Chemical synthesis and NMR characterization of structured polyunsaturated triacylglycerols.

PubMed

Fauconnot, Laëtitia; Robert, Fabien; Villard, Renaud; Dionisi, Fabiola

2006-02-01

The chemical synthesis of pure triacylglycerol (TAG) regioisomers, that contain long chain polyunsaturated fatty acids, such as arachidonic acid (AA) or docosahexaenoic acid (DHA), and saturated fatty acids, such as lauric acid (La) or palmitic acid (P), at defined positions, is described. A single step methodology using (benzotriazol-1-yloxy)-tripyrrolidinophosphonium hexafluorophosphate (PyBOP), an activator of carboxyl group commonly used in peptide synthesis and occasionally used in carboxylic acid esterification, has been developed for structured TAG synthesis. Identification of the fatty acyl chains for each TAG species was confirmed by atmospheric pressure chemical ionisation mass spectrometry (APCI-MS) and fatty acid positional distribution was determined by (1)H and (13)C NMR spectra. The generic described procedures can be applied to a large variety of substrates and was used for the production of specific triacylglycerols of defined molecular structures, with high regioisomeric purity. Combination of MS and NMR was shown to be an efficient tool for structural analysis of TAG. In particular, some NMR signals were demonstrated to be regioisomer specific, allowing rapid positional analysis of LC-PUFA containing TAG.

A novel alkaloid isolated from Crotalaria paulina and identified by NMR and DFT calculations

NASA Astrophysics Data System (ADS)

Oliveira, Ramon Prata; Demuner, Antonio Jacinto; Alvarenga, Elson Santiago; Barbosa, Luiz Claudio Almeida; de Melo Silva, Thiago

2018-01-01

Pyrrolizidine alkaloids (PAs) are secondary metabolites found in Crotalaria genus and are known to have several biological activities. A novel macrocycle bislactone alkaloid, coined ethylcrotaline, was isolated and purified from the aerial parts of Crotalaria paulina. The novel macrocycle was identified with the aid of high resolution mass spectrometry and advanced nuclear magnetic resonance techniques. The relative stereochemistry of the alkaloid was defined by comparing the calculated quantum mechanical hydrogen and carbon chemical shifts of eight candidate structures with the experimental NMR data. The best fit between the eight candidate structures and the experimental NMR chemical shifts was defined by the DP4 statistical analyses and the Mean Absolute Error (MAE) calculations.

Conformationally selective multidimensional chemical shift ranges in proteins from a PACSY database purged using intrinsic quality criteria

PubMed Central

Hong, Mei

2016-01-01

We have determined refined multidimensional chemical shift ranges for intra-residue correlations (13C–13C, 15N–13C, etc.) in proteins, which can be used to gain type-assignment and/or secondary-structure information from experimental NMR spectra. The chemical-shift ranges are the result of a statistical analysis of the PACSY database of >3000 proteins with 3D structures (1,200,207 13C chemical shifts and >3 million chemical shifts in total); these data were originally derived from the Biological Magnetic Resonance Data Bank. Using relatively simple non-parametric statistics to find peak maxima in the distributions of helix, sheet, coil and turn chemical shifts, and without the use of limited “hand-picked” data sets, we show that ~94 % of the 13C NMR data and almost all 15N data are quite accurately referenced and assigned, with smaller standard deviations (0.2 and 0.8 ppm, respectively) than recognized previously. On the other hand, approximately 6 % of the 13C chemical shift data in the PACSY database are shown to be clearly misreferenced, mostly by ca. −2.4 ppm. The removal of the misreferenced data and other outliers by this purging by intrinsic quality criteria (PIQC) allows for reliable identification of secondary maxima in the two-dimensional chemical-shift distributions already pre-separated by secondary structure. We demonstrate that some of these correspond to specific regions in the Ramachandran plot, including left-handed helix dihedral angles, reflect unusual hydrogen bonding, or are due to the influence of a following proline residue. With appropriate smoothing, significantly more tightly defined chemical shift ranges are obtained for each amino acid type in the different secondary structures. These chemical shift ranges, which may be defined at any statistical threshold, can be used for amino-acid type assignment and secondary-structure analysis of chemical shifts from intra-residue cross peaks by inspection or by using a provided command-line Python script (PLUQin), which should be useful in protein structure determination. The refined chemical shift distributions are utilized in a simple quality test (SQAT) that should be applied to new protein NMR data before deposition in a databank, and they could benefit many other chemical-shift based tools. PMID:26787537

Rapid Induction of Cerebral Organoids From Human Induced Pluripotent Stem Cells Using a Chemically Defined Hydrogel and Defined Cell Culture Medium.

PubMed

Lindborg, Beth A; Brekke, John H; Vegoe, Amanda L; Ulrich, Connor B; Haider, Kerri T; Subramaniam, Sandhya; Venhuizen, Scott L; Eide, Cindy R; Orchard, Paul J; Chen, Weili; Wang, Qi; Pelaez, Francisco; Scott, Carolyn M; Kokkoli, Efrosini; Keirstead, Susan A; Dutton, James R; Tolar, Jakub; O'Brien, Timothy D

2016-07-01

Tissue organoids are a promising technology that may accelerate development of the societal and NIH mandate for precision medicine. Here we describe a robust and simple method for generating cerebral organoids (cOrgs) from human pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. By using no additional neural induction components, cOrgs appeared on the hydrogel surface within 10-14 days, and under static culture conditions, they attained sizes up to 3 mm in greatest dimension by day 28. Histologically, the organoids showed neural rosette and neural tube-like structures and evidence of early corticogenesis. Immunostaining and quantitative reverse-transcription polymerase chain reaction demonstrated protein and gene expression representative of forebrain, midbrain, and hindbrain development. Physiologic studies showed responses to glutamate and depolarization in many cells, consistent with neural behavior. The method of cerebral organoid generation described here facilitates access to this technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable. Tissue organoids are a promising technology with many potential applications, such as pharmaceutical screens and development of in vitro disease models, particularly for human polygenic conditions where animal models are insufficient. This work describes a robust and simple method for generating cerebral organoids from human induced pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. This method, by virtue of its simplicity and use of defined materials, greatly facilitates access to cerebral organoid technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable. ©AlphaMed Press.

A parallel implementation of the Wuchty algorithm with additional experimental filters to more thoroughly explore RNA conformational space.

PubMed

Stone, Jonathan W; Bleckley, Samuel; Lavelle, Sean; Schroeder, Susan J

2015-01-01

We present new modifications to the Wuchty algorithm in order to better define and explore possible conformations for an RNA sequence. The new features, including parallelization, energy-independent lonely pair constraints, context-dependent chemical probing constraints, helix filters, and optional multibranch loops, provide useful tools for exploring the landscape of RNA folding. Chemical probing alone may not necessarily define a single unique structure. The helix filters and optional multibranch loops are global constraints on RNA structure that are an especially useful tool for generating models of encapsidated viral RNA for which cryoelectron microscopy or crystallography data may be available. The computations generate a combinatorially complete set of structures near a free energy minimum and thus provide data on the density and diversity of structures near the bottom of a folding funnel for an RNA sequence. The conformational landscapes for some RNA sequences may resemble a low, wide basin rather than a steep funnel that converges to a single structure.

An orthologous transcriptional signature differentiates responses towards closely related chemicals in Arabidopsis thaliana and brassica napus

EPA Science Inventory

Herbicides are structurally diverse chemicals that inhibit plant-specific targets, however their off-target and potentially differentiating side-effects are less well defined. In this study, genome-wide expression profiling based on Affymetrix AtH1 arrays was used to identify dis...

Predictive analysis of the influence of the chemical composition and pre-processing regimen on structural properties of steel alloys using machine learning techniques

NASA Astrophysics Data System (ADS)

Krishnamurthy, Narayanan; Maddali, Siddharth; Romanov, Vyacheslav; Hawk, Jeffrey

We present some structural properties of multi-component steel alloys as predicted by a random forest machine-learning model. These non-parametric models are trained on high-dimensional data sets defined by features such as chemical composition, pre-processing temperatures and environmental influences, the latter of which are based upon standardized testing procedures for tensile, creep and rupture properties as defined by the American Society of Testing and Materials (ASTM). We quantify the goodness of fit of these models as well as the inferred relative importance of each of these features, all with a conveniently defined metric and scale. The models are tested with synthetic data points, generated subject to the appropriate mathematical constraints for the various features. By this we highlight possible trends in the increase or degradation of the structural properties with perturbations in the features of importance. This work is presented as part of the Data Science Initiative at the National Energy Technology Laboratory, directed specifically towards the computational design of steel alloys.

Persistent hydrogen bonding in polymorphic crystal structures.

PubMed

Galek, Peter T A; Fábián, László; Allen, Frank H

2009-02-01

The significance of hydrogen bonding and its variability in polymorphic crystal structures is explored using new automated structural analysis methods. The concept of a chemically equivalent hydrogen bond is defined, which may be identified in pairs of structures, revealing those types of bonds that may persist, or not, in moving from one polymorphic form to another. Their frequency and nature are investigated in 882 polymorphic structures from the Cambridge Structural Database. A new method to compare conformations of equivalent molecules is introduced and applied to derive distinct subsets of conformational and packing polymorphs. The roles of chemical functionality and hydrogen-bond geometry in persistent interactions are systematically explored. Detailed structural comparisons reveal a large majority of persistent hydrogen bonds that are energetically crucial to structural stability.

Non a Priori Automatic Discovery of 3D Chemical Patterns: Application to Mutagenicity.

PubMed

Rabatel, Julien; Fannes, Thomas; Lepailleur, Alban; Le Goff, Jérémie; Crémilleux, Bruno; Ramon, Jan; Bureau, Ronan; Cuissart, Bertrand

2017-10-01

This article introduces a new type of structural fragment called a geometrical pattern. Such geometrical patterns are defined as molecular graphs that include a labelling of atoms together with constraints on interatomic distances. The discovery of geometrical patterns in a chemical dataset relies on the induction of multiple decision trees combined in random forests. Each computational step corresponds to a refinement of a preceding set of constraints, extending a previous geometrical pattern. This paper focuses on the mutagenicity of chemicals via the definition of structural alerts in relation with these geometrical patterns. It follows an experimental assessment of the main geometrical patterns to show how they can efficiently originate the definition of a chemical feature related to a chemical function or a chemical property. Geometrical patterns have provided a valuable and innovative approach to bring new pieces of information for discovering and assessing structural characteristics in relation to a particular biological phenotype. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

REPDOSE: A database on repeated dose toxicity studies of commercial chemicals--A multifunctional tool.

PubMed

Bitsch, A; Jacobi, S; Melber, C; Wahnschaffe, U; Simetska, N; Mangelsdorf, I

2006-12-01

A database for repeated dose toxicity data has been developed. Studies were selected by data quality. Review documents or risk assessments were used to get a pre-screened selection of available valid data. The structure of the chemicals should be rather simple for well defined chemical categories. The database consists of three core data sets for each chemical: (1) structural features and physico-chemical data, (2) data on study design, (3) study results. To allow consistent queries, a high degree of standardization categories and glossaries were developed for relevant parameters. At present, the database consists of 364 chemicals investigated in 1018 studies which resulted in a total of 6002 specific effects. Standard queries have been developed, which allow analyzing the influence of structural features or PC data on LOELs, target organs and effects. Furthermore, it can be used as an expert system. First queries have shown that the database is a very valuable tool.

Nano-fabricated superconducting radio-frequency composites, method for producing nano-fabricated superconducting rf composites

DOEpatents

Norem, James H.; Pellin, Michael J.

2013-06-11

Superconducting rf is limited by a wide range of failure mechanisms inherent in the typical manufacture methods. This invention provides a method for fabricating superconducting rf structures comprising coating the structures with single atomic-layer thick films of alternating chemical composition. Also provided is a cavity defining the invented laminate structure.

The Chemical Validation and Standardization Platform (CVSP): large-scale automated validation of chemical structure datasets.

PubMed

Karapetyan, Karen; Batchelor, Colin; Sharpe, David; Tkachenko, Valery; Williams, Antony J

2015-01-01

There are presently hundreds of online databases hosting millions of chemical compounds and associated data. As a result of the number of cheminformatics software tools that can be used to produce the data, subtle differences between the various cheminformatics platforms, as well as the naivety of the software users, there are a myriad of issues that can exist with chemical structure representations online. In order to help facilitate validation and standardization of chemical structure datasets from various sources we have delivered a freely available internet-based platform to the community for the processing of chemical compound datasets. The chemical validation and standardization platform (CVSP) both validates and standardizes chemical structure representations according to sets of systematic rules. The chemical validation algorithms detect issues with submitted molecular representations using pre-defined or user-defined dictionary-based molecular patterns that are chemically suspicious or potentially requiring manual review. Each identified issue is assigned one of three levels of severity - Information, Warning, and Error - in order to conveniently inform the user of the need to browse and review subsets of their data. The validation process includes validation of atoms and bonds (e.g., making aware of query atoms and bonds), valences, and stereo. The standard form of submission of collections of data, the SDF file, allows the user to map the data fields to predefined CVSP fields for the purpose of cross-validating associated SMILES and InChIs with the connection tables contained within the SDF file. This platform has been applied to the analysis of a large number of data sets prepared for deposition to our ChemSpider database and in preparation of data for the Open PHACTS project. In this work we review the results of the automated validation of the DrugBank dataset, a popular drug and drug target database utilized by the community, and ChEMBL 17 data set. CVSP web site is located at http://cvsp.chemspider.com/. A platform for the validation and standardization of chemical structure representations of various formats has been developed and made available to the community to assist and encourage the processing of chemical structure files to produce more homogeneous compound representations for exchange and interchange between online databases. While the CVSP platform is designed with flexibility inherent to the rules that can be used for processing the data we have produced a recommended rule set based on our own experiences with the large data sets such as DrugBank, ChEMBL, and data sets from ChemSpider.

Current ideas on the nature of comets

NASA Technical Reports Server (NTRS)

Rahe, J.

1984-01-01

The chemical composition, emission and line spectra, and structure of comet nuclei, cometary atmospheres, and comet tails are discussed. The role of ultraviolet and infrared astronomy in defining comets is examined.

Evolution of sequence-defined highly functionalized nucleic acid polymers

NASA Astrophysics Data System (ADS)

Chen, Zhen; Lichtor, Phillip A.; Berliner, Adrian P.; Chen, Jonathan C.; Liu, David R.

2018-03-01

The evolution of sequence-defined synthetic polymers made of building blocks beyond those compatible with polymerase enzymes or the ribosome has the potential to generate new classes of receptors, catalysts and materials. Here we describe a ligase-mediated DNA-templated polymerization and in vitro selection system to evolve highly functionalized nucleic acid polymers (HFNAPs) made from 32 building blocks that contain eight chemically diverse side chains on a DNA backbone. Through iterated cycles of polymer translation, selection and reverse translation, we discovered HFNAPs that bind proprotein convertase subtilisin/kexin type 9 (PCSK9) and interleukin-6, two protein targets implicated in human diseases. Mutation and reselection of an active PCSK9-binding polymer yielded evolved polymers with high affinity (KD = 3 nM). This evolved polymer potently inhibited the binding between PCSK9 and the low-density lipoprotein receptor. Structure-activity relationship studies revealed that specific side chains at defined positions in the polymers are required for binding to their respective targets. Our findings expand the chemical space of evolvable polymers to include densely functionalized nucleic acids with diverse, researcher-defined chemical repertoires.

Searching for life in the Universe: unconventional methods for an unconventional problem.

PubMed

Nealson, K H; Tsapin, A; Storrie-Lombardi, M

2002-12-01

The search for life, on and off our planet, can be done by conventional methods with which we are all familiar. These methods are sensitive and specific, and are often capable of detecting even single cells. However, if the search broadens to include life that may be different (even subtly different) in composition, the methods and even the approach must be altered. Here we discuss the development of what we call non-earthcentric life detection--detecting life with methods that could detect life no matter what its form or composition. To develop these methods, we simply ask, can we define life in terms of its general properties and particularly those that can be measured and quantified? Taking such an approach we can search for life using physics and chemistry to ask questions about structure, chemical composition, thermodynamics, and kinetics. Structural complexity can be searched for using computer algorithms that recognize complex structures. Once identified, these structures can be examined for a variety of chemical traits, including elemental composition, chirality, and complex chemistry. A second approach involves defining our environment in terms of energy sources (i.e., reductants), and oxidants (e.g. what is available to eat and breathe), and then looking for areas in which such phenomena are inexplicably out of chemical equilibrium. These disequilibria, when found, can then be examined in detail for the presence of the structural and chemical complexity that presumably characterizes any living systems. By this approach, we move the search for life to one that should facilitate the detection of any earthly life it encountered, as well as any non-conventional life forms that have structure, complex chemistry, and live via some form of redox chemistry.

Calculating the dermal flux of chemicals with OELs based on their molecular structure: An attempt to assign the skin notation.

PubMed

Kupczewska-Dobecka, Małgorzata; Jakubowski, Marek; Czerczak, Sławomir

2010-09-01

Our objectives included calculating the permeability coefficient and dermal penetration rates (flux value) for 112 chemicals with occupational exposure limits (OELs) according to the LFER (linear free-energy relationship) model developed using published methods. We also attempted to assign skin notations based on each chemical's molecular structure. There are many studies available where formulae for coefficients of permeability from saturated aqueous solutions (K(p)) have been related to physicochemical characteristics of chemicals. The LFER model is based on the solvation equation, which contains five main descriptors predicted from chemical structure: solute excess molar refractivity, dipolarity/polarisability, summation hydrogen bond acidity and basicity, and the McGowan characteristic volume. Descriptor values, available for about 5000 compounds in the Pharma Algorithms Database were used to calculate permeability coefficients. Dermal penetration rate was estimated as a ratio of permeability coefficient and concentration of chemical in saturated aqueous solution. Finally, estimated dermal penetration rates were used to assign the skin notation to chemicals. Defined critical fluxes defined from the literature were recommended as reference values for skin notation. The application of Abraham descriptors predicted from chemical structure and LFER analysis in calculation of permeability coefficients and flux values for chemicals with OELs was successful. Comparison of calculated K(p) values with data obtained earlier from other models showed that LFER predictions were comparable to those obtained by some previously published models, but the differences were much more significant for others. It seems reasonable to conclude that skin should not be characterised as a simple lipophilic barrier alone. Both lipophilic and polar pathways of permeation exist across the stratum corneum. It is feasible to predict skin notation on the basis of the LFER and other published models; from among 112 chemicals 94 (84%) should have the skin notation in the OEL list based on the LFER calculations. The skin notation had been estimated by other published models for almost 94% of the chemicals. Twenty-nine (25.8%) chemicals were identified to have significant absorption and 65 (58%) the potential for dermal toxicity. We found major differences between alternative published analytical models and their ability to determine whether particular chemicals were potentially dermotoxic. Copyright © 2010 Elsevier B.V. All rights reserved.

Symposium II: Mechanochemistry in Materials Science, MRS Fall Meeting, Nov 30-Dec 4, 2009, Boston, MA

DTIC Science & Technology

2010-09-02

Dynamic Mechanical Analysis (DMA). The fracture behavior of the mechanophore-linked polymer is also examined through the Double Cleavage Drilled ...multinary complex structures. Structural, microstructural, and chemical characterizations were explored by metrological tools to support this...simple hydrocarbons in order to quantitatively define structure-property relationships for reacting materials under shock compression. Embedded gauge

Dissolution Processes, Kinetics

EPA Science Inventory

Chemistry by its very nature is concerned with change. There are simple but significant interactions between air, water, and minerals that impact our natural environment. Minerals with well-defined structure are converted by various environmental chemical reactions into their e...

In situ growth, structure, and real-time chemical reactivity of well-defined CeO x-Ru(0001) model surfaces

DOE PAGES

Grinter, David C.; Senanayake, Sanjaya D.; Flege, Jan Ingo

2016-11-15

Ceria is an important material for chemical conversion processes in catalysis. Its intrinsic properties as a reducible oxide can be exploited to achieve catalytic selectivity and activity. However, numerous phenomenological characteristics of ceria remain unknown and its active nature is ever slowly being unraveled. Well defined models of ceria (111) are an important way to systematically study these properties and take advantage of new in situ methods that require pristine materials that allow for the interrogation of the most fundamental traits of this material. The ceria-Ru(0001) model is now the most well studied model surface with numerous aspects of itsmore » preparation, atomic structure and reactivity studied by several groups. The preparation of CeO x structures oriented with a (111) surface termination can be achieved through molecular beam deposition, facilitating the growth of well-defined nanostructures, microparticles, and films on the Ru(0001) surface. The growth mechanism exploits the epitaxial relationship between CeOx and Ru to form a carpet mode of well oriented layers of Osingle bondCesingle bondO. These models can be studied to unravel the atomic structure and the oxidation state (Ce 4+ and Ce 3+), as prepared and under redox conditions (reduction/oxidation) or with reaction using reactants (e.g., H 2, methanol). Here, we present a discussion of these most recent observations pertaining to the growth mode, arrangement of atoms on the surface, characteristic chemical state, and redox chemistry of the CeO x-Ru surface. As a result, with insights from these studies we propose new strategies to further unravel the chemistry of ceria.« less

Chemical Space Mapping and Structure-Activity Analysis of the ChEMBL Antiviral Compound Set.

PubMed

Klimenko, Kyrylo; Marcou, Gilles; Horvath, Dragos; Varnek, Alexandre

2016-08-22

Curation, standardization and data fusion of the antiviral information present in the ChEMBL public database led to the definition of a robust data set, providing an association of antiviral compounds to seven broadly defined antiviral activity classes. Generative topographic mapping (GTM) subjected to evolutionary tuning was then used to produce maps of the antiviral chemical space, providing an optimal separation of compound families associated with the different antiviral classes. The ability to pinpoint the specific spots occupied (responsibility patterns) on a map by various classes of antiviral compounds opened the way for a GTM-supported search for privileged structural motifs, typical for each antiviral class. The privileged locations of antiviral classes were analyzed in order to highlight underlying privileged common structural motifs. Unlike in classical medicinal chemistry, where privileged structures are, almost always, predefined scaffolds, privileged structural motif detection based on GTM responsibility patterns has the decisive advantage of being able to automatically capture the nature ("resolution detail"-scaffold, detailed substructure, pharmacophore pattern, etc.) of the relevant structural motifs. Responsibility patterns were found to represent underlying structural motifs of various natures-from very fuzzy (groups of various "interchangeable" similar scaffolds), to the classical scenario in medicinal chemistry (underlying motif actually being the scaffold), to very precisely defined motifs (specifically substituted scaffolds).

Conformational analysis of α-helical polypeptide included L-proline residue by high-resolution solid-state NMR measurement and quantum chemical calculation

NASA Astrophysics Data System (ADS)

Souma, Hiroyuki; Shoji, Akira; Kurosu, Hiromichi

2008-10-01

We challenged the problem about the stabilization mechanism of an α-helix formation for polypeptides containing L-proline (Pro) residue. We computed the optimized structure of α-helical poly( L-alanine) molecules including a Pro residue, H-(Ala) 8-Pro-(Ala) 9-OH, based on the molecular orbital calculation with density functional theory, B3LYP/6-31G(d) and the 13C and 15N chemical shift values based on the GIAO-CHF method with B3LYP/6-311G(d,p), respectively. It was found that two kinds of optimized structures, 'Bent structure' and 'Included α-helix structure', were preferred structures in H-(Ala) 8-Pro-(Ala) 9-OH. In addition, based on the precise 13C and 15N chemical shift data of the simple model, we successfully analyzed the secondary structure of well-defined synthetic polypeptide H-(Phe-Leu-Ala) 3-Phe C-Pro-Ala N-(Phe-Leu-Ala) 2-OH (FLA-11P), the secondary structure of which was proven to the 'Included α-helix structure'.

Positive electrodes of nickel-cadmium batteries

NASA Technical Reports Server (NTRS)

Wabner, D. W.; Kandler, L.; Krienke, W.

1985-01-01

Ni hydroxide sintered electrodes which are filled electrochemically are superior to chemically treated electrodes. In the electrochemical process, the hydroxide grows on the Ni grains and possesses a well-defined porous structure. Diffusion and conducting mechanisms are therefore facilitated.

A Way Forward Commentary

EPA Science Inventory

Models for predicting adverse outcomes can help reduce and focus animal testing with new and existing chemicals. This short "thought starter" describes how quantitative-structure activity relationship and systems biology models can be used to help define toxicity pathways and li...

Temporal Control over Transient Chemical Systems using Structurally Diverse Chemical Fuels.

PubMed

Chen, Jack L-Y; Maiti, Subhabrata; Fortunati, Ilaria; Ferrante, Camilla; Prins, Leonard J

2017-08-25

The next generation of adaptive, intelligent chemical systems will rely on a continuous supply of energy to maintain the functional state. Such systems will require chemical methodology that provides precise control over the energy dissipation process, and thus, the lifetime of the transiently activated function. This manuscript reports on the use of structurally diverse chemical fuels to control the lifetime of two different systems under dissipative conditions: transient signal generation and the transient formation of self-assembled aggregates. The energy stored in the fuels is dissipated at different rates by an enzyme, which installs a dependence of the lifetime of the active system on the chemical structure of the fuel. In the case of transient signal generation, it is shown that different chemical fuels can be used to generate a vast range of signal profiles, allowing temporal control over two orders of magnitude. Regarding self-assembly under dissipative conditions, the ability to control the lifetime using different fuels turns out to be particularly important as stable aggregates are formed only at well-defined surfactant/fuel ratios, meaning that temporal control cannot be achieved by simply changing the fuel concentration. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Overview of data and conceptual approaches for derivation of quantitative structure-activity relationships for ecotoxicological effects of organic chemicals.

PubMed

Bradbury, Steven P; Russom, Christine L; Ankley, Gerald T; Schultz, T Wayne; Walker, John D

2003-08-01

The use of quantitative structure-activity relationships (QSARs) in assessing potential toxic effects of organic chemicals on aquatic organisms continues to evolve as computational efficiency and toxicological understanding advance. With the ever-increasing production of new chemicals, and the need to optimize resources to assess thousands of existing chemicals in commerce, regulatory agencies have turned to QSARs as essential tools to help prioritize tiered risk assessments when empirical data are not available to evaluate toxicological effects. Progress in designing scientifically credible QSARs is intimately associated with the development of empirically derived databases of well-defined and quantified toxicity endpoints, which are based on a strategic evaluation of diverse sets of chemical structures, modes of toxic action, and species. This review provides a brief overview of four databases created for the purpose of developing QSARs for estimating toxicity of chemicals to aquatic organisms. The evolution of QSARs based initially on general chemical classification schemes, to models founded on modes of toxic action that range from nonspecific partitioning into hydrophobic cellular membranes to receptor-mediated mechanisms is summarized. Finally, an overview of expert systems that integrate chemical-specific mode of action classification and associated QSAR selection for estimating potential toxicological effects of organic chemicals is presented.

Building Scientific Confidence in the Development and ...

EPA Pesticide Factsheets

Read-across remains a popular data gap filling technique within category and analogue approaches for regulatory purposes. Acceptance of read-across is an ongoing challenge with several efforts underway for identifying and addressing uncertainties. Here we demonstrate an algorithmic approach to facilitate read-across using ToxCast in vitro bioactivity data in conjunction with chemical descriptor information to predict in vivo outcomes in guideline testing studies from ToxRefDB. Over 3400 different chemical structure descriptors were generated for a set of 976 chemicals and supplemented with the outcomes from 821 in vitro assays. The read-across prediction for a given chemical was based on the similarity weighted endpoint outcomes of its nearest neighbors calculated using in vitro bioactivity and chemical structure descriptors, called GenRA. GenRA is based on a computational approach for: (i) defining local validity domains using chemical and bioactivity descriptors, (ii) systematically deriving endpoint read-across predictions within these domains using similarity weighted activity of nearest neighbours, (iii) objectively evaluating predicted performance using tested chemicals, and (iv) assigning read-across predictions to untested chemicals along with estimates of uncertainty. We found in vitro bioactivity descriptors were often found to be more predictive of in vivo toxicity outcomes than chemical structure descriptors. We believe GenRA is an important first st

Redox-dependent structure change and hyperfine nuclear magnetic resonance shifts in cytochrome c

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

Feng, Yiquing; Roder, H.; Englander, S.W.

1990-04-10

Proton nuclear magnetic resonance assignments for reduced and oxidized equine cytochrome c show that many individual protons exhibit different chemical shifts in the two protein forms, reflecting diamagnetic shift effects due to structure change, and in addition contact and pseudocontact shifts that occur only in the paramagnetic oxidized form. To evaluate the chemical shift differences for structure change, the authors removed the pseudocontact shift contribution by a calculation based on knowledge of the electron spin g tensor. The g-tensor calculation, when repeated using only 12 available C{sub {alpha}}H proton resonances for cytochrom c from tuna, proved to be remarkably stable.more » The derived g tensor was then used together with spatial coordinates for the oxidized form to calculate the pseudocontact shift contribution to proton resonances at 400 identifiable sites throughout the protein, so that the redox-dependent chemical shift discrepancy, could be evaluated. Large residual changes in chemical shift define the Fermi contact shifts, where are found as expected to be limited to the immediate covalent structure of the heme and its ligands and to be asymmetrically distributed over the heme. The chemical shift discrepancies observed appear in the main to reflect structure-dependent diamagnetic shifts rather than hyperfine effects due to displacements in the pseudocontact shift field. Although 51 protons in 29 different residues exhibit significant chemical shift changes, the general impressions one of small structural adjustments to redox-dependent strain rather than sizeable structural displacements or rearrangements.« less

Molecular Descriptors

NASA Astrophysics Data System (ADS)

Consonni, Viviana; Todeschini, Roberto

In the last decades, several scientific researches have been focused on studying how to encompass and convert - by a theoretical pathway - the information encoded in the molecular structure into one or more numbers used to establish quantitative relationships between structures and properties, biological activities, or other experimental properties. Molecular descriptors are formally mathematical representations of a molecule obtained by a well-specified algorithm applied to a defined molecular representation or a well-specified experimental procedure. They play a fundamental role in chemistry, pharmaceutical sciences, environmental protection policy, toxicology, ecotoxicology, health research, and quality control. Evidence of the interest of the scientific community in the molecular descriptors is provided by the huge number of descriptors proposed up today: more than 5000 descriptors derived from different theories and approaches are defined in the literature and most of them can be calculated by means of dedicated software applications. Molecular descriptors are of outstanding importance in the research fields of quantitative structure-activity relationships (QSARs) and quantitative structure-property relationships (QSPRs), where they are the independent chemical information used to predict the properties of interest. Along with the definition of appropriate molecular descriptors, the molecular structure representation and the mathematical tools for deriving and assessing models are other fundamental components of the QSAR/QSPR approach. The remarkable progress during the last few years in chemometrics and chemoinformatics has led to new strategies for finding mathematical meaningful relationships between the molecular structure and biological activities, physico-chemical, toxicological, and environmental properties of chemicals. Different approaches for deriving molecular descriptors here reviewed and some of the most relevant descriptors are presented in detail with numerical examples.

Kohonen and counterpropagation neural networks applied for mapping and interpretation of IR spectra.

PubMed

Novic, Marjana

2008-01-01

The principles of learning strategy of Kohonen and counterpropagation neural networks are introduced. The advantages of unsupervised learning are discussed. The self-organizing maps produced in both methods are suitable for a wide range of applications. Here, we present an example of Kohonen and counterpropagation neural networks used for mapping, interpretation, and simulation of infrared (IR) spectra. The artificial neural network models were trained for prediction of structural fragments of an unknown compound from its infrared spectrum. The training set contained over 3,200 IR spectra of diverse compounds of known chemical structure. The structure-spectra relationship was encompassed by the counterpropagation neural network, which assigned structural fragments to individual compounds within certain probability limits, assessed from the predictions of test compounds. The counterpropagation neural network model for prediction of fragments of chemical structure is reversible, which means that, for a given structural domain, limited to the training data set in the study, it can be used to simulate the IR spectrum of a chemical defined with a set of structural fragments.

On Topological Indices of Certain Dendrimer Structures

NASA Astrophysics Data System (ADS)

Aslam, Adnan; Bashir, Yasir; Ahmad, Safyan; Gao, Wei

2017-05-01

A topological index can be considered as transformation of chemical structure in to real number. In QSAR/QSPR study, physicochemical properties and topological indices such as Randić, Zagreb, atom-bond connectivity ABC, and geometric-arithmetic GA index are used to predict the bioactivity of chemical compounds. Dendrimers are highly branched, star-shaped macromolecules with nanometer-scale dimensions. Dendrimers are defined by three components: a central core, an interior dendritic structure (the branches), and an exterior surface with functional surface groups. In this paper we determine generalised Randić, general Zagreb, general sum-connectivity indices of poly(propyl) ether imine, porphyrin, and zinc-Porphyrin dendrimers. We also compute ABC and GA indices of these families of dendrimers.

Predicting hepatotoxicity using ToxCast in vitro bioactivity and ...

EPA Pesticide Factsheets

Background: The U.S. EPA ToxCastTM program is screening thousands of environmental chemicals for bioactivity using hundreds of high-throughput in vitro assays to build predictive models of toxicity. We represented chemicals based on bioactivity and chemical structure descriptors then used supervised machine learning to predict their hepatotoxic effects.Results: A set of 677 chemicals were represented by 711 in vitro bioactivity descriptors (from ToxCast assays), 4,376 chemical structure descriptors (from QikProp, OpenBabel, PADEL, and PubChem), and three hepatotoxicity categories (from animal studies). Hepatotoxicants were defined by rat liver histopathology observed after chronic chemical testing and grouped into hypertrophy (161), injury (101) and proliferative lesions (99). Classifiers were built using six machine learning algorithms: linear discriminant analysis (LDA), Naïve Bayes (NB), support vector classification (SVM), classification and regression trees (CART), k-nearest neighbors (KNN) and an ensemble of classifiers (ENSMB). Classifiers of hepatotoxicity were built using chemical structure, ToxCast bioactivity, and a hybrid representation. Predictive performance was evaluated using 10-fold cross-validation testing and in-loop, filter-based, feature subset selection. Hybrid classifiers had the best balanced accuracy for predicting hypertrophy (0.78±0.08), injury (0.73±0.10) and proliferative lesions (0.72±0.09). Though chemical and bioactivity class

Development of a category approach to predict the testicular toxicity of chemical substances structurally related to ethylene glycol methyl ether.

PubMed

Yamada, Takashi; Tanaka, Yushiro; Hasegawa, Ryuichi; Sakuratani, Yuki; Yamazoe, Yasushi; Ono, Atsushi; Hirose, Akihiko; Hayashi, Makoto

2014-12-01

We propose a category approach to assessing the testicular toxicity of chemicals with a similar structure to ethylene glycol methyl ether (EGME). Based on toxicity information for EGME and related chemicals and accompanied by adverse outcome pathway information on the testicular toxicity of EGME, this category was defined as chemicals that are metabolized to methoxy- or ethoxyacetic acid, a substance responsible for testicular toxicity. A Japanese chemical inventory was screened using the Hazard Evaluation Support System, which we have developed to support a category approach for predicting the repeated-dose toxicity of chemical substances. Quantitative metabolic information on the related chemicals was then considered, and seventeen chemicals were finally obtained from the inventory as a shortlist for the category. Available data in the literature shows that chemicals for which information is available on the metabolic formation of EGME, ethylene glycol ethyl ether, methoxy- or ethoxyacetic acid do in fact possess testicular toxicity, suggesting that testicular toxicity is a concern, due to metabolic activation, for the remaining chemicals. Our results clearly demonstrate practical utility of AOP-based category approach for predicting repeated-dose toxicity of chemicals. Copyright © 2014 Elsevier Inc. All rights reserved.

The Vertex Version of Weighted Wiener Number for Bicyclic Molecular Structures

PubMed Central

Gao, Wei

2015-01-01

Graphs are used to model chemical compounds and drugs. In the graphs, each vertex represents an atom of molecule and edges between the corresponding vertices are used to represent covalent bounds between atoms. We call such a graph, which is derived from a chemical compound, a molecular graph. Evidence shows that the vertex-weighted Wiener number, which is defined over this molecular graph, is strongly correlated to both the melting point and boiling point of the compounds. In this paper, we report the extremal vertex-weighted Wiener number of bicyclic molecular graph in terms of molecular structural analysis and graph transformations. The promising prospects of the application for the chemical and pharmacy engineering are illustrated by theoretical results achieved in this paper. PMID:26640513

Electronegativity and hardness as coordinates in structure stability diagrams.

PubMed Central

Shankar, S; Parr, R G

1985-01-01

With electronegativity and hardness of an atom defined as 1/2(I + A) and 1/2(I - A), respectively, where I and A are the ionization potential and electron affinity, electronegativity difference and hardness sum are proposed as coordinates in structure stability diagrams. With these coordinates a successful topological classification of the crystal structures of octet and suboctet binary compounds is obtained, and a clear delineation of the structural classes portraying chemical periodicity is found. PMID:3855552

Chemical approaches toward graphene-based nanomaterials and their applications in energy-related areas.

PubMed

Luo, Bin; Liu, Shaomin; Zhi, Linjie

2012-03-12

A 'gold rush' has been triggered all over the world for exploiting the possible applications of graphene-based nanomaterials. For this purpose, two important problems have to be solved; one is the preparation of graphene-based nanomaterials with well-defined structures, and the other is the controllable fabrication of these materials into functional devices. This review gives a brief overview of the recent research concerning chemical and thermal approaches toward the production of well-defined graphene-based nanomaterials and their applications in energy-related areas, including solar cells, lithium ion secondary batteries, supercapacitors, and catalysis. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bioactive Structure of Membrane Lipids and Natural Products Elucidated by a Chemistry-Based Approach.

PubMed

Murata, Michio; Sugiyama, Shigeru; Matsuoka, Shigeru; Matsumori, Nobuaki

2015-08-01

Determining the bioactive structure of membrane lipids is a new concept, which aims to examine the functions of lipids with respect to their three-dimensional structures. As lipids are dynamic by nature, their "structure" does not refer solely to a static picture but also to the local and global motions of the lipid molecules. We consider that interactions with lipids, which are completely defined by their structures, are controlled by the chemical, functional, and conformational matching between lipids and between lipid and protein. In this review, we describe recent advances in understanding the bioactive structures of membrane lipids bound to proteins and related molecules, including some of our recent results. By examining recent works on lipid-raft-related molecules, lipid-protein interactions, and membrane-active natural products, we discuss current perspectives on membrane structural biology. © 2015 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using novel descriptor accounting for ligand-receptor interactions to define and visually explore biologically relevant chemical space.

PubMed

Rabal, Obdulia; Oyarzabal, Julen

2012-05-25

The definition and pragmatic implementation of biologically relevant chemical space is critical in addressing navigation strategies in the overlapping regions where chemistry and therapeutically relevant targets reside and, therefore, also key to performing an efficient drug discovery project. Here, we describe the development and implementation of a simple and robust method for representing biologically relevant chemical space as a general reference according to current knowledge, independently of any reference space, and analyzing chemical structures accordingly. Underlying our method is the generation of a novel descriptor (LiRIf) that converts structural information into a one-dimensional string accounting for the plausible ligand-receptor interactions as well as for topological information. Capitalizing on ligand-receptor interactions as a descriptor enables the clustering, profiling, and comparison of libraries of compounds from a chemical biology and medicinal chemistry perspective. In addition, as a case study, R-groups analysis is performed to identify the most populated ligand-receptor interactions according to different target families (GPCR, kinases, etc.), as well as to evaluate the coverage of biologically relevant chemical space by structures annotated in different databases (ChEMBL, Glida, etc.).

Lithographic fabrication of nanoapertures

DOEpatents

Fleming, James G.

2003-01-01

A new class of silicon-based lithographically defined nanoapertures and processes for their fabrication using conventional silicon microprocessing technology have been invented. The new ability to create and control such structures should significantly extend our ability to design and implement chemically selective devices and processes.

Greenstone belts: Their components and structure

NASA Technical Reports Server (NTRS)

Vearncombe, J. R.; Barton, J. M., Jr.; Vanreenen, D. D.; Phillips, G. N.; Wilson, A. H.

1986-01-01

Greenstone sucessions are defined as the nongranitoid component of granitoid-greenstone terrain and are linear to irregular in shape and where linear are termed belts. The chemical composition of greenstones is described. Also discussed are the continental environments of greenstone successions. The effects of contact with granitoids, geophysical properties, recumbent folds and late formation structures upon greenstones are examined. Large stratigraphy thicknesses are explained.

Development of a New De Novo Design Algorithm for Exploring Chemical Space.

PubMed

Mishima, Kazuaki; Kaneko, Hiromasa; Funatsu, Kimito

2014-12-01

In the first stage of development of new drugs, various lead compounds with high activity are required. To design such compounds, we focus on chemical space defined by structural descriptors. New compounds close to areas where highly active compounds exist will show the same degree of activity. We have developed a new de novo design system to search a target area in chemical space. First, highly active compounds are manually selected as initial seeds. Then, the seeds are entered into our system, and structures slightly different from the seeds are generated and pooled. Next, seeds are selected from the new structure pool based on the distance from target coordinates on the map. To test the algorithm, we used two datasets of ligand binding affinity and showed that the proposed generator could produce diverse virtual compounds that had high activity in docking simulations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation Aspects of Building Structures Reconstructed After a Failure or Catastrophe

NASA Astrophysics Data System (ADS)

Krentowski, Janusz R.; Knyziak, Piotr

2017-10-01

The article presents the characteristics of several steel structures, among others modernized industrial dye house, school sports hall, truck repair workshop, that have been rebuilt after a disaster or a catastrophe. The structures were analyzed in detail, and the evaluation and reconstruction processes were described. The emergencies that occurred during exploitation of the buildings were the result of multiple mistakes: incorrectly defined intervals between inspections, errors during periodic inspections, incorrect repair work recommendations. The concepts of reinforcement work implemented by the authors, enabling the long-term future failure-free operation of the objects, were presented. Recommendations for monitoring of the facilities, applied after reinforcement or reconstruction, have been formulated. The methodology for the implementation of specialized investigations, such as geodetic, optical, geological, chemical strength tests, both destructive and non-destructive, has been defined. The need to determine the limit values of deformations, deflections, damage or other faults of structural elements and the entire rebuilt facilities, as well as defining conditions for objects’ withdrawal from operation in subsequent exceptional situations was indicated.

