADS)

Lavi, Avi; Vermeuel, Michael P.; Novak, Gordon A.; Bertram, Timothy H.

2018-06-01

Benzene cluster cations are a sensitive and selective reagent ion for chemical ionization of select biogenic volatile organic compounds. We have previously reported the sensitivity of a field deployable chemical ionization time-of-flight mass spectrometer (CI-ToFMS), using benzene cluster cation ion chemistry, for detection of dimethyl sulfide, isoprene and α-pinene. Here, we present laboratory measurements of the sensitivity of the same instrument to a series of terpenes, including isoprene, α-pinene, β-pinene, D-limonene, ocimene, β-myrcene, farnesene, α-humulene, β-caryophyllene, and isolongifolene at atmospherically relevant mixing ratios (< 100 pptv). In addition, we determine the dependence of CI-ToFMS sensitivity on the reagent ion neutral delivery concentration and water vapor concentration. We show that isoprene is primarily detected as an adduct (C5H8 ṡ C6H6+) with a sensitivity ranging between 4 and 10 ncps ppt-1, which depends strongly on the reagent ion precursor concentration, de-clustering voltages, and specific humidity (SH). Monoterpenes are detected primarily as the molecular ion (C10H16+) with an average sensitivity, across the five measured compounds, of 14 ± 3 ncps ppt-1 for SH between 7 and 14 g kg-1, typical of the boreal forest during summer. Sesquiterpenes are detected primarily as the molecular ion (C15H24+) with an average sensitivity, across the four measured compounds, of 9.6 ± 2.3 ncps ppt-1, that is also independent of specific humidity. Comparable sensitivities across broad classes of terpenes (e.g., monoterpenes and sesquiterpenes), coupled to the limited dependence on specific humidity, suggest that benzene cluster cation CI-ToFMS is suitable for field studies of biosphere-atmosphere interactions.

C-SPADE: a web-tool for interactive analysis and visualization of drug screening experiments through compound-specific bioactivity dendrograms

PubMed Central

Alam, Zaid; Peddinti, Gopal

2017-01-01

Abstract The advent of polypharmacology paradigm in drug discovery calls for novel chemoinformatic tools for analyzing compounds’ multi-targeting activities. Such tools should provide an intuitive representation of the chemical space through capturing and visualizing underlying patterns of compound similarities linked to their polypharmacological effects. Most of the existing compound-centric chemoinformatics tools lack interactive options and user interfaces that are critical for the real-time needs of chemical biologists carrying out compound screening experiments. Toward that end, we introduce C-SPADE, an open-source exploratory web-tool for interactive analysis and visualization of drug profiling assays (biochemical, cell-based or cell-free) using compound-centric similarity clustering. C-SPADE allows the users to visually map the chemical diversity of a screening panel, explore investigational compounds in terms of their similarity to the screening panel, perform polypharmacological analyses and guide drug-target interaction predictions. C-SPADE requires only the raw drug profiling data as input, and it automatically retrieves the structural information and constructs the compound clusters in real-time, thereby reducing the time required for manual analysis in drug development or repurposing applications. The web-tool provides a customizable visual workspace that can either be downloaded as figure or Newick tree file or shared as a hyperlink with other users. C-SPADE is freely available at http://cspade.fimm.fi/. PMID:28472495

75 FR 16424 - Proposed Information Collection; Comment Request; Census Coverage Measurement Final Housing Unit...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-01

... unit is a block cluster, which consists of one or more geographically contiguous census blocks. As in... a number of distinct processes, ranging from forming block clusters, selecting the block clusters... sample of block clusters, while the E Sample is the census of housing units and enumerations in the same...

High Performance Computer Cluster for Theoretical Studies of Roaming in Chemical Reactions

DTIC Science & Technology

2016-08-30

High-performance Computer Cluster for Theoretical Studies of Roaming in Chemical Reactions A dedicated high-performance computer cluster was...SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS (ES) U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 Computer cluster ...peer-reviewed journals: Final Report: High-performance Computer Cluster for Theoretical Studies of Roaming in Chemical Reactions Report Title A dedicated

Asymmetries in Phonological Development: The Case of Word-Final Cluster Acquisition in Welsh-English Bilingual Children

ERIC Educational Resources Information Center

Mayr, Robert; Howells, Gwennan; Lewis, Rhonwen

2015-01-01

This study provides the first systematic account of word-final cluster acquisition in bilingual children. To this end, forty Welsh-English bilingual children differing in language dominance and age (2;6 to 5;0) participated in a picture-naming task in English and Welsh. The results revealed significant age and dominance effects on cluster…

Controlling transformations in the assembly of polyoxometalate clusters: {Mo11V7}, {Mo17V8} and {Mo72V30}.

PubMed

Miras, Haralampos N; Ochoa, M Nieves Corella; Long, De-Liang; Cronin, Leroy

2010-11-21

The reaction of molybdate with vanadium(V) in the presence of sulfite anions is explored showing how, via cation control, stepwise assembly through the {Mo(11)V(7)} cluster yields a {M(25)} cluster-based compound, [Mo(VI)(11)V(V)(5)V(IV)(2)O(52)(μ(9)-SO(3))(Mo(VI)(6)V(V)O(22))](10-) (1a), which was first discovered using cryospray mass spectrometry, whereas switching the cation away from ammonium allows the direct formation of the spherical 'Keplerate' {Mo(72)V(30)} cluster.

The association between chromaticity, phenolics, carotenoids, and in vitro antioxidant activity of frozen fruit pulp in Brazil: an application of chemometrics.

PubMed

Zielinski, Acácio Antonio Ferreira; Ávila, Suelen; Ito, Vivian; Nogueira, Alessandro; Wosiacki, Gilvan; Haminiuk, Charles Windson Isidoro

2014-04-01

A total of 19 Brazilian frozen pulps from the following fruits: açai (Euterpe oleracea), blackberry (Rubus sp.), cajá (Spondias mombin), cashew (Anacardium occidentale), cocoa (Theobroma cacao), coconut (Cocos nucifera), grape (Vitis sp.), graviola (Annona muricata), guava (Psidium guajava), papaya (Carica papaya), peach (Prunus persica), pineapple (Ananas comosus), pineapple and mint (A. comosus and Mentha spicata), red fruits (Rubus sp. and Fragaria sp.), seriguela (Spondias purpurea), strawberry (Fragaria sp.), tamarind (Tamarindus indica), umbu (Spondias tuberosa), and yellow passion fruit (Passiflora edulis) were analyzed in terms of chromaticity, phenolic compounds, carotenoids, and in vitro antioxidant activity using ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays. Data were processed using principal component analysis (PCA) and hierarchical cluster analysis (HCA). Antioxidant capacity was measured by DPPH and FRAP assays, which showed significant (P < 0.01) correlation with total phenolic compounds (r = 0.88 and 0.70, respectively), total flavonoids (r = 0.63 and 0.81, respectively), and total monomeric anthocyanins (r = 0.59 and 0.73, respectively). PCA explained 74.82% of total variance of data, and the separation into 3 groups in a scatter plot was verified. Three clusters also suggested by HCA, corroborated with PCA, in which cluster 3 was formed by strawberry, red fruits, blackberry, açaí, and grape pulps. This cluster showed the highest contents of total phenolic compounds, total flavonoids, and antioxidant activity. © 2014 Institute of Food Technologists®

A Model-Based Analysis of Chemical and Temporal Patterns of Cuticular Hydrocarbons in Male Drosophila melanogaster

PubMed Central

Kent, Clement; Azanchi, Reza; Smith, Ben; Chu, Adrienne; Levine, Joel

2007-01-01

Drosophila Cuticular Hydrocarbons (CH) influence courtship behaviour, mating, aggregation, oviposition, and resistance to desiccation. We measured levels of 24 different CH compounds of individual male D. melanogaster hourly under a variety of environmental (LD/DD) conditions. Using a model-based analysis of CH variation, we developed an improved normalization method for CH data, and show that CH compounds have reproducible cyclic within-day temporal patterns of expression which differ between LD and DD conditions. Multivariate clustering of expression patterns identified 5 clusters of co-expressed compounds with common chemical characteristics. Turnover rate estimates suggest CH production may be a significant metabolic cost. Male cuticular hydrocarbon expression is a dynamic trait influenced by light and time of day; since abundant hydrocarbons affect male sexual behavior, males may present different pheromonal profiles at different times and under different conditions. PMID:17896002

Metagenomic approaches to exploit the biotechnological potential of the microbial consortia of marine sponges.

PubMed

Kennedy, Jonathan; Marchesi, Julian R; Dobson, Alan D W

2007-05-01

Natural products isolated from sponges are an important source of new biologically active compounds. However, the development of these compounds into drugs has been held back by the difficulties in achieving a sustainable supply of these often-complex molecules for pre-clinical and clinical development. Increasing evidence implicates microbial symbionts as the source of many of these biologically active compounds, but the vast majority of the sponge microbial community remain uncultured. Metagenomics offers a biotechnological solution to this supply problem. Metagenomes of sponge microbial communities have been shown to contain genes and gene clusters typical for the biosynthesis of biologically active natural products. Heterologous expression approaches have also led to the isolation of secondary metabolism gene clusters from uncultured microbial symbionts of marine invertebrates and from soil metagenomic libraries. Combining a metagenomic approach with heterologous expression holds much promise for the sustainable exploitation of the chemical diversity present in the sponge microbial community.

[Ag115S34(SCH2C6H4 t Bu)47(dpph)6]: synthesis, crystal structure and NMR investigations of a soluble silver chalcogenide nanocluster.

PubMed

Bestgen, Sebastian; Fuhr, Olaf; Breitung, Ben; Kiran Chakravadhanula, Venkata Sei; Guthausen, Gisela; Hennrich, Frank; Yu, Wen; Kappes, Manfred M; Roesky, Peter W; Fenske, Dieter

2017-03-01

With the aim to synthesize soluble cluster molecules, the silver salt of (4-( tert -butyl)phenyl)methanethiol [AgSCH 2 C 6 H 4 t Bu] was applied as a suitable precursor for the formation of a nanoscale silver sulfide cluster. In the presence of 1,6-(diphenylphosphino)hexane (dpph), the 115 nuclear silver cluster [Ag 115 S 34 (SCH 2 C 6 H 4 t Bu) 47 (dpph) 6 ] was obtained. The molecular structure of this compound was elucidated by single crystal X-ray analysis and fully characterized by spectroscopic techniques. In contrast to most of the previously published cluster compounds with more than a hundred heavy atoms, this nanoscale inorganic molecule is soluble in organic solvents, which allowed a comprehensive investigation in solution by UV-Vis spectroscopy and one- and two-dimensional NMR spectroscopy including 31 P/ 109 Ag-HSQC and DOSY experiments. These are the first heteronuclear NMR investigations on coinage metal chalcogenides. They give some first insight into the behavior of nanoscale silver sulfide clusters in solution. Additionally, molecular weight determinations were performed by 2D analytical ultracentrifugation and HR-TEM investigations confirm the presence of size-homogeneous nanoparticles present in solution.

Theoretical Analysis of Optical Absorption and Emission in Mixed Noble Metal Nanoclusters.

PubMed

Day, Paul N; Pachter, Ruth; Nguyen, Kiet A

2018-04-26

In this work, we studied theoretically two hybrid gold-silver clusters, which were reported to have dual-band emission, using density functional theory (DFT) and linear and quadratic response time-dependent DFT (TDDFT). Hybrid functionals were found to successfully predict absorption and emission, although explanation of the NIR emission from the larger cluster (cluster 1) requires significant vibrational excitation in the final state. For the smaller cluster (cluster 2), the Δ H(0-0) value calculated for the T1 → S0 transition, using the PBE0 functional, is in good agreement with the measured NIR emission, and the calculated T2 → S0 value is in fair agreement with the measured visible emission. The calculated T1 → S0 phosphorescence Δ H(0-0) for cluster 1 is close to the measured visible emission energy. In order for the calculated phosphorescence for cluster 1 to agree with the intense NIR emission reported experimentally, the vibrational energy of the final state (S0) is required to be about 0.7 eV greater than the zero-point vibrational energy.

K-mean clustering algorithm for processing signals from compound semiconductor detectors

NASA Astrophysics Data System (ADS)

Tada, Tsutomu; Hitomi, Keitaro; Wu, Yan; Kim, Seong-Yun; Yamazaki, Hiromichi; Ishii, Keizo

2011-12-01

The K-mean clustering algorithm was employed for processing signal waveforms from TlBr detectors. The signal waveforms were classified based on its shape reflecting the charge collection process in the detector. The classified signal waveforms were processed individually to suppress the pulse height variation of signals due to the charge collection loss. The obtained energy resolution of a 137Cs spectrum measured with a 0.5 mm thick TlBr detector was 1.3% FWHM by employing 500 clusters.

Self-assembly of a tetrahedral 58-nuclear barium vanadium oxide cluster.

PubMed

Kastner, Katharina; Puscher, Bianka; Streb, Carsten

2013-01-07

We report the synthesis and characterization of a molecular barium vanadium oxide cluster featuring high nuclearity and high symmetry. The tetrameric, 2.3 nm cluster H(5)[Ba(10)(NMP)(14)(H(2)O)(8)[V(12)O(33)](4)Br] is based on a bromide-centred, octahedral barium scaffold which is capped by four previously unknown [V(12)O(33)](6-) clusters in a tetrahedral fashion. The compound represents the largest polyoxovanadate-based heterometallic cluster known to date. The cluster is formed in organic solution and it is suggested that the bulky N-methyl-2-pyrrolidone (NMP) solvent ligands allow the isolation of this giant molecule and prevent further condensation to a solid-state metal oxide. The cluster is fully characterized using single-crystal XRD, elemental analysis, ESI mass spectrometry and other spectroscopic techniques.

New target prediction and visualization tools incorporating open source molecular fingerprints for TB Mobile 2.0

PubMed Central

2014-01-01

Background We recently developed a freely available mobile app (TB Mobile) for both iOS and Android platforms that displays Mycobacterium tuberculosis (Mtb) active molecule structures and their targets with links to associated data. The app was developed to make target information available to as large an audience as possible. Results We now report a major update of the iOS version of the app. This includes enhancements that use an implementation of ECFP_6 fingerprints that we have made open source. Using these fingerprints, the user can propose compounds with possible anti-TB activity, and view the compounds within a cluster landscape. Proposed compounds can also be compared to existing target data, using a näive Bayesian scoring system to rank probable targets. We have curated an additional 60 new compounds and their targets for Mtb and added these to the original set of 745 compounds. We have also curated 20 further compounds (many without targets in TB Mobile) to evaluate this version of the app with 805 compounds and associated targets. Conclusions TB Mobile can now manage a small collection of compounds that can be imported from external sources, or exported by various means such as email or app-to-app inter-process communication. This means that TB Mobile can be used as a node within a growing ecosystem of mobile apps for cheminformatics. It can also cluster compounds and use internal algorithms to help identify potential targets based on molecular similarity. TB Mobile represents a valuable dataset, data-visualization aid and target prediction tool. PMID:25302078

New target prediction and visualization tools incorporating open source molecular fingerprints for TB Mobile 2.0.

PubMed

Clark, Alex M; Sarker, Malabika; Ekins, Sean

2014-01-01

We recently developed a freely available mobile app (TB Mobile) for both iOS and Android platforms that displays Mycobacterium tuberculosis (Mtb) active molecule structures and their targets with links to associated data. The app was developed to make target information available to as large an audience as possible. We now report a major update of the iOS version of the app. This includes enhancements that use an implementation of ECFP_6 fingerprints that we have made open source. Using these fingerprints, the user can propose compounds with possible anti-TB activity, and view the compounds within a cluster landscape. Proposed compounds can also be compared to existing target data, using a näive Bayesian scoring system to rank probable targets. We have curated an additional 60 new compounds and their targets for Mtb and added these to the original set of 745 compounds. We have also curated 20 further compounds (many without targets in TB Mobile) to evaluate this version of the app with 805 compounds and associated targets. TB Mobile can now manage a small collection of compounds that can be imported from external sources, or exported by various means such as email or app-to-app inter-process communication. This means that TB Mobile can be used as a node within a growing ecosystem of mobile apps for cheminformatics. It can also cluster compounds and use internal algorithms to help identify potential targets based on molecular similarity. TB Mobile represents a valuable dataset, data-visualization aid and target prediction tool.

Organotin Dyes Bearing Anionic Boron Clusters as Cell-Staining Fluorescent Probes.

PubMed

Muñoz-Flores, Blanca M; Cabrera-González, Justo; Viñas, Clara; Chávez-Reyes, Arturo; Dias, H V Rasika; Jiménez-Pérez, Víctor M; Núñez, Rosario

2018-04-11

Within the cell nucleus, in the nucleoli, ribosomal RNAs are synthesized and participate in several biological processes. To better understand nucleoli-related processes, their visualization is often required, for which specific markers are needed. Herein, we report the design of novel fluorescent organotin compounds derived from 4-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)benzohydrazide and their cytoplasm and nucleoli staining of B16F10 cells in vitro. Tin compounds bearing an aliphatic carbon chain (-C 12 H 25 ) and an electron-donating group (-OH) were prepared, and the latter could be derivatized to bear the boron cluster anions [B 12 H 12 ] 2- and [3,3'-Co(1,2-C 2 B 9 H 11 ) 2 ] - (COSAN). All of the conjugates have been fully characterized and their luminescence properties have been assessed. In general, they show good quantum yields in solution (24-49 %), those for the COSAN derivatives being lower. Remarkably, the linking of [B 12 H 12 ] 2- and COSAN to the complexes made them more soluble, without being detrimental to their luminescence properties. Living B16F10 cells were treated with all of the compounds to determine their fluorescence staining properties; the compounds bearing the aliphatic chain showed a reduced staining capacity due to the formation of aggregates. Notably, the complexes bearing different boron clusters showed different staining effects; those bearing [B 12 H 12 ] 2- showed extraordinary staining of the nucleoli and cytoplasm, whereas those bearing COSAN were only detected in the cytoplasm. The remarkable fluorescence staining properties shown by these organotin compounds make them excellent candidates for fluorescence bioimaging in vitro. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solvent-mediated secondary building units (SBUs) diversification in a series of MnII-based metal-organic frameworks (MOFs)

NASA Astrophysics Data System (ADS)

Niu, Yan-Fei; Cui, Li-Ting; Han, Jie; Zhao, Xiao-Li

2016-09-01

The role of auxiliary solvents in the formation of MOFs has been investigated for a series of MnII-based framework systems. Reactions of 4,4‧,4″-nitrilotribenzoic acid (H3L) with MnII through varying auxiliary solvents of the medium resulted in the formation of diversified multinuclear MnII subunits in four new coordination polymers: [Mn3(L)(HCOO)3(DEF)3] (1), [Mn3(L)2(EtOH)2]·DMF (2), [Mn5(L)4(H2O)2]·2(H2NMe2)+·4DMF·2H2O (3), and [Mn3(L)2(py)4(H2O)]·H2O (4) (H3L=4,4‧,4‧-nitrilotribenzoic acid, DMF=dimethylformamide, DEF=N,N-diethylformamide, py=pyridine). These four compounds were fully characterized by single-crystal X-ray diffraction, showing interesting SBUs variations. For compound 1, it displays a (3,6)-connected kgd net with wheel [Mn6] cluster serving as SBU, whereas in 2, the sequence of Mn3(COO)9(EtOH)2 is repeated by inversion centers located between Mn1 and Mn3 to form an infinite Mn-carboxylate chain, which are further interlinked by L3- ligands to form a 3D architecture. In 3, the pentanuclear Mn5(CO2)12 clusters are interlinked to form a layer, which are further pillared by L3- to generate a 3D network. Compound 4 has a (3,6)-connected network in which the SBU is a linear trimeric Mn3(COO)6(py)4(H2O) cluster. In addition, the thermal stabilities, X-ray powder diffraction of all the compounds were studied, photoluminescence behaviors of compounds 1, 3 and 4 are discussed.

Computational Chemistry Modeling of the Atmospheric Fate of Toxic Industrial Compounds (TICs)

DTIC Science & Technology

2007-06-01

1+G(3df,2p) number of atoms and number of basis functions) of the (LRG) compounds under study precludes the use of coupled 0 Zero Point Energy ( ZPE ...overlap (NDDO) The extrapolated energy = E(QCI) + E(LRG) - Hamiltonian that is reparameterized to accurately E(SML) + ZPE reproduce coupled cluster

The optimal design of stepped wedge trials with equal allocation to sequences and a comparison to other trial designs.

PubMed

Thompson, Jennifer A; Fielding, Katherine; Hargreaves, James; Copas, Andrew

2017-12-01

Background/Aims We sought to optimise the design of stepped wedge trials with an equal allocation of clusters to sequences and explored sample size comparisons with alternative trial designs. Methods We developed a new expression for the design effect for a stepped wedge trial, assuming that observations are equally correlated within clusters and an equal number of observations in each period between sequences switching to the intervention. We minimised the design effect with respect to (1) the fraction of observations before the first and after the final sequence switches (the periods with all clusters in the control or intervention condition, respectively) and (2) the number of sequences. We compared the design effect of this optimised stepped wedge trial to the design effects of a parallel cluster-randomised trial, a cluster-randomised trial with baseline observations, and a hybrid trial design (a mixture of cluster-randomised trial and stepped wedge trial) with the same total cluster size for all designs. Results We found that a stepped wedge trial with an equal allocation to sequences is optimised by obtaining all observations after the first sequence switches and before the final sequence switches to the intervention; this means that the first sequence remains in the control condition and the last sequence remains in the intervention condition for the duration of the trial. With this design, the optimal number of sequences is [Formula: see text], where [Formula: see text] is the cluster-mean correlation, [Formula: see text] is the intracluster correlation coefficient, and m is the total cluster size. The optimal number of sequences is small when the intracluster correlation coefficient and cluster size are small and large when the intracluster correlation coefficient or cluster size is large. A cluster-randomised trial remains more efficient than the optimised stepped wedge trial when the intracluster correlation coefficient or cluster size is small. A cluster-randomised trial with baseline observations always requires a larger sample size than the optimised stepped wedge trial. The hybrid design can always give an equally or more efficient design, but will be at most 5% more efficient. We provide a strategy for selecting a design if the optimal number of sequences is unfeasible. For a non-optimal number of sequences, the sample size may be reduced by allowing a proportion of observations before the first or after the final sequence has switched. Conclusion The standard stepped wedge trial is inefficient. To reduce sample sizes when a hybrid design is unfeasible, stepped wedge trial designs should have no observations before the first sequence switches or after the final sequence switches.

A novel organic-inorganic hybrid based on a dinuclear copper (II)-oxalate complex, a α-metatungstate cluster [H 2W 12O 40] 6- with catalytic activity in H 2O 2 decomposition

NASA Astrophysics Data System (ADS)

Sun, Ping; Liu, Shuxia; Feng, Dan; Ma, Fengji; Zhang, Wei; Ren, Yuanhang; Cao, Jianfang

2010-04-01

A novel organic-inorganic hybrid compound H 2[Cu 2(bpy) 2(H 2O) 2(μ-ox)] 2[H 2W 12O 40]·9H 2O ( 1) (2,2 '-bipyrine and ox = oxalate) has been successfully synthesized under open-air mild reaction condition and characterized by elemental analysis, IR spectrum, thermal stability analysis, single-crystal X-ray diffraction and magnetic susceptibility measurement. The main structural feature of compound 1 is the presence of α-metatungstate cluster [H 2W 12O 40] 6- as inorganic building blocks, on which the bridged-oxalate dinuclear copper metalorganic units are supported. Magnetic susceptibility studies reveal that the compound 1 shows paramagnetic property with a magnetic moment about the Cu 2+ ion, indicating antiferromagnetic coupling between the neighboring Cu 2+ ions in the structure. The compound 1 also displays a good catalytic activity with the conversion 42.4% for H 2O 2 decomposition.

Chemiomics: Network Reconstruction and Kinetics of Port Wine Aging

DOE PAGES

Monforte, Ana Rita; Jacobson, Dan; Silva Ferreira, A. C.

2015-02-11

Network reconstruction (NR) has proven to be useful in the detection and visualization of relationships among the compounds present in a Port wine aging data set. This view of the data provides a considerable amount of information with which to understand the kinetic contexts of the molecules represented by peaks in each chromatogram. The aim of this paper was to use NR together with the determination of kinetic parameters to extract more information about the mechanisms involved in Port wine aging. The volatile compounds present in samples of Port wines spanning 128 years in age were measured with the usemore » of GC-MS. After chromatogram alignment, a peak matrix was created, and all peak vectors were compared to one another to determine their Pearson correlations over time. A correlation network was created and filtered on the basis of the resulting correlation values. Some nodes in the network were further studied in experiments on Port wines stored under different conditions of oxygen and temperature in order to determine their kinetic parameters. The resulting network can be divided into three main branches. The first branch is related to compounds that do not directly correlate to age, the second branch contains compounds affected by temperature, and the third branch contains compounds associated with oxygen. Compounds clustered in the same branch of the network have similar expression patterns over time as well as the same kinetic order, thus are likely to be dependent on the same technological parameters. Network construction and visualization provides more information with which to understand the probable kinetic contexts of the molecules represented by peaks in each chromatogram. Finally, the approach described here is a powerful tool for the study of mechanisms and kinetics in complex systems and should aid in the understanding and monitoring of wine quality.« less

The Common Prescription Patterns Based on the Hierarchical Clustering of Herb-Pairs Efficacies

PubMed Central

2016-01-01

Prescription patterns are rules or regularities used to generate, recognize, or judge a prescription. Most of existing studies focused on the specific prescription patterns for diverse diseases or syndromes, while little attention was paid to the common patterns, which reflect the global view of the regularities of prescriptions. In this paper, we designed a method CPPM to find the common prescription patterns. The CPPM is based on the hierarchical clustering of herb-pair efficacies (HPEs). Firstly, HPEs were hierarchically clustered; secondly, the individual herbs are labeled by the HPEC (the clusters of HPEs); and then the prescription patterns were extracted from the combinations of HPEC; finally the common patterns are recognized statistically. The results showed that HPEs have hierarchical clustering structure. When the clustering level is 2 and the HPEs were classified into two clusters, the common prescription patterns are obvious. Among 332 candidate prescriptions, 319 prescriptions follow the common patterns. The description of the patterns is that if a prescription contains the herbs of the cluster (C 1), it is very likely to have other herbs of another cluster (C 2); while a prescription has the herbs of C 2, it may have no herbs of C 1. Finally, we discussed that the common patterns are mathematically coincident with the Blood-Qi theory. PMID:27190534

Efficient Synthesis of Ir-Polyoxometalate Cluster Using a Continuous Flow Apparatus and STM Investigation of Its Coassembly Behavior on HOPG Surface.

PubMed

Zhang, Junyong; Chang, Shaoqing; Suryanto, Bryan H R; Gong, Chunhua; Zeng, Xianghua; Zhao, Chuan; Zeng, Qingdao; Xie, Jingli

2016-06-06

Taking advantage of a continuous-flow apparatus, the iridium(III)-containing polytungstate cluster K12Na2H2[Ir2Cl8P2W20O72]·37H2O (1) was obtained in a reasonable yield (13% based on IrCl3·H2O). Compound 1 was characterized by Fourier transform IR, UV-visible, (31)P NMR, electrospray ionization mass spectrometry (ESI-MS), and thermogravimetric analysis measurements. (31)P NMR, ESI-MS, and elemental analysis all indicated 1 was a new polytungstate cluster compared with the reported K14[(IrCl4)KP2W20O72] compound. Intriguingly, the successful isolation of 1 relied on the custom-built flow apparatus, demonstrating the uniqueness of continuous-flow chemistry to achieve crystalline materials. The catalytic properties of 1 were assessed by investigating the activity on catalyzing the electro-oxidation of ruthenium tris-2,2'-bipyridine [Ru(bpy)3](2+/3+). The voltammetric behavior suggested a coupled catalytic behavior between [Ru(bpy)3](3+/2+) and 1. Furthermore, on the highly oriented pyrolytic graphite surface, 1,3,5-tris(10-carboxydecyloxy) benzene (TCDB) was used as the two-dimensional host network to coassemble cluster 1; the surface morphology was observed by scanning tunneling microscope technique. "S"-shape of 1 was observed, indicating that the cluster could be accommodated in the cavity formed by two TCDB host molecules, leading to a TCDB/cluster binary structure.

Hybrid Assembly of Different-Sized Supertetrahedral Clusters into a Unique Non-Interpenetrated Mn-In-S Open Framework with Large Cavity.

PubMed

Wang, Hongxiang; Wang, Wei; Hu, Dandan; Luo, Min; Xue, Chaozhuang; Li, Dongsheng; Wu, Tao

2018-06-04

Reported here is a unique crystalline semiconductor open-framework material built from the large-sized supertetrahedral T4 and T5 clusters with the Mn-In-S compositions. The hybrid assembly between T4 and T5 clusters by sharing terminal μ 2 -S 2- is for the first time observed among the cluster-based chalcogenide open frameworks. Such three-dimensional structure displays non-interpenetrated diamond-type topology with extra-large nonframework volume of 82%. Moreover, ion exchange, CO 2 adsorption, as well as photoluminescence properties of the title compound are also investigated.

Modeling the active site of [NiFe] hydrogenases and the [NiFeu] subsite of the C-cluster of carbon monoxide dehydrogenases: low-spin iron(II) versus high-spin iron(II).

PubMed

Weber, Katharina; Erdem, Özlen F; Bill, Eckhard; Weyhermüller, Thomas; Lubitz, Wolfgang

2014-06-16

A series of four [S2Ni(μ-S)2FeCp*Cl] compounds with different tetradentate thiolate/thioether ligands bound to the Ni(II) ion is reported (Cp* = C5Me5). The {S2Ni(μ-S)2Fe} core of these compounds resembles structural features of the active site of [NiFe] hydrogenases. Detailed analyses of the electronic structures of these compounds by Mössbauer and electron paramagnetic resonance spectroscopy, magnetic measurements, and density functional theory calculations reveal the oxidation states Ni(II) low spin and Fe(II) high spin for the metal ions. The same electronic configurations have been suggested for the Cred1 state of the C-cluster [NiFeu] subsite in carbon monoxide dehydrogenases (CODH). The Ni-Fe distance of ∼3 Å excludes a metal-metal bond between nickel and iron, which is in agreement with the computational results. Electrochemical experiments show that iron is the redox active site in these complexes, performing a reversible one-electron oxidation. The four complexes are discussed with regard to their similarities and differences both to the [NiFe] hydrogenases and the C-cluster of Ni-containing CODH.

DOVIS: an implementation for high-throughput virtual screening using AutoDock.

PubMed

Zhang, Shuxing; Kumar, Kamal; Jiang, Xiaohui; Wallqvist, Anders; Reifman, Jaques

2008-02-27

Molecular-docking-based virtual screening is an important tool in drug discovery that is used to significantly reduce the number of possible chemical compounds to be investigated. In addition to the selection of a sound docking strategy with appropriate scoring functions, another technical challenge is to in silico screen millions of compounds in a reasonable time. To meet this challenge, it is necessary to use high performance computing (HPC) platforms and techniques. However, the development of an integrated HPC system that makes efficient use of its elements is not trivial. We have developed an application termed DOVIS that uses AutoDock (version 3) as the docking engine and runs in parallel on a Linux cluster. DOVIS can efficiently dock large numbers (millions) of small molecules (ligands) to a receptor, screening 500 to 1,000 compounds per processor per day. Furthermore, in DOVIS, the docking session is fully integrated and automated in that the inputs are specified via a graphical user interface, the calculations are fully integrated with a Linux cluster queuing system for parallel processing, and the results can be visualized and queried. DOVIS removes most of the complexities and organizational problems associated with large-scale high-throughput virtual screening, and provides a convenient and efficient solution for AutoDock users to use this software in a Linux cluster platform.

Observation of magnetization reversal and magnetocaloric effect in manganese modified EuCrO3 orthochromites

NASA Astrophysics Data System (ADS)

Kumar, Surendra; Coondoo, Indrani; Vasundhara, M.; Puli, Venkata S.; Panwar, Neeraj

2017-08-01

We report here an investigation on the structural, magnetic and magnetocaloric properties of Mn doped EuCr0.85Mn0.15O3 (ECMO) chromites synthesized via ceramic route. The compound crystallized into distorted orthorhombic structure with Pnma space group similar to that of its parent EuCrO3 compound, as revealed from the refined of x-ray powder diffraction pattern, but with an increase in the lattice volume. Neel temperature, noticed at 162 K from the temperature variation of magnetization, smaller than that reported for pristine EuCrO3; indicated the influence of Mn3+ substitution in decreasing the antiferromagnetic ordering. Magnetization reversal evolved in the studied compound under lower field while such feature was absent in the undoped EuCrO3. Magnetocaloric effect was measured through the magnetic entropy change and relative cooling power. Near the spin reorientation transition temperature 40 K, the magnetic entropy change was equal to 3.788 J kg-1 K-1 under 90 kOe field with 215.22 J kg-1relative cooling power. The results have been understood in terms of the competition between Cr-rich clusters, Mn-rich clusters and local Mn-Cr ordered clusters and their different temperature dependency.

Ferroelectric Nematic and Ferrielectric Smectic Mesophases in an Achiral Bent-Core Azo Compound.

PubMed

Kumar, Jitendra; Prasad, Veena

2018-03-22

Here, we report the observation of ferroelectric nematic and ferrielectric smectic mesophases in an achiral bent-core azo compound consisting of nonsymmetrical molecules with a lateral fluoro substitution on one of the wings. These mesophases are enantiotropic in nature with fairly low transition temperatures and wide mesophase ranges. The liquid crystalline properties of this compound are investigated using polarizing optical microscope, differential scanning calorimeter, X-ray diffraction, and electro-optical studies. As revealed by X-ray diffraction measurements, the nematic mesophase is composed of skewed cybotactic clusters and, in the smectic mesophase, the molecules are tilted with respect to the layer normal. The polar order in these mesophases was confirmed by the electro-optical switching and dielectric spectroscopy measurements. The dielectric study in the nematic mesophase shows a single relaxation process at low frequency ( f < 1 kHz) measured in the range 10 Hz to 5 MHz, which is attributed to the collective motion of the molecules within cybotactic clusters. The formation of local polar order in these clusters leads to a ferroelectric-like polar switching in the nematic mesophase. Of particular interest is the fact that the smectic phase exhibits a field induced ferrielectric state, which can be exploited for designing of the potential optical devices due to multistate switching.

Identification of Secondary Metabolite Gene Clusters in the Pseudovibrio Genus Reveals Encouraging Biosynthetic Potential toward the Production of Novel Bioactive Compounds.

PubMed

Naughton, Lynn M; Romano, Stefano; O'Gara, Fergal; Dobson, Alan D W

2017-01-01

Increased incidences of antimicrobial resistance and the emergence of pan-resistant 'superbugs' have provoked an extreme sense of urgency amongst researchers focusing on the discovery of potentially novel antimicrobial compounds. A strategic shift in focus from the terrestrial to the marine environment has resulted in the discovery of a wide variety of structurally and functionally diverse bioactive compounds from numerous marine sources, including sponges. Bacteria found in close association with sponges and other marine invertebrates have recently gained much attention as potential sources of many of these novel bioactive compounds. Members of the genus Pseudovibrio are one such group of organisms. In this study, we interrogate the genomes of 21 Pseudovibrio strains isolated from a variety of marine sources, for the presence, diversity and distribution of biosynthetic gene clusters (BGCs). We expand on results obtained from antiSMASH analysis to demonstrate the similarity between the Pseudovibrio -related BGCs and those characterized in other bacteria and corroborate our findings with phylogenetic analysis. We assess how domain organization of the most abundant type of BGCs present among the isolates (Non-ribosomal peptide synthetases and Polyketide synthases) may influence the diversity of compounds produced by these organisms and highlight for the first time the potential for novel compound production from this genus of bacteria, using a genome guided approach.

Treatment of Mycobacterium intracellulare Infected Mice with Walter Reed Compound H

DTIC Science & Technology

1980-09-25

including Mycobacterium tuberculosis, Mycobacterium leprae , Staphylococcusaureus, Pseudomonas aeruginosa, Escherichia coli, enterococ----ci, Neissr•~n...97 SAD "Treatment of Mycobacterium intracellulare Infected Mice with Walter Reed Compound H" Final Comprehensive Report J. Kenneth McClatchy, Ph.D...REPORT & PERIOD COVERED "TREATMENT OF MYCOBACTERIUM INTRACELLULARE - Final Comprehensive Report INFECTED MICE WITH WALTER REED COMPOUND H"li G

antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences.

PubMed

Medema, Marnix H; Blin, Kai; Cimermancic, Peter; de Jager, Victor; Zakrzewski, Piotr; Fischbach, Michael A; Weber, Tilmann; Takano, Eriko; Breitling, Rainer

2011-07-01

Bacterial and fungal secondary metabolism is a rich source of novel bioactive compounds with potential pharmaceutical applications as antibiotics, anti-tumor drugs or cholesterol-lowering drugs. To find new drug candidates, microbiologists are increasingly relying on sequencing genomes of a wide variety of microbes. However, rapidly and reliably pinpointing all the potential gene clusters for secondary metabolites in dozens of newly sequenced genomes has been extremely challenging, due to their biochemical heterogeneity, the presence of unknown enzymes and the dispersed nature of the necessary specialized bioinformatics tools and resources. Here, we present antiSMASH (antibiotics & Secondary Metabolite Analysis Shell), the first comprehensive pipeline capable of identifying biosynthetic loci covering the whole range of known secondary metabolite compound classes (polyketides, non-ribosomal peptides, terpenes, aminoglycosides, aminocoumarins, indolocarbazoles, lantibiotics, bacteriocins, nucleosides, beta-lactams, butyrolactones, siderophores, melanins and others). It aligns the identified regions at the gene cluster level to their nearest relatives from a database containing all other known gene clusters, and integrates or cross-links all previously available secondary-metabolite specific gene analysis methods in one interactive view. antiSMASH is available at http://antismash.secondarymetabolites.org.

Effect of the fruit position on the cluster on fruit quality, carotenoids, phenolics and sugars in cherry tomatoes (Solanum lycopersicum L.).

PubMed

Coyago-Cruz, Elena; Corell, Mireia; Moriana, Alfonso; Hernanz, Dolores; Stinco, Carla M; Meléndez-Martínez, Antonio J

2017-10-01

Cherry tomato varieties are widely consumed in many countries. They contain nutrients and health-promoting compounds like phenolics and carotenoids. The main purpose of this study was to determine how the fruit position on the cluster affected quality parameters of diverse nature (weight, soluble solids, firmness, colour, carotenoids, phenolic compounds and sugars). For this purpose the fourth cluster of two cherry varieties (Summerbrix and Lazarino) were studied. The results indicated that the fruit position on the cluster decreased the fruit size between 14 and 16% and weight 40%; firmness in 'Lazarino' increased 56%; C* ab increased 12% in 'Lazarino' and decreased 13% in 'Summerbrix'; h ab increased 9% in 'Summerbrix'. Total carotenoid levels were not statistically different in two positions, and in the other position the contents were higher, with a difference of 36% between these two values. The highest total phenolic levels were observed in the PII position. However, total sugars increased 36%, fructose 36% and glucose 35% from the PI to PIII position in 'Lazarino', while, in 'Summerbrix' higher values were observed in the PIII position. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dynamic clustering threshold reduces conformer ensemble size while maintaining a biologically relevant ensemble

NASA Astrophysics Data System (ADS)

Yongye, Austin B.; Bender, Andreas; Martínez-Mayorga, Karina

2010-08-01

Representing the 3D structures of ligands in virtual screenings via multi-conformer ensembles can be computationally intensive, especially for compounds with a large number of rotatable bonds. Thus, reducing the size of multi-conformer databases and the number of query conformers, while simultaneously reproducing the bioactive conformer with good accuracy, is of crucial interest. While clustering and RMSD filtering methods are employed in existing conformer generators, the novelty of this work is the inclusion of a clustering scheme (NMRCLUST) that does not require a user-defined cut-off value. This algorithm simultaneously optimizes the number and the average spread of the clusters. Here we describe and test four inter-dependent approaches for selecting computer-generated conformers, namely: OMEGA, NMRCLUST, RMS filtering and averaged- RMS filtering. The bioactive conformations of 65 selected ligands were extracted from the corresponding protein:ligand complexes from the Protein Data Bank, including eight ligands that adopted dissimilar bound conformations within different receptors. We show that NMRCLUST can be employed to further filter OMEGA-generated conformers while maintaining biological relevance of the ensemble. It was observed that NMRCLUST (containing on average 10 times fewer conformers per compound) performed nearly as well as OMEGA, and both outperformed RMS filtering and averaged- RMS filtering in terms of identifying the bioactive conformations with excellent and good matches (0.5 < RMSD < 1.0 Å). Furthermore, we propose thresholds for OMEGA root-mean square filtering depending on the number of rotors in a compound: 0.8, 1.0 and 1.4 for structures with low (1-4), medium (5-9) and high (10-15) numbers of rotatable bonds, respectively. The protocol employed is general and can be applied to reduce the number of conformers in multi-conformer compound collections and alleviate the complexity of downstream data processing in virtual screening experiments.

The [Mo₆Cl14]2- Cluster is Biologically Secure and Has Anti-Rotavirus Activity In Vitro.

PubMed

Rojas-Mancilla, Edgardo; Oyarce, Alexis; Verdugo, Viviana; Morales-Verdejo, Cesar; Echeverria, Cesar; Velásquez, Felipe; Chnaiderman, Jonas; Valiente-Echeverría, Fernando; Ramirez-Tagle, Rodrigo

2017-07-05

The molybdenum cluster [Mo₆Cl 14 ] 2- is a fluorescent component with potential for use in cell labelling and pharmacology. Biological safety and antiviral properties of the cluster are as yet unknown. Here, we show the effect of acute exposition of human cells and red blood cells to the molybdenum cluster and its interaction with proteins and antiviral activity in vitro. We measured cell viability of HepG2 and EA.hy926 cell lines exposed to increasing concentrations of the cluster (0.1 to 250 µM), by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Hemolysis and morphological alterations of red blood cells, obtained from healthy donors, exposed to the cluster (10 to 200 µM) at 37 °C were analyzed. Furthermore, quenching of tryptophan residues of albumin was performed. Finally, plaque formation by rotavirus SA11 in MA104 cells treated with the cluster (100 to 300 µM) were analyzed. We found that all doses of the cluster showed similar cell viability, hemolysis, and morphology values, compared to control. Quenching of tryptophan residues of albumin suggests a protein-cluster complex formation. Finally, the cluster showed antiviral activity at 300 µM. These results indicate that the cluster [Mo₆Cl 14 ] 2- could be intravenously administered in animals at therapeutic doses for further in vivo studies and might be studied as an antiviral agent.

Spatial and Temporal Patterns of Biocide Action against Staphylococcus epidermidis Biofilms▿ ‡

PubMed Central

Davison, William M.; Pitts, Betsey; Stewart, Philip S.

2010-01-01

The dynamic antimicrobial action of chlorine, a quaternary ammonium compound, glutaraldehyde, and nisin within biofilm cell clusters of Staphylococcus epidermidis was investigated using time-lapse confocal scanning laser microscopy. The technique allowed for the simultaneous imaging of changes in biofilm structure and disruption of cellular membrane integrity through the loss of an unbound fluorophore loaded into bacterial cells prior to antimicrobial challenge. Each of the four antimicrobial agents produced distinct spatial and temporal patterns of fluorescence loss. The antimicrobial action of chlorine was localized around the periphery of biofilm cell clusters. Chlorine was the only antimicrobial agent that caused any biofilm removal. Treatment with the quaternary ammonium compound caused membrane permeabilization that started at the periphery of cell clusters, then migrated steadily inward. A secondary pattern superimposed on the penetration dynamic suggested a subpopulation of less-susceptible cells. These bacteria lost fluorescence much more slowly than the majority of the population. Nisin caused a rapid and uniform loss of green fluorescence from all parts of the biofilm without any removal of biofilm. Glutaraldehyde caused no biofilm removal and also no loss of membrane integrity. Measurements of biocide penetration and action time at the center of cell clusters yielded 46 min for 10 mg liter−1 chlorine, 21 min for 50 mg liter−1 chlorine, 25 min for the quaternary ammonium compound, and 4 min for nisin. These results underscore the distinction between biofilm removal and killing and reinforce the critical role of biocide reactivity in determining the rate of biofilm penetration. PMID:20457816

Rapid Parallel Screening for Strain Optimization

DTIC Science & Technology

2013-08-16

fermentation yields of industrially relevant biological compounds. Screening of the desired chemicals was completed previously. Microbes that can...reporter, and, 2) a yeast TAR cloning shuttle vector for transferring catabolic clusters to E. coli. 15. SUBJECT TERMS NA 16. SECURITY CLASSIFICATION OF... fermentation yields of industrially relevant biological compounds. Screening of the desired chemicals was completed previously. Microbes that can utilize

Rapid Parallel Screening for Strain Optimization

DTIC Science & Technology

2013-05-16

fermentation yields of industrially relevant biological compounds. Screening of the desired chemicals was completed previously. Microbes that can...reporter, and, 2) a yeast TAR cloning shuttle vector for transferring catabolic clusters to E. coli. 15. SUBJECT TERMS NA 16. SECURITY CLASSIFICATION OF... fermentation yields of industrially relevant biological compounds. Screening of the desired chemicals was completed previously. Microbes that can utilize

Deuterium cluster model for low energy nuclear reactions (LENR)

NASA Astrophysics Data System (ADS)

Miley, George; Hora, Heinrich

2007-11-01

For studying the possible reactions of high density deuterons on the background of a degenerate electron gas, a summary of experimental observations resulted in the possibility of reactions in pm distance and more than ksec duration similar to the K-shell electron capture [1]. The essential reason was the screening of the deuterons by a factor of 14 based on the observations. Using the bosonic properties for a cluster formation of the deuterons and a model of compound nuclear reactions [2], the measured distribution of the resulting nuclei may be explained as known from the Maruhn-Greiner theory for fission. The local maximum of the distribution at the main minimum indicates the excited states of the compound nuclei during their intermediary state. This measured local maximum may be an independent proof for the deuteron clusters at LENR. [1] H. Hora, G.H. Miley et al. Physics Letters A175, 138 (1993) [2] H. Hora and G.H. Miley, APS March Meeting 2007, Program p. 116

Development of a Hybrid Piezo Natural Rubber Piezoelectricity and Piezoresistivity Sensor with Magnetic Clusters Made by Electric and Magnetic Field Assistance and Filling with Magnetic Compound Fluid

PubMed Central

Shimada, Kunio; Saga, Norihiko

2017-01-01

Piezoelements used in robotics require large elasticity and extensibility to be installed in an artificial robot skin. However, the piezoelements used until recently are vulnerable to large forces because of the thin solid materials employed. To resolve this issue, we utilized a natural rubber and applied our proposed new method of aiding with magnetic and electric fields as well as filling with magnetic compound fluid (MCF) and doping. We have verified the piezoproperties of the resulting MCF rubber. The effect of the created magnetic clusters is featured in a new two types of multilayered structures of the piezoelement. By measuring the piezoelectricity response to pressure, the synergetic effects of the magnetic clusters, the doping and the electric polymerization on the piezoelectric effect were clarified. In addition, by examining the relation between the piezoelectricity and the piezoresistivity created in the MCF piezo element, we propose a hybrid piezoelement. PMID:28208625

The GSAM software: A global search algorithm of minima exploration for the investigation of low lying isomers of clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marchal, Rémi; Carbonnière, Philippe; Pouchan, Claude

2015-01-22

The study of atomic clusters has become an increasingly active area of research in the recent years because of the fundamental interest in studying a completely new area that can bridge the gap between atomic and solid state physics. Due to their specific properties, such compounds are of great interest in the field of nanotechnology [1,2]. Here, we would present our GSAM algorithm based on a DFT exploration of the PES to find the low lying isomers of such compounds. This algorithm includes the generation of an intial set of structure from which the most relevant are selected. Moreover, anmore » optimization process, called raking optimization, able to discard step by step all the non physically reasonnable configurations have been implemented to reduce the computational cost of this algorithm. Structural properties of Ga{sub n}Asm clusters will be presented as an illustration of the method.« less

Natural-product-derived fragments for fragment-based ligand discovery

NASA Astrophysics Data System (ADS)

Over, Björn; Wetzel, Stefan; Grütter, Christian; Nakai, Yasushi; Renner, Steffen; Rauh, Daniel; Waldmann, Herbert

2013-01-01

Fragment-based ligand and drug discovery predominantly employs sp2-rich compounds covering well-explored regions of chemical space. Despite the ease with which such fragments can be coupled, this focus on flat compounds is widely cited as contributing to the attrition rate of the drug discovery process. In contrast, biologically validated natural products are rich in stereogenic centres and populate areas of chemical space not occupied by average synthetic molecules. Here, we have analysed more than 180,000 natural product structures to arrive at 2,000 clusters of natural-product-derived fragments with high structural diversity, which resemble natural scaffolds and are rich in sp3-configured centres. The structures of the cluster centres differ from previously explored fragment libraries, but for nearly half of the clusters representative members are commercially available. We validate their usefulness for the discovery of novel ligand and inhibitor types by means of protein X-ray crystallography and the identification of novel stabilizers of inactive conformations of p38α MAP kinase and of inhibitors of several phosphatases.