Purity assessment of condensed tannin fractions by nuclear magnetic resonance (NMR) spectroscopy

USDA-ARS?s Scientific Manuscript database

Unambiguous investigation of condensed tannin (CT) structure-activity relationships in biological systems requires the use of highly enriched CT fractions of defined chemical purity. Purification of CTs from Sorghum bicolor, Trifolium repens, Theobroma cacao, Lespedeza cuneata, Lotus pedunculatus, a...

Branched terthiophenes in organic electronics: from small molecules to polymers.

PubMed

Scheuble, Martin; Goll, Miriam; Ludwigs, Sabine

2015-01-01

A zoo of chemical structures is accessible when the branched unit 2,2':3',2″-terthiophene (3T) is included both in structurally well-defined small molecules and polymer-like architectures. The first part of this review article highlights literature on all-thiophene based branched oligomers including dendrimers as well as combinations of 3T-units with functional moieties for light-harvesting systems. Motivated by the perfectly branched macromolecular dendrimers both electropolymerization as well as chemical approaches are presented as methods for the preparation of branched polythiophenes with different branching densities. Structure-function relationships between the molecular architecture and optical and electronic properties are discussed throughout the article. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Study of the Chemical Space of Selected Bacteriostatic Sulfonamides from an Information Theory Point of View.

PubMed

López-Rosa, Sheila; Molina-Espíritu, Moyocoyani; Esquivel, Rodolfo O; Soriano-Correa, Catalina; Dehesa, Jésus S

2016-12-05

The relative structural location of a selected group of 27 sulfonamide-like molecules in a chemical space defined by three information theory quantities (Shannon entropy, Fisher information, and disequilibrium) is discussed. This group is composed of 15 active bacteriostatic molecules, 11 theoretically designed ones, and para-aminobenzoic acid. This endeavor allows molecules that share common chemical properties through the molecular backbone, but with significant differences in the identity of the chemical substituents, which might result in bacteriostatic activity, to be structurally classified and characterized. This is performed by quantifying the structural changes on the electron density distribution due to different functional groups and number of electrons. The macroscopic molecular features are described by means of the entropy-like notions of spatial electronic delocalization, order, and uniformity. Hence, an information theory three-dimensional space (IT-3D) emerges that allows molecules with common properties to be gathered. This space witnesses the biological activity of the sulfonamides. Some structural aspects and information theory properties can be associated, as a result of the IT-3D chemical space, with the bacteriostatic activity of these molecules. Most interesting is that the active bacteriostatic molecules are more similar to para-aminobenzoic acid than to the theoretically designed analogues. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microscopy and Chemical Inversing Techniques to Determine the Photonic Crystal Structure of Iridescent Beetle Scales in the Cerambycidae Family

NASA Astrophysics Data System (ADS)

Richey, Lauren; Gardner, John; Standing, Michael; Jorgensen, Matthew; Bartl, Michael

2010-10-01

Photonic crystals (PCs) are periodic structures that manipulate electromagnetic waves by defining allowed and forbidden frequency bands known as photonic band gaps. Despite production of PC structures operating at infrared wavelengths, visible counterparts are difficult to fabricate because periodicities must satisfy the diffraction criteria. As part of an ongoing search for naturally occurring PCs [1], a three-dimensional array of nanoscopic spheres in the iridescent scales of the Cerambycidae insects A. elegans and G. celestis has been found. Such arrays are similar to opal gemstones and self-assembled colloidal spheres which can be chemically inverted to create a lattice-like PC. Through a chemical replication process [2], scanning electron microscopy analysis, sequential focused ion beam slicing and three-dimensional modeling, we analyzed the structural arrangement of the nanoscopic spheres. The study of naturally occurring structures and their inversing techniques into PCs allows for diversity in optical PC fabrication. [1] J.W. Galusha et al., Phys. Rev. E 77 (2008) 050904. [2] J.W. Galusha et al., J. Mater. Chem. 20 (2010) 1277.

[Construction of chemical information database based on optical structure recognition technique].

PubMed

Lv, C Y; Li, M N; Zhang, L R; Liu, Z M

2018-04-18

To create a protocol that could be used to construct chemical information database from scientific literature quickly and automatically. Scientific literature, patents and technical reports from different chemical disciplines were collected and stored in PDF format as fundamental datasets. Chemical structures were transformed from published documents and images to machine-readable data by using the name conversion technology and optical structure recognition tool CLiDE. In the process of molecular structure information extraction, Markush structures were enumerated into well-defined monomer molecules by means of QueryTools in molecule editor ChemDraw. Document management software EndNote X8 was applied to acquire bibliographical references involving title, author, journal and year of publication. Text mining toolkit ChemDataExtractor was adopted to retrieve information that could be used to populate structured chemical database from figures, tables, and textual paragraphs. After this step, detailed manual revision and annotation were conducted in order to ensure the accuracy and completeness of the data. In addition to the literature data, computing simulation platform Pipeline Pilot 7.5 was utilized to calculate the physical and chemical properties and predict molecular attributes. Furthermore, open database ChEMBL was linked to fetch known bioactivities, such as indications and targets. After information extraction and data expansion, five separate metadata files were generated, including molecular structure data file, molecular information, bibliographical references, predictable attributes and known bioactivities. Canonical simplified molecular input line entry specification as primary key, metadata files were associated through common key nodes including molecular number and PDF number to construct an integrated chemical information database. A reasonable construction protocol of chemical information database was created successfully. A total of 174 research articles and 25 reviews published in Marine Drugs from January 2015 to June 2016 collected as essential data source, and an elementary marine natural product database named PKU-MNPD was built in accordance with this protocol, which contained 3 262 molecules and 19 821 records. This data aggregation protocol is of great help for the chemical information database construction in accuracy, comprehensiveness and efficiency based on original documents. The structured chemical information database can facilitate the access to medical intelligence and accelerate the transformation of scientific research achievements.

The Architecture of Chemical Alternatives Assessment.

PubMed

Geiser, Kenneth; Tickner, Joel; Edwards, Sally; Rossi, Mark

2015-12-01

Chemical alternatives assessment is a method rapidly developing for use by businesses, governments, and nongovernment organizations seeking to substitute chemicals of concern in production processes and products. Chemical alternatives assessment is defined as a process for identifying, comparing, and selecting safer alternatives to chemicals of concern (including those in materials, processes, or technologies) on the basis of their hazards, performance, and economic viability. The process is intended to provide guidance for assuring that chemicals of concern are replaced with safer alternatives that are not likely to be later regretted. Conceptually, the assessment methods are developed from a set of three foundational pillars and five common principles. Based on a number of emerging alternatives assessment initiatives, in this commentary, we outline a chemical alternatives assessment blueprint structured around three broad steps: Scope, Assessment, and Selection and Implementation. Specific tasks and tools are identified for each of these three steps. While it is recognized that on-going practice will further refine and develop the method and tools, it is important that the structure of the assessment process remain flexible, adaptive, and focused on the substitution of chemicals of concern with safer alternatives. © 2015 Society for Risk Analysis.

Expanding the chemical information science gateway.

PubMed

Bajorath, Jürgen

2017-01-01

Broadly defined, chemical information science (CIS) covers chemical structure and data analysis including biological activity data as well as processing, organization, and retrieval of any form of chemical information. The CIS Gateway (CISG) of F1000Research was created to communicate research involving the entire spectrum of chemical information, including chem(o)informatics. CISG provides a forum for high-quality publications and a meaningful alternative to conventional journals. This gateway is supported by leading experts in the field recognizing the need for open science and a flexible publication platform enabling off-the-beaten path contributions. This editorial aims to further rationalize the scope of CISG, position it within its scientific environment, and open it up to a wider audience. Chemical information science is an interdisciplinary field with high potential to interface with experimental work.

Expanding the chemical information science gateway

PubMed Central

Bajorath, Jürgen

2017-01-01

Broadly defined, chemical information science (CIS) covers chemical structure and data analysis including biological activity data as well as processing, organization, and retrieval of any form of chemical information. The CIS Gateway (CISG) of F1000Research was created to communicate research involving the entire spectrum of chemical information, including chem(o)informatics. CISG provides a forum for high-quality publications and a meaningful alternative to conventional journals. This gateway is supported by leading experts in the field recognizing the need for open science and a flexible publication platform enabling off-the-beaten path contributions. This editorial aims to further rationalize the scope of CISG, position it within its scientific environment, and open it up to a wider audience. Chemical information science is an interdisciplinary field with high potential to interface with experimental work. PMID:29043072

Crystalline Structure and Surface Reactivity: Atomistic models are unique tools for dealing with the chemical and physical properties of surfaces.

PubMed

Gatos, H C

1962-08-03

The role of crystalline structure in the surface reactivity of predominantly covalent materials has been examined in terms of chemical bonding concepts. In this context a solid surface can be viewed as a giant lattice defect characterized by dangling bonds. Although it is difficult, at the present stage of development of the quantum mechanical approach to surfaces, to define precisely the perturbations resulting from the abrupt termination of the lattice at the surface, a host of experimental observations can be understood by assuming displacements of surface atoms and distortions of bonding configurations in accordance with simple chemical bonding principles. A purely atomistic approach has been shown to account not only for the chemical behavior but also for certain structural and electrical characteristics of the surfaces considered. A number of phenomena, such as crystal growth and the behavior of certain lattice defects (for example, dislocations), are intimately related to the presence of dangling bonds and the associated distortions of the lattice at the surface (32).

Relations between water physico-chemistry and benthic algal communities in a northern Canadian watershed: defining reference conditions using multiple descriptors of community structure.

PubMed

Thomas, Kathryn E; Hall, Roland I; Scrimgeour, Garry J

2015-09-01

Defining reference conditions is central to identifying environmental effects of anthropogenic activities. Using a watershed approach, we quantified reference conditions for benthic algal communities and their relations to physico-chemical conditions in rivers in the South Nahanni River watershed, NWT, Canada, in 2008 and 2009. We also compared the ability of three descriptors that vary in terms of analytical costs to define algal community structure based on relative abundances of (i) all algal taxa, (ii) only diatom taxa, and (iii) photosynthetic pigments. Ordination analyses showed that variance in algal community structure was strongly related to gradients in environmental variables describing water physico-chemistry, stream habitats, and sub-watershed structure. Water physico-chemistry and local watershed-scale descriptors differed significantly between algal communities from sites in the Selwyn Mountain ecoregion compared to sites in the Nahanni-Hyland ecoregions. Distinct differences in algal community types between ecoregions were apparent irrespective of whether algal community structure was defined using all algal taxa, diatom taxa, or photosynthetic pigments. Two algal community types were highly predictable using environmental variables, a core consideration in the development of Reference Condition Approach (RCA) models. These results suggest that assessments of environmental impacts could be completed using RCA models for each ecoregion. We suggest that use of algal pigments, a high through-put analysis, is a promising alternative compared to more labor-intensive and costly taxonomic approaches for defining algal community structure.

Iodine(III)-Mediated Selective Intermolecular C-H Amination for the Chemical Diversification of Tryptamines.

PubMed

Bosnidou, Alexandra E; Millán, Alba; Ceballos, Javier; Martínez, Claudio; Muñiz, Kilian

2016-08-05

Defined hypervalent iodine reagents of the general structure PhI[N(SO2R)(SO2R')]2 promote the selective direct C-H-amination of the indole core of various tryptamines. Starting from a general C2-amination strategy, subsequent transformations enable a variety of site-selective functionalizations, which proceed with noteworthy high chemoselectivity and provide an overall access to structurally diversified products.

Tantalum protective coatings for fusion reactor applications

NASA Astrophysics Data System (ADS)

Brossa, Francesco; Piatti, Giovanni; Bardy, Michel

Tantalum has a very low sputtering yield, high melting point, low vapour pressure and good mechanical properties at low and high temperatures, so it is a very interesting candidate for the first wall and blanket structural components. Tantalum coatings overcome the problems of fabrication and joining bulk Ta, thus reducing also dead weight and cost. Ta coatings were produced by chemical vapour deposition and plasma spraying on four conventional structural materials: Al, Cu, AISI 316 L and Inconel 600. The conditions which improve adherence have been studied. The composition of the films was determined by chemical means and by X-ray analysis. Metallographie examination was employed to define the morphological structure of the deposits. The adherence of the coatings was determined by subjecting the samples to bend tests and to thermal shocks.

Structural characteristics of fulvic acids from Continental Shelf sediments

USGS Publications Warehouse

Hatcher, P.G.; Breger, I.A.; Mattingly, M.A.

1980-01-01

Fulvic acids are those components of soil organic matter that remain soluble after a dilute alkaline extract of the soil is acidified to pH 2 (refs 1, 2). This extraction procedure has been applied to marine sediments, and the organic compounds so recovered have been called marine sedimentary fulvic acids. These fulvic acids are thought to form more complex humic substances in marine sediments by condensation reactions3. However, the chemical structural compositions of marine fulvic acids have not been defined sufficiently to allow this precursor relationship to be made. Here NMR spectroscopy is used to identify more clearly the chemical structural components of some marine sedimentary fulvic acids, thus enabling a more useful examination of their relationship to more complex humic substances. ?? 1980 Nature Publishing Group.

Organic chemistry as a language and the implications of chemical linguistics for structural and retrosynthetic analyses.

PubMed

Cadeddu, Andrea; Wylie, Elizabeth K; Jurczak, Janusz; Wampler-Doty, Matthew; Grzybowski, Bartosz A

2014-07-28

Methods of computational linguistics are used to demonstrate that a natural language such as English and organic chemistry have the same structure in terms of the frequency of, respectively, text fragments and molecular fragments. This quantitative correspondence suggests that it is possible to extend the methods of computational corpus linguistics to the analysis of organic molecules. It is shown that within organic molecules bonds that have highest information content are the ones that 1) define repeat/symmetry subunits and 2) in asymmetric molecules, define the loci of potential retrosynthetic disconnections. Linguistics-based analysis appears well-suited to the analysis of complex structural and reactivity patterns within organic molecules. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

THE FUTURE OF TOXICOLOGY-PREDICTIVE TOXICOLOGY ...

EPA Pesticide Factsheets

A chemistry approach to predictive toxicology relies on structure−activity relationship (SAR) modeling to predict biological activity from chemical structure. Such approaches have proven capabilities when applied to well-defined toxicity end points or regions of chemical space. These approaches are less well-suited, however, to the challenges of global toxicity prediction, i.e., to predicting the potential toxicity of structurally diverse chemicals across a wide range of end points of regulatory and pharmaceutical concern. New approaches that have the potential to significantly improve capabilities in predictive toxicology are elaborating the “activity” portion of the SAR paradigm. Recent advances in two areas of endeavor are particularly promising. Toxicity data informatics relies on standardized data schema, developed for particular areas of toxicological study, to facilitate data integration and enable relational exploration and mining of data across both historical and new areas of toxicological investigation. Bioassay profiling refers to large-scale high-throughput screening approaches that use chemicals as probes to broadly characterize biological response space, extending the concept of chemical “properties” to the biological activity domain. The effective capture and representation of legacy and new toxicity data into mineable form and the large-scale generation of new bioassay data in relation to chemical toxicity, both employing chemical stru

Designing a Quantitative Structure-Activity Relationship for the ...

EPA Pesticide Factsheets

Toxicokinetic models serve a vital role in risk assessment by bridging the gap between chemical exposure and potentially toxic endpoints. While intrinsic metabolic clearance rates have a strong impact on toxicokinetics, limited data is available for environmentally relevant chemicals including nearly 8000 chemicals tested for in vitro bioactivity in the Tox21 program. To address this gap, a quantitative structure-activity relationship (QSAR) for intrinsic metabolic clearance rate was developed to offer reliable in silico predictions for a diverse array of chemicals. Models were constructed with curated in vitro assay data for both pharmaceutical-like chemicals (ChEMBL database) and environmentally relevant chemicals (ToxCast screening) from human liver microsomes (2176 from ChEMBL) and human hepatocytes (757 from ChEMBL and 332 from ToxCast). Due to variability in the experimental data, a binned approach was utilized to classify metabolic rates. Machine learning algorithms, such as random forest and k-nearest neighbor, were coupled with open source molecular descriptors and fingerprints to provide reasonable estimates of intrinsic metabolic clearance rates. Applicability domains defined the optimal chemical space for predictions, which covered environmental chemicals well. A reduced set of informative descriptors (including relative charge and lipophilicity) and a mixed training set of pharmaceuticals and environmentally relevant chemicals provided the best intr

Control of peptide nanotube diameter by chemical modifications of an aromatic residue involved in a single close contact

PubMed Central

Tarabout, Christophe; Roux, Stéphane; Gobeaux, Frédéric; Fay, Nicolas; Pouget, Emilie; Meriadec, Cristelle; Ligeti, Melinda; Thomas, Daniel; IJsselstijn, Maarten; Besselievre, François; Buisson, David-Alexandre; Verbavatz, Jean-Marc; Petitjean, Michel; Valéry, Céline; Perrin, Lionel; Rousseau, Bernard; Artzner, Franck; Paternostre, Maité; Cintrat, Jean-Christophe

2011-01-01

Supramolecular self-assembly is an attractive pathway for bottom-up synthesis of novel nanomaterials. In particular, this approach allows the spontaneous formation of structures of well-defined shapes and monodisperse characteristic sizes. Because nanotechnology mainly relies on size-dependent physical phenomena, the control of monodispersity is required, but the possibility of tuning the size is also essential. For self-assembling systems, shape, size, and monodispersity are mainly settled by the chemical structure of the building block. Attempts to change the size notably by chemical modification usually end up with the loss of self-assembly. Here, we generated a library of 17 peptides forming nanotubes of monodisperse diameter ranging from 10 to 36 nm. A structural model taking into account close contacts explains how a modification of a few Å of a single aromatic residue induces a fourfold increase in nanotube diameter. The application of such a strategy is demonstrated by the formation of silica nanotubes of various diameters. PMID:21518895

Predictive Modeling of Chemical Hazard by Integrating Numerical Descriptors of Chemical Structures and Short-term Toxicity Assay Data

PubMed Central

Rusyn, Ivan; Sedykh, Alexander; Guyton, Kathryn Z.; Tropsha, Alexander

2012-01-01

Quantitative structure-activity relationship (QSAR) models are widely used for in silico prediction of in vivo toxicity of drug candidates or environmental chemicals, adding value to candidate selection in drug development or in a search for less hazardous and more sustainable alternatives for chemicals in commerce. The development of traditional QSAR models is enabled by numerical descriptors representing the inherent chemical properties that can be easily defined for any number of molecules; however, traditional QSAR models often have limited predictive power due to the lack of data and complexity of in vivo endpoints. Although it has been indeed difficult to obtain experimentally derived toxicity data on a large number of chemicals in the past, the results of quantitative in vitro screening of thousands of environmental chemicals in hundreds of experimental systems are now available and continue to accumulate. In addition, publicly accessible toxicogenomics data collected on hundreds of chemicals provide another dimension of molecular information that is potentially useful for predictive toxicity modeling. These new characteristics of molecular bioactivity arising from short-term biological assays, i.e., in vitro screening and/or in vivo toxicogenomics data can now be exploited in combination with chemical structural information to generate hybrid QSAR–like quantitative models to predict human toxicity and carcinogenicity. Using several case studies, we illustrate the benefits of a hybrid modeling approach, namely improvements in the accuracy of models, enhanced interpretation of the most predictive features, and expanded applicability domain for wider chemical space coverage. PMID:22387746

Catalytic diversity in self-propagating peptide assemblies

NASA Astrophysics Data System (ADS)

Omosun, Tolulope O.; Hsieh, Ming-Chien; Childers, W. Seth; Das, Dibyendu; Mehta, Anil K.; Anthony, Neil R.; Pan, Ting; Grover, Martha A.; Berland, Keith M.; Lynn, David G.

2017-08-01

The protein-only infectious agents known as prions exist within cellular matrices as populations of assembled polypeptide phases ranging from particles to amyloid fibres. These phases appear to undergo Darwinian-like selection and propagation, yet remarkably little is known about their accessible chemical and biological functions. Here we construct simple peptides that assemble into well-defined amyloid phases and define paracrystalline surfaces able to catalyse specific enantioselective chemical reactions. Structural adjustments of individual amino acid residues predictably control both the assembled crystalline order and their accessible catalytic repertoire. Notably, the density and proximity of the extended arrays of enantioselective catalytic sites achieve template-directed polymerization of new polymers. These diverse amyloid templates can now be extended as dynamic self-propagating templates for the construction of even more complex functional materials.

Precise structural analysis of α-helical polypeptide by quantum-chemical calculation related to reciprocal side-chain combination of two L-phenylalanine residues

NASA Astrophysics Data System (ADS)

Niimura, Subaru; Kurosu, Hiromichi; Shoji, Akira

2010-04-01

To clarify the positive role of side-chain conformation in the stability of protein secondary structure (main-chain conformation), we successfully calculated the optimization structure of a series of well-defined α-helical octadecapeptides composed of two L-phenylalanine (Phe) and 16 L-alanine (Ala) residues, based on the molecular orbital calculation with density functional theory (DFT/B3LYP/6-31G(d)). From the total energy calculation and the precise secondary structural analysis, we found that the conformational stability of the α-helix is closely related to the reciprocal side-chain combinations (such as positional relation and side-chain conformation) of two Phe residues in this system. Furthermore, we demonstrated that the 1H, 13C, 15N and 17O isotropic chemical shifts of each Phe residue depend on the respective side-chain conformations of the Phe residue.

Dynamics of liquids, molecules, and proteins measured with ultrafast 2D IR vibrational echo chemical exchange spectroscopy.

PubMed

Fayer, M D

2009-01-01

A wide variety of molecular systems undergo fast structural changes under thermal equilibrium conditions. Such transformations are involved in a vast array of chemical problems. Experimentally measuring equilibrium dynamics is a challenging problem that is at the forefront of chemical research. This review describes ultrafast 2D IR vibrational echo chemical exchange experiments and applies them to several types of molecular systems. The formation and dissociation of organic solute-solvent complexes are directly observed. The dissociation times of 13 complexes, ranging from 4 ps to 140 ps, are shown to obey a relationship that depends on the complex's formation enthalpy. The rate of rotational gauche-trans isomerization around a carbon-carbon single bond is determined for a substituted ethane at room temperature in a low viscosity solvent. The results are used to obtain an approximate isomerization rate for ethane. Finally, the time dependence of a well-defined single structural transformation of a protein is measured.

Atomically precise edge chlorination of nanographenes and its application in graphene nanoribbons

PubMed Central

Tan, Yuan-Zhi; Yang, Bo; Parvez, Khaled; Narita, Akimitsu; Osella, Silvio; Beljonne, David; Feng, Xinliang; Müllen, Klaus

2013-01-01

Chemical functionalization is one of the most powerful and widely used strategies to control the properties of nanomaterials, particularly in the field of graphene. However, the ill-defined structure of the present functionalized graphene inhibits atomically precise structural characterization and structure-correlated property modulation. Here we present a general edge chlorination protocol for atomically precise functionalization of nanographenes at different scales from 1.2 to 3.4 nm and its application in graphene nanoribbons. The well-defined edge chlorination is unambiguously confirmed by X-ray single-crystal analysis, which also discloses the characteristic non-planar molecular shape and detailed bond lengths of chlorinated nanographenes. Chlorinated nanographenes and graphene nanoribbons manifest enhanced solution processability associated with decreases in the optical band gap and frontier molecular orbital energy levels, exemplifying the structure-correlated property modulation by precise edge chlorination. PMID:24212200

NMR structure calculation for all small molecule ligands and non-standard residues from the PDB Chemical Component Dictionary.

PubMed

Yilmaz, Emel Maden; Güntert, Peter

2015-09-01

An algorithm, CYLIB, is presented for converting molecular topology descriptions from the PDB Chemical Component Dictionary into CYANA residue library entries. The CYANA structure calculation algorithm uses torsion angle molecular dynamics for the efficient computation of three-dimensional structures from NMR-derived restraints. For this, the molecules have to be represented in torsion angle space with rotations around covalent single bonds as the only degrees of freedom. The molecule must be given a tree structure of torsion angles connecting rigid units composed of one or several atoms with fixed relative positions. Setting up CYANA residue library entries therefore involves, besides straightforward format conversion, the non-trivial step of defining a suitable tree structure of torsion angles, and to re-order the atoms in a way that is compatible with this tree structure. This can be done manually for small numbers of ligands but the process is time-consuming and error-prone. An automated method is necessary in order to handle the large number of different potential ligand molecules to be studied in drug design projects. Here, we present an algorithm for this purpose, and show that CYANA structure calculations can be performed with almost all small molecule ligands and non-standard amino acid residues in the PDB Chemical Component Dictionary.

Evaluation of SARs for the prediction of eye irritation/corrosion potential: structural inclusion rules in the BfR decision support system.

PubMed

Tsakovska, I; Saliner, A Gallegos; Netzeva, T; Pavan, M; Worth, A P

2007-01-01

The proposed REACH regulation within the European Union (EU) aims to minimise the number of laboratory animals used for human hazard and risk assessment while ensuring adequate protection of human health and the environment. One way to achieve this goal is to develop non-testing methods, such as (quantitative) structure-activity relationships ([Q]SARs), suitable for identifying toxicological hazard from chemical structure and physicochemical properties alone. A database containing data submitted within the EU New Chemicals Notification procedure was compiled by the German Bundesinstitut für Risikobewertung (BfR). On the basis of these data, the BfR built a decision support system (DSS) for the prediction of several toxicological endpoints. For the prediction of eye irritation and corrosion potential, the DSS contains 31 physicochemical exclusion rules evaluated previously by the European Chemicals Bureau (ECB), and 27 inclusion rules that define structural alerts potentially responsible for eye irritation and/or corrosion. This work summarises the results of a study carried out by the ECB to assess the performance of the BfR structural rulebase. The assessment included: (a) evaluation of the structural alerts by using the training set of 1341 substances with experimental data for eye irritation and corrosion; and (b) external validation by using an independent test set of 199 chemicals. Recommendations are made for the further development of the structural rules in order to increase the overall predictivity of the DSS.

Fiber Optic Chemical Sensors

DTIC Science & Technology

1993-10-01

patent rights. A major problem was identification of the property of ST&E vs LLNL ST&E was formed to manage the activities of Dr. Hirschfeld and Dr...positions of the fields defined in a fixed format to allow its importation into file management programs both in the microcomputer and the minicomputer...Systems Inc., Perry, Florida. askSam is a free-form information manager . A few basic elements of structure can be used to create a highly structured

Magnesiothermic conversion of the silica-mineralizing golden algae Mallomonas caudata and Synura petersenii to elemental silicon with high geometric precision

PubMed Central

Petrack, Janina; Jost, Steffen; Boenigk, Jens

2014-01-01

Summary Chrysophyceae, also known as golden algae, contain characteristic, three-dimensional biomineralized silica structures. Their chemical composition and microscopic structure was studied. By high-temperature conversion of the skeleton of Mallomonas caudata and Synura petersenii into elementary silicon by magnesium vapour, nanostructured defined replicates were produced which were clearly seen after removal of the formed magnesium oxide with acid. PMID:24991491

Differentiating low-molecular-weight heparins based on chemical, biological, and pharmacologic properties: implications for the development of generic versions of low-molecular-weight heparins.

PubMed

Jeske, Walter P; Walenga, Jeanine M; Hoppensteadt, Debra A; Vandenberg, Curtis; Brubaker, Aleah; Adiguzel, Cafer; Bakhos, Mamdouh; Fareed, Jawed

2008-02-01

Low-molecular-weight heparins (LMWHs) are polypharmacologic drugs used to treat thrombotic and cardiovascular disorders. These drugs are manufactured using different chemical and enzymatic methods, resulting in products with distinct chemical and pharmacologic profiles. Generic LMWHs have been introduced in Asia and South America, and several generic suppliers are seeking regulatory approval in the United States and the European Union. For simple small-molecule drugs, generic drugs have the same chemical structure, potency, and bioavailability as the innovator drug. Applying this definition to complex biological products such as the LMWHs has proved difficult. One major issue is defining appropriate criteria to demonstrate bioequivalence; pharmacopoeial specifications alone appear to be inadequate. Whereas available generic versions of LMWHs exhibit similar molecular and pharmacopoeial profiles, marked differences in their biological and pharmacologic behavior have been noted. Preliminary studies have demonstrated differences in terms of anti-Xa activity and tissue factor pathway inhibitor release after subcutaneous administration, as well as antiplatelet and profibrinolytic effects. The current data emphasize the need to consider multiple functional parameters when defining bioequivalence of biologic drugs with complex structures and activities and also underscore the importance of further pharmacologic studies involving animal models and human clinical trials. The U.S. Food and Drug Administration and the European Medicine Evaluation Agency are currently developing guidelines for the acceptance of biosimilar agents including LMWHs. Until such guidelines are complete, generic interchange may not be feasible.

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

Strategies for the Conversion of Lignin to High-Value Polymeric Materials: Review and Perspective.

PubMed

Upton, Brianna M; Kasko, Andrea M

2016-02-24

The majority of commodity plastics and materials are derived from petroleum-based chemicals, illustrating the strong dependence on products derived from non-renewable energy sources. As the most accessible, renewable form of carbon (in comparison to CO2), lignocellulosic biomass (defined as organic matter available on a renewable basis) has been acknowledged as the most logical carbon-based feedstock for a variety of materials such as biofuels and chemicals. This Review focuses on methods developed to synthesize polymers derived from lignin, monolignols, and lignin-derived chemicals. Major topics include the structure and processing of lignocellulosic biomass to lignin, polymers utilizing lignin as a macromonomer, synthesis of monomers and polymers from monolignols, and polymers from lignin-derived chemicals, such as vanillin.

Photoluminescence of amorphous and crystalline silicon nanoclusters in silicon nitride and oxide superlattices

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

Shuleiko, D. V., E-mail: shuleyko.dmitriy@physics.msu.ru; Zabotnov, S. V.; Zhigunov, D. M.

2017-02-15

The photoluminescence properties of silicon nitride and oxide superlattices fabricated by plasmaenhanced chemical vapor deposition are studied. In the structures annealed at a temperature of 1150°C, photoluminescence peaks at about 1.45 eV are recorded. The peaks are defined by exciton recombination in silicon nanocrystals formed upon annealing. Along with the 1.45-eV peaks, a number of peaks defined by recombination at defects at the interface between the nanocrystals and silicon-nitride matrix are detected. The structures annealed at 900°C exhibit a number of photoluminescence peaks in the range 1.3–2.0 eV. These peaks are defined by both the recombination at defects and excitonmore » recombination in amorphous silicon nanoclusters formed at an annealing temperature of 900°C. The observed features of all of the photoluminescence spectra are confirmed by the nature of the photoluminescence kinetics.« less

Chemical abundances in low surface brightness galaxies: Implications for their evolution

NASA Technical Reports Server (NTRS)

Mcgaugh, S. S.; Bothun, G. D.

1993-01-01

Low Surface Brightness (LSB) galaxies are an important but often neglected part of the galaxy content of the universe. Their importance stems both from the selection effects which cause them to be under-represented in galaxy catalogs, and from what they can tell us about the physical processes of galaxy evolution that has resulted in something other than the traditional Hubble sequence of spirals. An important constraint for any evolutionary model is the present day chemical abundances of LSB disks. Towards this end, spectra for a sample of 75 H 2 regions distributed in 20 LSB disks galaxies were obtained. Structurally, this sample is defined as having B(0) fainter than 23.0 mag arcsec(sup -2) and scale lengths that cluster either around 3 kpc or 10 kpc. In fact, structurally, these galaxies are very similar to the high surface brightness spirals which define the Hubble sequence. Thus, our sample galaxies are not dwarf galaxies but instead have masses comparable to or in excess of the Milky Way. The basic results from these observations are summarized.

In search of new lead compounds for trypanosomiasis drug design: A protein structure-based linked-fragment approach

NASA Astrophysics Data System (ADS)

Verlinde, Christophe L. M. J.; Rudenko, Gabrielle; Hol, Wim G. J.

1992-04-01

A modular method for pursuing structure-based inhibitor design in the framework of a design cycle is presented. The approach entails four stages: (1) a design pathway is defined in the three-dimensional structure of a target protein; (2) this pathway is divided into subregions; (3) complementary building blocks, also called fragments, are designed in each subregion; complementarity is defined in terms of shape, hydrophobicity, hydrogen bond properties and electrostatics; and (4) fragments from different subregions are linked into potential lead compounds. Stages (3) and (4) are qualitatively guided by force-field calculations. In addition, the designed fragments serve as entries for retrieving existing compounds from chemical databases. This linked-fragment approach has been applied in the design of potentially selective inhibitors of triosephosphate isomerase from Trypanosoma brucei, the causative agent of sleeping sickness.

Development of an ecotoxicity QSAR model for the KAshinhou Tool for Ecotoxicity (KATE) system, March 2009 version.

PubMed

Furuhama, A; Toida, T; Nishikawa, N; Aoki, Y; Yoshioka, Y; Shiraishi, H

2010-07-01

The KAshinhou Tool for Ecotoxicity (KATE) system, including ecotoxicity quantitative structure-activity relationship (QSAR) models, was developed by the Japanese National Institute for Environmental Studies (NIES) using the database of aquatic toxicity results gathered by the Japanese Ministry of the Environment and the US EPA fathead minnow database. In this system chemicals can be entered according to their one-dimensional structures and classified by substructure. The QSAR equations for predicting the toxicity of a chemical compound assume a linear correlation between its log P value and its aquatic toxicity. KATE uses a structural domain called C-judgement, defined by the substructures of specified functional groups in the QSAR models. Internal validation by the leave-one-out method confirms that the QSAR equations, with r(2 )> 0.7, RMSE 5, give acceptable q(2) values. Such external validation indicates that a group of chemicals with an in-domain of KATE C-judgements exhibits a lower root mean square error (RMSE). These findings demonstrate that the KATE system has the potential to enable chemicals to be categorised as potential hazards.

Templated electrokinetic directed chemical assembly for the fabrication of close-packed plasmonic metamolecules

NASA Astrophysics Data System (ADS)

Thrift, W. J.; Darvishzadeh-Varcheie, M.; Capolino, F.; Ragan, R.

2017-08-01

Colloidal self-assembly combined with templated surfaces holds the promise of fabricating large area devices in a low cost facile manner. This directed assembly approach improves the complexity of assemblies that can be achieved with self-assembly while maintaining advantages of molecular scale control. In this work, electrokinetic driving forces, i.e., electrohydrodynamic flow, are paired with chemical crosslinking between colloidal particles to form close-packed plasmonic metamolecules. This method addresses challenges of obtaining uniformity in nanostructure geometry and nanometer scale gap spacings in structures. Electrohydrodynamic flows yield robust driving forces between the template and nanoparticles as well as between nanoparticles on the surface promoting the assembly of close-packed metamolecules. Here, electron beam lithography defined Au pillars are used as seed structures that generate electrohydrodynamic flows. Chemical crosslinking between Au surfaces enables molecular control over gap spacings between nanoparticles and Au pillars. An as-fabricated structure is analyzed via full wave electromagnetic simulations and shown to produce large magnetic field enhancements on the order of 3.5 at optical frequencies. This novel method for directed self-assembly demonstrates the synergy between colloidal driving forces and chemical crosslinking for the fabrication of plasmonic metamolecules with unique electromagnetic properties.

Raman structural studies of the nickel electrode

NASA Technical Reports Server (NTRS)

Cornilsen, Bahne C.

1994-01-01

The objectives of this investigation have been to define the structures of charged active mass, discharged active mass, and related precursor materials (alpha-phases), with the purpose of better understanding the chemical and electrochemical reactions, including failure mechanisms and cobalt incorporation, so that the nickel electrode may be improved. Although our primary tool has been Raman spectroscopy, the structural conclusions drawn from the Raman data have been supported and augmented by three other analysis methods: infrared spectroscopy, powder X-ray Diffraction (XRD), and x-ray absorption spectroscopy (in particular EXAFS, Extended X-ray Absorption Fine Structure spectroscopy).

A model to systematically employ professional judgment in the Bayesian Decision Analysis for a semiconductor industry exposure assessment.

PubMed

Torres, Craig; Jones, Rachael; Boelter, Fred; Poole, James; Dell, Linda; Harper, Paul

2014-01-01

Bayesian Decision Analysis (BDA) uses Bayesian statistics to integrate multiple types of exposure information and classify exposures within the exposure rating categorization scheme promoted in American Industrial Hygiene Association (AIHA) publications. Prior distributions for BDA may be developed from existing monitoring data, mathematical models, or professional judgment. Professional judgments may misclassify exposures. We suggest that a structured qualitative risk assessment (QLRA) method can provide consistency and transparency in professional judgments. In this analysis, we use a structured QLRA method to define prior distributions (priors) for BDA. We applied this approach at three semiconductor facilities in South Korea, and present an evaluation of the performance of structured QLRA for determination of priors, and an evaluation of occupational exposures using BDA. Specifically, the structured QLRA was applied to chemical agents in similar exposure groups to identify provisional risk ratings. Standard priors were developed for each risk rating before review of historical monitoring data. Newly collected monitoring data were used to update priors informed by QLRA or historical monitoring data, and determine the posterior distribution. Exposure ratings were defined by the rating category with the highest probability--i.e., the most likely. We found the most likely exposure rating in the QLRA-informed priors to be consistent with historical and newly collected monitoring data, and the posterior exposure ratings developed with QLRA-informed priors to be equal to or greater than those developed with data-informed priors in 94% of comparisons. Overall, exposures at these facilities are consistent with well-controlled work environments. That is, the 95th percentile of exposure distributions are ≤50% of the occupational exposure limit (OEL) for all chemical-SEG combinations evaluated; and are ≤10% of the limit for 94% of chemical-SEG combinations evaluated.

Well-defined porous membranes for robust omniphobic surfaces via microfluidic emulsion templating

NASA Astrophysics Data System (ADS)

Zhu, Pingan; Kong, Tiantian; Tang, Xin; Wang, Liqiu

2017-06-01

Durability is a long-standing challenge in designing liquid-repellent surfaces. A high-performance omniphobic surface must robustly repel liquids, while maintaining mechanical/chemical stability. However, liquid repellency and mechanical durability are generally mutually exclusive properties for many omniphobic surfaces--improving one performance inevitably results in decreased performance in another. Here we report well-defined porous membranes for durable omniphobic surfaces inspired by the springtail cuticle. The omniphobicity is shown via an amphiphilic material micro-textured with re-entrant surface morphology; the mechanical durability arises from the interconnected microstructures. The innovative fabrication method--termed microfluidic emulsion templating--is facile, cost-effective, scalable and can precisely engineer the structural topographies. The robust omniphobic surface is expected to open up new avenues for diverse applications due to its mechanical and chemical robustness, transparency, reversible Cassie-Wenzel transition, transferability, flexibility and stretchability.

Hybrid carrageenans: isolation, chemical structure, and gel properties.

PubMed

Hilliou, Loic

2014-01-01

Hybrid carrageenan is a special class of carrageenan with niche application in food industry. This polysaccharide is extracted from specific species of seaweeds belonging to the Gigartinales order. This chapter focuses on hybrid carrageenan showing the ability to form gels in water, which is known in the food industry as weak kappa or kappa-2 carrageenan. After introducing the general chemical structure defining hybrid carrageenan, the isolation of the polysaccharide will be discussed focusing on the interplay between seaweed species, extraction parameters, and the hybrid carrageenan chemistry. Then, the rheological experiments used to determine the small and large deformation behavior of gels will be detailed before reviewing the relationships between gel properties and hybrid carrageenan chemistry. © 2014 Elsevier Inc. All rights reserved.

Surfactants at the Design Limit.

PubMed

Czajka, Adam; Hazell, Gavin; Eastoe, Julian

2015-08-04

This article analyzes how the individual structural elements of surfactant molecules affect surface properties, in particular, the point of reference defined by the limiting surface tension at the aqueous cmc, γcmc. Particular emphasis is given to how the chemical nature and structure of the hydrophobic tails influence γcmc. By comparing the three different classes of surfactants, fluorocarbon, silicone, and hydrocarbon, a generalized surface packing index is introduced which is independent of the chemical nature of the surfactants. This parameter ϕcmc represents the volume fraction of surfactant chain fragments in a surface film at the aqueous cmc. It is shown that ϕcmc is a useful index for understanding the limiting surface tension of surfactants and can be useful for designing new superefficient surfactants.

Wet-chemical passivation of atomically flat and structured silicon substrates for solar cell application

NASA Astrophysics Data System (ADS)

Angermann, H.; Rappich, J.; Korte, L.; Sieber, I.; Conrad, E.; Schmidt, M.; Hübener, K.; Polte, J.; Hauschild, J.

2008-04-01

Special sequences of wet-chemical oxidation and etching steps were optimised with respect to the etching behaviour of differently oriented silicon to prepare very smooth silicon interfaces with excellent electronic properties on mono- and poly-crystalline substrates. Surface photovoltage (SPV) and photoluminescence (PL) measurements, atomic force microscopy (AFM) and scanning electron microscopy (SEM) investigations were utilised to develop wet-chemical smoothing procedures for atomically flat and structured surfaces, respectively. Hydrogen-termination as well as passivation by wet-chemical oxides were used to inhibit surface contamination and native oxidation during the technological processing. Compared to conventional pre-treatments, significantly lower micro-roughness and densities of surface states were achieved on mono-crystalline Si(100), on evenly distributed atomic steps, such as on vicinal Si(111), on silicon wafers with randomly distributed upside pyramids, and on poly-crystalline EFG ( Edge-defined Film-fed- Growth) silicon substrates. The recombination loss at a-Si:H/c-Si interfaces prepared on c-Si substrates with randomly distributed upside pyramids was markedly reduced by an optimised wet-chemical smoothing procedure, as determined by PL measurements. For amorphous-crystalline hetero-junction solar cells (ZnO/a-Si:H(n)/c-Si(p)/Al) with textured c-Si substrates the smoothening procedure results in a significant increase of short circuit current Isc, fill factor and efficiency η. The scatter in the cell parameters for measurements on different cells is much narrower, as compared to conventional pre-treatments, indicating more well-defined and reproducible surface conditions prior to a-Si:H emitter deposition and/or a higher stability of the c-Si surface against variations in the a-Si:H deposition conditions.

A three-dimensional numerical study on instability of sinusoidal flame induced by multiple shock waves

NASA Astrophysics Data System (ADS)

Chen, Xiao; Dong, Gang; Jiang, Hua

2017-04-01

The instabilities of a three-dimensional sinusoidally premixed flame induced by an incident shock wave with Mach = 1.7 and its reshock waves were studied by using the Navier-Stokes (NS) equations with a single-step chemical reaction and a high resolution, 9th-order weighted essentially non-oscillatory scheme. The computational results were validated by the grid independence test and the experimental results in the literature. The computational results show that after the passage of incident shock wave the flame interface develops in symmetric structure accompanied by large-scale transverse vortex structures. After the interactions by successive reshock waves, the flame interface is gradually destabilized and broken up, and the large-scale vortex structures are gradually transformed into small-scale vortex structures. The small-scale vortices tend to be isotropic later. The results also reveal that the evolution of the flame interface is affected by both mixing process and chemical reaction. In order to identify the relationship between the mixing and the chemical reaction, a dimensionless parameter, η , that is defined as the ratio of mixing time scale to chemical reaction time scale, is introduced. It is found that at each interaction stage the effect of chemical reaction is enhanced with time. The enhanced effect of chemical reaction at the interaction stage by incident shock wave is greater than that at the interaction stages by reshock waves. The result suggests that the parameter η can reasonably character the features of flame interface development induced by the multiple shock waves.

High-resolution structure of the Shigella type-III secretion needle by solid-state NMR and cryo-electron microscopy

NASA Astrophysics Data System (ADS)

Demers, Jean-Philippe; Habenstein, Birgit; Loquet, Antoine; Kumar Vasa, Suresh; Giller, Karin; Becker, Stefan; Baker, David; Lange, Adam; Sgourakis, Nikolaos G.

2014-09-01

We introduce a general hybrid approach for determining the structures of supramolecular assemblies. Cryo-electron microscopy (cryo-EM) data define the overall envelope of the assembly and rigid-body orientation of the subunits while solid-state nuclear magnetic resonance (ssNMR) chemical shifts and distance constraints define the local secondary structure, protein fold and inter-subunit interactions. Finally, Rosetta structure calculations provide a general framework to integrate the different sources of structural information. Combining a 7.7-Å cryo-EM density map and 996 ssNMR distance constraints, the structure of the type-III secretion system needle of Shigella flexneri is determined to a precision of 0.4 Å. The calculated structures are cross-validated using an independent data set of 691 ssNMR constraints and scanning transmission electron microscopy measurements. The hybrid model resolves the conformation of the non-conserved N terminus, which occupies a protrusion in the cryo-EM density, and reveals conserved pore residues forming a continuous pattern of electrostatic interactions, thereby suggesting a mechanism for effector protein translocation.

Automated Inference of Chemical Discriminants of Biological Activity.

PubMed

Raschka, Sebastian; Scott, Anne M; Huertas, Mar; Li, Weiming; Kuhn, Leslie A

2018-01-01

Ligand-based virtual screening has become a standard technique for the efficient discovery of bioactive small molecules. Following assays to determine the activity of compounds selected by virtual screening, or other approaches in which dozens to thousands of molecules have been tested, machine learning techniques make it straightforward to discover the patterns of chemical groups that correlate with the desired biological activity. Defining the chemical features that generate activity can be used to guide the selection of molecules for subsequent rounds of screening and assaying, as well as help design new, more active molecules for organic synthesis.The quantitative structure-activity relationship machine learning protocols we describe here, using decision trees, random forests, and sequential feature selection, take as input the chemical structure of a single, known active small molecule (e.g., an inhibitor, agonist, or substrate) for comparison with the structure of each tested molecule. Knowledge of the atomic structure of the protein target and its interactions with the active compound are not required. These protocols can be modified and applied to any data set that consists of a series of measured structural, chemical, or other features for each tested molecule, along with the experimentally measured value of the response variable you would like to predict or optimize for your project, for instance, inhibitory activity in a biological assay or ΔG binding . To illustrate the use of different machine learning algorithms, we step through the analysis of a dataset of inhibitor candidates from virtual screening that were tested recently for their ability to inhibit GPCR-mediated signaling in a vertebrate.

Quantifying the chemical composition of soil organic carbon with solid-state 13C NMR

NASA Astrophysics Data System (ADS)

Baldock, J. A.; Sanderman, J.

2011-12-01

The vulnerability of soil organic carbon (SOC) to biological decomposition and mineralisation to CO2 is defined at least partially by its chemical composition. Highly aromatic charcoal-like SOC components are more stable to biological decomposition than other forms of carbon including cellulose. Solid-state 13C NMR has gained wide acceptance as a method capable of defining SOC chemical composition and mathematical fitting processes have been developed to estimate biochemical composition. Obtaining accurate estimates depends on an ability to quantitatively detect all carbon present in a sample. Often little attention has been paid to defining the proportion of organic carbon present in a soil that is observable in solid-state 13C NMR analyses of soil samples. However, if such data is to be used to inform carbon cycling studies, it is critical that quantitative assessments of SOC observability be undertaken. For example, it is now well established that a significant discrimination exists against the detection of the low proton content polyaromatic structures typical of charcoal using cross polarisation 13C NMR analyses. Such discrimination does not exist where direct polarisation analyses are completed. In this study, the chemical composition of SOC as defined by cross polarisation and direct polarisation13C NMR analyses will be compared for Australian soils collected from under a diverse range of agricultural managements and climatic conditions. Results indicate that where significant charcoal C contents exist, it is highly under-represented in the acquired CP spectra. For some soils, a discrimination against alkyl carbon was also evident. The ability to derive correction factors to compensate for such discriminations will be assessed and presented.

Linguistic measures of chemical diversity and the "keywords" of molecular collections.

PubMed

Woźniak, Michał; Wołos, Agnieszka; Modrzyk, Urszula; Górski, Rafał L; Winkowski, Jan; Bajczyk, Michał; Szymkuć, Sara; Grzybowski, Bartosz A; Eder, Maciej

2018-05-15

Computerized linguistic analyses have proven of immense value in comparing and searching through large text collections ("corpora"), including those deposited on the Internet - indeed, it would nowadays be hard to imagine browsing the Web without, for instance, search algorithms extracting most appropriate keywords from documents. This paper describes how such corpus-linguistic concepts can be extended to chemistry based on characteristic "chemical words" that span more than traditional functional groups and, instead, look at common structural fragments molecules share. Using these words, it is possible to quantify the diversity of chemical collections/databases in new ways and to define molecular "keywords" by which such collections are best characterized and annotated.

A molecular engineering toolbox for the structural biologist

PubMed Central

Debelouchina, Galia T.; Muir, Tom W.

2018-01-01

Exciting new technological developments have pushed the boundaries of structural biology, and have enabled studies of biological macromolecules and assemblies that would have been unthinkable not long ago. Yet, the enhanced capabilities of structural biologists to pry into the complex molecular world have also placed new demands on the abilities of protein engineers to reproduce this complexity into the test tube. With this challenge in mind, we review the contents of the modern molecular engineering toolbox that allow the manipulation of proteins in a site-specific and chemically well-defined fashion. Thus, we cover concepts related to the modification of cysteines and other natural amino acids, native chemical ligation, intein and sortase-based approaches, amber suppression, as well as chemical and enzymatic bio-conjugation strategies. We also describe how these tools can be used to aid methodology development in X-ray crystallography, nuclear magnetic resonance, cryo-electron microscopy and in the studies of dynamic interactions. It is our hope that this monograph will inspire structural biologists and protein engineers alike to apply these tools to novel systems, and to enhance and broaden their scope to meet the outstanding challenges in understanding the molecular basis of cellular processes and disease. PMID:29233219

A molecular engineering toolbox for the structural biologist.

PubMed

Debelouchina, Galia T; Muir, Tom W

2017-01-01

Exciting new technological developments have pushed the boundaries of structural biology, and have enabled studies of biological macromolecules and assemblies that would have been unthinkable not long ago. Yet, the enhanced capabilities of structural biologists to pry into the complex molecular world have also placed new demands on the abilities of protein engineers to reproduce this complexity into the test tube. With this challenge in mind, we review the contents of the modern molecular engineering toolbox that allow the manipulation of proteins in a site-specific and chemically well-defined fashion. Thus, we cover concepts related to the modification of cysteines and other natural amino acids, native chemical ligation, intein and sortase-based approaches, amber suppression, as well as chemical and enzymatic bio-conjugation strategies. We also describe how these tools can be used to aid methodology development in X-ray crystallography, nuclear magnetic resonance, cryo-electron microscopy and in the studies of dynamic interactions. It is our hope that this monograph will inspire structural biologists and protein engineers alike to apply these tools to novel systems, and to enhance and broaden their scope to meet the outstanding challenges in understanding the molecular basis of cellular processes and disease.

Combined Approach for the Structural Characterization of Alkali Fluoroscandates: Solid-State NMR, Powder X-ray Diffraction, and Density Functional Theory Calculations.

PubMed

Rakhmatullin, Aydar; Polovov, Ilya B; Maltsev, Dmitry; Allix, Mathieu; Volkovich, Vladimir; Chukin, Andrey V; Boča, Miroslav; Bessada, Catherine

2018-02-05

The structures of several fluoroscandate compounds are presented here using a characterization approach combining powder X-ray diffraction and solid-state NMR. The structure of K 5 Sc 3 F 14 was fully determined from Rietveld refinement performed on powder X-ray diffraction data. Moreover, the local structures of NaScF 4 , Li 3 ScF 6 , KSc 2 F 7 , and Na 3 ScF 6 compounds were studied in detail from solid-state 19 F and 45 Sc NMR experiments. The 45 Sc chemical shift ranges for six- and seven-coordinated scandium environments were defined. The 19 F chemical shift ranges for bridging and terminal fluorine atoms were also determined. First-principles calculations of the 19 F and 45 Sc NMR parameters were carried out using plane-wave basis sets and periodic boundary conditions (CASTEP), and the results were compared with the experimental data. A good agreement between the calculated shielding constants and experimental chemical shifts was obtained. This demonstrates the good potential of computational methods in spectroscopic assignments of solid-state 45 Sc NMR spectroscopy.

Intrinsic Atomic Orbitals: An Unbiased Bridge between Quantum Theory and Chemical Concepts.

PubMed

Knizia, Gerald

2013-11-12

Modern quantum chemistry can make quantitative predictions on an immense array of chemical systems. However, the interpretation of those predictions is often complicated by the complex wave function expansions used. Here we show that an exceptionally simple algebraic construction allows for defining atomic core and valence orbitals, polarized by the molecular environment, which can exactly represent self-consistent field wave functions. This construction provides an unbiased and direct connection between quantum chemistry and empirical chemical concepts, and can be used, for example, to calculate the nature of bonding in molecules, in chemical terms, from first principles. In particular, we find consistency with electronegativities (χ), C 1s core-level shifts, resonance substituent parameters (σR), Lewis structures, and oxidation states of transition-metal complexes.

Trouble shooting in toxicopathology

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

Rousseaux, C.G.

2005-09-01

Toxicopathology, also referred to as toxicologic pathology, can be defined as the study of structural and functional changes in cells, tissues, and organs that are induced by toxicants (such as drugs, industrial and agricultural chemicals), toxins (chemicals of biological origin such as mycotoxins and phycotoxins), and physical agents (such as heat and radiation); the investigation of the mechanisms by which these changes are induced; and the development of risk assessment and risk management policies based on such information. Toxicologic pathology primarily deals with the morphologic or structural effects of the toxicant and the mechanism by which this structural effect ismore » induced. This article highlights some of the problems that toxicologic pathologists may encounter in obtaining and interpreting pathology lesions. By alerting toxicologists to some of these issues, it is hoped that a better understanding of the use and limitations of toxicologic pathology data will occur.« less

Reversibility of Pt-Skin and Pt-Skeleton Nanostructures in Acidic Media.

PubMed

Durst, Julien; Lopez-Haro, Miguel; Dubau, Laetitia; Chatenet, Marian; Soldo-Olivier, Yvonne; Guétaz, Laure; Bayle-Guillemaud, Pascale; Maillard, Frédéric

2014-02-06

Following a well-defined series of acid and heat treatments on a benchmark Pt3Co/C sample, three different nanostructures of interest for the electrocatalysis of the oxygen reduction reaction were tailored. These nanostructures could be sorted into the "Pt-skin" structure, made of one pure Pt overlayer, and the "Pt-skeleton" structure, made of 2-3 Pt overlayers surrounding the Pt-Co alloy core. Using a unique combination of high-resolution aberration-corrected STEM-EELS, XRD, EXAFS, and XANES measurements, we provide atomically resolved pictures of these different nanostructures, including measurement of the Pt-shell thickness forming in acidic media and the resulting changes of the bulk and core chemical composition. It is shown that the Pt-skin is reverted toward the Pt-skeleton upon contact with acid electrolyte. This change in structure causes strong variations of the chemical composition.

Fabrication of nano-gap electrode arrays by the construction and selective chemical etching of nano-crosswire stacks

NASA Technical Reports Server (NTRS)

Prokopuk, Nicholas (Inventor); Son, Kyung-Ah (Inventor)

2008-01-01

Methods of fabricating nano-gap electrode structures in array configurations, and the structures so produced. The fabrication method involves depositing first and second pluralities of electrodes comprising nanowires using processes such as lithography, deposition of metals, lift-off processes, and chemical etching that can be performed using conventional processing tools applicable to electronic materials processing. The gap spacing in the nano-gap electrode array is defined by the thickness of a sacrificial spacer layer that is deposited between the first and second pluralities of electrodes. The sacrificial spacer layer is removed by etching, thereby leaving a structure in which the distance between pairs of electrodes is substantially equal to the thickness of the sacrificial spacer layer. Electrode arrays with gaps measured in units of nanometers are produced. In one embodiment, the first and second pluralities of electrodes are aligned in mutually orthogonal orientations.

Mononuclear Cu/O2 Complexes

PubMed Central

Cramer, Christopher J.; Tolman, William B.

2008-01-01

Using interwoven experimental and theoretical methods, detailed studies of several structurally defined 1:1 Cu/O2 complexes have provided important fundamental chemical information useful for understanding the nature of intermediates involved in aerobic oxidations in synthetic and enzymatic copper-mediated catalysis. In particular, these studies have shed new light onto the factors that influence the mode of O2 coordination (end-on vs. side-on) and the electronic structure, which can vary between Cu(II)-superoxo and Cu(III)-peroxo extremes. PMID:17458929

Theoretical NMR correlations based Structure Discussion.

PubMed

Junker, Jochen

2011-07-28

The constitutional assignment of natural products by NMR spectroscopy is usually based on 2D NMR experiments like COSY, HSQC, and HMBC. The actual difficulty of the structure elucidation problem depends more on the type of the investigated molecule than on its size. The moment HMBC data is involved in the process or a large number of heteroatoms is present, a possibility of multiple solutions fitting the same data set exists. A structure elucidation software can be used to find such alternative constitutional assignments and help in the discussion in order to find the correct solution. But this is rarely done. This article describes the use of theoretical NMR correlation data in the structure elucidation process with WEBCOCON, not for the initial constitutional assignments, but to define how well a suggested molecule could have been described by NMR correlation data. The results of this analysis can be used to decide on further steps needed to assure the correctness of the structural assignment. As first step the analysis of the deviation of carbon chemical shifts is performed, comparing chemical shifts predicted for each possible solution with the experimental data. The application of this technique to three well known compounds is shown. Using NMR correlation data alone for the description of the constitutions is not always enough, even when including 13C chemical shift prediction.

Linear and Branched PEIs (Polyethylenimines) and Their Property Space.

PubMed

Lungu, Claudiu N; Diudea, Mircea V; Putz, Mihai V; Grudziński, Ireneusz P

2016-04-13

A chemical property space defines the adaptability of a molecule to changing conditions and its interaction with other molecular systems determining a pharmacological response. Within a congeneric molecular series (compounds with the same derivatization algorithm and thus the same brute formula) the chemical properties vary in a monotonic manner, i.e., congeneric compounds share the same chemical property space. The chemical property space is a key component in molecular design, where some building blocks are functionalized, i.e., derivatized, and eventually self-assembled in more complex systems, such as enzyme-ligand systems, of which (physico-chemical) properties/bioactivity may be predicted by QSPR/QSAR (quantitative structure-property/activity relationship) studies. The system structure is determined by the binding type (temporal/permanent; electrostatic/covalent) and is reflected in its local electronic (and/or magnetic) properties. Such nano-systems play the role of molecular devices, important in nano-medicine. In the present article, the behavior of polyethylenimine (PEI) macromolecules (linear LPEI and branched BPEI, respectively) with respect to the glucose oxidase enzyme GOx is described in terms of their (interacting) energy, geometry and topology, in an attempt to find the best shape and size of PEIs to be useful for a chosen (nanochemistry) purpose.

Linear and Branched PEIs (Polyethylenimines) and Their Property Space

PubMed Central

Lungu, Claudiu N.; Diudea, Mircea V.; Putz, Mihai V.; Grudziński, Ireneusz P.

2016-01-01

A chemical property space defines the adaptability of a molecule to changing conditions and its interaction with other molecular systems determining a pharmacological response. Within a congeneric molecular series (compounds with the same derivatization algorithm and thus the same brute formula) the chemical properties vary in a monotonic manner, i.e., congeneric compounds share the same chemical property space. The chemical property space is a key component in molecular design, where some building blocks are functionalized, i.e., derivatized, and eventually self-assembled in more complex systems, such as enzyme-ligand systems, of which (physico-chemical) properties/bioactivity may be predicted by QSPR/QSAR (quantitative structure-property/activity relationship) studies. The system structure is determined by the binding type (temporal/permanent; electrostatic/covalent) and is reflected in its local electronic (and/or magnetic) properties. Such nano-systems play the role of molecular devices, important in nano-medicine. In the present article, the behavior of polyethylenimine (PEI) macromolecules (linear LPEI and branched BPEI, respectively) with respect to the glucose oxidase enzyme GOx is described in terms of their (interacting) energy, geometry and topology, in an attempt to find the best shape and size of PEIs to be useful for a chosen (nanochemistry) purpose. PMID:27089324

Encoding of Fundamental Chemical Entities of Organic Reactivity Interest using chemical ontology and XML.

PubMed

Durairaj, Vijayasarathi; Punnaivanam, Sankar

2015-09-01

Fundamental chemical entities are identified in the context of organic reactivity and classified as appropriate concept classes namely ElectronEntity, AtomEntity, AtomGroupEntity, FunctionalGroupEntity and MolecularEntity. The entity classes and their subclasses are organized into a chemical ontology named "ChemEnt" for the purpose of assertion, restriction and modification of properties through entity relations. Individual instances of entity classes are defined and encoded as a library of chemical entities in XML. The instances of entity classes are distinguished with a unique notation and identification values in order to map them with the ontology definitions. A model GUI named Entity Table is created to view graphical representations of all the entity instances. The detection of chemical entities in chemical structures is achieved through suitable algorithms. The possibility of asserting properties to the entities at different levels and the mechanism of property flow within the hierarchical entity levels is outlined. Copyright © 2015 Elsevier Inc. All rights reserved.

Using operational and defined fractions to assess soil organic matter stabilization and structure

NASA Astrophysics Data System (ADS)

Horwath, W. R.

2015-12-01

Studies on soil organic matter (SOM) began with alkaline solvents revealing a dark colored substance that could be isolated under low pH. Further studies revealed fulvic and humic acids and humin fractions leading to theories on functional groups and metal-clay bridging mechanisms. The fate of isotopes in these fractions revealed soil carbon pools with varying turnover rates with half the soil carbon (C) in humin and acid hydrolyzed fractions over 1000 years old. These results are the basis of the three pool conceptual framework used in many biogeochemical models. Theories on the role of functional groups and compound classes further elaborated concepts on physical (aggregates) and chemical mechanisms of C stabilization. With the advance of analytical instrumentation, the operational fractions were further defined to the compound and molecular levels. These studies confirmed the majority of soil C is microbially derived. Our observation that all microbial groups contributed nonselectively to soil C maintenance independent of mineralogy suggests that compound characteristics within integrated structures are more important than the source of individual compounds for stabilizing soil C. In dissolved organic C floccing studies using Near Edge X-ray Fine Structure analysis, we found that aromatic compounds interacted first with Fe, however, the majority of direct bonds to Fe were polysaccharides, reinforcing that an integrative chemical structure rather than direct bonds imparted stability in organo-metal interactions. Using a novel differential scanning calorimeter coupled to an isotope ratio mass spectrometer setup, we confirmed that the presence of clays (independent of clay type) increased the microbial utilization of calcium stabilized high versus low temperature compounds, asserting that higher temperature compounds (i.e., phenolics) are likely less tightly bound by clay minerals. The integration of operational and defined fractions of SOM remains a legitimate approach to examine SOM structure and stabilization across scales of soil development and management.

ClassyFire: automated chemical classification with a comprehensive, computable taxonomy.

PubMed

Djoumbou Feunang, Yannick; Eisner, Roman; Knox, Craig; Chepelev, Leonid; Hastings, Janna; Owen, Gareth; Fahy, Eoin; Steinbeck, Christoph; Subramanian, Shankar; Bolton, Evan; Greiner, Russell; Wishart, David S

2016-01-01

Scientists have long been driven by the desire to describe, organize, classify, and compare objects using taxonomies and/or ontologies. In contrast to biology, geology, and many other scientific disciplines, the world of chemistry still lacks a standardized chemical ontology or taxonomy. Several attempts at chemical classification have been made; but they have mostly been limited to either manual, or semi-automated proof-of-principle applications. This is regrettable as comprehensive chemical classification and description tools could not only improve our understanding of chemistry but also improve the linkage between chemistry and many other fields. For instance, the chemical classification of a compound could help predict its metabolic fate in humans, its druggability or potential hazards associated with it, among others. However, the sheer number (tens of millions of compounds) and complexity of chemical structures is such that any manual classification effort would prove to be near impossible. We have developed a comprehensive, flexible, and computable, purely structure-based chemical taxonomy (ChemOnt), along with a computer program (ClassyFire) that uses only chemical structures and structural features to automatically assign all known chemical compounds to a taxonomy consisting of >4800 different categories. This new chemical taxonomy consists of up to 11 different levels (Kingdom, SuperClass, Class, SubClass, etc.) with each of the categories defined by unambiguous, computable structural rules. Furthermore each category is named using a consensus-based nomenclature and described (in English) based on the characteristic common structural properties of the compounds it contains. The ClassyFire webserver is freely accessible at http://classyfire.wishartlab.com/. Moreover, a Ruby API version is available at https://bitbucket.org/wishartlab/classyfire_api, which provides programmatic access to the ClassyFire server and database. ClassyFire has been used to annotate over 77 million compounds and has already been integrated into other software packages to automatically generate textual descriptions for, and/or infer biological properties of over 100,000 compounds. Additional examples and applications are provided in this paper. ClassyFire, in combination with ChemOnt (ClassyFire's comprehensive chemical taxonomy), now allows chemists and cheminformaticians to perform large-scale, rapid and automated chemical classification. Moreover, a freely accessible API allows easy access to more than 77 million "ClassyFire" classified compounds. The results can be used to help annotate well studied, as well as lesser-known compounds. In addition, these chemical classifications can be used as input for data integration, and many other cheminformatics-related tasks.

Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.

PubMed

Heinzlmeir, Stephanie; Kudlinzki, Denis; Sreeramulu, Sridhar; Klaeger, Susan; Gande, Santosh Lakshmi; Linhard, Verena; Wilhelm, Mathias; Qiao, Huichao; Helm, Dominic; Ruprecht, Benjamin; Saxena, Krishna; Médard, Guillaume; Schwalbe, Harald; Kuster, Bernhard

2016-12-16

The receptor tyrosine kinase EPHA2 (Ephrin type-A receptor 2) plays important roles in oncogenesis, metastasis, and treatment resistance, yet therapeutic targeting, drug discovery, or investigation of EPHA2 biology is hampered by the lack of appropriate inhibitors and structural information. Here, we used chemical proteomics to survey 235 clinical kinase inhibitors for their kinase selectivity and identified 24 drugs with submicromolar affinities for EPHA2. NMR-based conformational dynamics together with nine new cocrystal structures delineated drug-EPHA2 interactions in full detail. The combination of selectivity profiling, structure determination, and kinome wide sequence alignment allowed the development of a classification system in which amino acids in the drug binding site of EPHA2 are categorized into key, scaffold, potency, and selectivity residues. This scheme should be generally applicable in kinase drug discovery, and we anticipate that the provided information will greatly facilitate the development of selective EPHA2 inhibitors in particular and the repurposing of clinical kinase inhibitors in general.

Structural investigation of chemically synthesized ferrite magnetic nanomaterials

NASA Astrophysics Data System (ADS)

Uyanga, E.; Sangaa, D.; Hirazawa, H.; Tsogbadrakh, N.; Jargalan, N.; Bobrikov, I. A.; Balagurov, A. M.

2018-05-01

In recent times, interest in ferrite magnetic nanomaterials has considerably grown, mainly due to their highly promising medical and biological applications. Spinel ferrite powder samples, with high heat generation abilities in AC magnetic fields, were studied for their application to the hyperthermia treatment of cancer tumors. These properties of ferrites strongly depend on their chemical composition, ion distribution between crystallographic positions, magnetic structure and method of preparation. In this study, crystal and magnetic structures of several magnetic spinels were investigated by neutron diffraction. The explanation of the mechanism triggering the heat generation ability in the magnetic materials, and the electronic and magnetic states of ferrite-spinel type structures, were theoretically defined by a first-principles method. Ferrites with the composition of CuxMg1-xFe2O4 have been investigated as a heat generating magnetic nanomaterial. Atomic fraction of copper in ferrite was varied between 0 and 100% (that is, x between 0 and 1.0 with 0.2 steps), with the copper dope limit corresponding to appear a tetragonal phase.

Nano-Enabled Approaches to Chemical Imaging in Biosystems

DOE PAGES

Retterer, Scott T.; Morrell-Falvey, Jennifer L.; Doktycz, Mitchel John

2018-02-28

Understanding and predicting how biosystems function require knowledge about the dynamic physicochemical environments with which they interact and alter by their presence. Yet, identifying specific components, tracking the dynamics of the system, and monitoring local environmental conditions without disrupting biosystem function present significant challenges for analytical measurements. Nanomaterials, by their very size and nature, can act as probes and interfaces to biosystems and offer solutions to some of these challenges. At the nanoscale, material properties emerge that can be exploited for localizing biomolecules and making chemical measurements at cellular and subcellular scales. Here, we review advances in chemical imaging enabledmore » by nanoscale structures, in the use of nanoparticles as chemical and environmental probes, and in the development of micro- and nanoscale fluidic devices to define and manipulate local environments and facilitate chemical measurements of complex biosystems. As a result, integration of these nano-enabled methods will lead to an unprecedented understanding of biosystem function.« less

Nano-Enabled Approaches to Chemical Imaging in Biosystems

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

Retterer, Scott T.; Morrell-Falvey, Jennifer L.; Doktycz, Mitchel John

Understanding and predicting how biosystems function require knowledge about the dynamic physicochemical environments with which they interact and alter by their presence. Yet, identifying specific components, tracking the dynamics of the system, and monitoring local environmental conditions without disrupting biosystem function present significant challenges for analytical measurements. Nanomaterials, by their very size and nature, can act as probes and interfaces to biosystems and offer solutions to some of these challenges. At the nanoscale, material properties emerge that can be exploited for localizing biomolecules and making chemical measurements at cellular and subcellular scales. Here, we review advances in chemical imaging enabledmore » by nanoscale structures, in the use of nanoparticles as chemical and environmental probes, and in the development of micro- and nanoscale fluidic devices to define and manipulate local environments and facilitate chemical measurements of complex biosystems. As a result, integration of these nano-enabled methods will lead to an unprecedented understanding of biosystem function.« less

[Application of quantum-chemical methods to prediction of the carcinogenicity of chemical substances].

PubMed

Zholdikova, Z I; Kharchevnikova, N V

2006-01-01

A version of logical-combinatorial JSM type intelligent system was used to predict the presence and the degree of a carcinogenic effect. This version was based on combined description of chemical substances including both structural and numeric parameters. The new version allows for the fact that the toxicity and danger caused by chemical substances often depend on their biological activation in the organism. The authors substantiate classifying chemicals according to their carcinogenic activity, and illustrate the use of the system to predict the carcinogenicity of polycyclic aromatic hydrocarbons using a model of bioactivation via the formation of diolepoxides, and the carcinogenicity of halogenated alkanes using a model of bioactivation via oxidative dehalogenation. The paper defined the boundary level of an energetic parameter, the exceeding of which correlated with the inhibition of halogenated alkanes's metabolism and the absence of carcinogenic activity.

Well-defined porous membranes for robust omniphobic surfaces via microfluidic emulsion templating

PubMed Central

Zhu, Pingan; Kong, Tiantian; Tang, Xin; Wang, Liqiu

2017-01-01

Durability is a long-standing challenge in designing liquid-repellent surfaces. A high-performance omniphobic surface must robustly repel liquids, while maintaining mechanical/chemical stability. However, liquid repellency and mechanical durability are generally mutually exclusive properties for many omniphobic surfaces—improving one performance inevitably results in decreased performance in another. Here we report well-defined porous membranes for durable omniphobic surfaces inspired by the springtail cuticle. The omniphobicity is shown via an amphiphilic material micro-textured with re-entrant surface morphology; the mechanical durability arises from the interconnected microstructures. The innovative fabrication method—termed microfluidic emulsion templating—is facile, cost-effective, scalable and can precisely engineer the structural topographies. The robust omniphobic surface is expected to open up new avenues for diverse applications due to its mechanical and chemical robustness, transparency, reversible Cassie–Wenzel transition, transferability, flexibility and stretchability. PMID:28604698

DEFINING THE CHEMICAL SPACE OF PUBLIC GENOMIC DATA (S)

EPA Science Inventory

The current project aims to chemically index the genomics content of public genomic databases to make these data accessible in relation to other publicly available, chemically-indexed toxicological information. By defining the chemical space of public genomic data, it is possibl...

Hard and soft acids and bases: atoms and atomic ions.

PubMed

Reed, James L

2008-07-07

The structural origin of hard-soft behavior in atomic acids and bases has been explored using a simple orbital model. The Pearson principle of hard and soft acids and bases has been taken to be the defining statement about hard-soft behavior and as a definition of chemical hardness. There are a number of conditions that are imposed on any candidate structure and associated property by the Pearson principle, which have been exploited. The Pearson principle itself has been used to generate a thermodynamically based scale of relative hardness and softness for acids and bases (operational chemical hardness), and a modified Slater model has been used to discern the electronic origin of hard-soft behavior. Whereas chemical hardness is a chemical property of an acid or base and the operational chemical hardness is an experimental measure of it, the absolute hardness is a physical property of an atom or molecule. A critical examination of chemical hardness, which has been based on a more rigorous application of the Pearson principle and the availability of quantitative measures of chemical hardness, suggests that the origin of hard-soft behavior for both acids and bases resides in the relaxation of the electrons not undergoing transfer during the acid-base interaction. Furthermore, the results suggest that the absolute hardness should not be taken as synonymous with chemical hardness but that the relationship is somewhat more complex. Finally, this work provides additional groundwork for a better understanding of chemical hardness that will inform the understanding of hardness in molecules.

Tailoring lumazine synthase assemblies for bionanotechnology.

PubMed

Azuma, Yusuke; Edwardson, Thomas G W; Hilvert, Donald

2018-05-21

Nanoscale compartments formed by hierarchical protein self-assembly are valuable platforms for nanotechnology development. The well-defined structure and broad chemical functionality of protein cages, as well as their amenability to genetic and chemical modification, have enabled their repurposing for diverse applications. In this review, we summarize progress in the engineering of the cage-forming enzyme lumazine synthase. This bacterial nanocompartment has proven to be a malleable scaffold. The natural protein has been diversified to afford a family of unique proteinaceous capsules that have been modified, evolved and assembled with other components to produce nanoreactors, artificial organelles, delivery vehicles and virus mimics.

Chemical Etching of Zinc Oxide for Thin-Film Silicon Solar Cells

PubMed Central

Hüpkes, Jürgen; Owen, Jorj I; Pust, Sascha E; Bunte, Eerke

2012-01-01

Abstract Chemical etching is widely applied to texture the surface of sputter-deposited zinc oxide for light scattering in thin-film silicon solar cells. Based on experimental findings from the literature and our own results we propose a model that explains the etching behavior of ZnO depending on the structural material properties and etching agent. All grain boundaries are prone to be etched to a certain threshold, that is defined by the deposition conditions and etching solution. Additionally, several approaches to modify the etching behavior through special preparation and etching steps are provided. PMID:22162035

Evidence of land plant affinity for the Devonian fossil Protosalvinia (Foerstia)

USGS Publications Warehouse

Romankiw, L.A.; Hatcher, P.G.; Roen, J.B.

1988-01-01

The Devonian plant fossil Protosalvinia (Foerstia) has been examined by solid-state 13C nuclear magnetic resonance spectroscopy (NMR) and pyrolysis-gas chromatography-mass spectrometry (PY-GC-MS). Results of these studies reveal that the chemical structure of Protosalvinia is remarkably similar to that of coalified wood. A well-defined phenolic carbon peak in the NMR spectra and the appearance of phenol and alkylated phenols in pyrolysis products are clearly indicative of lignin-like compounds. These data represent significant new information on the chemical nature of Protosalvinia and provide the first substantial organic geochemical evidence for land plant affinity. -Authors

Streptothricin derivatives from Streptomyces sp. I08A 1776.

PubMed

Gan, Maoluo; Zheng, Xudong; Gan, Lishe; Guan, Yan; Hao, Xueqin; Liu, Yishuang; Si, Shuyi; Zhang, Yuqin; Yu, Liyan; Xiao, Chunling

2011-05-27

Five new streptothricin derivatives with a carbamoyl group substituted at C-12 (1-5) and three known analogues have been isolated from the culture broth of Streptomyces sp. I08A 1776 by ion exchange and hydrophilic interaction chromatographic techniques. Their structures were determined by spectroscopic and chemical methods. Compound 3 was a streptothricin derivative possessing a cis-streptolidine moiety. Its absolute configuration was defined by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Compound 5 and streptothricin E (6) displayed antibacterial and antifungal activity with MIC values in the range 1-64 μg/mL.

Prediction of biodegradability from chemical structure: Modeling or ready biodegradation test data

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

Loonen, H.; Lindgren, F.; Hansen, B.

1999-08-01

Biodegradation data were collected and evaluated for 894 substances with widely varying chemical structures. All data were determined according to the Japanese Ministry of International Trade and Industry (MITI) I test protocol. The MITI I test is a screening test for ready biodegradability and has been described by Organization for Economic Cooperation and Development (OECD) test guideline 301 C and European Union (EU) test guideline C4F. The chemicals were characterized by a set of 127 predefined structural fragments. This data set was used to develop a model for the prediction of the biodegradability of chemicals under standardized OECD and EUmore » ready biodegradation test conditions. Partial least squares (PLS) discriminant analysis was used for the model development. The model was evaluated by means of internal cross-validation and repeated external validation. The importance of various structural fragments and fragment interactions was investigated. The most important fragments include the presence of a long alkyl chain; hydroxy, ester, and acid groups (enhancing biodegradation); and the presence of one or more aromatic rings and halogen substituents (regarding biodegradation). More than 85% of the model predictions were correct for using the complete data set. The not readily biodegradable predictions were slightly better than the readily biodegradable predictions (86 vs 84%). The average percentage of correct predictions from four external validation studies was 83%. Model optimization by including fragment interactions improve the model predicting capabilities to 89%. It can be concluded that the PLS model provides predictions of high reliability for a diverse range of chemical structures. The predictions conform to the concept of readily biodegradable (or not readily biodegradable) as defined by OECD and EU test guidelines.« less

A Framework for Evaluating Chemical Hazards.

ERIC Educational Resources Information Center

Coble, Charles R.; Hounshell, Paul B.

1980-01-01

Lists questions that teachers should ask relating to use of all chemicals in the school laboratory, as well as chemicals with known and suspected dangerous properties. Tables list Occupational Safety and Health Administration (OSHA)-defined carcinogens, American Chemical Society-defined teratogens, suspected carcinogens, and other hazardous…

IR spectroscopic studies in microchannel structures

NASA Astrophysics Data System (ADS)

Guber, A. E.; Bier, W.

1998-06-01

By means of the various microengineering methods available, microreaction systems can be produced among others. These microreactors consist of microchannels, where chemical reactions take place under defined conditions. For optimum process control, continuous online analytics is envisaged in the microchannels. For this purpose, a special analytical module has been developed. It may be applied for IR spectroscopic studies at any point of the microchannel.

Organization of 'nanocrystal molecules' using DNA

NASA Astrophysics Data System (ADS)

Alivisatos, A. Paul; Johnsson, Kai P.; Peng, Xiaogang; Wilson, Troy E.; Loweth, Colin J.; Bruchez, Marcel P.; Schultz, Peter G.

1996-08-01

PATTERNING matter on the nanometre scale is an important objective of current materials chemistry and physics. It is driven by both the need to further miniaturize electronic components and the fact that at the nanometre scale, materials properties are strongly size-dependent and thus can be tuned sensitively1. In nanoscale crystals, quantum size effects and the large number of surface atoms influence the, chemical, electronic, magnetic and optical behaviour2-4. 'Top-down' (for example, lithographic) methods for nanoscale manipulation reach only to the upper end of the nanometre regime5; but whereas 'bottom-up' wet chemical techniques allow for the preparation of mono-disperse, defect-free crystallites just 1-10 nm in size6-10, ways to control the structure of nanocrystal assemblies are scarce. Here we describe a strategy for the synthesis of'nanocrystal molecules', in which discrete numbers of gold nanocrystals are organized into spatially defined structures based on Watson-Crick base-pairing interactions. We attach single-stranded DNA oligonucleotides of defined length and sequence to individual nanocrystals, and these assemble into dimers and trimers on addition of a complementary single-stranded DNA template. We anticipate that this approach should allow the construction of more complex two-and three-dimensional assemblies.

Promoting the 3Rs to enhance the OECD fish toxicity testing framework.

PubMed

Hutchinson, Thomas H; Wheeler, James R; Gourmelon, Anne; Burden, Natalie

2016-04-01

Fish toxicity testing has been conducted since the 1860's in order to help define safe levels of chemical contaminants in lakes, rivers and coastal waters. The historical emphasis on acute lethality testing of chemicals has more recently focussed on long term sublethal effects of chemicals on fish and their prey species. Fish toxicity testing is now embedded in much environment legislation on chemical safety while it is recognized that animal use should be Replaced, Reduced and Refined (the 3Rs) where possible. The OECD Fish Toxicity Testing Framework provides a useful structure with which to address the needs of environmental safety assessment whilst implementing the 3Rs. This commentary aims to promote the implementation of the recommendations of the OECD Fish Toxicity Testing Framework. Copyright © 2016 Elsevier Inc. All rights reserved.

Mass Spectrometry Imaging and GC-MS Profiling of the Mammalian Peripheral Sensory-Motor Circuit

NASA Astrophysics Data System (ADS)

Rubakhin, Stanislav S.; Ulanov, Alexander; Sweedler, Jonathan V.

2015-06-01

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has evolved to become an effective discovery tool in science and clinical diagnostics. Here, chemical imaging approaches are applied to well-defined regions of the mammalian peripheral sensory-motor system, including the dorsal root ganglia (DRG) and adjacent nerves. By combining several MSI approaches, analyte coverage is increased and 195 distinct molecular features are observed. Principal component analysis suggests three chemically different regions within the sensory-motor system, with the DRG and adjacent nerve regions being the most distinct. Investigation of these regions using gas chromatography-mass spectrometry corroborate these findings and reveal important metabolic markers related to the observed differences. The heterogeneity of the structurally, physiologically, and functionally connected regions demonstrates the intricate chemical and spatial regulation of their chemical composition.

In-Space Chemical Propulsion System Model

NASA Technical Reports Server (NTRS)

Byers, David C.; Woodcock, Gordon; Benfield, Michael P. J.

2004-01-01

Multiple, new technologies for chemical systems are becoming available and include high temperature rockets, very light propellant tanks and structures, new bipropellant and monopropellant options, lower mass propellant control components, and zero boil off subsystems. Such technologies offer promise of increasing the performance of in-space chemical propulsion for energetic space missions. A mass model for pressure-fed, Earth and space-storable, advanced chemical propulsion systems (ACPS) was developed in support of the NASA MSFC In-Space Propulsion Program. Data from flight systems and studies defined baseline system architectures and subsystems and analyses were formulated for parametric scaling relationships for all ACPS subsystem. The paper will first provide summary descriptions of the approaches used for the systems and the subsystems and then present selected analyses to illustrate use of the model for missions with characteristics of current interest.

In-Space Chemical Propulsion System Model

NASA Technical Reports Server (NTRS)

Byers, David C.; Woodcock, Gordon; Benfield, M. P. J.

2004-01-01

Multiple, new technologies for chemical systems are becoming available and include high temperature rockets, very light propellant tanks and structures, new bipropellant and monopropellant options, lower mass propellant control components, and zero boil off subsystems. Such technologies offer promise of increasing the performance of in-space chemical propulsion for energetic space missions. A mass model for pressure-fed, Earth and space-storable, advanced chemical propulsion systems (ACPS) was developed in support of the NASA MSFC In-Space Propulsion Program. Data from flight systems and studies defined baseline system architectures and subsystems and analyses were formulated for parametric scaling relationships for all ACPS subsystems. The paper will first provide summary descriptions of the approaches used for the systems and the subsystems and then present selected analyses to illustrate use of the model for missions with characteristics of current interest.