The diversity of anti-microbial secondary metabolites produced by fungal endophytes: an interdisciplinary perspective.

PubMed

Mousa, Walaa Kamel; Raizada, Manish N

2013-01-01

Endophytes are microbes that inhabit host plants without causing disease and are reported to be reservoirs of metabolites that combat microbes and other pathogens. Here we review diverse classes of secondary metabolites, focusing on anti-microbial compounds, synthesized by fungal endophytes including terpenoids, alkaloids, phenylpropanoids, aliphatic compounds, polyketides, and peptides from the interdisciplinary perspectives of biochemistry, genetics, fungal biology, host plant biology, human and plant pathology. Several trends were apparent. First, host plants are often investigated for endophytes when there is prior indigenous knowledge concerning human medicinal uses (e.g., Chinese herbs). However, within their native ecosystems, and where investigated, endophytes were shown to produce compounds that target pathogens of the host plant. In a few examples, both fungal endophytes and their hosts were reported to produce the same compounds. Terpenoids and polyketides are the most purified anti-microbial secondary metabolites from endophytes, while flavonoids and lignans are rare. Examples are provided where fungal genes encoding anti-microbial compounds are clustered on chromosomes. As different genera of fungi can produce the same metabolite, genetic clustering may facilitate sharing of anti-microbial secondary metabolites between fungi. We discuss gaps in the literature and how more interdisciplinary research may lead to new opportunities to develop bio-based commercial products to combat global crop and human pathogens.

The Diversity of Anti-Microbial Secondary Metabolites Produced by Fungal Endophytes: An Interdisciplinary Perspective

PubMed Central

Mousa, Walaa Kamel; Raizada, Manish N.

2013-01-01

Endophytes are microbes that inhabit host plants without causing disease and are reported to be reservoirs of metabolites that combat microbes and other pathogens. Here we review diverse classes of secondary metabolites, focusing on anti-microbial compounds, synthesized by fungal endophytes including terpenoids, alkaloids, phenylpropanoids, aliphatic compounds, polyketides, and peptides from the interdisciplinary perspectives of biochemistry, genetics, fungal biology, host plant biology, human and plant pathology. Several trends were apparent. First, host plants are often investigated for endophytes when there is prior indigenous knowledge concerning human medicinal uses (e.g., Chinese herbs). However, within their native ecosystems, and where investigated, endophytes were shown to produce compounds that target pathogens of the host plant. In a few examples, both fungal endophytes and their hosts were reported to produce the same compounds. Terpenoids and polyketides are the most purified anti-microbial secondary metabolites from endophytes, while flavonoids and lignans are rare. Examples are provided where fungal genes encoding anti-microbial compounds are clustered on chromosomes. As different genera of fungi can produce the same metabolite, genetic clustering may facilitate sharing of anti-microbial secondary metabolites between fungi. We discuss gaps in the literature and how more interdisciplinary research may lead to new opportunities to develop bio-based commercial products to combat global crop and human pathogens. PMID:23543048

ClusterMine360: a database of microbial PKS/NRPS biosynthesis

PubMed Central

Conway, Kyle R.; Boddy, Christopher N.

2013-01-01

ClusterMine360 (http://www.clustermine360.ca/) is a database of microbial polyketide and non-ribosomal peptide gene clusters. It takes advantage of crowd-sourcing by allowing members of the community to make contributions while automation is used to help achieve high data consistency and quality. The database currently has >200 gene clusters from >185 compound families. It also features a unique sequence repository containing >10 000 polyketide synthase/non-ribosomal peptide synthetase domains. The sequences are filterable and downloadable as individual or multiple sequence FASTA files. We are confident that this database will be a useful resource for members of the polyketide synthases/non-ribosomal peptide synthetases research community, enabling them to keep up with the growing number of sequenced gene clusters and rapidly mine these clusters for functional information. PMID:23104377

A Putative Gene Cluster from a Lyngbya wollei Bloom that Encodes Paralytic Shellfish Toxin Biosynthesis

PubMed Central

Mihali, Troco K.; Carmichael, Wayne W.; Neilan, Brett A.

2011-01-01

Saxitoxin and its analogs cause the paralytic shellfish-poisoning syndrome, adversely affecting human health and coastal shellfish industries worldwide. Here we report the isolation, sequencing, annotation, and predicted pathway of the saxitoxin biosynthetic gene cluster in the cyanobacterium Lyngbya wollei. The gene cluster spans 36 kb and encodes enzymes for the biosynthesis and export of the toxins. The Lyngbya wollei saxitoxin gene cluster differs from previously identified saxitoxin clusters as it contains genes that are unique to this cluster, whereby the carbamoyltransferase is truncated and replaced by an acyltransferase, explaining the unique toxin profile presented by Lyngbya wollei. These findings will enable the creation of toxin probes, for water monitoring purposes, as well as proof-of-concept for the combinatorial biosynthesis of these natural occurring alkaloids for the production of novel, biologically active compounds. PMID:21347365

Dynamics of cD Clusters of Galaxies. 4; Conclusion of a Survey of 25 Abell Clusters

NASA Technical Reports Server (NTRS)

Oegerle, William R.; Hill, John M.; Fisher, Richard R. (Technical Monitor)

2001-01-01

We present the final results of a spectroscopic study of a sample of cD galaxy clusters. The goal of this program has been to study the dynamics of the clusters, with emphasis on determining the nature and frequency of cD galaxies with peculiar velocities. Redshifts measured with the MX Spectrometer have been combined with those obtained from the literature to obtain typically 50 - 150 observed velocities in each of 25 galaxy clusters containing a central cD galaxy. We present a dynamical analysis of the final 11 clusters to be observed in this sample. All 25 clusters are analyzed in a uniform manner to test for the presence of substructure, and to determine peculiar velocities and their statistical significance for the central cD galaxy. These peculiar velocities were used to determine whether or not the central cD galaxy is at rest in the cluster potential well. We find that 30 - 50% of the clusters in our sample possess significant subclustering (depending on the cluster radius used in the analysis), which is in agreement with other studies of non-cD clusters. Hence, the dynamical state of cD clusters is not different than other present-day clusters. After careful study, four of the clusters appear to have a cD galaxy with a significant peculiar velocity. Dressler-Shectman tests indicate that three of these four clusters have statistically significant substructure within 1.5/h(sub 75) Mpc of the cluster center. The dispersion 75 of the cD peculiar velocities is 164 +41/-34 km/s around the mean cluster velocity. This represents a significant detection of peculiar cD velocities, but at a level which is far below the mean velocity dispersion for this sample of clusters. The picture that emerges is one in which cD galaxies are nearly at rest with respect to the cluster potential well, but have small residual velocities due to subcluster mergers.

Cluster kinetics model for mixtures of glassformers

NASA Astrophysics Data System (ADS)

Brenskelle, Lisa A.; McCoy, Benjamin J.

2007-10-01

For glassformers we propose a binary mixture relation for parameters in a cluster kinetics model previously shown to represent pure compound data for viscosity and dielectric relaxation as functions of either temperature or pressure. The model parameters are based on activation energies and activation volumes for cluster association-dissociation processes. With the mixture parameters, we calculated dielectric relaxation times and compared the results to experimental values for binary mixtures. Mixtures of sorbitol and glycerol (seven compositions), sorbitol and xylitol (three compositions), and polychloroepihydrin and polyvinylmethylether (three compositions) were studied.

Steven's orbital reduction factor in ionic clusters

NASA Astrophysics Data System (ADS)

Gajek, Z.; Mulak, J.

1985-11-01

General expressions for reduction coefficients of matrix elements of angular momentum operator in ionic clusters or molecular systems have been derived. The reduction in this approach results from overlap and covalency effects and plays an important role in the reconciling of magnetic and spectroscopic experimental data. The formulated expressions make possible a phenomenological description of the effect with two independent parameters for typical equidistant clusters. Some detailed calculations also suggest the possibility of a one-parameter description. The results of these calculations for some ionic uranium compounds are presented as an example.

Formation of intermediate-mass black holes through runaway collisions in the first star clusters

NASA Astrophysics Data System (ADS)

Sakurai, Yuya; Yoshida, Naoki; Fujii, Michiko S.; Hirano, Shingo

2017-12-01

We study the formation of massive black holes in the first star clusters. We first locate star-forming gas clouds in protogalactic haloes of ≳107 M⊙ in cosmological hydrodynamics simulations and use them to generate the initial conditions for star clusters with masses of ∼105 M⊙. We then perform a series of direct-tree hybrid N-body simulations to follow runaway stellar collisions in the dense star clusters. In all the cluster models except one, runaway collisions occur within a few million years, and the mass of the central, most massive star reaches ∼400-1900 M⊙. Such very massive stars collapse to leave intermediate-mass black holes (IMBHs). The diversity of the final masses may be attributed to the differences in a few basic properties of the host haloes such as mass, central gas velocity dispersion and mean gas density of the central core. Finally, we derive the IMBH mass to cluster mass ratios, and compare them with the observed black hole to bulge mass ratios in the present-day Universe.

Cationic cluster formation versus disproportionation of low-valent indium and gallium complexes of 2,2'-bipyridine

PubMed Central

Lichtenthaler, Martin R.; Stahl, Florian; Kratzert, Daniel; Heidinger, Lorenz; Schleicher, Erik; Hamann, Julian; Himmel, Daniel; Weber, Stefan; Krossing, Ingo

2015-01-01

Group 13 MI compounds often disproportionate into M0 and MIII. Here, however, we show that the reaction of the MI salt of the weakly coordinating alkoxyaluminate [GaI(C6H5F)2]+[Al(ORF)4]− (RF=C(CF3)3) with 2,2'-bipyridine (bipy) yields the paramagnetic and distorted octahedral [Ga(bipy)3]2+•{[Al(ORF)4]−}2 complex salt. While the latter appears to be a GaII compound, both, EPR and DFT investigations assign a ligand-centred [GaIII{(bipy)3}•]2+ radical dication. Surprisingly, the application of the heavier homologue [InI(C6H5F)2]+[Al(ORF)4]− leads to aggregation and formation of the homonuclear cationic triangular and rhombic [In3(bipy)6]3+, [In3(bipy)5]3+ and [In4(bipy)6]4+ metal atom clusters. Typically, such clusters are formed under strongly reductive conditions. Analysing the unexpected redox-neutral cationic cluster formation, DFT studies suggest a stepwise formation of the clusters, possibly via their triplet state and further investigations attribute the overall driving force of the reactions to the strong In−In bonds and the high lattice enthalpies of the resultant ligand stabilized [M3]3+{[Al(ORF)4]−}3 and [M4]4+{[Al(ORF)4]−}4 salts. PMID:26478464

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Michelle J.; Zoerb, Matthew C.; Campbell, Nicole R.

Here, benzene cluster cations were revisited as a sensitive and selective reagent ion for the chemical ionization of dimethyl sulfide (DMS) and a select group of volatile organic compounds (VOCs). Laboratory characterization was performed using both a new set of compounds (i.e., DMS, β-caryophyllene) as well as previously studied VOCs (i.e., isoprene, α-pinene). Using a field deployable chemical-ionization time-of-flight mass spectrometer (CI-ToFMS), benzene cluster cations demonstrated high sensitivity (> 1 ncps ppt −1) to DMS, isoprene, and α-pinene standards. Parallel measurements conducted using a chemical-ionization quadrupole mass spectrometer, with a much weaker electric field, demonstrated that ion–molecule reactions likely proceed through amore » combination of ligand-switching and direct charge transfer mechanisms. Laboratory tests suggest that benzene cluster cations may be suitable for the selective ionization of sesquiterpenes, where minimal fragmentation (< 25 %) was observed for the detection of β-caryophyllene, a bicyclic sesquiterpene. The in-field stability of benzene cluster cations using CI-ToFMS was examined in the marine boundary layer during the High Wind Gas Exchange Study (HiWinGS). The use of benzene cluster cation chemistry for the selective detection of DMS was validated against an atmospheric pressure ionization mass spectrometer, where measurements from the two instruments were highly correlated ( R 2 > 0.95, 10 s averages) over a wide range of sampling conditions.« less

Horizontal acquisition of toxic alkaloid synthesis in a clade of plant associated fungi.

PubMed

Marcet-Houben, Marina; Gabaldón, Toni

2016-01-01

Clavicipitaceae is a fungal group that comprises species that closely interact with plants as pathogens, parasites or symbionts. A key factor in these interactions is the ability of these fungi to synthesize toxic alkaloid compounds that contribute to the protection of the plant host against herbivores. Some of these compounds such as ergot alkaloids are toxic to humans and have caused important epidemics throughout history. The gene clusters encoding the proteins responsible for the synthesis of ergot alkaloids and lolines in Clavicipitaceae have been elucidated. Notably, homologs to these gene clusters can be found in distantly related species such as Aspergillus fumigatus and Penicillium expansum, which diverged from Clavicipitaceae more than 400 million years ago. We here use a phylogenetic approach to analyze the evolution of these gene clusters. We found that the gene clusters conferring the ability to synthesize ergot alkaloids and loline emerged first in Eurotiomycetes and were then likely transferred horizontally to Clavicipitaceae. Horizontal gene transfer is known to play a role in shaping the distribution of secondary metabolism clusters across distantly related fungal species. We propose that HGT events have played an important role in the capability of Clavicipitaceae to produce two key secondary metabolites that have enhanced the ability of these species to protect their plant hosts, therefore favoring their interactions. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Populational divergence in the impact of three nitrogenous compounds and their combination on larvae of the frog Pelophylax perezi (Seoane, 1885).

PubMed

Egea-Serrano, Andrés; Tejedo, Miguel; Torralva, Mar

2009-08-01

Pollution by nitrogenous compounds is a putative stressful factor that may be causally linked to the decline of amphibians. One way to understand the potentially detrimental consequences of eutrophication on amphibian populations is to investigate variation among populations differing in exposure to nitrogen, this variation potentially indicating evolutionary potential to cope with this stressor. We have examined the effect of nitrogenous compounds (NH(4)(+); NO(2)(-); NO(3)(-), both alone and in combination) on fitness-related larval traits in four populations of Pelophylax perezi naturally exposed to different degrees of eutrophication. The results indicate that both survival and larval final size decrease at higher concentrations of these compounds, either singly or in combination. Additionally, the nitrogenous compounds were more lethal and larval food consumption and final mass were significantly reduced when they were exposed to combinations of compounds. Populations inhabiting highly polluted aquatic environments tolerated higher levels of nitrogenous compounds and showed higher survival rates and larger final size than the populations of less polluted environments, suggesting the potential to adapt to increased nitrogenous contamination in this species.

Comparative Genomic and Transcriptomic Analysis of Wangiella dermatitidis, A Major Cause of Phaeohyphomycosis and a Model Black Yeast Human Pathogen

PubMed Central

Chen, Zehua; Martinez, Diego A.; Gujja, Sharvari; Sykes, Sean M.; Zeng, Qiandong; Szaniszlo, Paul J.; Wang, Zheng; Cuomo, Christina A.

2014-01-01

Black or dark brown (phaeoid) fungi cause cutaneous, subcutaneous, and systemic infections in humans. Black fungi thrive in stressful conditions such as intense light, high radiation, and very low pH. Wangiella (Exophiala) dermatitidis is arguably the most studied phaeoid fungal pathogen of humans. Here, we report our comparative analysis of the genome of W. dermatitidis and the transcriptional response to low pH stress. This revealed that W. dermatitidis has lost the ability to synthesize alpha-glucan, a cell wall compound many pathogenic fungi use to evade the host immune system. In contrast, W. dermatitidis contains a similar profile of chitin synthase genes as related fungi and strongly induces genes involved in cell wall synthesis in response to pH stress. The large portfolio of transporters may provide W. dermatitidis with an enhanced ability to remove harmful products as well as to survive on diverse nutrient sources. The genome encodes three independent pathways for producing melanin, an ability linked to pathogenesis; these are active during pH stress, potentially to produce a barrier to accumulated oxidative damage that might occur under stress conditions. In addition, a full set of fungal light-sensing genes is present, including as part of a carotenoid biosynthesis gene cluster. Finally, we identify a two-gene cluster involved in nucleotide sugar metabolism conserved with a subset of fungi and characterize a horizontal transfer event of this cluster between fungi and algal viruses. This work reveals how W. dermatitidis has adapted to stress and survives in diverse environments, including during human infections. PMID:24496724

Characterization of distinct Arctic aerosol accumulation modes and their sources

NASA Astrophysics Data System (ADS)

Lange, R.; Dall'Osto, M.; Skov, H.; Nøjgaard, J. K.; Nielsen, I. E.; Beddows, D. C. S.; Simo, R.; Harrison, R. M.; Massling, A.

2018-06-01

In this work we use cluster analysis of long term particle size distribution data to expand an array of different shorter term atmospheric measurements, thereby gaining insights into longer term patterns and properties of Arctic aerosol. Measurements of aerosol number size distributions (9-915 nm) were conducted at Villum Research Station (VRS), Station Nord in North Greenland during a 5 year record (2012-2016). Alongside this, measurements of aerosol composition, meteorological parameters, gaseous compounds and cloud condensation nuclei (CCN) activity were performed during different shorter occasions. K-means clustering analysis of particle number size distributions on daily basis identified several clusters. Clusters of accumulation mode aerosols (main size modes > 100 nm) accounted for 56% of the total aerosol during the sampling period (89-91% during February-April, 1-3% during June-August). By association to chemical composition, cloud condensation nuclei properties, and meteorological variables, three typical accumulation mode aerosol clusters were identified: Haze (32% of the time), Bimodal (14%) and Aged (6%). In brief: (1) Haze accumulation mode aerosol shows a single mode at 150 nm, peaking in February-April, with highest loadings of sulfate and black carbon concentrations. (2) Accumulation mode Bimodal aerosol shows two modes, at 38 nm and 150 nm, peaking in June-August, with the highest ratio of organics to sulfate concentrations. (3) Aged accumulation mode aerosol shows a single mode at 213 nm, peaking in September-October and is associated with cloudy and humid weather conditions during autumn. The three aerosol clusters were considered alongside CCN concentrations. We suggest that organic compounds, that are likely marine biogenic in nature, greatly influence the Bimodal cluster and contribute significantly to its CCN activity. This stresses the importance of better characterizing the marine ecosystem and the aerosol-mediated climate effects in the Arctic.

Singlet Excited States of Cl and Br Molecules: New Theories Applied to the -XO and -XO2 (X=C1 and Br) Chromophores

NASA Technical Reports Server (NTRS)

Lee, Timothy J.; Srinivasan, Parthiban; Head-Gordon, Martin; Huo, Winifred (Technical Monitor)

1998-01-01

Electronic excitation energies are determined using single-reference based theories derived from response equations involving perturbation theory and coupled-cluster theory. These methods are applied to the singlet manifold of excited electronic states of the HClO, HBrO, HOClO, HOBrO, HClO2, and HBrO2 molecules. The reliability of the various perturbation theory approaches is assessed by comparison to the linear-response singles and doubles coupled-cluster (LRCCSD) method. The excitation energies for the Y-XO compounds are compared and contrasted for Y=H and HO, and X=Cl and Br. A similar comparison is performed for the H-XO2 compounds.

White Dwarfs in Star Clusters: The Initial-Final Mass Relation for Stars from 0.85 to 8 M$_\\odot$

NASA Astrophysics Data System (ADS)

Cummings, Jeffrey; Kalirai, Jason; Tremblay, P.-E.; Ramírez-Ruiz, Enrico

2018-01-01

The spectroscopic study of white dwarfs provides both their mass, cooling age, and intrinsic photometric properties. For white dwarfs in the field of well-studied star clusters, this intrinsic photometry can be used to determine if they are members of that star cluster. Comparison of a member white dwarf's cooling age to its total cluster's age provides the evolutionary timescale of its progenitor star, and hence the mass. This is the initial-final mass relation (IFMR) for stars, which gives critical information on how a progenitor star evolves and loses mass throughout its lifetime, and how this changes with progenitor mass. Our work, for the first time, presents a uniform analysis of 85 white dwarf cluster members spanning from progenitor masses of 0.85 to 8 M$_\\odot$. Comparison of our work to theoretical IFMRs shows remarkable consistency in their shape but differences remain. We will discuss possible explanations for these differences, including the effects of stellar rotation.

Rhizovarins A-F, Indole-Diterpenes from the Mangrove-Derived Endophytic Fungus Mucor irregularis QEN-189.

PubMed

Gao, Shu-Shan; Li, Xiao-Ming; Williams, Katherine; Proksch, Peter; Ji, Nai-Yun; Wang, Bin-Gui

2016-08-26

Genome mining of the fungus Mucor irregularis (formerly known as Rhizomucor variabilis) revealed the presence of various gene clusters for secondary metabolite biosynthesis, including several terpene-based clusters. Investigation into the chemical diversity of M. irregularis QEN-189, an endophytic fungus isolated from the fresh inner tissue of the marine mangrove plant Rhizophora stylosa, resulted in the discovery of 20 structurally diverse indole-diterpenes including six new compounds, namely, rhizovarins A-F (1-6). Among them, compounds 1-3 represent the most complex members of the reported indole-diterpenes. The presence of an unusual acetal linked to a hemiketal (1) or a ketal (2 and 3) in an unprecedented 4,6,6,8,5,6,6,6,6-fused indole-diterpene ring system makes them chemically unique. Their structures and absolute configurations were elucidated by spectroscopic analysis, modified Mosher's method, and chemical calculations. Each of the isolated compounds was evaluated for antitumor activity against HL-60 and A-549 cell lines.

Oxaphosphinanes: new therapeutic perspectives for glioblastoma.

PubMed

Clarion, Ludovic; Jacquard, Carine; Sainte-Catherine, Odile; Loiseau, Séverine; Filippini, Damien; Hirlemann, Marie-Hélène; Volle, Jean-Noël; Virieux, David; Lecouvey, Marc; Pirat, Jean-Luc; Bakalara, Norbert

2012-03-08

This paper reports the design and the synthesis of a new family of compounds, the phostines, belonging to the [1,2]oxaphosphinane family. Twenty-six compounds have been screened for their antiproliferative activity against a large panel of NCI cancer cell lines. Because of its easy synthesis and low EC(50) value (500 nM against the C6 rat glioma cell line), compound 3.1a was selected for further biological study. Moreover, the specific biological effect of 3.1a on the glioblastoma phylogenetic cluster from the NCI is dependent on its stereochemistry. Within that cluster, 3.1a has a higher antiproliferative activity than Temozolomide and is more potent than paclitaxel for the SF295 and SNB75 cell lines. In constrast with paclitaxel and vincristine, 3.1a is devoid of astrocyte toxicity. The original activity spectrum of 3.1a on the NCI cancer cell line panel allows the development of this family for use in association with existing drugs, opening new therapeutic perspectives.

Synthesis and Characterization of Novel Compound Clusters

DTIC Science & Technology

1997-08-26

also be intrinsically stable, they cannot be formed by this plasma chemistry presumably because the metals are less reactive. Plasma chemistry reactions...samples without the presence of hydrogen. Vaporization of these composite samples produces the metal carbide clusters in many cases where plasma chemistry does...antimony or bismuth cannot be produced by the hydrocarbon plasma chemistry method, but they are produced readily from composite sample (metal film on

An empirical method to cluster objective nebulizer adherence data among adults with cystic fibrosis.

PubMed

Hoo, Zhe H; Campbell, Michael J; Curley, Rachael; Wildman, Martin J

2017-01-01

The purpose of using preventative inhaled treatments in cystic fibrosis is to improve health outcomes. Therefore, understanding the relationship between adherence to treatment and health outcome is crucial. Temporal variability, as well as absolute magnitude of adherence affects health outcomes, and there is likely to be a threshold effect in the relationship between adherence and outcomes. We therefore propose a pragmatic algorithm-based clustering method of objective nebulizer adherence data to better understand this relationship, and potentially, to guide clinical decisions. This clustering method consists of three related steps. The first step is to split adherence data for the previous 12 months into four 3-monthly sections. The second step is to calculate mean adherence for each section and to score the section based on mean adherence. The third step is to aggregate the individual scores to determine the final cluster ("cluster 1" = very low adherence; "cluster 2" = low adherence; "cluster 3" = moderate adherence; "cluster 4" = high adherence), and taking into account adherence trend as represented by sequential individual scores. The individual scores should be displayed along with the final cluster for clinicians to fully understand the adherence data. We present three cases to illustrate the use of the proposed clustering method. This pragmatic clustering method can deal with adherence data of variable duration (ie, can be used even if 12 months' worth of data are unavailable) and can cluster adherence data in real time. Empirical support for some of the clustering parameters is not yet available, but the suggested classifications provide a structure to investigate parameters in future prospective datasets in which there are accurate measurements of nebulizer adherence and health outcomes.

Identification and Functional Analysis of the Nocardithiocin Gene Cluster in Nocardia pseudobrasiliensis

PubMed Central

Sakai, Kanae; Komaki, Hisayuki; Gonoi, Tohru

2015-01-01

Nocardithiocin is a thiopeptide compound isolated from the opportunistic pathogen Nocardia pseudobrasiliensis. It shows a strong activity against acid-fast bacteria and is also active against rifampicin-resistant Mycobacterium tuberculosis. Here, we report the identification of the nocardithiocin gene cluster in N. pseudobrasiliensis IFM 0761 based on conserved thiopeptide biosynthesis gene sequence and the whole genome sequence. The predicted gene cluster was confirmed by gene disruption and complementation. As expected, strains containing the disrupted gene did not produce nocardithiocin while gene complementation restored nocardithiocin production in these strains. The predicted cluster was further analyzed using RNA-seq which showed that the nocardithiocin gene cluster contains 12 genes within a 15.2-kb region. This finding will promote the improvement of nocardithiocin productivity and its derivatives production. PMID:26588225

Detecting Statistically Significant Communities of Triangle Motifs in Undirected Networks

DTIC Science & Technology

2016-04-26

REPORT TYPE Final 3. DATES COVERED (From - To) 15 Oct 2014 to 14 Jan 2015 4. TITLE AND SUBTITLE Detecting statistically significant clusters of...extend the work of Perry et al. [6] by developing a statistical framework that supports the detection of triangle motif-based clusters in complex...priori, the need for triangle motif-based clustering . 2. Developed an algorithm for clustering undirected networks, where the triangle con guration was

The improvement and simulation for LEACH clustering routing protocol

NASA Astrophysics Data System (ADS)

Ji, Ai-guo; Zhao, Jun-xiang

2017-01-01

An energy-balanced unequal multi-hop clustering routing protocol LEACH-EUMC is proposed in this paper. The candidate cluster head nodes are elected firstly, then they compete to be formal cluster head nodes by adding energy and distance factors, finally the date are transferred to sink through multi-hop. The results of simulation show that the improved algorithm is better than LEACH in network lifetime, energy consumption and the amount of data transmission.

Final Report of the Evaluation of the 1969-1970 Benjamin Franklin Cluster Program: Programs and Patterns for Disadvantaged High School Students. ESEA Title I.

ERIC Educational Resources Information Center

Hoffman, Louis J.

The Cluster Program at Benjamin Franklin High School, funded under Title I of the 1965 Elementary Secondary Education Act, is designed to be a school within a school in which 249 ninth grade students attend classes in two separate clusters. Each cluster is formulated such that all students receive instruction from five teachers in classes whose…

Cohesive Energies of Some Transition Metal Compounds Using Embedded Clusters

NASA Astrophysics Data System (ADS)

Press, Mehernosh Rustom

The molecular-clusters approach to electronic structure calculation is especially well-suited to the study of properties that depend primarily on the local environment of a system, especially those with no translational symmetry, e.g. systems with defects and structural deformations. The presence of the rest of the crystal environment can be accounted for approximately by embedding the cluster in a self-consistent crystal potential. This thesis makes a contribution in the area of investigating the capability of embedded molecular-clusters to yield reliable bulk structural properties. To this end, an algorithm for calculating the cohesive energies of clusters within the discrete-variational X(,(alpha)) LCAO-MO formulation is set up and verified on simple solids: Li, Na, Cu and LiF. We then use this formulation to study transition metal compounds, for which the interesting physics lies in local lattice defects, foreign impurities and structural deformations. In a self -consistent calculation of the lattice energies and stability of defect clusters in wustite, Fe(,1-x)O, corner-sharing aggregates of the 4:1 defect are identified as the most stable defect configurations due to efficient compensation of the cluster charge. The intercalation properties of layered-transition-metal-dichalcogenides continues to be a fertile experimental working area, backed by comparatively little theoretical study. We find that intercalation of ZrS(,2) with Na perturbs the valence energy level structure sufficiently to induce a more ionic Zr-S bond, a narrowing of the optical gap and filling of the lowest unoccupied host lattice orbitals with the electron donated by Na. Fe - intercalation in ZrS(,2) is accommodated via a strong Fe-S bond, impurity-like band levels in the optical gap of the host and hybridization-driven compression and lowering of the conduction band energy levels. The piezoelectric cuprous halides, CuCl and CuBr, exhibit a host of intriguing properties due to a filled and very active d('10) shell at the Fermi energy. A self-consistent calculation via energy minimization of the internal strain in these compounds shows both Cu-halide bonds to be very rigid with little charge delocalization under strain. Piezoelectric response is calculated in terms of effective charges and quadrupolar moments, e(,T) and (DELTA)Q.

Tetravalent Ce in the Nitrate-Decorated Hexanuclear Cluster [Ce 6 (μ 3 -O) 4 (μ 3 -OH) 4 ] 12+ : A Structural End Point for Ceria Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Estes, Shanna L.; Antonio, Mark R.; Soderholm, L.

2016-03-17

We describe the synthesis and characterization of three glycine-stabilized hexanuclear Cely cluster compounds, each containing the [Ce-6(mu(3)-O)(4)(mu(3)-OH)(4)](12+) core structure. Crystallized from aqueous nitrate solutions with pH < 0, the core cluster structures exhibit variable decoration by nitrate, glycine, and water ligands depending on solution conditions, where increased nitrate and glycine decoration of the cluster core was observed for crystals synthesized at high Ce and nitrate concentrations. No other crystalline products were observed using this synthetic route. In addition to confirming the tetravalent oxidation state of cerium in one of the reported clusters, cyclic voltammetry also indicates that Ce-IV is reducedmore » at similar to+0.60 V vs Ag/AgCl (3 M NaCl), which is significantly less than the standard electrode potential. This large decrease in the Ce-IV/Ce-III reduction potential suggests that Ce-IV is significantly stabilized relative to Ce-III within the examined cluster. These compounds are discussed in terms of their importance as small, end member, ceric oxide nanoparticles. Single-crystal structural solutions, together with voltammetry and electrolysis data, permit the decoupling of Ce-III defects and substoichiometry. In addition, Ce-Ce distances can be used to determine an "effective" CeO2-x lattice constant, providing a simple method for comparing literature descriptions. The results are discussed in terms of their potential implications for the mechanisms by which nanoparticle ceria serve as catalysts and oxygen-storage materials.« less

Antifungal activity improved by coproduction of cyclodextrins and anabaenolysins in Cyanobacteria

PubMed Central

Shishido, Tania K.; Jokela, Jouni; Kolehmainen, Clara-Theresia; Fewer, David P.; Wahlsten, Matti; Wang, Hao; Rouhiainen, Leo; Rizzi, Ermanno; De Bellis, Gianluca; Permi, Perttu; Sivonen, Kaarina

2015-01-01

Cyclodextrins are cyclic oligosaccharides widely used in the pharmaceutical industry to improve drug delivery and to increase the solubility of hydrophobic compounds. Anabaenolysins are lipopeptides produced by cyanobacteria with potent lytic activity in cholesterol-containing membranes. Here, we identified the 23- to 24-kb gene clusters responsible for the production of the lipopeptide anabaenolysin. The hybrid nonribosomal peptide synthetase and polyketide synthase biosynthetic gene cluster is encoded in the genomes of three anabaenolysin-producing strains of Anabaena. We detected previously unidentified strains producing known anabaenolysins A and B and discovered the production of new variants of anabaenolysins C and D. Bioassays demonstrated that anabaenolysins have weak antifungal activity against Candida albicans. Surprisingly, addition of the hydrophilic fraction of the whole-cell extracts increased the antifungal activity of the hydrophobic anabaenolysins. The fraction contained compounds identified by NMR as α-, β-, and γ-cyclodextrins, which undergo acetylation. Cyclodextrins have been used for decades to improve the solubility and bioavailability of many drugs including antifungal compounds. This study shows a natural example of cyclodextrins improving the solubility and efficacy of an antifungal compound in an ancient lineage of photosynthetic bacteria. PMID:26474830

Nano-sized manganese oxides as biomimetic catalysts for water oxidation in artificial photosynthesis: a review

PubMed Central

Najafpour, Mohammad Mahdi; Rahimi, Fahimeh; Aro, Eva-Mari; Lee, Choon-Hwan; Allakhverdiev, Suleyman I.

2012-01-01

There has been a tremendous surge in research on the synthesis of various metal compounds aimed at simulating the water-oxidizing complex (WOC) of photosystem II (PSII). This is crucial because the water oxidation half reaction is overwhelmingly rate-limiting and needs high over-voltage (approx. 1 V), which results in low conversion efficiencies when working at current densities required for hydrogen production via water splitting. Particular attention has been given to the manganese compounds not only because manganese has been used by nature to oxidize water but also because manganese is cheap and environmentally friendly. The manganese–calcium cluster in PSII has a dimension of about approximately 0.5 nm. Thus, nano-sized manganese compounds might be good structural and functional models for the cluster. As in the nanometre-size of the synthetic models, most of the active sites are at the surface, these compounds could be more efficient catalysts than micrometre (or bigger) particles. In this paper, we focus on nano-sized manganese oxides as functional and structural models of the WOC of PSII for hydrogen production via water splitting and review nano-sized manganese oxides used in water oxidation by some research groups. PMID:22809849

Investigations in Science Education, Vol. 3, No. 3. Expanded Abstracts and Critical Analyses of Recent Research.

ERIC Educational Resources Information Center

Helgeson, Stanley L., Ed.; Blosser, Patricia E., Ed.

This issue contains expanded abstracts of research reports grouped into two clusters and a section of individual studies. The first cluster contains abstracts of two research reports dealing with trait-treatment interaction studies. The second cluster deals with examination items categorized according to Bloom's Taxonomy. The final section,…

78 FR 32161 - Oklahoma: Final Authorization of State Hazardous Waste Management Program Revision

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-29

... statutory and regulatory provisions necessary to administer the provisions of RCRA Cluster XXI, and... July 1, 2010 Through June 30, 2011 RCRA Cluster XXI prepared on June 14, 2012. The DEQ incorporates the... the authorizations at 77 FR 1236-1262, 75 FR 15273 through 15276 for RCRA Cluster XXI. The Federal...

Self-assembled decanuclear Na(I)2Mn(II)4Mn(III)4 complexes: from discrete clusters to 1-D and 2-D structures, with the Mn(II)4Mn(III)4 unit displaying a large spin ground state and probable SMM behaviour.

PubMed

Langley, Stuart K; Chilton, Nicholas F; Moubaraki, Boujemaa; Murray, Keith S

2011-12-07

The synthesis, magnetic characterization and X-ray crystal structures are reported for five new manganese compounds, [Mn(III)(teaH(2))(sal)]·(1/2)H(2)O (1), [Na(I)(2)Mn(II)(4)Mn(III)(4)(teaH)(6)(sal)(4)(N(3))(2)(MeOH)(4)]·6MeOH (2), [Na(I)(2)Mn(II)(4)Mn(III)(4)(teaH)(6)(sal)(4)(N(3))(2)(MeOH)(2)](n)·7MeOH (3), [Na(I)(2)Mn(II)(4)Mn(III)(4)(teaH)(6)(sal)(4)(N(3))(2)(MeOH)(2)](n)·2MeOH·Et(2)O (4) and [K(I)(2)Mn(II)(4)Mn(III)(4)(teaH)(6)(sal)(4)(N(3))(2)(H(2)O)(2)](n)·5MeOH (5). Complex 1 is a mononuclear compound, formed via the reaction of Mn(NO(3))(2)·4H(2)O, triethanolamine (teaH(3)) and salicylic acid (salH(2)) in a basic methanolic solution. Compound 2 is a mixed-valent hetero-metallic cluster made up of a Mn(8)Na(2) decanuclear core and is formed via the reaction of sodium azide (NaN(3)) with 1. Compounds 3-5 are isolated as 1- or 2-D coordination polymers, each containing the decanuclear Mn(8)M(2) (M = Na(+) or K(+)) core building block as the repeating unit. Compound 3 is isolated when 1 is reacted with NaN(3) over a very short reaction time and forms a 1-D coordination polymer. Each unit displays inter-cluster bridges via the O-atoms of teaH(2-) ligands bonding to the sodium ions of an adjacent cluster. Increasing the reaction time appears to drive the formation of 4 which forms 2-D polymeric sheets and is a packing polymorph of 3. The addition of KMnO(4) and NaN(3) to 1 resulted in compound 5, which also forms a 1-D coordination polymer of the decanuclear core unit. The 1-D chains are now linked via inter-cluster potassium and salicylate bridges. Solid state DC susceptibility measurements were performed on compounds 1-5. The data for 1 are as expected for an S = 2 Mn(III) ion, with the isothermal M vs. H data being fitted by matrix diagonalization methods to give values of g and the axial (D) and rhombic (E) zero field splitting parameters of 2.02, -2.70 cm(-1) and 0.36 cm(-1) respectively. The data for 2-5, each with an identical Mn(II)(4)Mn(III)(4) metallic core, indicates large spin ground states, with likely values of S = 16 (±1) for each. Solid state AC susceptibility measurements confirm the large spin ground state values and is also suggestive of SMM behaviour for 2-5 as observed via the onset of frequency dependent out-of-phase peaks.

Cluster evolution during the early stages of heating explosives and its relationship to sensitivity: a comparative study of TATB, β-HMX and PETN by molecular reactive force field simulations.

PubMed

Wen, Yushi; Zhang, Chaoyang; Xue, Xianggui; Long, Xinping

2015-05-14

Clustering is experimentally and theoretically verified during the complicated processes involved in heating high explosives, and has been thought to influence their detonation properties. However, a detailed description of the clustering that occurs has not been fully elucidated. We used molecular dynamic simulations with an improved reactive force field, ReaxFF_lg, to carry out a comparative study of cluster evolution during the early stages of heating for three representative explosives: 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), β-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) and pentaerythritol tetranitrate (PETN). These representatives vary greatly in their oxygen balance (OB), molecular structure, stability and experimental sensitivity. We found that when heated, TATB, HMX and PETN differ in the size, amount, proportion and lifetime of their clusters. We also found that the clustering tendency of explosives decreases as their OB becomes less negative. We propose that the relationship between OB and clustering can be attributed to the role of clustering in detonation. That is, clusters can form more readily in a high explosive with a more negative OB, which retard its energy release, secondary decomposition, further decomposition to final small molecule products and widen its detonation reaction zone. Moreover, we found that the carbon content of the clusters increases during clustering, in accordance with the observed soot, which is mainly composed of carbon as the final product of detonation or deflagration.

Iterative Stable Alignment and Clustering of 2D Transmission Electron Microscope Images

PubMed Central

Yang, Zhengfan; Fang, Jia; Chittuluru, Johnathan; Asturias, Francisco J.; Penczek, Pawel A.

2012-01-01

SUMMARY Identification of homogeneous subsets of images in a macromolecular electron microscopy (EM) image data set is a critical step in single-particle analysis. The task is handled by iterative algorithms, whose performance is compromised by the compounded limitations of image alignment and K-means clustering. Here we describe an approach, iterative stable alignment and clustering (ISAC) that, relying on a new clustering method and on the concepts of stability and reproducibility, can extract validated, homogeneous subsets of images. ISAC requires only a small number of simple parameters and, with minimal human intervention, can eliminate bias from two-dimensional image clustering and maximize the quality of group averages that can be used for ab initio three-dimensional structural determination and analysis of macromolecular conformational variability. Repeated testing of the stability and reproducibility of a solution within ISAC eliminates heterogeneous or incorrect classes and introduces critical validation to the process of EM image clustering. PMID:22325773

Molecular growth from a Mo176 to a Mo248 cluster

NASA Astrophysics Data System (ADS)

Müller, A.; Shah, Syed Q. N.; Bögge, H.; Schmidtmann, M.

1999-01-01

In polyoxometalate chemistry a large variety of compounds, clusters and solid-state structures can be formed by the linking together of well-defined metal-oxygen building blocks, . These species exhibit unusual topological and electronic properties, andfind applications ranging from medicine to industrial processes. The recently reported ring-shaped mixed-valence polyoxomolybdates of the type {Mo154} (refs 5, 6) and {Mo176} (refs 7, 8) represent a new class of giant clusters with nanometre-sized cavities and interesting properties for host-guest chemistry. Here we describe the formation of related clusters of the type {Mo248} formed by addition of further units to the inner surface of the {Mo176 } `wheel'. The additional units arrange themselves into two {Mo36} `hub-caps' on the initial wheel-clusters that are not stable in isolation. These findings reveal a new pathway to the development of complex coordination clusters.

Structural and functional characterization of solute binding proteins for aromatic compounds derived from lignin: p-coumaric acid and related aromatic acids.

PubMed

Tan, Kemin; Chang, Changsoo; Cuff, Marianne; Osipiuk, Jerzy; Landorf, Elizabeth; Mack, Jamey C; Zerbs, Sarah; Joachimiak, Andrzej; Collart, Frank R

2013-10-01

Lignin comprises 15-25% of plant biomass and represents a major environmental carbon source for utilization by soil microorganisms. Access to this energy resource requires the action of fungal and bacterial enzymes to break down the lignin polymer into a complex assortment of aromatic compounds that can be transported into the cells. To improve our understanding of the utilization of lignin by microorganisms, we characterized the molecular properties of solute binding proteins of ATP-binding cassette transporter proteins that interact with these compounds. A combination of functional screens and structural studies characterized the binding specificity of the solute binding proteins for aromatic compounds derived from lignin such as p-coumarate, 3-phenylpropionic acid and compounds with more complex ring substitutions. A ligand screen based on thermal stabilization identified several binding protein clusters that exhibit preferences based on the size or number of aromatic ring substituents. Multiple X-ray crystal structures of protein-ligand complexes for these clusters identified the molecular basis of the binding specificity for the lignin-derived aromatic compounds. The screens and structural data provide new functional assignments for these solute-binding proteins which can be used to infer their transport specificity. This knowledge of the functional roles and molecular binding specificity of these proteins will support the identification of the specific enzymes and regulatory proteins of peripheral pathways that funnel these compounds to central metabolic pathways and will improve the predictive power of sequence-based functional annotation methods for this family of proteins. Copyright © 2013 Wiley Periodicals, Inc.

Structural and functional characterization of solute binding proteins for aromatic compounds derived from lignin: p-coumaric acid and related aromatic acids

PubMed Central

Tan, Kemin; Chang, Changsoo; Cuff, Marianne; Osipiuk, Jerzy; Landorf, Elizabeth; Mack, Jamey C.; Zerbs, Sarah; Joachimiak, Andrzej; Collart, Frank R.