Local structural and chemical ordering of nanosized Pt3±δCo probed by multiple-scattering x-ray absorption spectroscopy

NASA Astrophysics Data System (ADS)

Greco, Giorgia; Witkowska, Agnieszka; Principi, Emiliano; Minicucci, Marco; di Cicco, Andrea

2011-04-01

This work reports a detailed investigation of the local structure and chemical disorder of a Pt3±δCo thin film and Pt3±δCo nanoparticles. We have used a combination of techniques including x-ray absorption spectroscopy (XAS), x-ray diffraction (XRD), and high-resolution transmission electron microscopy (TEM). High-quality XAS spectra at the Co K edge and Pt L3 edge have been analyzed using double-edge multiple-scattering data analysis. Structural extended x-ray absorption fine structure (EXAFS) refinements have been performed accounting for the reduction of the coordination numbers and degeneracy of three-atom configurations, resulting from the measured size distribution and stoichiometry. The important effect of chemical ordering on pair and three-atom configurations has been studied using computer simulations based on a simple model accounting for substitutional disorder, defined by an order parameter s. It has been found that individual EXAFS signals related to the minority species (Co) are extremely sensitive to substitutional disorder so their intensities, especially those of the collinear three-atom configurations, can be used as a measure of the ordering level. The thin film has been found to be chemically disordered (s⩽0.4), in agreement with previous estimates. The Pt3±δCo nanoalloy has been found to be partially ordered (s=0.6±0.1) while the local structure around Co atoms is characterized by a higher level of structural disorder as compared to the bulk-like thin film. The robust approach for nanomaterial characterization used in this work combining different techniques can, in principle, be applied for structural refinements of any binary nanocrystalline functional system.

A one-pot gold seed-assisted synthesis of gold/platinum wire nanoassemblies and their enhanced electrocatalytic activity for the oxidation of oxalic acid

NASA Astrophysics Data System (ADS)

Bai, Juan; Fang, Chun-Long; Liu, Zong-Huai; Chen, Yu

2016-01-01

Three-dimensional (3D) noble metal nanoassemblies composed of one-dimensional (1D) nanowires have been attracting much interest due to the unique physical and chemical properties of 1D nanowires as well as the particular interconnected open-pore structure of 3D nanoassemblies. In this work, well-defined Au/Pt wire nanoassemblies were synthesized by using a facile NaBH4 reduction method in the presence of a branched form of polyethyleneimine (PEI). A study of the growth mechanism indicated the morphology of the final product to be highly related to the molecular structure of the polymeric amine. Also, the preferred Pt-on-Pt deposition contributed to the formation of the 1D Pt nanowires. The Au/Pt wire nanoassemblies were functionalized with PEI at the same time that these nanoassemblies were synthesized due to the strong N-Pt bond. The chemically functionalized Au/Pt wire nanoassemblies exhibited better electrocatalytic activity for the electro-oxidation of oxalic acid than did commercial Pt black.Three-dimensional (3D) noble metal nanoassemblies composed of one-dimensional (1D) nanowires have been attracting much interest due to the unique physical and chemical properties of 1D nanowires as well as the particular interconnected open-pore structure of 3D nanoassemblies. In this work, well-defined Au/Pt wire nanoassemblies were synthesized by using a facile NaBH4 reduction method in the presence of a branched form of polyethyleneimine (PEI). A study of the growth mechanism indicated the morphology of the final product to be highly related to the molecular structure of the polymeric amine. Also, the preferred Pt-on-Pt deposition contributed to the formation of the 1D Pt nanowires. The Au/Pt wire nanoassemblies were functionalized with PEI at the same time that these nanoassemblies were synthesized due to the strong N-Pt bond. The chemically functionalized Au/Pt wire nanoassemblies exhibited better electrocatalytic activity for the electro-oxidation of oxalic acid than did commercial Pt black. Electronic supplementary information (ESI) available: Experimental details and additional physical characterization. See DOI: 10.1039/c5nr08150e

[Studies on the recovery of pharmaceutical drug substances from surfaces made of defined stainless-steel alloys].

PubMed

Kloss, S; Müller, U; Oelschläger, H

2005-09-01

Facilities for the manufacturing of pharmaceutical drug substances on the pilot-plant and the industrial scale as well as chemical reactors and vessels used for chemical work-up mainly consist of alloyed stainless steel. The influence of the alloy composition and the surface condition, i.e. of the roughness of the stainless-steel materials, on the adsorption of structurally diverse steroidal substances and, hence, on the quality of the products was studied. In general, stainless-steel alloys with smooth, not so rough surfaces are to be favored as reactor material. However, it was demonstrated in this study that, on account of the weak interaction between active substances and steel materials, mechanically polished materials of a medium roughness up to approx. 0.4 microm can be employed instead of the considerably more cost-intensive electrochemically polished stainless-steel surfaces. The type of surface finishing up to a defined roughness, then, has no influence on the quality of these pharmaceutical products. Substances that, because of their molecular structure, can function as "anions" in the presence of polar solvents, are adsorbed on very smooth surfaces prepared by electrochemical methods, forming an amorphous surface film. For substances with this structural characteristics, the lower-cost mechanically polished reactor materials of a medium roughness up to approx. 0.5 microm should be used exclusively.

Chemically Active, Porous 3D-Printed Thermoplastic Composites.

PubMed

Evans, Kent A; Kennedy, Zachary C; Arey, Bruce W; Christ, Josef F; Schaef, Herbert T; Nune, Satish K; Erikson, Rebecca L

2018-05-02

Metal-organic frameworks (MOFs) exhibit exceptional properties and are widely investigated because of their structural and functional versatility relevant to catalysis, separations, and sensing applications. However, their commercial or large-scale application is often limited by their powder forms which make integration into devices challenging. Here, we report the production of MOF-thermoplastic polymer composites in well-defined and customizable forms and with complex internal structural features accessed via a standard three-dimensional (3D) printer. MOFs (zeolitic imidazolate framework; ZIF-8) were incorporated homogeneously into both poly(lactic acid) (PLA) and thermoplastic polyurethane (TPU) matrices at high loadings (up to 50% by mass), extruded into filaments, and utilized for on-demand access to 3D structures by fused deposition modeling. Printed, rigid PLA/MOF composites display a large surface area (SA avg = 531 m 2 g -1 ) and hierarchical pore features, whereas flexible TPU/MOF composites achieve a high surface area (SA avg = 706 m 2 g -1 ) by employing a simple method developed to expose obstructed micropores postprinting. Critically, embedded particles in the plastic matrices retain their ability to participate in chemical interactions characteristic of the parent framework. The fabrication strategies were extended to other MOFs and illustrate the potential of 3D printing to create unique porous and high surface area chemically active structures.

Chemical Mapping of Proterozoic Organic Matter at Sub-Micron Spatial Resolution

NASA Technical Reports Server (NTRS)

Oehler, Dorothy Z.; Robert, Francois; Mostefaoui, Smail; Meibom, Anders; Selo, Madeleine; McKay, David S.

2006-01-01

We have used a NanoSIMS ion microprobe to map sub-micron-scale distributions of carbon, nitrogen, sulfur, silicon, and oxygen in organic microfossils and laminae from the approximately 0.85 Ga Bitter Springs Formation of Australia. The data provide clues about the original chemistry of the microfossils, the silicification process, and biosignatures of specific microorganisms and microbial communities. Chemical maps of fossil unicells and filaments reveal distinct wall-and sheath-like structures enriched in C, N and S, consistent with their accepted biological origin. Surprisingly, organic laminae, previously considered to be amorphous, also exhibit filamentous and apparently compressed spheroidal structures defined by strong enrichments in C, N and S. By analogy to data from the well-preserved microfossils, these structures are interpreted as being of biological origin, most likely representing densely packed remnants of microbial mats. Because the preponderance of organic matter in Precambrian sediments is similarly "amorphous," our findings open a large body of generally neglected material to in situ structural, chemical, and isotopic study. Our results also offer new criteria for assessing biogenicity of problematic kerogenous materials and thus can be applied to assessments of poorly preserved or fragmentary organic residues in early Archean sediments and any that might occur in meteorites or other extraterrestrial samples.

SerpentinaDB: a database of plant-derived molecules of Rauvolfia serpentina.

PubMed

Pathania, Shivalika; Ramakrishnan, Sai Mukund; Randhawa, Vinay; Bagler, Ganesh

2015-08-04

Plant-derived molecules (PDMs) are known to be a rich source of diverse scaffolds that could serve as a basis for rational drug design. Structured compilation of phytochemicals from traditional medicinal plants can facilitate prospection for novel PDMs and their analogs as therapeutic agents. Rauvolfia serpentina is an important medicinal plant, endemic to Himalayan mountain ranges of Indian subcontinent, reported to be of immense therapeutic value against various diseases. We present SerpentinaDB, a structured compilation of 147 R. serpentina PDMs, inclusive of their plant part source, chemical classification, IUPAC, SMILES, physicochemical properties, and 3D chemical structures with associated references. It also provides refined search option for identification of analogs of natural molecules against ZINC database at user-defined cut-off. SerpentinaDB is an exhaustive resource of R. serpentina molecules facilitating prospection for therapeutic molecules from a medicinally important source of natural products. It also provides refined search option to explore the neighborhood of chemical space against ZINC database to identify analogs of natural molecules obtained as leads. In a previous study, we have demonstrated the utility of this resource by identifying novel aldose reductase inhibitors towards intervention of complications of diabetes.

Structure-based predictions of 13C-NMR chemical shifts for a series of 2-functionalized 5-(methylsulfonyl)-1-phenyl-1H-indoles derivatives using GA-based MLR method

NASA Astrophysics Data System (ADS)

Ghavami, Raouf; Sadeghi, Faridoon; Rasouli, Zolikha; Djannati, Farhad

2012-12-01

Experimental values for the 13C NMR chemical shifts (ppm, TMS = 0) at 300 K ranging from 96.28 ppm (C4' of indole derivative 17) to 159.93 ppm (C4' of indole derivative 23) relative to deuteride chloroform (CDCl3, 77.0 ppm) or dimethylsulfoxide (DMSO, 39.50 ppm) as internal reference in CDCl3 or DMSO-d6 solutions have been collected from literature for thirty 2-functionalized 5-(methylsulfonyl)-1-phenyl-1H-indole derivatives containing different substituted groups. An effective quantitative structure-property relationship (QSPR) models were built using hybrid method combining genetic algorithm (GA) based on stepwise selection multiple linear regression (SWS-MLR) as feature-selection tools and correlation models between each carbon atom of indole derivative and calculated descriptors. Each compound was depicted by molecular structural descriptors that encode constitutional, topological, geometrical, electrostatic, and quantum chemical features. The accuracy of all developed models were confirmed using different types of internal and external procedures and various statistical tests. Furthermore, the domain of applicability for each model which indicates the area of reliable predictions was defined.

Studies on the chemical synthesis and characterization of lead oxide nanoparticles with different organic capping agents

NASA Astrophysics Data System (ADS)

Arulmozhi, K. T.; Mythili, N.

2013-12-01

Lead oxide (PbO) nanoparticles were chemically synthesized using Lead (II) acetate as precursor. The effects of organic capping agents such as Oleic acid, Ethylene Diamine Tetra Acetic acid (EDTA) and Cetryl Tri Methyl Butoxide (CTAB) on the size and morphology of the nanoparticles were studied. Characterization techniques such as X-ray diffraction (XRD), Fourier Transform-Infrared spectroscopy (FT-IR), Photoluminescence (PL) Field Emission Scanning Electron Microscopy (FE-SEM), Energy Dispersive Spectroscopy (EDS) and Transmission Electron Microscopy (TEM) were used to analyse the prepared nanoparticles for their physical, structural and optical properties. The characterization studies reveal that the synthesized PbO nanoparticles had well defined crystalline structure and sizes in the range of 25 nm to 36 nm for capping agents used and 40 nm for pure PbO nanoparticles.

Structurally Defined 3D Nanographene Assemblies via Bottom-Up Chemical Synthesis for Highly Efficient Lithium Storage

DOE PAGES

Yen, Hung-Ju; Tsai, Hsinhan; Zhou, Ming; ...

2016-10-10

In this paper, functionalized 3D nanographenes with controlled electronic properties have been synthesized through a multistep organic synthesis method and are further used as promising anode materials for lithium-ion batteries, exhibiting a much increased capacity (up to 950 mAh g -1), three times higher than that of the graphite anode (372 mAh g -1).

Polymers application in proton exchange membranes for fuel cells (PEMFCs)

NASA Astrophysics Data System (ADS)

Walkowiak-Kulikowska, Justyna; Wolska, Joanna; Koroniak, Henryk

2017-07-01

This review presents the most important research on alternative polymer membranes with ionic groups attached, provides examples of materials with a well-defined chemical structure that are described in the literature. Furthermore, it elaborates on the synthetic methods used for preparing PEMs, the current status of fuel cell technology and its application. It also briefly discusses the development of the PEMFC market.

Structure-activity relationships for selected fragrance allergens.

PubMed

Patlewicz, G Y; Wright, Z M; Basketter, D A; Pease, C K; Lepoittevin, J-P; Arnau, E Giménez

2002-10-01

Fragrance substances represent a very diverse group of chemicals, a proportion of them providing not only desirable aroma characteristics, but also being associated with adverse effects, notably the ability to cause allergic reactions in the skin. However, efforts to find substitute materials are hampered by the need to undertake animal testing to evaluate both the presence and the degree of skin sensitization hazard. One potential route to avoid such testing is to understand the relationships between chemical structure and skin sensitization. In the present work we have evaluated two groups of fragrance chemicals, saturated aldehydes (aryl substituted and aliphatic aldehydes) and alpha,beta-unsaturated aldehydes. Data on their skin sensitization potency defined using the local lymph node assay has been evaluated in relation to their physicochemical properties. The initial outcome has been consistent with the concept that alpha,beta-unsaturated aldehydes react largely via Michael addition, whilst the group of saturated aldehydes form Schiff bases with proteins. Simple models of chemical reactivity based on these mechanisms suggest that it may be possible to predict allergenic potency. Accordingly, the evaluation of an additional group of similar aldehydes is now underway to assess the robustness of these models, with some emphasis being based on ensuring a wider spread of chemical reactivity.

Importance of Kier-Hall topological indices in the QSAR of anticancer drug design.

PubMed

Nandi, Sisir; Bagchi, Manish C

2012-06-01

An important area of theoretical drug design research is quantitative structure activity relationship (QSAR) using structural invariants. The impetus for this research trend comes from various directions. Researchers in chemical documentation have searched for a set of invariants which will be more convenient than the adjacency matrix (or connection table) for the storage and comparison of chemical structures. Molecular structure can be looked upon as the representation of the relationship among its various constituents. The term molecular structure represents a set of nonequivalent and probably disjoint concepts. There is no reason to believe that when we discuss diverse topics (e.g. chemical synthesis, reaction rates, spectroscopic transitions, reaction mechanisms, and ab initio calculations) using the notion of molecular structure, the different meanings we attach to the single term molecular structure originate from the same fundamental concept. On the contrary, there is a theoretical and philosophical basis for the non-homogeneity of concepts covered by the term molecular structure. In the context of molecular science, the various concepts of molecular structure (e.g. classical valence bond representations, various chemical graph-theoretic representations, ball and spoke model of a molecule, representation of a molecule by minimum energy conformation, semi symbolic contour map of a molecule, or symbolic representation of chemical species by Hamiltonian operators) are model objects derived through different abstractions of the same chemical reality. In each instance, the equivalence class (concept or model of molecular structure) is generated by selecting certain aspects while ignoring some unique properties of those actual events. This explains the plurality of the concept of molecular structure and their autonomous nature, the word autonomous being used in the same sense that one concept is not logically derived from the other. At the most fundamental level, the structural model of an assembled entity (e.g. a molecule consisting of atoms) may be defined as the pattern of relationship among its parts as distinct from the values associated with them. Constitutional formulae of molecules are graphs where vertices represent the set of atoms and edges represent chemical bonds. The pattern of connectedness of atoms in a molecule is preserved by constitutional graphs. A graph (more correctly a non-directed graph) G = [V, E] consists of a finite non-empty set V of points together with a prescribed set E of unordered pairs of distinct points of V. Thus the mathematical characterization of structures represents structural invariants having successful applications in chemical documentation, characterization of molecular branching, enumeration of molecular constitutional associated with a particular empirical formula, calculation of quantum chemical parameters for the generation of quantitative structure-property-activity correlations. Kier developed a number of structural invariants which are now-a-days called as topological indices with wide range of practical applications for QSAR and drug design. The present paper is restricted to the review of Kier-Hall topological indices for QSAR and anticancer drug design for 2,5-bis(1-aziridinyl) 1,4-benzoquinone (BABQ), pyridopyrimidine, 4-anilinoquinazoline and 2-Phenylindoles compounds utilizing various statistical multivariate regression analyses.

The chemical evolution of oligonucleotide therapies of clinical utility

PubMed Central

Khvorova, Anastasia; Watts, Jonathan K.

2017-01-01

After nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency properties are derived primarily from the chemical structure of the oligonucleotide, while their target is defined by the base sequence. Thus, as oligonucleotides with a particular chemical design demonstrate appropriate distribution and safety profiles for clinical gene silencing in a particular tissue, this will open the door to the rapid development of additional drugs targeting other disease-associated genes in the same tissue. To achieve clinical productivity, the chemical architecture of the oligonucleotide needs to be optimized as a whole, using a combination of sugar, backbone, nucleobase and 3′/5′-terminal modifications. A portfolio of chemistries can be used to confer drug like properties onto the oligonucleotide as a whole, with minor chemical changes often translating into major improvements in clinical efficacy. Outstanding challenges in oligonucleotide chemical development include optimization of chemical architectures to ensure long-term safety and to enable robust clinical activity beyond the liver. PMID:28244990

Evaluation of food-relevant chemicals in the ToxCast high-throughput screening program

EPA Pesticide Factsheets

Thousands of chemicals are directly added to or come in contact with food, many of which have undergone little to no toxicological evaluation. The landscape of the food-relevant chemical universe was evaluated using cheminformatics, and subsequently the bioactivity of food-relevant chemicals across the publicly available ToxCast highthroughput screening program was assessed. In total, 8659 food-relevant chemicals were compiled including direct food additives, food contact substances, and pesticides. Of these food-relevant chemicals, 4719 had curated structure definition files amenable to defining chemical fingerprints, which were used to cluster chemicals using a selforganizing map approach. Pesticides, and direct food additives clustered apart from one another with food contact substances generally in between, supporting that these categories not only reflect different uses but also distinct chemistries. Subsequently, 1530 food-relevant chemicals were identified in ToxCast comprising 616 direct food additives, 371 food contact substances, and 543 pesticides. Bioactivity across ToxCast was filtered for cytotoxicity to identify selective chemical effects. Initiating analyses from strictly chemical-based methodology or bioactivity/cytotoxicity-driven evaluation presents unbiased approaches for prioritizing chemicals. Although bioactivity in vitro is not necessarily predictive of adverse effects in vivo, these data provide insight into chemical properties and cellu

Evaluation of food-relevant chemicals in the ToxCast high ...

EPA Pesticide Factsheets

There are thousands of chemicals that are directly added to or come in contact with food, many of which have undergone little to no toxicological evaluation. The ToxCast high-throughput screening (HTS) program has evaluated over 1,800 chemicals in concentration-response across ~820 assay endpoints and continues to grow; with all data completely available to the public, this resource serves as a unique opportunity to evaluate the bioactivity of chemicals in vitro. This study investigated the chemical landscape of the food-relevant chemical universe using cheminformatics analyses, and subsequently evaluated the bioactivity of food-relevant chemicals included in the ToxCast HTS program. Initially, a list of 9,437 food-relevant chemicals was compiled by comprehensively mining publicly available sources for direct food additives, food contact substances, indirect food additives, and pesticides. Of these food-relevant chemicals, 4,638 were associated with curated structure definition files amenable to defining physical/chemical features used to generate chemical fingerprints. Clustering was conducted based on the chemical fingerprints using a self-organizing map approach. This revealed that pesticides, food contact substances, and direct food additives generally clustered apart from one another, supporting that these categories reflect not only different uses but also distinct chemistries. Subsequently, 967 of the 9,437 food-relevant chemicals were identified in the T

Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold

NASA Astrophysics Data System (ADS)

Li, Yizhou; De Luca, Roberto; Cazzamalli, Samuele; Pretto, Francesca; Bajic, Davor; Scheuermann, Jörg; Neri, Dario

2018-03-01

In nature, specific antibodies can be generated as a result of an adaptive selection and expansion of lymphocytes with suitable protein binding properties. We attempted to mimic antibody-antigen recognition by displaying multiple chemical diversity elements on a defined macrocyclic scaffold. Encoding of the displayed combinations was achieved using distinctive DNA tags, resulting in a library size of 35,393,112. Specific binders could be isolated against a variety of proteins, including carbonic anhydrase IX, horseradish peroxidase, tankyrase 1, human serum albumin, alpha-1 acid glycoprotein, calmodulin, prostate-specific antigen and tumour necrosis factor. Similar to antibodies, the encoded display of multiple chemical elements on a constant scaffold enabled practical applications, such as fluorescence microscopy procedures or the selective in vivo delivery of payloads to tumours. Furthermore, the versatile structure of the scaffold facilitated the generation of protein-specific chemical probes, as illustrated by photo-crosslinking.

The structure of the "amorphous" matrix of keratins.

PubMed

Kadir, Murat; Wang, Xinwei; Zhu, Bowen; Liu, Jing; Harland, Duane; Popescu, Crisan

2017-05-01

Various keratin fibers, particularly human hairs, were investigated by transmission electron microscopy, TEM, solid-state 1 H NMR and Transient Electro-Thermal Technique, TET. The results converge to suggest that the matrix of keratin fiber cortex, far from being amorphous, has a well-defined nano-scale grainy structure, the size of these grains being around 2-4nm. The size of the grains appears to strongly depend on the chemical treatment of the fiber, on the temperature and on the relative humidity of the environment, as well as on the physiological factors at the level of fiber production in follicle. By suggesting an organization at the nano-scale of the protein chains in these grains, likely to be Keratin Associated Proteins, the results challenge the view of matrix as a homogeneous glassy material. Moreover, they indicate the potential of further investigating the purpose of this structure that appears to reflect not only chemical treatments of keratins but also biological processes at the level of the follicle. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Dynamically Tunable Cell Culture Platforms for Tissue Engineering and Mechanobiology

PubMed Central

Uto, Koichiro; Tsui, Jonathan H.; DeForest, Cole A.; Kim, Deok-Ho

2016-01-01

Human tissues are sophisticated ensembles of many distinct cell types embedded in the complex, but well-defined, structures of the extracellular matrix (ECM). Dynamic biochemical, physicochemical, and mechano-structural changes in the ECM define and regulate tissue-specific cell behaviors. To recapitulate this complex environment in vitro, dynamic polymer-based biomaterials have emerged as powerful tools to probe and direct active changes in cell function. The rapid evolution of polymerization chemistries, structural modulation, and processing technologies, as well as the incorporation of stimuli-responsiveness, now permit synthetic microenvironments to capture much of the dynamic complexity of native tissue. These platforms are comprised not only of natural polymers chemically and molecularly similar to ECM, but those fully synthetic in origin. Here, we review recent in vitro efforts to mimic the dynamic microenvironment comprising native tissue ECM from the viewpoint of material design. We also discuss how these dynamic polymer-based biomaterials are being used in fundamental cell mechanobiology studies, as well as towards efforts in tissue engineering and regenerative medicine. PMID:28522885

Optical filter including a sub-wavelength periodic structure and method of making

DOEpatents

Kaushik, Sumanth; Stallard, Brian R.

1998-01-01

An optical filter includes a dielectric layer formed within a resonant optical cavity, with the dielectric layer having formed therein a sub-wavelength periodic structure to define, at least in part, a wavelength for transmission of light through the resonant optical cavity. The sub-wavelength periodic structure can be formed either by removing material from the dielectric layer (e.g. by etching through an electron-beam defined mask), or by altering the composition of the layer (e.g. by ion implantation). Different portions of the dielectric layer can be patterned to form one or more optical interference filter elements having different light transmission wavelengths so that the optical filter can filter incident light according to wavelength and/or polarization. For some embodiments, the optical filter can include a detector element in optical alignment with each optical interference filter element to quantify or measure the filtered light for analysis thereof. The optical filter has applications to spectrometry, colorimetry, and chemical sensing.

Optical filter including a sub-wavelength periodic structure and method of making

DOEpatents

Kaushik, S.; Stallard, B.R.

1998-03-10

An optical filter includes a dielectric layer formed within a resonant optical cavity, with the dielectric layer having formed therein a sub-wavelength periodic structure to define, at least in part, a wavelength for transmission of light through the resonant optical cavity. The sub-wavelength periodic structure can be formed either by removing material from the dielectric layer (e.g. by etching through an electron-beam defined mask), or by altering the composition of the layer (e.g. by ion implantation). Different portions of the dielectric layer can be patterned to form one or more optical interference filter elements having different light transmission wavelengths so that the optical filter can filter incident light according to wavelength and/or polarization. For some embodiments, the optical filter can include a detector element in optical alignment with each optical interference filter element to quantify or measure the filtered light for analysis thereof. The optical filter has applications to spectrometry, colorimetry, and chemical sensing. 17 figs.

ODEion--a software module for structural identification of ordinary differential equations.

PubMed

Gennemark, Peter; Wedelin, Dag

2014-02-01

In the systems biology field, algorithms for structural identification of ordinary differential equations (ODEs) have mainly focused on fixed model spaces like S-systems and/or on methods that require sufficiently good data so that derivatives can be accurately estimated. There is therefore a lack of methods and software that can handle more general models and realistic data. We present ODEion, a software module for structural identification of ODEs. Main characteristic features of the software are: • The model space is defined by arbitrary user-defined functions that can be nonlinear in both variables and parameters, such as for example chemical rate reactions. • ODEion implements computationally efficient algorithms that have been shown to efficiently handle sparse and noisy data. It can run a range of realistic problems that previously required a supercomputer. • ODEion is easy to use and provides SBML output. We describe the mathematical problem, the ODEion system itself, and provide several examples of how the system can be used. Available at: http://www.odeidentification.org.

NMR Crystallography of Enzyme Active Sites: Probing Chemically-Detailed, Three-Dimensional Structure in Tryptophan Synthase

PubMed Central

Dunn, Michael F.

2013-01-01

Conspectus NMR crystallography – the synergistic combination of X-ray diffraction, solid-state NMR spectroscopy, and computational chemistry – offers unprecedented insight into three-dimensional, chemically-detailed structure. From its initial role in refining diffraction data of organic and inorganic solids, NMR crystallography is now being developed for application to active sites in biomolecules, where it reveals chemically-rich detail concerning the interactions between enzyme site residues and the reacting substrate that is not achievable when X-ray, NMR, or computational methodologies are applied in isolation. For example, typical X-ray crystal structures (1.5 to 2.5 Å resolution) of enzyme-bound intermediates identify possible hydrogen-bonding interactions between site residues and substrate, but do not directly identify the protonation state of either. Solid-state NMR can provide chemical shifts for selected atoms of enzyme-substrate complexes, but without a larger structural framework in which to interpret them, only empirical correlations with local chemical structure are possible. Ab initio calculations and molecular mechanics can build models for enzymatic processes, but rely on chemical details that must be specified. Together, however, X-ray diffraction, solid-state NMR spectroscopy, and computational chemistry can provide consistent and testable models for structure and function of enzyme active sites: X-ray crystallography provides a coarse framework upon which models of the active site can be developed using computational chemistry; these models can be distinguished by comparison of their calculated NMR chemical shifts with the results of solid-state NMR spectroscopy experiments. Conceptually, each technique is a puzzle piece offering a generous view of the big picture. Only when correctly pieced together, however, can they reveal the big picture at highest resolution. In this Account, we detail our first steps in the development of NMR crystallography for application to enzyme catalysis. We begin with a brief introduction to NMR crystallography and then define the process that we have employed to probe the active site in the β-subunit of tryptophan synthase with unprecedented atomic-level resolution. This approach has resulted in a novel structural hypothesis for the protonation state of the quinonoid intermediate in tryptophan synthase and its surprising role in directing the next step in the catalysis of L-Trp formation. PMID:23537227

Triplex molecular layers with nonlinear nanomechanical response

NASA Astrophysics Data System (ADS)

Tsukruk, V. V.; Ahn, H.-S.; Kim, D.; Sidorenko, A.

2002-06-01

The molecular design of surface structures with built-in mechanisms for mechanical energy dissipation under nanomechanical deformation and compression resistance provided superior nanoscale wear stability. We designed robust, well-defined trilayer surface nanostructures chemically grafted to a silicon oxide surface with an effective composite modulus of about 1 GPa. The total thickness was within 20-30 nm and included an 8 nm rubber layer sandwiched between two hard layers. The rubber layer provides an effective mechanism for energy dissipation, facilitated by nonlinear, giant, reversible elastic deformations of the rubber matrix, restoring the initial status due to the presence of an effective nanodomain network and chemical grafting within the rubber matrix.

Ta-Nb-Mo-W refractory high-entropy alloys: Anomalous ordering behavior and its intriguing electronic origin

DOE PAGES

Singh, Prashant; Smirnov, A. V.; Johnson, Duane D.

2018-05-31

From electronic-structure-based thermodynamic linear response, we establish chemical ordering behavior in complex solid solutions versus how Gibbs' space is traversed—applying it on prototype refractory A2 Ta-Nb-Mo-W high-entropy alloys. Near ideal stoichiometry, this alloy has anomalous, intricate chemical ordering tendencies, with long-ranged chemical interactions that produce competing short-range order (SRO) with a crossover to spinodal segregation. This atypical SRO arises from canonical band behavior that, with alloying, creates features near the Fermi surface (well defined even with disorder) that change to simple commensurate SRO with (un)filling of these states. In conclusion, our results reveal how complexity and competing electronic effects controlmore » ordering in these alloys.« less

Ta-Nb-Mo-W refractory high-entropy alloys: Anomalous ordering behavior and its intriguing electronic origin

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

Singh, Prashant; Smirnov, A. V.; Johnson, Duane D.

From electronic-structure-based thermodynamic linear response, we establish chemical ordering behavior in complex solid solutions versus how Gibbs' space is traversed—applying it on prototype refractory A2 Ta-Nb-Mo-W high-entropy alloys. Near ideal stoichiometry, this alloy has anomalous, intricate chemical ordering tendencies, with long-ranged chemical interactions that produce competing short-range order (SRO) with a crossover to spinodal segregation. This atypical SRO arises from canonical band behavior that, with alloying, creates features near the Fermi surface (well defined even with disorder) that change to simple commensurate SRO with (un)filling of these states. In conclusion, our results reveal how complexity and competing electronic effects controlmore » ordering in these alloys.« less

A perspective on the complexity of dietary fiber structures and their potential effect on the gut microbiota.

PubMed

Hamaker, Bruce R; Tuncil, Yunus E

2014-11-25

Even though there are many factors that determine the human colon microbiota composition, diet is an important one because most microorganisms in the colon obtain energy for their growth by degrading complex dietary compounds, particularly dietary fibers. While fiber carbohydrates that escape digestion in the upper gastrointestinal tract are recognized to have a range of structures, the vastness in number of chemical structures from the perspective of the bacteria is not well appreciated. In this article, we introduce the concept of "discrete structure" that is defined as a unique chemical structure, often within a fiber molecule, which aligns with encoded gene clusters in bacterial genomes. The multitude of discrete structures originates from the array of different fiber types coupled with structural variations within types due to genotype and growing environment, anatomical parts of the grain or plant, discrete regions within polymers, and size of oligosaccharides and small polysaccharides. These thousands of discrete structures conceivably could be used to favor bacteria in the competitive colon environment. A global framework needs to be developed to better understand how dietary fibers can be used to obtain predicted changes in microbiota composition for improved health. This will require a multi-disciplinary effort that includes biological scientists, clinicians, and carbohydrate specialists. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ion-implanted Si-nanostructures buried in a SiO{sub 2} substrate studied with soft-x-ray spectroscopy

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

Williams, R.; Rubensson, J.E.; Eisebitt, S.

1997-04-01

In recent years silicon nanostructures have gained great interest because of their optical luminescence, which immediately suggests several applications, e.g., in optoelectronic devices. Nanostructures are also investigated because of the fundamental physics involved in the underlying luminescence mechanism, especially attention has been drawn to the influence of the reduced dimensions on the electronic structure. The forming of stable and well-defined nanostructured materials is one goal of cluster physics. For silicon nanostructures this goal has so far not been reached, but various indirect methods have been established, all having the problem of producing less well defined and/or unstable nanostructures. Ion implantationmore » and subsequent annealing is a promising new technique to overcome some of these difficulties. In this experiment the authors investigate the electronic structure of ion-implanted silicon nanoparticles buried in a stabilizing SiO{sub 2} substrate. Soft X-ray emission (SXE) spectroscopy features the appropriate information depth to investigate such buried structures. SXE spectra to a good approximation map the local partial density of occupied states (LPDOS) in broad band materials like Si. The use of monochromatized synchrotron radiation (MSR) allows for selective excitation of silicon atoms in different chemical environments. Thus, the emission from Si atom sites in the buried structure can be separated from contributions from the SiO{sub 2} substrate. In this preliminary study strong size dependent effects are found, and the electronic structure of the ion-implanted nanoparticles is shown to be qualitatively different from porous silicon. The results can be interpreted in terms of quantum confinement and chemical shifts due to neighboring oxygen atoms at the interface to SiO{sub 2}.« less

The source, discharge, and chemical characteristics of water from Agua Caliente Spring, Palm Springs, California

USGS Publications Warehouse

Brandt, Justin; Catchings, Rufus D.; Christensen, Allen H.; Flint, Alan L.; Gandhok, Gini; Goldman, Mark R.; Halford, Keith J.; Langenheim, V.E.; Martin, Peter; Rymer, Michael J.; Schroeder, Roy A.; Smith, Gregory A.; Sneed, Michelle; Martin, Peter

2011-01-01

Agua Caliente Spring, in downtown Palm Springs, California, has been used for recreation and medicinal therapy for hundreds of years and currently (2008) is the source of hot water for the Spa Resort owned by the Agua Caliente Band of the Cahuilla Indians. The Agua Caliente Spring is located about 1,500 feet east of the eastern front of the San Jacinto Mountains on the southeast-sloping alluvial plain of the Coachella Valley. The objectives of this study were to (1) define the geologic structure associated with the Agua Caliente Spring; (2) define the source(s), and possibly the age(s), of water discharged by the spring; (3) ascertain the seasonal and longer-term variability of the natural discharge, water temperature, and chemical characteristics of the spring water; (4) evaluate whether water-level declines in the regional aquifer will influence the temperature of the spring discharge; and, (5) estimate the quantity of spring water that leaks out of the water-collector tank at the spring orifice.

Scaffold explorer: an interactive tool for organizing and mining structure-activity data spanning multiple chemotypes.

PubMed

Agrafiotis, Dimitris K; Wiener, John J M

2010-07-08

We introduce Scaffold Explorer, an interactive tool that allows medicinal chemists to define hierarchies of chemical scaffolds and use them to explore their project data. Scaffold Explorer allows the user to construct a tree, where each node corresponds to a specific scaffold. Each node can have multiple children, each of which represents a more refined substructure relative to its parent node. Once the tree is defined, it can be mapped onto any collection of compounds and be used as a navigational tool to explore structure-activity relationships (SAR) across different chemotypes. The rich visual analytics of Scaffold Explorer afford the user a "bird's-eye" view of the chemical space spanned by a particular data set, map any physicochemical property or biological activity of interest onto the individual scaffold nodes, serve as an aggregator for the properties of the compounds represented by these nodes, and quickly distinguish promising chemotypes from less interesting or problematic ones. Unlike previous approaches, which focused on automated extraction and classification of scaffolds, the utility of the new tool rests on its interactivity and ability to accommodate the medicinal chemists' intuition by allowing the use of arbitrary substructures containing variable atoms, bonds, and/or substituents such as those employed in substructure search.

Spectroscopic Characterization of the Water Oxidation Intermediates in the Blue Dimer Ru-Based Catalyst for Artificial Photosynthesis

NASA Astrophysics Data System (ADS)

Moonshiram, Dooshaye; Pushkar, Yulia; Jurss, Jonah; Concepcion, Javier; Meyer, Thomas; Zakharova, Taisiya; Alperovich, Igor

2012-02-01

Utilization of sunlight requires solar capture, light-to-energy conversion and storage. One effective way to store energy is to convert it into chemical energy by fuel-forming reactions, such as water splitting into hydrogen and oxygen. Ruthenium complexes are among few molecular-defined catalysts capable of water splitting. Mechanistic insights about such catalysts can be acquired by spectroscopic analysis of short-lived intermediates of catalytic water oxidation. Use of techniques such as EPR and X-ray absorption spectroscopy (XAS) are used to determine electronic requirements of catalytic water oxidation. About 30 years ago Meyer and coworkers reported first ruthenium-based catalyst for water oxidation, the ``blue dimer''. We performed EPR studies and characterized structures and electronic configurations of intermediates of water oxidation by the ``blue dimer''. Intermediates were prepared chemically by oxidation of Ru-complexes with defined number of Ce (IV) equivalents and freeze-quenched at controlled times. Changes in oxidation state of Ru atom were detected by XANES at Ru K-edges. K-edges are sensitive to changes in Ru oxidation state for Blue Dimer [3,3]^4+, [3,4]^4+, [3,4]'^4+ and [4,5]^3+ allowing a clear assignment of Ru oxidation state in intermediates. EXAFS demonstrated structural changes.

Topsoil structure stability in a restored floodplain: Impacts of fluctuating water levels, soil parameters and ecosystem engineers.

PubMed

Schomburg, A; Schilling, O S; Guenat, C; Schirmer, M; Le Bayon, R C; Brunner, P

2018-10-15

Ecosystem services provided by floodplains are strongly controlled by the structural stability of soils. The development of a stable structure in floodplain soils is affected by a complex and poorly understood interplay of hydrological, physico-chemical and biological processes. This paper aims at analysing relations between fluctuating groundwater levels, soil physico-chemical and biological parameters on soil structure stability in a restored floodplain. Water level fluctuations in the soil are modelled using a numerical surface-water-groundwater flow model and correlated to soil physico-chemical parameters and abundances of plants and earthworms. Causal relations and multiple interactions between the investigated parameters are tested through structural equation modelling (SEM). Fluctuating water levels in the soil did not directly affect the topsoil structure stability, but indirectly through affecting plant roots and soil parameters that in turn determine topsoil structure stability. These relations remain significant for mean annual days of complete and partial (>25%) water saturation. Ecosystem functioning of a restored floodplain might already be affected by the fluctuation of groundwater levels alone, and not only through complete flooding by surface water during a flood period. Surprisingly, abundances of earthworms did not show any relation to other variables in the SEM. These findings emphasise that earthworms have efficiently adapted to periodic stress and harsh environmental conditions. Variability of the topsoil structure stability is thus stronger driven by the influence of fluctuating water levels on plants than by the abundance of earthworms. This knowledge about the functional network of soil engineering organisms, soil parameters and fluctuating water levels and how they affect soil structural stability is of fundamental importance to define management strategies of near-natural or restored floodplains in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

Integration of QSAR and in vitro toxicology.

PubMed Central

Barratt, M D

1998-01-01

The principles of quantitative structure-activity relationships (QSAR) are based on the premise that the properties of a chemical are implicit in its molecular structure. Therefore, if a mechanistic hypothesis can be proposed linking a group of related chemicals with a particular toxic end point, the hypothesis can be used to define relevant parameters to establish a QSAR. Ways in which QSAR and in vitro toxicology can complement each other in development of alternatives to live animal experiments are described and illustrated by examples from acute toxicological end points. Integration of QSAR and in vitro methods is examined in the context of assessing mechanistic competence and improving the design of in vitro assays and the development of prediction models. The nature of biological variability is explored together with its implications for the selection of sets of chemicals for test development, optimization, and validation. Methods are described to support the use of data from in vivo tests that do not meet today's stringent requirements of acceptability. Integration of QSAR and in vitro methods into strategic approaches for the replacement, reduction, and refinement of the use of animals is described with examples. PMID:9599692

Extensive Chemical Modifications in the Primary Protein Structure of IgG1 Subvisible Particles Are Necessary for Breaking Immune Tolerance.

PubMed

Boll, Björn; Bessa, Juliana; Folzer, Emilien; Ríos Quiroz, Anacelia; Schmidt, Roland; Bulau, Patrick; Finkler, Christof; Mahler, Hanns-Christian; Huwyler, Jörg; Iglesias, Antonio; Koulov, Atanas V

2017-04-03

A current concern with the use of therapeutic proteins is the likely presence of aggregates and submicrometer, subvisible, and visible particles. It has been proposed that aggregates and particles may lead to unwanted increases in the immune response with a possible impact on safety or efficacy. The aim of this study was thus to evaluate the ability of subvisible particles of a therapeutic antibody to break immune tolerance in an IgG1 transgenic mouse model and to understand the particle attributes that might play a role in this process. We investigated the immunogenic properties of subvisible particles (unfractionated, mixed populations, and well-defined particle size fractions) using a transgenic mouse model expressing a mini-repertoire of human IgG1 (hIgG1 tg). Immunization with proteinaceous subvisible particles generated by artificial stress conditions demonstrated that only subvisible particles bearing very extensive chemical modifications within the primary amino acid structure could break immune tolerance in the hIgG1 transgenic mouse model. Protein particles exhibiting low levels of chemical modification were not immunogenic in this model.

Toward an atomistic description of the urea-denatured state of proteins.

PubMed

Candotti, Michela; Esteban-Martín, Santiago; Salvatella, Xavier; Orozco, Modesto

2013-04-09

We present here the characterization of the structural, dynamics, and energetics of properties of the urea-denatured state of ubiquitin, a small prototypical soluble protein. By combining state-of-the-art molecular dynamics simulations with NMR and small-angle X-ray scattering data, we were able to: (i) define the unfolded state ensemble, (ii) understand the energetics stabilizing unfolded structures in urea, (iii) describe the dedifferential nature of the interactions of the fully unfolded proteins with urea and water, and (iv) characterize the early stages of protein refolding when chemically denatured proteins are transferred to native conditions. The results presented herein are unique in providing a complete picture of the chemically unfolded state of proteins and contribute to deciphering the mechanisms that stabilize the native state of proteins, as well as those that maintain them unfolded in the presence of urea.

Toward an atomistic description of the urea-denatured state of proteins

PubMed Central

Candotti, Michela; Esteban-Martín, Santiago; Salvatella, Xavier; Orozco, Modesto

2013-01-01

We present here the characterization of the structural, dynamics, and energetics of properties of the urea-denatured state of ubiquitin, a small prototypical soluble protein. By combining state-of-the-art molecular dynamics simulations with NMR and small-angle X-ray scattering data, we were able to: (i) define the unfolded state ensemble, (ii) understand the energetics stabilizing unfolded structures in urea, (iii) describe the dedifferential nature of the interactions of the fully unfolded proteins with urea and water, and (iv) characterize the early stages of protein refolding when chemically denatured proteins are transferred to native conditions. The results presented herein are unique in providing a complete picture of the chemically unfolded state of proteins and contribute to deciphering the mechanisms that stabilize the native state of proteins, as well as those that maintain them unfolded in the presence of urea. PMID:23536295

Bright Side of Lignin Depolymerization: Toward New Platform Chemicals

PubMed Central

2018-01-01

Lignin, a major component of lignocellulose, is the largest source of aromatic building blocks on the planet and harbors great potential to serve as starting material for the production of biobased products. Despite the initial challenges associated with the robust and irregular structure of lignin, the valorization of this intriguing aromatic biopolymer has come a long way: recently, many creative strategies emerged that deliver defined products via catalytic or biocatalytic depolymerization in good yields. The purpose of this review is to provide insight into these novel approaches and the potential application of such emerging new structures for the synthesis of biobased polymers or pharmacologically active molecules. Existing strategies for functionalization or defunctionalization of lignin-based compounds are also summarized. Following the whole value chain from raw lignocellulose through depolymerization to application whenever possible, specific lignin-based compounds emerge that could be in the future considered as potential lignin-derived platform chemicals. PMID:29337543

Definitive Mineralogical Analysis of Mars Analog Rocks Using the CheMin XRD/XRF Instrument

NASA Technical Reports Server (NTRS)

Blake, D. F.; Sarrazin, P.; Bish, D. L.; Feldman, S.; Chipera, S. J.; Vaniman, D. T.; Collins, S.

2004-01-01

Mineral identification is a critical component of Mars Astrobiological missions. Chemical or elemental data alone are not definitive because a single elemental or chemical composition or even a single bonding type can represent a range of substances or mineral assemblages. Minerals are defined as unique structural and compositional phases that occur naturally. There are about 15,000 minerals that have been described on Earth, all uniquely identifiable via diffraction methods. There are likely many minerals yet undiscovered on Earth, and likewise on Mars. If an unknown phase is identified on Mars, it can be fully characterized by structural (X-ray Diffraction, XRD) and elemental analysis (X-ray Fluorescence, XRF) without recourse to other data because XRD relies on the principles of atomic arrangement for its determinations. XRD is the principal means of identification and characterization of minerals on Earth.

Functional groups of ecosystem engineers: a proposed classification with comments on current issues.

PubMed

Berke, Sarah K

2010-08-01

Ecologists have long known that certain organisms fundamentally modify, create, or define habitats by altering the habitat's physical properties. In the past 15 years, these processes have been formally defined as "ecosystem engineering", reflecting a growing consensus that environmental structuring by organisms represents a fundamental class of ecological interactions occurring in most, if not all, ecosystems. Yet, the precise definition and scope of ecosystem engineering remains debated, as one should expect given the complexity, enormity, and variability of ecological systems. Here I briefly comment on a few specific current points of contention in the ecosystem engineering concept. I then suggest that ecosystem engineering can be profitably subdivided into four narrower functional categories reflecting four broad mechanisms by which ecosystem engineering occurs: structural engineers, bioturbators, chemical engineers, and light engineers. Finally, I suggest some conceptual model frameworks that could apply broadly within these functional groups.

A Protein Structure Initiative Approach to Expression, Purification, and In Situ Delivery of Human Cytochrome b5 to Membrane Vesicles†

PubMed Central

Sobrado, Pablo; Goren, Michael A.; James, Declan; Amundson, Carissa K.; Fox, Brian G.

2008-01-01

A specialized vector backbone from the Protein Structure Initiative was used to express full-length human cytochrome b5 as a C-terminal fusion to His8-maltose binding protein in Escherichia coli. The fusion protein could be completely cleaved by tobacco etch virus protease, and a yield of ~18 mg of purified full-length human cytochrome b5 per liter of culture medium was obtained (2.3 mg per]of wet weight bacterial cells). In situ proteolysis of the fusion protein in the presence of chemically defined synthetic liposomes allowed facile spontaneous delivery of the functional peripheral membrane protein into a defined membrane environment without prior exposure to detergents or other lipids. The utility of this approach as a delivery method for production and incorporation of monotopic (peripheral) membrane proteins is discussed. PMID:18226920

A Protein Structure Initiative approach to expression, purification, and in situ delivery of human cytochrome b5 to membrane vesicles.

PubMed

Sobrado, Pablo; Goren, Michael A; James, Declan; Amundson, Carissa K; Fox, Brian G

2008-04-01

A specialized vector backbone from the Protein Structure Initiative was used to express full-length human cytochrome b5 as a C-terminal fusion to His8-maltose binding protein in Escherichia coli. The fusion protein could be completely cleaved by tobacco etch virus protease, and a yield of approximately 18 mg of purified full-length human cytochrome b5 per liter of culture medium was obtained (2.3mg per g of wet weight bacterial cells). In situ proteolysis of the fusion protein in the presence of chemically defined synthetic liposomes allowed facile spontaneous delivery of the functional peripheral membrane protein into a defined membrane environment without prior exposure to detergents or other lipids. The utility of this approach as a delivery method for production and incorporation of monotopic (peripheral) membrane proteins is discussed.

Structural flexibility in magnetocaloric RE 5T 4 (RE=rare-earth; T=Si,Ge,Ga) materials: Effect of chemical substitution on structure, bonding and properties

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

Misra, Sumohan

The binary, ternary and multicomponent intermetallic compounds of rare-earth metals (RE) with group 14 elements (Tt) at the RE 5Tt 4 stoichiometry have been known for over 30 years, but only in the past decade have these materials become a gold mine for solid-state chemistry, materials science and condensed matter physics. It all started with the discovery of a giant magnetocaloric effect in Gd 5Si 2Ge 2, along with other extraordinary magnetic properties, such as a colossal magnetostriction and giant magnetoresistance. The distinctiveness of this series is in the remarkable flexibility of the chemical bonding between well-defined, subnanometer-thick slabs andmore » the resultant magnetic, transport, and thermodynamic properties of these materials. This can be controlled by varying either or both RE and Tt elements, including mixed rare-earth elements on the RE sites and different group 14 (or T = group 13 or 15) elements occupying the Tt sites. In addition to chemical means, the interslab interactions are also tunable by temperature, pressure, and magnetic field. Thus, this system provides a splendid 'playground' to investigate the interrelationships among composition, structure, physical properties, and chemical bonding. The work presented in this dissertation involving RE 5T 4 materials has resulted in the successful synthesis, characterization, property measurements, and theoretical analyses of various new intermetallic compounds. The results provide significant insight into the fundamental magnetic and structural behavior of these materials and help us better understand the complex link between a compound's composition, its observed structure, and its properties.« less

Organometallic compounds: an opportunity for chemical biology?

PubMed

Patra, Malay; Gasser, Gilles

2012-06-18

Organometallic compounds are renowned for their remarkable applications in the field of catalysis, but much less is known about their potential in chemical biology. Indeed, such compounds have long been considered to be either unstable under physiological conditions or cytotoxic. As a consequence, little attention has been paid to their possible utilisation for biological purposes. Because of their outstanding physicochemical properties, which include chemical stability, structural diversity and unique photo- and electrochemical properties, however, organometallic compounds have the ability to play a leading role in the field of chemical biology. Indeed, remarkable examples of the use of such compounds-notably as enzyme inhibitors and as luminescent agents-have recently been reported. Here we summarise recent advances in the use of organometallic compounds for chemical biology purposes, an area that we define as "organometallic chemical biology". We also demonstrate that these recent discoveries are only a beginning and that many other organometallic complexes are likely to be found useful in this field of research in the near future. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Alternative Life Styles for Extraterrestrial Chemists

NASA Astrophysics Data System (ADS)

Benner, S.

2002-12-01

Life is no more (and no less) than a special type of organic chemistry, one that combines a frequently encountered property of organic molecules (the ability to undergo spontaneous chemical transformation) with an uncommon property (the ability to direct the synthesis of self-copies) in a way that allows new molecular features arising through spontaneous transformation to themselves be copied. Any chemical system having this combination will undergo natural selection, evolving in structure to replicate faster through more efficient use of molecular resources and energy. Axiomatically, life cannot exist in an environment at thermodynamic equilibrium. If it were, by the second law of thermodynamics, no net chemical transformation would be possible. Beyond this constraint, it is difficult to define environmental conditions or chemical structures necessary for life. Water is certainly not required for a chemical system to copy itself; in the laboratory, non-aqueous environments appear to support this behavior better. Chemical transformations that might support energy and chemical metabolisms are known in environments as acidic as the aerosols in the atmosphere of Venus, or as basic as the atmosphere of Jupiter. Laboratory experiments with analogs of the nucleic acids, proteins, sugars, and lipids show that the particular molecular structures found in terrean life need not be universal, even those life in water near neutral pH. Indeed, while both water and biological macromolecules are commonly regarded as essential for terrean-like life, water destroys terrean biological macromolecules. These chemical realities create a complex decision environment as NASA attempts to design instrumentation carried by missions, select places in the solar system to send them, and chose laboratory studies on Earth to provide their scientific support. This talk will review a hierarchy of chemical possibilities and constraints that start with the chemistry of terrean life, and takes steps towards weird life. We shall consider alternative amino acid building blocks for proteins, alternative building blocks for nucleic acids, alternative structural features of genetic and catalytic molecules, alternative nucleophile-electrophile pairs to support metabolism, non-polar reaction modes that might support metabolism, non-terrean pH (< 0, > 14) and solvent environments for life, extreme temperature ranges (especially sub zero Celsius) low temperature ranges, alternative thermodynamic design for metabolic pathways, alternative dimensionalities of genetic and catalytic molecules, and approaches for isolating life other than conventional cell structures. Each of these discussions will combine experimental and theoretical information. The first involves organic chemical synthesis that creates new forms of chemical matter to ask "What if?" and "Why not?" questions. The second draws on a century of literature in physical organic chemistry to formulate general constraints on the structure and transformation of organic matter to provide constraints on possible Darwinian chemistries in the galaxy.

Evaluation of food-relevant chemicals in the ToxCast high-throughput screening program.

PubMed

Karmaus, Agnes L; Filer, Dayne L; Martin, Matthew T; Houck, Keith A

2016-06-01

Thousands of chemicals are directly added to or come in contact with food, many of which have undergone little to no toxicological evaluation. The landscape of the food-relevant chemical universe was evaluated using cheminformatics, and subsequently the bioactivity of food-relevant chemicals across the publicly available ToxCast highthroughput screening program was assessed. In total, 8659 food-relevant chemicals were compiled including direct food additives, food contact substances, and pesticides. Of these food-relevant chemicals, 4719 had curated structure definition files amenable to defining chemical fingerprints, which were used to cluster chemicals using a selforganizing map approach. Pesticides, and direct food additives clustered apart from one another with food contact substances generally in between, supporting that these categories not only reflect different uses but also distinct chemistries. Subsequently, 1530 food-relevant chemicals were identified in ToxCast comprising 616 direct food additives, 371 food contact substances, and 543 pesticides. Bioactivity across ToxCast was filtered for cytotoxicity to identify selective chemical effects. Initiating analyses from strictly chemical-based methodology or bioactivity/cytotoxicity-driven evaluation presents unbiased approaches for prioritizing chemicals. Although bioactivity in vitro is not necessarily predictive of adverse effects in vivo, these data provide insight into chemical properties and cellular targets through which foodrelevant chemicals elicit bioactivity. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparative NMR Analysis of an 80-Residue G Protein-Coupled Receptor Fragment in Two Membrane Mimetic Environments

PubMed Central

LS, Cohen; B, Arshava; A, Neumoin; JM, Becker; P, Güntert; O, Zerbe; Naider, F

2011-01-01

Fragments of integral membrane proteins have been used to study the physical chemical properties of regions of transporters and receptors. Ste2p(G31-T110) is an 80-residue polypeptide which contains a portion of the N-terminal domain, transmembrane domain 1 (TM1), intracellular loop 1, TM2 and part of extracellular loop 2 of the α-factor receptor (Ste2p) from Saccharomyces cerevisiae. The structure of this peptide was previously determined to form a helical hairpin in lyso-palmitoylphosphatidyl-glycerol micelles (LPPG)[1]. Herein, we perform a systematic comparison of the structure of this protein fragment in micelles and trifluoroethanol(TFE):water in order to understand whether spectra recorded in organic:aqueous medium can facilitate the structure determination in a micellar environment. Using uniformly labeled peptide and peptide selectively protonated on Ile, Val and Leu methyl groups in a perdeuterated background and a broad set of 3D NMR experiments we assigned 89% of the observable atoms. NOEs and chemical shift analysis were used to define the helical regions of the fragment. Together with constraints from paramagnetic spin labeling, NOEs were used to calculate a transiently folded helical hairpin structure for this peptide in TFE:water. Correlation of chemical shifts was insufficient to transfer assignments from TFE:water to LPPG spectra in the absence of further information. PMID:21791199

Accurate protein structure modeling using sparse NMR data and homologous structure information.

PubMed

Thompson, James M; Sgourakis, Nikolaos G; Liu, Gaohua; Rossi, Paolo; Tang, Yuefeng; Mills, Jeffrey L; Szyperski, Thomas; Montelione, Gaetano T; Baker, David

2012-06-19

While information from homologous structures plays a central role in X-ray structure determination by molecular replacement, such information is rarely used in NMR structure determination because it can be incorrect, both locally and globally, when evolutionary relationships are inferred incorrectly or there has been considerable evolutionary structural divergence. Here we describe a method that allows robust modeling of protein structures of up to 225 residues by combining (1)H(N), (13)C, and (15)N backbone and (13)Cβ chemical shift data, distance restraints derived from homologous structures, and a physically realistic all-atom energy function. Accurate models are distinguished from inaccurate models generated using incorrect sequence alignments by requiring that (i) the all-atom energies of models generated using the restraints are lower than models generated in unrestrained calculations and (ii) the low-energy structures converge to within 2.0 Å backbone rmsd over 75% of the protein. Benchmark calculations on known structures and blind targets show that the method can accurately model protein structures, even with very remote homology information, to a backbone rmsd of 1.2-1.9 Å relative to the conventional determined NMR ensembles and of 0.9-1.6 Å relative to X-ray structures for well-defined regions of the protein structures. This approach facilitates the accurate modeling of protein structures using backbone chemical shift data without need for side-chain resonance assignments and extensive analysis of NOESY cross-peak assignments.

Effect of mixed Ge/Si cross-linking on the physical properties of amorphous Ge-Si-Te networks

NASA Astrophysics Data System (ADS)

Gunasekera, K.; Boolchand, P.; Micoulaut, M.

2014-04-01

Amorphous GexSixTe1-2x glasses are studied as a function of composition by a combination of experimental and theoretical methods, allowing for a full description of the network structure in relationship with physico-chemical properties. Calorimetric and thermal measurements reveal that such glasses display an anomalous behavior across a range of compositions xc1=7.5% and

A crystal-chemical classification of borate structures with emphasis on hydrated borates

USGS Publications Warehouse

Christ, C.L.; Clark, J.R.

1977-01-01

The rules governing formation of hydrated borate polyanions that were proposed by C.L. Christ in 1960 are critically reviewed and new rules added on the basis of recent crystal structure determinations. Principles and classifications previously published by others are also critically reviewed briefly. The fundamental building blocks from which borate polyanions can be constructed are defined on the basis of the number n of boron atoms, and the fully hydrated polyanions are illustrated. Known structures are grouped accordingly, and a shorthand notation using n and symbols ?? = triangle, T = tetrahedron is introduced so that the polyanions can be easily characterized. For example, 3:??+2T describes [B3O3(OH)5]2-. Correct structural formulas are assigned borates with known structures whereas borates of unknown structure are grouped separately. ?? 1977 Springer-Verlag.

Research progress on synthesis and characteristic about dendrimers

NASA Astrophysics Data System (ADS)

Tang, Zitao

2017-12-01

Dendrimers are hyper-branched polymers which have perfectly defined structures. Different from the common polymers, dendrimers are synthesized by a step-by-step iterative style, which starts from a central core and forms branching parts outward. The dendrimers also have different physical and chemical characteristics from common polymers. In this paper, contributions to dendrimer synthesis from different researchers with different scientific background, synthesis of different dendrimers, and applications of them will be reviewed.

Stable Fe nanomagnets encapsulated inside vertically-aligned carbon nanotubes.

PubMed

Bondino, Federica; Magnano, Elena; Ciancio, Regina; Castellarin Cudia, Carla; Barla, Alessandro; Carlino, Elvio; Yakhou-Harris, Flora; Rupesinghe, Nalin; Cepek, Cinzia

2017-12-06

Well-defined sized (5-10 nm) metallic iron nanoparticles (NPs) with body-centered cubic structure encapsulated inside the tip of millimeter-long vertically aligned carbon nanotubes (VACNTs) of uniform length have been investigated with high-resolution transmission electron microscopy and soft X-ray spectroscopy techniques. Surface-sensitive and chemically-selective measurements have been used to evaluate the magnetic properties of the encapsulated NPs. The encapsulated Fe NPs display magnetic remanence up to room temperature, low coercivity, high chemical stability and no significant anisotropy. Our surface-sensitive measurements combined with the specific morphology of the studied VACNTs allow us to pinpoint the contribution of the surface oxidized or hydroxidized iron catalysts present at the VACNT-substrate interface.

NMR studies of protein-nucleic acid interactions.

PubMed

Varani, Gabriele; Chen, Yu; Leeper, Thomas C

2004-01-01

Protein-DNA and protein-RNA complexes play key functional roles in every living organism. Therefore, the elucidation of their structure and dynamics is an important goal of structural and molecular biology. Nuclear magnetic resonance (NMR) studies of protein and nucleic acid complexes have common features with studies of protein-protein complexes: the interaction surfaces between the molecules must be carefully delineated, the relative orientation of the two species needs to be accurately and precisely determined, and close intermolecular contacts defined by nuclear Overhauser effects (NOEs) must be obtained. However, differences in NMR properties (e.g., chemical shifts) and biosynthetic pathways for sample productions generate important differences. Chemical shift differences between the protein and nucleic acid resonances can aid the NMR structure determination process; however, the relatively limited dispersion of the RNA ribose resonances makes the process of assigning intermolecular NOEs more difficult. The analysis of the resulting structures requires computational tools unique to nucleic acid interactions. This chapter summarizes the most important elements of the structure determination by NMR of protein-nucleic acid complexes and their analysis. The main emphasis is on recent developments (e.g., residual dipolar couplings and new Web-based analysis tools) that have facilitated NMR studies of these complexes and expanded the type of biological problems to which NMR techniques of structural elucidation can now be applied.

Directed self-assembly of block copolymer films on atomically-thin graphene chemical patterns

DOE PAGES

Chang, Tzu-Hsuan; Xiong, Shisheng; Jacobberger, Robert M.; ...

2016-08-16

Directed self-assembly of block copolymers is a scalable method to fabricate well-ordered patterns over the wafer scale with feature sizes below the resolution of conventional lithography. Typically, lithographically-defined prepatterns with varying chemical contrast are used to rationally guide the assembly of block copolymers. The directed self-assembly to obtain accurate registration and alignment is largely influenced by the assembly kinetics. Furthermore, a considerably broad processing window is favored for industrial manufacturing. Using an atomically-thin layer of graphene on germanium, after two simple processing steps, we create a novel chemical pattern to direct the assembly of polystyreneblock-poly(methyl methacrylate). Faster assembly kinetics aremore » observed on graphene/germanium chemical patterns than on conventional chemical patterns based on polymer mats and brushes. This new chemical pattern allows for assembly on a wide range of guiding periods and along designed 90° bending structures. We also achieve density multiplication by a factor of 10, greatly enhancing the pattern resolution. Lastly, the rapid assembly kinetics, minimal topography, and broad processing window demonstrate the advantages of inorganic chemical patterns composed of hard surfaces.« less

The chemical evolution of oligonucleotide therapies of clinical utility.

PubMed

Khvorova, Anastasia; Watts, Jonathan K

2017-03-01

After nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency are derived primarily from the chemical structure of the oligonucleotide whereas their target is defined by the base sequence. Thus, as oligonucleotides with a particular chemical design show appropriate distribution and safety profiles for clinical gene silencing in a particular tissue, this will open the door to the rapid development of additional drugs targeting other disease-associated genes in the same tissue. To achieve clinical productivity, the chemical architecture of the oligonucleotide needs to be optimized with a combination of sugar, backbone, nucleobase, and 3'- and 5'-terminal modifications. A portfolio of chemistries can be used to confer drug-like properties onto the oligonucleotide as a whole, with minor chemical changes often translating into major improvements in clinical efficacy. One outstanding challenge in oligonucleotide chemical development is the optimization of chemical architectures to ensure long-term safety. There are multiple designs that enable effective targeting of the liver, but a second challenge is to develop architectures that enable robust clinical efficacy in additional tissues.

Design, Synthesis, and Self-Assembly of Well-Defined Hybrid Materials Including Polymer Amphiphiles and Giant Tetrahedra Molecules Based on Poss Nanoparticles

NASA Astrophysics Data System (ADS)

Huang, Mingjun

"Bottom-up" techniques-based self-assembly are always attracting people's interests since this technology provides relatively low economic cost and fast route to construct organized structures at different scales. Considering unprecedented benefits from polymer materials, self-assemblies utilizing polymer building blocks have been extensively studied to achieve diverse hierarchical structures and various attractive properties. However, precise controls of chemical primary structures and compositions and exact constructions of hierarchal ordered structures in synthetic polymers are far from being fully appreciated. In this dissertation, a novel approach has been utilized to construct diverse well-defined nano-building blocks, giant molecules, via conjugating different, and functionalized molecular nanoparticles (MNPs) which are shape- and volume-persistent nano-objects with precise molecular structure and specific symmetry. The representative examples of the three basic categories of giant molecules, "giant polyhedra", "giant surfactants", and "giant shape amphiphiles" were discussed in details. First, a class of precisely defined, nanosized giant tetrahedra was constructed by placing different polyhedral oligomeric silsesquioxane (POSS) molecular nanoparticles at the vertices of a rigid tetrahedral framework. Designed symmetry breaking of these giant tetrahedra introduces accurate positional interactions and results in diverse selectively assembled, highly ordered supramolecular lattices including a Frank-Kasper (FK) A15 phase. The FK and quasicrystal phases are originally identified in metal alloys and only sporadically observed in soft matters. It remains unclear how to correlate their stability with the chemical composition and molecular topology in the self-assembling systems. We then for this purpose designed and studied the self-assembly phase transition sequences of four series of hybrid giant surfactants based on hydrophilic POSS cages tethered with one to four polystyrene (PS) tails. With increasing the number of tails, molecular topological variations not only affect phase boundaries in terms of the PS volume fraction, but also open a window to stabilize supramolecular FK and quasicrystal phases in the spherical phase region, demonstrating the critical role of molecular topology in dictating the formation of unconventional supramolecular lattices of "soft" spherical motifs. The FK A15 phase was even surprisingly observed in the giant shape amphiphile molecule, triphenylene-6BPOSS, which has a disk-like flat triphenylene core connected with six hydrophobic POSS cages by sides. Without conical molecular shape, triphenylene-6BPOSS self-assembled and stabilized into supramolecular sphere via pi-pi interactions through a completely different mechanism with precious two cases. These studies indicate that "bottom-up" self-assemble based on well-defined giant molecules approach can be rather powerful to fabricate usually complicated hierarchical structures and open up a wide field of supramolecular self-assembly with unexpected structure and properties.

3-Dimensional atomic scale structure of the ionic liquid-graphite interface elucidated by AM-AFM and quantum chemical simulations

NASA Astrophysics Data System (ADS)

Page, Alister J.; Elbourne, Aaron; Stefanovic, Ryan; Addicoat, Matthew A.; Warr, Gregory G.; Voïtchovsky, Kislon; Atkin, Rob

2014-06-01

In situ amplitude modulated atomic force microscopy (AM-AFM) and quantum chemical simulations are used to resolve the structure of the highly ordered pyrolytic graphite (HOPG)-bulk propylammonium nitrate (PAN) interface with resolution comparable with that achieved for frozen ionic liquid (IL) monolayers using STM. This is the first time that (a) molecular resolution images of bulk IL-solid interfaces have been achieved, (b) the lateral structure of the IL graphite interface has been imaged for any IL, (c) AM-AFM has elucidated molecular level structure immersed in a viscous liquid and (d) it has been demonstrated that the IL structure at solid surfaces is a consequence of both thermodynamic and kinetic effects. The lateral structure of the PAN-graphite interface is highly ordered and consists of remarkably well-defined domains of a rhomboidal superstructure composed of propylammonium cations preferentially aligned along two of the three directions in the underlying graphite lattice. The nanostructure is primarily determined by the cation. Van der Waals interactions between the propylammonium chains and the surface mean that the cation is enriched in the surface layer, and is much less mobile than the anion. The presence of a heterogeneous lateral structure at an ionic liquid-solid interface has wide ranging ramifications for ionic liquid applications, including lubrication, capacitive charge storage and electrodeposition.In situ amplitude modulated atomic force microscopy (AM-AFM) and quantum chemical simulations are used to resolve the structure of the highly ordered pyrolytic graphite (HOPG)-bulk propylammonium nitrate (PAN) interface with resolution comparable with that achieved for frozen ionic liquid (IL) monolayers using STM. This is the first time that (a) molecular resolution images of bulk IL-solid interfaces have been achieved, (b) the lateral structure of the IL graphite interface has been imaged for any IL, (c) AM-AFM has elucidated molecular level structure immersed in a viscous liquid and (d) it has been demonstrated that the IL structure at solid surfaces is a consequence of both thermodynamic and kinetic effects. The lateral structure of the PAN-graphite interface is highly ordered and consists of remarkably well-defined domains of a rhomboidal superstructure composed of propylammonium cations preferentially aligned along two of the three directions in the underlying graphite lattice. The nanostructure is primarily determined by the cation. Van der Waals interactions between the propylammonium chains and the surface mean that the cation is enriched in the surface layer, and is much less mobile than the anion. The presence of a heterogeneous lateral structure at an ionic liquid-solid interface has wide ranging ramifications for ionic liquid applications, including lubrication, capacitive charge storage and electrodeposition. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01219d

Theoretical Investigations of Well-Defined Graphene Nanostructures: Catalysis, Spectroscopy, and Development of Novel Fragment-Based Models

NASA Astrophysics Data System (ADS)

Noffke, Benjamin W.

Carbon materials have the potential to replace some precious metals in renewable energy applications. These materials are particularly attractive because of the elemental abundance and relatively low nuclear mass of carbon, implying economically feasible and lightweight materials. Targeted design of carbon materials is hindered by the lack of fundamental understanding that is required to tailor their properties for the desired application. However, most available synthetic methods to create carbon materials involve harsh conditions that limit the control of the resulting structure. Without a well-defined structure, the system is too complex and fundamental studies cannot be definitive. This work seeks to gain fundamental understanding through the development and application of efficient computational models for these systems, in conjunction with experiments performed on soluble, well-defined graphene nanostructures prepared by our group using a bottom-up synthetic approach. Theory is used to determine mechanistic details for well-defined carbon systems in applications of catalysis and electrochemical transformations. The resulting computational models do well to explain previous observations of carbon materials and provide suggestions for future directions. However, as the system size of the nanostructures gets larger, the computational cost can become prohibitive. To reduce the computational scaling of quantum chemical calculations, a new fragmentation scheme has been developed that addresses the challenges of fragmenting conjugated molecules. By selecting fragments that retain important structural characteristics in graphene, a more efficient method is achieved. The new method paves the way for an automated, systematic fragmentation scheme of graphene molecules.

Synthesis of monolithic graphene – graphite integrated electronics

PubMed Central

Park, Jang-Ung; Nam, SungWoo; Lee, Mi-Sun; Lieber, Charles M.

2013-01-01

Encoding electronic functionality into nanoscale elements during chemical synthesis has been extensively explored over the past decade as the key to developing integrated nanosystems1 with functions defined by synthesis2-6. Graphene7-12 has been recently explored as a two-dimensional nanoscale material, and has demonstrated simple device functions based on conventional top-down fabrication13-20. However, the synthetic approach to encoding electronic functionality and thus enabling an entire integrated graphene electronics in a chemical synthesis had not previously been demonstrated. Here we report an unconventional approach for the synthesis of monolithically-integrated electronic devices based on graphene and graphite. Spatial patterning of heterogeneous catalyst metals permits the selective growth of graphene and graphite, with controlled number of graphene layers. Graphene transistor arrays with graphitic electrodes and interconnects were formed from synthesis. These functional, all-carbon structures were transferrable onto a variety of substrates. The integrated transistor arrays were used to demonstrate real-time, multiplexed chemical sensing, and more significantly, multiple carbon layers of the graphene-graphite device components were vertically assembled to form a three-dimensional flexible structure which served as a top-gate transistor array. These results represent a substantial progress towards encoding electronic functionality via chemical synthesis and suggest future promise for one-step integration of graphene-graphite based electronics. PMID:22101813

Synthesis of monolithic graphene-graphite integrated electronics.

PubMed

Park, Jang-Ung; Nam, SungWoo; Lee, Mi-Sun; Lieber, Charles M

2011-11-20

Encoding electronic functionality into nanoscale elements during chemical synthesis has been extensively explored over the past decade as the key to developing integrated nanosystems with functions defined by synthesis. Graphene has been recently explored as a two-dimensional nanoscale material, and has demonstrated simple device functions based on conventional top-down fabrication. However, the synthetic approach to encoding electronic functionality and thus enabling an entire integrated graphene electronics in a chemical synthesis had not previously been demonstrated. Here we report an unconventional approach for the synthesis of monolithically integrated electronic devices based on graphene and graphite. Spatial patterning of heterogeneous metal catalysts permits the selective growth of graphene and graphite, with a controlled number of graphene layers. Graphene transistor arrays with graphitic electrodes and interconnects were formed from the synthesis. These functional, all-carbon structures were transferable onto a variety of substrates. The integrated transistor arrays were used to demonstrate real-time, multiplexed chemical sensing and more significantly, multiple carbon layers of the graphene-graphite device components were vertically assembled to form a three-dimensional flexible structure which served as a top-gate transistor array. These results represent substantial progress towards encoding electronic functionality through chemical synthesis and suggest the future promise of one-step integration of graphene-graphite based electronics.

Total chemical synthesis and biological activities of glycosylated and non-glycosylated forms of the chemokines CCL1 and Ser-CCL1.

PubMed

Okamoto, Ryo; Mandal, Kalyaneswar; Ling, Morris; Luster, Andrew D; Kajihara, Yasuhiro; Kent, Stephen B H

2014-05-12

CCL1 is a naturally glycosylated chemokine protein that is secreted by activated T-cells and acts as a chemoattractant for monocytes. Originally, CCL1 was identified as a 73 amino acid protein having one N-glycosylation site, and a variant 74 residue non-glycosylated form, Ser-CCL1, has also been described. There are no systematic studies of the effect of glycosylation on the biological activities of either CCL1 or Ser-CCL1. Here we report the total chemical syntheses of both N-glycosylated and non-glycosylated forms of (Ser-)CCL1, by convergent native chemical ligation. We used an N-glycan isolated from hen egg yolk together with the Nbz linker for Fmoc chemistry solid phase synthesis of the glycopeptide-(α) thioester building block. Chemotaxis assays of these glycoproteins and the corresponding non-glycosylated proteins were carried out. The results were correlated with the chemical structures of the (glyco)protein molecules. To the best of our knowledge, these are the first investigations of the effect of glycosylation on the chemotactic activity of the chemokine (Ser-)CCL1 using homogeneous N-glycosylated protein molecules of defined covalent structure. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Process development for waveguide chemical sensors with integrated polymeric sensitive layers

NASA Astrophysics Data System (ADS)

Amberkar, Raghu; Gao, Zhan; Park, Jongwon; Henthorn, David B.; Kim, Chang-Soo

2008-02-01

Due to the proper optical property and flexibility in the process development, an epoxy-based, high-aspect ratio photoresist SU-8 is now attracting attention in optical sensing applications. Manipulation of the surface properties of SU-8 waveguides is critical to attach functional films such as chemically-sensitive layers. We describe a new integration process to immobilize fluorescence molecules on SU-8 waveguide surface for application to intensity-based optical chemical sensors. We use two polymers for this application. Spin-on, hydrophobic, photopatternable silicone is a convenient material to contain fluorophore molecules and to pattern a photolithographically defined thin layer on the surface of SU-8. We use fumed silica powders as an additive to uniformly disperse the fluorophores in the silicone precursor. In general, additional processes are not critically required to promote the adhesion between the SU-8 and silicone. The other material is polyethylene glycol diacrylate (PEGDA). Recently we demonstrated a novel photografting method to modify the surface of SU-8 using a surface bound initiator to control its wettability. The activated surface is then coated with a monomer precursor solution. Polymerization follows when the sample is exposed to UV irradiation, resulting in a grafted PEGDA layer incorporating fluorophores within the hydrogel matrix. Since this method is based the UV-based photografting reaction, it is possible to grow off photolithographically defined hydrogel patterns on the waveguide structures. The resulting films will be viable integrated components in optical bioanalytical sensors. This is a promising technique for integrated chemical sensors both for planar type waveguide and vertical type waveguide chemical sensors.

The Physics and Chemistry of Materials

NASA Astrophysics Data System (ADS)

Gersten, Joel I.; Smith, Frederick W.

2001-06-01

A comprehensive introduction to the structure, properties, and applications of materials This title provides the first unified treatment for the broad subject of materials. Authors Gersten and Smith use a fundamental approach to define the structure and properties of a wide range of solids on the basis of the local chemical bonding and atomic order present in the material. Emphasizing the physical and chemical origins of material properties, the book focuses on the most technologically important materials being utilized and developed by scientists and engineers. Appropriate for use in advanced materials courses, The Physics and Chemistry of Materials provides the background information necessary to assimilate the current academic and patent literature on materials and their applications. Problem sets, illustrations, and helpful tables complete this well-rounded new treatment. Five sections cover these important topics: * Structure of materials, including crystal structure, bonding in solids, diffraction and the reciprocal lattice, and order and disorder in solids * Physical properties of materials, including electrical, thermal, optical, magnetic, and mechanical properties * Classes of materials, including semiconductors, superconductors, magnetic materials, and optical materials in addition to metals, ceramics, polymers, dielectrics, and ferroelectrics * A section on surfaces, thin films, interfaces, and multilayers discusses the effects of spatial discontinuities in the physical and chemical structure of materials * A section on synthesis and processing examines the effects of synthesis on the structure and properties of various materials This book is enhanced by a Web-based supplement that offers advanced material together with an entire electronic chapter on the characterization of materials. The Physics and Chemistry of Materials is a complete introduction to the structure and properties of materials for students and an excellent reference for scientists and engineers.

Heparin/heparan sulfate 6-O-sulfatase from Flavobacterium heparinum: integrated structural and biochemical investigation of enzyme active site and substrate specificity.

PubMed

Myette, James R; Soundararajan, Venkataramanan; Shriver, Zachary; Raman, Rahul; Sasisekharan, Ram

2009-12-11

Heparin and heparan sulfate glycosaminoglycans (HSGAGs) comprise a chemically heterogeneous class of sulfated polysaccharides. The development of structure-activity relationships for this class of polysaccharides requires the identification and characterization of degrading enzymes with defined substrate specificity and enzymatic activity. Toward this end, we report here the molecular cloning and extensive structure-function analysis of a 6-O-sulfatase from the Gram-negative bacterium Flavobacterium heparinum. In addition, we report the recombinant expression of this enzyme in Escherichia coli in a soluble, active form and identify it as a specific HSGAG sulfatase. We further define the mechanism of action of the enzyme through biochemical and structural studies. Through the use of defined substrates, we investigate the kinetic properties of the enzyme. This analysis was complemented by homology-based molecular modeling studies that sought to rationalize the substrate specificity of the enzyme and mode of action through an analysis of the active-site topology of the enzyme including identifying key enzyme-substrate interactions and assigning key amino acids within the active site of the enzyme. Taken together, our structural and biochemical studies indicate that 6-O-sulfatase is a predominantly exolytic enzyme that specifically acts on N-sulfated or N-acetylated 6-O-sulfated glucosamines present at the non-reducing end of HSGAG oligosaccharide substrates. This requirement for the N-acetyl or N-sulfo groups on the glucosamine substrate can be explained through eliciting favorable interactions with key residues within the active site of the enzyme. These findings provide a framework that enables the use of 6-O-sulfatase as a tool for HSGAG structure-activity studies as well as expand our biochemical and structural understanding of this important class of enzymes.

The importance of chemistry in creating well-defined nanoscopic embedded therapeutics: devices capable of the dual functions of imaging and therapy.

PubMed

Nyström, Andreas M; Wooley, Karen L

2011-10-18

Nanomedicine is a rapidly evolving field, for which polymer building blocks are proving useful for the construction of sophisticated devices that provide enhanced diagnostic imaging and treatment of disease, known as theranostics. These well-defined nanoscopic objects have high loading capacities, can protect embedded therapeutic cargo, and offer control over the conditions and rates of release. Theranostics also offer external surface area for the conjugation of ligands to impart stealth characteristics and/or direct their interactions with biological receptors and provide a framework for conjugation of imaging agents to track delivery to diseased site(s). The nanoscopic dimensions allow for extensive biological circulation. The incorporation of such multiple functions is complicated, requiring exquisite chemical control during production and rigorous characterization studies to confirm the compositions, structures, properties, and performance. We are particularly interested in the study of nanoscopic objects designed for treatment of lung infections and acute lung injury, urinary tract infections, and cancer. This Account highlights our work over several years to tune the assembly of unique nanostructures. We provide examples of how the composition, structure, dimensions, and morphology of theranostic devices can tune their performance as drug delivery agents for the treatment of infectious diseases and cancer. The evolution of nanostructured materials from relatively simple overall shapes and internal morphologies to those of increasing complexity is driving the development of synthetic methodologies for the preparation of increasingly complex nanomedicine devices. Our nanomedicine devices are derived from macromolecules that have well-defined compositions, structures, and topologies, which provide a framework for their programmed assembly into nanostructures with controlled sizes, shapes, and morphologies. The inclusion of functional units within selective compartments/domains allows us to create (multi)functional materials. We employ combinations of controlled radical and ring-opening polymerizations, chemical transformations, and supramolecular assembly to construct such materials as functional entities. The use of multifunctional monomers with selective polymerization chemistries affords regiochemically functionalized polymers. Further supramolecular assembly processes in water with further chemical transformations provide discrete nanoscopic objects within aqueous solutions. This approach echoes processes in nature, whereby small molecules (amino acids, nucleic acids, saccharides) are linked into polymers (proteins, DNA/RNA, polysaccharides, respectively) and then those polymers fold into three-dimensional conformations that can lead to nanoscopic functional entities.

Inhibition of strigolactone receptors by N-phenylanthranilic acid derivatives: Structural and functional insights.

PubMed

Hamiaux, Cyril; Drummond, Revel S M; Luo, Zhiwei; Lee, Hui Wen; Sharma, Prachi; Janssen, Bart J; Perry, Nigel B; Denny, William A; Snowden, Kimberley C

2018-04-27

The strigolactone (SL) family of plant hormones regulates a broad range of physiological processes affecting plant growth and development and also plays essential roles in controlling interactions with parasitic weeds and symbiotic fungi. Recent progress elucidating details of SL biosynthesis, signaling, and transport offers many opportunities for discovering new plant-growth regulators via chemical interference. Here, using high-throughput screening and downstream biochemical assays, we identified N -phenylanthranilic acid derivatives as potent inhibitors of the SL receptors from petunia (DAD2), rice (OsD14), and Arabidopsis (AtD14). Crystal structures of DAD2 and OsD14 in complex with inhibitors further provided detailed insights into the inhibition mechanism, and in silico modeling of 19 other plant strigolactone receptors suggested that these compounds are active across a large range of plant species. Altogether, these results provide chemical tools for investigating SL signaling and further define a framework for structure-based approaches to design and validate optimized inhibitors of SL receptors for specific plant targets. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Phenylpyrrolidine structural mimics of pirfenidone lacking antifibrotic activity: A new tool for mechanism of action studies.

PubMed

Haak, Andrew J; Girtman, Megan A; Ali, Mohamed F; Carmona, Eva M; Limper, Andrew H; Tschumperlin, Daniel J

2017-09-15

Pirfenidone recently received FDA approval as one of the first two drugs designed to treat idiopathic pulmonary fibrosis. While the clinical data continues to support the efficacy of pirfenidone, the specific molecular mechanism of action of this drug has not been fully defined. From a chemical perspective the comparatively simple and lipophilic structure of pirfenidone combined with its administration at high doses, both experimentally and clinically, complicates some of the basic tenants of drug action and drug design. Our objective here was to identify a commercially available structural mimic of pirfenidone which retains key aspects of its physical chemical properties but does not display any of its antifibrotic effects. We tested these molecules using lung fibroblasts derived from patients with idiopathic pulmonary fibrosis and found phenylpyrrolidine based analogs of pirfenidone that were non-toxic and lacked antifibrotic activity even when applied at millimolar concentrations. Based on our findings, these molecules represent pharmacological tools for future studies delineating pirfenidone's mechanism of action. Copyright © 2017 Elsevier B.V. All rights reserved.