2013-01-01

Lignin comprises 15.25% of plant biomass and represents a major environmental carbon source for utilization by soil microorganisms. Access to this energy resource requires the action of fungal and bacterial enzymes to break down the lignin polymer into a complex assortment of aromatic compounds that can be transported into the cells. To improve our understanding of the utilization of lignin by microorganisms, we characterized the molecular properties of solute binding proteins of ATP.binding cassette transporter proteins that interact with these compounds. A combination of functional screens and structural studies characterized the binding specificity of the solute binding proteins for aromatic compounds derived from lignin such as p-coumarate, 3-phenylpropionic acid and compounds with more complex ring substitutions. A ligand screen based on thermal stabilization identified several binding protein clusters that exhibit preferences based on the size or number of aromatic ring substituents. Multiple X-ray crystal structures of protein-ligand complexes for these clusters identified the molecular basis of the binding specificity for the lignin-derived aromatic compounds. The screens and structural data provide new functional assignments for these solute.binding proteins which can be used to infer their transport specificity. This knowledge of the functional roles and molecular binding specificity of these proteins will support the identification of the specific enzymes and regulatory proteins of peripheral pathways that funnel these compounds to central metabolic pathways and will improve the predictive power of sequence-based functional annotation methods for this family of proteins. PMID:23606130

Cu-containing Keggin-type polyoxometalates-based organic-inorganic hybrids with double electro-catalytic behaviors

NASA Astrophysics Data System (ADS)

Zhou, Wanli; Zheng, Yanping; Peng, Jun

2018-02-01

Four new organic-inorganic hybrids consisting of Keggin-type polyoxometalates: [Cu5(bimpy)5(α-BW12O40)]·4H2O (1), [Cu4(bimpy)4(α-SiW12O40)]·2H2O (2), [Cu4(bimpy)4(α-HPMo12O40)2]·2H2O (3), [Cu2(bimpy)4(H2O)2(α-HPW12O40)2]·8H2O (4) (bimpy = 2,5-bis(1H-imidazol-1-yl)pyridine), have been hydrothermally synthesized. Compounds 1-4 are constructed from Cu/bimpy segments modified different types of Keggin POMs. The 1D double chains of compound 1 are featured by {-Cu/bimpy-POM-Cu/bimpy-}n chains and {-Cu-bimpy-Cu-}n metal-organic chains; compound 2 with 1D "ladder-like" structure stemmed from {-Cu-bimpy-Cu-}n wave-like chains and α-SiW12 clusters; In compound 3, [Cu4(bimpy)4]4+ motifs are linked by α-PMo12 clusters to give rise to a (3,4)-connected two-dimensional architecture with the (83)(86) topology, while compound 4 has a (3,4,5)-connected 3D framework with the (42,6)(42,6,83)(42,65,83) topology. Cyclic voltammetries of compounds 1-4 show discrepant double electro-catalytic properties for reduction of nitrite and oxidation of ascorbic acid owing to variant Keggin-type POMs and Cu/bimpy complexes.

In silico identification and construction of microbial gene clusters associated with biodegradation of xenobiotic compounds.

PubMed

Awasthi, Garima; Kumari, Anjani; Pant, Aditya Bhushan; Srivastava, Prachi

2018-01-01

Chemical substances not showing any importance in existence of biological systems and causing serious health hazards may be designated as Xenobiotic compound. Elimination or degradation of these unwanted substances is a major issue of concern for current time research. Process of biodegradation is a very important aspect of current research as discussed in current manuscript. Current study focuses on the detailed mining of data for the construction of microbial consortia for wide range of xenobiotics compounds. Intensive literature search was done for the construction of this library. Desired data was retrieved from NCBI in fasta format. Data was analysed through homology approaches by using BLAST. This homology based searched enriched with a great vision that not only bacterial population but many other cheap and potential sources are available for different xenobiotic degradation. Though it was focused that bacterial population covers a major part of biodegradation which is near about 90.6% but algae and fungi are also showing promising future in degradation of some important xenobiotic compounds. Analysis of data reveals that Pseudomonas putida has potential for degrading maximum compounds. Establishment of correlation through cluster analysis signifies that Pseudomonas putida, Aspergillus niger and Skeletonema costatum can have combined traits that can be used in finding out actual evolutionary relationship between these species. These findings may also givea new outcome in terms of much cheaper and eco-friendly source in the area of biodegradation of specified xenobiotic compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interactions of ionic liquids and acetone: thermodynamic properties, quantum-chemical calculations, and NMR analysis.

PubMed

Ruiz, Elia; Ferro, Victor R; Palomar, Jose; Ortega, Juan; Rodriguez, Juan Jose

2013-06-20

The interactions between ionic liquids (ILs) and acetone have been studied to obtain a further understanding of the behavior of their mixtures, which generally give place to an exothermic process, mutual miscibility, and negative deviation of Raoult's law. COSMO-RS was used as a suitable computational method to systematically analyze the excess enthalpy of IL-acetone systems (>300), in terms of the intermolecular interactions contributing to the mixture behavior. Spectroscopic and COSMO-RS results indicated that acetone, as a polar compound with strong hydrogen bond acceptor character, in most cases, establishes favorable hydrogen bonding with ILs. This interaction is strengthened by the presence of an acidic cation and an anion with dispersed charge and non-HB acceptor character in the IL. COSMO-RS predictions indicated that gas-liquid and vapor-liquid equilibrium data for IL-acetone systems can be finely tuned by the IL selection, that is, acting on the intermolecular interactions between the molecular and ionic species in the liquid phase. NMR measurements for IL-acetone mixtures at different concentrations were also carried out. Quantum-chemical calculations by using molecular clusters of acetone and IL species were finally performed. These results provided additional evidence of the main role played by hydrogen bonding in the behavior of systems containing ILs and HB acceptor compounds, such as acetone.

The Noscapine Chronicle: A Pharmaco-Historic Biography of the Opiate Alkaloid Family and its Clinical Applications

PubMed Central

Rida, Padmashree C. G.; LiVecche, Dillon; Ogden, Angela; Zhou, Jun; Aneja, Ritu

2016-01-01

Given its manifold potential therapeutic applications and amenability to modification, noscapine is a veritable “Renaissance drug” worthy of commemoration. Perhaps the only facet of noscapine’s profile more astounding than its versatility is its virtual lack of side effects and addictive properties, which distinguishes it from other denizens of Papaver somniferum. This review intimately chronicles the rich intellectual and pharmacological history behind the noscapine family of compounds, the length of whose arms was revealed over decades of patient scholarship and experimentation. We discuss the intriguing story of this family of nontoxic alkaloids, from noscapine’s purification from opium at the turn of the 19th century in Paris to the recent torrent of rationally designed analogs with tremendous anticancer potential. In between, noscapine’s unique pharmacology; impact on cellular signaling pathways, the mitotic spindle, and centrosome clustering; use as an antimalarial drug and cough suppressant; and exceptional potential as a treatment for polycystic ovarian syndrome, strokes, and diverse malignancies are catalogued. Seminal experiments involving some of its more promising analogs, such as amino-noscapine, 9-nitronoscapine, 9-bromonoscapine, and reduced bromonoscapine, are also detailed. Finally, the bright future of these oftentimes even more exceptional derivatives is described, rounding out a portrait of a truly remarkable family of compounds. PMID:26179481

Degradation of oil products in a soil from a Russian Barents hot-spot during electrodialytic remediation.

PubMed

Pedersen, Kristine B; Lejon, Tore; Jensen, Pernille E; Ottosen, Lisbeth M

2016-01-01

A highly oil-polluted soil from Krasnoe in North-West Russia was used to investigate the degradation of organic pollutants during electrodialytic remediation. Removal efficiencies were up to 70 % for total hydrocarbons (THC) and up to 65 % for polyaromatic hydrocarbons (PAH). Relatively more of the lighter PAH compounds and THC fractions were degraded. A principal component analysis (PCA) revealed a difference in the distribution of PAH compounds after the remediation. The observed clustering of experiments in the PCA scores plot was assessed to be related to the stirring rate. Multivariate analysis of the experimental settings and final concentrations in the 12 experiments revealed that the stirring rate of the soil suspension was by far the most important parameter for the remediation for both THC and PAH. Light was the second most important variable for PAH and seems to influence degradation. The experimental variables current density and remediation time did not significantly influence the degradation of the organic pollutants. Despite current density not influencing the remediation, there is potential for degrading organic pollutants during electrodialytic removal of heavy metals, as long as a stirred set-up is applied. Depending on remediation objectives, further optimisation may be needed in order to develop efficient remediation strategies.

The Noscapine Chronicle: A Pharmaco-Historic Biography of the Opiate Alkaloid Family and its Clinical Applications.

PubMed

Rida, Padmashree C G; LiVecche, Dillon; Ogden, Angela; Zhou, Jun; Aneja, Ritu

2015-09-01

Given its manifold potential therapeutic applications and amenability to modification, noscapine is a veritable "Renaissance drug" worthy of commemoration. Perhaps the only facet of noscapine's profile more astounding than its versatility is its virtual lack of side effects and addictive properties, which distinguishes it from other denizens of Papaver somniferum. This review intimately chronicles the rich intellectual and pharmacological history behind the noscapine family of compounds, the length of whose arms was revealed over decades of patient scholarship and experimentation. We discuss the intriguing story of this family of nontoxic alkaloids, from noscapine's purification from opium at the turn of the 19th century in Paris to the recent torrent of rationally designed analogs with tremendous anticancer potential. In between, noscapine's unique pharmacology; impact on cellular signaling pathways, the mitotic spindle, and centrosome clustering; use as an antimalarial drug and cough suppressant; and exceptional potential as a treatment for polycystic ovarian syndrome, strokes, and diverse malignancies are catalogued. Seminal experiments involving some of its more promising analogs, such as amino-noscapine, 9-nitronoscapine, 9-bromonoscapine, and reduced bromonoscapine, are also detailed. Finally, the bright future of these oftentimes even more exceptional derivatives is described, rounding out a portrait of a truly remarkable family of compounds. © 2015 Wiley Periodicals, Inc.

Dual Induction of New Microbial Secondary Metabolites by Fungal Bacterial Co-cultivation.

PubMed

Wakefield, Jennifer; Hassan, Hossam M; Jaspars, Marcel; Ebel, Rainer; Rateb, Mostafa E

2017-01-01

The frequent re-isolation of known compounds is one of the major challenges in drug discovery. Many biosynthetic genes are not expressed under standard culture conditions, thus limiting the chemical diversity of microbial compounds that can be obtained through fermentation. On the other hand, the competition during co-cultivation of two or more different microorganisms in most cases leads to an enhanced production of constitutively present compounds or an accumulation of cryptic compounds that are not detected in axenic cultures of the producing strain under different fermentation conditions. Herein, we report the dual induction of newly detected bacterial and fungal metabolites by the co-cultivation of the marine-derived fungal isolate Aspergillus fumigatus MR2012 and two hyper-arid desert bacterial isolates Streptomyces leeuwenhoekii strain C34 and strain C58. Co-cultivation of the fungal isolate MR2012 with the bacterial strain C34 led to the production of luteoride D, a new luteoride derivative and pseurotin G, a new pseurotin derivative in addition to the production of terezine D and 11- O -methylpseurotin A which were not traced before from this fungal strain under different fermentation conditions. In addition to the previously detected metabolites in strain C34, the lasso peptide chaxapeptin was isolated under co-culture conditions. The gene cluster for the latter compound had been identified through genome scanning, but it had never been detected before in the axenic culture of strain C34. Furthermore, when the fungus MR2012 was co-cultivated with the bacterial strain C58, the main producer of chaxapeptin, the titre of this metabolite was doubled, while additionally the bacterial metabolite pentalenic acid was detected and isolated for the first time from this strain, whereas the major fungal metabolites that were produced under axenic culture were suppressed. Finally, fermentation of the MR2012 by itself led to the isolation of the new diketopiperazine metabolite named brevianamide X.

Chemical indices and methods of multivariate statistics as a tool for odor classification.

PubMed

Mahlke, Ingo T; Thiesen, Peter H; Niemeyer, Bernd

2007-04-01

Industrial and agricultural off-gas streams are comprised of numerous volatile compounds, many of which have substantially different odorous properties. State-of-the-art waste-gas treatment includes the characterization of these molecules and is directed at, if possible, either the avoidance of such odorants during processing or the use of existing standardized air purification techniques like bioscrubbing or afterburning, which however, often show low efficiency under ecological and economical regards. Selective odor separation from the off-gas streams could ease many of these disadvantages but is not yet widely applicable. Thus, the aim of this paper is to identify possible model substances in selective odor separation research from 155 volatile molecules mainly originating from livestock facilities, fat refineries, and cocoa and coffee production by knowledge-based methods. All compounds are examined with regard to their structure and information-content using topological and information-theoretical indices. Resulting data are fitted in an observation matrix, and similarities between the substances are computed. Principal component analysis and k-means cluster analysis are conducted showing that clustering of indices data can depict odor information correlating well to molecular composition and molecular shape. Quantitative molecule describtion along with the application of such statistical means therefore provide a good classification tool of malodorant structure properties with no thermodynamic data needed. The approximate look-alike shape of odorous compounds within the clusters suggests a fair choice of possible model molecules.

Nonlocal screening effects on core-level photoemission spectra investigated by large-cluster models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okada, K.; Kotani, A.

1995-08-15

The copper 2{ital p} core-level x-ray photoemission spectrum in CuO{sub 2} plane systems is calculated by means of large-cluster models to investigate in detail the nonlocal screening effects, which were pointed out by van Veenendaal {ital et} {ital al}. [Phys. Rev. B 47, 11 462 (1993)]. Calculating the hole distributions for the initial and final states of photoemission, we show that the atomic coordination in a cluster strongly affects accessible final states. Accordingly, we point out that the interpretation for Cu{sub 3}O{sub 10} given by van Veenendaal {ital et} {ital al}. is not always general. Moreover, it is shown thatmore » the spectrum can be remarkably affected by whether or not the O 2{ital p}{sub {pi}} orbits are taken into account in the calculations. We also introduce a Hartree-Fock approximation in order to treat much larger-cluster models.« less

Brimstone chemistry under laser light assists mass spectrometric detection and imaging the distribution of arsenic in minerals.

PubMed

Lal, Swapnil; Zheng, Zhaoyu; Pavlov, Julius; Attygalle, Athula B

2018-05-23

Singly charged As2n+1 ion clusters (n = 2-11) were generated from elemental arsenic by negative-ion laser-ablation mass spectrometry. The overall abundance of the gaseous As ions generated upon laser irradiation was enhanced nearly a hundred times when As-bearing samples were admixed with sulfur. However, sulfur does not act purely as an inert matrix: irradiating arsenic-sulfur mixtures revealed a novel pathway to generate and detect a series of [AsSn]- clusters (n = 2-6). Intriguingly, the spectra recorded from As2O3, NaAsO2, Na3AsO4, cacodylic acid and 3-amino-4-hydroxyphenylarsonic acid together with sulfur as the matrix were remarkably similar to that acquired from an elemental arsenic and sulfur mixture. This result indicated that arsenic sulfide cluster-ions are generated directly from arsenic compounds by a hitherto unknown pathway. The mechanism of elemental sulfur extracting chemically bound arsenic from compounds and forming [AsSn]- clusters is enigmatic; however, this discovery has a practical value as a general detection method for arsenic compounds. For example, the method was employed for the detection of As in its minerals, and for the imaging of arsenic distribution in minerals such as domeykite. LDI-MS data recorded from a latent image imprinted on a piece of paper from a flat mineral surface, and wetting the paper with a solution of sulfur, enabled the localization of arsenic in the mineral. The distribution of As was visualized as false-color images by extracting from acquired data the relative intensities of m/z 139 (AsS2-) and m/z 171 (AsS3-) ions.

A Computational Cluster for Multiscale Simulations of Ionic Liquids

DTIC Science & Technology

2008-09-16

AND SUBTITLE DURIP: A Computational Cluster for Multiscale Simulations of Ionic Liquids 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA955007-1-0512 5c...AVAILABILITY STATEMENT ZO\\5oc\\\\%1>^ 13. SUPPLEMENTARY NOTES 14. ABSTRACT The focus of this project was to acquire and use computer cluster nodes...by ANSI Std. Z39.18 Adobe Professional 7.0 Comprehensive Final Report: Gregory A. Voth, PI Contract/Grant Title: DURIP: A Computational Cluster for

Establishment of the Inducible Tet-On System for the Activation of the Silent Trichosetin Gene Cluster in Fusarium fujikuroi

PubMed Central

Janevska, Slavica; Arndt, Birgit; Baumann, Leonie; Apken, Lisa Helene; Mauriz Marques, Lucas Maciel; Humpf, Hans-Ulrich; Tudzynski, Bettina

2017-01-01

The PKS-NRPS-derived tetramic acid equisetin and its N-desmethyl derivative trichosetin exhibit remarkable biological activities against a variety of organisms, including plants and bacteria, e.g., Staphylococcus aureus. The equisetin biosynthetic gene cluster was first described in Fusarium heterosporum, a species distantly related to the notorious rice pathogen Fusarium fujikuroi. Here we present the activation and characterization of a homologous, but silent, gene cluster in F. fujikuroi. Bioinformatic analysis revealed that this cluster does not contain the equisetin N-methyltransferase gene eqxD and consequently, trichosetin was isolated as final product. The adaption of the inducible, tetracycline-dependent Tet-on promoter system from Aspergillus niger achieved a controlled overproduction of this toxic metabolite and a functional characterization of each cluster gene in F. fujikuroi. Overexpression of one of the two cluster-specific transcription factor (TF) genes, TF22, led to an activation of the three biosynthetic cluster genes, including the PKS-NRPS key gene. In contrast, overexpression of TF23, encoding a second Zn(II)2Cys6 TF, did not activate adjacent cluster genes. Instead, TF23 was induced by the final product trichosetin and was required for expression of the transporter-encoding gene MFS-T. TF23 and MFS-T likely act in consort and contribute to detoxification of trichosetin and therefore, self-protection of the producing fungus. PMID:28379186

Establishment of the Inducible Tet-On System for the Activation of the Silent Trichosetin Gene Cluster in Fusarium fujikuroi.

PubMed

Janevska, Slavica; Arndt, Birgit; Baumann, Leonie; Apken, Lisa Helene; Mauriz Marques, Lucas Maciel; Humpf, Hans-Ulrich; Tudzynski, Bettina

2017-04-05

The PKS-NRPS-derived tetramic acid equisetin and its N -desmethyl derivative trichosetin exhibit remarkable biological activities against a variety of organisms, including plants and bacteria, e.g., Staphylococcus aureus . The equisetin biosynthetic gene cluster was first described in Fusarium heterosporum , a species distantly related to the notorious rice pathogen Fusarium fujikuroi . Here we present the activation and characterization of a homologous, but silent, gene cluster in F. fujikuroi . Bioinformatic analysis revealed that this cluster does not contain the equisetin N -methyltransferase gene eqxD and consequently, trichosetin was isolated as final product. The adaption of the inducible, tetracycline-dependent Tet-on promoter system from Aspergillus niger achieved a controlled overproduction of this toxic metabolite and a functional characterization of each cluster gene in F. fujikuroi . Overexpression of one of the two cluster-specific transcription factor (TF) genes, TF22 , led to an activation of the three biosynthetic cluster genes, including the PKS-NRPS key gene. In contrast, overexpression of TF23 , encoding a second Zn(II)₂Cys₆ TF, did not activate adjacent cluster genes. Instead, TF23 was induced by the final product trichosetin and was required for expression of the transporter-encoding gene MFS-T . TF23 and MFS-T likely act in consort and contribute to detoxification of trichosetin and therefore, self-protection of the producing fungus.

Star cluster formation in a turbulent molecular cloud self-regulated by photoionization feedback

NASA Astrophysics Data System (ADS)

Gavagnin, Elena; Bleuler, Andreas; Rosdahl, Joakim; Teyssier, Romain

2017-12-01

Most stars in the Galaxy are believed to be formed within star clusters from collapsing molecular clouds. However, the complete process of star formation, from the parent cloud to a gas-free star cluster, is still poorly understood. We perform radiation-hydrodynamical simulations of the collapse of a turbulent molecular cloud using the RAMSES-RT code. Stars are modelled using sink particles, from which we self-consistently follow the propagation of the ionizing radiation. We study how different feedback models affect the gas expulsion from the cloud and how they shape the final properties of the emerging star cluster. We find that the star formation efficiency is lower for stronger feedback models. Feedback also changes the high-mass end of the stellar mass function. Stronger feedback also allows the establishment of a lower density star cluster, which can maintain a virial or sub-virial state. In the absence of feedback, the star formation efficiency is very high, as well as the final stellar density. As a result, high-energy close encounters make the cluster evaporate quickly. Other indicators, such as mass segregation, statistics of multiple systems and escaping stars confirm this picture. Observations of young star clusters are in best agreement with our strong feedback simulation.

The clustering of galaxies in the completed SDSS-III Baryon Oscillation Spectroscopic Survey: combining correlated Gaussian posterior distributions

DOE PAGES

Sánchez, Ariel G.; Grieb, Jan Niklas; Salazar-Albornoz, Salvador; ...

2016-09-30

The cosmological information contained in anisotropic galaxy clustering measurements can often be compressed into a small number of parameters whose posterior distribution is well described by a Gaussian. Here, we present a general methodology to combine these estimates into a single set of consensus constraints that encode the total information of the individual measurements, taking into account the full covariance between the different methods. We also illustrate this technique by applying it to combine the results obtained from different clustering analyses, including measurements of the signature of baryon acoustic oscillations and redshift-space distortions, based on a set of mock cataloguesmore » of the final SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS). Our results show that the region of the parameter space allowed by the consensus constraints is smaller than that of the individual methods, highlighting the importance of performing multiple analyses on galaxy surveys even when the measurements are highly correlated. Our paper is part of a set that analyses the final galaxy clustering data set from BOSS. The methodology presented here is used in Alam et al. to produce the final cosmological constraints from BOSS.« less

The hierarchical cluster analysis of oral health attitudes and behaviour using the Hiroshima University--Dental Behavioural Inventory (HU-DBI) among final year dental students in 17 countries.

PubMed

Komabayashi, Takashi; Kawamura, Makoto; Kim, Kang-Ju; Wright, Fredrick A C; Declerck, Dominique; Goiâs, Maria do Carmo Matias Freire; Hu, De-Yu; Honkala, Eino; Lévy, Gérard; Kalwitzki, Matthias; Polychronopoulou, Argy; Yip, Kevin Hak-Kong; Eli, Ilana; Kinirons, Martin J; Petti, Stefano; Srisilapanan, Patcharawan; Kwan, Stella Y L; Centore, Linda S

2006-10-01

To explore and describe international oral health attitudes/ behaviours among final year dental students. Validated translated versions of the Hiroshima University-Dental Behavioural Inventory (HU-DBI) questionnaire were administered to 1,096 final-year dental students in 17 countries. Hierarchical cluster analysis was conducted within the data to detect patterns and groupings. The overall response rate was 72%. The cluster analysis identified two main groups among the countries. Group 1 consisted of twelve countries: one Oceanic (Australia), one Middle-Eastern (Israel), seven European (Northern Ireland, England, Finland, Greece, Germany, Italy, and France) and three Asian (Korea, Thailand and Malaysia) countries. Group 2 consisted of five countries: one South American (Brazil), one European (Belgium) and three Asian (China, Indonesia and Japan) countries. The percentages of 'agree' responses in three HU-DBI questionnaire items were significantly higher in Group 2 than in Group 1. They include: "I worry about the colour of my teeth."; "I have noticed some white sticky deposits on my teeth."; and "I am bothered by the colour of my gums." Grouping the countries into international clusters yielded useful information for dentistry and dental education.

Construction of a novel Mo/Cu/S cluster with a closed double-cubane-like polyhedron and a chain polymer of W/Cu/S clusters.

PubMed

Li, Zhihua; Du, Shaowu; Wu, Xintao

2004-08-09

Reaction of [MoOS(3)](2)(-) and [WS(4)](2)(-) with Cudtp (dtp = diethyl dithiophosphate) gave rise to the clusters [Bu(4)N](2)[(MoOS(3))(4)Cu(12)(dtp)(6)], 1, and [Et(4)N][(WS(4)Cu(4))(dtp)(3)], 2, respectively. In cluster 1, the dtp- ligands act as both monodentate and bidentate ligands that bridge between Cu atoms and link together a closed double-cubane-like [Mo(2)O(2)S(6)Cu(6)](2+) core and two incomplete cubane-like [MoOS(3)Cu(3)]+ units. In cluster 2, the [WS(4)Cu(4)](2+) fragments were connected via bidentate and doubly bridging dtp- bridges to give a chain polymeric anion. Cluster 1 is the first example of a Mo/Cu/S cluster that contains a closed double-cubane-like structure. Compound 2 is also rare and the first W/Cu/S polymer with dtp- linkages.

UFVA, A Combined Linear and Nonlinear Factor Analysis Program Package for Chemical Data Evaluation.

DTIC Science & Technology

1980-11-01

that one cluster consists of the monoterpenes and Isoprene; the second is of the sesquiterpenes. Compound 8 (Caryophyllene) should therefore belong to...two clusters very clearly (Fig. 6). Figure 6 The very similar fragmentation pattern of Isoprene and the monoterpenes is reflected by their close...13 of another set of 13 terpene components. These are Isoprene, four monoterpenes (Myrcene, Menthol, Camphene, Umbellulone), four sesquiterpenes

Packing of Russian doll clusters to form a nanometer-scale CsCl-type compound in a Cr–Zn–Sn complex metallic alloy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Weiwei; Cava, Robert J.; Miller, Gordon J.

A new cubic complex metallic alloy phase, Cr 22Zn 72Sn 24, with a lattice parameter near 2.5 nm was discovered in crystals grown using a Zn/Sn flux. The structure consists of Russian doll clusters or a 3-d network of Cr-centered icosahedra (shown) with bcc-metal fragments in void spaces.

Packing of Russian doll clusters to form a nanometer-scale CsCl-type compound in a Cr–Zn–Sn complex metallic alloy

DOE PAGES

Xie, Weiwei; Cava, Robert J.; Miller, Gordon J.

2017-07-03

A new cubic complex metallic alloy phase, Cr 22Zn 72Sn 24, with a lattice parameter near 2.5 nm was discovered in crystals grown using a Zn/Sn flux. The structure consists of Russian doll clusters or a 3-d network of Cr-centered icosahedra (shown) with bcc-metal fragments in void spaces.

Dynamics of 28,30S i* compound nuclei formed at sub-barrier energies

NASA Astrophysics Data System (ADS)

Kaur, Manpreet; Singh, Bir Bikram; Kaur, Sarbjeet

2018-05-01

The decay of 28S i* and 30S i* compound nuclei (CN) formed at sub-barrier energies, in the reactions induced by stable projectile 16O and exotic projectile 18O, respectively, has been investigated within the quantum mechanical fragmentation theory based dynamical cluster-decay model (DCM). The collective potential energy surface shows that xα-type (x is an integer) clusters are minimized in the decay of 28S i* while in case of 30S i* in addition to xα-type clusters, np-xα (n, p are neutron and proton, respectively) type clusters are also minimized. These minimized fragments have more preformation probability P0, which is an important factor through which nuclear structure effects of decaying CN are probed, within DCM. The results show that light particles (LPs) are contributing mostly in the fusion cross-section, σfusion. In case of 30S i*, the contribution of 1n is highest and more compared to 4He in case of 28S i*, which seems to play an important role in fusion enhancement. The DCM calculated σfusion for both the CN formed with same Ec.m. = 7.0 MeV gives more value for σfusion of 30S i*, in agreement with the experimental data.

Understanding drugs in breast cancer through drug sensitivity screening.

PubMed

Uhr, Katharina; Prager-van der Smissen, Wendy J C; Heine, Anouk A J; Ozturk, Bahar; Smid, Marcel; Göhlmann, Hinrich W H; Jager, Agnes; Foekens, John A; Martens, John W M

2015-01-01

With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC50 values and thus grouped together when the cell lines were hierarchically clustered based on IC50 values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC50 values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between drugs which might have implications for cancer treatment regimens.

Recent developments with boron as a platform for novel drug design.

PubMed

Leśnikowski, Zbigniew J

2016-06-01

After decades of development, the medicinal chemistry of compounds that contain a single boron atom has matured to the present status of having equal rights with other branches of drug discovery, although it remains a relative newcomer. In contrast, the medicinal chemistry of boron clusters is less advanced, but it is expanding and may soon become a productive area of drug discovery. The author reviews the current developments of medicinal chemistry of boron and its applications in drug design. First generation boron drugs that bear a single boron atom and second generation boron drugs that utilize boron clusters as pharmacophores or modulators of bioactive molecules are discussed. The advantages and gaps in our current understanding of boron medicinal chemistry, with a special focus on boron clusters, are highlighted. Boron is not a panacea for every drug discovery problem, but there is a good chance that it will become a useful addition to the medicinal chemistry tool box. The present status of boron resembles the medicinal chemistry status of fluorine three decades ago; indeed, currently, approximately 20% of pharmaceuticals on the market contain fluorine. The fact that novel boron compounds, especially those based on abiotic polyhedral boron hydrides, are currently unfamiliar could be advantageous because organisms may be less prone to developing resistance against boron cluster-based drugs.

Structural and magnetic behavior of (Ni, Cu) substituted Nd0.67Sr0.33MnO3 perovskite compounds

NASA Astrophysics Data System (ADS)

Arun, B.; Sudakshina, B.; Akshay, V. R.; Chandrasekhar, K. Devi; Yang, H. D.; Vasundhara, M.

2018-05-01

Structural and magnetic phase transition of Ni and Cu substituted Nd0.67Sr0.33MnO3 perovskite compounds have been investigated. The Rietveld refinement of X-ray powder diffraction patterns confirms that both compounds have crystallized into an orthorhombic structure with Pbnm space group same as that of Nd0.67Sr0.33MnO3 compound. X-ray absorption spectra studies completely ruled out the possibility of existence of any impurities. Both compounds do not obey the Curie-Weiss law indicates the presence of some ferromagnetic clusters within the paramagnetic matrix. Ni substituted compound shows a lower value of TC and Cu substituted compound shows a higher value of TC than that of the parent. Non-saturating tendency of magnetization is more prominently seen in the case of Cu substituted compound, indicating an increase in the AFM component.

An Overview of the History of Cluster Conferences

NASA Astrophysics Data System (ADS)

Horiuchi, H.

2017-06-01

An overview is given on the historical development of the cluster conference series which started at Bohum in 1969. I start with the discussion of the philosophy of Karl Wildermuth and then I make a review on the main subjects and topics in cluster conferences. Since the cluster dynamics is a main nuclear dynamics together with the mean-field dynamics, we see that development of the cluster conference has been along with the rises of many new subjects in nuclear physics itself. Examples of them include superheavy nuclei, nuclear astrophysics, neutron-rich nuclei, cluster-gas states and ab initio calculations. Finally I discuss that more activities in and attention to cluster physics are seen in recent days.

Analysis of 3D vortex motion in a dusty plasma

NASA Astrophysics Data System (ADS)

Mulsow, M.; Himpel, M.; Melzer, A.

2017-12-01

Dust clusters of about 50-1000 particles have been confined near the sheath region of a gaseous radio-frequency plasma discharge. These compact clusters exhibit a vortex motion which has been reconstructed in full three dimensions from stereoscopy. Smaller clusters are found to show a competition between solid-like cluster structure and vortex motion, whereas larger clusters feature very pronounced vortices. From the three-dimensional analysis, the dust flow field has been found to be nearly incompressible. The vortices in all observed clusters are essentially poloidal. The dependence of the vorticity on the cluster size is discussed. Finally, the vortex motion has been quantitatively attributed to radial gradients of the ion drag force.

ELECTROMECHANICAL INSTALLATION AND REPAIR CLUSTER--AN INVESTIGATION AND DEVELOPMENT OF THE CLUSTER CONCEPT AS A PROGRAM IN VOCATIONAL EDUCATION AT THE SECONDARY SCHOOL LEVEL.

ERIC Educational Resources Information Center

MALEY, DONALD

THIS COURSE OUTLINE ON ELECTROMECHANICAL INSTALLATION AND REPAIR IS PART OF THE FINAL REPORT ON "CLUSTER CONCEPT" COURSES IN VOCATIONAL EDUCATION FOR SECONDARY EDUCATION (ED 010 301). EACH JOB ENTRY TASK WAS ANALYZED FOR HUMAN REQUIREMENTS (COMMUNICATION, MEASUREMENT, MATHEMATICS, SCIENCE, SKILLS, AND INFORMATION) NECESSARY TO…

Reviewing Sonority for Word-Final Sonorant+Obstruent Consonant Cluster Development in Turkish

ERIC Educational Resources Information Center

Topbas, Seyhun; Kopkalli-Yavuz, Handan

2008-01-01

The purpose of this study is to investigate the acquisition patterns of sonorant+obstruent coda clusters in Turkish to determine whether Turkish data support the prediction the Sonority Sequencing Principle (SSP) makes as to which consonant (i.e. C1 or C2) is more likely to be preserved in sonorant+obstruent clusters, and the error patterns of…

Opening the Window on Galaxy Assembly: Ages and Structural Parameters of Globular Clusters Towards the Galactic Bulge

NASA Astrophysics Data System (ADS)

Cohen, Roger

2015-10-01

The primary aim of this program is to undertake a systematic investigation of highly reddened Galactic globular clusters (GGCs) located towards the Galactic bulge. These clusters have been excluded from deep space-based photometric surveys due to their severe total and differential extinction. We will exploit the photometric depth and homogeneity of two existing Treasury programs (the ACS GGC Treasury Survey and the WFC3 Bulge Treasury Program) along with the unique optical+IR parallel imaging capabilities of HST to finally place the bulge GGCs in the context of their optically well-studied counterparts. Specifically, by leveraging ACS/WFC together with WFC3/IR, we first exploit the reddening sensitivity at optical wavelengths to map severe, small-scale differential reddening in the cluster cores. Corrected two-color WFC3/IR photometry will then be used to measure cluster ages to better than 1 Gyr relative precision, finally completing the age-metallicity relation of the Milky Way GGC system. Ages are obtained using a demonstrated procedure which is strictly differential, and therefore insensitive to total distance, reddening, reddening law, or photometric calibration uncertainties. At the same time, deep archival Treasury survey imaging of the Galactic bulge will be used to decontaminate cluster luminosity functions, yielding measurements of bulge GGC mass functions and mass segregation on par with results from the ACS GGC Treasury survey. Finally, the imaging which we propose will be combined with existing wide-field near-IR PSF photometry, yielding complete radial number density profiles, structural and morphological parameters.

Characterisation of volatile profiles in 50 native Peruvian chili pepper using solid phase microextraction-gas chromatography mass spectrometry (SPME-GCMS).

PubMed

Patel, Kirti; Ruiz, Candy; Calderon, Rosa; Marcelo, Mavel; Rojas, Rosario

2016-11-01

The volatiles were characterised by headspace solid phase micro extraction (HS-SPME), gas chromatography mass spectrometry (GC-FID/MS). A total of 127 compounds were identified with terpenes (including mono terpenes and sesquiterpenes - a total of 45 compounds), esters (31 compounds) and hydrocarbons (20 compounds) were the predominant volatile compounds. Principal component analysis (PCA) of the volatile compounds yielded 2 significant PC's, which together accounted for 90.3% of the total variance in the data set and the scatter plot generated between PC1 and PC2 successfully segregated the 50 chili pepper samples into 7 groups. Clusters of hydrocarbons, esters, terpenes, aldehyde and ketones formed the major determinants of the difference. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fundamental Studies and Isolation Strategies for Metal Compound Nanoclusters

DTIC Science & Technology

2009-02-28

probe nanocluster structure, bonding and stability, metal oxide, carbide and silicide clusters with up to 50 atoms were investigated with mass...transition metal compounds (carbides, oxides, silicides ) that are expected to have high stability, an essential property for their isolation...Metal carbide, oxide and silicide nanoclusters are studied in the size range from a few up to about 300 atoms. New infrared laser spectroscopy

Nucleophilic ring opening of bridging thietanes in open triosmium cluster complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, R.D.; Belinski, J.A.

1992-07-01

The complexes Os{sub 3}(CO){sub 9}({mu}{sub 3}-S)[{mu}-SCH{sub 2}CMe{sub 2}CMe{sub 2}CH{sub 2}] (1) and Os{sub 3}(CO){sub 9}({mu}{sub 3}-S)[{mu}-SCH{sub 2}CH{sub 2}CH{sub 2}] (2) were obtained from the reactions of Os{sub 3}(CO){sub 10}({mu}{sub 3}-S) with 3,3-dimethylthietane (DMT) and thietane, respectively, at -42 {degree}C in the presence of Me{sub 3}NO. Compound 1 was characterized by a single-crystal X-ray diffraction analysis and was found to contain a DMT group bridging two of the nonbonded metal atoms in the open cluster of three metal atoms by using both lone pairs of electrons on the sulfur atom. Compound 1 reacted with bis(triphenylphosphine)nitrogen(1+) chloride ([PPN]Cl) at 25 {degrees}C tomore » yield the salt [PPN][Os{sub 3}-(CO){sub 9}({mu}-SCH{sub 2}CMe{sub 2}CH{sub 2}Cl)({mu}{sub 3}-S)] (3; 76%), in which the chloride ion was added to one of the methylene groups of the DMT ring in a process that caused the ring to open by cleavage of one of the carbon-sulfur bonds. A 4-chloro-3,3-dimethylpropanethiolate ligand bridges the open edge of the anionic triosmium cluster. Compound 3 was converted to the neutral complex Os{sub 3}(CO){sub 9}[{mu}-SCH{sub 2}CMe{sub 2}CMe{sub 2}CH{sub 2}Cl]({mu}{sub 3}-S)({mu}-H) (4) by reaction with HCl at 25 {degrees}C. Compound 4 is structurally similar to 3, except that is contains a hydride ligand bridging one of the two metal-metal bonds. Compounds 1 and 2 react with HCl in CH{sub 2}Cl{sub 2} solvent to yield the neutral compounds 4 and Os{sub 3}(CO){sub 9}[{mu}-SCH{sub 2}CH{sub 2}CH{sub 2}Cl]({mu}{sub 3}-S)({mu}-H) (5) in 89% and 90% yields, respectively, in one step. 11 refs., 3 figs., 10 tabs.« less

Higher-order clustering in networks

NASA Astrophysics Data System (ADS)

Yin, Hao; Benson, Austin R.; Leskovec, Jure

2018-05-01

A fundamental property of complex networks is the tendency for edges to cluster. The extent of the clustering is typically quantified by the clustering coefficient, which is the probability that a length-2 path is closed, i.e., induces a triangle in the network. However, higher-order cliques beyond triangles are crucial to understanding complex networks, and the clustering behavior with respect to such higher-order network structures is not well understood. Here we introduce higher-order clustering coefficients that measure the closure probability of higher-order network cliques and provide a more comprehensive view of how the edges of complex networks cluster. Our higher-order clustering coefficients are a natural generalization of the traditional clustering coefficient. We derive several properties about higher-order clustering coefficients and analyze them under common random graph models. Finally, we use higher-order clustering coefficients to gain new insights into the structure of real-world networks from several domains.

Discovery of Novel Anti-prion Compounds Using In Silico and In Vitro Approaches

PubMed Central

Hyeon, Jae Wook; Choi, Jiwon; Kim, Su Yeon; Govindaraj, Rajiv Gandhi; Jam Hwang, Kyu; Lee, Yeong Seon; An, Seong Soo A.; Lee, Myung Koo; Joung, Jong Young; No, Kyoung Tai; Lee, Jeongmin

2015-01-01

Prion diseases are associated with the conformational conversion of the physiological form of cellular prion protein (PrPC) to the pathogenic form, PrPSc. Compounds that inhibit this process by blocking conversion to the PrPSc could provide useful anti-prion therapies. However, no suitable drugs have been identified to date. To identify novel anti-prion compounds, we developed a combined structure- and ligand-based virtual screening system in silico. Virtual screening of a 700,000-compound database, followed by cluster analysis, identified 37 compounds with strong interactions with essential hotspot PrP residues identified in a previous study of PrPC interaction with a known anti-prion compound (GN8). These compounds were tested in vitro using a multimer detection system, cell-based assays, and surface plasmon resonance. Some compounds effectively reduced PrPSc levels and one of these compounds also showed a high binding affinity for PrPC. These results provide a promising starting point for the development of anti-prion compounds. PMID:26449325

Regulation of specialised metabolites in Actinobacteria - expanding the paradigms.

PubMed

Hoskisson, Paul A; Fernández-Martínez, Lorena T

2018-06-01

The increase in availability of actinobacterial whole genome sequences has revealed huge numbers of specialised metabolite biosynthetic gene clusters, encoding a range of bioactive molecules such as antibiotics, antifungals, immunosuppressives and anticancer agents. Yet the majority of these clusters are not expressed under standard laboratory conditions in rich media. Emerging data from studies of specialised metabolite biosynthesis suggest that the diversity of regulatory mechanisms is greater than previously thought and these act at multiple levels, through a range of signals such as nutrient limitation, intercellular signalling and competition with other organisms. Understanding the regulation and environmental cues that lead to the production of these compounds allows us to identify the role that these compounds play in their natural habitat as well as provide tools to exploit this untapped source of specialised metabolites for therapeutic uses. Here, we provide an overview of novel regulatory mechanisms that act in physiological, global and cluster-specific regulatory manners on biosynthetic pathways in Actinobacteria and consider these alongside their ecological and evolutionary implications. © 2018 The Authors. Environmental Microbiology published by Society for Applied Microbiology and JohnWiley & Sons Ltd.

A novel complex networks clustering algorithm based on the core influence of nodes.

PubMed

Tong, Chao; Niu, Jianwei; Dai, Bin; Xie, Zhongyu

2014-01-01

In complex networks, cluster structure, identified by the heterogeneity of nodes, has become a common and important topological property. Network clustering methods are thus significant for the study of complex networks. Currently, many typical clustering algorithms have some weakness like inaccuracy and slow convergence. In this paper, we propose a clustering algorithm by calculating the core influence of nodes. The clustering process is a simulation of the process of cluster formation in sociology. The algorithm detects the nodes with core influence through their betweenness centrality, and builds the cluster's core structure by discriminant functions. Next, the algorithm gets the final cluster structure after clustering the rest of the nodes in the network by optimizing method. Experiments on different datasets show that the clustering accuracy of this algorithm is superior to the classical clustering algorithm (Fast-Newman algorithm). It clusters faster and plays a positive role in revealing the real cluster structure of complex networks precisely.

Proposed Oral Reference Dose (RfD) for Barium and Compounds (Final Report, 2004)

EPA Science Inventory

This document is the final report from the 2004 external peer review of the Proposed Oral Reference Dose (RfD) for Barium and Compounds, prepared by the U.S. Environmental Protection Agency (EPA), National Center for Environmental Assessment (NCEA), for the Integrated Risk...

Evaluation of epoxy compounds as a material for patching and protecting concrete : final report.

DOT National Transportation Integrated Search

1971-01-01

The final report summarizes the results of a study of the use of epoxy compounds in the shallow surface repair and sealing of concrete bridge decks. The research effort concentrated on the use of epoxy resin systems as bonded overlays and included ev...

Heterologous Production of a Novel Cyclic Peptide Compound, KK-1, in Aspergillus oryzae.

PubMed

Yoshimi, Akira; Yamaguchi, Sigenari; Fujioka, Tomonori; Kawai, Kiyoshi; Gomi, Katsuya; Machida, Masayuki; Abe, Keietsu

2018-01-01

A novel cyclic peptide compound, KK-1, was originally isolated from the plant-pathogenic fungus Curvularia clavata . It consists of 10 amino acid residues, including five N -methylated amino acid residues, and has potent antifungal activity. Recently, the genome-sequencing analysis of C. clavata was completed, and the biosynthetic genes involved in KK-1 production were predicted by using a novel gene cluster mining tool, MIDDAS-M. These genes form an approximately 75-kb cluster, which includes nine open reading frames, containing a non-ribosomal peptide synthetase (NRPS) gene. To determine whether the predicted genes were responsible for the biosynthesis of KK-1, we performed heterologous production of KK-1 in Aspergillus oryzae by introduction of the cluster genes into the genome of A. oryzae . The NRPS gene was split in two fragments and then reconstructed in the A. oryzae genome, because the gene was quite large (approximately 40 kb). The remaining seven genes in the cluster, excluding the regulatory gene kkR , were simultaneously introduced into the strain of A. oryzae in which NRPS had already been incorporated. To evaluate the heterologous production of KK-1 in A. oryzae , gene expression was analyzed by RT-PCR and KK-1 productivity was quantified by HPLC. KK-1 was produced in variable quantities by a number of transformed strains, along with expression of the cluster genes. The amount of KK-1 produced by the strain with the greatest expression of all genes was lower than that produced by the original producer, C. clavata . Therefore, expression of the cluster genes is necessary and sufficient for the heterologous production of KK-1 in A. oryzae , although there may be unknown factors limiting productivity in this species.

Heterologous Production of a Novel Cyclic Peptide Compound, KK-1, in Aspergillus oryzae

PubMed Central

Yoshimi, Akira; Yamaguchi, Sigenari; Fujioka, Tomonori; Kawai, Kiyoshi; Gomi, Katsuya; Machida, Masayuki; Abe, Keietsu

2018-01-01

A novel cyclic peptide compound, KK-1, was originally isolated from the plant-pathogenic fungus Curvularia clavata. It consists of 10 amino acid residues, including five N-methylated amino acid residues, and has potent antifungal activity. Recently, the genome-sequencing analysis of C. clavata was completed, and the biosynthetic genes involved in KK-1 production were predicted by using a novel gene cluster mining tool, MIDDAS-M. These genes form an approximately 75-kb cluster, which includes nine open reading frames, containing a non-ribosomal peptide synthetase (NRPS) gene. To determine whether the predicted genes were responsible for the biosynthesis of KK-1, we performed heterologous production of KK-1 in Aspergillus oryzae by introduction of the cluster genes into the genome of A. oryzae. The NRPS gene was split in two fragments and then reconstructed in the A. oryzae genome, because the gene was quite large (approximately 40 kb). The remaining seven genes in the cluster, excluding the regulatory gene kkR, were simultaneously introduced into the strain of A. oryzae in which NRPS had already been incorporated. To evaluate the heterologous production of KK-1 in A. oryzae, gene expression was analyzed by RT-PCR and KK-1 productivity was quantified by HPLC. KK-1 was produced in variable quantities by a number of transformed strains, along with expression of the cluster genes. The amount of KK-1 produced by the strain with the greatest expression of all genes was lower than that produced by the original producer, C. clavata. Therefore, expression of the cluster genes is necessary and sufficient for the heterologous production of KK-1 in A. oryzae, although there may be unknown factors limiting productivity in this species. PMID:29686660

Patterns of long-term care services use in a suburban municipality of Japan: a population-based study.