Biosorption of six basic and acidic dyes on brown alga Sargassum ilicifolium: optimization, kinetic and isotherm studies.

PubMed

Tabaraki, Reza; Sadeghinejad, Negar

2017-06-01

Biosorption of Methyl Blue (MB), Fuchsin Acid (FA), Rhodamine B (RB), Methylene Blue (MEB), Bromocresol purple (BC) and Methyl Orange (MO) onto Sargassum ilicifolium was studied in a batch system. Effect of dye structure on biosorption by Sargassum ilicifolium was studied to define the correlation between chemical structure and biosorption capacity. Different dye groups such as triarylmethane (MB, FA and BC), monoazo (MO), thiazine (MEB) and xanthene (RB) were studied. At optimum experimental conditions for each dye, biosorption capacity was determined and compared. The results indicate that the chemical structure (triarylmethane, monoazo, thiazine, xanthene), number of sulfonic groups, basicity (element of chromophore group: S, N, O) and molecular weight of dye molecules influence their biosorption capacity. Experimental parameters such as biosorbent dose, pH, contact time, and initial dye concentration were optimized for each dye. The biosorption kinetic data were successfully described by the pseudo second-order model. The biosorption results were also analyzed by the Langmuir and Freundlich isotherms. Finally, biosorption capacities obtained using Sargassum ilicifolium were compared with the ones presented in the literature.

The activation of fibroblast growth factors by heparin: synthesis, structure, and biological activity of heparin-like oligosaccharides.

PubMed

de Paz, J L; Angulo, J; Lassaletta, J M; Nieto, P M; Redondo-Horcajo, M; Lozano, R M; Giménez-Gallego, G; Martín-Lomas, M

2001-09-03

An effective strategy has been designed for the synthesis of oligosaccharides of different sizes structurally related to the regular region of heparin; this is illustrated by the preparation of hexasaccharide 1 and octasaccharide 2. This synthetic strategy provides the oligosaccharide sequence containing a D-glucosamine unit at the nonreducing end that is not available either by enzymatic or chemical degradation of heparin. It may permit, after slight modifications, the preparation of oligosaccharide fragments with different charge distribution as well. NMR spectroscopy and molecular dynamics simulations have shown that the overall structure of 1 in solution is a stable right-hand helix with four residues per turn. Hexasaccharide 1 and, most likely, octasaccharide 2 are, therefore, chemically well-defined structural models of naturally occurring heparin-like oligosaccharides for use in binding and biological activity studies. Both compounds 1 and 2 induce the mitogenic activity of acid fibroblast growth factor (FGF1), with the half-maximum activating concentration of 2 being equivalent to that of heparin. Sedimentation equilibrium analysis with compound 2 suggests that heparin-induced FGF1 dimerization is not an absolute requirement for biological activity.

Growth-dissolution-regrowth transitions of Fe3O4 nanoparticles as building blocks for 3D magnetic nanoparticle clusters under hydrothermal conditions.

PubMed

Lin, Mouhong; Huang, Haoliang; Liu, Zuotao; Liu, Yingju; Ge, Junbin; Fang, Yueping

2013-12-10

Magnetic nanoparticle clusters (MNCs) are a class of secondary structural materials that comprise chemically defined nanoparticles assembled into clusters of defined size. Herein, MNCs are fabricated through a one-pot solvothermal reaction featuring self-limiting assembly of building blocks and the controlled reorganization process. Such growth-dissolution-regrowth fabrication mechanism overcomes some limitations of conventional solvothermal fabrication methods with regard to restricted available feature size and structural complexity, which can be extended to other oxides (as long as one can be chelated by EDTA-2Na). Based on this method, the nanoparticle size of MNCs is tuned between 6.8 and 31.2 nm at a fixed cluster diameter of 120 nm, wherein the critical size for superparamagnetic-ferromagnetic transition is estimated from 13.5 to 15.7 nm. Control over the nature and secondary structure of MNCs gives an excellent model system to understand the nanoparticle size-dependent magnetic properties of MNCs. MNCs have potential applications in many different areas, while this work evaluates their cytotoxicity and Pb(2+) adsorption capacity as initial application study.

Development of smart textiles with embedded fiber optic chemical sensors

NASA Astrophysics Data System (ADS)

Khalil, Saif E.; Yuan, Jianming; El-Sherif, Mahmoud A.

2004-03-01

Smart textiles are defined as textiles capable of monitoring their own health conditions or structural behavior, as well as sensing external environmental conditions. Smart textiles appear to be a future focus of the textile industry. As technology accelerates, textiles are found to be more useful and practical for potential advanced technologies. The majority of textiles are used in the clothing industry, which set up the idea of inventing smart clothes for various applications. Examples of such applications are medical trauma assessment and medical patients monitoring (heart and respiration rates), and environmental monitoring for public safety officials. Fiber optics have played a major role in the development of smart textiles as they have in smart structures in general. Optical fiber integration into textile structures (knitted, woven, and non-woven) is presented, and defines the proper methodology for the manufacturing of smart textiles. Samples of fabrics with integrated optical fibers were processed and tested for optical signal transmission. This was done in order to investigate the effect of textile production procedures on optical fiber performance. The tests proved the effectiveness of the developed methodology for integration of optical fibers without changing their optical performance or structural integrity.

Toward Single Electron Nanoelectronics Using Self-Assembled DNA Structure.

PubMed

Tapio, Kosti; Leppiniemi, Jenni; Shen, Boxuan; Hytönen, Vesa P; Fritzsche, Wolfgang; Toppari, J Jussi

2016-11-09

DNA based structures offer an adaptable and robust way to develop customized nanostructures for various purposes in bionanotechnology. One main aim in this field is to develop a DNA nanobreadboard for a controllable attachment of nanoparticles or biomolecules to form specific nanoelectronic devices. Here we conjugate three gold nanoparticles on a defined size TX-tile assembly into a linear pattern to form nanometer scale isolated islands that could be utilized in a room temperature single electron transistor. To demonstrate this, conjugated structures were trapped using dielectrophoresis for current-voltage characterization. After trapping only high resistance behavior was observed. However, after extending the islands by chemical growth of gold, several structures exhibited Coulomb blockade behavior from 4.2 K up to room temperature, which gives a good indication that self-assembled DNA structures could be used for nanoelectronic patterning and single electron devices.

Towards interoperable and reproducible QSAR analyses: Exchange of datasets.

PubMed

Spjuth, Ola; Willighagen, Egon L; Guha, Rajarshi; Eklund, Martin; Wikberg, Jarl Es

2010-06-30

QSAR is a widely used method to relate chemical structures to responses or properties based on experimental observations. Much effort has been made to evaluate and validate the statistical modeling in QSAR, but these analyses treat the dataset as fixed. An overlooked but highly important issue is the validation of the setup of the dataset, which comprises addition of chemical structures as well as selection of descriptors and software implementations prior to calculations. This process is hampered by the lack of standards and exchange formats in the field, making it virtually impossible to reproduce and validate analyses and drastically constrain collaborations and re-use of data. We present a step towards standardizing QSAR analyses by defining interoperable and reproducible QSAR datasets, consisting of an open XML format (QSAR-ML) which builds on an open and extensible descriptor ontology. The ontology provides an extensible way of uniquely defining descriptors for use in QSAR experiments, and the exchange format supports multiple versioned implementations of these descriptors. Hence, a dataset described by QSAR-ML makes its setup completely reproducible. We also provide a reference implementation as a set of plugins for Bioclipse which simplifies setup of QSAR datasets, and allows for exporting in QSAR-ML as well as old-fashioned CSV formats. The implementation facilitates addition of new descriptor implementations from locally installed software and remote Web services; the latter is demonstrated with REST and XMPP Web services. Standardized QSAR datasets open up new ways to store, query, and exchange data for subsequent analyses. QSAR-ML supports completely reproducible creation of datasets, solving the problems of defining which software components were used and their versions, and the descriptor ontology eliminates confusions regarding descriptors by defining them crisply. This makes is easy to join, extend, combine datasets and hence work collectively, but also allows for analyzing the effect descriptors have on the statistical model's performance. The presented Bioclipse plugins equip scientists with graphical tools that make QSAR-ML easily accessible for the community.

Towards interoperable and reproducible QSAR analyses: Exchange of datasets

PubMed Central

2010-01-01

Background QSAR is a widely used method to relate chemical structures to responses or properties based on experimental observations. Much effort has been made to evaluate and validate the statistical modeling in QSAR, but these analyses treat the dataset as fixed. An overlooked but highly important issue is the validation of the setup of the dataset, which comprises addition of chemical structures as well as selection of descriptors and software implementations prior to calculations. This process is hampered by the lack of standards and exchange formats in the field, making it virtually impossible to reproduce and validate analyses and drastically constrain collaborations and re-use of data. Results We present a step towards standardizing QSAR analyses by defining interoperable and reproducible QSAR datasets, consisting of an open XML format (QSAR-ML) which builds on an open and extensible descriptor ontology. The ontology provides an extensible way of uniquely defining descriptors for use in QSAR experiments, and the exchange format supports multiple versioned implementations of these descriptors. Hence, a dataset described by QSAR-ML makes its setup completely reproducible. We also provide a reference implementation as a set of plugins for Bioclipse which simplifies setup of QSAR datasets, and allows for exporting in QSAR-ML as well as old-fashioned CSV formats. The implementation facilitates addition of new descriptor implementations from locally installed software and remote Web services; the latter is demonstrated with REST and XMPP Web services. Conclusions Standardized QSAR datasets open up new ways to store, query, and exchange data for subsequent analyses. QSAR-ML supports completely reproducible creation of datasets, solving the problems of defining which software components were used and their versions, and the descriptor ontology eliminates confusions regarding descriptors by defining them crisply. This makes is easy to join, extend, combine datasets and hence work collectively, but also allows for analyzing the effect descriptors have on the statistical model's performance. The presented Bioclipse plugins equip scientists with graphical tools that make QSAR-ML easily accessible for the community. PMID:20591161

Amino acids in the cultivation of mammalian cells.

PubMed

Salazar, Andrew; Keusgen, Michael; von Hagen, Jörg

2016-05-01

Amino acids are crucial for the cultivation of mammalian cells. This importance of amino acids was realized soon after the development of the first cell lines, and a solution of a mixture of amino acids has been supplied to cultured cells ever since. The importance of amino acids is further pronounced in chemically defined mammalian cell culture media, making the consideration of their biological and chemical properties necessary. Amino acids concentrations have been traditionally adjusted to their cellular consumption rates. However, since changes in the metabolic equilibrium of amino acids can be caused by changes in extracellular concentrations, metabolomics in conjunction with flux balance analysis is being used in the development of culture media. The study of amino acid transporters is also gaining importance since they control the intracellular concentrations of these molecules and are influenced by conditions in cell culture media. A better understanding of the solubility, stability, dissolution kinetics, and interactions of these molecules is needed for an exploitation of these properties in the development of dry powdered chemically defined media for mammalian cells. Due to the complexity of these mixtures however, this has proven to be challenging. Studying amino acids in mammalian cell culture media will help provide a better understanding of how mammalian cells in culture interact with their environment. It would also provide insight into the chemical behavior of these molecules in solutions of complex mixtures, which is important in the understanding of the contribution of individual amino acids to protein structure.

Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate.

PubMed

Oyler, Benjamin L; Khan, Mohd M; Smith, Donald F; Harberts, Erin M; Kilgour, David P A; Ernst, Robert K; Cross, Alan S; Goodlett, David R

2018-06-01

Recent advances in lipopolysaccharide (LPS) biology have led to its use in drug discovery pipelines, including vaccine and vaccine adjuvant discovery. Desirable characteristics for LPS vaccine candidates include both the ability to produce a specific antibody titer in patients and a minimal host inflammatory response directed by the innate immune system. However, in-depth chemical characterization of most LPS extracts has not been performed; hence, biological activities of these extracts are unpredictable. Additionally, the most widely adopted workflow for LPS structure elucidation includes nonspecific chemical decomposition steps before analyses, making structures inferred and not necessarily biologically relevant. In this work, several different mass spectrometry workflows that have not been previously explored were employed to show proof-of-principle for top down LPS primary structure elucidation, specifically for a rough-type mutant (J5) E. coli-derived LPS component of a vaccine candidate. First, ion mobility filtered precursor ions were subjected to collision induced dissociation (CID) to define differences in native J5 LPS v. chemically detoxified J5 LPS (dLPS). Next, ultra-high mass resolving power, accurate mass spectrometry was employed for unequivocal precursor and product ion empirical formulae generation. Finally, MS 3 analyses in an ion trap instrument showed that previous knowledge about dissociation of LPS components can be used to reconstruct and sequence LPS in a top down fashion. A structural rationale is also explained for differential inflammatory dose-response curves, in vitro, when HEK-Blue hTLR4 cells were administered increasing concentrations of native J5 LPS v. dLPS, which will be useful in future drug discovery efforts. Graphical Abstract ᅟ.

Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate

NASA Astrophysics Data System (ADS)

Oyler, Benjamin L.; Khan, Mohd M.; Smith, Donald F.; Harberts, Erin M.; Kilgour, David P. A.; Ernst, Robert K.; Cross, Alan S.; Goodlett, David R.

2018-02-01

Recent advances in lipopolysaccharide (LPS) biology have led to its use in drug discovery pipelines, including vaccine and vaccine adjuvant discovery. Desirable characteristics for LPS vaccine candidates include both the ability to produce a specific antibody titer in patients and a minimal host inflammatory response directed by the innate immune system. However, in-depth chemical characterization of most LPS extracts has not been performed; hence, biological activities of these extracts are unpredictable. Additionally, the most widely adopted workflow for LPS structure elucidation includes nonspecific chemical decomposition steps before analyses, making structures inferred and not necessarily biologically relevant. In this work, several different mass spectrometry workflows that have not been previously explored were employed to show proof-of-principle for top down LPS primary structure elucidation, specifically for a rough-type mutant (J5) E. coli-derived LPS component of a vaccine candidate. First, ion mobility filtered precursor ions were subjected to collision induced dissociation (CID) to define differences in native J5 LPS v. chemically detoxified J5 LPS (dLPS). Next, ultra-high mass resolving power, accurate mass spectrometry was employed for unequivocal precursor and product ion empirical formulae generation. Finally, MS3 analyses in an ion trap instrument showed that previous knowledge about dissociation of LPS components can be used to reconstruct and sequence LPS in a top down fashion. A structural rationale is also explained for differential inflammatory dose-response curves, in vitro, when HEK-Blue hTLR4 cells were administered increasing concentrations of native J5 LPS v. dLPS, which will be useful in future drug discovery efforts. [Figure not available: see fulltext.

Improving Recovery from Catastrophic Bone Injuries: An Animal Model for Assessing the Bone Reparative Potential of Progenitor Cell Therapy

DTIC Science & Technology

2009-08-01

make structurally different bone in vivo – Although calvarial and BMSC have osteogenic potential, they make a very different type of bone. The two...calvarial defect model. Extracel™ hydrogel is based on thiolated hyaluronate (Glycosil) and thiolated gelatin (Gelin- S) which are crosslinked by...for encapsulation of cells for 3D cultures and in vivo study. Each component of Extracel™ is chemically defined. Variation of the hydrogel

Pyroelectric A1GaN/GaN HEMTs for ion-, gas- and Polar-Liquid Sensors

DTIC Science & Technology

2004-08-17

including the manipulation of pico- and nanofluid volumes on chemical or structural modified surfaces and defining suitable interfaces to the macroworld. A... nanofluidic dispensers based on piezo actuators, the micro periphery and the electronics for measuring biochemical assay systems (in vivo and in vitro...interface without the need of a modulation doped barrier. The carrier concentration and electron mobility within the 2DEG can be very high and build

Versatile fabrication of paper-based microfluidic devices with high chemical resistance using scholar glue and magnetic masks.

PubMed

Cardoso, Thiago M G; de Souza, Fabrício R; Garcia, Paulo T; Rabelo, Denilson; Henry, Charles S; Coltro, Wendell K T

2017-06-29

Simple methods have been developed for fabricating microfluidic paper-based analytical devices (μPADs) but few of these devices can be used with organic solvents and/or aqueous solutions containing surfactants. This study describes a simple fabrication strategy for μPADs that uses readily available scholar glue to create the hydrophobic flow barriers that are resistant to surfactants and organic solvents. Microfluidic structures were defined by magnetic masks designed with either neodymium magnets or magnetic sheets to define the patter, and structures were created by spraying an aqueous solution of glue on the paper surface. The glue-coated paper was then exposed to UV/Vis light for cross-linking to maximize chemical resistance. Examples of microzone arrays and microfluidic devices are demonstrated. μPADs fabricated with scholar glue retained their barriers when used with surfactants, organic solvents, and strong/weak acids and bases unlike common wax-printed barriers. Paper microzones and microfluidic devices were successfully used for colorimetric assays of clinically relevant analytes commonly detected in urinalysis to demonstrate the low background of the barrier material and generally applicability to sensing. The proposed fabrication method is attractive for both its ability to be used with diverse chemistries and the low cost and simplicity of the materials and process. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Grinter, David C.; Senanayake, Sanjaya D.; Flege, Jan Ingo

Ceria is an important material for chemical conversion processes in catalysis. Its intrinsic properties as a reducible oxide can be exploited to achieve catalytic selectivity and activity. However, numerous phenomenological characteristics of ceria remain unknown and its active nature is ever slowly being unraveled. Well defined models of ceria (111) are an important way to systematically study these properties and take advantage of new in situ methods that require pristine materials that allow for the interrogation of the most fundamental traits of this material. The ceria-Ru(0001) model is now the most well studied model surface with numerous aspects of itsmore » preparation, atomic structure and reactivity studied by several groups. The preparation of CeO x structures oriented with a (111) surface termination can be achieved through molecular beam deposition, facilitating the growth of well-defined nanostructures, microparticles, and films on the Ru(0001) surface. The growth mechanism exploits the epitaxial relationship between CeOx and Ru to form a carpet mode of well oriented layers of Osingle bondCesingle bondO. These models can be studied to unravel the atomic structure and the oxidation state (Ce 4+ and Ce 3+), as prepared and under redox conditions (reduction/oxidation) or with reaction using reactants (e.g., H 2, methanol). Here, we present a discussion of these most recent observations pertaining to the growth mode, arrangement of atoms on the surface, characteristic chemical state, and redox chemistry of the CeO x-Ru surface. As a result, with insights from these studies we propose new strategies to further unravel the chemistry of ceria.« less

Selective host molecules obtained by dynamic adaptive chemistry.

PubMed

Matache, Mihaela; Bogdan, Elena; Hădade, Niculina D

2014-02-17

Up till 20 years ago, in order to endow molecules with function there were two mainstream lines of thought. One was to rationally design the positioning of chemical functionalities within candidate molecules, followed by an iterative synthesis-optimization process. The second was the use of a "brutal force" approach of combinatorial chemistry coupled with advanced screening for function. Although both methods provided important results, "rational design" often resulted in time-consuming efforts of modeling and synthesis only to find that the candidate molecule was not performing the designed job. "Combinatorial chemistry" suffered from a fundamental limitation related to the focusing of the libraries employed, often using lead compounds that limit its scope. Dynamic constitutional chemistry has developed as a combination of the two approaches above. Through the rational use of reversible chemical bonds together with a large plethora of precursor libraries, one is now able to build functional structures, ranging from quite simple molecules up to large polymeric structures. Thus, by introduction of the dynamic component within the molecular recognition processes, a new perspective of deciphering the world of the molecular events has aroused together with a new field of chemistry. Since its birth dynamic constitutional chemistry has continuously gained attention, in particular due to its ability to easily create from scratch outstanding molecular structures as well as the addition of adaptive features. The fundamental concepts defining the dynamic constitutional chemistry have been continuously extended to currently place it at the intersection between the supramolecular chemistry and newly defined adaptive chemistry, a pivotal feature towards evolutive chemistry. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electron-beam-induced topographical, chemical, and structural patterning of amorphous titanium oxide films.

PubMed

Kern, P; Müller, Y; Patscheider, J; Michler, J

2006-11-30

Electrolytically deposited amorphous TiO2 films on steel are remarkably sensitive to electron beam (e-beam) irradiation at moderate energies at 20 keV, resulting in controlled local oxide reduction and crystallization, opening the possibility for local topographical, chemical, and structural modifications within a biocompatible, amorphous, and semiconducting matrix. The sensitivity is shown to vary significantly with the annealing temperature of as-deposited films. Well-defined irradiation conditions in terms of probe current IP (5 microA) and beam size were achieved with an electron probe microanalyzer. As shown by atomic force and optical microscopy, micro-Raman spectroscopy, wavelength-dispersive X-ray (WDX), and Auger analyses, e-beam exposure below 1 Acm-2 immediately leads to electron-stimulated oxygen desorption, resulting in a well-defined volume loss primarily limited to the irradiated zone under the electron probe and in a blue color shift in this zone because of the presence of Ti2O3. Irradiation at 5 Acm(-2) (IP = 5 microA) results in local crystallization into anatase phase within 1 s of exposure and in reduction to TiO after an extended exposure of 60 s. Further reduction to the metallic state could be observed after 60 s of exposure at approximately 160 Acm(-2). The local reduction could be qualitatively sensed with WDX analysis and Auger line scans. An estimation of the film temperature in the beam center indicates that crystallization occurs at less than 150 degrees C, well below the atmospheric crystallization temperature of the present films. The high e-beam sensitivity in combination with the well-defined volume loss from oxygen desorption allows for precise electron lithographic topographical patterning of the present oxides. Irradiation effects leading to the observed reduction and crystallization phenomena under moderate electron energies are discussed.

Conceptual, self-assembling graphene nanocontainers

NASA Astrophysics Data System (ADS)

Boothroyd, Simon; Anwar, Jamshed

2015-07-01

We show that graphene nano-sheets, when appropriately functionalised, can form self-assembling nanocontainers which may be opened or closed using a chemical trigger such as pH or polarity of solvent. Conceptual design rules are presented for different container structures, whose ability to form and encapsulate guest molecules is verified by molecular dynamics simulations. The structural simplicity of the graphene nanocontainers offers considerable scope for scaling the capacity, modulating the nature of the internal environment, and defining the trigger for encapsulation or release of the guest molecule(s). This design study will serve to provide additional impetus to developing synthetic approaches for selective functionalisation of graphene.

Inside out: Speed-dependent barriers to reactive mixing

NASA Astrophysics Data System (ADS)

Kelley, Douglas; Nevins, Thomas

2015-11-01

Reactive mixing occurs wherever fluid flow and chemical or biological growth interact over time and space. Those interactions often lead to steep gradients in reactant and product concentration, arranged in complex spatial structures that can cause wide variation in the global reaction rate and concentrations. By simultaneously measuring fluid velocity and reaction front locations in laboratory experiments with the Belousov-Zhabotinsky reaction, we find that the barriers defining those structures vary dramatically with speed. In particular, we find that increasing flow speed causes reacted regions to move from vortex edges to vortex cores, thus turning the barriers ``inside out''. This observation has implications for reactive mixing of phytoplankton in global oceans.

Enzymatic synthesis of structured lipids.

PubMed

Iwasaki, Yugo; Yamane, Tsuneo

2004-01-01

Structured lipids (SLs) are defined as lipids that are modified chemically or enzymatically in order to change their structure. This review deals with structured triacylglycerols (STGs) and structured phospholipids (SPLs). The most typical STGs are MLM-type STGs, having medium chain fatty acids (FAs) at the 1- and 3-positions and a long chain fatty acid at the 2- position. MLM-type STGs are synthesized by: 1) 1,3-position-specific lipase-catalyzed acyl exchange of TG with FA or with FA ethylester (FAEt); 2) 1,3-position-specific lipase-catalyzed acylation of glycerol with FA, giving symmetric 1,3-diacyl-sn-glycerol, followed by chemical acylation at the sn-2 position, and; 3) 1,3-position-specific lipase-catalyzed deacylation of TG, giving 2-monoacylglycerol, followed by reacylation at the 1- and 3-positions with FA or with (FAEt). Enzymatic preparation of SPLs requires: 1) acyl group modification, and 2) head group modification of phospholipids. Acyl group modification is performed using lipases or phospholipase A2-mediated transesterification or ester synthesis to introduce arbitrary fatty acid to phospholipids. Head group modification is carried out by phospholipase D-catalyzed transphosphatidylation. A wide range of compounds can be introduced into the polar head of phospholipids, making it possible to prepare various SPLs.

QSAR modeling for predicting mutagenic toxicity of diverse chemicals for regulatory purposes.

PubMed

Basant, Nikita; Gupta, Shikha

2017-06-01

The safety assessment process of chemicals requires information on their mutagenic potential. The experimental determination of mutagenicity of a large number of chemicals is tedious and time and cost intensive, thus compelling for alternative methods. We have established local and global QSAR models for discriminating low and high mutagenic compounds and predicting their mutagenic activity in a quantitative manner in Salmonella typhimurium (TA) bacterial strains (TA98 and TA100). The decision treeboost (DTB)-based classification QSAR models discriminated among two categories with accuracies of >96% and the regression QSAR models precisely predicted the mutagenic activity of diverse chemicals yielding high correlations (R 2 ) between the experimental and model-predicted values in the respective training (>0.96) and test (>0.94) sets. The test set root mean squared error (RMSE) and mean absolute error (MAE) values emphasized the usefulness of the developed models for predicting new compounds. Relevant structural features of diverse chemicals that were responsible and influence the mutagenic activity were identified. The applicability domains of the developed models were defined. The developed models can be used as tools for screening new chemicals for their mutagenicity assessment for regulatory purpose.

Capillarics: pre-programmed, self-powered microfluidic circuits built from capillary elements.

PubMed

Safavieh, Roozbeh; Juncker, David

2013-11-07

Microfluidic capillary systems employ surface tension effects to manipulate liquids, and are thus self-powered and self-regulated as liquid handling is structurally and chemically encoded in microscale conduits. However, capillary systems have been limited to perform simple fluidic operations. Here, we introduce complex capillary flow circuits that encode sequential flow of multiple liquids with distinct flow rates and flow reversal. We first introduce two novel microfluidic capillary elements including (i) retention burst valves and (ii) robust low aspect ratio trigger valves. These elements are combined with flow resistors, capillary retention valves, capillary pumps, and open and closed reservoirs to build a capillary circuit that, following sample addition, autonomously delivers a defined sequence of multiple chemicals according to a preprogrammed and predetermined flow rate and time. Such a circuit was used to measure the concentration of C-reactive protein. This work illustrates that as in electronics, complex capillary circuits may be built by combining simple capillary elements. We define such circuits as "capillarics", and introduce symbolic representations. We believe that more complex circuits will become possible by expanding the library of building elements and formulating abstract design rules.

Systematic development and optimization of chemically defined medium supporting high cell density growth of Bacillus coagulans.

PubMed

Chen, Yu; Dong, Fengqing; Wang, Yonghong

2016-09-01

With determined components and experimental reducibility, the chemically defined medium (CDM) and the minimal chemically defined medium (MCDM) are used in many metabolism and regulation studies. This research aimed to develop the chemically defined medium supporting high cell density growth of Bacillus coagulans, which is a promising producer of lactic acid and other bio-chemicals. In this study, a systematic methodology combining the experimental technique with flux balance analysis (FBA) was proposed to design and simplify a CDM. The single omission technique and single addition technique were employed to determine the essential and stimulatory compounds, before the optimization of their concentrations by the statistical method. In addition, to improve the growth rationally, in silico omission and addition were performed by FBA based on the construction of a medium-size metabolic model of B. coagulans 36D1. Thus, CDMs were developed to obtain considerable biomass production of at least five B. coagulans strains, in which two model strains B. coagulans 36D1 and ATCC 7050 were involved.

Nanosensors: towards morphological control of gas sensing activity. SnO2, In2O3, ZnO and WO3 case studies.

PubMed

Gurlo, Aleksander

2011-01-01

Anisotropy is a basic property of single crystals. Dissimilar facets/surfaces have different geometric and electronic structure that results in dissimilar functional properties. Several case studies unambiguously demonstrated that the gas sensing activity of metal oxides is determined by the nature of surfaces exposed to ambient gas. Accordingly, a control over crystal morphology, i.e. over the angular relationships, size and shape of faces in a crystal, is required for the development of better sensors with increased selectivity and sensitivity in the chemical determination of gases. The first step toward this nanomorphological control of the gas sensing properties is the design and synthesis of well-defined nanocrystals which are uniform in size, shape and surface structure. These materials possess the planes of the symmetrical set {hkl} and must therefore behave identically in chemical reactions and adsorption processes. Because of these characteristics, the form-controlled nanocrystals are ideal candidates for fundamental studies of mechanisms of gas sensing which should involve (i) gas sensing measurements on specific surfaces, (ii) their atomistic/quantum chemical modelling and (ii) spectroscopic information obtained on same surfaces under operation conditions of sensors.

NIR and Py-mbms coupled with multivariate data analysis as a high-throughput biomass characterization technique: a review

PubMed Central

Xiao, Li; Wei, Hui; Himmel, Michael E.; Jameel, Hasan; Kelley, Stephen S.

2014-01-01

Optimizing the use of lignocellulosic biomass as the feedstock for renewable energy production is currently being developed globally. Biomass is a complex mixture of cellulose, hemicelluloses, lignins, extractives, and proteins; as well as inorganic salts. Cell wall compositional analysis for biomass characterization is laborious and time consuming. In order to characterize biomass fast and efficiently, several high through-put technologies have been successfully developed. Among them, near infrared spectroscopy (NIR) and pyrolysis-molecular beam mass spectrometry (Py-mbms) are complementary tools and capable of evaluating a large number of raw or modified biomass in a short period of time. NIR shows vibrations associated with specific chemical structures whereas Py-mbms depicts the full range of fragments from the decomposition of biomass. Both NIR vibrations and Py-mbms peaks are assigned to possible chemical functional groups and molecular structures. They provide complementary information of chemical insight of biomaterials. However, it is challenging to interpret the informative results because of the large amount of overlapping bands or decomposition fragments contained in the spectra. In order to improve the efficiency of data analysis, multivariate analysis tools have been adapted to define the significant correlations among data variables, so that the large number of bands/peaks could be replaced by a small number of reconstructed variables representing original variation. Reconstructed data variables are used for sample comparison (principal component analysis) and for building regression models (partial least square regression) between biomass chemical structures and properties of interests. In this review, the important biomass chemical structures measured by NIR and Py-mbms are summarized. The advantages and disadvantages of conventional data analysis methods and multivariate data analysis methods are introduced, compared and evaluated. This review aims to serve as a guide for choosing the most effective data analysis methods for NIR and Py-mbms characterization of biomass. PMID:25147552

Comparison of the applicability domain of a quantitative structure-activity relationship for estrogenicity with a large chemical inventory.

PubMed

Netzeva, Tatiana I; Gallegos Saliner, Ana; Worth, Andrew P

2006-05-01

The aim of the present study was to illustrate that it is possible and relatively straightforward to compare the domain of applicability of a quantitative structure-activity relationship (QSAR) model in terms of its physicochemical descriptors with a large inventory of chemicals. A training set of 105 chemicals with data for relative estrogenic gene activation, obtained in a recombinant yeast assay, was used to develop the QSAR. A binary classification model for predicting active versus inactive chemicals was developed using classification tree analysis and two descriptors with a clear physicochemical meaning (octanol-water partition coefficient, or log Kow, and the number of hydrogen bond donors, or n(Hdon)). The model demonstrated a high overall accuracy (90.5%), with a sensitivity of 95.9% and a specificity of 78.1%. The robustness of the model was evaluated using the leave-many-out cross-validation technique, whereas the predictivity was assessed using an artificial external test set composed of 12 compounds. The domain of the QSAR training set was compared with the chemical space covered by the European Inventory of Existing Commercial Chemical Substances (EINECS), as incorporated in the CDB-EC software, in the log Kow / n(Hdon) plane. The results showed that the training set and, therefore, the applicability domain of the QSAR model covers a small part of the physicochemical domain of the inventory, even though a simple method for defining the applicability domain (ranges in the descriptor space) was used. However, a large number of compounds are located within the narrow descriptor window.

Molecular Treatment of Nano-Kaolinite Generations.

PubMed

Táborosi, Attila; Szilagyi, Robert K; Zsirka, Balázs; Fónagy, Orsolya; Horváth, Erzsébet; Kristóf, János

2018-06-18

A procedure is developed for defining a compositionally and structurally realistic, atomic-scale description of exfoliated clay nanoparticles from the kaolinite family of phylloaluminosilicates. By use of coordination chemical principles, chemical environments within a nanoparticle can be separated into inner, outer, and peripheral spheres. The edges of the molecular models of nanoparticles were protonated in a validated manner to achieve charge neutrality. Structural optimizations using semiempirical methods (NDDO Hamiltonians and DFTB formalism) and ab initio density functionals with a saturated basis set revealed previously overlooked molecular origins of morphological changes as a result of exfoliation. While the use of semiempirical methods is desirable for the treatment of nanoparticles composed of tens of thousands of atoms, the structural accuracy is rather modest in comparison to DFT methods. We report a comparative survey of our infrared data for untreated crystalline and various exfoliated states of kaolinite and halloysite. Given the limited availability of experimental techniques for providing direct structural information about nano-kaolinite, the vibrational spectra can be considered as an essential tool for validating structural models. The comparison of experimental and calculated stretching and bending frequencies further justified the use of the preferred level of theory. Overall, an optimal molecular model of the defect-free, ideal nano-kaolinite can be composed with respect to stationary structure and curvature of the potential energy surface using the PW91/SVP level of theory with empirical dispersion correction (PW91+D) and polarizable continuum solvation model (PCM) without the need for a scaled quantum chemical force field. This validated theoretical approach is essential in order to follow the formation of exfoliated clays and their surface reactivity that is experimentally unattainable.

The Proximal Lilly Collection: Mapping, Exploring and Exploiting Feasible Chemical Space.

PubMed

Nicolaou, Christos A; Watson, Ian A; Hu, Hong; Wang, Jibo

2016-07-25

Venturing into the immensity of the small molecule universe to identify novel chemical structure is a much discussed objective of many methods proposed by the chemoinformatics community. To this end, numerous approaches using techniques from the fields of computational de novo design, virtual screening and reaction informatics, among others, have been proposed. Although in principle this objective is commendable, in practice there are several obstacles to useful exploitation of the chemical space. Prime among them are the sheer number of theoretically feasible compounds and the practical concern regarding the synthesizability of the chemical structures conceived using in silico methods. We present the Proximal Lilly Collection initiative implemented at Eli Lilly and Co. with the aims to (i) define the chemical space of small, drug-like compounds that could be synthesized using in-house resources and (ii) facilitate access to compounds in this large space for the purposes of ongoing drug discovery efforts. The implementation of PLC relies on coupling access to available synthetic knowledge and resources with chemo/reaction informatics techniques and tools developed for this purpose. We describe in detail the computational framework supporting this initiative and elaborate on the characteristics of the PLC virtual collection of compounds. As an example of the opportunities provided to drug discovery researchers by easy access to a large, realistically feasible virtual collection such as the PLC, we describe a recent application of the technology that led to the discovery of selective kinase inhibitors.

Hierarchical super-structure identified by polarized light microscopy, electron microscopy and nanoindentation: Implications for the limits of biological control over the growth mode of abalone sea shells

PubMed Central

2012-01-01

Background Mollusc shells are commonly investigated using high-resolution imaging techniques based on cryo-fixation. Less detailed information is available regarding the light-optical properties. Sea shells of Haliotis pulcherina were embedded for polishing in defined orientations in order to investigate the interface between prismatic calcite and nacreous aragonite by standard materialographic methods. A polished thin section of the interface was prepared with a defined thickness of 60 μm for quantitative birefringence analysis using polarized light and LC-PolScope microscopy. Scanning electron microscopy images were obtained for comparison. In order to study structural-mechanical relationships, nanoindentation experiments were performed. Results Incident light microscopy revealed a super-structure in semi-transparent regions of the polished cross-section under a defined angle. This super-structure is not visible in transmitted birefringence analysis due to the blurred polarization of small nacre platelets and numerous organic interfaces. The relative orientation and homogeneity of calcite prisms was directly identified, some of them with their optical axes exactly normal to the imaging plane. Co-oriented "prism colonies" were identified by polarized light analyses. The nacreous super-structure was also visualized by secondary electron imaging under defined angles. The domains of the super-structure were interpreted to consist of crystallographically aligned platelet stacks. Nanoindentation experiments showed that mechanical properties changed with the same periodicity as the domain size. Conclusions In this study, we have demonstrated that insights into the growth mechanisms of nacre can be obtained by conventional light-optical methods. For example, we observed super-structures formed by co-oriented nacre platelets as previously identified using X-ray Photo-electron Emission Microscopy (X-PEEM) [Gilbert et al., Journal of the American Chemical Society 2008, 130:17519–17527]. Polarized optical microscopy revealed unprecedented super-structures in the calcitic shell part. This bears, in principle, the potential for in vivo studies, which might be useful for investigating the growth modes of nacre and other shell types. PMID:22967319

Chemical Interactions and Their Role in the Microphase Separation of Block Copolymer Thin Films

PubMed Central

Farrell, Richard A.; Fitzgerald, Thomas G.; Borah, Dipu; Holmes, Justin D.; Morris, Michael A.

2009-01-01

The thermodynamics of self-assembling systems are discussed in terms of the chemical interactions and the intermolecular forces between species. It is clear that there are both theoretical and practical limitations on the dimensions and the structural regularity of these systems. These considerations are made with reference to the microphase separation that occurs in block copolymer (BCP) systems. BCP systems self-assemble via a thermodynamic driven process where chemical dis-affinity between the blocks driving them part is balanced by a restorative force deriving from the chemical bond between the blocks. These systems are attracting much interest because of their possible role in nanoelectronic fabrication. This form of self-assembly can obtain highly regular nanopatterns in certain circumstances where the orientation and alignment of chemically distinct blocks can be guided through molecular interactions between the polymer and the surrounding interfaces. However, for this to be possible, great care must be taken to properly engineer the interactions between the surfaces and the polymer blocks. The optimum methods of structure directing are chemical pre-patterning (defining regions on the substrate of different chemistry) and graphoepitaxy (topographical alignment) but both centre on generating alignment through favourable chemical interactions. As in all self-assembling systems, the problems of defect formation must be considered and the origin of defects in these systems is explored. It is argued that in these nanostructures equilibrium defects are relatively few and largely originate from kinetic effects arising during film growth. Many defects also arise from the confinement of the systems when they are ‘directed’ by topography. The potential applications of these materials in electronics are discussed. PMID:19865513

Silver iodide microstructures of a uniform towerlike shape: morphology purification via a chemical dissolution, simultaneously boosted catalytic durability, and enhanced catalytic performances.

PubMed

Lei, Bin; Zhu, Mingshan; Chen, Penglei; Chen, Chuncheng; Ma, Wanhong; Li, Tiesheng; Liu, Minghua

2014-03-26

The fabrication of microstructures/nanostructures of a uniform yet well-defined morphology has attracted broad interest from a variety of fields of advanced functional materials, especially catalysts. Most of the conventional methods generally suffer from harsh synthesis conditions, requirement of bulky apparatus, or incapability of scalable production, etc. To meet these formidable challenges, it is strongly desired to develop a facile, cost-effective, scalable method to fulfill a morphology purification. By a precipitation reaction between AgNO3 and KI, we report that irregular AgI structures, or their mixture with towerlike AgI architectures could be fabricated. Compared to the former, the mixed structures exhibit enhanced catalytic reactivity toward the photodegradation of Methyl Orange pollutant. However, its catalytic durability, which is one of the most crucial criteria that are required by superior catalysts, is poor. We further show that the irregular structures could be facilely removed from the mixture via a KI-assisted chemical dissolution, producing AgI of a uniform towerlike morphology. Excitingly, after such simple morphology purification, our towerlike AgI displays not only a boosted catalytic durability but also an enhanced catalytic reactivity. Our chemical dissolution-based morphology purification protocol might be extended to other systems, wherein high-quality advanced functional materials of desired properties might be developed.

Effects of structural and chemical disorders on the vis/UV spectra of carbonaceous interstellar grains

NASA Astrophysics Data System (ADS)

Papoular, Robert J.; Yuan, Shengjun; Roldán, Rafael; Katsnelson, Mikhail I.; Papoular, Renaud

2013-07-01

The recent spectacular progress in the experimental and theoretical understanding of graphene, the basic constituent of graphite, is applied here to compute, from first principles, the ultraviolet extinction of nanoparticles made of stacks of graphene layers. The theory also covers cases where graphene is affected by structural, chemical or orientation disorder, each disorder type being quantitatively defined by a single parameter. The extinction bumps carried by such model materials are found to have positions and widths falling in the same range as the known astronomical 2175 Å features: as the disorder parameter increases, the bump width increases from 0.85 to 2.5 μm-1, while its peak position shifts from 4.65 to 4.75 μm-1. Moderate degrees of disorder are enough to cover the range of widths of the vast majority of observed bumps (0.75 to 1.3 μm-1). Higher degrees account for outliers, also observed in the sky. The introduction of structural or chemical disorder amounts to changing the initial sp2 bondings into sp3 or sp1, so the optical properties of the model material become similar to those of the more or less amorphous carbon-rich materials studied in the laboratory: a-C, a-C:H, HAC, ACH, coals, etc. The present treatment thus bridges gaps between physically different model materials.

Hydrocarbon-Based Polymer Electrolyte Membranes: Importance of Morphology on Ion Transport and Membrane Stability.