PubMed

Igarashi, Ayumi; Yamamoto-Mitani, Noriko; Yoshie, Satoru; Iijima, Katsuya

2017-05-01

Increasing service use under the long-term care insurance (LTCI) system in Japan requires a comprehensive understanding of how the services are actually used. This study aimed to identify patterns of LTCI service use and to examine the characteristics of the patterns. We analyzed data from a population of 4,339 older adults living in the community who were certified as "Needing Care" and were using at least one LTCI service in a suburban municipality of Japan. We identified six patterns of service use using cluster analysis based on the amount of fees for LTCI services and compared characteristics among the clusters. The clusters were: 1) light use of care services (n = 1,852); 2) day care-centered (n = 1,071); 3) day care with rehabilitation-centered (n = 616); 4) home help-centered (n = 365); 5) short-stay respite service-centered (n = 246); and 6) compound uses of visiting services (n = 189). "Home help-centered" and "short-stay respite service-centered" clusters used a large number of fees, whereas "compound uses of visiting services" clusters did not despite their severe conditions. The "day care-centered (with rehabilitation)" classification included few people who needed medical procedures, likely due to the lack of medical facilities in those agencies. The results show the impact of social and medical factors on LTCI service use, suggesting possible difficulties in the socialization of care. The clusters could be used as typical service use patterns, providing a framework for further studies, such as those evaluating the services' effects. Geriatr Gerontol Int 2017; 17: 753-759. © 2016 Japan Geriatrics Society.

Oxygen-Centered Hexatantalum Tetradecaimido Cluster Complexes

PubMed Central

Krinsky, Jamin L.; Anderson, Laura L.; Arnold, John; Bergman, Robert G.

2008-01-01

The syntheses and characterization of several octahedral hexatantalum cluster compounds of formula (ArN)14Ta6O are described (Ar = Ph, p-MeC6H4, p-MeOC6H4, p-t-BuC6H4, p-BrC6H4, m-ClC6H4). Treatment of Bn3Ta=N-t-Bu (Bn = CH2C6H5) or pentakis(dimethylamido)tantalum with an excess of the appropriate aniline and stoichiometric water or tantalum oxide afforded varying yields of arylimido clusters. The structures of two species were confirmed by X-ray diffraction (XRD), while the identity of the central oxygen atom was elucidated by electrospray mass spectrometry (MS) using 17O/18O-enriched material. The title species are very air- and moisture-sensitive but quite thermally stable in solution. Experimentally determined optical properties and oxidation/reduction potentials, as well as some computational results, indicate that they possess an electronic structure wherein the highest occupied molecular orbitals are ligand-centered, while the lowest unoccupied orbitals are metal-centered and delocalized throughout the tantalum cage. Whereas chemical oxidation resulted in cluster decomposition, reduction with decamethylcobaltocene yielded stable salts of formula [Cp*2Co][(ArN)14Ta6O] (Ar = Ph, Ar = p-MeC6H4). Small-molecule reactivity studies on one of these clusters showed that its imido functionalities are moderately reactive toward oxide donors but inert with respect to metallaheterocycle-forming processes. Clean imido/oxo exchange was observed with aldehydes and ketones, leading cleanly to organic imines with no soluble byproducts being observed. This exchange was also observed with a rhenium oxo compound (generating an imidorhenium complex as the only soluble species). All 14 imido groups were transferred in these reactions, and no mixed-ligand cluster intermediates were ever observed. PMID:18163614

Analysis of LAC Observations of Clusters of Galaxies and Supernova Remnants

NASA Technical Reports Server (NTRS)

Hughes, J.

1996-01-01

The following publications are included and serve as the final report: The X-ray Spectrum of Abell 665; Clusters of Galaxies; Ginga Observation of an Oxygen-rich Supernova Remnant; Ginga Observations of the Coma Cluster and Studies of the Spatial Distribution of Iron; A Measurement of the Hubble Constant from the X-ray Properties and the Sunyaev-Zel'dovich Effect of Abell 2218; Non-polytropic Model for the Coma Cluster; and Abundance Gradients in Cooling Flow Clusters: Ginga LAC (Large Area Counter) and Einstein SSS (Solid State Spectrometer) Spectra of A496, A1795, A2142, and A2199.

Synthesis and Electrochemistry of Cyclopentadienylcarbonyliron Tetramer: An Advanced Experiment.

ERIC Educational Resources Information Center

White, A. J.; Cunningham, Alice J.

1980-01-01

Describes an advanced level experiment in which a transition metal cluster compound, cyclopentadienylcarbonyliron tetramer, is synthesized and characterized spectroscopically. Its redox properties are then explored through cyclic voltammetry. (CS)

Dynamic clustering threshold reduces conformer ensemble size while maintaining a biologically relevant ensemble

PubMed Central

Yongye, Austin B.; Bender, Andreas

2010-01-01

Representing the 3D structures of ligands in virtual screenings via multi-conformer ensembles can be computationally intensive, especially for compounds with a large number of rotatable bonds. Thus, reducing the size of multi-conformer databases and the number of query conformers, while simultaneously reproducing the bioactive conformer with good accuracy, is of crucial interest. While clustering and RMSD filtering methods are employed in existing conformer generators, the novelty of this work is the inclusion of a clustering scheme (NMRCLUST) that does not require a user-defined cut-off value. This algorithm simultaneously optimizes the number and the average spread of the clusters. Here we describe and test four inter-dependent approaches for selecting computer-generated conformers, namely: OMEGA, NMRCLUST, RMS filtering and averaged-RMS filtering. The bioactive conformations of 65 selected ligands were extracted from the corresponding protein:ligand complexes from the Protein Data Bank, including eight ligands that adopted dissimilar bound conformations within different receptors. We show that NMRCLUST can be employed to further filter OMEGA-generated conformers while maintaining biological relevance of the ensemble. It was observed that NMRCLUST (containing on average 10 times fewer conformers per compound) performed nearly as well as OMEGA, and both outperformed RMS filtering and averaged-RMS filtering in terms of identifying the bioactive conformations with excellent and good matches (0.5 < RMSD < 1.0 Å). Furthermore, we propose thresholds for OMEGA root-mean square filtering depending on the number of rotors in a compound: 0.8, 1.0 and 1.4 for structures with low (1–4), medium (5–9) and high (10–15) numbers of rotatable bonds, respectively. The protocol employed is general and can be applied to reduce the number of conformers in multi-conformer compound collections and alleviate the complexity of downstream data processing in virtual screening experiments. Electronic supplementary material The online version of this article (doi:10.1007/s10822-010-9365-1) contains supplementary material, which is available to authorized users. PMID:20499135

Development of a gene expression database and related analysis programs for evaluation of anticancer compounds.

PubMed

Ushijima, Masaru; Mashima, Tetsuo; Tomida, Akihiro; Dan, Shingo; Saito, Sakae; Furuno, Aki; Tsukahara, Satomi; Seimiya, Hiroyuki; Yamori, Takao; Matsuura, Masaaki

2013-03-01

Genome-wide transcriptional expression analysis is a powerful strategy for characterizing the biological activity of anticancer compounds. It is often instructive to identify gene sets involved in the activity of a given drug compound for comparison with different compounds. Currently, however, there is no comprehensive gene expression database and related application system that is; (i) specialized in anticancer agents; (ii) easy to use; and (iii) open to the public. To develop a public gene expression database of antitumor agents, we first examined gene expression profiles in human cancer cells after exposure to 35 compounds including 25 clinically used anticancer agents. Gene signatures were extracted that were classified as upregulated or downregulated after exposure to the drug. Hierarchical clustering showed that drugs with similar mechanisms of action, such as genotoxic drugs, were clustered. Connectivity map analysis further revealed that our gene signature data reflected modes of action of the respective agents. Together with the database, we developed analysis programs that calculate scores for ranking changes in gene expression and for searching statistically significant pathways from the Kyoto Encyclopedia of Genes and Genomes database in order to analyze the datasets more easily. Our database and the analysis programs are available online at our website (http://scads.jfcr.or.jp/db/cs/). Using these systems, we successfully showed that proteasome inhibitors are selectively classified as endoplasmic reticulum stress inducers and induce atypical endoplasmic reticulum stress. Thus, our public access database and related analysis programs constitute a set of efficient tools to evaluate the mode of action of novel compounds and identify promising anticancer lead compounds. © 2012 Japanese Cancer Association.

In Vitro Evaluation of Antileishmanial Activity of Computationally Screened Compounds against Ascorbate Peroxidase To Combat Amphotericin B Drug Resistance

PubMed Central

Mansuri, Rani; Kumar, Ashish; Rana, Sindhuprava; Panthi, Bhavana; Ansari, M. Yousuf; Das, Sushmita; Dikhit, Manas Ranjan

2017-01-01

ABSTRACT In visceral leishmaniasis (VL), the host macrophages generate oxidative stress to destroy the pathogen, while Leishmania combats the harmful effect of radicals by redox homeostasis through its unique trypanothione cascade. Leishmania donovani ascorbate peroxidase (LdAPx) is a redox enzyme that regulates the trypanothione cascade and detoxifies the effect of H2O2. The absence of an LdAPx homologue in humans makes it an excellent drug target. In this study, the homology model of LdAPx was built, including heme, and diverse compounds were prefiltered (PAINS, ADMET, and Lipinski's rule of five) and thereafter screened against the LdAPx model. Compounds having good affinity in terms of the Glide XP (extra precision) score were clustered to select diverse compounds for experimental validation. A total of 26 cluster representatives were procured and tested on promastigote culture, yielding 12 compounds with good antileishmanial activity. Out of them, six compounds were safer on the BALB/c peritoneal macrophages and were also effective against disease-causing intracellular amastigotes. Three out of six compounds inhibited recombinant LdAPx in a noncompetitive manner and also demonstrated partial reversion of the resistance property in an amphotericin B (AmB)-resistant strain, which may be due to an increased level of reactive oxygen species (ROS) and decrease of glutathione (GSH) content. However, inhibition of LdAPx in resistant parasites enhanced annexin V staining and activation of metacaspase-like protease activity, which may help in DNA fragmentation and apoptosis-like cell death. Thus, the present study will help in the search for specific hits and templates of potential therapeutic interest and therefore may facilitate the development of new drugs for combination therapy against VL. PMID:28461317

Personality characteristics and trait clusters in final stage astronaut selection.

PubMed

Musson, David M; Sandal, Gro M; Helmreich, Robert L

2004-04-01

This paper presents personality testing data from final stage applicants to the NASA astronaut program. Questions addressed include whether personality predicted final selection into the astronaut corps, whether women and men demonstrated typical gender differences in personality, and whether three characteristic clusters found in other high performance populations replicated in this group. Between 1989 and 1995, 259 final stage astronauts completed the Personal Characteristic Inventory (PCI) which assesses personality characteristics related to the broad traits of Instrumentality and Expressivity. In addition, 147 of these individuals also completed an abbreviated version of the NEO Five Factor Inventory (NEO-FFI) which assesses the "Big Five" traits of Neuroticism, Extraversion, Openness, Agreeableness, And Conscientiousness. Three previously identified trait clusters (Right, Wrong, and No Stuff) were found to replicate in this population. No differences were found on the PCI or on the modified NEO-FFI between applicants who were chosen to become astronauts (n = 63) and those who were not (n = 196). Men scored higher than women on competitiveness, but lower on expressivity and achievement strivings. These analyses suggest that the "Right Stuff," "Wrong Stuff" and "No Stuff" clusters originally described in airline pilots and other high performance groups also exist within this population. Consistent with findings from other high performance populations, men and women tend to differ to a lesser extent than found in the general population, particularly on traits related to achievement motivation. Personality trait testing did not predict which applicants were most likely to be accepted into the astronaut corps.

Molecular dynamics simulation study of PTP1B with allosteric inhibitor and its application in receptor based pharmacophore modeling

NASA Astrophysics Data System (ADS)

Bharatham, Kavitha; Bharatham, Nagakumar; Kwon, Yong Jung; Lee, Keun Woo

2008-12-01

Allosteric inhibition of protein tyrosine phosphatase 1B (PTP1B), has paved a new path to design specific inhibitors for PTP1B, which is an important drug target for the treatment of type II diabetes and obesity. The PTP1B1-282-allosteric inhibitor complex crystal structure lacks α7 (287-298) and moreover there is no available 3D structure of PTP1B1-298 in open form. As the interaction between α7 and α6-α3 helices plays a crucial role in allosteric inhibition, α7 was modeled to the PTP1B1-282 in open form complexed with an allosteric inhibitor (compound-2) and a 5 ns MD simulation was performed to investigate the relative orientation of the α7-α6-α3 helices. The simulation conformational space was statistically sampled by clustering analyses. This approach was helpful to reveal certain clues on PTP1B allosteric inhibition. The simulation was also utilized in the generation of receptor based pharmacophore models to include the conformational flexibility of the protein-inhibitor complex. Three cluster representative structures of the highly populated clusters were selected for pharmacophore model generation. The three pharmacophore models were subsequently utilized for screening databases to retrieve molecules containing the features that complement the allosteric site. The retrieved hits were filtered based on certain drug-like properties and molecular docking simulations were performed in two different conformations of protein. Thus, performing MD simulation with α7 to investigate the changes at the allosteric site, then developing receptor based pharmacophore models and finally docking the retrieved hits into two distinct conformations will be a reliable methodology in identifying PTP1B allosteric inhibitors.

Identification of natural metabolites in mixture: a pattern recognition strategy based on (13)C NMR.

PubMed

Hubert, Jane; Nuzillard, Jean-Marc; Purson, Sylvain; Hamzaoui, Mahmoud; Borie, Nicolas; Reynaud, Romain; Renault, Jean-Hugues

2014-03-18

Because of their highly complex metabolite profile, the chemical characterization of bioactive natural extracts usually requires time-consuming multistep purification procedures to achieve the structural elucidation of pure individual metabolites. The aim of the present work was to develop a dereplication strategy for the identification of natural metabolites directly within mixtures. Exploiting the polarity range of metabolites, the principle was to rapidly fractionate a multigram quantity of a crude extract by centrifugal partition extraction (CPE). The obtained fractions of simplified chemical composition were subsequently analyzed by (13)C NMR. After automatic collection and alignment of (13)C signals across spectra, hierarchical clustering analysis (HCA) was performed for pattern recognition. As a result, strong correlations between (13)C signals of a single structure within the mixtures of the fraction series were visualized as chemical shift clusters. Each cluster was finally assigned to a molecular structure with the help of a locally built (13)C NMR chemical shift database. The proof of principle of this strategy was achieved on a simple model mixture of commercially available plant secondary metabolites and then applied to a bark extract of the African tree Anogeissus leiocarpus Guill. & Perr. (Combretaceae). Starting from 5 g of this genuine extract, the fraction series was generated by CPE in only 95 min. (13)C NMR analyses of all fractions followed by pattern recognition of (13)C chemical shifts resulted in the unambiguous identification of seven major compounds, namely, sericoside, trachelosperogenin E, ellagic acid, an epimer mixture of (+)-gallocatechin and (-)-epigallocatechin, 3,3'-di-O-methylellagic acid 4'-O-xylopyranoside, and 3,4,3'-tri-O-methylflavellagic acid 4'-O-glucopyranoside.

Correlating the magic numbers of inorganic nanomolecular assemblies with a {Pd84} molecular-ring Rosetta Stone

PubMed Central

Xu, Feng; Miras, Haralampos N.; Scullion, Rachel A.; Long, De-Liang; Thiel, Johannes; Cronin, Leroy

2012-01-01

Molecular self-assembly has often been suggested as the ultimate route for the bottom-up construction of building blocks atom-by-atom for functional nanotechnology, yet structural design or prediction of nanomolecular assemblies is still far from reach. Whereas nature uses complex machinery such as the ribosome, chemists use painstakingly engineered step-by-step approaches to build complex molecules but the size and complexity of such molecules, not to mention the accessible yields, can be limited. Herein we present the discovery of a palladium oxometalate {Pd84}-ring cluster 3.3 nm in diameter; [Pd84O42(OAc)28(PO4)42]70- ({Pd84} ≡ {Pd12}7) that is formed in water just by mixing two reagents at room temperature, giving crystals of the compound in just a few days. The structure of the {Pd84}-ring has sevenfold symmetry, comprises 196 building blocks, and we also show, using mass spectrometry, that a large library of other related nanostructures is present in solution. Finally, by analysis of the symmetry and the building block library that construct the {Pd84} we show that the correlation of the symmetry, subunit number, and overall cluster nuclearity can be used as a “Rosetta Stone” to rationalize the “magic numbers” defining a number of other systems. This is because the discovery of {Pd84} allows the relationship between seemingly unrelated families of molecular inorganic nanosystems to be decoded from the overall cluster magic-number nuclearity, to the symmetry and building blocks that define such structures allowing the prediction of other members of these nanocluster families. PMID:22753516

Isolation and characterization of a sulfur-oxidizing chemolithotroph growing on crude oil under anaerobic conditions.

PubMed

Kodama, Yumiko; Watanabe, Kazuya

2003-01-01

Molecular approaches have shown that a group of bacteria (called cluster 1 bacteria) affiliated with the epsilon subclass of the class Proteobacteria constituted major populations in underground crude-oil storage cavities. In order to unveil their physiology and ecological niche, this study isolated bacterial strains (exemplified by strain YK-1) affiliated with the cluster 1 bacteria from an oil storage cavity at Kuji in Iwate, Japan. 16S rRNA gene sequence analysis indicated that its closest relative was Thiomicrospira denitrificans (90% identity). Growth experiments under anaerobic conditions showed that strain YK-1 was a sulfur-oxidizing obligate chemolithotroph utilizing sulfide, elemental sulfur, thiosulfate, and hydrogen as electron donors and nitrate as an electron acceptor. Oxygen also supported its growth only under microaerobic conditions. Strain YK-1 could not grow on nitrite, and nitrite was the final product of nitrate reduction. Neither sugars, organic acids (including acetate), nor hydrocarbons could serve as carbon and energy sources. A typical stoichiometry of its energy metabolism followed an equation: S(2-) + 4NO(3)(-) --> SO(4)(2-) + 4NO(2)(-) (Delta G(0) = -534 kJ mol(-1)). In a difference from other anaerobic sulfur-oxidizing bacteria, this bacterium was sensitive to NaCl; growth in medium containing more than 1% NaCl was negligible. When YK-1 was grown anaerobically in a sulfur-depleted inorganic medium overlaid with crude oil, sulfate was produced, corresponding to its growth. On the contrary, YK-1 could not utilize crude oil as a carbon source. These results suggest that the cluster 1 bacteria yielded energy for growth in oil storage cavities by oxidizing petroleum sulfur compounds. Based on its physiology, ecological interactions with other members of the groundwater community are discussed.

An efficient procedure for marker-free mutagenesis of S. coelicolor by site-specific recombination for secondary metabolite overproduction.

PubMed

Zhang, Bo; Zhang, Lin; Dai, Ruixue; Yu, Meiying; Zhao, Guoping; Ding, Xiaoming

2013-01-01

Streptomyces bacteria are known for producing important natural compounds by secondary metabolism, especially antibiotics with novel biological activities. Functional studies of antibiotic-biosynthesizing gene clusters are generally through homologous genomic recombination by gene-targeting vectors. Here, we present a rapid and efficient method for construction of gene-targeting vectors. This approach is based on Streptomyces phage φBT1 integrase-mediated multisite in vitro site-specific recombination. Four 'entry clones' were assembled into a circular plasmid to generate the destination gene-targeting vector by a one-step reaction. The four 'entry clones' contained two clones of the upstream and downstream flanks of the target gene, a selectable marker and an E. coli-Streptomyces shuttle vector. After targeted modification of the genome, the selectable markers were removed by φC31 integrase-mediated in vivo site-specific recombination between pre-placed attB and attP sites. Using this method, part of the calcium-dependent antibiotic (CDA) and actinorhodin (Act) biosynthetic gene clusters were deleted, and the rrdA encoding RrdA, a negative regulator of Red production, was also deleted. The final prodiginine production of the engineered strain was over five times that of the wild-type strain. This straightforward φBT1 and φC31 integrase-based strategy provides an alternative approach for rapid gene-targeting vector construction and marker removal in streptomycetes.

How native yeasts may influence the chemical profile of the Brazilian spirit, cachaça?

PubMed

Portugal, Cauré B; de Silva, Arthur Paron; Bortoletto, Aline M; Alcarde, André R

2017-01-01

Cachaça is the typical Brazilian spirit, obtained by distillation of fermented sugarcane must, whose production is closely related to regional heritage and geographical traits. In this work, we investigate the influence of different autochthonous yeast species, in comparison to other commercial strains, on the chemical profile of cachaça. Fermentations were performed with four different wild species, a mixed starter culture with native yeasts, and two commercial strains. Procedures were carried out simulating traditional practices, the distillates analyzed by gas chromatography, and data analyzed by multivariate statistics. Results show that the overgrowth of some non-Saccharomyces during fermentation can lead to higher concentration of contaminant compounds in the distillate. However, those microorganisms do not impress negative traits when working in cluster association, and may indeed contribute to the distinctive chemical quality and flavor of cachaça. Spontaneous fermentation are still the traditional method used for the production of cachaça, and our results indeed suggest that higher diversity, and evened fermentative environments, enable yeasts to act as a complex cluster and imprint a distinctive, quality chemical profile to the distillate. Finally, this study may help to understand the role of the native microbiota and its influence on cachaça's chemical and sensory profiles, besides demonstrating the importance of adopting insightful handling practices and strict control of technical guidelines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-lived, charge-shift states in heterometallic, porphyrin-based dendrimers formed via click chemistry.

PubMed

Le Pleux, Loïc; Pellegrin, Yann; Blart, Errol; Odobel, Fabrice; Harriman, Anthony

2011-05-26

A series of multiporphyrin clusters has been synthesized and characterized in which there exists a logical gradient for either energy or electron transfer between the porphyrins. A central free-base porphyrin (FbP), for example, is equipped with peripheral zinc(II) porphyrins (ZnP) which act as ancillary light harvesters and transfer excitation energy to the FbP under visible light illumination. Additional energy-transfer steps occur at the triplet level, and the series is expanded by including magnesium(II) porphyrins and/or tin(IV) porphyrins as chromophores. Light-induced electron transfer is made possible by incorporating a gold(III) porphyrin (AuP(+)) into the array. Although interesting by themselves, these clusters serve as control compounds by which to understand the photophysical processes occurring within a three-stage dendrimer comprising an AuP(+) core, a second layer formed from four FbP units, and an outer layer containing 12 ZnP residues. Here, illumination into a peripheral ZnP leads to highly efficient electronic energy transfer to FbP, followed by charge transfer to the central AuP(+). Charge recombination within the resultant charge-shift state is intercepted by secondary hole transfer to the ZnP, which occurs with a quantum yield of around 20%. The final charge-shift state survives for some microseconds in fluid solution at room temperature.

Fabrication and Testing of High-Speed-Single-Rotor and Compound-Rotor Systems

DTIC Science & Technology

2016-05-04

pitch link loads, hub loads, rotor wakes and performance of high -speed single-rotor and compound-rotor systems to support 1. REPORT DATE (DD-MM-YYYY) 4...Public Release; Distribution Unlimited UU UU UU UU 05-04-2016 14-Jul-2014 13-Jan-2016 Final Report: Fabrication and Testing of High -Speed Single- Rotor and...Final Report: Fabrication and Testing of High -Speed Single-Rotor and Compound-Rotor Systems Report Title The Alfred Gessow Rotorcraft Center has

Fabrication and Testing of High-Speed Single-Rotor and Compound-Rotor Systems

DTIC Science & Technology

2016-04-05

pitch link loads, hub loads, rotor wakes and performance of high -speed single-rotor and compound-rotor systems to support 1. REPORT DATE (DD-MM-YYYY) 4...Public Release; Distribution Unlimited UU UU UU UU 05-04-2016 14-Jul-2014 13-Jan-2016 Final Report: Fabrication and Testing of High -Speed Single- Rotor and...Final Report: Fabrication and Testing of High -Speed Single-Rotor and Compound-Rotor Systems Report Title The Alfred Gessow Rotorcraft Center has

Unique DC-SIGN clustering activity of a small glycomimetic: A lesson for ligand design.

PubMed

Sutkeviciute, Ieva; Thépaut, Michel; Sattin, Sara; Berzi, Angela; McGeagh, John; Grudinin, Sergei; Weiser, Jörg; Le Roy, Aline; Reina, Jose J; Rojo, Javier; Clerici, Mario; Bernardi, Anna; Ebel, Christine; Fieschi, Franck

2014-06-20

DC-SIGN is a dendritic cell-specific C-type lectin receptor that recognizes highly glycosylated ligands expressed on the surface of various pathogens. This receptor plays an important role in the early stages of many viral infections, including HIV, which makes it an interesting therapeutic target. Glycomimetic compounds are good drug candidates for DC-SIGN inhibition due to their high solubility, resistance to glycosidases, and nontoxicity. We studied the structural properties of the interaction of the tetrameric DC-SIGN extracellular domain (ECD), with two glycomimetic antagonists, a pseudomannobioside (1) and a linear pseudomannotrioside (2). Though the inhibitory potency of 2, as measured by SPR competition experiments, was 1 order of magnitude higher than that of 1, crystal structures of the complexes within the DC-SIGN carbohydrate recognition domain showed the same binding mode for both compounds. Moreover, when conjugated to multivalent scaffolds, the inhibitory potencies of these compounds became uniform. Combining isothermal titration microcalorimetry, analytical ultracentrifugation, and dynamic light scattering techniques to study DC-SIGN ECD interaction with these glycomimetics revealed that 2 is able, without any multivalent presentation, to cluster DC-SIGN tetramers leading to an artificially overestimated inhibitory potency. The use of multivalent scaffolds presenting 1 or 2 in HIV trans-infection inhibition assay confirms the loss of potency of 2 upon conjugation and the equal efficacy of chemically simpler compound 1. This study documents a unique case where, among two active compounds chemically derived, the compound with the lower apparent activity is the optimal lead for further drug development.

Determination of the ultrasound power effects on flavonoid compounds from Psidium guajava L. using ANFIS

NASA Astrophysics Data System (ADS)

Ratu Ayu, Humairoh; Suryono, Suryono; Endro Suseno, Jatmiko; Kurniawati, Ratna

2018-05-01

The Adaptive Neural Fuzzy Inference System (ANFIS) model was used to predict and optimize the content of flavonoid compounds in guava leaves (Psidium Guajava L.). The extraction process was carried out by using ultrasound assisted extraction (UAE) with the variable parameters: temperature ranging from 25°C to 35°C, ultrasonic frequency (30 - 40 kHz) and extraction time (20 - 40 minutes). ANFIS learning procedure began by providing the input variable data set (temperature, frequency and time) and the output of the flavonoid compounds from the experiments that had been done. Subtractive clustering methods was used in the manufacture of FIS (fuzzy inference system) structures by varying the range of influence parameters to generate the ANFIS system. The ANFIS trainingsconducted wereaimed at minimum error value. The results showed that the best ANFIS models used a subtractive clustering method, in which the ranges of influence 0.1 were 0.70 x 10-4 for training RMSE, 8.11 for testing RMSE, 2.7 % MAPE, and 7.72 MAE. The optimum condition was obtained at a temperature of 35°C and frequency of 40 kHz, for 30 minutes. This result proves that the ANFIS model can be used to predict the content of flavonoid compounds in guava leaves.

Three 3D metal coordination polymers based on triazol-functionalized rigid ligand: Synthesis, topological structure and properties

NASA Astrophysics Data System (ADS)

Meng, Lingkun; Liu, Kang; Liang, Chen; Guo, Xiaolei; Han, Xu; Ren, Siyuan; Ma, Dingxuan; Li, Guanghua; Shi, Zhan; Feng, Shouhua

2018-02-01

By using a triazol-functionalized tricarboxylate, three novel metal coordination polymers, namely, [Zn2L(OH)]·0.5H2O (1), [Co2L(OH)(H2O)]·5.5H2O (2), [Cu2(HL)] (3) L = ［5-(3-(4-carboxyphenyl)-5-methyl-4H-1,2,4-triazol-4-yl)isophthalate］ were synthesized under hydrothermal reactions. All the compounds were characterized by element analysis, IR spectroscopy, thermogravimetric analysis, power X-ray diffrcation and single-crystal X-ray diffrcation. Structural analysis reveals that compounds 1 and 2 have 3D networks with flu topologies where rigid trizaol-functionalized ligands as 4-connected nodes and Zn4(COO)6 or Co4(COO)6 clusters serves as 8-connected secondary building units. Compound 3 has 3D network with pcu topology where Cu4(COO)4 clusters serve as 6-connected secondary building units. Gas adsorption studies reveal that desolvated compoud 1 exhibits high H2 absorption capacity at 77 K and highly selective separation abilities of CO2 and C3H8 over CH4 at room temperature. The results suggest that 1 has potential application in gas storage and separation. In addition, the magnetic properties of compound 2 were also investigated.

Determination of the phenolic content, profile, and antioxidant activity of seeds from nine tree peony (Paeonia section Moutan DC.) species native to China.

PubMed

Zhang, Xiao-Xiao; Shi, Qian-Qian; Ji, Duo; Niu, Li-Xin; Zhang, Yan-Long

2017-07-01

As an important resource of functional food, the seeds of tree peony are rich in phenolic compounds, which are associated with antioxidant activity. However, so far there has not been systematic study on phenolic compositions and antioxidant activity of the seeds from wild tree peony species. The aim of this study was to determine the phenolic content, antioxidant compounds and antioxidant activity of seeds from nine tree peony species native to China. Among the seed samples, Paeonia rockii had the highest total flavonoid content, strongest DPPH and ABTS radical scavenging activities, and strongest cupric reducing capacity; P. decomposita subsp. rotundiloba had the highest total phenolic and flavanol contents, as well as the strongest hydroxyl radical scavenging activity. Sixteen individual phenolic compounds were quantitatively measured, with (+)-catechin being the most abundant component. The content of the phenolic compounds luteolin, paeonol, and the total flavonoid content were significantly correlated with four antioxidant activities. Hierarchical cluster analysis showed that P. rockii and P. decomposita subsp. rotundiloba could be clustered in a group having a high phenolic content and strong antioxidant activity. These results suggest P. rockii and P. decomposita subsp. rotundiloba are the most promising candidates as useful sources of natural antioxidants. Copyright © 2017. Published by Elsevier Ltd.

Characterization of the chemical composition of Adenostemma lavenia (L.) Kuntze and Adenostemma platyphyllum Cass

NASA Astrophysics Data System (ADS)

Fauzan, A.; Praseptiangga, D.; Hartanto, R.; Pujiasmanto, B.

2018-01-01

The purpose of this study was to characterize the chemical compounds of Adenostemma lavenia (L.) Kuntze (Al) and Adenostemma platyphyllum Cass (Ap) using Pyrolysis-gas chromatography/mass spectrometry (Py-GCMS) and proximate analysis. Two species of Adenostemma samples (roots, stem and leaves) about 1 mg was pyrolyzed directly at the optimum temperature of 600°C. Py-GCMS was relatively fast, easy to use and without samples preparation and identification of the chemical compounds was carried out by comparison of the mass spectra obtained with those stored in Wiley 7th libraries. The data of proximate analysis were statistically analysed using Friedman test followed and hierarchical cluster analysis (HCA) for data of Py-GCMS. The result of proximate analysis showed that A. lavenia (L.) Kuntze (Al) and A. platyphyllum Cass (Ap) contained 8.27% (Al) and 9.18% (Ap) of water, 11.52% (Al) and 17.84% (Ap) of protein, 5.67% (Al) and 6.33% (Ap) of fat, and 17.32% (Al) and 19.94 (Ap) of ash. Amines, aldehydes, fatty acids, terpenoids-steroids, alkaloids, aromatic and aliphatic hydrocarbons, phenolic, and oligopeptides as part of 125 chemical compounds of each species are identified by Py-GCMS analysis. Hierarchical cluster analysis of pyrolysis products indicate not similitary of major chemical compounds of two Adenostemma species.

Chemical Composition and Crystal Morphology of Epicuticular Wax in Mature Fruits of 35 Pear (Pyrus spp.) Cultivars

PubMed Central

Wu, Xiao; Yin, Hao; Shi, Zebin; Chen, Yangyang; Qi, Kaijie; Qiao, Xin; Wang, Guoming; Cao, Peng; Zhang, Shaoling

2018-01-01

An evaluation of fruit wax components will provide us with valuable information for pear breeding and enhancing fruit quality. Here, we dissected the epicuticular wax concentration, composition and structure of mature fruits from 35 pear cultivars belonging to five different species and hybrid interspecies. A total of 146 epicuticular wax compounds were detected, and the wax composition and concentration varied dramatically among species, with the highest level of 1.53 mg/cm2 in Pyrus communis and the lowest level of 0.62 mg/cm2 in Pyrus pyrifolia. Field emission scanning electron microscopy (FESEM) analysis showed amorphous structures of the epicuticular wax crystals of different pear cultivars. Cluster analysis revealed that the Pyrus bretschneideri cultivars were grouped much closer to Pyrus pyrifolia and Pyrus ussuriensis, and the Pyrus sinkiangensis cultivars were clustered into a distant group. Based on the principal component analysis (PCA), the cultivars could be divided into three groups and five groups according to seven main classes of epicuticular wax compounds and 146 wax compounds, respectively. PMID:29875784

Temporal dynamics of halogenated organic compounds in Marcellus Shale flowback.

PubMed

Luek, Jenna L; Harir, Mourad; Schmitt-Kopplin, Philippe; Mouser, Paula J; Gonsior, Michael

2018-06-01

The chemistry of hydraulic fracturing fluids and wastewaters is complex and is known to vary by operator, geologic formation, and fluid age. A time series of hydraulic fracturing fluids, flowback fluids, and produced waters was collected from two adjacent Marcellus Shale gas wells for organic chemical composition analyses using ultrahigh resolution mass spectrometry. Hierarchical clustering was used to compare and extract ions related to different fluid ages and many halogenated organic molecular ions were identified in flowback fluids and early produced waters based on exact mass. Iodinated organic compounds were the dominant halogen class in these clusters and were nearly undetectable in hydraulic fracturing fluid prior to injection. The iodinated ions increased in flowback and remained elevated after ten months of well production. We suggest that these trends are mainly driven by dissolved organic matter reacting with reactive halogen species formed abiotically through oxidizing chemical additives applied to the well and biotically via iodide-oxidizing bacteria. Understanding the implications of these identified halogenated organic compounds will require future investigation in to their structures and environmental fate. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Influence of antitumor system rhenium-platinum on biochemical state of the liver].

PubMed

Ivchuk, V V; Polishko, T M; Golichenko, O A; Shtemenko, O V; Shtemenko, N I

2011-01-01

Influence of the antitumour rhenium-platinum system on biochemical liver characteristics in the model of tumor growth (Guerin carcinoma) was studied and possible hepatoprotective activity of rhenium cluster compounds when introducing them in different forms was shown, that was confirmed by decreasing of diagnostic enzymes activity in blood (aminotransferase--AST 6 times and ALT 5.6 times, lactatedehydrogenase 4.9 times, gamma-glutamyltranspeptidase 3.6 times) and normalization of morphological state of the liver cells. The hepatoprotective activity of the cluster rhenium compound with adamanthyl ligands was confirmed in the model of acute toxic hepatitis. Introduction of this compound led to reduction of the concentration of MDA in homogenates of liver tissue (2 times), and in blood plasma (3.8 times); to reduction of levels of diagnostic liver enzymes in blood--AST and ALT 5.8 and 5.5 times respectively in comparison with control group. Some aspects of the mechanism of hepatoprotection were discussed, that included the presence of conjugated systems around the quadrupol rhenium-rhenium bond and alkyl radicals with significant positive inductive effects.

Cosmology from galaxy clusters as observed by Planck

NASA Astrophysics Data System (ADS)

Pierpaoli, Elena

We propose to use current all-sky data on galaxy clusters in the radio/infrared bands in order to constrain cosmology. This will be achieved performing parameter estimation with number counts and power spectra for galaxy clusters detected by Planck through their Sunyaev—Zeldovich signature. The ultimate goal of this proposal is to use clusters as tracers of matter density in order to provide information about fundamental properties of our Universe, such as the law of gravity on large scale, early Universe phenomena, structure formation and the nature of dark matter and dark energy. We will leverage on the availability of a larger and deeper cluster catalog from the latest Planck data release in order to include, for the first time, the cluster power spectrum in the cosmological parameter determination analysis. Furthermore, we will extend clusters' analysis to cosmological models not yet investigated by the Planck collaboration. These aims require a diverse set of activities, ranging from the characterization of the clusters' selection function, the choice of the cosmological cluster sample to be used for parameter estimation, the construction of mock samples in the various cosmological models with correct correlation properties in order to produce reliable selection functions and noise covariance matrices, and finally the construction of the appropriate likelihood for number counts and power spectra. We plan to make the final code available to the community and compatible with the most widely used cosmological parameter estimation code. This research makes use of data from the NASA satellites Planck and, less directly, Chandra, in order to constrain cosmology; and therefore perfectly fits the NASA objectives and the specifications of this solicitation.

Infant Discrimination of a Morphologically Relevant Word-Final Contrast

ERIC Educational Resources Information Center

Fais, Laurel; Kajikawa, Sachiyo; Amano, Shigeaki; Werker, Janet F.

2009-01-01

Six-, 12-, and 18-month-old English-hearing infants were tested on their ability to discriminate nonword forms ending in the final stop consonants /k/ and /t/ from their counterparts with final /s/ added, resulting in final clusters /ks/ and /ts/, in a habituation-dishabituation, looking time paradigm. Infants at all 3 ages demonstrated an ability…

Elastic K-means using posterior probability.

PubMed

Zheng, Aihua; Jiang, Bo; Li, Yan; Zhang, Xuehan; Ding, Chris

2017-01-01

The widely used K-means clustering is a hard clustering algorithm. Here we propose a Elastic K-means clustering model (EKM) using posterior probability with soft capability where each data point can belong to multiple clusters fractionally and show the benefit of proposed Elastic K-means. Furthermore, in many applications, besides vector attributes information, pairwise relations (graph information) are also available. Thus we integrate EKM with Normalized Cut graph clustering into a single clustering formulation. Finally, we provide several useful matrix inequalities which are useful for matrix formulations of learning models. Based on these results, we prove the correctness and the convergence of EKM algorithms. Experimental results on six benchmark datasets demonstrate the effectiveness of proposed EKM and its integrated model.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ben-Naim, Eli; Krapivsky, Paul

Here we generalize the ordinary aggregation process to allow for choice. In ordinary aggregation, two random clusters merge and form a larger aggregate. In our implementation of choice, a target cluster and two candidate clusters are randomly selected and the target cluster merges with the larger of the two candidate clusters.We study the long-time asymptotic behavior and find that as in ordinary aggregation, the size density adheres to the standard scaling form. However, aggregation with choice exhibits a number of different features. First, the density of the smallest clusters exhibits anomalous scaling. Second, both the small-size and the large-size tailsmore » of the density are overpopulated, at the expense of the density of moderate-size clusters. Finally, we also study the complementary case where the smaller candidate cluster participates in the aggregation process and find an abundance of moderate clusters at the expense of small and large clusters. Additionally, we investigate aggregation processes with choice among multiple candidate clusters and a symmetric implementation where the choice is between two pairs of clusters.« less

Two Fe-S clusters catalyse sulfur insertion by Radical-SAM methylthiotransferases

PubMed Central

Forouhar, Farhad; Arragain, Simon; Atta, Mohamed; Gambarelli, Serge; Mouesca, Jean-Marie; Hussain, Munif; Xiao, Rong; Kieffer-Jaquinod, Sylvie; Seetharaman, Jayaraman; Acton, Thomas B.; Montelione, Gaetano T.

2014-01-01

How living organisms create carbon-sulfur bonds during biosynthesis of critical sulphur-containing compounds is still poorly understood. The methylthiotransferases MiaB and RimO catalyze sulfur insertion into tRNAs and ribosomal protein S12, respectively. Both belong to a sub-group of Radical-SAM enzymes that bear two [4Fe-4S] clusters. One cluster binds S-Adenosylmethionine and generates an Ado• radical via a well- established mechanism. However, the precise role of the second cluster is unclear. For some sulfur-inserting Radical-SAM enzymes, this cluster has been proposed to act as a sacrificial source of sulfur for the reaction. In this paper, we report parallel enzymological, spectroscopic and crystallographic investigations of RimO and MiaB, which provide the first evidence that these enzymes are true catalysts and support a new sulfation mechanism involving activation of an exogenous sulfur co-substrate at an exchangeable coordination site on the second cluster, which remains intact during the reaction. PMID:23542644

Multielectron donors based on TTF-phosphine and ferrocene-phosphine hybrid complexes of a hexarhenium(III) octahedral cluster core.

PubMed

Perruchas, Sandrine; Avarvari, Narcis; Rondeau, David; Levillain, Eric; Batail, Patrick

2005-05-16

Electroactive molecular materials precursors are obtained through coordination chemistry of the hexarhenium cluster core [Re(6)Se(8)](2+) on the six available apical positions with redox-active phosphines bearing tetrathiafulvalene- or ferrocene-based moieties. Single-crystal X-ray diffraction study and electrospray mass spectrometry ascertain the synthesis of these hexasubstituted electroactive clusters, containing up to 12 redox active sites. Cyclic voltammetry experiments demonstrate that these compounds can be reversibly oxidized at rather low potentials, thus allowing an easy access to the corresponding radical species which should provide new conducting and/or magnetic molecular materials.

Quantum chemical analysis of thermodynamics of 2D cluster formation of alkanes at the water/vapor interface in the presence of aliphatic alcohols.

PubMed

Vysotsky, Yu B; Kartashynska, E S; Belyaeva, E A; Fainerman, V B; Vollhardt, D; Miller, R

2015-11-21

Using the quantum chemical semi-empirical PM3 method it is shown that aliphatic alcohols favor the spontaneous clusterization of vaporous alkanes at the water surface due to the change of adsorption from the barrier to non-barrier mechanism. A theoretical model of the non-barrier mechanism for monolayer formation is developed. In the framework of this model alcohols (or any other surfactants) act as 'floats', which interact with alkane molecules of the vapor phase using their hydrophobic part, whereas the hydrophilic part is immersed into the water phase. This results in a significant increase of contact effectiveness of alkanes with the interface during the adsorption and film formation. The obtained results are in good agreement with the existing experimental data. To test the model the thermodynamic and structural parameters of formation and clusterization are calculated for vaporous alkanes C(n)H(2n+2) (n(CH3) = 6-16) at the water surface in the presence of aliphatic alcohols C(n)H(2n+1)OH (n(OH) = 8-16) at 298 K. It is shown that the values of clusterization enthalpy, entropy and Gibbs' energy per one monomer of the cluster depend on the chain lengths of corresponding alcohols and alkanes, the alcohol molar fraction in the monolayers formed, and the shift of the alkane molecules with respect to the alcohol molecules Δn. Two possible competitive structures of mixed 2D film alkane-alcohol are considered: 2D films 1 with single alcohol molecules enclosed by alkane molecules (the alcohols do not form domains) and 2D films 2 that contain alcohol domains enclosed by alkane molecules. The formation of the alkane films of the first type is nearly independent of the surfactant type present at the interface, but depends on their molar fraction in the monolayer formed and the chain length of the compounds participating in the clusterization, whereas for the formation of the films of the second type the interaction between the hydrophilic parts of the surfactant is essential and different for various types of amphiphilic compounds. The energetic preference of the film formation of both types depends significantly on the chain length of compounds. The surfactant concentration (in the range of X = 0-10%) exerts a slight influence on the process of film formation.

Exchange coupling transformations in Cu (II) heterospin complexes of “breathing crystals” under structural phase transitions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morozov, Vitaly A.; Petrova, Marina V.; Lukzen, Nikita N., E-mail: luk@tomo.nsc.ru

2015-08-15

Family of “breathing crystals” is the polymer-chain complexes of Cu(hfac){sub 2} with nitroxides. The polymer chains consist of one-, two- or three-spin clusters. The “breathing crystals” experience simultaneous magnetic and Jahn-Teller type structural phase transitions with change of total cluster spin and drastic change of bond lengths (ca. 10-12%). For the first time the intra-cluster magnetic couplings in ”breathing crystals” have been calculated both by band structure methods GGA + U and hybrid DFT (B3LYP and PBE0) for the isolated exchange clusters. The temperature dependence of the magnetic coupling constant was calculated for two polymer-chain compounds of the “breathing crystal”more » family - C{sub 21}H{sub 19}CuF{sub 12}N{sub 4}O{sub 6} with the chains containing two-spin clusters and C{sub 22}H{sub 21}CuF{sub 12}N{sub 4}O{sub 6} with the chains of alternating three-spin clusters and one-spin sites. It was found that adding a Hubbard-like parameter not only to the copper 3d electrons but also to the oxygen 2p electrons (GGA + U{sub d} + U{sub p} approach) results in an improved description of exchange coupling in the “breathing crystal” compounds. At the same time treatment of the isolated clusters by a large basis hybrid DFT with high computational cost provides a similar quality fit of the experimental magneto-chemical data as that for the GGA + U{sub d} + U{sub p} band structure calculation scheme. Our calculations also showed that in spite of the abrupt transformation of the magnetic coupling constant under the phase transition, the band gap in the “breathing crystals” remains about the same value with temperature decrease.« less

Gene expression pattern recognition algorithm inferences to classify samples exposed to chemical agents

NASA Astrophysics Data System (ADS)

Bushel, Pierre R.; Bennett, Lee; Hamadeh, Hisham; Green, James; Ableson, Alan; Misener, Steve; Paules, Richard; Afshari, Cynthia

2002-06-01

We present an analysis of pattern recognition procedures used to predict the classes of samples exposed to pharmacologic agents by comparing gene expression patterns from samples treated with two classes of compounds. Rat liver mRNA samples following exposure for 24 hours with phenobarbital or peroxisome proliferators were analyzed using a 1700 rat cDNA microarray platform. Sets of genes that were consistently differentially expressed in the rat liver samples following treatment were stored in the MicroArray Project System (MAPS) database. MAPS identified 238 genes in common that possessed a low probability (P < 0.01) of being randomly detected as differentially expressed at the 95% confidence level. Hierarchical cluster analysis on the 238 genes clustered specific gene expression profiles that separated samples based on exposure to a particular class of compound.