PubMed

Shin, Dong Won; Guiver, Michael D; Lee, Young Moo

2017-03-22

A fundamental understanding of polymer microstructure is important in order to design novel polymer electrolyte membranes (PEMs) with excellent electrochemical performance and stabilities. Hydrocarbon-based polymers have distinct microstructure according to their chemical structure. The ionic clusters and/or channels play a critical role in PEMs, affecting ion conductivity and water transport, especially at medium temperature and low relative humidity (RH). In addition, physical properties such as water uptake and dimensional swelling behavior depend strongly on polymer morphology. Over the past few decades, much research has focused on the synthetic development and microstructural characterization of hydrocarbon-based PEM materials. Furthermore, blends, composites, pressing, shear field, electrical field, surface modification, and cross-linking have also been shown to be effective approaches to obtain/maintain well-defined PEM microstructure. This review summarizes recent work on developments in advanced PEMs with various chemical structures and architecture and the resulting polymer microstructures and morphologies that arise for potential application in fuel cell, lithium ion battery, redox flow battery, actuators, and electrodialysis.

Magnetic microgels for drug targeting applications: Physical-chemical properties and cytotoxicity evaluation

NASA Astrophysics Data System (ADS)

Turcu, Rodica; Craciunescu, Izabell; Garamus, Vasil M.; Janko, Christina; Lyer, Stefan; Tietze, Rainer; Alexiou, Christoph; Vekas, Ladislau

2015-04-01

Magnetoresponsive microgels with high saturation magnetization values have been obtained by a strategy based on the miniemulsion method using high colloidal stability organic carrier ferrofluid as primary material. Hydrophobic nanoparticles Fe3O4/oleic acid are densely packed into well-defined spherical nanoparticle clusters coated with polymers with sizes in the range 40-350 nm. Physical-chemical characteristics of magnetic microgels were investigated by TEM, SAXS, XPS and VSM measurements with the focus on the structure-properties relationship. The impact of magnetic microgels loaded with anticancer drug mitoxantrone (MTO) on the non-adherent human T cell leukemia line Jurkat was investigated in multiparameter flow cytometry. We showed that both MTO and microgel-loaded MTO penetrate into cells and both induce apoptosis and later secondary necrosis in a time- and dose dependent manner. In contrast, microgels without MTO are not cytotoxic in the corresponding concentrations. Our results show that MTO-loaded microgels are promising structures for application in magnetic drug targeting.

Role of structural relaxations and chemical substitutions on piezoelectric fields and potential lineup in GaN/Al junctions

NASA Astrophysics Data System (ADS)

Picozzi, S.; Profeta, G.; Continenza, A.; Massidda, S.; Freeman, A. J.

2002-04-01

First-principles full-potential linearized augmented plane wave calculations are performed to clarify the role of the interface geometry on piezoelectric fields and potential lineups in [0001] wurtzite and [111]-zincblende GaN/Al junctions. The electric field (polarity and magnitude) is found to be strongly affected by atomic relaxations in the interface region. A procedure is used to evaluate the Schottky-barrier height in the presence of electric fields, showing that their effect is relatively small (a few tenths of an eV). These calculations assess the rectifying behavior of the GaN/Al contact, in agreement with experimental values for the barrier. We disentangle chemical and structural effects on the relevant properties (such as the potential discontinuity and the electric field) by studying unrelaxed ideal nitride/metal systems. Using simple electronegativity arguments, we outline the leading mechanisms that define the values of the electric field and Schottky barrier in these ideal systems. Finally, the transitivity rule is proved to be well satisfied.

Defining Life

PubMed Central

2010-01-01

Abstract Any definition is intricately connected to a theory that gives it meaning. Accordingly, this article discusses various definitions of life held in the astrobiology community by considering their connected “theories of life.” These include certain “list” definitions and a popular definition that holds that life is a “self-sustaining chemical system capable of Darwinian evolution.” We then act as “anthropologists,” studying what scientists do to determine which definition-theories of life they constructively hold as they design missions to seek non-terran life. We also look at how constructive beliefs about biosignatures change as observational data accumulate. And we consider how a definition centered on Darwinian evolution might itself be forced to change as supra-Darwinian species emerge, including in our descendents, and consider the chances of our encountering supra-Darwinian species in our exploration of the Cosmos. Last, we ask what chemical structures might support Darwinian evolution universally; these structures might be universal biosignatures. Key Words: Evolution—Life—Life detection—Biosignatures. Astrobiology 10, 1021–1030. PMID:21162682

Simultaneous synthesis and self-assembly of inorganic nanomaterials towards active and stable nanocatalysts

NASA Astrophysics Data System (ADS)

Yao, Zhou

The synthetic process in which the formation of nanoparticles and the self-assembly of those nanoparticles as building blocks are coupled together represents an efficient strategy towards stable nanostructures with relatively large geometric dimensions, well-defined shapes, structural hierarchicy and desirable porosities. In this dissertation, through employing appropriate soft/hard templates and controlling the reaction kinetics and thermodynamics, a series of novel physicochemical processes were developed to generate a wide variety of hierarchical 1D, 2D and 3D nanostructures with complex chemical compositions, structural integrities and/or porosities, which were then evaluated as electrocatalysts, heterogeneous catalysts and adsorbents. Based on the properties of their chemical compositions and potential applications, two types of inorganic nanostructures were obtained, including the noble metal-based nanostructures which could be employed as electrocatalysts and the Al-silicate-based hierarchical nanocomposites which could be used for preparation of supported nanocatalysts. The formation mechanisms underlying different processes are also well investigated.

The role of SO{sub 4}{sup 2−} surface distribution in arsenic removal by iron oxy-hydroxides

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

Tresintsi, S.; Simeonidis, K., E-mail: ksime@physics.auth.gr; Department of Mechanical Engineering, University of Thessaly, 38334 Volos

2014-05-01

This study investigates the contribution of chemisorbed SO{sub 4}{sup 2−} in improving arsenic removal properties of iron oxy-hydroxides through an ion-exchange mechanism. An analytical methodology was developed for the accurate quantification of sulfate ion (SO{sub 4}{sup 2−}) distribution onto the surface and structural compartments of iron oxy-hydroxides synthesized by FeSO{sub 4} precipitation. The procedure is based on the sequential determination of SO{sub 4}{sup 2−} presence in the diffuse and Stern layers, and the structure of these materials as defined by the sulfate-rich environments during the reaction and the variation in acidity (pH 3–12). Physically sorbed SO{sub 4}{sup 2−}, extracted inmore » distilled water, and physically/chemically adsorbed ions on the oxy-hydroxide's surface leached by a 5 mM NaOH solution, were determined using ion chromatography. Total sulfate content was gravimetrically measured by precipitation as BaSO{sub 4}. To validate the suggested method, results were verified by X-ray photoelectron and Fourier-transformed infrared spectroscopy. Results showed that low precipitation pH-values favor the incorporation of sulfate ions into the structure and the inner double layer, while under alkaline conditions ions shift to the diffuse layer. - Graphical abstract: An analytical methodology for the accurate quantification of sulfate ions (SO{sub 4}{sup 2−}) distribution onto the diffuse layer, the Stern layer and the structure of iron oxy-hydroxides used as arsenic removal agents. - Highlights: • Quantification of sulfate ions presence in FeOOH surface compartments. • Preparation pH defines the distribution of sulfates. • XPS and FTIR verify the presence of SO{sub 4}{sup 2−} in the structure, the Stern layer the diffuse layer of FeOOH. • Chemically adsorbed sulfates control the arsenic removal efficiency of iron oxyhydroxides.« less

Medicinal chemistry of adenosine, P2Y and P2X receptors.

PubMed

Jacobson, Kenneth A; Müller, Christa E

2016-05-01

Pharmacological tool compounds are now available to define action at the adenosine (ARs), P2Y and P2X receptors. We present a selection of the most commonly used agents to study purines in the nervous system. Some of these compounds, including A1 and A3 AR agonists, P2Y1R and P2Y12R antagonists, and P2X3, P2X4 and P2X7 antagonists, are potentially of clinical use in treatment of disorders of the nervous system, such as chronic pain, neurodegeneration and brain injury. Agonists of the A2AAR and P2Y2R are already used clinically, P2Y12R antagonists are widely used antithrombotics and an antagonist of the A2AAR is approved in Japan for treating Parkinson's disease. The selectivity defined for some of the previously introduced compounds has been revised with updated pharmacological characterization, for example, various AR agonists and antagonists were deemed A1AR or A3AR selective based on human data, but species differences indicated a reduction in selectivity ratios in other species. Also, many of the P2R ligands still lack bioavailability due to charged groups or hydrolytic (either enzymatic or chemical) instability. X-ray crystallographic structures of AR and P2YRs have shifted the mode of ligand discovery to structure-based approaches rather than previous empirical approaches. The X-ray structures can be utilized either for in silico screening of chemically diverse libraries for the discovery of novel ligands or for enhancement of the properties of known ligands by chemical modification. Although X-ray structures of the zebrafish P2X4R have been reported, there is scant structural information about ligand recognition in these trimeric ion channels. In summary, there are definitive, selective agonists and antagonists for all of the ARs and some of the P2YRs; while the pharmacochemistry of P2XRs is still in nascent stages. The therapeutic potential of selectively modulating these receptors is continuing to gain interest in such fields as cancer, inflammation, pain, diabetes, ischemic protection and many other conditions. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. Published by Elsevier Ltd.

Assessment of human epidermal model LabCyte EPI-MODEL for in vitro skin irritation testing according to European Centre for the Validation of Alternative Methods (ECVAM)-validated protocol.

PubMed

Katoh, Masakazu; Hamajima, Fumiyasu; Ogasawara, Takahiro; Hata, Ken-Ichiro

2009-06-01

A validation study of an in vitro skin irritation testing method using a reconstructed human skin model has been conducted by the European Centre for the Validation of Alternative Methods (ECVAM), and a protocol using EpiSkin (SkinEthic, France) has been approved. The structural and performance criteria of skin models for testing are defined in the ECVAM Performance Standards announced along with the approval. We have performed several evaluations of the new reconstructed human epidermal model LabCyte EPI-MODEL, and confirmed that it is applicable to skin irritation testing as defined in the ECVAM Performance Standards. We selected 19 materials (nine irritants and ten non-irritants) available in Japan as test chemicals among the 20 reference chemicals described in the ECVAM Performance Standard. A test chemical was applied to the surface of the LabCyte EPI-MODEL for 15 min, after which it was completely removed and the model then post-incubated for 42 hr. Cell v iability was measured by MTT assay and skin irritancy of the test chemical evaluated. In addition, interleukin-1 alpha (IL-1alpha) concentration in the culture supernatant after post-incubation was measured to provide a complementary evaluation of skin irritation. Evaluation of the 19 test chemicals resulted in 79% accuracy, 78% sensitivity and 80% specificity, confirming that the in vitro skin irritancy of the LabCyte EPI-MODEL correlates highly with in vivo skin irritation. These results suggest that LabCyte EPI-MODEL is applicable to the skin irritation testing protocol set out in the ECVAM Performance Standards.

Multiple conformations are a conserved and regulatory feature of the RB1 5′ UTR

PubMed Central

Kutchko, Katrina M.; Sanders, Wes; Ziehr, Ben; Phillips, Gabriela; Solem, Amanda; Halvorsen, Matthew; Weeks, Kevin M.; Moorman, Nathaniel

2015-01-01

Folding to a well-defined conformation is essential for the function of structured ribonucleic acids (RNAs) like the ribosome and tRNA. Structured elements in the untranslated regions (UTRs) of specific messenger RNAs (mRNAs) are known to control expression. The importance of unstructured regions adopting multiple conformations, however, is still poorly understood. High-resolution SHAPE-directed Boltzmann suboptimal sampling of the Homo sapiens Retinoblastoma 1 (RB1) 5′ UTR yields three distinct conformations compatible with the experimental data. Private single nucleotide variants (SNVs) identified in two patients with retinoblastoma each collapse the structural ensemble to a single but distinct well-defined conformation. The RB1 5′ UTRs from Bos taurus (cow) and Trichechus manatus latirostris (manatee) are divergent in sequence from H. sapiens (human) yet maintain structural compatibility with high-probability base pairs. SHAPE chemical probing of the cow and manatee RB1 5′ UTRs reveals that they also adopt multiple conformations. Luciferase reporter assays reveal that 5′ UTR mutations alter RB1 expression. In a traditional model of disease, causative SNVs disrupt a key structural element in the RNA. For the subset of patients with heritable retinoblastoma-associated SNVs in the RB1 5′ UTR, the absence of multiple structures is likely causative of the cancer. Our data therefore suggest that selective pressure will favor multiple conformations in eukaryotic UTRs to regulate expression. PMID:25999316

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

Computational design of water-soluble α-helical barrels.

PubMed

Thomson, Andrew R; Wood, Christopher W; Burton, Antony J; Bartlett, Gail J; Sessions, Richard B; Brady, R Leo; Woolfson, Derek N

2014-10-24

The design of protein sequences that fold into prescribed de novo structures is challenging. General solutions to this problem require geometric descriptions of protein folds and methods to fit sequences to these. The α-helical coiled coils present a promising class of protein for this and offer considerable scope for exploring hitherto unseen structures. For α-helical barrels, which have more than four helices and accessible central channels, many of the possible structures remain unobserved. Here, we combine geometrical considerations, knowledge-based scoring, and atomistic modeling to facilitate the design of new channel-containing α-helical barrels. X-ray crystal structures of the resulting designs match predicted in silico models. Furthermore, the observed channels are chemically defined and have diameters related to oligomer state, which present routes to design protein function. Copyright © 2014, American Association for the Advancement of Science.

Project on Advanced Systems and Concepts for Countering Weapons of Mass Destruction (PASCC)

DTIC Science & Technology

2015-09-01

Proliferation of weapons of mass destruction (WMD, defined as nuclear, chemical , and biological) and weapons of mass effect (WME, defined as other high... Chemical Weapons • Scoping Study for a U.S.-Israel Strategic Dialogued 5 • U.S.-India Strategic Dialogue • Implications of Indian Tactical...of Chemical Weapons : Strategic Dialogue, Research, and Report Performer: Arizona State University (ASU) Principal Investigator: Orde Kittrie Cost

Self-assembly of crystalline nanotubes from monodisperse amphiphilic diblock copolypeptoid tiles

DOE PAGES

Sun, Jing; Jiang, Xi; Lund, Reidar; ...

2016-03-28

The folding and assembly of sequence-defined polymers into precisely ordered nanostructures promises a class of well-defined biomimetic architectures with specific function. Amphiphilic diblock copolymers are known to self-assemble in water to form a variety of nanostructured morphologies including spheres, disks, cylinders, and vesicles. In all of these cases, the predominant driving force for assembly is the formation of a hydrophobic core that excludes water, whereas the hydrophilic blocks are solvated and extend into the aqueous phase. However, such polymer systems typically have broad molar mass distributions and lack the purity and sequence-defined structure often associated with biologically derived polymers. Here,more » we demonstrate that purified, monodisperse amphiphilic diblock copolypeptoids, with chemically distinct domains that are congruent in size and shape, can behave like molecular tile units that spontaneously assemble into hollow, crystalline nanotubes in water. The nanotubes consist of stacked, porous crystalline rings, and are held together primarily by side-chain van der Waals interactions. The peptoid nanotubes form without a central hydrophobic core, chirality, a hydrogen bond network, and electrostatic or π-π interactions. These results demonstrate the remarkable structure-directing influence of n-alkane and ethyleneoxy side chains in polymer self-assembly. More broadly, this work suggests that flexible, low-molecular-weight sequence-defined polymers can serve as molecular tile units that can assemble into precision supramolecular architectures.« less

Self-assembly of crystalline nanotubes from monodisperse amphiphilic diblock copolypeptoid tiles

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

Sun, Jing; Jiang, Xi; Lund, Reidar

The folding and assembly of sequence-defined polymers into precisely ordered nanostructures promises a class of well-defined biomimetic architectures with specific function. Amphiphilic diblock copolymers are known to self-assemble in water to form a variety of nanostructured morphologies including spheres, disks, cylinders, and vesicles. In all of these cases, the predominant driving force for assembly is the formation of a hydrophobic core that excludes water, whereas the hydrophilic blocks are solvated and extend into the aqueous phase. However, such polymer systems typically have broad molar mass distributions and lack the purity and sequence-defined structure often associated with biologically derived polymers. Here,more » we demonstrate that purified, monodisperse amphiphilic diblock copolypeptoids, with chemically distinct domains that are congruent in size and shape, can behave like molecular tile units that spontaneously assemble into hollow, crystalline nanotubes in water. The nanotubes consist of stacked, porous crystalline rings, and are held together primarily by side-chain van der Waals interactions. The peptoid nanotubes form without a central hydrophobic core, chirality, a hydrogen bond network, and electrostatic or π-π interactions. These results demonstrate the remarkable structure-directing influence of n-alkane and ethyleneoxy side chains in polymer self-assembly. More broadly, this work suggests that flexible, low-molecular-weight sequence-defined polymers can serve as molecular tile units that can assemble into precision supramolecular architectures.« less

COOLAIR Antisense RNAs Form Evolutionarily Conserved Elaborate Secondary Structures

DOE PAGES

Hawkes, Emily J.; Hennelly, Scott P.; Novikova, Irina V.; ...

2016-09-20

There is considerable debate about the functionality of long non-coding RNAs (lncRNAs). Lack of sequence conservation has been used to argue against functional relevance. Here, we investigated antisense lncRNAs, called COOLAIR, at the A. thaliana FLC locus and experimentally determined their secondary structure. The major COOLAIR variants are highly structured, organized by exon. The distally polyadenylated transcript has a complex multi-domain structure, altered by a single non-coding SNP defining a functionally distinct A. thaliana FLC haplotype. The A. thaliana COOLAIR secondary structure was used to predict COOLAIR exons in evolutionarily divergent Brassicaceae species. These predictions were validated through chemical probingmore » and cloning. Despite the relatively low nucleotide sequence identity, the structures, including multi-helix junctions, show remarkable evolutionary conservation. In a number of places, the structure is conserved through covariation of a non-contiguous DNA sequence. This structural conservation supports a functional role for COOLAIR transcripts rather than, or in addition to, antisense transcription.« less

COOLAIR Antisense RNAs Form Evolutionarily Conserved Elaborate Secondary Structures

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

Hawkes, Emily J.; Hennelly, Scott P.; Novikova, Irina V.

There is considerable debate about the functionality of long non-coding RNAs (lncRNAs). Lack of sequence conservation has been used to argue against functional relevance. Here, we investigated antisense lncRNAs, called COOLAIR, at the A. thaliana FLC locus and experimentally determined their secondary structure. The major COOLAIR variants are highly structured, organized by exon. The distally polyadenylated transcript has a complex multi-domain structure, altered by a single non-coding SNP defining a functionally distinct A. thaliana FLC haplotype. The A. thaliana COOLAIR secondary structure was used to predict COOLAIR exons in evolutionarily divergent Brassicaceae species. These predictions were validated through chemical probingmore » and cloning. Despite the relatively low nucleotide sequence identity, the structures, including multi-helix junctions, show remarkable evolutionary conservation. In a number of places, the structure is conserved through covariation of a non-contiguous DNA sequence. This structural conservation supports a functional role for COOLAIR transcripts rather than, or in addition to, antisense transcription.« less

Influence of samarium substitution on structural, dielectric, and piezoelectric properties of PZT ceramics

NASA Astrophysics Data System (ADS)

Juneja, J. K.; Thakur, O. P.; Prakash, Chandra

2003-10-01

The structural, dielectric and piezoelectric properties have been studied in detail for the samarium modified PZT system. The samples, with chemical formula Pb1-xSmxZr0.52Ti0.48O3 with x varying from 0 to 0.02 in steps of 0.0025, were prepared by standard double sintering ceramic method. XRD analysis showed all the samples to be of single phase with tetragonal structure. Tetragonality (c/a) decreases gradually with samarium concentration (x) and the experimental density increases with x. Dielectric properties were studied as a function of temperature and frequency. All the samples show well-defined ferroelectric behavior. The remanance ratio (Pr/Ps) was found to increase with increasing Sm3+ concentration. Piezoelectric charge coefficient d33 decreases with x.

Cost-effective MEMS piezoresistive cantilever-based sensor fabrication for gait movement analysis

NASA Astrophysics Data System (ADS)

Saadon, Salem; Anuar, A. F. M.; Wahab, Yufridin

2017-03-01

The conventional photolithography of crystalline silicon technique is limited to two-dimensional and structure scaling. It's also requiring a lot of time and chemical involves for the whole process. These problems can be overcome by using laser micromachining technique, that capable to produce three-dimensional structure and simultaneously avoiding the photo mask needs. In this paper, we reported on the RapidX-250 Excimer laser micromachining with 248 nm KrF to create in-time mask design and assisting in the fabrication process of piezo-resistive micro cantilever structures. Firstly, laser micromachining parameters have been investigated in order to fabricate the acceleration sensor to analyzing human gait movement. Preliminary result shows that the fabricated sensor able to define the movement difference of human motion regarding the electrical characteristic of piezo-resistor.

Modelling the effect of structural QSAR parameters on skin penetration using genetic programming

NASA Astrophysics Data System (ADS)

Chung, K. K.; Do, D. Q.

2010-09-01

In order to model relationships between chemical structures and biological effects in quantitative structure-activity relationship (QSAR) data, an alternative technique of artificial intelligence computing—genetic programming (GP)—was investigated and compared to the traditional method—statistical. GP, with the primary advantage of generating mathematical equations, was employed to model QSAR data and to define the most important molecular descriptions in QSAR data. The models predicted by GP agreed with the statistical results, and the most predictive models of GP were significantly improved when compared to the statistical models using ANOVA. Recently, artificial intelligence techniques have been applied widely to analyse QSAR data. With the capability of generating mathematical equations, GP can be considered as an effective and efficient method for modelling QSAR data.

Identifying chemicals that are planetary boundary threats.

PubMed

MacLeod, Matthew; Breitholtz, Magnus; Cousins, Ian T; de Wit, Cynthia A; Persson, Linn M; Rudén, Christina; McLachlan, Michael S

2014-10-07

Rockström et al. proposed a set of planetary boundaries that delimit a "safe operating space for humanity". Many of the planetary boundaries that have so far been identified are determined by chemical agents. Other chemical pollution-related planetary boundaries likely exist, but are currently unknown. A chemical poses an unknown planetary boundary threat if it simultaneously fulfills three conditions: (1) it has an unknown disruptive effect on a vital Earth system process; (2) the disruptive effect is not discovered until it is a problem at the global scale, and (3) the effect is not readily reversible. In this paper, we outline scenarios in which chemicals could fulfill each of the three conditions, then use the scenarios as the basis to define chemical profiles that fit each scenario. The chemical profiles are defined in terms of the nature of the effect of the chemical and the nature of exposure of the environment to the chemical. Prioritization of chemicals in commerce against some of the profiles appears feasible, but there are considerable uncertainties and scientific challenges that must be addressed. Most challenging is prioritizing chemicals for their potential to have a currently unknown effect on a vital Earth system process. We conclude that the most effective strategy currently available to identify chemicals that are planetary boundary threats is prioritization against profiles defined in terms of environmental exposure combined with monitoring and study of the biogeochemical processes that underlie vital Earth system processes to identify currently unknown disruptive effects.

Guidelines for chemical peeling in Japan (3rd edition).

PubMed

2012-04-01

Chemical peeling may be defined as the therapies, procedures and techniques used for the treatment of certain cutaneous diseases or conditions, and for aesthetic improvement. The procedures include the application of one or more chemical agents to the skin. Chemical peeling has been very popular in both medical and aesthetic fields. Because neither its scientific background is well understood nor a systematic approach established, medical and social problems have taken place. This prompted us to establish and distribute a standard guideline of care for chemical peeling. Previous guidelines such as the 2001 and 2004 versions included minimum standards of care such as indications, chemicals, applications, and any associated precautions, including post-peeling care. The principles in this updated version of chemical peeling are as follows: (i) chemical peeling should be performed under the strict technical control and responsibility of a physician; (ii) the physician should have sufficient knowledge of the structure and physiology of the skin and subcutaneous tissues, and understand the mechanisms of wound-healing induced by chemical peeling; (iii) the physician should be board-certified in an appropriate specialty such as dermatology; and (iv) the ultimate judgment regarding the appropriateness of any specific chemical peeling procedure must be made by the physician while considering all standard therapeutic protocols, which should be presented to each individual patient. Keeping these concepts in mind, this new version of the guidelines includes a more scientific and detailed approach from the viewpoint of evidence-based medicine. © 2011 Japanese Dermatological Association.

Phytochemica: a platform to explore phytochemicals of medicinal plants

PubMed Central

Pathania, Shivalika; Ramakrishnan, Sai Mukund; Bagler, Ganesh

2015-01-01

Plant-derived molecules (PDMs) are known to be a rich source of diverse scaffolds that could serve as the basis for rational drug design. Structured compilation of phytochemicals from traditional medicinal plants can facilitate prospection for novel PDMs and their analogs as therapeutic agents. Atropa belladonna, Catharanthus roseus, Heliotropium indicum, Picrorhiza kurroa and Podophyllum hexandrum are important Himalayan medicinal plants, reported to have immense therapeutic properties against various diseases. We present Phytochemica, a structured compilation of 963 PDMs from these plants, inclusive of their plant part source, chemical classification, IUPAC names, SMILES notations, physicochemical properties and 3-dimensional structures with associated references. Phytochemica is an exhaustive resource of natural molecules facilitating prospection for therapeutic molecules from medicinally important plants. It also offers refined search option to explore the neighbourhood of chemical space against ZINC database to identify analogs of natural molecules at user-defined cut-off. Availability of phytochemical structured dataset may enable their direct use in in silico drug discovery which will hasten the process of lead identification from natural products under proposed hypothesis, and may overcome urgent need for phytomedicines. Compilation and accessibility of indigenous phytochemicals and their derivatives can be a source of considerable advantage to research institutes as well as industries. Database URL: home.iitj.ac.in/∼bagler/webservers/Phytochemica PMID:26255307

Precise side-chain conformation analysis of L-phenylalanine in α-helical polypeptide by quantum-chemical calculation and 13C CP-MAS NMR measurement

NASA Astrophysics Data System (ADS)

Niimura, Subaru; Suzuki, Junya; Kurosu, Hiromichi; Yamanobe, Takeshi; Shoji, Akira

2010-04-01

To clarify the positive role of side-chain conformation in the stability of protein secondary structure (main-chain conformation), we successfully calculated the optimization structure of a well-defined α-helical octadecapeptide composed of L-alanine (Ala) and L-phenylalanine (Phe) residues, H-(Ala) 8-Phe-(Ala) 9-OH, based on the molecular orbital calculation with density functional theory (DFT/B3LYP/6-31G(d)). From the total energy and the precise secondary structural parameters such as main-chain dihedral angles and hydrogen-bond parameters of the optimized structure, we confirmed that the conformational stability of an α-helix is affected dominantly by the side-chain conformation ( χ1) of the Phe residue in this system: model A ( T form: around 180° of χ1) is most stable in α-helix and model B ( G + form: around -60° of χ1) is next stable, but model C ( G - form: around 60° of χ1) is less stable. In addition, we demonstrate that the stable conformation of poly( L-phenylalanine) is an α-helix with the side-chain T form, by comparison of the carbonyl 13C chemical shift measured by 13C CP-MAS NMR and the calculated one.

A universal reduced glass transition temperature for liquids

NASA Technical Reports Server (NTRS)

Fedors, R. F.

1979-01-01

Data on the dependence of the glass transition temperature on the molecular structure for low-molecular-weight liquids are analyzed in order to determine whether Boyer's reduced glass transition temperature (1952) is a universal constant as proposed. It is shown that the Boyer ratio varies widely depending on the chemical nature of the molecule. It is pointed out that a characteristic temperature ratio, defined by the ratio of the sum of the melting temperature and the boiling temperature to the sum of the glass transition temperature and the boiling temperature, is a universal constant independent of the molecular structure of the liquid. The average value of the ratio obtained from data for 65 liquids is 1.15.

Investigations on Sm- and Nb-SUBSTITUTED PZT Ceramics

NASA Astrophysics Data System (ADS)

Prakash, Chandra; Juneja, J. K.

In the present paper, we report the effect of Samarium substitution and Niobium doping on the properties of a PZT(52:48). The properties studied are: structural, dielectric and ferroelectric. The samples with chemical formula Pb0.99Sm0.01Zr0.52Ti0.48O3 were prepared by solid-state dry ceramic method. Small amount (0.5 wt%) of Nb2O5 was also added. X-ray diffraction (XRD) analysis showed formation of a single phase with tetragonal structure. Dielectric properties were studied as a function of temperature and frequency. Transition temperature, Tc, was determined from dielectric constant versus temperature plot. The material shows well-defined ferroelectric (PE) hysteresis loop.

Fine-tuning of electronic properties in donor-acceptor conjugated polymers based on oligothiophenes

NASA Astrophysics Data System (ADS)

Imae, Ichiro; Sagawa, Hitoshi; Harima, Yutaka

2018-03-01

A novel series of donor-acceptor conjugated polymers having oligothiophenes with well-defined structures were synthesized and their optical, electrochemical, and photovoltaic properties were investigated. It was found that the absorption bands of polymers were red-shifted with increasing number of ethylenedioxy groups added to each oligothiophene unit and that their band edges reached over 1000 nm. The systematical fine-tuning of the electronic properties was achieved using the chemical structures of oligothiophene units. Photovoltaic cells based on polymer/(6,6)-phenyl C61 butyric acid methyl ester (PC61BM) exhibited power conversion efficiencies in the range from 0.004 to 1.10%, reflecting the electronic properties of the polymers.

Structural Transitions and Energy Landscape for Cowpea Chlorotic Mottle Virus Capsid Mechanics from Nanomanipulation in Vitro and in Silico

NASA Astrophysics Data System (ADS)

Kononova, Olga; Snijder, Joost; Brasch, Melanie; Cornelissen, Jeroen; Dima, Ruxandra I.; Marx, Kenneth A.; Wuite, Gijs J. L.; Roos, Wouter H.; Barsegov, Valeri

2013-10-01

Physical properties of capsids of plant and animal viruses are important factors in capsid self-assembly, survival of viruses in the extracellular environment, and their cell infectivity. Virus shells can have applications as nanocontainers and delivery vehicles in biotechnology and medicine. Combined AFM experiments and computational modeling on sub-second timescales of the indentation nanomechanics of Cowpea Chlorotic Mottle Virus (CCMV) capsid show that the capsid's physical properties are dynamic and local characteristics of the structure, which depend on the magnitude and geometry of mechanical input. Surprisingly, under large deformations the CCMV capsid transitions to the collapsed state without substantial local structural alterations. The enthalpy change in this deformation state dH = 11.5 - 12.8 MJ/mol is mostly due to large-amplitude out-of-plane excitations, which contribute to the capsid bending, and the entropy change TdS = 5.1 - 5.8 MJ/mol is mostly due to coherent in-plane rearrangements of protein chains, which result in the capsid stiffening. Dynamic coupling of these modes defines the extent of elasticity and reversibility of capsid mechanical deformation. This emerging picture illuminates how unique physico-chemical properties of protein nanoshells help define their structure and morphology, and determine their viruses' biological function.

Geographic variation in Northwest Atlantic fin whale (Balaenoptera physalus) song: implications for stock structure assessment.

PubMed

Delarue, Julien; Todd, Sean K; Van Parijs, Sofie M; Di Iorio, Lucia

2009-03-01

Passive acoustic data are increasingly being used as a tool for helping to define marine mammal populations and stocks. Fin whale (Balaenoptera physalus) songs present a unique opportunity to determine interstock differences. Their highly stereotyped interpulse interval has been shown to vary between geographic areas and to remain stable over time in some areas. In this study the structure of songs recorded at two geographically close feeding aggregations in the Gulf of St. Lawrence (GSL) and Gulf of Maine (GoM) was compared. Recordings were made from September 2005 through February 2006 in the GSL and intermittently between January 2006 and September 2007 at two locations in the GoM. 6257 pulse intervals corresponding to 19 GSL and 29 GoM songs were measured to characterize songs from both areas. Classification trees showed that GSL songs differ significantly from those in the GoM. The results are consistent with those derived from other stock structure assessment methodologies, such as chemical signature and photoidentification analysis, suggesting that fin whales in these areas may form separate management stocks. Song structure analysis could therefore provide a useful and cost-efficient tool for defining conservation units over temporal and geographical scales relevant to management objectives in fin whales.

Characterization of the Cretaceous aquifer structure of the Meskala region of the Essaouira Basin, Morocco

USGS Publications Warehouse

Hanich, L.; Zouhri, L.; Dinger, J.

2011-01-01

The aquifer of early Cretaceous age in the Meskala region of the Essaouira Basin is defined by interpretation of geological drilling data of oil and hydrogeological wells, field measurement and analysis of in situ fracture orientations, and the application of a morphostructural method to identify lineaments. These analyzes are used to develop a stratigraphic-structural model of the aquifer delimited by fault zones of two principal orientations: NNE and WNW. These fault zones define fault blocks that range in area from 4 to 150km2. These blocks correspond either to elevated zones (horsts) or depressed zones (grabens). This structural setting with faults blocks of Meskala region is in accordance with the structure of the whole Essaouira Basin. Fault zones disrupt the continuity of the aquifer throughout the study area, create recharge and discharge zones, and create dip to the units from approximately 10?? to near vertical in various orientations. Fracture measurements and morphometric-lineament analyzes help to identify unmapped faults, and represent features important to groundwater hydraulics and water quality within fault blocks. The above geologic features will enable a better understanding of the behaviour and hydro-geo-chemical and hydrodynamics of groundwater in the Meskala aquifer. ?? 2010 Elsevier Ltd.

Redox biotransformation and delivery of anthracycline anticancer antibiotics: How interpretable structure-activity relationships of lethality using electrophilicity and the London formula for dispersion interaction work.

PubMed

Pang, Siu-Kwong

2017-03-30

Quantum chemical methods and molecular mechanics approaches face a lot of challenges in drug metabolism study because of their either insufficient accuracy or huge computational cost, or lack of clear molecular level pictures for building computational models. Low-cost QSAR methods can often be carried out even though molecular level pictures are not well defined; however, they show difficulty in identifying the mechanisms of drug metabolism and delineating the effects of chemical structures on drug toxicity because a certain amount of molecular descriptors are difficult to be interpreted. In order to make a breakthrough, it was proposed that mechanistically interpretable molecular descriptors were used to correlate with biological activity to establish structure-activity plots. The mechanistically interpretable molecular descriptors used in this study include electrophilicity and the mathematical function in the London formula for dispersion interaction, and they were calculated using quantum chemical methods. The biological activity is the lethality of anthracycline anticancer antibiotics denoted as log LD50, which were obtained by intraperitoneal injection into mice. The results reveal that the plots for electrophilicity, which can be interpreted as redox reactivity of anthracyclines, can describe oxidative degradation for detoxification and reductive bioactivation for toxicity induction. The plots for the dispersion interaction function, which represent the attraction between anthracyclines and biomolecules, can describe efflux from and influx into target cells of toxicity. The plots can also identify three structural scaffolds of anthracyclines that have different metabolic pathways, resulting in their different toxicity behavior. This structure-dependent toxicity behavior revealed in the plots can provide perspectives on design of anthracycline anticancer antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Drug Repositioning by Kernel-Based Integration of Molecular Structure, Molecular Activity, and Phenotype Data

PubMed Central

Wang, Yongcui; Chen, Shilong; Deng, Naiyang; Wang, Yong

2013-01-01

Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately. Here, we propose a new method for drug repositioning, PreDR (Predict Drug Repositioning), to integrate molecular structure, molecular activity, and phenotype data. Specifically, we characterize drug by profiling in chemical structure, target protein, and side-effects space, and define a kernel function to correlate drugs with diseases. Then we train a support vector machine (SVM) to computationally predict novel drug-disease interactions. PreDR is validated on a well-established drug-disease network with 1,933 interactions among 593 drugs and 313 diseases. By cross-validation, we find that chemical structure, drug target, and side-effects information are all predictive for drug-disease relationships. More experimentally observed drug-disease interactions can be revealed by integrating these three data sources. Comparison with existing methods demonstrates that PreDR is competitive both in accuracy and coverage. Follow-up database search and pathway analysis indicate that our new predictions are worthy of further experimental validation. Particularly several novel predictions are supported by clinical trials databases and this shows the significant prospects of PreDR in future drug treatment. In conclusion, our new method, PreDR, can serve as a useful tool in drug discovery to efficiently identify novel drug-disease interactions. In addition, our heterogeneous data integration framework can be applied to other problems. PMID:24244318

A MODELING AND SIMULATION LANGUAGE FOR BIOLOGICAL CELLS WITH COUPLED MECHANICAL AND CHEMICAL PROCESSES

PubMed Central

Somogyi, Endre; Glazier, James A.

2017-01-01

Biological cells are the prototypical example of active matter. Cells sense and respond to mechanical, chemical and electrical environmental stimuli with a range of behaviors, including dynamic changes in morphology and mechanical properties, chemical uptake and secretion, cell differentiation, proliferation, death, and migration. Modeling and simulation of such dynamic phenomena poses a number of computational challenges. A modeling language describing cellular dynamics must naturally represent complex intra and extra-cellular spatial structures and coupled mechanical, chemical and electrical processes. Domain experts will find a modeling language most useful when it is based on concepts, terms and principles native to the problem domain. A compiler must then be able to generate an executable model from this physically motivated description. Finally, an executable model must efficiently calculate the time evolution of such dynamic and inhomogeneous phenomena. We present a spatial hybrid systems modeling language, compiler and mesh-free Lagrangian based simulation engine which will enable domain experts to define models using natural, biologically motivated constructs and to simulate time evolution of coupled cellular, mechanical and chemical processes acting on a time varying number of cells and their environment. PMID:29303160

A MODELING AND SIMULATION LANGUAGE FOR BIOLOGICAL CELLS WITH COUPLED MECHANICAL AND CHEMICAL PROCESSES.

PubMed

Somogyi, Endre; Glazier, James A

2017-04-01

Biological cells are the prototypical example of active matter. Cells sense and respond to mechanical, chemical and electrical environmental stimuli with a range of behaviors, including dynamic changes in morphology and mechanical properties, chemical uptake and secretion, cell differentiation, proliferation, death, and migration. Modeling and simulation of such dynamic phenomena poses a number of computational challenges. A modeling language describing cellular dynamics must naturally represent complex intra and extra-cellular spatial structures and coupled mechanical, chemical and electrical processes. Domain experts will find a modeling language most useful when it is based on concepts, terms and principles native to the problem domain. A compiler must then be able to generate an executable model from this physically motivated description. Finally, an executable model must efficiently calculate the time evolution of such dynamic and inhomogeneous phenomena. We present a spatial hybrid systems modeling language, compiler and mesh-free Lagrangian based simulation engine which will enable domain experts to define models using natural, biologically motivated constructs and to simulate time evolution of coupled cellular, mechanical and chemical processes acting on a time varying number of cells and their environment.

Process Model of A Fusion Fuel Recovery System for a Direct Drive IFE Power Reactor

NASA Astrophysics Data System (ADS)

Natta, Saswathi; Aristova, Maria; Gentile, Charles

2008-11-01

A task has been initiated to develop a detailed representative model for the fuel recovery system (FRS) in the prospective direct drive inertial fusion energy (IFE) reactor. As part of the conceptual design phase of the project, a chemical process model is developed in order to observe the interaction of system components. This process model is developed using FEMLAB Multiphysics software with the corresponding chemical engineering module (CEM). Initially, the reactants, system structure, and processes are defined using known chemical species of the target chamber exhaust. Each step within the Fuel recovery system is modeled compartmentally and then merged to form the closed loop fuel recovery system. The output, which includes physical properties and chemical content of the products, is analyzed after each step of the system to determine the most efficient and productive system parameters. This will serve to attenuate possible bottlenecks in the system. This modeling evaluation is instrumental in optimizing and closing the fusion fuel cycle in a direct drive IFE power reactor. The results of the modeling are presented in this paper.

Pressure dependence of backbone chemical shifts in the model peptides Ac-Gly-Gly-Xxx-Ala-NH2.

PubMed

Erlach, Markus Beck; Koehler, Joerg; Crusca, Edson; Kremer, Werner; Munte, Claudia E; Kalbitzer, Hans Robert

2016-06-01

For a better understanding of nuclear magnetic resonance (NMR) detected pressure responses of folded as well as unstructured proteins the availability of data from well-defined model systems are indispensable. In this work we report the pressure dependence of chemical shifts of the backbone atoms (1)H(α), (13)C(α) and (13)C' in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH2 (Xxx one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of these nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The polynomial pressure coefficients B 1 and B 2 are dependent on the type of amino acid studied. The coefficients of a given nucleus show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure are also weakly correlated.

A Review: Fundamental Aspects of Silicate Mesoporous Materials

PubMed Central

ALOthman, Zeid A.

2012-01-01

Silicate mesoporous materials have received widespread interest because of their potential applications as supports for catalysis, separation, selective adsorption, novel functional materials, and use as hosts to confine guest molecules, due to their extremely high surface areas combined with large and uniform pore sizes. Over time a constant demand has developed for larger pores with well-defined pore structures. Silicate materials, with well-defined pore sizes of about 2.0–10.0 nm, surpass the pore-size constraint (<2.0 nm) of microporous zeolites. They also possess extremely high surface areas (>700 m2 g−1) and narrow pore size distributions. Instead of using small organic molecules as templating compounds, as in the case of zeolites, long chain surfactant molecules were employed as the structure-directing agent during the synthesis of these highly ordered materials. The structure, composition, and pore size of these materials can be tailored during synthesis by variation of the reactant stoichiometry, the nature of the surfactant molecule, the auxiliary chemicals, the reaction conditions, or by post-synthesis functionalization techniques. This review focuses mainly on a concise overview of silicate mesoporous materials together with their applications. Perusal of the review will enable researchers to obtain succinct information about microporous and mesoporous materials.

Label-free imaging of mammalian cell nucleoli by Raman microspectroscopy.