Polymer-mediated formation of polyoxomolybdate nanomaterials

NASA Astrophysics Data System (ADS)

Wan, Quan

A polymer-mediated synthetic pathway to a polyoxomolybdate nanomaterial is investigated in this work. Block copolymers or homopolymers containing poly(ethylene oxide) (PEO) are mixed with a MoO2(OH)(OOH) aqueous solution to form a golden gel or viscous solution. As revealed by synchrotron X-ray scattering measurements, electron microscopy, and other characterization techniques, the final dark blue polyoxomolybdate product is a highly ordered simple cubic network similar to certain zeolite structure but with a much larger lattice constant of ˜5.2 nm. The average size of the cube-like single crystals is close to 1 mum. Based on its relatively low density (˜2.2 g/cm3), the nanomaterial can be highly porous if the amount of the residual polymer can be substantially reduced. The valence of molybdenum is ˜5.7 based on cerimetric titration, representing the mixed-valence nature of the polyoxomolybdate structure. The self-assembled structures (if any) of the polymer gel do not have any correlation with the final polyoxomolybdate nanostructure, excluding the possible role of polymers being a structure-directing template. On the other hand, the PEO polymer stabilizes the precursor molybdenum compound through coordination between its ether oxygen atoms and molybdenum atoms, and reduces the molybdenum (VI) precursor compound with its hydroxyl group being a reducing agent. The rare simple cubic ordering necessitates the existence of special affinities among the polyoxomolybdate nanosphere units resulted from the reduction reaction. Our mechanism study shows that the acidified condition is necessary for the synthesis of the mixed-valence polyoxomolybdate clusters, while H2O2 content modulates the rate of the reduction reaction. The polymer degradation is evidenced by the observation of a huge viscosity change, and is likely through a hydrolysis process catalyzed by molybdenum compounds. Cube-like polyoxomolybdate nanocrystals with size of ˜40 nm are obtained by means of inversed microemulsions. Reducing agents such as di(ethylene glycol) and glycerol are utilized to synthesize various nanoscale ordering polyoxomolybdate structures. Only PEO-containing polymers are capable of producing the simple cubic polyoxomolybdate nanomaterials. Such a synthetic strategy may open up new pathways to prepare similar functional nanomaterials.

Design of polystyrene latex particles covered with polyoxometalate clusters via multiple covalent bonding

DOE PAGES

Chen, Xinyue; Li, Hui; Yin, Panchao; ...

2015-02-27

In this study, polyoxometalates (POMs) covalently functionalized with methyl methacrylate groups were applied as surfactants in the emulsion polymerization reaction of styrene. Due to the copolymerization of the methyl methacrylate groups and the styrene monomers, the polyoxometalate clusters are covalently grafted onto the surface of polystyrene latex nanoparticles. Finally, such latex particles are fully covered with catalytic POM clusters and might serve as quasi-homogeneous catalysts.

AN INVESTIGATION AND DEVELOPMENT OF THE CLUSTER CONCEPT AS A PROGRAM IN VOCATIONAL EDUCATION AT THE SECONDARY SCHOOL LEVEL--FINAL REPORT, PHASE 1.

ERIC Educational Resources Information Center

MALEY, DONALD

THE INVESTIGATION AND DEVELOPMENT OF THE CLUSTER CONCEPT AS A PROGRAM IN VOCATIONAL EDUCATION AT THE SECONDARY SCHOOL LEVEL WERE REPORTED. THE "CLUSTER CONCEPT" PROGRAM IS AIMED AT THE DEVELOPMENT OF SKILLS AND UNDERSTANDINGS RELATED TO A NUMBER OF ALLIED FIELDS, AND WOULD PREPARE THE PERSON TO ENTER INTO A FAMILY OF OCCUPATIONS RATHER…

Skill and Working Memory.

DTIC Science & Technology

1982-04-30

clusters of rooms or areas. The fairly localized property of architectural patterns at the lowest level in the hierarchy is reminiscent of the localized...three digits. We have termed these clusters of groups "supergroups". Finally, when these supergroups became too large (more than 4 or 5 groups), SF...Supergroups -.> Clusters of Supergroups. Insert Figure 4 about here .... .... o.... In another study, run separately on SF and DD, after an hour’s

Potential human cholesterol esterase inhibitor design: benefits from the molecular dynamics simulations and pharmacophore modeling studies.

PubMed

John, Shalini; Thangapandian, Sundarapandian; Lee, Keun Woo

2012-01-01

Human pancreatic cholesterol esterase (hCEase) is one of the lipases found to involve in the digestion of large and broad spectrum of substrates including triglycerides, phospholipids, cholesteryl esters, etc. The presence of bile salts is found to be very important for the activation of hCEase. Molecular dynamic simulations were performed for the apoform and bile salt complexed form of hCEase using the co-ordinates of two bile salts from bovine CEase. The stability of the systems throughout the simulation time was checked and two representative structures from the highly populated regions were selected using cluster analysis. These two representative structures were used in pharmacophore model generation. The generated pharmacophore models were validated and used in database screening. The screened hits were refined for their drug-like properties based on Lipinski's rule of five and ADMET properties. The drug-like compounds were further refined by molecular docking simulation using GOLD program based on the GOLD fitness score, mode of binding, and molecular interactions with the active site amino acids. Finally, three hits of novel scaffolds were selected as potential leads to be used in novel and potent hCEase inhibitor design. The stability of binding modes and molecular interactions of these final hits were re-assured by molecular dynamics simulations.

Anthocyanins in the bracts of Curcuma species and relationship of the species based on anthocyanin composition.

PubMed

Koshioka, Masaji; Umegaki, Naoko; Boontiang, Kriangsuk; Pornchuti, Witayaporn; Thammasiri, Kanchit; Yamaguchi, Satoshi; Tatsuzawa, Fumi; Nakayama, Masayoshi; Tateishi, Akira; Kubota, Satoshi

2015-03-01

Five anthocyanins, delphinidin 3-O-rutinoside, cyanidin 3-O-rutinoside, petunidin 3-O-rutinoside, malvidin 3-O-glucoside and malvidin 3-O-rutinoside, were identified. Three anthocyanins, delphinidin 3-O-glucoside, cyanidin 3-O-glucoside and pelargonidin 3-O-rutinoside, were putatively identified based on C18 HPLC retention time, absorption spectrum, including λmax, and comparisons with those of corresponding standard anthocyanins, as the compounds responsible for the pink to purple-red pigmentation of the bracts of Curcuma alismatifolia and five related species. Cluster analysis based on four major anthocyanins formed two clusters. One consisted of only one species, C. alismatifolia, and the other consisted of five. Each cluster further formed sub-clusters depending on either species or habitats.

Organometallic chemistry of heterobimetallic compounds: Final report for the period August 1, 1985-June 30, 1988

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casey, C.P.

1988-03-01

Work is reported on the following: formyl compounds, cyclopentadienyl ring slippage, ..mu..-hydrocarbyl diiron complexes, heterobimetallic compounds linked by heterodifunctional ligands, heterobimetallic dihydrides, reactions of heterobimetallic dihydrides, early-late transition metal bimetallic compounds, and heterobimetallic ..mu..-alkylidene complexes. (DLC)

Automated clustering of probe molecules from solvent mapping of protein surfaces: new algorithms applied to hot-spot mapping and structure-based drug design

NASA Astrophysics Data System (ADS)

Lerner, Michael G.; Meagher, Kristin L.; Carlson, Heather A.

2008-10-01

Use of solvent mapping, based on multiple-copy minimization (MCM) techniques, is common in structure-based drug discovery. The minima of small-molecule probes define locations for complementary interactions within a binding pocket. Here, we present improved methods for MCM. In particular, a Jarvis-Patrick (JP) method is outlined for grouping the final locations of minimized probes into physical clusters. This algorithm has been tested through a study of protein-protein interfaces, showing the process to be robust, deterministic, and fast in the mapping of protein "hot spots." Improvements in the initial placement of probe molecules are also described. A final application to HIV-1 protease shows how our automated technique can be used to partition data too complicated to analyze by hand. These new automated methods may be easily and quickly extended to other protein systems, and our clustering methodology may be readily incorporated into other clustering packages.

A hybrid sales forecasting scheme by combining independent component analysis with K-means clustering and support vector regression.

PubMed

Lu, Chi-Jie; Chang, Chi-Chang

2014-01-01

Sales forecasting plays an important role in operating a business since it can be used to determine the required inventory level to meet consumer demand and avoid the problem of under/overstocking. Improving the accuracy of sales forecasting has become an important issue of operating a business. This study proposes a hybrid sales forecasting scheme by combining independent component analysis (ICA) with K-means clustering and support vector regression (SVR). The proposed scheme first uses the ICA to extract hidden information from the observed sales data. The extracted features are then applied to K-means algorithm for clustering the sales data into several disjoined clusters. Finally, the SVR forecasting models are applied to each group to generate final forecasting results. Experimental results from information technology (IT) product agent sales data reveal that the proposed sales forecasting scheme outperforms the three comparison models and hence provides an efficient alternative for sales forecasting.

A Hybrid Sales Forecasting Scheme by Combining Independent Component Analysis with K-Means Clustering and Support Vector Regression

PubMed Central

2014-01-01

Sales forecasting plays an important role in operating a business since it can be used to determine the required inventory level to meet consumer demand and avoid the problem of under/overstocking. Improving the accuracy of sales forecasting has become an important issue of operating a business. This study proposes a hybrid sales forecasting scheme by combining independent component analysis (ICA) with K-means clustering and support vector regression (SVR). The proposed scheme first uses the ICA to extract hidden information from the observed sales data. The extracted features are then applied to K-means algorithm for clustering the sales data into several disjoined clusters. Finally, the SVR forecasting models are applied to each group to generate final forecasting results. Experimental results from information technology (IT) product agent sales data reveal that the proposed sales forecasting scheme outperforms the three comparison models and hence provides an efficient alternative for sales forecasting. PMID:25045738

Integrative analysis of signaling pathways and diseases associated with the miR-106b/25 cluster and their function study in berberine-induced multiple myeloma cells.

PubMed

Gu, Chunming; Li, Tianfu; Yin, Zhao; Chen, Shengting; Fei, Jia; Shen, Jianping; Zhang, Yuan

2017-05-01

Berberine (BBR), a traditional Chinese herbal medicine compound, has emerged as a novel class of anti-tumor agent. Our previous microRNA (miRNA) microarray demonstrated that miR-106b/25 was significantly down-regulated in BBR-treated multiple myeloma (MM) cells. Here, systematic integration showed that miR-106b/25 cluster is involved in multiple cancer-related signaling pathways and tumorigenesis. MiREnvironment database revealed that multiple environmental factors (drug, ionizing radiation, hypoxia) affected the miR-106b/25 cluster expression. By targeting the seed region in the miRNA, tiny anti-mir106b/25 cluster (t-anti-mir106b/25 cluster) significantly induced suppression in cell viability and colony formation. Western blot validated that t-anti-miR-106b/25 cluster effectively inhibited the expression of P38 MAPK and phospho-P38 MAPK in MM cells. These findings indicated the miR-106b/25 cluster functioned as oncogene and might provide a novel molecular insight into MM.

Modularity of Plant Metabolic Gene Clusters: A Trio of Linked Genes That Are Collectively Required for Acylation of Triterpenes in Oat[W][OA

PubMed Central

Mugford, Sam T.; Louveau, Thomas; Melton, Rachel; Qi, Xiaoquan; Bakht, Saleha; Hill, Lionel; Tsurushima, Tetsu; Honkanen, Suvi; Rosser, Susan J.; Lomonossoff, George P.; Osbourn, Anne

2013-01-01

Operon-like gene clusters are an emerging phenomenon in the field of plant natural products. The genes encoding some of the best-characterized plant secondary metabolite biosynthetic pathways are scattered across plant genomes. However, an increasing number of gene clusters encoding the synthesis of diverse natural products have recently been reported in plant genomes. These clusters have arisen through the neo-functionalization and relocation of existing genes within the genome, and not by horizontal gene transfer from microbes. The reasons for clustering are not yet clear, although this form of gene organization is likely to facilitate co-inheritance and co-regulation. Oats (Avena spp) synthesize antimicrobial triterpenoids (avenacins) that provide protection against disease. The synthesis of these compounds is encoded by a gene cluster. Here we show that a module of three adjacent genes within the wider biosynthetic gene cluster is required for avenacin acylation. Through the characterization of these genes and their encoded proteins we present a model of the subcellular organization of triterpenoid biosynthesis. PMID:23532069

Candicidin Biosynthesis Gene Cluster Is Widely Distributed among Streptomyces spp. Isolated from the Sediments and the Neuston Layer of the Trondheim Fjord, Norway▿ †

PubMed Central

Jørgensen, Hanne; Fjærvik, Espen; Hakvåg, Sigrid; Bruheim, Per; Bredholt, Harald; Klinkenberg, Geir; Ellingsen, Trond E.; Zotchev, Sergey B.

2009-01-01

A large number of Streptomyces bacteria with antifungal activity isolated from samples collected in the Trondheim fjord (Norway) were found to produce polyene compounds. Investigation of polyene-containing extracts revealed that most of the isolates produced the same compound, which had an atomic mass and UV spectrum corresponding to those of candicidin D. The morphological diversity of these isolates prompted us to speculate about the involvement of a mobile genetic element in dissemination of the candicidin biosynthesis gene cluster (can). Eight candicidin-producing isolates were analyzed by performing a 16S rRNA gene-based taxonomic analysis, pulsed-field gel electrophoresis, PCR, and Southern blot hybridization with can-specific probes. These analyses revealed that most of the isolates were related, although they were morphologically diverse, and that all of them contained can genes. The majority of the isolates studied contained large plasmids, and two can-specific probes hybridized to a 250-kb plasmid in one isolate. Incubation of the latter isolate at a high temperature resulted in loss of the can genes and candicidin production, while mating of the “cured” strain with a plasmid-containing donor restored candicidin production. The latter result suggested that the 250-kb plasmid contains the complete can gene cluster and could be responsible for conjugative transfer of this cluster to other streptomycetes. PMID:19286787

Structural variation from heterometallic cluster-based 1D chain to heterometallic tetranuclear cluster: Syntheses, structures and magnetic properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Shu-Hua, E-mail: zsh720108@163.com; Zhao, Ru-Xia; Li, He-Ping

Using the solvothermal method, we present the comparative preparation of ([Co{sub 3}Na(dmaep){sub 3}(ehbd)(N{sub 3}){sub 3}]·DMF){sub n} (1) and [Co{sub 2}Na{sub 2}(hmbd){sub 4}(N{sub 3}){sub 2}(DMF){sub 2}] (2), where Hehbd is 3-ethoxy-2-hydroxy-benzaldehyde, Hhmbd is 3-methoxy-2-hydroxy-benzaldehyde, and Hdmaep is 2-dimethylaminomethyl-6-ethoxy-phenol, which was synthesized by an in-situ reaction. Complexes 1 and 2 were characterized by elemental analysis, IR spectroscopy, and X-ray single-crystal diffraction. Complex 1 is a novel heterometallic cluster-based 1-D chain and 2 is a heterometallic tetranuclear cluster. The (Co{sub 3}{sup II}Na) and (Co{sub 2}{sup II}Na{sub 2}) cores display dominant ferromagnetic interaction from the nature of the binding modes through μ{sub 1,1,1}-N{sub 3}{supmore » –} (end-on, EO). - Graphical abstract: Two novel cobalt complexes have been prepared. Compound 1 consists of tetranuclear (Co{sub 3}{sup II}Na) units, which further formed a 1-D chain. Compound 2 is heterometallic tetranuclear cluster. Two complexes display dominant ferromagnetic interaction. - Highlights: • Two new heterometallic complexes have been synthesized by solvothermal method. • The stereospecific blockade of the ligands in the synthesis system seems to be the most important synthetic parameter. • The magnetism studies show that 1 and 2 exhibit ferromagnetic interactions. • Complex 1 shows slowing down of magnetization and not blocking of magnetization.« less

Library fingerprints: a novel approach to the screening of virtual libraries.

PubMed

Klon, Anthony E; Diller, David J

2007-01-01

We propose a novel method to prioritize libraries for combinatorial synthesis and high-throughput screening that assesses the viability of a particular library on the basis of the aggregate physical-chemical properties of the compounds using a naïve Bayesian classifier. This approach prioritizes collections of related compounds according to the aggregate values of their physical-chemical parameters in contrast to single-compound screening. The method is also shown to be useful in screening existing noncombinatorial libraries when the compounds in these libraries have been previously clustered according to their molecular graphs. We show that the method used here is comparable or superior to the single-compound virtual screening of combinatorial libraries and noncombinatorial libraries and is superior to the pairwise Tanimoto similarity searching of a collection of combinatorial libraries.

Molecular adsorption of hydrogen peroxide on N- and Fe-doped titania nanoclusters

NASA Astrophysics Data System (ADS)

Mohajeri, Afshan; Dashti, Nasimeh Lari

2017-06-01

Titanium dioxide (titania) nanoparticles have been extensively investigated for photocatalytic applications such as the decomposition and adsorption of pollutant and undesirable compound in air and waste water. In this context, the present article reports the molecular adsorption of hydrogen peroxide on the surface of doped titania clusters. Density functional theory calculations were performed to investigate the structures and electronic properties of two nanoscale (TiO2)n clusters (n = 5,6) modified by nitrogen and iron dopants. The relative stability of all possible N-doped and Fe-doped isomers has been compared with each other and with the parent cluster. It was found that the Fe-doped clusters are in general more stable than the N-doped counterparts. Moreover, after N/Fe doping an enhanced in the magnetization of the clusters is observed. In the second part, we have investigated different modes of H2O2 adsorption on the lowest-energy isomers of doped clusters. In almost all the cases, the adsorptions on the doped clusters are found to be less exothermic than on the corresponding undoped parent cluster. Our results highlight the essential role of charge transfer into the interaction between H2O2 and doped (TiO2)n clusters, especially for Fe-doped clusters.

Adsorption of organic molecules may explain growth of newly nucleated clusters and new particle formation

NASA Astrophysics Data System (ADS)

Wang, Jian; Wexler, Anthony S.

2013-05-01

New particle formation consists of formation of thermodynamically stable clusters from trace gas molecules (homogeneous nucleation) followed by growth of these clusters to a detectable size. Because of the large coagulation rate of clusters smaller than 3 nm with the preexisting aerosol population, for new particle formation to take place, these clusters need to grow sufficiently fast to escape removal by coagulation. Previous studies have indicated that condensation of low-volatility organic vapor may play an important role in the initial growth of the clusters. However, due to the relatively high vapor pressure and partial molar volume of even highly oxidized organic compounds, the strong Kelvin effect may prevent typical ambient organics from condensing on these small clusters. Earlier studies did not consider that adsorption of organic molecules on the cluster surface, due to the intermolecular forces between the organic molecule and cluster, may occur and substantially alter the growth process under sub-saturated conditions. Using the Brunauer-Emmett-Teller (BET) isotherm, we show that the adsorption of organic molecules onto the surface of clusters may significantly reduce the saturation ratio required for condensation of organics to occur, and therefore may provide a physico-chemical explanation for the enhanced initial growth by condensation of organics despite the strong Kelvin effect.

Applications of Some Artificial Intelligence Methods to Satellite Soundings

NASA Technical Reports Server (NTRS)

Munteanu, M. J.; Jakubowicz, O.

1985-01-01

Hard clustering of temperature profiles and regression temperature retrievals were used to refine the method using the probabilities of membership of each pattern vector in each of the clusters derived with discriminant analysis. In hard clustering the maximum probability is taken and the corresponding cluster as the correct cluster are considered discarding the rest of the probabilities. In fuzzy partitioned clustering these probabilities are kept and the final regression retrieval is a weighted regression retrieval of several clusters. This method was used in the clustering of brightness temperatures where the purpose was to predict tropopause height. A further refinement is the division of temperature profiles into three major regions for classification purposes. The results are summarized in the tables total r.m.s. errors are displayed. An approach based on fuzzy logic which is intimately related to artificial intelligence methods is recommended.

Ultra-small rhenium clusters supported on graphene.

PubMed

Miramontes, Orlando; Bonafé, Franco; Santiago, Ulises; Larios-Rodriguez, Eduardo; Velázquez-Salazar, Jesús J; Mariscal, Marcelo M; Yacaman, Miguel José

2015-03-28

The adsorption of very small rhenium clusters (2-13 atoms) supported on graphene was studied by high-angle annular dark field-scanning transmission electron microscopy (HAADF-STEM). The atomic structure of the clusters was fully resolved with the aid of density functional theory calculations and STEM simulations. It was found that octahedral and tetrahedral structures work as seeds to obtain more complex morphologies. Finally, a detailed analysis of the electronic structure suggested that a higher catalytic effect can be expected in Re clusters when adsorbed on graphene than in isolated ones.

Ultra-small rhenium clusters supported on graphene

PubMed Central

Miramontes, Orlando; Bonafé, Franco; Santiago, Ulises; Larios-Rodriguez, Eduardo; Velázquez-Salazar, Jesús J.; Mariscal, Marcelo M.; Yacaman, Miguel José

2015-01-01

The adsorption of very small rhenium clusters (2 – 13 atoms) supported on graphene was studied with high annular dark field - scanning transmission electron microscopy (HAADF-STEM). The atomic structure of the clusters was fully resolved with the aid of density functional calculations and STEM simulations. It was found that octahedral and tetrahedral structures work as seeds to obtain more complex morphologies. Finally, a detailed analysis of the electronic structure suggested that a higher catalytic effect can be expected in Re clusters when adsorbed on graphene than in isolated ones. PMID:25721176

Theoretical and experimental study of polycyclic aromatic compounds as β-tubulin inhibitors.

PubMed

Olazarán, Fabian E; García-Pérez, Carlos A; Bandyopadhyay, Debasish; Balderas-Rentería, Isaias; Reyes-Figueroa, Angel D; Henschke, Lars; Rivera, Gildardo

2017-03-01

In this work, through a docking analysis of compounds from the ZINC chemical library on human β-tubulin using high performance computer cluster, we report new polycyclic aromatic compounds that bind with high energy on the colchicine binding site of β-tubulin, suggesting three new key amino acids. However, molecular dynamic analysis showed low stability in the interaction between ligand and receptor. Results were confirmed experimentally in in vitro and in vivo models that suggest that molecular dynamics simulation is the best option to find new potential β-tubulin inhibitors. Graphical abstract Bennett's acceptance ratio (BAR) method.

The cluster compound In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} containing Mo{sub 14} clusters and the new mono- and bi-capped trioctahedral Mo{sub 15} and Mo{sub 16} clusters: Synthesis, crystal structure, and electrical and magnetic properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gall, Philippe; Guizouarn, Thierry; Gougeon, Patrick, E-mail: Patrick.Gougeon@univ-rennes1.fr

2015-07-15

Single crystals of the new quaternary compound In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} were obtained by solid state reaction. The crystal structure was determined by single-crystal X-ray diffraction. In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} crystallizes in the orthorhombic space group Pbca with unit-cell parameters a=9.4432(14) Å, b=11.4828(12) Å, c=20.299(4) Å and Z=4. Full-matrix least-squares refinement on F{sup 2} using 3807 independent reflections for 219 refinable parameters resulted in R{sub 1}=0.0259 and wR{sub 2}=0.0591. The crystal structure contains in addition to Mo{sub 14} clusters the first examples of mono- and bi-capped trioctahedral Mo{sub 14} i.e. Mo{sub 15} and Mo{sub 16} clusters.more » The oxygen framework derives from a stacking along the a direction of close-packed layers with sequence (…ABAC…). The Mo–Mo distances range between 2.6938(5) and 2.8420(6) Å and the Mo–O distances between 1.879(5) and 2.250(3) Å, as usually observed in molybdenum oxide clusters. The indium atoms form In{sub 4}{sup 6+} bent chains with In–In distances of 2.6682(5) and 2.6622(8) Å and the Ti atoms are in highly distorted octahedral sites of oxygen atoms with Ti–O distances ranging between 1.865(4) and 2.161(4) Å. Magnetic susceptibility measurements confirm the presence of Ti{sup 4+} cations and the absence of localized moments on the Mo network. Electrical resistivity measurements on a single crystal of In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} show a semimetallic behavior. - Graphical abstract: We present here the synthesis, the crystal structure, and the electrical and magnetic properties of the new compound In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} in which Mo{sub 14} clusters coexist statistically with mono- and bi-capped trioctahedral Mo{sub 14} that is Mo{sub 15} and Mo{sub 16} clusters. - Highlights: • Single crystals of In{sub 4}Ti{sub 1.5}Mo{sub 0.5}Mo{sub 14}O{sub 26} were obtained by solid state reaction. • The crystal structure contains Mo{sub 14}, Mo{sub 15} and Mo{sub 16} clusters. • The indium atoms form In{sub 4}{sup 6+} bent chains. • Poorly metallic behavior. • Absence of localized moments on the Mo network as well as on the Ti atoms.« less

Mapping Emission from Clusters of CdSe/ZnS Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryan, Duncan P.; Goodwin, Peter M.; Sheehan, Chris J.

In this paper, we have carried out correlated super-resolution and SEM imaging studies of clusters of CdSe/ZnS nanoparticles containing up to ten particles to explore how the fluorescence behavior of these clusters depends on the number of particles, the specific cluster geometry, the shell thickness, and the technique used to produce the clusters. The total emission yield was less than proportional to the number of particles in the clusters for both thick and thin shells. With super-resolution imaging, the emission center of the cluster could be spatially resolved at distance scales on the order of the cluster size. The intrinsicmore » fluorescence intermittency of the nanoparticles altered the emission distribution across the cluster, which enabled the identification of relative emission intensities of individual particles or small groups of particles within the cluster. Finally, for clusters undergoing interparticle energy transfer, donor/acceptor pairs and regions where energy was funneled could be identified.« less

Mapping Emission from Clusters of CdSe/ZnS Nanoparticles

DOE PAGES

Ryan, Duncan P.; Goodwin, Peter M.; Sheehan, Chris J.; ...

2018-01-24

In this paper, we have carried out correlated super-resolution and SEM imaging studies of clusters of CdSe/ZnS nanoparticles containing up to ten particles to explore how the fluorescence behavior of these clusters depends on the number of particles, the specific cluster geometry, the shell thickness, and the technique used to produce the clusters. The total emission yield was less than proportional to the number of particles in the clusters for both thick and thin shells. With super-resolution imaging, the emission center of the cluster could be spatially resolved at distance scales on the order of the cluster size. The intrinsicmore » fluorescence intermittency of the nanoparticles altered the emission distribution across the cluster, which enabled the identification of relative emission intensities of individual particles or small groups of particles within the cluster. Finally, for clusters undergoing interparticle energy transfer, donor/acceptor pairs and regions where energy was funneled could be identified.« less

A search for X-ray bright distant clusters of galaxies

NASA Technical Reports Server (NTRS)

Nichol, R. C.; Ulmer, M. P.; Kron, R. G.; Wirth, G. D.; Koo, D. C.

1994-01-01

We present the results of a search for X-ray luminous distant clusters of galaxies. We found extended X-ray emission characteristic of a cluster toward two of our candidate clusters of galaxies. They both have a luminosity in the ROSAT bandpass of approximately equals 10(exp 44) ergs/s and a redshift greater than 0.5; thus making them two of the most distant X-ray clusters ever observed. Furthermore, we show that both clusters are optically rich and have a known radio source associated with them. We compare our result with other recent searches for distant X-ray luminous clusters and present a lower limit of 1.2 x 10(exp -7)/cu Mpc for the number density of such high-redshift clusters. This limit is consistent with the expected abundance of such clusters in a standard (b = 2) cold dark matter universe. Finally, our clusters provide important high-redshift targets for further study into the origin and evolution of massive clusters of galaxies.

Clustering of Variables for Mixed Data

NASA Astrophysics Data System (ADS)

Saracco, J.; Chavent, M.

2016-05-01

This chapter presents clustering of variables which aim is to lump together strongly related variables. The proposed approach works on a mixed data set, i.e. on a data set which contains numerical variables and categorical variables. Two algorithms of clustering of variables are described: a hierarchical clustering and a k-means type clustering. A brief description of PCAmix method (that is a principal component analysis for mixed data) is provided, since the calculus of the synthetic variables summarizing the obtained clusters of variables is based on this multivariate method. Finally, the R packages ClustOfVar and PCAmixdata are illustrated on real mixed data. The PCAmix and ClustOfVar approaches are first used for dimension reduction (step 1) before applying in step 2 a standard clustering method to obtain groups of individuals.

Clustering effects in ionic polymers: Molecular dynamics simulations

DOE PAGES

Agrawal, Anupriya; Perahia, Dvora; Grest, Gary S.

2015-08-18

Ionic clusters control the structure, dynamics, and transport in soft matter. Incorporating a small fraction of ionizable groups in polymers substantially reduces the mobility of the macromolecules in melts. Furthermore, these ionic groups often associate into random clusters in melts, where the distribution and morphology of the clusters impact the transport in these materials. Here, using molecular dynamic simulations we demonstrate a clear correlation between cluster size and morphology with the polymer mobility in melts of sulfonated polystyrene. We show that in low dielectric media ladderlike clusters that are lower in energy compared with spherical assemblies are formed. Reducing themore » electrostatic interactions by enhancing the dielectric constant leads to morphological transformation from ladderlike clusters to globular assemblies. Finally, decrease in electrostatic interaction significantly enhances the mobility of the polymer.« less

Targeted Single-Site MOF Node Modification: Trivalent Metal Loading via Atomic Layer Deposition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, In Soo; Borycz, Joshua; Platero-Prats, Ana E.

Postsynthetic functionalization of metal organic frameworks (MOFs) enables the controlled, high-density incorporation of new atoms on a crystallographically precise framework. Leveraging the broad palette of known atomic layer deposition (ALD) chemistries, ALD in MOFs (AIM) is one such targeted approach to construct diverse, highly functional, few-atom clusters. We here demonstrate the saturating reaction of trimethylindium (InMe3) with the node hydroxyls and ligated water of NU-1000, which takes place without significant loss of MOF crystallinity or internal surface area. We computationally identify the elementary steps by which trimethylated trivalent metal compounds (ALD precursors) react with this Zr-based MOF node to generatemore » a uniform and well characterized new surface layer on the node itself, and we predict a final structure that is fully consistent with experimental X-ray pair distribution function (PDF) analysis. We further demonstrate tunable metal loading through controlled number density of the reactive handles (-OH and -OH2) achieved through node dehydration at elevated temperatures.« less

Option pricing for stochastic volatility model with infinite activity Lévy jumps

NASA Astrophysics Data System (ADS)

Gong, Xiaoli; Zhuang, Xintian

2016-08-01

The purpose of this paper is to apply the stochastic volatility model driven by infinite activity Lévy processes to option pricing which displays infinite activity jumps behaviors and time varying volatility that is consistent with the phenomenon observed in underlying asset dynamics. We specially pay attention to three typical Lévy processes that replace the compound Poisson jumps in Bates model, aiming to capture the leptokurtic feature in asset returns and volatility clustering effect in returns variance. By utilizing the analytical characteristic function and fast Fourier transform technique, the closed form formula of option pricing can be derived. The intelligent global optimization search algorithm called Differential Evolution is introduced into the above highly dimensional models for parameters calibration so as to improve the calibration quality of fitted option models. Finally, we perform empirical researches using both time series data and options data on financial markets to illustrate the effectiveness and superiority of the proposed method.

An Amidinohydrolase Provides the Missing Link in the Biosynthesis of Amino Marginolactone Antibiotics.

PubMed

Hong, Hui; Samborskyy, Markiyan; Lindner, Frederick; Leadlay, Peter F

2016-01-18

Desertomycin A is an aminopolyol polyketide containing a macrolactone ring. We have proposed that desertomycin A and similar compounds (marginolactones) are formed by polyketide synthases primed not with γ-aminobutanoyl-CoA but with 4-guanidinylbutanoyl-CoA, to avoid facile cyclization of the starter unit. This hypothesis requires that there be a final-stage de-amidination of the corresponding guanidino-substituted natural product, but no enzyme for such a process has been described. We have now identified candidate amidinohydrolase genes within the desertomycin and primycin clusters. Deletion of the putative desertomycin amidinohydrolase gene dstH in Streptomyces macronensis led to the accumulation of desertomycin B, the guanidino form of the antibiotic. Also, purified DstH efficiently catalyzed the in vitro conversion of desertomycin B into the A form. Hence this amidinohydrolase furnishes the missing link in this proposed naturally evolved example of protective-group chemistry. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Structure-Based Design of Molecules to Reactivate Tumor-Derived p53 Mutations

DTIC Science & Technology

2007-06-01

cluster in conserved regions or “hot spots” (Hainaut and Hollstein, 2000). Missense mutations leading to amino acid changes are the most common p53...domain stabilization compounds. Analysis of the residue-specific temperature factors of the high resolution core domain structure, coupled with a...second scoring results, 13 compounds (10 from the SPECS database and 3 from the TimTec database) were selected for further analysis using solution

Fault and Defect Tolerant Computer Architectures: Reliable Computing with Unreliable Devices

DTIC Science & Technology

2006-08-31

supply voltage, the delay of the inverter increases parabolically . 2.2.2.5 High Field Effects. A consequence of maintaining a higher Vdd than...be explained by dispro- portionate scaling of QCRIT with respect to collector efficiency. 78 Technology trends, then, indicate a moderate increase in...using clustered defects, a compounding procedure is used. Compounding considers λ as a random variable rather than a constant. Let l be this defect

Investigating Cancer Clusters, Brooks AFB, Texas

DTIC Science & Technology

1990-10-01

based dyes Bladder Benzotrichloride Lung? Cadmium and related compounds Prostate, lung Chloroform Bladder, brain, kidney, lymphoma? Chlorophenols Soft...Dioxine) Vinyl chloride Lung Acrylonitrile Aldrin/dieldrin Arsenic Asbestos Benzo[a]pyrene Benzotrichloride Beryllium Cadmium Chloroprene Chromium Coal

LiGe(SiMe₃)₃: A New Substituent for the Synthesis of Metalloid Tin Clusters from Metastable Sn(I) Halide Solutions.

PubMed

Binder, Mareike; Schrenk, Claudio; Block, Theresa; Pöttgen, Rainer; Schnepf, Andreas

2018-04-26

The most fruitful synthetic route to metalloid tin clusters applies the disproportionation reaction of metastable Sn(I) halide solutions, whereby Si(SiMe₃)₃ is mostly used as the stabilizing substituent. Here, we describe the synthesis and application of the slightly modified substituent Ge(SiMe₃)₃, which can be used for the synthesis of metalloid tin clusters to give the neutral cluster Sn 10 [Ge(SiMe₃)₃]₆ as well as the charged clusters {Sn 10 [Ge(SiMe₃)₃]₅} − and {Sn 10 [Ge(SiMe₃)₃]₄} 2− . The obtained metalloid clusters are structurally similar to their Si(SiMe₃)₃ derivatives. However, differences with respect to the stability in solution are observed. Additionally, a different electronic situation for the tin atoms is realized as shown by 119m Sn Mössbauer spectroscopy, giving further insight into the different kinds of tin atoms within the metalloid cluster {Sn 10 [Ge(SiMe₃)₃]₄} 2− . The synthesis of diverse derivatives gives the opportunity to check the influence of the substituent for further investigations of metalloid tin cluster compounds.

Applying Petri nets to modeling the chemical stage of radiobiological mechanism

NASA Astrophysics Data System (ADS)

Barilla, J.; Lokajíček, M.; Pisaková, H.; Simr, P.

2015-03-01

The chemical stage represents important part of radiological mechanism as double strand breaks of DNA molecules represent main damages leading to final biological effect. These breaks are formed mainly by water radicals arising in clusters formed by densely ionizing ends of primary or secondary charged particles in neighborhood of a DNA molecule. The given effect may be significantly influenced by other species present in water, which may depend on the size and diffusion of corresponding clusters. We have already proposed a model describing the corresponding process (i.e., the combined effect of cluster diffusion and chemical reactions) running in individual radical clusters and influencing the formation probability of main damages (i.e., DSBs). Now a full number of corresponding species will be considered. With the help of Continuous Petri nets it will then be possible to follow the time evolution of corresponding species in individual clusters, which might be important especially in the case of studying the biological effect of very low-LET radiation. The results in deoxygenated water will be presented; the ratio of final and initial contents of corresponding species being in good agreement with values established experimentally.

Pattern recognition and classification of vibrational spectra by artificial neural networks

NASA Astrophysics Data System (ADS)

Yang, Husheng

1999-10-01

A drawback of current open-path Fourier transform infrared (OP/FT-IR) systems is that they need a human expert to determine those compounds that may be quantified from a given spectrum. In this study, three types of artificial neural networks were used to alleviate this problem. Firstly, multi-layer feed-forward neural networks were used to automatically recognize compounds in an OP/FT-IR spectrum. Each neural network was trained to recognize one compound in the presence of up to ten interferents in an OP/FT-IR spectrum. The networks were successfully used to recognize five alcohols and two chlorinated compounds in field-measured controlled-release OP/FT-IR spectra of mixtures of these compounds. It has also been demonstrated that a neural network could correctly identify a spectrum in the presence of an interferent that was not included in the training set and could also reject interferents it has not seen before. Secondly, the possibility of using one- and two- dimensional Kohonen self-organizing maps (SOMs) to recognize similarities in low-resolution vapor-phase infrared spectra without any additional information has been investigated. Both full-range reference spectra and open-path window reference spectra were used to train the networks and the trained networks were then used to classify the reference spectra into several groups. The results showed that the SOMs obtained from the two different training sets were quite different, and it is more appropriate to use the second SOM in OP/FT-IR spectrometry. Thirdly, vapor-phase FT-IR reference spectra of five alcohols along with four baseline spectra were encoded as prototype vectors for a Hopfield network. Inclusion of the baseline spectra allowed the network to classify spectra as unknowns, when the reference spectra of these compounds were not stored as prototype vectors in the network. The network could identify each of the 5 alcohols correctly even in the presence of noise and interfering compounds. Finally, one- and two-dimensional Kohonen SOMs were also successfully used for the unsupervised differentiation of the Fourier transform Raman spectra of hardwoods from softwoods. A semi-quantitative method that is based on the Euclidean distances of the weight matrix has been developed to assist the automatic clustering of the neurons in a two-dimensional SOM.

Elastic K-means using posterior probability

PubMed Central

Zheng, Aihua; Jiang, Bo; Li, Yan; Zhang, Xuehan; Ding, Chris

2017-01-01

The widely used K-means clustering is a hard clustering algorithm. Here we propose a Elastic K-means clustering model (EKM) using posterior probability with soft capability where each data point can belong to multiple clusters fractionally and show the benefit of proposed Elastic K-means. Furthermore, in many applications, besides vector attributes information, pairwise relations (graph information) are also available. Thus we integrate EKM with Normalized Cut graph clustering into a single clustering formulation. Finally, we provide several useful matrix inequalities which are useful for matrix formulations of learning models. Based on these results, we prove the correctness and the convergence of EKM algorithms. Experimental results on six benchmark datasets demonstrate the effectiveness of proposed EKM and its integrated model. PMID:29240756

Coagulation-fragmentation for a finite number of particles and application to telomere clustering in the yeast nucleus

NASA Astrophysics Data System (ADS)

Hozé, Nathanaël; Holcman, David

2012-01-01

We develop a coagulation-fragmentation model to study a system composed of a small number of stochastic objects moving in a confined domain, that can aggregate upon binding to form local clusters of arbitrary sizes. A cluster can also dissociate into two subclusters with a uniform probability. To study the statistics of clusters, we combine a Markov chain analysis with a partition number approach. Interestingly, we obtain explicit formulas for the size and the number of clusters in terms of hypergeometric functions. Finally, we apply our analysis to study the statistical physics of telomeres (ends of chromosomes) clustering in the yeast nucleus and show that the diffusion-coagulation-fragmentation process can predict the organization of telomeres.

Constraints on dark matter annihilation in clusters of galaxies with the Fermi large area telescope

DOE PAGES

Ackermann, M.; Ajello, M.; Allafort, A.; ...

2010-05-20

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~ 200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits excludemore » large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~ 5 over a smooth-halo assumption. Here, we also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. Finally, in this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.« less

From hormones to secondary metabolism: the emergence of metabolic gene clusters in plants.

PubMed

Chu, Hoi Yee; Wegel, Eva; Osbourn, Anne

2011-04-01

Gene clusters for the synthesis of secondary metabolites are a common feature of microbial genomes. Well-known examples include clusters for the synthesis of antibiotics in actinomycetes, and also for the synthesis of antibiotics and toxins in filamentous fungi. Until recently it was thought that genes for plant metabolic pathways were not clustered, and this is certainly true in many cases; however, five plant secondary metabolic gene clusters have now been discovered, all of them implicated in synthesis of defence compounds. An obvious assumption might be that these eukaryotic gene clusters have arisen by horizontal gene transfer from microbes, but there is compelling evidence to indicate that this is not the case. This raises intriguing questions about how widespread such clusters are, what the significance of clustering is, why genes for some metabolic pathways are clustered and those for others are not, and how these clusters form. In answering these questions we may hope to learn more about mechanisms of genome plasticity and adaptive evolution in plants. It is noteworthy that for the five plant secondary metabolic gene clusters reported so far, the enzymes for the first committed steps all appear to have been recruited directly or indirectly from primary metabolic pathways involved in hormone synthesis. This may or may not turn out to be a common feature of plant secondary metabolic gene clusters as new clusters emerge. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

Brainstorming: weighted voting prediction of inhibitors for protein targets.

PubMed

Plewczynski, Dariusz

2011-09-01

The "Brainstorming" approach presented in this paper is a weighted voting method that can improve the quality of predictions generated by several machine learning (ML) methods. First, an ensemble of heterogeneous ML algorithms is trained on available experimental data, then all solutions are gathered and a consensus is built between them. The final prediction is performed using a voting procedure, whereby the vote of each method is weighted according to a quality coefficient calculated using multivariable linear regression (MLR). The MLR optimization procedure is very fast, therefore no additional computational cost is introduced by using this jury approach. Here, brainstorming is applied to selecting actives from large collections of compounds relating to five diverse biological targets of medicinal interest, namely HIV-reverse transcriptase, cyclooxygenase-2, dihydrofolate reductase, estrogen receptor, and thrombin. The MDL Drug Data Report (MDDR) database was used for selecting known inhibitors for these protein targets, and experimental data was then used to train a set of machine learning methods. The benchmark dataset (available at http://bio.icm.edu.pl/∼darman/chemoinfo/benchmark.tar.gz ) can be used for further testing of various clustering and machine learning methods when predicting the biological activity of compounds. Depending on the protein target, the overall recall value is raised by at least 20% in comparison to any single machine learning method (including ensemble methods like random forest) and unweighted simple majority voting procedures.

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

PubMed

Henry, Marc

2002-07-02

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

Assessing and grouping chemicals applying partial ordering Alkyl anilines as an illustrative example.

PubMed

Carlsen, Lars; Bruggemann, Rainer

2018-06-03

In chemistry there is a long tradition in classification. Usually methods are adopted from the wide field of cluster analysis. Here, based on the example of 21 alkyl anilines we show that also concepts taken out from the mathematical discipline of partially ordered sets may also be applied. The chemical compounds are described by a multi-indicator system. For the present study four indicators, mainly taken from the field of environmental chemistry were applied and a Hasse diagram was constructed. A Hasse diagram is an acyclic, transitively reduced, triangle free graph that may have several components. The crucial question is, whether or not the Hasse diagram can be interpreted from a structural chemical point of view. This is indeed the case, but it must be clearly stated that a guarantee for meaningful results in general cannot be given. For that further theoretical work is needed. Two cluster analysis methods are applied (K-means and a hierarchical cluster method). In both cases the partitioning of the set of 21 compounds by the component structure of the Hasse diagram appears to be better interpretable. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Structure and Energetics of Clusters Relevant to Thorium Tetrachloride Melts

NASA Astrophysics Data System (ADS)

Akdeniz, Z.; Tosi, M. P.

2000-10-01

We study within an ionic model the structure and energetics of neutral and charged molecular clusters which may be relevant to molten ThCl4 and to its liquid mixtures with alkali chlorides, with reference to Raman scattering experiments by Photiadis and Papatheodorou. As stressed by these authors, the most striking facts for ThCl4 in comparison to other tetrachloride compounds (and in particular to ZrCl4) are the appreciable ionic conductivity of the pure melt and the continuous structural changes which occur in the melt mixtures with varying composition. After adjusting our model to data on the isolated ThCl4 tetrahedral molecule, we evaluate (i) the Th2Cl8 dimer and the singly charged species obtained from it by chlorine-ion transfer between two such neutral dimers; (ii) the ThCl6 and ThCl7 clusters both as charged anions and as alkali-compensated species; and (iii) various oligomers carrying positive or negative double charges. Our study shows that the characteristic structural properties of the ThCl4 compound and of the alkali-Th chloride systems are the consequence of the relatively high ionic character of the binding, which is already evident in the isolated ThCl4 monomer.

Patterns of victimization between and within peer clusters in a high school social network.

PubMed

Swartz, Kristin; Reyns, Bradford W; Wilcox, Pamela; Dunham, Jessica R

2012-01-01

This study presents a descriptive analysis of patterns of violent victimization between and within the various cohesive clusters of peers comprising a sample of more than 500 9th-12th grade students from one high school. Social network analysis techniques provide a visualization of the overall friendship network structure and allow for the examination of variation in victimization across the various peer clusters within the larger network. Social relationships among clusters with varying levels of victimization are also illustrated so as to provide a sense of possible spatial clustering or diffusion of victimization across proximal peer clusters. Additionally, to provide a sense of the sorts of peer clusters that support (or do not support) victimization, characteristics of clusters at both the high and low ends of the victimization scale are discussed. Finally, several of the peer clusters at both the high and low ends of the victimization continuum are "unpacked", allowing examination of within-network individual-level differences in victimization for these select clusters.

Distributive Education Competency-Based Curriculum Models by Occupational Clusters. Final Report.

ERIC Educational Resources Information Center

Davis, Rodney E.; Husted, Stewart W.

To meet the needs of distributive education teachers and students, a project was initiated to develop competency-based curriculum models for marketing and distributive education clusters. The models which were developed incorporate competencies, materials and resources, teaching methodologies/learning activities, and evaluative criteria for the…

78 FR 54178 - Virginia: Final Authorization of State Hazardous Waste Management Program Revisions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-03

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Accounting Cluster Demonstration Program at Aloha High School. Final Report.

ERIC Educational Resources Information Center

Beaverton School District 48, OR.

A model high school accounting cluster program was planned, developed, implemented, and evaluated in the Beaverton, Oregon, school district. The curriculum was developed with the help of representatives from the accounting occupations in the Portland metropolitan area. Through management interviews, identification of on-the job requirements, and…

Fe-S Proteins that Regulate Gene Expression

PubMed Central

Mettert, Erin L.; Kiley, Patricia J.

2014-01-01

Iron-sulfur (Fe-S) cluster containing proteins that regulate gene expression are present in most organisms. The innate chemistry of their Fe-S cofactors makes these regulatory proteins ideal for sensing environmental signals, such as gases (e.g. O2 and NO), levels of Fe and Fe-S clusters, reactive oxygen species, and redox cycling compounds, to subsequently mediate an adaptive response. Here we review the recent findings that have provided invaluable insight into the mechanism and function of these highly significant Fe-S regulatory proteins. PMID:25450978

Structural evolution in the crystallization of rapid cooling silver melt

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Z.A., E-mail: ze.tian@gmail.com; Laboratory for Simulation and Modelling of Particulate Systems School of Materials Science and Engineering, University of New South Wales, Sydney, NSW 2052; Dong, K.J.

2015-03-15

The structural evolution in a rapid cooling process of silver melt has been investigated at different scales by adopting several analysis methods. The results testify Ostwald’s rule of stages and Frank conjecture upon icosahedron with many specific details. In particular, the cluster-scale analysis by a recent developed method called LSCA (the Largest Standard Cluster Analysis) clarified the complex structural evolution occurred in crystallization: different kinds of local clusters (such as ico-like (ico is the abbreviation of icosahedron), ico-bcc like (bcc, body-centred cubic), bcc, bcc-like structures) in turn have their maximal numbers as temperature decreases. And in a rather wide temperaturemore » range the icosahedral short-range order (ISRO) demonstrates a saturated stage (where the amount of ico-like structures keeps stable) that breeds metastable bcc clusters. As the precursor of crystallization, after reaching the maximal number bcc clusters finally decrease, resulting in the final solid being a mixture mainly composed of fcc/hcp (face-centred cubic and hexagonal-closed packed) clusters and to a less degree, bcc clusters. This detailed geometric picture for crystallization of liquid metal is believed to be useful to improve the fundamental understanding of liquid–solid phase transition. - Highlights: • A comprehensive structural analysis is conducted focusing on crystallization. • The involved atoms in our analysis are more than 90% for all samples concerned. • A series of distinct intermediate states are found in crystallization of silver melt. • A novelty icosahedron-saturated state breeds the metastable bcc state.« less

Micro-optical artificial compound eyes.

PubMed

Duparré, J W; Wippermann, F C

2006-03-01

Natural compound eyes combine small eye volumes with a large field of view at the cost of comparatively low spatial resolution. For small invertebrates such as flies or moths, compound eyes are the perfectly adapted solution to obtaining sufficient visual information about their environment without overloading their brains with the necessary image processing. However, to date little effort has been made to adopt this principle in optics. Classical imaging always had its archetype in natural single aperture eyes which, for example, human vision is based on. But a high-resolution image is not always required. Often the focus is on very compact, robust and cheap vision systems. The main question is consequently: what is the better approach for extremely miniaturized imaging systems-just scaling of classical lens designs or being inspired by alternative imaging principles evolved by nature in the case of small insects? In this paper, it is shown that such optical systems can be achieved using state-of-the-art micro-optics technology. This enables the generation of highly precise and uniform microlens arrays and their accurate alignment to the subsequent optics-, spacing- and optoelectronics structures. The results are thin, simple and monolithic imaging devices with a high accuracy of photolithography. Two different artificial compound eye concepts for compact vision systems have been investigated in detail: the artificial apposition compound eye and the cluster eye. Novel optical design methods and characterization tools were developed to allow the layout and experimental testing of the planar micro-optical imaging systems, which were fabricated for the first time by micro-optics technology. The artificial apposition compound eye can be considered as a simple imaging optical sensor while the cluster eye is capable of becoming a valid alternative to classical bulk objectives but is much more complex than the first system.

A Survey on Clustering Routing Protocols in Wireless Sensor Networks

PubMed Central

Liu, Xuxun

2012-01-01

The past few years have witnessed increased interest in the potential use of wireless sensor networks (WSNs) in a wide range of applications and it has become a hot research area. Based on network structure, routing protocols in WSNs can be divided into two categories: flat routing and hierarchical or clustering routing. Owing to a variety of advantages, clustering is becoming an active branch of routing technology in WSNs. In this paper, we present a comprehensive and fine grained survey on clustering routing protocols proposed in the literature for WSNs. We outline the advantages and objectives of clustering for WSNs, and develop a novel taxonomy of WSN clustering routing methods based on complete and detailed clustering attributes. In particular, we systematically analyze a few prominent WSN clustering routing protocols and compare these different approaches according to our taxonomy and several significant metrics. Finally, we summarize and conclude the paper with some future directions. PMID:23112649

A survey on clustering routing protocols in wireless sensor networks.

PubMed

Liu, Xuxun

2012-01-01

The past few years have witnessed increased interest in the potential use of wireless sensor networks (WSNs) in a wide range of applications and it has become a hot research area. Based on network structure, routing protocols in WSNs can be divided into two categories: flat routing and hierarchical or clustering routing. Owing to a variety of advantages, clustering is becoming an active branch of routing technology in WSNs. In this paper, we present a comprehensive and fine grained survey on clustering routing protocols proposed in the literature for WSNs. We outline the advantages and objectives of clustering for WSNs, and develop a novel taxonomy of WSN clustering routing methods based on complete and detailed clustering attributes. In particular, we systematically analyze a few prominent WSN clustering routing protocols and compare these different approaches according to our taxonomy and several significant metrics. Finally, we summarize and conclude the paper with some future directions.

Assessment of chimeric mice with humanized livers in new drug development: generation of pharmacokinetics, metabolism and toxicity data for selecting the final candidate compound.

PubMed

Kamimura, Hidetaka; Ito, Satoshi

2016-01-01

1. Chimeric mice with humanized livers are expected to be a novel tool for new drug development. This review discusses four applications where these animals can be used efficiently to collect supportive data for selecting the best compound in the final stage of drug discovery. 2. The first application is selection of the final compound based on estimated pharmacokinetic parameters in humans. Since chimeric mouse livers are highly repopulated with human hepatocytes, hepatic clearance values in vivo could be used preferentially to estimate pharmacokinetic profiles for humans. 3. The second is prediction of human-specific or disproportionate metabolites. Chimeric mice reproduce human-specific metabolites of drugs under development to conform to ICH guidance M3(R2), except for compounds that were extensively eliminated by co-existing mouse hepatocytes. 4. The third is identifying metabolites with distinct pharmacokinetic profiles in humans. Slow metabolite elimination specifically in humans increases its exposure level, but if its elimination is faster in laboratory animals, the animal exposure level might not satisfy ICH guidance M3(R2). 5. Finally, two examples of reproducing acute liver toxicity in chimeric mice are introduced. Integrated pharmacokinetics, metabolism and toxicity information are expected to assist pharmaceutical scientists in selecting the best candidate compound in new drug development.

VizieR Online Data Catalog: Full spectroscopic data release of the SPT-GMOS (Bayliss+, 2016)

NASA Astrophysics Data System (ADS)

Bayliss, M. B.; Ruel, J.; Stubbs, C. W.; Allen, S. W.; Applegate, D. E.; Ashby, M. L. N.; Bautz, M.; Benson, B. A.; Bleem, L. E.; Bocquet, S.; Brodwin, M.; Capasso, R.; Carlstrom, J. E.; Chang, C. L.; Chiu, I.; Cho, H.-M.; Clocchiatti, A.; Crawford, T. M.; Crites, A. T.; de Haan, T.; Desai, S.; Dietrich, J. P.; Dobbs, M. A.; Doucouliagos, A. N.; Foley, R. J.; Forman, W. R.; Garmire, G. P.; George, E. M.; Gladders, M. D.; Gonzalez, A. H.; Gupta, N.; Halverson, N. W.; Hlavacek-Larrondo, J.; Hoekstra, H.; Holder, G. P.; Holzapfel, W. L.; Hou, Z.; Hrubes, J. D.; Huang, N.; Jones, C.; Keisler, R.; Knox, L.; Lee, A. T.; Leitch, E. M.; von der Linden, A.; Luong-van, D.; Mantz, A.; Marrone, D. P.; McDonald, M.; McMahon, J. J.; Meyer, S. S.; Mocanu, L. M.; Mohr, J. J.; Murray, S. S.; Padin, S.; Pryke, C.; Rapetti, D.; Reichardt, C. L.; Rest, A.; Ruhl, J. E.; Saliwanchik, B. R.; Saro, A.; Sayre, J. T.; Schaffer, K. K.; Schrabback, T.; Shirokoff, E.; Song, J.; Spieler, H. G.; Stalder, B.; Stanford, S. A.; Staniszewski, Z.; Stark, A. A.; Story, K. T.; Vanderlinde, K.; Vieira, J. D.; Vikhlinin, A.; Williamson, R.; Zenteno, A.

2016-11-01

The data presented in this paper follow the same observational design described by Ruel et al. (2014ApJ...792...45R). The final Gemini-S observing allocation for SPT-GMOS concluded at the end of the 2015B semester. Over the course of the entire survey we observed 121 individual spectroscopic masks targeting 62 SPT-SZ galaxy clusters (see table 1). All final data products from SPT-GMOS are publicly released via the Harvard Dataverse Network (http://dataverse.harvard.edu/dataverse/SPT_Clusters). The galaxy clusters observed in the SPT-GMOS are all drawn from the SPT-SZ survey, completed in 2011 November. The full SPT-SZ survey covered approximately 2500deg2 of the southern sky at 95, 150, and 220GHz with an angular resolution of ~1'. (4 data files).

Assessing the sensitivity of benzene cluster cation chemical ionization mass spectrometry toward a wide array of biogenic volatile organic compounds

NASA Astrophysics Data System (ADS)

Lavi, Avi; Vermeuel, Michael; Novak, Gordon; Bertram, Timothy

2017-04-01

Chemical ionization mass spectrometry is a real-time, sensitive and selective measurement technique for the detection of volatile organic compounds (VOCs). The benefits of CIMS technology make it highly suitable for field measurements that requires fast (10Hz and higher) response rates, such as the study of surface-atmosphere exchange processes by the eddy covariance method. The use of benzene cluster cations as a regent ion was previously demonstrated as a sensitive and selective method for the detection of select biogenic VOCs (e.g. isoprene, monoterpenes and sesquiterpenes) [Kim et al., 2016; Leibrock and Huey, 2000]. Quantitative analysis of atmospheric trace gases necessitates calibration for each analyte as a function of atmospheric conditions. We describe a custom designed calibration system, based on liquid evaporation, for determination of the sensitivity of the benzene-CIMS to a wide range of organic compounds at atmospherically relevant mixing ratios (<200 ppt). We report on the effect of atmospheric water vapor and oxygen concentrations on instrument response for isoprene and a wide range of monoterpenes and sesquiterpenes. To gain mechanistic insight into the ion-molecule reactions and the role of water vapor and oxygen, we compare our measured sensitivities with a computational analysis of the charge distribution between the analyte, reagent ion and water molecules in the gas phase. These parameters provide insight on the ionization mechanism and provide parameters for quantification of organic molecules measured during field campaigns. References Kim, M. J., M. C. Zoerb, N. R. Campbell, K. J. Zimmermann, B. W. Blomquist, B. J. Huebert, and T. H. Bertram (2016), Revisiting benzene cluster cations for the chemical ionization of dimethyl sulfide and select volatile organic compounds, Atmos Meas Tech, 9(4), 1473-1484, doi:10.5194/amt-9-1473-2016. Leibrock, E., and L. G. Huey (2000), Ion chemistry for the detection of isoprene and other volatile organic compounds in ambient air, Geophys Res Lett, 27(12), 1719-1722, doi:Doi 10.1029/1999gl010804.

Regulatory cross talk and microbial induction of fungal secondary metabolite gene clusters.

PubMed

Nützmann, Hans-Wilhelm; Schroeckh, Volker; Brakhage, Axel A

2012-01-01

Filamentous fungi are well-known producers of a wealth of secondary metabolites with various biological activities. Many of these compounds such as penicillin, cyclosporine, or lovastatin are of great importance for human health. Genome sequences of filamentous fungi revealed that the encoded potential to produce secondary metabolites is much higher than the actual number of compounds produced during cultivation in the laboratory. This finding encouraged research groups to develop new methods to exploit the silent reservoir of secondary metabolites. In this chapter, we present three successful strategies to induce the expression of secondary metabolite gene clusters. They are based on the manipulation of the molecular processes controlling the biosynthesis of secondary metabolites and the simulation of stimulating environmental conditions leading to altered metabolic profiles. The presented methods were successfully applied to identify novel metabolites. They can be also used to significantly increase product yields. Copyright © 2012 Elsevier Inc. All rights reserved.

A Mössbauer effect study of the bonding in several organoiron carbonyl clusters

NASA Astrophysics Data System (ADS)

Long, Gary J.; O'Brien, James F.

1988-02-01

After a brief review of the applications of the Mössbauer effect to cyclopentadienyl containing compounds, the chemistry and spectral properties of the various iron carbonyl complexes are described. The electronic properties of a series of trinuclear and tetranuclear organoiron clusters have been investigated through Fenske-Hall self-consistent field molecular orbital calculations, and the results are compared with the Mössbauer effect isomer shifts. A linear correlation is found between the Slater effective nuclear charge, as calculated from the Fenske-Hall partial orbital occupancy factors, and the isomer shift. In these compounds the 4s orbital populations are rather constant. However, the cis and trans isomers of [CpFe(CO)2]2 have a significantly lower 4s orbital populations. In this case, the reduced 4s population must be accounted for by adding it to the effective nuclear charge to obtain a good correlation with the isomer shift.

Impact of Heavy Metal Pollution on Ammonia Oxidizers in Soils in the Vicinity of a Tailings Dam, Baotou, China.

PubMed

Liu, Jumei; Cao, Weiwei; Jiang, Haiming; Cui, Jing; Shi, Chunfang; Qiao, Xiaohui; Zhao, Ji; Si, Wantong

2018-05-09

Soil heavy metal pollution has received increasing attention due to their toxicity to soil microorganisms. We have analyzed the effects of heavy metal pollution on ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in soils in the vicinity of a tailings dam of Baotou region, China. Results showed that AOB were dominated with Nitrosomonas-like clusters, while AOA was dominated by group1.1b (Nitrososphaera cluster). Single Cd and Cr contents, as well as compound heavy metal pollution levels, had a significant negative impact on soil potential nitrification rate and both diversities of AOA and AOB. No clear relationship was found between any single heavy metal and abundance of AOA or AOB. But compound pollution could significantly decrease AOA abundance. The results indicated that heavy metal pollution had an obviously deleterious effect on the abundance, diversity, activity and composition of ammonia oxidizers in natural soils.

DCE: A Distributed Energy-Efficient Clustering Protocol for Wireless Sensor Network Based on Double-Phase Cluster-Head Election.

PubMed

Han, Ruisong; Yang, Wei; Wang, Yipeng; You, Kaiming

2017-05-01

Clustering is an effective technique used to reduce energy consumption and extend the lifetime of wireless sensor network (WSN). The characteristic of energy heterogeneity of WSNs should be considered when designing clustering protocols. We propose and evaluate a novel distributed energy-efficient clustering protocol called DCE for heterogeneous wireless sensor networks, based on a Double-phase Cluster-head Election scheme. In DCE, the procedure of cluster head election is divided into two phases. In the first phase, tentative cluster heads are elected with the probabilities which are decided by the relative levels of initial and residual energy. Then, in the second phase, the tentative cluster heads are replaced by their cluster members to form the final set of cluster heads if any member in their cluster has more residual energy. Employing two phases for cluster-head election ensures that the nodes with more energy have a higher chance to be cluster heads. Energy consumption is well-distributed in the proposed protocol, and the simulation results show that DCE achieves longer stability periods than other typical clustering protocols in heterogeneous scenarios.

Hypo-electronic triple-decker sandwich complexes: synthesis and structural characterization of [(Cp*Mo)2{μ-η(6):η(6)-B4H4E-Ru(CO)3}] (E = S, Se, Te or Ru(CO)3 and Cp* = η(5)-C5Me5).

PubMed

Mondal, Bijan; Bhattacharyya, Moulika; Varghese, Babu; Ghosh, Sundargopal

2016-07-05

The syntheses and structural characterization of hypo-electronic di-molybdenum triple-decker sandwich clusters are reported. Thermolysis of [Ru3(CO)12] with an in situ generated intermediate obtained from the reaction of [Cp*MoCl4] with [LiBH4·THF] yielded an electron deficient triple-decker sandwich complex, [(Cp*Mo)2{μ-η(6):η(6)-B4H4Ru2(CO)6}], . In an effort to generate analogous triple-deckers containing group-16 elements, we isolated [(Cp*Mo)2{μ-η(6):η(6)-B4H4ERu(CO)3}] (: E = Te; : E = S; : E = Se). These clusters show a high metal coordination number and cross cluster Mo-Mo bond. The formal cluster electron count of these compounds is four or three skeletal electron pairs less than required for a canonical closo-structure of the same nuclearity. Therefore, these compounds represent a novel class of triple-decker sandwich complex with 22 or 24 valence-electrons (VE), wherein the "chair" like hexagonal middle ring is composed of B, Ru and chalcogen. One of the key differences among the synthesized triple-decker molecules is the puckering nature of the middle ring [B4RuE], which increases in the order S < Se < Ru(CO)3 < Te. In addition, Fenske-Hall and quantum-chemical calculations with DFT methods at the BP86 level of theory have been used to analyze the bonding of these novel complexes. The studies not only explain the electron unsaturation of the molecules, but also reveal the reason for the significant puckering of the middle deck. All the compounds have been characterized by IR, (1)H, (11)B, and (13)C NMR spectroscopy in solution and the solid state structures were established by crystallographic analysis.

An effective fuzzy kernel clustering analysis approach for gene expression data.

PubMed

Sun, Lin; Xu, Jiucheng; Yin, Jiaojiao

2015-01-01

Fuzzy clustering is an important tool for analyzing microarray data. A major problem in applying fuzzy clustering method to microarray gene expression data is the choice of parameters with cluster number and centers. This paper proposes a new approach to fuzzy kernel clustering analysis (FKCA) that identifies desired cluster number and obtains more steady results for gene expression data. First of all, to optimize characteristic differences and estimate optimal cluster number, Gaussian kernel function is introduced to improve spectrum analysis method (SAM). By combining subtractive clustering with max-min distance mean, maximum distance method (MDM) is proposed to determine cluster centers. Then, the corresponding steps of improved SAM (ISAM) and MDM are given respectively, whose superiority and stability are illustrated through performing experimental comparisons on gene expression data. Finally, by introducing ISAM and MDM into FKCA, an effective improved FKCA algorithm is proposed. Experimental results from public gene expression data and UCI database show that the proposed algorithms are feasible for cluster analysis, and the clustering accuracy is higher than the other related clustering algorithms.

Suppression of vacancy cluster growth in concentrated solid solution alloys

DOE PAGES

Zhao, Shijun; Velisa, Gihan; Xue, Haizhou; ...

2016-12-13

Large vacancy clusters, such as stacking-fault tetrahedra, are detrimental vacancy-type defects in ion-irradiated structural alloys. Suppression of vacancy cluster formation and growth is highly desirable to improve the irradiation tolerance of these materials. In this paper, we demonstrate that vacancy cluster growth can be inhibited in concentrated solid solution alloys by modifying cluster migration pathways and diffusion kinetics. The alloying effects of Fe and Cr on the migration of vacancy clusters in Ni concentrated alloys are investigated by molecular dynamics simulations and ion irradiation experiment. While the diffusion coefficients of small vacancy clusters in Ni-based binary and ternary solid solutionmore » alloys are higher than in pure Ni, they become lower for large clusters. This observation suggests that large clusters can easily migrate and grow to very large sizes in pure Ni. In contrast, cluster growth is suppressed in solid solution alloys owing to the limited mobility of large vacancy clusters. Finally, the differences in cluster sizes and mobilities in Ni and in solid solution alloys are consistent with the results from ion irradiation experiments.« less

Kinetics of Aggregation with Choice

DOE PAGES

Ben-Naim, Eli; Krapivsky, Paul

2016-12-01

Here we generalize the ordinary aggregation process to allow for choice. In ordinary aggregation, two random clusters merge and form a larger aggregate. In our implementation of choice, a target cluster and two candidate clusters are randomly selected and the target cluster merges with the larger of the two candidate clusters.We study the long-time asymptotic behavior and find that as in ordinary aggregation, the size density adheres to the standard scaling form. However, aggregation with choice exhibits a number of different features. First, the density of the smallest clusters exhibits anomalous scaling. Second, both the small-size and the large-size tailsmore » of the density are overpopulated, at the expense of the density of moderate-size clusters. Finally, we also study the complementary case where the smaller candidate cluster participates in the aggregation process and find an abundance of moderate clusters at the expense of small and large clusters. Additionally, we investigate aggregation processes with choice among multiple candidate clusters and a symmetric implementation where the choice is between two pairs of clusters.« less

A heptadecanuclear Mn(III)9Dy(III)8 cluster derived from triethanolamine with two edge sharing supertetrahedra as the core and displaying SMM behaviour.

PubMed

Langley, Stuart K; Moubarakia, Boujemaa; Murray, Keith S

2010-06-07

A heterometallic, heptadecanuclear cluster of formula [Mn(III)9Dy(III)8O8(OH)8(tea)2(teaH)2(teaH2)4(Ac)4(NO3)2(H2O)4](NO3)7·8H2O (1) is reported. The core of 1 displays two edge sharing Mn(III)5Dy(III)5 supertetrahedra and represents one of the largest Mn/4f cluster compound so far reported. Magnetic studies show that 1 displays probable SMM behaviour as observed via non-zero values in the χM''vs T plot.

Comparative analysis of machine learning methods in ligand-based virtual screening of large compound libraries.

PubMed

Ma, Xiao H; Jia, Jia; Zhu, Feng; Xue, Ying; Li, Ze R; Chen, Yu Z

2009-05-01

Machine learning methods have been explored as ligand-based virtual screening tools for facilitating drug lead discovery. These methods predict compounds of specific pharmacodynamic, pharmacokinetic or toxicological properties based on their structure-derived structural and physicochemical properties. Increasing attention has been directed at these methods because of their capability in predicting compounds of diverse structures and complex structure-activity relationships without requiring the knowledge of target 3D structure. This article reviews current progresses in using machine learning methods for virtual screening of pharmacodynamically active compounds from large compound libraries, and analyzes and compares the reported performances of machine learning tools with those of structure-based and other ligand-based (such as pharmacophore and clustering) virtual screening methods. The feasibility to improve the performance of machine learning methods in screening large libraries is discussed.

Tire traces - discrimination and classification of pyrolysis-GC/MS profiles.

PubMed

Gueissaz, Line; Massonnet, Geneviève

2013-07-10

Tire traces can be observed on several crime scenes as vehicles are often used by criminals. The tread abrasion on the road, while braking or skidding, leads to the production of small rubber particles which can be collected for comparison purposes. This research focused on the statistical comparison of Py-GC/MS profiles of tire traces and tire treads. The optimisation of the analytical method was carried out using experimental designs. The aim was to determine the best pyrolysis parameters regarding the repeatability of the results. Thus, the pyrolysis factor effect could also be calculated. The pyrolysis temperature was found to be five time more important than time. Finally, a pyrolysis at 650°C during 15s was selected. Ten tires of different manufacturers and models were used for this study. Several samples were collected on each tire, and several replicates were carried out to study the variability within each tire (intravariability). More than eighty compounds were integrated for each analysis and the variability study showed that more than 75% presented a relative standard deviation (RSD) below 5% for the ten tires, thus supporting a low intravariability. The variability between the ten tires (intervariability) presented higher values and the ten most variant compounds had a RSD value above 13%, supporting their high potential of discrimination between the tires tested. Principal Component Analysis (PCA) was able to fully discriminate the ten tires with the help of the first three principal components. The ten tires were finally used to perform braking tests on a racetrack with a vehicle equipped with an anti-lock braking system. The resulting tire traces were adequately collected using sheets of white gelatine. As for tires, the intravariability for the traces was found to be lower than the intervariability. Clustering methods were carried out and the Ward's method based on the squared Euclidean distance was able to correctly group all of the tire traces replicates in the same cluster than the replicates of their corresponding tire. Blind tests on traces were performed and were correctly assigned to their tire source. These results support the hypothesis that the tested tires, of different manufacturers and models, can be discriminated by a statistical comparison of their chemical profiles. The traces were found to be not differentiable from their source but differentiable from all the other tires present in the subset. The results are promising and will be extended on a larger sample set. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Correlated proton-electron hole dynamics in protonated water clusters upon extreme ultraviolet photoionization

PubMed Central

Li, Zheng; Vendrell, Oriol

2016-01-01

The ultrafast nuclear and electronic dynamics of protonated water clusters H+(H2O)n after extreme ultraviolet photoionization is investigated. In particular, we focus on cluster cations with n = 3, 6, and 21. Upon ionization, two positive charges are present in the cluster related to the excess proton and the missing electron, respectively. A correlation is found between the cluster's geometrical conformation and initial electronic energy with the size of the final fragments produced. For situations in which the electron hole and proton are initially spatially close, the two entities become correlated and separate in a time-scale of 20 to 40 fs driven by strong non-adiabatic effects. PMID:26798842

Concept design and cluster control of advanced space connectable intelligent microsatellite

NASA Astrophysics Data System (ADS)

Wang, Xiaohui; Li, Shuang; She, Yuchen

2017-12-01

In this note, a new type of advanced space connectable intelligent microsatellite is presented to extend the range of potential application of microsatellite and improve the efficiency of cooperation. First, the overall concept of the micro satellite cluster is described, which is characterized by autonomously connecting with each other and being able to realize relative rotation through the external interfaces. Second, the multi-satellite autonomous assembly algorithm and control algorithm of the cluster motion are developed to make the cluster system combine into a variety of configurations in order to achieve different types of functionality. Finally, the design of the satellite cluster system is proposed, and the possible applications are discussed.

Consumer palatability scores and volatile beef flavor compounds of five USDA quality grades and four muscles.

PubMed

Legako, J F; Brooks, J C; O'Quinn, T G; Hagan, T D J; Polkinghorne, R; Farmer, L J; Miller, M F

2015-02-01

Proximate data, consumer palatability scores and volatile compounds were investigated for four beef muscles (Longissimus lumborum, Psoas major, Semimembranosus and Gluteus medius) and five USDA quality grades(Prime, Upper 2/3 Choice, Low Choice, Select, and Standard). Quality grade did not directly affect consumer scores or volatiles but interactions (P < 0.05) between muscle and grade were determined. Consumer scores and volatiles differed (P < 0.05) between muscles. Consumers scored Psoas major highest for tenderness, juiciness, flavor liking and overall liking, followed by Longissimus lumborum, Gluteus medius, and Semimembranosus (P < 0.05). Principal component analysis revealed clustering of compound classes, formed by related mechanisms. Volatile n-aldehydes were inversely related to percent fat. Increases in lipid oxidation compounds were associated with Gluteus medius and Semimembranosus, while greater quantities of sulfur-containing compounds were associated with Psoas major. Relationships between palatability scores and volatile compound classes suggest that differences in the pattern of volatile compounds may play a valuable role in explaining consumer liking.

"More than Honey": Investigation on Volatiles from Monovarietal Honeys Using New Analytical and Sensory Approaches.

PubMed

Siegmund, Barbara; Urdl, Katharina; Jurek, Andrea; Leitner, Erich

2018-03-14

Eight monovarietal honeys from dandelion, fir tree, linden tree, chestnut tree, robinia, orange, lavender, and rape were investigated with respect to their volatile compounds and sensory properties. Analysis of the volatile compounds was performed by gas chromatographic techniques (one-dimensional GC-MS as well as comprehensive GC×GC-MS). For sensory evaluation Napping in combination with ultraflash profiling was applied using sensory experts. For dandelion honey, 34 volatile compounds are described for the first time to be present in dandelion honey. PCA and cluster analysis of the volatile compounds, respectively, show high correlation with the PCA obtained from sensory evaluation. Lavender and linden honey showed sensory characteristics that were not expected from these honey types. Analysis of the volatile compounds resulted in the identification of odor-active compounds that are very likely derived from sources other than the respective honeyflow. Contamination with essential oils used in apiculture is very likely to be the reason for the occurrence of these compounds in the investigated honeys.

An adaptive enhancement algorithm for infrared video based on modified k-means clustering

NASA Astrophysics Data System (ADS)

Zhang, Linze; Wang, Jingqi; Wu, Wen

2016-09-01

In this paper, we have proposed a video enhancement algorithm to improve the output video of the infrared camera. Sometimes the video obtained by infrared camera is very dark since there is no clear target. In this case, infrared video should be divided into frame images by frame extraction, in order to carry out the image enhancement. For the first frame image, which can be divided into k sub images by using K-means clustering according to the gray interval it occupies before k sub images' histogram equalization according to the amount of information per sub image, we used a method to solve a problem that final cluster centers close to each other in some cases; and for the other frame images, their initial cluster centers can be determined by the final clustering centers of the previous ones, and the histogram equalization of each sub image will be carried out after image segmentation based on K-means clustering. The histogram equalization can make the gray value of the image to the whole gray level, and the gray level of each sub image is determined by the ratio of pixels to a frame image. Experimental results show that this algorithm can improve the contrast of infrared video where night target is not obvious which lead to a dim scene, and reduce the negative effect given by the overexposed pixels adaptively in a certain range.

Sunlight Modulates Fruit Metabolic Profile and Shapes the Spatial Pattern of Compound Accumulation within the Grape Cluster.

PubMed

Reshef, Noam; Walbaum, Natasha; Agam, Nurit; Fait, Aaron

2017-01-01

Vineyards are characterized by their large spatial variability of solar irradiance (SI) and temperature, known to effectively modulate grape metabolism. To explore the role of sunlight in shaping fruit composition and cluster uniformity, we studied the spatial pattern of incoming irradiance, fruit temperature and metabolic profile within individual grape clusters under three levels of sunlight exposure. The experiment was conducted in a vineyard of Cabernet Sauvignon cv. located in the Negev Highlands, Israel, where excess SI and midday temperatures are known to degrade grape quality. Filtering SI lowered the surface temperature of exposed fruits and increased the uniformity of irradiance and temperature in the cluster zone. SI affected the overall levels and patterns of accumulation of sugars, organic acids, amino acids and phenylpropanoids, across the grape cluster. Increased exposure to sunlight was associated with lower accumulation levels of malate, aspartate, and maleate but with higher levels of valine, leucine, and serine, in addition to the stress-related proline and GABA. Flavan-3-ols metabolites showed a negative response to SI, whereas flavonols were highly induced. The overall levels of anthocyanins decreased with increased sunlight exposure; however, a hierarchical cluster analysis revealed that the members of this family were grouped into three distinct accumulation patterns, with malvidin anthocyanins and cyanidin-glucoside showing contrasting trends. The flavonol-glucosides, quercetin and kaempferol, exhibited a logarithmic response to SI, leading to improved cluster uniformity under high-light conditions. Comparing the within-cluster variability of metabolite accumulation highlighted the stability of sugars, flavan-3-ols, and cinnamic acid metabolites to SI, in contrast to the plasticity of flavonols. A correlation-based network analysis revealed that extended exposure to SI modified metabolic coordination, increasing the number of negative correlations between metabolites in both pulp and skin. This integrated study of micrometeorology and metabolomics provided insights into the grape-cluster pattern of accumulation of 70 primary and secondary metabolites as a function of spatial variations in SI. Studying compound-specific responses against an extended gradient of quantified conditions improved our knowledge regarding the modulation of berry metabolism by SI, with the aim of using sunlight regulation to accurately modulate fruit composition in warm and arid/semi-arid regions.

Sunlight Modulates Fruit Metabolic Profile and Shapes the Spatial Pattern of Compound Accumulation within the Grape Cluster

PubMed Central

Reshef, Noam; Walbaum, Natasha; Agam, Nurit; Fait, Aaron

2017-01-01

Vineyards are characterized by their large spatial variability of solar irradiance (SI) and temperature, known to effectively modulate grape metabolism. To explore the role of sunlight in shaping fruit composition and cluster uniformity, we studied the spatial pattern of incoming irradiance, fruit temperature and metabolic profile within individual grape clusters under three levels of sunlight exposure. The experiment was conducted in a vineyard of Cabernet Sauvignon cv. located in the Negev Highlands, Israel, where excess SI and midday temperatures are known to degrade grape quality. Filtering SI lowered the surface temperature of exposed fruits and increased the uniformity of irradiance and temperature in the cluster zone. SI affected the overall levels and patterns of accumulation of sugars, organic acids, amino acids and phenylpropanoids, across the grape cluster. Increased exposure to sunlight was associated with lower accumulation levels of malate, aspartate, and maleate but with higher levels of valine, leucine, and serine, in addition to the stress-related proline and GABA. Flavan-3-ols metabolites showed a negative response to SI, whereas flavonols were highly induced. The overall levels of anthocyanins decreased with increased sunlight exposure; however, a hierarchical cluster analysis revealed that the members of this family were grouped into three distinct accumulation patterns, with malvidin anthocyanins and cyanidin-glucoside showing contrasting trends. The flavonol-glucosides, quercetin and kaempferol, exhibited a logarithmic response to SI, leading to improved cluster uniformity under high-light conditions. Comparing the within-cluster variability of metabolite accumulation highlighted the stability of sugars, flavan-3-ols, and cinnamic acid metabolites to SI, in contrast to the plasticity of flavonols. A correlation-based network analysis revealed that extended exposure to SI modified metabolic coordination, increasing the number of negative correlations between metabolites in both pulp and skin. This integrated study of micrometeorology and metabolomics provided insights into the grape-cluster pattern of accumulation of 70 primary and secondary metabolites as a function of spatial variations in SI. Studying compound-specific responses against an extended gradient of quantified conditions improved our knowledge regarding the modulation of berry metabolism by SI, with the aim of using sunlight regulation to accurately modulate fruit composition in warm and arid/semi-arid regions. PMID:28203242

Perceptual mapping of chemesthetic stimuli in naïve assessors

PubMed Central

Byrnes, Nadia; Nestrud, Michael A.; Hayes, John E.

2015-01-01

Chemesthetic compounds, responsible for sensations such as burning, cooling, and astringency, are difficult stimuli to work with, especially when the evaluation task requires retasting. Here, we developed a protocol by which chemesthetic compounds can be assessed using sorting. We compared the performance of two cohorts of untrained assessors on this task, one with nose clips and the other without. Similarity matrices were analyzed using multidimensional scaling (MDS) to produce perceptual maps for the two cohorts. Overall, the groupings from the nose open cohort tended to follow a biological basis, consistent with previous findings that suggest compounds that activate a common receptor will elicit similar sensations. The nose-open and nose-pinched cohorts generated significantly different maps. The nose-pinched cohort had a higher variance in the MDS solution than the nose-open group. While the nose-open cohort generated seven clusters, the nose-pinched cohort generated only two clusters, seemingly based on the ready identification of chemesthetic sensations or not. There was less consensus regarding the attributes used to describe the samples in the nose-pinched cohort than in the nose-open cohort as well, as this cohort collectively generated more attributes but fewer were significant in regression. PMID:26236421

The chemistry of the superheavy elements. II. The stability of high oxidation states in group 11 elements: Relativistic coupled cluster calculations for the di-, tetra- and hexafluoro metallates of Cu, Ag, Au, and element 111

NASA Astrophysics Data System (ADS)

Seth, Michael; Cooke, Fiona; Schwerdtfeger, Peter; Heully, Jean-Louis; Pelissier, Michel

1998-09-01

The stability of the high oxidation states +3 and +5 in Group 11 fluorides is studied by relativistic Møller-Plesset (MP) and coupled cluster methods. Higher metal oxidation states are stabilized by relativistic effects. As a result, the hexafluoro complex of the Group 11 element with nuclear charge 111 and oxidation state +5 is the most stable compared to the other congeners. The results also suggest that AgF6- is thermodynamically stable and, therefore, it might be feasable to synthesize this compound. For the copper fluorides we observe very large oscillations in the Møller-Plesset series up to the fourth order. Nonrelativistic calculations lead to the expected trend in the metal-fluorine bond distances for the MF2- compounds, CuF2-

Geographic information systems and pharmacoepidemiology: using spatial cluster detection to monitor local patterns of prescription opioid abuse.

PubMed

Brownstein, John S; Green, Traci C; Cassidy, Theresa A; Butler, Stephen F

2010-06-01

Understanding the spatial distribution of opioid abuse at the local level may facilitate public health interventions. Using patient-level data from addiction treatment facilities in New Mexico from ASI-MV Connect, we applied geographic information system (GIS) in combination with a spatial scan statistic to generate risk maps of prescription opioid abuse and identify clusters of product- and compound-specific abuse. Prescribed opioid volume data was used to determine whether identified clusters are beyond geographic differences in availability. Data on 24 452 patients residing in New Mexico were collected. Among those patients, 1779 (7.3%) reported abusing any prescription opioid (past 30 days). According to opioid type, 979 patients (4.0%) reported abuse of any hydrocodone, 1007 (4.1%) for any oxycodone, 108 (0.4%) for morphine, 507 (2.1%) for Vicodin or generic equivalent, 390 (1.6%) for OxyContin, and 63 (0.2%) for MS Contin or generic equivalent. Highest rates of abuse were found in the area surrounding Albuquerque with 8.6 patients indicating abuse per 100 interviewed patients. We found clustering of abuse around Albuquerque (P = 0.001; Relative Risk = 1.35, and a radius of 146 km). At the compound level, we found that drug availability was partly responsible for clustering of prescription opioid abuse. After accounting for drug availability, we identified a second foci of Vicodin abuse in the southern rural portion of the state near Las Cruces, NM and El Paso, Texas and bordering Mexico (RR = 2.1; P = 0.001). A better understanding of local risk distribution may have implications for response strategies to future introductions of prescription opioids.

Geographic Informations Systems and Pharmacoepidemiology: Using spatial cluster detection to monitor local patterns of prescription opioid abuse

PubMed Central

Brownstein, John S.; Green, Traci C.; Cassidy, Theresa A.; Butler, Stephen F.

2010-01-01

Purpose Understanding the spatial distribution of opioid abuse at the local level may facilitate public health interventions. Methods Using patient-level data from addiction treatment facilities in New Mexico from ASI-MV® Connect, we applied geographic information system in combination with a spatial scan statistics to generate risk maps of prescription opioid abuse and identify clusters of product- and compound-specific abuse. Prescribed opioid volume data was used to determine whether identified clusters are beyond geographic differences in availability. Results Data on 24,452 patients residing in New Mexico was collected. Among those patients, 1779 (7.3%) reported abusing any prescription opioid (past 30 days). According to opioid type, 979 patients (4.0%) reported abuse of any hydrocodone, 1007 (4.1%) for any oxycodone, 108 (0.4%) for morphine, 507 (2.1%) for Vicodin® or generic equivalent, 390 (1.6%) for OxyContin®, and 63 (0.2%) for MS Contin® or generic equivalent. Highest rates of abuse were found in the area surrounding Albuquerque with 8.6 patients indicating abuse per 100 interviewed patients. We found clustering of abuse around Albuquerque (P=0.001; Relative Risk=1.35 and a radius of 146 km). At the compound level, we found that drug availability was partly responsible for clustering of prescription opioid abuse. After accounting for drug availability, we identified a second foci of Vicodin® abuse in the southern rural portion of the state near Las Cruces, NM and El Paso, Texas and bordering Mexico (RR=2.1; P=0.001). Conclusions A better understanding of local risk distribution may have implications for response strategies to future introductions of prescription opioids. PMID:20535759

[Ag115S34(SCH2C6H4 tBu)47(dpph)6]: synthesis, crystal structure and NMR investigations of a soluble silver chalcogenide nanocluster† †Dedicated to Evamarie Hey-Hawkins on the occasion of her 60th birthday. ‡ ‡Electronic supplementary information (ESI) available: CCDC 1507868. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6sc04578b Click here for additional data file. Click here for additional data file.

PubMed Central

Fuhr, Olaf; Breitung, Ben; Kiran Chakravadhanula, Venkata Sei; Guthausen, Gisela; Hennrich, Frank; Yu, Wen; Kappes, Manfred M.; Roesky, Peter W.

2017-01-01

With the aim to synthesize soluble cluster molecules, the silver salt of (4-(tert-butyl)phenyl)methanethiol [AgSCH2C6H4 tBu] was applied as a suitable precursor for the formation of a nanoscale silver sulfide cluster. In the presence of 1,6-(diphenylphosphino)hexane (dpph), the 115 nuclear silver cluster [Ag115S34(SCH2C6H4 tBu)47(dpph)6] was obtained. The molecular structure of this compound was elucidated by single crystal X-ray analysis and fully characterized by spectroscopic techniques. In contrast to most of the previously published cluster compounds with more than a hundred heavy atoms, this nanoscale inorganic molecule is soluble in organic solvents, which allowed a comprehensive investigation in solution by UV-Vis spectroscopy and one- and two-dimensional NMR spectroscopy including 31P/109Ag-HSQC and DOSY experiments. These are the first heteronuclear NMR investigations on coinage metal chalcogenides. They give some first insight into the behavior of nanoscale silver sulfide clusters in solution. Additionally, molecular weight determinations were performed by 2D analytical ultracentrifugation and HR-TEM investigations confirm the presence of size-homogeneous nanoparticles present in solution. PMID:28507679

Mixing and matching siderophore clusters: structure and biosynthesis of serratiochelins from Serratia sp. V4.

PubMed

Seyedsayamdost, Mohammad R; Cleto, Sara; Carr, Gavin; Vlamakis, Hera; João Vieira, Maria; Kolter, Roberto; Clardy, Jon

2012-08-22

Interrogation of the evolutionary history underlying the remarkable structures and biological activities of natural products has been complicated by not knowing the functions they have evolved to fulfill. Siderophores-soluble, low molecular weight compounds-have an easily understood and measured function: acquiring iron from the environment. Bacteria engage in a fierce competition to acquire iron, which rewards the production of siderophores that bind iron tightly and cannot be used or pirated by competitors. The structures and biosyntheses of "odd" siderophores can reveal the evolutionary strategy that led to their creation. We report a new Serratia strain that produces serratiochelin and an analog of serratiochelin. A genetic approach located the serratiochelin gene cluster, and targeted mutations in several genes implicated in serratiochelin biosynthesis were generated. Bioinformatic analyses and mutagenesis results demonstrate that genes from two well-known siderophore clusters, the Escherichia coli enterobactin cluster and the Vibrio cholera vibriobactin cluster, were shuffled to produce a new siderophore biosynthetic pathway. These results highlight how modular siderophore gene clusters can be mixed and matched during evolution to generate structural diversity in siderophores.

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

A novel artificial immune algorithm for spatial clustering with obstacle constraint and its applications.

PubMed

Sun, Liping; Luo, Yonglong; Ding, Xintao; Zhang, Ji

2014-01-01

An important component of a spatial clustering algorithm is the distance measure between sample points in object space. In this paper, the traditional Euclidean distance measure is replaced with innovative obstacle distance measure for spatial clustering under obstacle constraints. Firstly, we present a path searching algorithm to approximate the obstacle distance between two points for dealing with obstacles and facilitators. Taking obstacle distance as similarity metric, we subsequently propose the artificial immune clustering with obstacle entity (AICOE) algorithm for clustering spatial point data in the presence of obstacles and facilitators. Finally, the paper presents a comparative analysis of AICOE algorithm and the classical clustering algorithms. Our clustering model based on artificial immune system is also applied to the case of public facility location problem in order to establish the practical applicability of our approach. By using the clone selection principle and updating the cluster centers based on the elite antibodies, the AICOE algorithm is able to achieve the global optimum and better clustering effect.

Word-initial rhotic clusters in typically developing children: European Portuguese.

PubMed

Ramalho, Ana Margarida; Freitas, M João

2018-01-01

Rhotic clusters are complex structures segmentally and prosodically and are frequently one of the last structures acquired by Portuguese-speaking children. This paper describes cross-sectional data for word-initial (WI) rhotic tap clusters in typically developing 3-4- and 5-year-olds in Portugal. Additional information is provided on WI /l/ as a singleton and in clusters. A native speaker audio-recorded and transcribed single words in a story-telling task. Results for WI rhotic clusters show an age effect consistent with previous research on European Portuguese. Singleton /l/ was in advance of /l/-clusters as expected, but the tap clusters were in advance of the /l/-clusters, possibly reflecting the velarized characteristics of the lateral. The prosodic variables word stress and word length were relevant for the WI rhotic clusters: shorter words and stressed syllables showed higher accuracy. Finally, mismatches ('errors') mainly reflected negative structural constraints (deletion of C2 and epenthesis) rather than segmental constraints (substitutions).

Boron-containing chlorins and tetraazaporphyrins: synthesis and cell uptake of boronated pyropheophorbide a derivatives.

PubMed

Ratajski, Michal; Osterloh, Jens; Gabel, Detlef

2006-03-01

The literature on the synthesis and the biological properties of boron-containing chlorins and phthalocyanines is reviewed. A series of homologous derivatives of pyropheophorbide A is described. The compounds contain the B(12)H(11)SH(2-) cluster attached to the single carboxyl group and vary in the length of the alkyl chain (methyl, propyl, pentyl, heptyl and nonyl) attached via an ether linkage to the former vinyl group. Cellular uptake was found for all derivatives except the nonyl sidechain. The compounds were moderately cell-toxic. Localization in lysosomes could be excluded; the compounds localized probably in the mitochondria.

Electron-Poor Polar Intermetallics: Complex Structures, Novel Clusters, and Intriguing Bonding with Pronounced Electron Delocalization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Qisheng; Miller, Gordon J.

Intermetallic compounds represent an extensive pool of candidates for energy related applications stemming from magnetic, electric, optic, caloric, and catalytic properties. The discovery of novel intermetallic compounds can enhance understanding of the chemical principles that govern structural stability and chemical bonding as well as finding new applications. Valence electron-poor polar intermetallics with valence electron concentrations (VECs) between 2.0 and 3.0 e –/atom show a plethora of unprecedented and fascinating structural motifs and bonding features. Furthermore, establishing simple structure-bonding-property relationships is especially challenging for this compound class because commonly accepted valence electron counting rules are inappropriate.

Electron-Poor Polar Intermetallics: Complex Structures, Novel Clusters, and Intriguing Bonding with Pronounced Electron Delocalization

DOE PAGES

Lin, Qisheng; Miller, Gordon J.

2017-12-18

Intermetallic compounds represent an extensive pool of candidates for energy related applications stemming from magnetic, electric, optic, caloric, and catalytic properties. The discovery of novel intermetallic compounds can enhance understanding of the chemical principles that govern structural stability and chemical bonding as well as finding new applications. Valence electron-poor polar intermetallics with valence electron concentrations (VECs) between 2.0 and 3.0 e –/atom show a plethora of unprecedented and fascinating structural motifs and bonding features. Furthermore, establishing simple structure-bonding-property relationships is especially challenging for this compound class because commonly accepted valence electron counting rules are inappropriate.

Charge-doping and chemical composition-driven magnetocrystalline anisotropy in CoPt core-shell alloy clusters

NASA Astrophysics Data System (ADS)

Ruiz-Díaz, P.; Muñoz-Navia, M.; Dorantes-Dávila, J.

2018-03-01

Charge-doping together with 3 d-4 d alloying emerges as promising mechanisms for tailoring the magnetic properties of low-dimensional systems. Here, throughout ab initio calculations, we present a systematic overview regarding the impact of both electron(hole) charge-doping and chemical composition on the magnetocrystalline anisotropy (MA) of CoPt core-shell alloy clusters. By taking medium-sized Co n Pt m ( N = n + m = 85) octahedral-like alloy nanoparticles for some illustrative core-sizes as examples, we found enhanced MA energies and large induced spin(orbital) moments in Pt-rich clusters. Moreover, depending on the Pt-core-size, both in-plane and off-plane directions of magnetization are observed. In general, the MA of these binary compounds further stabilizes upon charge-doping. In addition, in the clusters with small MA, the doping promotes magnetization switching. Insights into the microscopical origins of the MA behavior are associated to changes in the electronic structure of the clusters. [Figure not available: see fulltext.

IMG-ABC: new features for bacterial secondary metabolism analysis and targeted biosynthetic gene cluster discovery in thousands of microbial genomes

DOE PAGES

Hadjithomas, Michalis; Chen, I-Min A.; Chu, Ken; ...

2016-11-29

Secondary metabolites produced by microbes have diverse biological functions, which makes them a great potential source of biotechnologically relevant compounds with antimicrobial, anti-cancer and other activities. The proteins needed to synthesize these natural products are often encoded by clusters of co-located genes called biosynthetic gene clusters (BCs). In order to advance the exploration of microbial secondary metabolism, we developed the largest publically available database of experimentally verified and predicted BCs, the Integrated Microbial Genomes Atlas of Biosynthetic gene Clusters (IMG-ABC) (https://img.jgi.doe.gov/abc/). Here, we describe an update of IMG-ABC, which includes ClusterScout, a tool for targeted identification of custom biosynthetic genemore » clusters across 40 000 isolate microbial genomes, and a new search capability to query more than 700 000 BCs from isolate genomes for clusters with similar Pfam composition. Additional features enable fast exploration and analysis of BCs through two new interactive visualization features, a BC function heatmap and a BC similarity network graph. These new tools and features add to the value of IMG-ABC's vast body of BC data, facilitating their in-depth analysis and accelerating secondary metabolite discovery.« less

IMG-ABC: new features for bacterial secondary metabolism analysis and targeted biosynthetic gene cluster discovery in thousands of microbial genomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hadjithomas, Michalis; Chen, I-Min A.; Chu, Ken

Secondary metabolites produced by microbes have diverse biological functions, which makes them a great potential source of biotechnologically relevant compounds with antimicrobial, anti-cancer and other activities. The proteins needed to synthesize these natural products are often encoded by clusters of co-located genes called biosynthetic gene clusters (BCs). In order to advance the exploration of microbial secondary metabolism, we developed the largest publically available database of experimentally verified and predicted BCs, the Integrated Microbial Genomes Atlas of Biosynthetic gene Clusters (IMG-ABC) (https://img.jgi.doe.gov/abc/). Here, we describe an update of IMG-ABC, which includes ClusterScout, a tool for targeted identification of custom biosynthetic genemore » clusters across 40 000 isolate microbial genomes, and a new search capability to query more than 700 000 BCs from isolate genomes for clusters with similar Pfam composition. Additional features enable fast exploration and analysis of BCs through two new interactive visualization features, a BC function heatmap and a BC similarity network graph. These new tools and features add to the value of IMG-ABC's vast body of BC data, facilitating their in-depth analysis and accelerating secondary metabolite discovery.« less

Synthesis, structure and research on quasi-aromaticity of a new organically templated aluminoborate: [NH0.5C4H4NH0.5][AlB12O14(OH)12

NASA Astrophysics Data System (ADS)

Hu, HengBin; Chen, XiangYi; Deng, Song; Cai, Feng; Sun, YanQiong; Chen, YiPing

2012-02-01

By employing hydrothermal method, we identify a new organically templated aluminoborate [NH0.5C4H4NH0.5][AlB12O14(OH)12] which is structurally determined by single crystal X-ray diffraction and characterized by simulated and experimental IR, 2D IR COS (two-dimensional infrared correlation spectroscopy), NICS (nucleus-independent chemical shifts) and Mulliken charges calculations. Although the cluster anions [AlB12O14(OH)12]- is identical to the counterpart of compound reported by Lin et al. at 2008, we firstly bring up its quasi-aromaticity, discuss and confirm it by NICS, Mulliken charges calculations and magnetic-induced 2D IR COS, and conclude that three isolated and non-coplanar four-center six-electron π bonds of cluster could cooperate and interact with each other to form a closed conjugated large π orbital system, endowing the cluster anions with quasi-aromaticity. Thus, a one-dimensional chain is constructed by π-π stacked interaction between quasi-aromatic clusters and aromatic pyrazine along [1 0¯ 1] direction. The title compound crystallizes in monoclinic space group C2/c with a = 18.397(4), b = 12.0670(16), c = 11.075(2) Å, α = 90.00, β = 116.483(11), γ = 90.00°, Z = 4, V = 2200.6(7) Å, R = 0.0442 and wR = 0.1128 for 2689 observed reflections.

Physical linkage of metabolic genes in fungi is an adaptation against the accumulation of toxic intermediate compounds.

PubMed

McGary, Kriston L; Slot, Jason C; Rokas, Antonis

2013-07-09

Genomic analyses have proliferated without being tied to tangible phenotypes. For example, although coordination of both gene expression and genetic linkage have been offered as genetic mechanisms for the frequently observed clustering of genes participating in fungal metabolic pathways, elucidation of the phenotype(s) favored by selection, resulting in cluster formation and maintenance, has not been forthcoming. We noted that the cause of certain well-studied human metabolic disorders is the accumulation of toxic intermediate compounds (ICs), which occurs when the product of an enzyme is not used as a substrate by a downstream neighbor in the metabolic network. This raises the hypothesis that the phenotype favored by selection to drive gene clustering is the mitigation of IC toxicity. To test this, we examined 100 diverse fungal genomes for the simplest type of cluster, gene pairs that are both metabolic neighbors and chromosomal neighbors immediately adjacent to each other, which we refer to as "double neighbor gene pairs" (DNGPs). Examination of the toxicity of their corresponding ICs shows that, compared with chromosomally nonadjacent metabolic neighbors, DNGPs are enriched for ICs that have acutely toxic LD50 doses or reactive functional groups. Furthermore, DNGPs are significantly more likely to be divergently oriented on the chromosome; remarkably, ∼40% of these DNGPs have ICs known to be toxic. We submit that the structure of synteny in metabolic pathways of fungi is a signature of selection for protection against the accumulation of toxic metabolic intermediates.

Ion Mobility Mass Spectrometry Analysis of Isomeric Disaccharide Precursor, Product and Cluster Ions

PubMed Central

Li, Hongli; Bendiak, Brad; Siems, William F.; Gang, David R.; Hill, Herbert H.

2015-01-01

RATIONALE Carbohydrates are highly variable in structure owing to differences in their anomeric configurations, monomer stereochemistry, inter-residue linkage positions and general branching features. The separation of carbohydrate isomers poses a great challenge for current analytical techniques. METHODS The isomeric heterogeneity of disaccharide ions and monosaccharideglycolaldehyde product ions evaluated using electrospray traveling wave ion mobility mass spectrometry (Synapt G2 high definition mass spectrometer) in both positive and negative ion modes investigation. RESULTS The separation of isomeric disaccharide ions was observed but not fully achieved based on their mobility profiles. The mobilities of isomeric product ions, the monosaccharide-glycolaldehydes, derived from different disaccharide isomers were measured. Multiple mobility peaks were observed for both monosaccharide-glycolaldehyde cations and anions, indicating that there was more than one structural configuration in the gas phase as verified by NMR in solution. More importantly, the mobility patterns for isomeric monosaccharide-glycolaldehyde product ions were different, which enabled partial characterization of their respective disaccharide ions. Abundant disaccharide cluster ions were also observed. The Results showed that a majority of isomeric cluster ions had different drift times and, moreover, more than one mobility peak was detected for a number of specific cluster ions. CONCLUSIONS It is demonstrated that ion mobility mass spectrometry is an advantageous method to assess the isomeric heterogeneity of carbohydrate compounds. It is capable of differentiating different types of carbohydrate ions having identical m/z values as well as multiple structural configurations of single compounds. PMID:24591031

Physical linkage of metabolic genes in fungi is an adaptation against the accumulation of toxic intermediate compounds

PubMed Central

McGary, Kriston L.; Slot, Jason C.; Rokas, Antonis

2013-01-01

Genomic analyses have proliferated without being tied to tangible phenotypes. For example, although coordination of both gene expression and genetic linkage have been offered as genetic mechanisms for the frequently observed clustering of genes participating in fungal metabolic pathways, elucidation of the phenotype(s) favored by selection, resulting in cluster formation and maintenance, has not been forthcoming. We noted that the cause of certain well-studied human metabolic disorders is the accumulation of toxic intermediate compounds (ICs), which occurs when the product of an enzyme is not used as a substrate by a downstream neighbor in the metabolic network. This raises the hypothesis that the phenotype favored by selection to drive gene clustering is the mitigation of IC toxicity. To test this, we examined 100 diverse fungal genomes for the simplest type of cluster, gene pairs that are both metabolic neighbors and chromosomal neighbors immediately adjacent to each other, which we refer to as “double neighbor gene pairs” (DNGPs). Examination of the toxicity of their corresponding ICs shows that, compared with chromosomally nonadjacent metabolic neighbors, DNGPs are enriched for ICs that have acutely toxic LD50 doses or reactive functional groups. Furthermore, DNGPs are significantly more likely to be divergently oriented on the chromosome; remarkably, ∼40% of these DNGPs have ICs known to be toxic. We submit that the structure of synteny in metabolic pathways of fungi is a signature of selection for protection against the accumulation of toxic metabolic intermediates. PMID:23798424

Bipolar Mass Spectrometry of Labile Coordination Complexes, Redox Active Inorganic Compounds, and Proteins Using a Glass Nebulizer for Sonic-Spray Ionization

NASA Astrophysics Data System (ADS)

Antonakis, Manolis M.; Tsirigotaki, Alexandra; Kanaki, Katerina; Milios, Constantinos J.; Pergantis, Spiros A.

2013-08-01

In this study, we report on the development of a novel nebulizer configuration for sonic-spray ionization (SSI) mass spectrometry (MS), more specifically for a version of SSI that is referred to as Venturi easy ambient sonic-spray ionization (V-EASI) MS. The developed nebulizer configuration is based on a commercially available pneumatic glass nebulizer that has been used extensively for aerosol formation in atomic spectrometry. In the present study, the nebulizer was modified in order to achieve efficient V-EASI-MS operation. Upon evaluating this system, it has been demonstrated that V-EASI-MS offers some distinct advantages for the analysis of coordination compounds and redox active inorganic compounds over the predominantly used electrospray ionization (ESI) technique. Such advantages, for this type of compounds, are demonstrated here for the first time. More specifically, a series of labile heptanuclear heterometallic [CuII 6LnIII] clusters held together with artificial amino acid ligands, in addition to easily oxidized inorganic oxyanions of selenium and arsenic, were analyzed. The observed advantages pertain to V-EASI appearing to be a "milder" ionization source than ESI, not requiring electrical potentials for gas phase ion formation, thus eliminating the possibility of unwanted redox transformations, allowing for the "simultaneous" detection of negative and positive ions (bipolar analysis) without the need to change source ionization conditions, and also not requiring the use of syringes and delivery pumps. Because of such features, especially because of the absence of ionization potentials, EASI can be operated with minimal requirements for source parameter optimization. We observed that source temperature and accelerating voltage do not seem to affect labile compounds to the extent they do in ESI-MS. In addition, bipolar analysis of proteins was demonstrated here by acquiring both positive and negative ion mass spectra from the same protein solutions, without the need to independently adjust solution and source conditions in each mode. Finally, the simple and efficient operation of a dual-nebulizer configuration was demonstrated for V-EASI-MS for the first time.

Bipolar mass spectrometry of labile coordination complexes, redox active inorganic compounds, and proteins using a glass nebulizer for sonic-spray ionization.

PubMed

Antonakis, Manolis M; Tsirigotaki, Alexandra; Kanaki, Katerina; Milios, Constantinos J; Pergantis, Spiros A

2013-08-01

In this study, we report on the development of a novel nebulizer configuration for sonic-spray ionization (SSI) mass spectrometry (MS), more specifically for a version of SSI that is referred to as Venturi easy ambient sonic-spray ionization (V-EASI) MS. The developed nebulizer configuration is based on a commercially available pneumatic glass nebulizer that has been used extensively for aerosol formation in atomic spectrometry. In the present study, the nebulizer was modified in order to achieve efficient V-EASI-MS operation. Upon evaluating this system, it has been demonstrated that V-EASI-MS offers some distinct advantages for the analysis of coordination compounds and redox active inorganic compounds over the predominantly used electrospray ionization (ESI) technique. Such advantages, for this type of compounds, are demonstrated here for the first time. More specifically, a series of labile heptanuclear heterometallic [Cu(II) 6Ln(III)] clusters held together with artificial amino acid ligands, in addition to easily oxidized inorganic oxyanions of selenium and arsenic, were analyzed. The observed advantages pertain to V-EASI appearing to be a "milder" ionization source than ESI, not requiring electrical potentials for gas phase ion formation, thus eliminating the possibility of unwanted redox transformations, allowing for the "simultaneous" detection of negative and positive ions (bipolar analysis) without the need to change source ionization conditions, and also not requiring the use of syringes and delivery pumps. Because of such features, especially because of the absence of ionization potentials, EASI can be operated with minimal requirements for source parameter optimization. We observed that source temperature and accelerating voltage do not seem to affect labile compounds to the extent they do in ESI-MS. In addition, bipolar analysis of proteins was demonstrated here by acquiring both positive and negative ion mass spectra from the same protein solutions, without the need to independently adjust solution and source conditions in each mode. Finally, the simple and efficient operation of a dual-nebulizer configuration was demonstrated for V-EASI-MS for the first time.

Cluster Dynamics: Laying the Foundation for Tailoring the Design of Cluster ASSE

DTIC Science & Technology

2016-02-25

UNIVERSITY 201 OLD MAIN UNIVERSITY PARK, PA 16802-1505 02/25/2016 Final Report DISTRIBUTION A: Distribution approved for public release. Air Force...5f.  WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) PENNSYLVANIA STATE UNIVERSITY 201 OLD MAIN UNIVERSITY PARK, PA 16802-1505 US 8

Adult Speakers' Tongue-Palate Contact Patterns for Bilabial Stops within Complex Clusters

ERIC Educational Resources Information Center

Zharkova, Natalia; Schaeffler, Sonja; Gibbon, Fiona E.

2009-01-01

Previous studies using Electropalatography (EPG) have shown that individuals with speech disorders sometimes produce articulation errors that affect bilabial targets, but currently there is limited normative data available. In this study, EPG and acoustic data were recorded during complex word final sps clusters spoken by 20 normal adults. A total…

Synthesis and Molecular Structure of a Novel Compound Containing a Carbonate-Bridged Hexacalcium Cluster Cation Assembled on a Trimeric Trititanium(IV)-Substituted Wells-Dawson Polyoxometalate.

PubMed

Hoshino, Takahiro; Isobe, Rina; Kaneko, Takuya; Matsuki, Yusuke; Nomiya, Kenji

2017-08-21

A novel compound containing a hexacalcium cluster cation, one carbonate anion, and one calcium cation assembled on a trimeric trititanium(IV)-substituted Wells-Dawson polyoxometalate (POM), [{Ca 6 (CO 3 )(μ 3 -OH)(OH 2 ) 18 }(P 2 W 15 Ti 3 O 61 ) 3 Ca(OH 2 ) 3 ] 19- (Ca 7 Ti 9 Trimer), was obtained as the Na 7 Ca 6 salt (NaCa-Ca 7 Ti 9 Trimer) by the reaction of calcium chloride with the monomeric trititanium(IV)-substituted Wells-Dawson POM species "[P 2 W 15 Ti 3 O 59 (OH) 3 ] 9- " (Ti 3 Monomer). Ti 3 Monomer was generated in situ under basic conditions from the separately prepared tetrameric species with bridging Ti(OH 2 ) 3 groups and an encapsulated Cl - ion, [{P 2 W 15 Ti 3 O 59 (OH) 3 } 4 {μ 3 -Ti(H 2 O) 3 } 4 Cl] 21- (Ti 16 Tetramer). The Na 7 Ca 6 salt of Ca 7 Ti 9 Trimer was characterized by complete elemental analysis, thermogravimetric (TG) and differential thermal analyses (DTA), FTIR, single-crystal X-ray structure analysis, and solution 183 W and 31 P NMR spectroscopy. X-ray crystallography revealed that the [Ca 6 (CO 3 )(μ 3 -OH)(OH 2 ) 18 ] 9+ cluster cation was composed of six calcium cations linked by one μ 6 -carbonato anion and one μ 3 -OH - anion. The cluster cation was assembled, together with one calcium ion, on a trimeric species composed of three tri-Ti(IV)-substituted Wells-Dawson subunits linked by Ti-O-Ti bonds. Ca 7 Ti 9 Trimer is an unprecedented POM species containing an alkaline-earth-metal cluster cation and is the first example of alkaline-earth-metal ions clustered around a titanium(IV)-substituted POM.

Three-dimensional visualization of cultural clusters in the 1878 yellow fever epidemic of New Orleans

PubMed Central

Curtis, Andrew J

2008-01-01

Background An epidemic may exhibit different spatial patterns with a change in geographic scale, with each scale having different conduits and impediments to disease spread. Mapping disease at each of these scales often reveals different cluster patterns. This paper will consider this change of geographic scale in an analysis of yellow fever deaths for New Orleans in 1878. Global clustering for the whole city, will be followed by a focus on the French Quarter, then clusters of that area, and finally street-level patterns of a single cluster. The three-dimensional visualization capabilities of a GIS will be used as part of a cluster creation process that incorporates physical buildings in calculating mortality-to-mortality distance. Including nativity of the deceased will also capture cultural connection. Results Twenty-two yellow fever clusters were identified for the French Quarter. These generally mirror the results of other global cluster and density surfaces created for the entire epidemic in New Orleans. However, the addition of building-distance, and disease specific time frame between deaths reveal that disease spread contains a cultural component. Same nativity mortality clusters emerge in a similar time frame irrespective of proximity. Italian nativity mortalities were far more densely grouped than any of the other cohorts. A final examination of mortalities for one of the nativity clusters reveals that further sub-division is present, and that this pattern would only be revealed at this scale (street level) of investigation. Conclusion Disease spread in an epidemic is complex resulting from a combination of geographic distance, geographic distance with specific connection to the built environment, disease-specific time frame between deaths, impediments such as herd immunity, and social or cultural connection. This research has shown that the importance of cultural connection may be more important than simple proximity, which in turn might mean traditional quarantine measures should be re-evaluated. PMID:18721469

Three-dimensional visualization of cultural clusters in the 1878 yellow fever epidemic of New Orleans.

PubMed

Curtis, Andrew J

2008-08-22

An epidemic may exhibit different spatial patterns with a change in geographic scale, with each scale having different conduits and impediments to disease spread. Mapping disease at each of these scales often reveals different cluster patterns. This paper will consider this change of geographic scale in an analysis of yellow fever deaths for New Orleans in 1878. Global clustering for the whole city, will be followed by a focus on the French Quarter, then clusters of that area, and finally street-level patterns of a single cluster. The three-dimensional visualization capabilities of a GIS will be used as part of a cluster creation process that incorporates physical buildings in calculating mortality-to-mortality distance. Including nativity of the deceased will also capture cultural connection. Twenty-two yellow fever clusters were identified for the French Quarter. These generally mirror the results of other global cluster and density surfaces created for the entire epidemic in New Orleans. However, the addition of building-distance, and disease specific time frame between deaths reveal that disease spread contains a cultural component. Same nativity mortality clusters emerge in a similar time frame irrespective of proximity. Italian nativity mortalities were far more densely grouped than any of the other cohorts. A final examination of mortalities for one of the nativity clusters reveals that further sub-division is present, and that this pattern would only be revealed at this scale (street level) of investigation. Disease spread in an epidemic is complex resulting from a combination of geographic distance, geographic distance with specific connection to the built environment, disease-specific time frame between deaths, impediments such as herd immunity, and social or cultural connection. This research has shown that the importance of cultural connection may be more important than simple proximity, which in turn might mean traditional quarantine measures should be re-evaluated.

Clustering pesticides according to their molecular properties and their impacts by considering additional ecotoxicological parameters in the TyPol method

NASA Astrophysics Data System (ADS)

Traore, Harouna; Crouzet, Olivier; Mamy, Laure; Sireyjol, Christine; Rossard, Virginie; Servien, Remy; Latrille, Eric; Benoit, Pierre

2017-04-01

The understanding of the fate of pesticides and their environmental impacts largely relies on their molecular properties. We recently developed 'TyPol' (Typology of Pollutants), a clustering method based on statistical analyses combining several environmental endpoints (i.e. environmental parameters such as sorption coefficient, degradation half-life) and one ecotoxicological one (bioconcentration factor), and structural molecular descriptors (number of atoms in the molecule, molecular surface, dipole moment, energy of orbitals…). TyPol has been conceived on the available knowledge on QSAR of a wide diversity of organic compounds (Mamy et al., 2015). This approach also allows to focus on transformation products present in different clusters and to infer possible changes in environmental fate consecutively to different degradation processes (Servien et al., 2014; Benoit et al., 2016). The initial version of TyPol did not include any ecotoxicological parameters except the bioconcentration factor (BCF), which informs more on the transfer along the trophic chain rather than on the effects on non-target organisms. The objective was to implement the TyPol database with a data set of ecotoxicological data concerning pesticides and several aquatic and terrestrial organisms, in order to test the possibility to extend TyPol to ecotoxicological effects on various organisms. The data analysis (available literature and databases) revealed that relevant ecotoxicological endpoints for terrestrial organisms such as soil microorganisms and macroinvertebrates are lacking compared to aquatic organisms. We have added seven parameters for acute (EC50, LC50) and chronic (NOEC) toxicological effects for the following organisms: Daphnia, Algae, Lemna and Earthworm. In this new configuration, TyPol was used to classify about 45 pesticides in different behavioural and ecotoxicity clusters. The clustering results were analyzed to reveals relationships between molecular descriptors, environmental parameters and the added toxicological parameters. Some trends between soil adsorption or Kow coefficient and the acute toxicity towards earthworms or algae were highlighted, and discussed on the basis of the concept of contaminant bioavailability. This proof-of-concept study also showed that the in silico clustering method TyPol can successfully address new questions and can be expanded with other parameters of interest. Keywords: pesticides, toxicity, QSAR, clustering, PLS References : Servien R., Mamy L., Li Z., Rossard V., Latrille E., Bessac F., Patureau D., Benoit P., 2014. TyPol - A new methodology for organic compounds clustering based on their molecular characteristics and environmental behavior. Chemosphere, 111, 613-622. Mamy L., Patureau D., Barriuso E., Bedos C., Bessac F., Louchart X., Martin-Laurent F., Miege C., Benoit P., 2015. Prediction of the fate of organic compounds in the environment from their molecular properties: A review. Critical Reviews in Environmental Science and Technology, 45, 12, 1277-1377 (Open access). Benoit P., Mamy L., Servien R., Li Z., Latrille E., Rossard V., Bessac F., Patureau D., Martin-Laurent F. 2017. Categorizing chlordecone potential degradation products to explore their environmental fate. Science of the Total Environment, 574, 781-795.

[Study on the relationship between structure and spectroscopy of two compounds containing 2,2'-bipy and [MoO3] cluster skeletons].

PubMed

Zhang, Zi-Ming; Chen, Yi-Ping; You, Zhu-Chai; Su, Liu-Qin; Wang, Hao; Sun, Yan-Qiong

2013-11-01

Two compounds of molybdate with 2, 2'-bipy and [MoO3]: [(2, 2'-bipy)2 (MoO3)3]n (I) and [(2, 2'-bipy) (MoO3)]n (II) were successfully synthesized by hydrothermal synthesis method with programmable temperature control. In order to clarify the relationship between the structure and spectroscopy of these two compounds, both of them were characterized by means of X-ray powder diffraction (XRD), Fourier transform infrared spectra(FTIR), thermal perturbation 2D-IR correlation spectrum (2D-IR COS), thermogravimetric analysis(TGA), scanning electron microscopy(SEM), High temperature infrared analysis, UV-Vis DRS adsorption spectra and solid fluorescence spectrum to investigate the relationship between structure and properties of the title compounds. The powder XRD patterns of the complexes are well matched with the simulation based on single-crystal analysis, which indicate that compound I and II are in a pure phase. The characteristics of vibration frequency of FTIR and thermal perturbation relative spectral response of 2D-IR peak is consistent with thecompound I and II structure analysis. The synchronous and asynchronous correlation 2D-IR spectra of compounds also identified the compounds I and II molybdenum-oxygen cluster skeletons sequencing of vibration intensity change with temperature consistent with the high temperature infrared analysis. Through the TGA and high temperature infrared analysis it was found that the decomposition temperature was more than 300 degrees C and maximum weight losses rates above 800 degrees C, which suggest that they have good thermal stability. According to the UV-Vis DRS spectrum of the compound I and II there exists a wide ultraviolet absorption band in a range of 225 to 350 nm. The compound I and II steady-state fluorescence spectrum under the excitation of 277 and 295 nm respectively revealed compound I and II have the strongest emission peak at 460 and 480 nm respectively. This paper illustrates the coordination situation of these two compounds, and reveals the inherent law of valence electrons in molecule energy level transition. In the meantime it was verified that the weak interaction not only plays a role of stability in the frame of the structure of the complexes, but also plays an important role in heat resistance.

Mutagenic Azo Dyes, Rather Than Flame Retardants, Are the Predominant Brominated Compounds in House Dust.

PubMed

Peng, Hui; Saunders, David M V; Sun, Jianxian; Jones, Paul D; Wong, Chris K C; Liu, Hongling; Giesy, John P

2016-12-06

Characterization of toxicological profiles by use of traditional targeted strategies might underestimate the risk of environmental mixtures. Unbiased identification of prioritized compounds provides a promising strategy for meeting regulatory needs. In this study, untargeted screening of brominated compounds in house dust was conducted using a data-independent precursor isolation and characteristic fragment (DIPIC-Frag) approach, which used data-independent acquisition (DIA) and a chemometric strategy to detect peaks and align precursor ions. A total of 1008 brominated compound peaks were identified in 23 house dust samples. Precursor ions and formulas were identified for 738 (73%) of the brominated compounds. A correlation matrix was used to cluster brominated compounds; three large groups were found for the 140 high-abundance brominated compounds, and only 24 (17%) of these compounds were previously known flame retardants. The predominant class of unknown brominated compounds was predicted to consist of nitrogen-containing compounds. Following further validation by authentic standards, these compounds (56%) were determined to be novel brominated azo dyes. The mutagenicity of one major component was investigated, and mutagenicity was observed at environmentally relevant concentrations. Results of this study demonstrated the existence of numerous unknown brominated compounds in house dust, with mutagenic azo dyes unexpectedly being identified as the predominant compounds.

Transcriptome Analysis of Aspergillus flavus Reveals veA-Dependent Regulation of Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster

PubMed Central

Cary, J. W.; Han, Z.; Yin, Y.; Lohmar, J. M.; Shantappa, S.; Harris-Coward, P. Y.; Mack, B.; Ehrlich, K. C.; Wei, Q.; Arroyo-Manzanares, N.; Uka, V.; Vanhaecke, L.; Bhatnagar, D.; Yu, J.; Nierman, W. C.; Johns, M. A.; Sorensen, D.; Shen, H.; De Saeger, S.; Diana Di Mavungu, J.

2015-01-01

The global regulatory veA gene governs development and secondary metabolism in numerous fungal species, including Aspergillus flavus. This is especially relevant since A. flavus infects crops of agricultural importance worldwide, contaminating them with potent mycotoxins. The most well-known are aflatoxins, which are cytotoxic and carcinogenic polyketide compounds. The production of aflatoxins and the expression of genes implicated in the production of these mycotoxins are veA dependent. The genes responsible for the synthesis of aflatoxins are clustered, a signature common for genes involved in fungal secondary metabolism. Studies of the A. flavus genome revealed many gene clusters possibly connected to the synthesis of secondary metabolites. Many of these metabolites are still unknown, or the association between a known metabolite and a particular gene cluster has not yet been established. In the present transcriptome study, we show that veA is necessary for the expression of a large number of genes. Twenty-eight out of the predicted 56 secondary metabolite gene clusters include at least one gene that is differentially expressed depending on presence or absence of veA. One of the clusters under the influence of veA is cluster 39. The absence of veA results in a downregulation of the five genes found within this cluster. Interestingly, our results indicate that the cluster is expressed mainly in sclerotia. Chemical analysis of sclerotial extracts revealed that cluster 39 is responsible for the production of aflavarin. PMID:26209694

Novel layered clustering-based approach for generating ensemble of classifiers.

PubMed

Rahman, Ashfaqur; Verma, Brijesh

2011-05-01

This paper introduces a novel concept for creating an ensemble of classifiers. The concept is based on generating an ensemble of classifiers through clustering of data at multiple layers. The ensemble classifier model generates a set of alternative clustering of a dataset at different layers by randomly initializing the clustering parameters and trains a set of base classifiers on the patterns at different clusters in different layers. A test pattern is classified by first finding the appropriate cluster at each layer and then using the corresponding base classifier. The decisions obtained at different layers are fused into a final verdict using majority voting. As the base classifiers are trained on overlapping patterns at different layers, the proposed approach achieves diversity among the individual classifiers. Identification of difficult-to-classify patterns through clustering as well as achievement of diversity through layering leads to better classification results as evidenced from the experimental results.

Colloidal heteroaggregation: a strategy to prepare composite materials

NASA Astrophysics Data System (ADS)

López-López, J. M.; Schmitt, A.; Moncho-Jordá, A.; Hidalgo-Álvarez, R.

2009-01-01

In this work, we make use of single-cluster light-scattering (SCLS) experiments and Brownian dynamics (BD) simulations in order to investigate the formation of binary clusters of oppositely-charged colloidal particles by heteroaggregation processes. Two parameters determinate the stability, size and structure of the clusters: the relative concentration of both species x and the range of the particle-particle interactions κa. SCLS experiments reveal that stable binary clusters arise in asymmetric systems when particle-particle interactions are long-ranged. These stable aggregates group in bell-shaped distributions that correspond to compact clusters with different orders, i.e., with a given number of minority particles. It is found that x controls the distribution of the clusters among the different orders and κa determine the average size of the clusters belonging to each order. Finally, BD simulations allow us to interpret all these results within the the frame of the classic Hogg-Healy-Fuersternau theory.

XMM-Newton Observations of the Cluster of Galaxies Sersic 159-03

NASA Technical Reports Server (NTRS)

Kaastra, J. S.; Ferrigno, C.; Tamura, T.; Paerels, F. B. S.; Peterson, J. R.; Mittaz, J. P. D.

2000-01-01

The cluster of galaxies Sersic 159-03 was observed with the XMM-Newton X-ray observatory as part of the Guaranteed Time program. X-ray spectra taken with the EPIC and RGS instruments show no evidence for the strong cooling flow derived from previous X-ray observations. There is a significant lack of cool gas below 1.5 keV as compared to standard isobaric cooling flow models. While the oxygen is distributed more or less uniformly over the cluster, iron shows a strong concentration in the center of the cluster, slightly offset from the brightness center but within the central cD galaxy. This points to enhanced type Ia supernova activity in the center of the cluster. There is also an elongated iron-rich structure ex- tending to the east of the cluster, showing the inhomogeneity of the iron distribution. Finally, the temperature drops rapidly beyond 4' from the cluster center.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ali, Amjad Majid; Albert, Don; Andersson, Par

SLURM is an open source, fault-tolerant, and highly scalable cluster management and job scheduling system for large and small computer clusters. As a cluster resource manager, SLURM has three key functions. First, it allocates exclusive and/or non-exclusive access to resources (compute nodes) to users for some duration of time so they can perform work. Second, it provides a framework for starting, executing, and monitoring work 9normally a parallel job) on the set of allocated nodes. Finally, it arbitrates conflicting requests for resources by managing a queue of pending work.

Cluster-modified function projective synchronisation of complex networks with asymmetric coupling

NASA Astrophysics Data System (ADS)

Wang, Shuguo

2018-02-01

This paper investigates the cluster-modified function projective synchronisation (CMFPS) of a generalised linearly coupled network with asymmetric coupling and nonidentical dynamical nodes. A novel synchronisation scheme is proposed to achieve CMFPS in community networks. We use adaptive control method to derive CMFPS criteria based on Lyapunov stability theory. Each cluster of networks is synchronised with target system by state transformation with scaling function matrix. Numerical simulation results are presented finally to illustrate the effectiveness of this method.

Assessing an ensemble docking-based virtual screening strategy for kinase targets by considering protein flexibility.

PubMed

Tian, Sheng; Sun, Huiyong; Pan, Peichen; Li, Dan; Zhen, Xuechu; Li, Youyong; Hou, Tingjun

2014-10-27

In this study, to accommodate receptor flexibility, based on multiple receptor conformations, a novel ensemble docking protocol was developed by using the naïve Bayesian classification technique, and it was evaluated in terms of the prediction accuracy of docking-based virtual screening (VS) of three important targets in the kinase family: ALK, CDK2, and VEGFR2. First, for each target, the representative crystal structures were selected by structural clustering, and the capability of molecular docking based on each representative structure to discriminate inhibitors from non-inhibitors was examined. Then, for each target, 50 ns molecular dynamics (MD) simulations were carried out to generate an ensemble of the conformations, and multiple representative structures/snapshots were extracted from each MD trajectory by structural clustering. On average, the representative crystal structures outperform the representative structures extracted from MD simulations in terms of the capabilities to separate inhibitors from non-inhibitors. Finally, by using the naïve Bayesian classification technique, an integrated VS strategy was developed to combine the prediction results of molecular docking based on different representative conformations chosen from crystal structures and MD trajectories. It was encouraging to observe that the integrated VS strategy yields better performance than the docking-based VS based on any single rigid conformation. This novel protocol may provide an improvement over existing strategies to search for more diverse and promising active compounds for a target of interest.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rana, Abhinandan; Jana, Swapan Kumar; Datta, Sayanti

The synthesis of two new lead(II) coordination polymers, [Pb{sub 2}(mpic){sub 4}(H{sub 2}O)]·0.5H{sub 2}O (1) and [Pb{sub 2}(phen){sub 2}(cit)(mes)]·2H{sub 2}O (2) has been reported, where mpic=3-methyl picolinate, phen=o-phenanthroline, H{sub 2}cit=citraconic acid, H{sub 2}mes mesaconic acid. X-ray single crystal diffraction analyses showed that the complexes comprise topologically different 1D polymeric chains stabilized by weak interactions and both containing tetranuclear Pb{sub 4} units connected by carboxylate groups. In compound 1 3-methylpicolinic acid is formed in situ from 3-methyl piconitrile, and mesaconate and citraconate anions were surprisingly formed from itaconic acid during the synthesis of 2. The photoluminescence and thermal properties of the complexesmore » have been studied. - Graphical abstract: Two new topologically different 1D coordination polymers formed by Pb{sub 4} clusters have been synthesized and characterized by X-ray analysis. The luminescence and thermal properties have been studied. Display Omitted - Highlights: • Both the complexes, made up of different ligands, forms topologycally different 1D polymeric chains containing Pb{sub 4} clusters. • The final structures are stabilized by weak interactions (H-bond, π∙∙∙π stacking). • In complex 1, the 3-methylpicolinic acid is generated in situ from 3-methyl piconitrile. • Mesaconate and citraconate anions are surprisingly formed in situ from itaconic acid during the synthesis of complex 2, indicating an exceptional transformation.« less

Electrospray ionization mass spectrometry for the hydrolysis complexes of cisplatin: implications for the hydrolysis process of platinum complexes.

PubMed

Feifan, Xie; Pieter, Colin; Jan, Van Bocxlaer

2017-07-01

Non-enzyme-dependent hydrolysis of the drug cisplatin is important for its mode of action and toxicity. However, up until today, the hydrolysis process of cisplatin is still not completely understood. In the present study, the hydrolysis of cisplatin in an aqueous solution was systematically investigated by using electrospray ionization mass spectrometry coupled to liquid chromatography. A variety of previously unreported hydrolysis complexes corresponding to monomeric, dimeric and trimeric species were detected and identified. The characteristics of the Pt-containing complexes were investigated by using collision-induced dissociation (CID). The hydrolysis complexes demonstrate distinctive and correlative CID characteristics, which provides tools for an informative identification. The most frequently observed dissociation mechanism was sequential loss of NH 3 , H 2 O and HCl. Loss of the Pt atom was observed as the final step during the CID process. The formation mechanisms of the observed complexes were explored and experimentally examined. The strongly bound dimeric species, which existed in solution, are assumed to be formed from the clustering of the parent compound and its monohydrated or dihydrated complexes. The role of the electrospray process in the formation of some of the observed ions was also evaluated, and the electrospray ionization-related cold clusters were identified. The previously reported hydrolysis equilibria were tested and subsequently refined via a hydrolysis study resulting in a renewed mechanistic equilibrium system of cisplatin as proposed from our results. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Nearest neighbor-density-based clustering methods for large hyperspectral images

NASA Astrophysics Data System (ADS)

Cariou, Claude; Chehdi, Kacem

2017-10-01

We address the problem of hyperspectral image (HSI) pixel partitioning using nearest neighbor - density-based (NN-DB) clustering methods. NN-DB methods are able to cluster objects without specifying the number of clusters to be found. Within the NN-DB approach, we focus on deterministic methods, e.g. ModeSeek, knnClust, and GWENN (standing for Graph WatershEd using Nearest Neighbors). These methods only require the availability of a k-nearest neighbor (kNN) graph based on a given distance metric. Recently, a new DB clustering method, called Density Peak Clustering (DPC), has received much attention, and kNN versions of it have quickly followed and showed their efficiency. However, NN-DB methods still suffer from the difficulty of obtaining the kNN graph due to the quadratic complexity with respect to the number of pixels. This is why GWENN was embedded into a multiresolution (MR) scheme to bypass the computation of the full kNN graph over the image pixels. In this communication, we propose to extent the MR-GWENN scheme on three aspects. Firstly, similarly to knnClust, the original labeling rule of GWENN is modified to account for local density values, in addition to the labels of previously processed objects. Secondly, we set up a modified NN search procedure within the MR scheme, in order to stabilize of the number of clusters found from the coarsest to the finest spatial resolution. Finally, we show that these extensions can be easily adapted to the three other NN-DB methods (ModeSeek, knnClust, knnDPC) for pixel clustering in large HSIs. Experiments are conducted to compare the four NN-DB methods for pixel clustering in HSIs. We show that NN-DB methods can outperform a classical clustering method such as fuzzy c-means (FCM), in terms of classification accuracy, relevance of found clusters, and clustering speed. Finally, we demonstrate the feasibility and evaluate the performances of NN-DB methods on a very large image acquired by our AISA Eagle hyperspectral imaging sensor.

Kinetic Investigation of Homogeneous H(2)-D(2) Equilibration Catalyzed by Pt-Au Cluster Compounds. Characterization of the Cluster [(H)Pt(AuPPh(3))(9)](NO(3))(2).

PubMed

Rubinstein, Leon I.; Pignolet, Louis H.

1996-11-06

The new Pt-Au hydrido cluster compound [(H)Pt(AuPPh(3))(9)](NO(3))(2) (3) has been synthesized and characterized by NMR, FABMS, and single-crystal X-ray diffraction [triclinic, P&onemacr;, a = 17.0452(1) Å, b = 17.4045(2) Å, c = 55.2353(1) Å, alpha = 89.891(1) degrees, beta = 85.287(1) degrees, gamma = 75.173(1) degrees, V = 15784.0(2) Å(3), Z = 4 (two molecules in asymmetric unit), residual R = 0.089 for 45 929 observed reflections and 3367 variables, Mo Kalpha radiation]. The Pt(AuP)(9) core geometry is a distorted icosahedron with three vertices vacant. The Pt-Au, Au-Au, and Au-P distances are within the normal ranges observed in other Pt-Au clusters. This cluster is a catalyst for H(2)-D(2) equilibration in homogeneous solution phase and has been used in a general mechanistic study of this reaction catalyzed by Pt-Au clusters. We previously proposed that a key step in the mechanism for catalytic H(2)-D(2) equilibration is the dissociation of a PPh(3) ligand to give a cluster with an open Au site for bonding of H(2) or D(2). This was based on qualitative observations that PPh(3) inhibited the rate of HD production with [Pt(AuPPh(3))(8)](NO(3))(2) (1) as catalyst. In order to test this hypothesis, phosphine inhibition (on the rate of HD production) and phosphine ligand exchange kinetic experiments were carried out with [(H)(PPh(3))Pt(AuPPh(3))(7)](NO(3))(2) (2) and 3. In this paper we show that the rate constant for phosphine dissociation determined from the PPh(3) inhibition rate study of H(2)-D(2) equilibration with cluster 2 is nearly identical to the rate constant for dissociative phosphine ligand exchange. The slower rate for H(2)-D(2) equilibration observed with 3 compared with 2 (5.5 x 10(-3) vs 7.7 x 10(-2) turnover s(-1)) is explained by its smaller rate constant for phosphine dissociation (2.8 x 10(-5) vs 2.9 x 10(-4) s(-1)). The fact that clusters 2 and 3 show similar kinetic behaviors suggests that the PPh(3) dissociation step in the catalytic H(2)-D(2) equilibration is general for 18-electron hydrido Pt-AuPPh(3) clusters.

The clustering of galaxies in the completed SDSS-III Baryon Oscillation Spectroscopic Survey: Cosmological implications of the Fourier space wedges of the final sample

NASA Astrophysics Data System (ADS)

Grieb, Jan Niklas; Sánchez, Ariel G.; Salazar-Albornoz, Salvador; Scoccimarro, Román; Crocce, Martín; Dalla Vecchia, Claudio; Montesano, Francesco; Gil-Marín, Héctor; Ross, Ashley J.; Beutler, Florian; Rodríguez-Torres, Sergio; Chuang, Chia-Hsun; Prada, Francisco; Kitaura, Francisco-Shu; Cuesta, Antonio J.; Eisenstein, Daniel J.; Percival, Will J.; Vargas-Magaña, Mariana; Tinker, Jeremy L.; Tojeiro, Rita; Brownstein, Joel R.; Maraston, Claudia; Nichol, Robert C.; Olmstead, Matthew D.; Samushia, Lado; Seo, Hee-Jong; Streblyanska, Alina; Zhao, Gong-bo

2017-05-01

We extract cosmological information from the anisotropic power-spectrum measurements from the recently completed Baryon Oscillation Spectroscopic Survey (BOSS), extending the concept of clustering wedges to Fourier space. Making use of new fast-Fourier-transform-based estimators, we measure the power-spectrum clustering wedges of the BOSS sample by filtering out the information of Legendre multipoles ℓ > 4. Our modelling of these measurements is based on novel approaches to describe non-linear evolution, bias and redshift-space distortions, which we test using synthetic catalogues based on large-volume N-body simulations. We are able to include smaller scales than in previous analyses, resulting in tighter cosmological constraints. Using three overlapping redshift bins, we measure the angular-diameter distance, the Hubble parameter and the cosmic growth rate, and explore the cosmological implications of our full-shape clustering measurements in combination with cosmic microwave background and Type Ia supernova data. Assuming a Λ cold dark matter (ΛCDM) cosmology, we constrain the matter density to Ω M= 0.311_{-0.010}^{+0.009} and the Hubble parameter to H_0 = 67.6_{-0.6}^{+0.7} km s^{-1 Mpc^{-1}}, at a confidence level of 68 per cent. We also allow for non-standard dark energy models and modifications of the growth rate, finding good agreement with the ΛCDM paradigm. For example, we constrain the equation-of-state parameter to w = -1.019_{-0.039}^{+0.048}. This paper is part of a set that analyses the final galaxy-clustering data set from BOSS. The measurements and likelihoods presented here are combined with others in Alam et al. to produce the final cosmological constraints from BOSS.

Response to traumatic brain injury neurorehabilitation through an artificial intelligence and statistics hybrid knowledge discovery from databases methodology.

PubMed

Gibert, Karina; García-Rudolph, Alejandro; García-Molina, Alberto; Roig-Rovira, Teresa; Bernabeu, Montse; Tormos, José María

2008-01-01

Develop a classificatory tool to identify different populations of patients with Traumatic Brain Injury based on the characteristics of deficit and response to treatment. A KDD framework where first, descriptive statistics of every variable was done, data cleaning and selection of relevant variables. Then data was mined using a generalization of Clustering based on rules (CIBR), an hybrid AI and Statistics technique which combines inductive learning (AI) and clustering (Statistics). A prior Knowledge Base (KB) is considered to properly bias the clustering; semantic constraints implied by the KB hold in final clusters, guaranteeing interpretability of the resultis. A generalization (Exogenous Clustering based on rules, ECIBR) is presented, allowing to define the KB in terms of variables which will not be considered in the clustering process itself, to get more flexibility. Several tools as Class panel graph are introduced in the methodology to assist final interpretation. A set of 5 classes was recommended by the system and interpretation permitted profiles labeling. From the medical point of view, composition of classes is well corresponding with different patterns of increasing level of response to rehabilitation treatments. All the patients initially assessable conform a single group. Severe impaired patients are subdivided in four profiles which clearly distinct response patterns. Particularly interesting the partial response profile, where patients could not improve executive functions. Meaningful classes were obtained and, from a semantics point of view, the results were sensibly improved regarding classical clustering, according to our opinion that hybrid AI & Stats techniques are more powerful for KDD than pure ones.

Low energy isomers of (H{sub 2}O){sub 25} from a hierarchical method based on Monte Carlo temperature basin paving and molecular tailoring approaches benchmarked by MP2 calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahu, Nityananda; Gadre, Shridhar R., E-mail: gadre@iitk.ac.in, E-mail: sotiris.xantheas@pnnl.gov; Rakshit, Avijit

2014-10-28

We report new global minimum candidate structures for the (H{sub 2}O){sub 25} cluster that are lower in energy than the ones reported previously and correspond to hydrogen bonded networks with 42 hydrogen bonds and an interior, fully coordinated water molecule. These were obtained as a result of a hierarchical approach based on initial Monte Carlo Temperature Basin Paving sampling of the cluster's Potential Energy Surface with the Effective Fragment Potential, subsequent geometry optimization using the Molecular Tailoring Approach with the fragments treated at the second order Møller-Plesset (MP2) perturbation (MTA-MP2) and final refinement of the entire cluster at the MP2more » level of theory. The MTA-MP2 optimized cluster geometries, constructed from the fragments, were found to be within <0.5 kcal/mol from the minimum geometries obtained from the MP2 optimization of the entire (H{sub 2}O){sub 25} cluster. In addition, the grafting of the MTA-MP2 energies yields electronic energies that are within <0.3 kcal/mol from the MP2 energies of the entire cluster while preserving their energy rank order. Finally, the MTA-MP2 approach was found to reproduce the MP2 harmonic vibrational frequencies, constructed from the fragments, quite accurately when compared to the MP2 ones of the entire cluster in both the HOH bending and the OH stretching regions of the spectra.« less

The Coulombic Lattice Potential of Ionic Compounds: The Cubic Perovskites.

ERIC Educational Resources Information Center

Francisco, E.; And Others

1988-01-01

Presents coulombic models representing the particles of a system by point charges interacting through Coulomb's law to explain coulombic lattice potential. Uses rubidium manganese trifluoride as an example of cubic perovskite structure. Discusses the effects on cluster properties. (CW)

Photoelectron Spectroscopic and Theoretical Study of B-16(-) and B-16(2-): An All-Boron Naphthalene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sergeeva, Alina P.; Zubarev, Dmitry Y.; Zhai, Hua Jin

Although boron clusters were experimentally studied shortly after the discovery of the fullerenes, their structural characterization was only possible fairly recently when we combined photoelectron spectroscopy (PES) and theoretical calculations to investigate the structures and bonding of boron clusters. Early theoretical studies indicated that small boron clusters do not assume cage-like structures, which are common in bulk boron and compounds; instead, planar or quasi-planar structures were suggested. The combined PES and theoretical studies show indeed boron clusters with up to 15 atom are planar, and only at B20 does a three-dimensional (3D) structure (double ring) become energetically competitive, whereas B20-more » still remains planar. A recent ion mobility and theoretical study showed that for Bn + the doublering 3D structure becomes competitive at B16 +7.« less

Antisense oligonucleotide therapeutics for iron-sulphur cluster deficiency myopathy.

PubMed

Kollberg, Gittan; Holme, Elisabeth

2009-12-01

Iron-sulphur cluster deficiency myopathy is caused by a deep intronic mutation in ISCU resulting in inclusion of a cryptic exon in the mature mRNA. ISCU encodes the iron-sulphur cluster assembly protein IscU. Iron-sulphur clusters are essential for most basic redox transformations including the respiratory-chain function. Most patients are homozygous for the mutation with a phenotype characterized by a non-progressive myopathy with childhood onset of early fatigue, dyspnoea and palpitation on trivial exercise. A more severe phenotype with early onset of a slowly progressive severe muscle weakness, severe exercise intolerance and cardiomyopathy is caused by a missense mutation in compound with the intronic mutation. Treatment of cultured fibroblasts derived from three homozygous patients with an antisense phosphorodiamidate morpholino oligonucleotide for 48 h resulted in 100% restoration of the normal splicing pattern. The restoration was stable and after 21 days the correctly spliced mRNA still was the dominating RNA species.

Multiple co-clustering based on nonparametric mixture models with heterogeneous marginal distributions

PubMed Central

Yoshimoto, Junichiro; Shimizu, Yu; Okada, Go; Takamura, Masahiro; Okamoto, Yasumasa; Yamawaki, Shigeto; Doya, Kenji

2017-01-01

We propose a novel method for multiple clustering, which is useful for analysis of high-dimensional data containing heterogeneous types of features. Our method is based on nonparametric Bayesian mixture models in which features are automatically partitioned (into views) for each clustering solution. This feature partition works as feature selection for a particular clustering solution, which screens out irrelevant features. To make our method applicable to high-dimensional data, a co-clustering structure is newly introduced for each view. Further, the outstanding novelty of our method is that we simultaneously model different distribution families, such as Gaussian, Poisson, and multinomial distributions in each cluster block, which widens areas of application to real data. We apply the proposed method to synthetic and real data, and show that our method outperforms other multiple clustering methods both in recovering true cluster structures and in computation time. Finally, we apply our method to a depression dataset with no true cluster structure available, from which useful inferences are drawn about possible clustering structures of the data. PMID:29049392

Semisupervised Clustering by Iterative Partition and Regression with Neuroscience Applications

PubMed Central

Qian, Guoqi; Wu, Yuehua; Ferrari, Davide; Qiao, Puxue; Hollande, Frédéric

2016-01-01

Regression clustering is a mixture of unsupervised and supervised statistical learning and data mining method which is found in a wide range of applications including artificial intelligence and neuroscience. It performs unsupervised learning when it clusters the data according to their respective unobserved regression hyperplanes. The method also performs supervised learning when it fits regression hyperplanes to the corresponding data clusters. Applying regression clustering in practice requires means of determining the underlying number of clusters in the data, finding the cluster label of each data point, and estimating the regression coefficients of the model. In this paper, we review the estimation and selection issues in regression clustering with regard to the least squares and robust statistical methods. We also provide a model selection based technique to determine the number of regression clusters underlying the data. We further develop a computing procedure for regression clustering estimation and selection. Finally, simulation studies are presented for assessing the procedure, together with analyzing a real data set on RGB cell marking in neuroscience to illustrate and interpret the method. PMID:27212939

Correlated proton-electron hole dynamics in protonated water clusters upon extreme ultraviolet photoionization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zheng; Vendrell, Oriol

2016-01-13

The ultrafast nuclear and electronic dynamics of protonated water clusters H+(H2O)n after extreme ultraviolet photoionization is investigated. In particular, we focus on cluster cations with n = 3, 6, and 21. Upon ionization, two positive charges are present in the cluster related to the excess proton and the missing electron, respectively. A correlation is found between the cluster's geometrical conformation and initial electronic energy with the size of the final fragments produced. As a result, for situations in which the electron hole and proton are initially spatially close, the two entities become correlated and separate in a time-scale of 20more » to 40 fs driven by strong non-adiabatic effects.« less

Effects of temperature and pressure on the nucleation and growth of silver clusters from supersaturated vapor: A molecular dynamics analysis

NASA Astrophysics Data System (ADS)

Wang, Qin; Xie, Hui; Chen, Yongshi; Liu, Chao

2017-04-01

The nucleation and growth of silver nanoparticles in the supersaturated system are investigated by molecular dynamics simulation at different temperatures and pressures. The variety of the atoms in the biggest cluster and the size of average clusters in the system versus the time are estimated to reveal the relationship between the nucleation as well as cluster growth. The nucleation rates in different situations are calculated with the threshold method. The effect of temperature and pressure on the nucleation rate is identified as obeying a linear function. Finally, the development of basal elements, such as monomers, dimers and trimmers, is revealed how the temperature and pressure affect the nucleation and growth of the silver cluster.

The cluster galaxy circular velocity function

NASA Astrophysics Data System (ADS)

Desai, V.; Dalcanton, J. J.; Mayer, L.; Reed, D.; Quinn, T.; Governato, F.

2004-06-01

We present galaxy circular velocity functions (GCVFs) for 34 low-redshift (z<~ 0.15) clusters identified in the Sloan Digital Sky Survey (SDSS), for 15 clusters drawn from dark matter simulations of hierarchical structure growth in a ΛCDM cosmology, and for ~22 000 SDSS field galaxies. We find that the simulations successfully reproduce the shape, amplitude and scatter in the observed distribution of cluster galaxy circular velocities. The power-law slope of the observed cluster GCVF is ~-2.4, independent of cluster velocity dispersion. The average slope of the simulated GCVFs is somewhat steeper, although formally consistent given the errors. We find that the effects of baryons on galaxy rotation curves is to flatten the simulated cluster GCVF into better agreement with observations. The cumulative GCVFs of the simulated clusters are very similar across a wide range of cluster masses, provided individual subhalo circular velocities are scaled by the circular velocities of the parent cluster. The scatter is consistent with that measured in the cumulative, scaled observed cluster GCVF. Finally, the observed field GCVF deviates significantly from a power law, being flatter than the cluster GCVF at circular velocities less than 200 km s-1.

CO2 Cluster Ion Beam, an Alternative Projectile for Secondary Ion Mass Spectrometry

NASA Astrophysics Data System (ADS)

Tian, Hua; Maciążek, Dawid; Postawa, Zbigniew; Garrison, Barbara J.; Winograd, Nicholas

2016-09-01

The emergence of argon-based gas cluster ion beams for SIMS experiments opens new possibilities for molecular depth profiling and 3D chemical imaging. These beams generally leave less surface chemical damage and yield mass spectra with reduced fragmentation compared with smaller cluster projectiles. For nanoscale bioimaging applications, however, limited sensitivity due to low ionization probability and technical challenges of beam focusing remain problematic. The use of gas cluster ion beams based upon systems other than argon offer an opportunity to resolve these difficulties. Here we report on the prospects of employing CO2 as a simple alternative to argon. Ionization efficiency, chemical damage, sputter rate, and beam focus are investigated on model compounds using a series of CO2 and Ar cluster projectiles (cluster size 1000-5000) with the same mass. The results show that the two projectiles are very similar in each of these aspects. Computer simulations comparing the impact of Ar2000 and (CO2)2000 on an organic target also confirm that the CO2 molecules in the cluster projectile remain intact, acting as a single particle of m/z 44. The imaging resolution employing CO2 cluster projectiles is improved by more than a factor of two. The advantage of CO2 versus Ar is also related to the increased stability which, in addition, facilitates the operation of the gas cluster ion beams (GCIB) system at lower backing pressure.

Cluster analysis based on dimensional information with applications to feature selection and classification

NASA Technical Reports Server (NTRS)

Eigen, D. J.; Fromm, F. R.; Northouse, R. A.

1974-01-01

A new clustering algorithm is presented that is based on dimensional information. The algorithm includes an inherent feature selection criterion, which is discussed. Further, a heuristic method for choosing the proper number of intervals for a frequency distribution histogram, a feature necessary for the algorithm, is presented. The algorithm, although usable as a stand-alone clustering technique, is then utilized as a global approximator. Local clustering techniques and configuration of a global-local scheme are discussed, and finally the complete global-local and feature selector configuration is shown in application to a real-time adaptive classification scheme for the analysis of remote sensed multispectral scanner data.

The application of mixed recommendation algorithm with user clustering in the microblog advertisements promotion

NASA Astrophysics Data System (ADS)

Gong, Lina; Xu, Tao; Zhang, Wei; Li, Xuhong; Wang, Xia; Pan, Wenwen

2017-03-01

The traditional microblog recommendation algorithm has the problems of low efficiency and modest effect in the era of big data. In the aim of solving these issues, this paper proposed a mixed recommendation algorithm with user clustering. This paper first introduced the situation of microblog marketing industry. Then, this paper elaborates the user interest modeling process and detailed advertisement recommendation methods. Finally, this paper compared the mixed recommendation algorithm with the traditional classification algorithm and mixed recommendation algorithm without user clustering. The results show that the mixed recommendation algorithm with user clustering has good accuracy and recall rate in the microblog advertisements promotion.

Temporal Clustering of Regional-Scale Extreme Precipitation Events in Southern Switzerland

NASA Astrophysics Data System (ADS)

Barton, Yannick; Giannakaki, Paraskevi; Von Waldow, Harald; Chevalier, Clément; Pfhal, Stephan; Martius, Olivia

2017-04-01

Temporal clustering of extreme precipitation events on subseasonal time scales is a form of compound extremes and is of crucial importance for the formation of large-scale flood events. Here, the temporal clustering of regional-scale extreme precipitation events in southern Switzerland is studied. These precipitation events are relevant for the flooding of lakes in southern Switzerland and northern Italy. This research determines whether temporal clustering is present and then identifies the dynamics that are responsible for the clustering. An observation-based gridded precipitation dataset of Swiss daily rainfall sums and ECMWF reanalysis datasets are used. To analyze the clustering in the precipitation time series a modified version of Ripley's K function is used. It determines the average number of extreme events in a time period, to characterize temporal clustering on subseasonal time scales and to determine the statistical significance of the clustering. Significant clustering of regional-scale precipitation extremes is found on subseasonal time scales during the fall season. Four high-impact clustering episodes are then selected and the dynamics responsible for the clustering are examined. During the four clustering episodes, all heavy precipitation events were associated with an upperlevel breaking Rossby wave over western Europe and in most cases strong diabatic processes upstream over the Atlantic played a role in the amplification of these breaking waves. Atmospheric blocking downstream over eastern Europe supported this wave breaking during two of the clustering episodes. During one of the clustering periods, several extratropical transitions of tropical cyclones in the Atlantic contributed to the formation of high-amplitude ridges over the Atlantic basin and downstream wave breaking. During another event, blocking over Alaska assisted the phase locking of the Rossby waves downstream over the Atlantic.

Systems and methods for producing metal clusters; functionalized surfaces; and droplets including solvated metal ions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cooks, Robert Graham; Li, Anyin; Luo, Qingjie

The invention generally relates to systems and methods for producing metal clusters; functionalized surfaces; and droplets including solvated metal ions. In certain aspects, the invention provides methods that involve providing a metal and a solvent. The methods additionally involve applying voltage to the solvated metal to thereby produce solvent droplets including ions of the metal containing compound, and directing the solvent droplets including the metal ions to a target. In certain embodiments, once at the target, the metal ions can react directly or catalyze reactions.

Systems and methods for producing metal clusters; functionalized surfaces; and droplets including solvated metal ions

DOEpatents

Cooks, Robert Graham; Li, Anyin; Luo, Qingjie

2017-01-24

The invention generally relates to systems and methods for producing metal clusters; functionalized surfaces; and droplets including solvated metal ions. In certain aspects, the invention provides methods that involve providing a metal and a solvent. The methods additionally involve applying voltage to the solvated metal to thereby produce solvent droplets including ions of the metal containing compound, and directing the solvent droplets including the metal ions to a target. In certain embodiments, once at the target, the metal ions can react directly or catalyze reactions.

How African American English-Speaking First Graders Segment and Rhyme Words and Nonwords With Final Consonant Clusters.

PubMed

Shollenbarger, Amy J; Robinson, Gregory C; Taran, Valentina; Choi, Seo-Eun

2017-10-05

This study explored how typically developing 1st grade African American English (AAE) speakers differ from mainstream American English (MAE) speakers in the completion of 2 common phonological awareness tasks (rhyming and phoneme segmentation) when the stimulus items were consonant-vowel-consonant-consonant (CVCC) words and nonwords. Forty-nine 1st graders met criteria for 2 dialect groups: AAE and MAE. Three conditions were tested in each rhyme and segmentation task: Real Words No Model, Real Words With a Model, and Nonwords With a Model. The AAE group had significantly more responses that rhymed CVCC words with consonant-vowel-consonant words and segmented CVCC words as consonant-vowel-consonant than the MAE group across all experimental conditions. In the rhyming task, the presence of a model in the real word condition elicited more reduced final cluster responses for both groups. In the segmentation task, the MAE group was at ceiling, so only the AAE group changed across the different stimulus presentations and reduced the final cluster less often when given a model. Rhyming and phoneme segmentation performance can be influenced by a child's dialect when CVCC words are used.

Synthesis and structures of new niobium cluster compounds with pyridinium cations: (PyrH){sub 2}[Nb{sub 6}Cl{sub 18}].EtOH (Pyr: pyridine, Et: ethyl) and the cubic modification of (PyrH){sub 2}[Nb{sub 6}Cl{sub 18}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flemming, Anke; Hoppe, Alessandra; Koeckerling, Martin

2008-10-15

Slow crystallization of (PyrH){sub 2}[Nb{sub 6}Cl{sub 18}] from hot ethanol solution affords triclinic (PyrH){sub 2}[Nb{sub 6}Cl{sub 18}].EtOH. Treatment of [Nb{sub 6}Cl{sub 14}(H{sub 2}O){sub 4}].4H{sub 2}O with pyridine in a methanol solution gives the second title compound, the cubic modification of (PyrH){sub 2}[Nb{sub 6}Cl{sub 18}]. Both structures were determined by single crystal X-ray diffraction, (PyrH){sub 2}[Nb{sub 6}Cl{sub 18}].EtOH: P1-bar , a=9.3475(3), b=9.3957(3), c=10.8600(3) A, {alpha}=82.582(1){sup o}, {beta}=78.608(1){sup o}, and {gamma}=78.085(1){sup o}, Z=1, R{sub 1}(F)/wR{sub 2}(F{sup 2})=0.0254/0.0573, cub.-(PyrH){sub 2}[Nb{sub 6}Cl{sub 18}]: Fd3-bar m, a=19.935(2) A, Z=8, R{sub 1}(F)/wR{sub 2}(F{sup 2})=0.0557/0.1796. The cluster compounds contain isolated, molecular [Nb{sub 6}Cl{sup i}{sub 12}Cl{sup a}{sub 6}]{supmore » 2-} cluster anions with an octahedron of metal atoms edge bridged by chlorido ligands with additional ones on all the six exo positions. These cluster anions are separated by the pyridinium cations and ethanol solvent molecules, respectively. For the cubic modification of (PyrH){sub 2}[Nb{sub 6}Cl{sub 18}], a structural comparison is given to the known rhombohedral modification using the group-subgroup relations as expressed by a Baernighausen tree. - Graphical abstract: The synthesis and structure of a second cubic modification of (PyrH){sub 2}[Nb{sub 6}Cl{sub 18}] and of the new (PyrH){sub 2}[Nb{sub 6}Cl{sub 18}].EtOH are reported, both of which contain isolated niobium halide cluster anions with an octahedral core of metal atoms.« less

Selection of quantum chemical descriptors by chemometric methods in the study of antioxidant activity of flavonoid compounds

NASA Astrophysics Data System (ADS)

Weber, K. C.; Honório, K. M.; da Silva, S. L.; Mercadante, R.; da Silva, A. B. F.

In the present study, the aim was to select electronic properties responsible for free radical scavenging ability of a set of 25 flavonoid compounds employing chemometric methods. Electronic parameters were calculated using the AM1 semiempirical method, and chemometric methods (principal component analysis, hierarchical cluster analysis, and k-nearest neighbor) were used with the aim to build models able to find relationships between electronic features and the antioxidant activity presented by the compounds studied. According to these models, four electronic variables can be considered important to discriminate more and less antioxidant flavonoid compounds: polarizability (α), charge at carbon 3 (QC3), total charge at substituent 5 (QS5), and total charge at substituent 3' (QS3'). The features found as being responsible for the antioxidant activity of the flavonoid compounds studied are consistent with previous results found in the literature. The results obtained can also bring improvements in the search for better antioxidant flavonoid compounds.

Japanese Listeners' Perceptions of Phonotactic Violations

ERIC Educational Resources Information Center

Fais, Laurel; Kajikawa, Sachiyo; Werker, Janet; Amano, Shigeaki

2005-01-01

The canonical form for Japanese words is (Consonant)Vowel(Consonant) Vowel[approximately]. However, a regular process of high vowel devoicing between voiceless consonants and word-finally after voiceless consonants results in consonant clusters and word-final consonants, apparent violations of that phonotactic pattern. We investigated Japanese…

Aroma compounds generation in citrate metabolism of Enterococcus faecium: Genetic characterization of type I citrate gene cluster.

PubMed

Martino, Gabriela P; Quintana, Ingrid M; Espariz, Martín; Blancato, Victor S; Magni, Christian

2016-02-02

Enterococcus is one of the most controversial genera belonging to Lactic Acid Bacteria. Research involving this microorganism reflects its dual behavior as regards its safety. Although it has also been associated to nosocomial infections, natural occurrence of Enterococcus faecium in food contributes to the final quality of cheese. This bacterium is capable of fermenting citrate, which is metabolized to pyruvate and finally derives in the production of the aroma compounds diacetyl, acetoin and 2,3 butanediol. Citrate metabolism was studied in E. faecium but no data about genes related to these pathways have been described. A bioinformatic approach allowed us to differentiate cit(-) (no citrate metabolism genes) from cit(+) strains in E. faecium. Furthermore, we could classify them according to genes encoding for the transcriptional regulator, the oxaloacetate decarboxylase and the citrate transporter. Thus we defined type I organization having CitI regulator (DeoR family), CitM cytoplasmic soluble oxaloacetate decarboxylase (Malic Enzyme family) and CitP citrate transporter (2-hydroxy-carboxylate transporter family) and type II organization with CitO regulator (GntR family), OAD membrane oxaloacetate decarboxylase complex (Na(+)-transport decarboxylase enzyme family) and CitH citrate transporter (CitMHS family). We isolated and identified 17 E. faecium strains from regional cheeses. PCR analyses allowed us to classify them as cit(-) or cit(+). Within the latter classification we could differentiate type I but no type II organization. Remarkably, we came upon E. faecium GM75 strain which carries the insertion sequence IS256, involved in adaptative and evolution processes of bacteria related to Staphylococcus and Enterococcus genera. In this work we describe the differential behavior in citrate transport, metabolism and aroma generation of three strains and we present results that link citrate metabolism and genetic organizations in E. faecium for the first time. Copyright © 2015 Elsevier B.V. All rights reserved.

Prediction of tautomer ratios by embedded-cluster integral equation theory

NASA Astrophysics Data System (ADS)

Kast, Stefan M.; Heil, Jochen; Güssregen, Stefan; Schmidt, K. Friedemann

2010-04-01

The "embedded cluster reference interaction site model" (EC-RISM) approach combines statistical-mechanical integral equation theory and quantum-chemical calculations for predicting thermodynamic data for chemical reactions in solution. The electronic structure of the solute is determined self-consistently with the structure of the solvent that is described by 3D RISM integral equation theory. The continuous solvent-site distribution is mapped onto a set of discrete background charges ("embedded cluster") that represent an additional contribution to the molecular Hamiltonian. The EC-RISM analysis of the SAMPL2 challenge set of tautomers proceeds in three stages. Firstly, the group of compounds for which quantitative experimental free energy data was provided was taken to determine appropriate levels of quantum-chemical theory for geometry optimization and free energy prediction. Secondly, the resulting workflow was applied to the full set, allowing for chemical interpretations of the results. Thirdly, disclosure of experimental data for parts of the compounds facilitated a detailed analysis of methodical issues and suggestions for future improvements of the model. Without specifically adjusting parameters, the EC-RISM model yields the smallest value of the root mean square error for the first set (0.6 kcal mol-1) as well as for the full set of quantitative reaction data (2.0 kcal mol-1) among the SAMPL2 participants.

Investigation of electronic structure of tri- and tetranuclear molybdenum clusters by X-ray photoelectron and emission spectroscopies and quantum chemical methods

NASA Astrophysics Data System (ADS)

Kryuchkova, Natalya A.; Syrokvashin, Mikhail M.; Gushchin, Artem L.; Korotaev, Evgeniy V.; Kalinkin, Alexander V.; Laricheva, Yuliya A.; Sokolov, Maxim N.

2018-02-01

Charge state studies of compounds [Mo3S4(tu)8(H2O)]Cl4·4H2O (1), [Mo3S4Cl3(dbbpy)3]Cl·5H2O (2), [Mo3S4(CuCl)Cl3(dbbpy)3][CuCl2] (3), containing {Mo3S4}4+ and {Mo3CuS4}5+ cluster cores bearing terminal thiourea (tu) or 4,4‧-di-tert-butyl-2,2‧-bipyridine (dbbpy) ligands, have been performed by X-ray photoelectron and X-ray emission spectroscopies combined with quantum chemical calculations. The best agreement between theory and experiments has been obtained using the B3LYP method. According to the experimental and calculated data, the Mo atoms are in the oxidation state 4+ for all compounds. The energies and shapes of the Cu2p lines indicate formal oxidation states of Cu as 1+. The coordination of Cu(I) to the cluster {Mo3S4} in 3 does not lead to significant changes in the charge state of the molybdenum atoms and the {Mo3S4} unit can be considered as a tridentate metallothia crown ether.

Complete genome sequence of Jiangella gansuensis strain YIM 002T (DSM 44835T), the type species of the genus Jiangella and source of new antibiotic compounds

DOE PAGES

Jiao, Jian-Yu; Carro, Lorena; Liu, Lan; ...

2017-02-03

Jiangella gansuensis strain YIM 002 T is the type strain of the type species of the genus Jiangella, which is at the present time composed of five species, and was isolated from desert soil sample in Gansu Province (China). The five strains of this genus are clustered in a monophyletic group when closer actinobacterial genera are used to infer a 16S rRNA gene sequence phylogeny. The study of this genome is part of the Genomic Encyclopedia of Bacteria and Archaea project, and here we describe the complete genome sequence and annotation of this taxon. The genome of J. gansuensis strainmore » YIM 002T contains a single scaffold of size 5,585,780 bp, which involves 149 pseudogenes, 4905 protein-coding genes and 50 RNA genes, including 2520 hypothetical proteins and 4 rRNA genes. From the investigation of genome sizes of Jiangella species, J. gansuensis shows a smaller size, which indicates this strain might have discarded too much genetic information to adapt to desert environment. Seven new compounds from this bacterium have recently been described; however, its potential should be higher, as secondary metabolite gene cluster analysis predicted 60 gene clusters, including the potential to produce the pristinamycin.« less

Complete genome sequence of Jiangella gansuensis strain YIM 002T (DSM 44835T), the type species of the genus Jiangella and source of new antibiotic compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiao, Jian-Yu; Carro, Lorena; Liu, Lan

Jiangella gansuensis strain YIM 002 T is the type strain of the type species of the genus Jiangella, which is at the present time composed of five species, and was isolated from desert soil sample in Gansu Province (China). The five strains of this genus are clustered in a monophyletic group when closer actinobacterial genera are used to infer a 16S rRNA gene sequence phylogeny. The study of this genome is part of the Genomic Encyclopedia of Bacteria and Archaea project, and here we describe the complete genome sequence and annotation of this taxon. The genome of J. gansuensis strainmore » YIM 002T contains a single scaffold of size 5,585,780 bp, which involves 149 pseudogenes, 4905 protein-coding genes and 50 RNA genes, including 2520 hypothetical proteins and 4 rRNA genes. From the investigation of genome sizes of Jiangella species, J. gansuensis shows a smaller size, which indicates this strain might have discarded too much genetic information to adapt to desert environment. Seven new compounds from this bacterium have recently been described; however, its potential should be higher, as secondary metabolite gene cluster analysis predicted 60 gene clusters, including the potential to produce the pristinamycin.« less

Tunable Quantum Spin Liquidity in Mo3O13 Cluster Mott Insulators

NASA Astrophysics Data System (ADS)

Akbari-Sharbaf, Arash; Ziat, Djamel; Verrier, Aime; Quilliam, Jeffrey A.; Sinclair, Ryan; Zhou, Haidong D.; Sun, Xuefeng F.

A study of a tunable quantum spin liquid (QSL) phase in the compound Li2In1- x ScxMo3O8 (x = 0.2, 0.4, 0.6, 0.8, 1) will be presented. Crystal structure of these compounds can be viewed as Mo ions arranged on an asymmetric Kagome lattice (KL), with two different Mo-Mo bond lengths, separated by nonmagnetic layers composed of Li, In, and Sc ions. Using X-ray diffraction spectroscopy, muon spin relaxation spectroscopy, bulk magnetic susceptibility and specific heat measurements we show that by changing the composition of the nonmagnetic layers we can drive the system from an ordered antiferromagnetic state to a quantum spin liquid state. The mechanism responsible for the tunability of the magnetic phase in this class of materials may be associated with the degree of asymmetry of the KL controlled by the composition of the nonmagnetic layers. For high degree of asymmetry the constraint on the electronic distribution leads to a configuration of Mo3O8 clusters with net spin-1/2 per cluster arrange on a triangular lattice and long range antiferromagnetic order. For low degree of asymmetry the electronic distribution leads to a magnetic phase with QSL character. We acknowledge support from NSERC and CFREF.

CHIPMUNK: A Virtual Synthesizable Small-Molecule Library for Medicinal Chemistry, Exploitable for Protein-Protein Interaction Modulators.

PubMed

Humbeck, Lina; Weigang, Sebastian; Schäfer, Till; Mutzel, Petra; Koch, Oliver

2018-03-20

A common issue during drug design and development is the discovery of novel scaffolds for protein targets. On the one hand the chemical space of purchasable compounds is rather limited; on the other hand artificially generated molecules suffer from a grave lack of accessibility in practice. Therefore, we generated a novel virtual library of small molecules which are synthesizable from purchasable educts, called CHIPMUNK (CHemically feasible In silico Public Molecular UNiverse Knowledge base). Altogether, CHIPMUNK covers over 95 million compounds and encompasses regions of the chemical space that are not covered by existing databases. The coverage of CHIPMUNK exceeds the chemical space spanned by the Lipinski rule of five to foster the exploration of novel and difficult target classes. The analysis of the generated property space reveals that CHIPMUNK is well suited for the design of protein-protein interaction inhibitors (PPIIs). Furthermore, a recently developed structural clustering algorithm (StruClus) for big data was used to partition the sub-libraries into meaningful subsets and assist scientists to process the large amount of data. These clustered subsets also contain the target space based on ChEMBL data which was included during clustering. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modelling the magnetic behaviour of square-pyramidal Co(II)5 aggregates: tuning SMM behaviour through variations in the ligand shell.

PubMed

Klöwer, Frederik; Lan, Yanhua; Nehrkorn, Joscha; Waldmann, Oliver; Anson, Christopher E; Powell, Annie K

2009-07-27

Three new mu4-bridged Co(II)5 clusters with similar core motifs have been synthesised with the use of N-tert-butyldiethanolamine (tbdeaH2) and pivalic acid (piv): [Co(II)5(mu4-N3)(tbdea)2(mu-piv)4(piv)(CH3CN)2].CH3CN (1), [Co(II)5(mu4-Cl)(Cl)(tbdea)2(mu-piv)4(pivH)2] (2) and [Co(II)5(mu4-N3)(Cl)(tbdea)2(mu-piv)4(pivH)2] (3). Magnetic measurements were performed for all three compounds. It was found that while the chloride-bridged cluster 2 does not show an out-of-phase signal, which excludes single-molecule magnet (SMM) behaviour, the azide-bridged compounds 1 and 3 show out-of-phase signals as well as frequency dependence of the ac susceptibility, as expected for SMMs. We confirmed that 1 is a SMM with zero-field quantum tunnelling of the magnetisation at 1.8 K. Compound 3 is likely a SMM with a blocking temperature well below 1.8 K. We established a physical model to fit the chiT versus T and M versus B curves of the three compounds to reproduce the observed SMM trend. The analysis showed that small changes in the ligand shell modify not only the magnitude of exchange constants, but also affect the J and g matrices in a non-trivial way.

Interactive K-Means Clustering Method Based on User Behavior for Different Analysis Target in Medicine.

PubMed

Lei, Yang; Yu, Dai; Bin, Zhang; Yang, Yang

2017-01-01

Clustering algorithm as a basis of data analysis is widely used in analysis systems. However, as for the high dimensions of the data, the clustering algorithm may overlook the business relation between these dimensions especially in the medical fields. As a result, usually the clustering result may not meet the business goals of the users. Then, in the clustering process, if it can combine the knowledge of the users, that is, the doctor's knowledge or the analysis intent, the clustering result can be more satisfied. In this paper, we propose an interactive K -means clustering method to improve the user's satisfactions towards the result. The core of this method is to get the user's feedback of the clustering result, to optimize the clustering result. Then, a particle swarm optimization algorithm is used in the method to optimize the parameters, especially the weight settings in the clustering algorithm to make it reflect the user's business preference as possible. After that, based on the parameter optimization and adjustment, the clustering result can be closer to the user's requirement. Finally, we take an example in the breast cancer, to testify our method. The experiments show the better performance of our algorithm.

The chemical nature of phenolic compounds determines their toxicity and induces distinct physiological responses in Saccharomyces cerevisiae in lignocellulose hydrolysates

PubMed Central

2014-01-01

We investigated the severity of the inhibitory effects of 13 phenolic compounds usually found in spruce hydrolysates (4-hydroxy-3-methoxycinnamaldehyde, homovanilyl alcohol, vanillin, syringic acid, vanillic acid, gallic acid, dihydroferulic acid, p-coumaric acid, hydroquinone, ferulic acid, homovanillic acid, 4-hydroxybenzoic acid and vanillylidenacetone). The effects of the selected compounds on cell growth, biomass yield and ethanol yield were studied and the toxic concentration threshold was defined for each compound. Using Ethanol Red, the popular industrial strain of Saccharomyces cerevisiae, we found the most toxic compound to be 4-hydroxy-3-methoxycinnamaldehyde which inhibited growth at a concentration of 1.8 mM. We also observed that toxicity did not generally follow a trend based on the aldehyde, acid, ketone or alcohol classification of phenolic compounds, but rather that other structural properties such as additional functional groups attached to the compound may determine its toxicity. Three distinctive growth patterns that effectively clustered all the compounds involved in the screening into three categories. We suggest that the compounds have different cellular targets, and that. We suggest that the compounds have different cellular targets and inhibitory mechanisms in the cells, also compounds who share similar pattern on cell growth may have similar inhibitory effect and mechanisms of inhibition. PMID:24949277

Identifying microbially mediated transformations of DOC across season and tide from simultaneous changes in whole community gene expression and in mass spectra generated by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FTICR-MS)

NASA Astrophysics Data System (ADS)

Ballantyne, F.; Medeiros, P. M.; Moran, M. A.; Song, C.; Whitman, W. B.; Washington, B.; Yu, M.; Lee, J.

2017-12-01

Despite the advent of methods enabling high resolution characterization of metabolic activity and of organic matter, linking microbial metabolism to organic matter transformations remains a challenge. By sequencing metatranscriptomes and using Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FTICR-MS) to characterize organic matter (OM) at the beginning and at the end of incubations of estuarine water across tide and season, we sought to link observed a changes in OM composition to microbial metabolism. We used linear models and K means clustering to identify clusters of genes that responded coherently across season, which accounted for most of the variability in gene expression, over tidal regime, which explained the majority of the remaining variation, and over time during the 24 hour incubations. We used an approach from the field of signal processing, that to our knowledge has not been used to analyze FTICR-MS data, to identify formulae of compounds that changed in concentration during the incubations. This approach, based on the discrete wavelet transform (DWT), allowed us to overcome some of the challenges associated with analyzing FTICR-MS data: variable ionization of organic compounds, signal suppression by high concentration compounds, and uncertainty about how to normalize changes across spectra. We were able to link clusters of metabolic and transporter genes to changes in OM composition, and uniquely identify genes based on their cross correlation with changes in FTICR mass spectra. Our approach for analyzing FTICR- MS data enables more robust inference about OM transformations, and linking high resolution changes in gene expression and in OM data during incubations represents an important step toward formulating models of microbial metabolism relevant for predicting biogeochemically relevant C fluxes.

Metabolomic Profiling and Genomic Study of a Marine Sponge-Associated Streptomyces sp

PubMed Central

Viegelmann, Christina; Margassery, Lekha Menon; Kennedy, Jonathan; Zhang, Tong; O’Brien, Ciarán; O’Gara, Fergal; Morrissey, John P.; Dobson, Alan D. W.; Edrada-Ebel, RuAngelie

2014-01-01

Metabolomics and genomics are two complementary platforms for analyzing an organism as they provide information on the phenotype and genotype, respectively. These two techniques were applied in the dereplication and identification of bioactive compounds from a Streptomyces sp. (SM8) isolated from the sponge Haliclona simulans from Irish waters. Streptomyces strain SM8 extracts showed antibacterial and antifungal activity. NMR analysis of the active fractions proved that hydroxylated saturated fatty acids were the major components present in the antibacterial fractions. Antimycin compounds were initially putatively identified in the antifungal fractions using LC-Orbitrap. Their presence was later confirmed by comparison to a standard. Genomic analysis of Streptomyces sp. SM8 revealed the presence of multiple secondary metabolism gene clusters, including a gene cluster for the biosynthesis of the antifungal antimycin family of compounds. The antimycin gene cluster of Streptomyces sp. SM8 was inactivated by disruption of the antimycin biosynthesis gene antC. Extracts from this mutant strain showed loss of antimycin production and significantly less antifungal activity than the wild-type strain. Three butenolides, 4,10-dihydroxy-10-methyl-dodec-2-en-1,4-olide (1), 4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olide (2), and 4-hydroxy-10-methyl-11-oxo-dodec-2-en-1,4-olide (3) that had previously been reported from marine Streptomyces species were also isolated from SM8. Comparison of the extracts of Streptomyces strain SM8 and its host sponge, H. simulans, using LC-Orbitrap revealed the presence of metabolites common to both extracts, providing direct evidence linking sponge metabolites to a specific microbial symbiont. PMID:24893324

Canonical PSO Based K-Means Clustering Approach for Real Datasets.

PubMed

Dey, Lopamudra; Chakraborty, Sanjay

2014-01-01

"Clustering" the significance and application of this technique is spread over various fields. Clustering is an unsupervised process in data mining, that is why the proper evaluation of the results and measuring the compactness and separability of the clusters are important issues. The procedure of evaluating the results of a clustering algorithm is known as cluster validity measure. Different types of indexes are used to solve different types of problems and indices selection depends on the kind of available data. This paper first proposes Canonical PSO based K-means clustering algorithm and also analyses some important clustering indices (intercluster, intracluster) and then evaluates the effects of those indices on real-time air pollution database, wholesale customer, wine, and vehicle datasets using typical K-means, Canonical PSO based K-means, simple PSO based K-means, DBSCAN, and Hierarchical clustering algorithms. This paper also describes the nature of the clusters and finally compares the performances of these clustering algorithms according to the validity assessment. It also defines which algorithm will be more desirable among all these algorithms to make proper compact clusters on this particular real life datasets. It actually deals with the behaviour of these clustering algorithms with respect to validation indexes and represents their results of evaluation in terms of mathematical and graphical forms.

Nitrodifluoraminoterphenyl compounds and processes

DOEpatents

Lerom, M.W.; Peters, H.M.

1975-07-08

This patent relates to the nitrodifluoraminoterphenyl compounds: 3,3''-bis (difluoramino)-2,2'' 4,4', 4'',6,6',6''-octanitro-m-terphenyl (DDONT) and 3,3''-bis(difluoramino)-2,2',2''4,4',4'',6,6',6''-nonanitro-m-terphenyl (DDNONA). Procedures are described wherein diamino precursors of the indicated compounds are prepared and the final compounds are obtained by a fluorination operation. The compounds are highly energetic and suitable for use as explosives and particularly in exploding bridge wire (EBW) detonators. (auth)

The Effect of Cu Powder During Friction Stir Welding on Microstructure and Mechanical Properties of AA3003-H18

NASA Astrophysics Data System (ADS)

Abnar, B.; Kazeminezhad, M.; Kokabi, A. H.

2014-08-01

Friction stir welding (FSW) was used to join 3003-H18 non-heat-treatable aluminum alloy plates by adding copper powder. The copper powder was first added to the gap (0.1 and 0.2 mm) between two plates and then the FSW was performed. The specimens were joined at various rotational speeds of 800, 1000, and 1200 rpm at traveling speeds of 70 and 100 mm/min. The effects of rotational speed, second pass of FSW, and direction of second pass also were studied on copper particle distribution and formation of Al-Cu intermetallic compounds in the stir zone. The second pass of FSW was carried out in two ways; in line with the first pass direction (2F) and in the reverse direction of the first pass (FB). The microstructure, mechanical properties, and formation of intermetallic compounds type were investigated. In high copper powder compaction into the gap, large clusters were formed in the stir zone, while fine clusters and sound copper particles distribution were obtained in low powder compaction. The copper particle distribution and amount of Al-Cu intermetallic compounds were increased in the stir zone with increasing the rotational speed and applying the second pass. Al2Cu and AlCu intermetallic phases were formed in the stir zone and consequently the hardness was significantly increased. The copper particles and in situ intermetallic compounds were symmetrically distributed in both advancing and retreating sides of weld zone after FB passes. Thus, the wider area was reinforced by the intermetallic compounds. Also, the tensile test specimens tend to fracture from the coarse copper aggregation at the low rotational speeds. At high rotational speeds, the fracture locations are placed in HAZ and TMAZ.

Unusual analyte-matrix adduct ions and mechanism of their formation in MALDI TOF MS of benzene-1,3,5-tricarboxamide and urea compounds.

PubMed

Lou, Xianwen; Fransen, Michel; Stals, Patrick J M; Mes, Tristan; Bovee, Ralf; van Dongen, Joost J L; Meijer, E W

2013-09-01

Analyte-matrix adducts are normally absent under typical matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) conditions. Interestingly, though, in the analysis of several types of organic compounds synthesized in our laboratory, analyte-matrix adduct ion peaks were always recorded when common MALDI matrices such as 4-hydroxy-α-cyanocinnamic acid (CHCA) were used. These compounds are mainly those with a benzene-1,3,5-tricarboxamide (BTA) or urea moiety, which are important building blocks to make new functional supramolecular materials. The possible mechanism of the adduct formation was investigated. A shared feature of the compounds studied is that they can form intermolecular hydrogen bonding with matrices like CHCA. The intermolecular hydrogen bonding will make the association between analyte ions and matrix molecules stronger. As a result, the analyte ions and matrix molecules in MALDI clusters will become more difficult to be separated from each other. Furthermore, it was found that analyte ions were mainly adducted with matrix salts, which is probably due to the much lower volatility of the salts compared with that of their corresponding matrix acids. It seems that the analyte-matrix adduct formation for our compounds are caused by the incomplete evaporation of matrix molecules from the MALDI clusters because of the combined effects of enhanced intermolecular interaction between analyte-matrix and of the low volatility of matrix salts. Based on these findings, strategies to suppress the analyte-matrix adduction are briefly discussed. In return, the positive results of using these strategies support the proposed mechanism of the analyte-matrix adduct formation.

MCloud: Secure Provenance for Mobile Cloud Users

DTIC Science & Technology

2016-10-03

Feasibility of Smartphone Clouds , 2015 15th IEEE/ACM International Symposium on Cluster, Cloud and Grid Computing (CCGrid). 04-MAY- 15, Shenzhen, China...final decision. MCloud: Secure Provenance for Mobile Cloud Users Final Report Bogdan Carbunar Florida International University Computing and...Release; Distribution Unlimited UU UU UU UU 03-10-2016 31-May-2013 30-May-2016 Final Report: MCloud: Secure Provenance for Mobile Cloud Users The views

Identification of an unusual type II thioesterase in the dithiolopyrrolone antibiotics biosynthetic pathway.

PubMed

Zhai, Ying; Bai, Silei; Liu, Jingjing; Yang, Liyuan; Han, Li; Huang, Xueshi; He, Jing

2016-04-22

Dithiolopyrrolone group antibiotics characterized by an electronically unique dithiolopyrrolone heterobicyclic core are known for their antibacterial, antifungal, insecticidal and antitumor activities. Recently the biosynthetic gene clusters for two dithiolopyrrolone compounds, holomycin and thiomarinol, have been identified respectively in different bacterial species. Here, we report a novel dithiolopyrrolone biosynthetic gene cluster (aut) isolated from Streptomyces thioluteus DSM 40027 which produces two pyrrothine derivatives, aureothricin and thiolutin. By comparison with other characterized dithiolopyrrolone clusters, eight genes in the aut cluster were verified to be responsible for the assembly of dithiolopyrrolone core. The aut cluster was further confirmed by heterologous expression and in-frame gene deletion experiments. Intriguingly, we found that the heterogenetic thioesterase HlmK derived from the holomycin (hlm) gene cluster in Streptomyces clavuligerus significantly improved heterologous biosynthesis of dithiolopyrrolones in Streptomyces albus through coexpression with the aut cluster. In the previous studies, HlmK was considered invalid because it has a Ser to Gly point mutation within the canonical Ser-His-Asp catalytic triad of thioesterases. However, gene inactivation and complementation experiments in our study unequivocally demonstrated that HlmK is an active distinctive type II thioesterase that plays a beneficial role in dithiolopyrrolone biosynthesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Streptomyces scabies 87-22 contains a coronafacic acid-like biosynthetic cluster that contributes to plant-microbe interactions.

PubMed

Bignell, Dawn R D; Seipke, Ryan F; Huguet-Tapia, José C; Chambers, Alan H; Parry, Ronald J; Loria, Rosemary

2010-02-01

Plant-pathogenic Streptomyces spp. cause scab disease on economically important root and tuber crops, the most important of which is potato. Key virulence determinants produced by these species include the cellulose synthesis inhibitor, thaxtomin A, and the secreted Nec1 protein that is required for colonization of the plant host. Recently, the genome sequence of Streptomyces scabies 87-22 was completed, and a biosynthetic cluster was identified that is predicted to synthesize a novel compound similar to coronafacic acid (CFA), a component of the virulence-associated coronatine phytotoxin produced by the plant-pathogenic bacterium Pseudomonas syringae. Southern analysis indicated that the cfa-like cluster in S. scabies 87-22 is likely conserved in other strains of S. scabies but is absent from two other pathogenic streptomycetes, S. turgidiscabies and S. acidiscabies. Transcriptional analyses demonstrated that the cluster is expressed during plant-microbe interactions and that expression requires a transcriptional regulator embedded in the cluster as well as the bldA tRNA. A knockout strain of the biosynthetic cluster displayed a reduced virulence phenotype on tobacco seedlings compared with the wild-type strain. Thus, the cfa-like biosynthetic cluster is a newly discovered locus in S. scabies that contributes to host-pathogen interactions.

IMG-ABC: new features for bacterial secondary metabolism analysis and targeted biosynthetic gene cluster discovery in thousands of microbial genomes.

PubMed

Hadjithomas, Michalis; Chen, I-Min A; Chu, Ken; Huang, Jinghua; Ratner, Anna; Palaniappan, Krishna; Andersen, Evan; Markowitz, Victor; Kyrpides, Nikos C; Ivanova, Natalia N

2017-01-04

Secondary metabolites produced by microbes have diverse biological functions, which makes them a great potential source of biotechnologically relevant compounds with antimicrobial, anti-cancer and other activities. The proteins needed to synthesize these natural products are often encoded by clusters of co-located genes called biosynthetic gene clusters (BCs). In order to advance the exploration of microbial secondary metabolism, we developed the largest publically available database of experimentally verified and predicted BCs, the Integrated Microbial Genomes Atlas of Biosynthetic gene Clusters (IMG-ABC) (https://img.jgi.doe.gov/abc/). Here, we describe an update of IMG-ABC, which includes ClusterScout, a tool for targeted identification of custom biosynthetic gene clusters across 40 000 isolate microbial genomes, and a new search capability to query more than 700 000 BCs from isolate genomes for clusters with similar Pfam composition. Additional features enable fast exploration and analysis of BCs through two new interactive visualization features, a BC function heatmap and a BC similarity network graph. These new tools and features add to the value of IMG-ABC's vast body of BC data, facilitating their in-depth analysis and accelerating secondary metabolite discovery. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.