PubMed

Schulze, H Georg; Konorov, Stanislav O; Piret, James M; Blades, Michael W; Turner, Robin F B

2013-06-21

The nucleolus is a prominent subnuclear structure whose major function is the transcription and assembly of ribosome subunits. The size of the nucleolus varies with the cell cycle, proliferation rate and stress. Changes in nucleolar size, number, chemical composition, and shape can be used to characterize malignant cells. We used spontaneous Raman microscopy as a label-free technique to examine nucleolar spatial and chemical features. Raman images of the 1003 cm(-1) phenylalanine band revealed large, well-defined subnuclear protein structures in MFC-7 breast cancer cells. The 783 cm(-1) images showed that nucleic acids were similarly distributed, but varied more in intensity, forming observable high-intensity regions. High subnuclear RNA concentrations were observed within some of these regions as shown by 809 cm(-1) Raman band images. Principal component analyses of sub-images and library spectra validated the subnuclear presence of RNA. They also revealed that an actin-like protein covaried with DNA within the nucleolus, a combination that accounted for 64% or more of the spectral variance. Embryonic stem cells are another rapidly proliferating cell type, but their nucleoli were not as large or well defined. Estimating the size of the larger MCF-7 nucleolus was used to show the utility of Raman microscopy for morphometric analyses. It was concluded that imaging based on Raman microscopy provides a promising new method for the study of nucleolar function and organization, in the evaluation of drug and experimental effects on the nucleolus, and in clinical diagnostics and prognostics.

Reproductive toxicity: Male and female reproductive systems as targets for chemical injury

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

Mattison, D.R.; Plowchalk, D.R.; Meadows, M.J.

On the basis of current knowledge of reproductive biology and toxicology, it is apparent that chemicals affecting reproduction may elicit their effects at a number of sites in both the male and the female reproductive system. This multiplicity of targets is attributable to the dynamic nature of the reproductive system, in which the hypothalamic-pituitary-gonadal axis is controlled by precise positive and negative feedback mechanisms among its components. Interference by a xenobiotic at any level in either the male or the female reproductive system may ultimately impair hypothalamic or pituitary function. Normal gonadal processes such as spermatogenesis or oogenesis, ejaculation ormore » ovulation, hormone production by Leydig or granulosa cells, and the structure or function of the accessory reproductive structures (e.g., epididymis, fallopian tube) also appear vulnerable to xenobiotics. The reproductive system is a complex one that requires local and circulating hormones for control. This brief review illustrates a system for characterizing the mechanism of action of reproductive toxicants, as well as for defining the sites available for disruption of reproduction. Unfortunately, at present, data addressing the actual vulnerability of reproduction are sorely lacking. However, when experiments have been conducted and combined with epidemiologic data or clinical observation, it has been possible to demonstrate impairment of reproductive processes by xenobiotics. The role of environmental exposure to xenobiotics in the increase in infertility that has been observed remains to be defined. 87 references.« less

Nanoassemblies from homostructured polypeptides as efficient nanoplatforms for oral drug delivery.

PubMed

Jia, Yi; Tang, Yuan; He, Hongmei; Li, Shuhui; Che, Ling; Zhou, Xing; Dou, Yin; Zhang, Jianxiang; Li, Xiaohui

2013-04-01

The assembly of homostructured polypeptides bearing various side groups into well-defined nanostructures was presented, with their size and topology mainly dominated by the chemical structure and molecular weight of peptides. Pharmacokinetic and pharmacodynamic studies based on rat models suggested these newly constructed nanoassemblies with low cytotoxicity may function as novel nanoplatforms to efficiently and safely deliver therapeutics to achieve better efficacy but lower side effects. Other applications in biomedical fields, such as biotechnology, medical imaging, and tissue engineering, may also be expected. This research team investigated the assembly of homostructured polypeptides bearing various side groups into well-defined nanostructures, and demonstrated low cytotoxicity in rat disease models, suggesting that these novel nanoplatforms may safely and efficiently deliver therapeutics with low side effects. Copyright © 2013 Elsevier Inc. All rights reserved.

FunTree: advances in a resource for exploring and contextualising protein function evolution.

PubMed

Sillitoe, Ian; Furnham, Nicholas

2016-01-04

FunTree is a resource that brings together protein sequence, structure and functional information, including overall chemical reaction and mechanistic data, for structurally defined domain superfamilies. Developed in tandem with the CATH database, the original FunTree contained just 276 superfamilies focused on enzymes. Here, we present an update of FunTree that has expanded to include 2340 superfamilies including both enzymes and proteins with non-enzymatic functions annotated by Gene Ontology (GO) terms. This allows the investigation of how novel functions have evolved within a structurally defined superfamily and provides a means to analyse trends across many superfamilies. This is done not only within the context of a protein's sequence and structure but also the relationships of their functions. New measures of functional similarity have been integrated, including for enzymes comparisons of overall reactions based on overall bond changes, reaction centres (the local environment atoms involved in the reaction) and the sub-structure similarities of the metabolites involved in the reaction and for non-enzymes semantic similarities based on the GO. To identify and highlight changes in function through evolution, ancestral character estimations are made and presented. All this is accessible through a new re-designed web interface that can be found at http://www.funtree.info. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

3D Printing Polymers with Supramolecular Functionality for Biological Applications.

PubMed

Pekkanen, Allison M; Mondschein, Ryan J; Williams, Christopher B; Long, Timothy E

2017-09-11

Supramolecular chemistry continues to experience widespread growth, as fine-tuned chemical structures lead to well-defined bulk materials. Previous literature described the roles of hydrogen bonding, ionic aggregation, guest/host interactions, and π-π stacking to tune mechanical, viscoelastic, and processing performance. The versatility of reversible interactions enables the more facile manufacturing of molded parts with tailored hierarchical structures such as tissue engineered scaffolds for biological applications. Recently, supramolecular polymers and additive manufacturing processes merged to provide parts with control of the molecular, macromolecular, and feature length scales. Additive manufacturing, or 3D printing, generates customizable constructs desirable for many applications, and the introduction of supramolecular interactions will potentially increase production speed, offer a tunable surface structure for controlling cell/scaffold interactions, and impart desired mechanical properties through reinforcing interlayer adhesion and introducing gradients or self-assembled structures. This review details the synthesis and characterization of supramolecular polymers suitable for additive manufacture and biomedical applications as well as the use of supramolecular polymers in additive manufacturing for drug delivery and complex tissue scaffold formation. The effect of supramolecular assembly and its dynamic behavior offers potential for controlling the anisotropy of the printed objects with exquisite geometrical control. The potential for supramolecular polymers to generate well-defined parts, hierarchical structures, and scaffolds with gradient properties/tuned surfaces provides an avenue for developing next-generation biomedical devices and tissue scaffolds.

Application of chemical reaction mechanistic domains to an ecotoxicity QSAR model, the KAshinhou Tool for Ecotoxicity (KATE).

PubMed

Furuhama, A; Hasunuma, K; Aoki, Y; Yoshioka, Y; Shiraishi, H

2011-01-01

The validity of chemical reaction mechanistic domains defined by skin sensitisation in the Quantitative Structure-Activity Relationship (QSAR) ecotoxicity system, KAshinhou Tools for Ecotoxicity (KATE), March 2009 version, has been assessed and an external validation of the current KATE system carried out. In the case of the fish end-point, the group of chemicals with substructures reactive to skin sensitisation always exhibited higher root mean square errors (RMSEs) than chemicals without reactive substructures under identical C- or log P-judgements in KATE. However, in the case of the Daphnia end-point this was not so, and the group of chemicals with reactive substructures did not always have higher RMSEs: the Schiff base mechanism did not function as a high error detector. In addition to the RMSE findings, the presence of outliers suggested that the KATE classification rules needs to be reconsidered, particularly for the amine group. Examination of the dependency of the organism on the toxic action of chemicals in fish and Daphnia revealed that some of the reactive substructures could be applied to the improvement of the KATE system. It was concluded that the reaction mechanistic domains of toxic action for skin sensitisation could provide useful complementary information in predicting acute aquatic ecotoxicity, especially at the fish end-point.

14 CFR 23.1450 - Chemical oxygen generators.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Chemical oxygen generators. 23.1450 Section... Equipment § 23.1450 Chemical oxygen generators. (a) For the purpose of this section, a chemical oxygen generator is defined as a device which produces oxygen by chemical reaction. (b) Each chemical oxygen...

14 CFR 23.1450 - Chemical oxygen generators.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Chemical oxygen generators. 23.1450 Section... Equipment § 23.1450 Chemical oxygen generators. (a) For the purpose of this section, a chemical oxygen generator is defined as a device which produces oxygen by chemical reaction. (b) Each chemical oxygen...

14 CFR 23.1450 - Chemical oxygen generators.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Chemical oxygen generators. 23.1450 Section... Equipment § 23.1450 Chemical oxygen generators. (a) For the purpose of this section, a chemical oxygen generator is defined as a device which produces oxygen by chemical reaction. (b) Each chemical oxygen...

14 CFR 23.1450 - Chemical oxygen generators.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Chemical oxygen generators. 23.1450 Section... Equipment § 23.1450 Chemical oxygen generators. (a) For the purpose of this section, a chemical oxygen generator is defined as a device which produces oxygen by chemical reaction. (b) Each chemical oxygen...

14 CFR 23.1450 - Chemical oxygen generators.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Chemical oxygen generators. 23.1450 Section... Equipment § 23.1450 Chemical oxygen generators. (a) For the purpose of this section, a chemical oxygen generator is defined as a device which produces oxygen by chemical reaction. (b) Each chemical oxygen...

Intelligent system design for bionanorobots in drug delivery.

PubMed

Fletcher, Mark; Biglarbegian, Mohammad; Neethirajan, Suresh

A nanorobot is defined as any smart structure which is capable of actuation, sensing, manipulation, intelligence, and swarm behavior at the nanoscale. In this study, we designed an intelligent system using fuzzy logic for diagnosis and treatment of tumors inside the human body using bionanorobots. We utilize fuzzy logic and a combination of thermal, magnetic, optical, and chemical nanosensors to interpret the uncertainty associated with the sensory information. Two different fuzzy logic structures, for diagnosis (Mamdani structure) and for cure (Takagi-Sugeno structure), were developed to efficiently identify the tumors and treat them through delivery of effective dosages of a drug. Validation of the designed system with simulated conditions proved that the drug delivery of bionanorobots was robust to reasonable noise that may occur in the bionanorobot sensors during navigation, diagnosis, and curing of the cancer cells. Bionanorobots represent a great hope for successful cancer therapy in the near future.

Structural Sensitivity of a Prokaryotic Pentameric Ligand-gated Ion Channel to Its Membrane Environment*

PubMed Central

Labriola, Jonathan M.; Pandhare, Akash; Jansen, Michaela; Blanton, Michael P.; Corringer, Pierre-Jean; Baenziger, John E.

2013-01-01

Although the activity of the nicotinic acetylcholine receptor (nAChR) is exquisitely sensitive to its membrane environment, the underlying mechanisms remain poorly defined. The homologous prokaryotic pentameric ligand-gated ion channel, Gloebacter ligand-gated ion channel (GLIC), represents an excellent model for probing the molecular basis of nAChR sensitivity because of its high structural homology, relative ease of expression, and amenability to crystallographic analysis. We show here that membrane-reconstituted GLIC exhibits structural and biophysical properties similar to those of the membrane-reconstituted nAChR, although GLIC is substantially more thermally stable. GLIC, however, does not possess the same exquisite lipid sensitivity. In particular, GLIC does not exhibit the same propensity to adopt an uncoupled conformation where agonist binding is uncoupled from channel gating. Structural comparisons provide insight into the chemical features that may predispose the nAChR to the formation of an uncoupled state. PMID:23463505

Structure of the Rigor Actin-Tropomyosin-Myosin Complex

PubMed Central

Behrmann, Elmar; Müller, Mirco; Penczek, Pawel A.; Mannherz, Hans Georg; Manstein, Dietmar J.; Raunser, Stefan

2014-01-01

The interaction of myosin with actin filaments is the central feature of muscle contraction and cargo movement along actin filaments of the cytoskeleton. Myosin converts the chemical energy stored in ATP into force and movement along actin filaments. Myosin binding to actin induces conformational changes that are coupled to the nucleotide-binding pocket and amplified by a specialized region of the motor domain for efficient force generation. Tropomyosin plays a key role in regulating the productive interaction between myosins and actin. Here, we report the 8 Å resolution structure of the actin-tropomyosin-myosin complex determined by cryo electron microscopy. The pseudo-atomic model of the complex obtained from fitting crystal structures into the map defines the large actin-myosin-tropomyosin interface and the molecular interactions between the proteins in detail and allows us to propose a structural model for tropomyosin dependent myosin binding to actin and actin-induced nucleotide release from myosin. PMID:22817895

Intercalation of sulfonated melamine formaldehyde polycondensates into a hydrocalumite LDH structure

NASA Astrophysics Data System (ADS)

von Hoessle, F.; Plank, J.; Leroux, F.

2015-05-01

A series of sulfonated melamine formaldehyde (SMF) polycondensates possessing different anionic charge amounts and molecular weights was synthesized and incorporated into a hydrocalumite type layered double hydroxide structure using the rehydration method. For this purpose, tricalcium aluminate was dispersed in water and hydrated in the presence of these polymers. Defined inorganic-organic hybrid materials were obtained as reaction products. All SMF polymers tested intercalated readily into the hydrocalumite structure, independent of their different molecular weights (chain lengths) and anionic charge amounts. X-ray diffraction revealed typical patterns for weakly ordered, highly polymer loaded LDH materials which was confirmed via elemental analysis and thermogravimetry. IR spectroscopy suggests that the SMF polymers are interleaved between the [Ca2Al(OH)6]+ main sheets via electrostatic interaction, and that no chemical bond between the host matrix and the guest anion is formed. The SMF polymers well ensconced within the LDH structure exhibit significantly slower thermal degradation.

40 CFR 63.1323 - Batch process vents-methods and procedures for group determination.

Code of Federal Regulations, 2014 CFR

2014-07-01

... accepted chemical engineering principles, measurable process parameters, or physical or chemical laws or... paragraph (b)(5) of this section. Engineering assessment may be used to estimate emissions from a batch... defined in paragraph (b)(5) of this section, through engineering assessment, as defined in paragraph (b)(6...

40 CFR 63.1323 - Batch process vents-methods and procedures for group determination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... accepted chemical engineering principles, measurable process parameters, or physical or chemical laws or... paragraph (b)(5) of this section. Engineering assessment may be used to estimate emissions from a batch... defined in paragraph (b)(5) of this section, through engineering assessment, as defined in paragraph (b)(6...

40 CFR 63.1323 - Batch process vents-methods and procedures for group determination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... accepted chemical engineering principles, measurable process parameters, or physical or chemical laws or... paragraph (b)(5) of this section. Engineering assessment may be used to estimate emissions from a batch... defined in paragraph (b)(5) of this section, through engineering assessment, as defined in paragraph (b)(6...

40 CFR 63.1323 - Batch process vents-methods and procedures for group determination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... accepted chemical engineering principles, measurable process parameters, or physical or chemical laws or... paragraph (b)(5) of this section. Engineering assessment may be used to estimate emissions from a batch... defined in paragraph (b)(5) of this section, through engineering assessment, as defined in paragraph (b)(6...

Acidification in the Adirondacks: Defining the Biota in trophic Levels of 30 Chemically Diverse Acid-Impacted Lakes

EPA Science Inventory

The Adirondack Mountains in New York State have a varied surficial geology and chemically diverse surface waters that are among the most impacted by acid deposition in the U.S. No single Adirondack investigation has been comprehensive in defining the effects of acidification on ...

Phase transformations in 40-60-GPa shocked gneisses from the Haughton Crater (Canada): An Analytical Transmission Electron Microscopy (ATEM) study

NASA Technical Reports Server (NTRS)

Martinez, I.; Guyot, F.; Schaerer, U.

1992-01-01

In order to better understand phase transformations, chemical migration, and isotopic disequilibrium in highly shocked rocks, we have performed a microprobe and an ATEM study on gneisses shocked up to 60 GPa from the Haughton Crater. This study reveals the following chemical and structural characteristics: (1) SiO2 dominant areas are formed by a mixture of pure SiO2 polycrystalline quartz identified by electron diffraction pattern and chemical analysis and a silica-rich amorphous phase containing minor amounts of aluminium, potassium, and iron; (2) Areas with biotitelike composition are formed by less than 200-nm grains of iron-rich spinels embedded in a silica-rich amorphous phase that is very similar to the one described above; (3) Layers with feldsparlike composition are constituted by 100-200-nm-sized alumina-rich grains (the indexation of the crystalline structure is under progress) and the silica-rich amorphous phase; (4) Zones characterized by the unusual Al/Si ratio close to 1 are formed by spinel grains (200-nm-sized) embedded in the same silica-rich amorphous phase; and (5) The fracturated sillimanites contain domains with a lamellar structure, defined by the intercalation of 100-nm-wide lamellae of mullite crystals and of a silica-rich amorphous phase. These mullite crystals preserved the crystallographical orientation of the preshock sillimanite. All compositional domains, identified at the microprobe scale, can thus be explained by a mixture in different proportion between the following phases: (1) a silica-rich amorphous phase, with minor Al and K; (2) quartz crystals; (3) spinel crystals and alumina-rich crystals; (4) sillimanite; and (5) mullite. Such mixtures of amorphous phases and crystals in different proportions explain disturbed isotope systems in these rocks and chemical heterogeneities observed on the microprobe.

To Model Chemical Reactivity in Heterogeneous Emulsions, Think Homogeneous Microemulsions.

PubMed

Bravo-Díaz, Carlos; Romsted, Laurence Stuart; Liu, Changyao; Losada-Barreiro, Sonia; Pastoriza-Gallego, Maria José; Gao, Xiang; Gu, Qing; Krishnan, Gunaseelan; Sánchez-Paz, Verónica; Zhang, Yongliang; Dar, Aijaz Ahmad

2015-08-25

Two important and unsolved problems in the food industry and also fundamental questions in colloid chemistry are how to measure molecular distributions, especially antioxidants (AOs), and how to model chemical reactivity, including AO efficiency in opaque emulsions. The key to understanding reactivity in organized surfactant media is that reaction mechanisms are consistent with a discrete structures-separate continuous regions duality. Aggregate structures in emulsions are determined by highly cooperative but weak organizing forces that allow reactants to diffuse at rates approaching their diffusion-controlled limit. Reactant distributions for slow thermal bimolecular reactions are in dynamic equilibrium, and their distributions are proportional to their relative solubilities in the oil, interfacial, and aqueous regions. Our chemical kinetic method is grounded in thermodynamics and combines a pseudophase model with methods for monitoring the reactions of AOs with a hydrophobic arenediazonium ion probe in opaque emulsions. We introduce (a) the logic and basic assumptions of the pseudophase model used to define the distributions of AOs among the oil, interfacial, and aqueous regions in microemulsions and emulsions and (b) the dye derivatization and linear sweep voltammetry methods for monitoring the rates of reaction in opaque emulsions. Our results show that this approach provides a unique, versatile, and robust method for obtaining quantitative estimates of AO partition coefficients or partition constants and distributions and interfacial rate constants in emulsions. The examples provided illustrate the effects of various emulsion properties on AO distributions such as oil hydrophobicity, emulsifier structure and HLB, temperature, droplet size, surfactant charge, and acidity on reactant distributions. Finally, we show that the chemical kinetic method provides a natural explanation for the cut-off effect, a maximum followed by a sharp reduction in AO efficiency with increasing alkyl chain length of a particular AO. We conclude with perspectives and prospects.

Optical and Calorimetric Studies of Cholesterol-Rich Filamentous, Helical Ribbon and Crystal Microstructures

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

Miroshnikova, Y. A.; Elsenbeck, M.; Zastavker, Y. V.

2009-04-19

Formation of biological self-assemblies at all scales is a focus of studies in fields ranging from biology to physics to biomimetics. Understanding the physico-chemical properties of these self-assemblies may lead to the design of bio-inspired structures and technological applications. Here we examine self-assembled filamentous, helical ribbon, and crystal microstructures formed in chemically defined lipid concentrate (CDLC), a model system for cholesterol crystallization in gallbladder bile. CDLC consists of cholesterol, bilayer-forming amphiphiles, micelle-forming amphiphiles, and water. Phase contrast and differential interference contrast (DIC) microscopy indicate the presence of three microstructure types in all samples studied, and allow for an investigation ofmore » the structures' unique geometries. Additionally, confocal microscopy is used for qualitative assessment of surface and internal composition. To complement optical observations, calorimetric (differential-scanning and modulation) experiments, provide the basis for an in-depth understanding of collective and individual thermal behavior. Observed ''transition'' features indicate clustering and ''straightening'' of helical ribbons into short, increasingly thickening, filaments that dissolve with increasing temperature. These results suggest that all microstructures formed in CDLC may coexist in a metastable chemical equilibrium. Further investigation of the CDLC thermal profile should uncover the process of cholesterol crystallization as well as the unique design and function of microstructures formed in this system.« less

Physiological enzymology: The next frontier in understanding protein structure and function at the cellular level.

PubMed

Lee, Irene; Berdis, Anthony J

2016-01-01

Historically, the study of proteins has relied heavily on characterizing the activity of a single purified protein isolated from other cellular components. This classic approach allowed scientists to unambiguously define the intrinsic kinetic and chemical properties of that protein. The ultimate hope was to extrapolate this information toward understanding how the enzyme or receptor behaves within its native cellular context. These types of detailed in vitro analyses were necessary to reduce the innate complexities of measuring the singular activity and biochemical properties of a specific enzyme without interference from other enzymes and potential competing substrates. However, recent developments in fields encompassing cell biology, molecular imaging, and chemical biology now provide the unique chemical tools and instrumentation to study protein structure, function, and regulation in their native cellular environment. These advancements provide the foundation for a new field, coined physiological enzymology, which quantifies the function and regulation of enzymes and proteins at the cellular level. In this Special Edition, we explore the area of Physiological Enzymology and Protein Function through a series of review articles that focus on the tools and techniques used to measure the cellular activity of proteins inside living cells. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions. Copyright © 2015 Elsevier B.V. All rights reserved.

Extending (Q)SARs to incorporate proprietary knowledge for regulatory purposes: A case study using aromatic amine mutagenicity.

PubMed

Ahlberg, Ernst; Amberg, Alexander; Beilke, Lisa D; Bower, David; Cross, Kevin P; Custer, Laura; Ford, Kevin A; Van Gompel, Jacky; Harvey, James; Honma, Masamitsu; Jolly, Robert; Joossens, Elisabeth; Kemper, Raymond A; Kenyon, Michelle; Kruhlak, Naomi; Kuhnke, Lara; Leavitt, Penny; Naven, Russell; Neilan, Claire; Quigley, Donald P; Shuey, Dana; Spirkl, Hans-Peter; Stavitskaya, Lidiya; Teasdale, Andrew; White, Angela; Wichard, Joerg; Zwickl, Craig; Myatt, Glenn J

2016-06-01

Statistical-based and expert rule-based models built using public domain mutagenicity knowledge and data are routinely used for computational (Q)SAR assessments of pharmaceutical impurities in line with the approach recommended in the ICH M7 guideline. Knowledge from proprietary corporate mutagenicity databases could be used to increase the predictive performance for selected chemical classes as well as expand the applicability domain of these (Q)SAR models. This paper outlines a mechanism for sharing knowledge without the release of proprietary data. Primary aromatic amine mutagenicity was selected as a case study because this chemical class is often encountered in pharmaceutical impurity analysis and mutagenicity of aromatic amines is currently difficult to predict. As part of this analysis, a series of aromatic amine substructures were defined and the number of mutagenic and non-mutagenic examples for each chemical substructure calculated across a series of public and proprietary mutagenicity databases. This information was pooled across all sources to identify structural classes that activate or deactivate aromatic amine mutagenicity. This structure activity knowledge, in combination with newly released primary aromatic amine data, was incorporated into Leadscope's expert rule-based and statistical-based (Q)SAR models where increased predictive performance was demonstrated. Copyright © 2016 Elsevier Inc. All rights reserved.

Fast deuterium fractionation in magnetized and turbulent filaments

NASA Astrophysics Data System (ADS)

Körtgen, B.; Bovino, S.; Schleicher, D. R. G.; Stutz, A.; Banerjee, R.; Giannetti, A.; Leurini, S.

2018-07-01

Deuterium fractionation is considered as an important process to infer the chemical ages of prestellar cores in filaments. We present here the first magnetohydrodynamical simulations including a chemical network to study deuterium fractionation in magnetized and turbulent filaments, with a line-mass of Mlin = 42 M⊙ pc-1 within a radius of R= 0.1 pc, and their sub-structures. The filaments typically show widespread deuterium fractionation with average values ≳0.01. For individual cores of similar age, we observe the deuteration fraction to increase with time, but also to be independent of their average properties such as density, virial, or mass-to-magnetic flux ratio. We further find a correlation of the deuteration fraction with core mass, average H2 density, and virial parameter only at late evolutionary stages of the filament and attribute this to the lifetime of the individual cores. Specifically, chemically old cores reveal higher deuteration fractions. Within the radial profiles of selected cores, we notice differences in the structure of the deuteration fraction or surface density, which we can attribute to their different turbulent properties. High deuteration fractions of the order of 0.01-0.1 may be reached within approximately 200 kyr, corresponding to two free-fall times, as defined for cylindrical systems, of the filaments.

In Situ SIMS and IR Spectroscopy of Well-defined Surfaces Prepared by Soft Landing of Mass-selected Ions

PubMed Central

Johnson, Grant E.; Gunaratne, K. Don Dasitha; Laskin, Julia

2014-01-01

Soft landing of mass-selected ions onto surfaces is a powerful approach for the highly-controlled preparation of materials that are inaccessible using conventional synthesis techniques. Coupling soft landing with in situ characterization using secondary ion mass spectrometry (SIMS) and infrared reflection absorption spectroscopy (IRRAS) enables analysis of well-defined surfaces under clean vacuum conditions. The capabilities of three soft-landing instruments constructed in our laboratory are illustrated for the representative system of surface-bound organometallics prepared by soft landing of mass-selected ruthenium tris(bipyridine) dications, [Ru(bpy)3]2+ (bpy = bipyridine), onto carboxylic acid terminated self-assembled monolayer surfaces on gold (COOH-SAMs). In situ time-of-flight (TOF)-SIMS provides insight into the reactivity of the soft-landed ions. In addition, the kinetics of charge reduction, neutralization and desorption occurring on the COOH-SAM both during and after ion soft landing are studied using in situ Fourier transform ion cyclotron resonance (FT-ICR)-SIMS measurements. In situ IRRAS experiments provide insight into how the structure of organic ligands surrounding metal centers is perturbed through immobilization of organometallic ions on COOH-SAM surfaces by soft landing. Collectively, the three instruments provide complementary information about the chemical composition, reactivity and structure of well-defined species supported on surfaces. PMID:24961913

In Situ SIMS and IR Spectroscopy of Well-Defined Surfaces Prepared by Soft Landing of Mass-Selected Ions

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

Johnson, Grant E.; Gunaratne, Kalupathirannehelage Don D.; Laskin, Julia

2014-06-16

Soft landing of mass-selected ions onto surfaces is a powerful approach for the highly-controlled preparation of materials that are inaccessible using conventional synthesis techniques. Coupling soft landing with in situ characterization using secondary ion mass spectrometry (SIMS) and infrared reflection absorption spectroscopy (IRRAS) enables analysis of well-defined surfaces under clean vacuum conditions. The capabilities of three soft-landing instruments constructed in our laboratory are illustrated for the representative system of surface-bound organometallics prepared by soft landing of mass-selected ruthenium tris(bipyridine) dications, [Ru(bpy)3]2+, onto carboxylic acid terminated self-assembled monolayer surfaces on gold (COOH-SAMs). In situ time-of-flight (TOF)-SIMS provides insight into the reactivitymore » of the soft-landed ions. In addition, the kinetics of charge reduction, neutralization and desorption occurring on the COOH-SAM both during and after ion soft landing are studied using in situ Fourier transform ion cyclotron resonance (FT-ICR)-SIMS measurements. In situ IRRAS experiments provide insight into how the structure of organic ligands surrounding metal centers is perturbed through immobilization of organometallic ions on COOH-SAM surfaces by soft landing. Collectively, the three instruments provide complementary information about the chemical composition, reactivity and structure of well-defined species supported on surfaces.« less

Gamma radiation effects on siloxane-based additive manufactured structures

NASA Astrophysics Data System (ADS)

Schmalzer, Andrew M.; Cady, Carl M.; Geller, Drew; Ortiz-Acosta, Denisse; Zocco, Adam T.; Stull, Jamie; Labouriau, Andrea

2017-01-01

Siloxane-basedadditive manufactured structures prepared by the direct ink write (DIW) technology were exposed to ionizing irradiation in order to gauge radiolysis effects on structure-property relationships. These well-defined 3-D structures were subjected to moderate doses of gamma irradiation in an inert atmosphere and characterized by a suite of experimental methods. Changes in thermal, chemical, microstructure, and mechanical properties were evaluated by DSC, TGA, FT-IR, mass spectroscopy, EPR, solvent swelling, SEM, and uniaxial compressive load techniques. Our results demonstrated that 3-D structures made from aromatic-free siloxane resins exhibited hardening after being exposed to gamma radiation. This effect was accompanied by gas evolution, decreasing in crystallization levels, decreasing in solvent swelling and damage to the microstructure. Furthermore, long-lived radiation-induced radicals were not detected by EPR methods. Our results are consistent with cross-link formation being the dominant degradation mechanism over chain scission reactions. On the other hand, 3-D structures made from high phenyl content siloxane resins showed little radiation damage as evidenced by low off gassing.

Coffee melanoidins: structures, mechanisms of formation and potential health impacts.

PubMed

Moreira, Ana S P; Nunes, Fernando M; Domingues, M Rosário; Coimbra, Manuel A

2012-09-01

During the roasting process, coffee bean components undergo structural changes leading to the formation of melanoidins, which are defined as high molecular weight nitrogenous and brown-colored compounds. As coffee brew is one of the main sources of melanoidins in the human diet, their health implications are of great interest. In fact, several biological activities, such as antioxidant, antimicrobial, anticariogenic, anti-inflammatory, antihypertensive, and antiglycative activities, have been attributed to coffee melanoidins. To understand the potential of coffee melanoidin health benefits, it is essential to know their chemical structures. The studies undertaken to date dealing with the structural characterization of coffee melanoidins have shown that polysaccharides, proteins, and chlorogenic acids are involved in coffee melanoidin formation. However, exact structures of coffee melanoidins and mechanisms involved in their formation are far to be elucidated. This paper systematizes the available information and provides a critical overview of the knowledge obtained so far about the structure of coffee melanoidins, mechanisms of their formation, and their potential health implications.

Comparison of bioactive chemical space networks generated using substructure- and fingerprint-based measures of molecular similarity

NASA Astrophysics Data System (ADS)

Zhang, Bijun; Vogt, Martin; Maggiora, Gerald M.; Bajorath, Jürgen

2015-07-01

Chemical space networks (CSNs) have recently been introduced as a conceptual alternative to coordinate-based representations of chemical space. CSNs were initially designed as threshold networks using the Tanimoto coefficient as a continuous similarity measure. The analysis of CSNs generated from sets of bioactive compounds revealed that many statistical properties were strongly dependent on their edge density. While it was difficult to compare CSNs at pre-defined similarity threshold values, CSNs with constant edge density were directly comparable. In the current study, alternative CSN representations were constructed by applying the matched molecular pair (MMP) formalism as a substructure-based similarity criterion. For more than 150 compound activity classes, MMP-based CSNs (MMP-CSNs) were compared to corresponding threshold CSNs (THR-CSNs) at a constant edge density by applying different parameters from network science, measures of community structure distributions, and indicators of structure-activity relationship (SAR) information content. MMP-CSNs were found to be an attractive alternative to THR-CSNs, yielding low edge densities and well-resolved topologies. MMP-CSNs and corresponding THR-CSNs often had similar topology and closely corresponding community structures, although there was only limited overlap in similarity relationships. The homophily principle from network science was shown to affect MMP-CSNs and THR-CSNs in different ways, despite the presence of conserved topological features. Moreover, activity cliff distributions in alternative CSN designs markedly differed, which has important implications for SAR analysis.

Metabolite proving fungal cleavage of the aromatic core part of a fluoroquinolone antibiotic

PubMed Central

2012-01-01

Liquid cultures of the basidiomycetous fungus Gloeophyllum striatum were employed to study the biodegradation of pradofloxacin, a new veterinary fluoroquinolone antibiotic carrying a CN group at position C-8. After 16 days of incubation, metabolites were purified by micro-preparative high-performance liquid chromatography. Four metabolites could be identified by co-chromatography with chemically synthesized standards. The chemical structures of three compounds were resolved by 1H-nuclear magnetic resonance spectroscopy plus infrared spectroscopy in one case. All metabolites were confirmed by high resolution mass spectrometry-derived molecular formulae. They comprised compounds in which the carboxyl group or the fluorine atom had been exchanged for a hydroxyl group. Furthermore, replacement of the CN group and the intact amine moiety by a hydroxyl group as well as degradation of the amine substituent were observed. The chemical structure of a catechol-type fluoroquinolone metabolite (F-5) could be fully defined for the first time. The latter initiated a hypothetical degradation sequence providing a unique metabolite, F-13, which consisted of the cyclopropyl-substituted pyridone ring still carrying C-7 and C-8 of pradofloxacin, now linked by a double bond and substituted by a hydroxyl and the CN group, respectively. Most likely, all reactions were hydroxyl radical-driven. Metabolite F-13 proves fungal cleavage of the aromatic fluoroquinolone core for the first time. Hence, two decades after the emergence of the notion of the non-biodegradability of fluoroquinolones, fungal degradation of all key structural elements has been proven. PMID:22214407

Concrete alteration due to 55 years of exposure to river water: Chemical and mineralogical characterisation

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

Rosenqvist, Martin; Bertron, Alexandra; Fridh, Katja

This article presents a study on concrete alteration mechanisms due to 55 years of exposure to river water. Many hydro power structures in cold regions suffer from concrete deterioration at the waterline. Progressive disintegration of the concrete surface leads to exposure of the coarse aggregate and eventually the reinforcing steel. Concrete cylinders drilled out at four vertically different locations on the upstream face of a concrete dam were analysed by electron microprobe analysis, X-ray diffraction, thermogravimetry and scanning electron microscopy. Long-term exposure to the river water, which is regarded as soft water, has led to chemical and mineralogical zonation ofmore » the cement paste. Up to five zones with different chemical and mineralogical composition, parallel to the upstream face, were observed in the outermost 8–9 mm of the concrete. Decalcification, precipitation of secondary ettringite and the formation of a magnesium-rich silica gel constitute the major changes that define the zones.« less

Recent breakthroughs in metabolomics promise to reveal the cryptic chemical traits that mediate plant community composition, character evolution and lineage diversification.

PubMed

Sedio, Brian E

2017-05-01

Contents 952 I. 952 II. 953 III. 955 IV. 956 V. 957 957 References 957 SUMMARY: Much of our understanding of the mechanisms by which biotic interactions shape plant communities has been constrained by the methods available to study the diverse secondary chemistry that defines plant relationships with other organisms. Recent innovations in analytical chemistry and bioinformatics promise to reveal the cryptic chemical traits that mediate plant ecology and evolution by facilitating simultaneous structural comparisons of hundreds of unknown molecules to each other and to libraries of known compounds. Here, I explore the potential for mass spectrometry and nuclear magnetic resonance metabolomics to enable unprecedented tests of seminal, but largely untested hypotheses that propose a fundamental role for plant chemical defenses against herbivores and pathogens in the evolutionary origins and ecological coexistence of plant species diversity. © 2017 The Author. New Phytologist © 2017 New Phytologist Trust.

Electrifying model catalysts for understanding electrocatalytic reactions in liquid electrolytes.

PubMed

Faisal, Firas; Stumm, Corinna; Bertram, Manon; Waidhas, Fabian; Lykhach, Yaroslava; Cherevko, Serhiy; Xiang, Feifei; Ammon, Maximilian; Vorokhta, Mykhailo; Šmíd, Břetislav; Skála, Tomáš; Tsud, Nataliya; Neitzel, Armin; Beranová, Klára; Prince, Kevin C; Geiger, Simon; Kasian, Olga; Wähler, Tobias; Schuster, Ralf; Schneider, M Alexander; Matolín, Vladimír; Mayrhofer, Karl J J; Brummel, Olaf; Libuda, Jörg

2018-07-01

Electrocatalysis is at the heart of our future transition to a renewable energy system. Most energy storage and conversion technologies for renewables rely on electrocatalytic processes and, with increasing availability of cheap electrical energy from renewables, chemical production will witness electrification in the near future 1-3 . However, our fundamental understanding of electrocatalysis lags behind the field of classical heterogeneous catalysis that has been the dominating chemical technology for a long time. Here, we describe a new strategy to advance fundamental studies on electrocatalytic materials. We propose to 'electrify' complex oxide-based model catalysts made by surface science methods to explore electrocatalytic reactions in liquid electrolytes. We demonstrate the feasibility of this concept by transferring an atomically defined platinum/cobalt oxide model catalyst into the electrochemical environment while preserving its atomic surface structure. Using this approach, we explore particle size effects and identify hitherto unknown metal-support interactions that stabilize oxidized platinum at the nanoparticle interface. The metal-support interactions open a new synergistic reaction pathway that involves both metallic and oxidized platinum. Our results illustrate the potential of the concept, which makes available a systematic approach to build atomically defined model electrodes for fundamental electrocatalytic studies.

The consequences of the intracellular retention of pathogen-derived T-cell-independent antigens on protein presentation to T cells.

PubMed

Leyva-Cobián, F; Outschoorn, I M; Carrasco-Marín, E; Alvarez-Domínguez, C

1997-10-01

Intracellular pathogens can be considered as particulate antigens chemically composed of a complex mixture of T-cell-dependent antigens (TD) (peptides and proteins) and T-cell-independent antigens (TI) (glycolipids and complex polysaccharides). A large range of saccharides (from oligosaccharides to complex polysaccharides) derived from pathogenic microorganisms are being isolated and characterized. They are currently implicated in signaling systems and concomitant host-parasite relationships. However, there are not many structure-function relationships described for these pathogens. This is particularly true of polysaccharides. In this report we have reviewed the role of defined TI antigens in the processing and presentation of defined TD antigens to specific T cells by antigen-presenting cells (APC). We also considered the importance of some of the chemical characteristics shared by different carbohydrates implicated in the inhibition of antigen presentation. These findings are discussed in relation to the clear immunopathological consequences of long retention periods of complex carbohydrate molecules derived from intracellular parasites inside certain APC and the absence of antigen presentation impairment in physiological situations such as the removal of senescent or damaged red blood cells by splenic macrophages or intracellular accumulation of carbohydrates in colostrum and milk macrophages during lactation.

Identification of Novel Fluorochemicals in Aqueous Film-Forming Foams (AFFF) Used by the US Military

PubMed Central

Place, Benjamin J.; Field, Jennifer A.

2012-01-01

Aqueous film-forming foams (AFFFs) are a vital tool to fight large hydrocarbon fires and can be used by public, commercial, and military firefighting organizations. In order to possess these superior firefighting capabilities, AFFFs contain fluorochemical surfactants, of which many of the chemical identities are listed as proprietary. Large-scale controlled (e.g. training activities) and uncontrolled releases of AFFF have resulted in contamination of groundwater. Information on the composition of AFFF formulations is needed to fully define the extent of groundwater contamination and the first step is to fully define the fluorochemical composition of AFFFs used by the US military. Fast atom bombardment mass spectrometry (FAB-MS) and high resolution quadrupole-time-of-flight mass spectrometry (QTOF-MS) were combined to elucidate chemical formulas for the fluorochemicals in AFFF mixtures and, along with patent-based information, structures were assigned. Sample collection and analysis was focused on AFFFs that have been designated as certified for US military use. Ten different fluorochemical classes were identified in the seven military-certified AFFF formulations, and include anionic, cationic, and zwitterionic surfactants with perfluoroalkyl chain lengths ranging from 4-12. The environmental implications are discussed and research needs are identified. PMID:22681548

Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation

PubMed Central

Zydziak, Nicolas; Konrad, Waldemar; Feist, Florian; Afonin, Sergii; Weidner, Steffen; Barner-Kowollik, Christopher

2016-01-01

Designing artificial macromolecules with absolute sequence order represents a considerable challenge. Here we report an advanced light-induced avenue to monodisperse sequence-defined functional linear macromolecules up to decamers via a unique photochemical approach. The versatility of the synthetic strategy—combining sequential and modular concepts—enables the synthesis of perfect macromolecules varying in chemical constitution and topology. Specific functions are placed at arbitrary positions along the chain via the successive addition of monomer units and blocks, leading to a library of functional homopolymers, alternating copolymers and block copolymers. The in-depth characterization of each sequence-defined chain confirms the precision nature of the macromolecules. Decoding of the functional information contained in the molecular structure is achieved via tandem mass spectrometry without recourse to their synthetic history, showing that the sequence information can be read. We submit that the presented photochemical strategy is a viable and advanced concept for coding individual monomer units along a macromolecular chain. PMID:27901024

Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation.

PubMed

Zydziak, Nicolas; Konrad, Waldemar; Feist, Florian; Afonin, Sergii; Weidner, Steffen; Barner-Kowollik, Christopher

2016-11-30

Designing artificial macromolecules with absolute sequence order represents a considerable challenge. Here we report an advanced light-induced avenue to monodisperse sequence-defined functional linear macromolecules up to decamers via a unique photochemical approach. The versatility of the synthetic strategy-combining sequential and modular concepts-enables the synthesis of perfect macromolecules varying in chemical constitution and topology. Specific functions are placed at arbitrary positions along the chain via the successive addition of monomer units and blocks, leading to a library of functional homopolymers, alternating copolymers and block copolymers. The in-depth characterization of each sequence-defined chain confirms the precision nature of the macromolecules. Decoding of the functional information contained in the molecular structure is achieved via tandem mass spectrometry without recourse to their synthetic history, showing that the sequence information can be read. We submit that the presented photochemical strategy is a viable and advanced concept for coding individual monomer units along a macromolecular chain.

Dovetailing biology and chemistry: integrating the Gene Ontology with the ChEBI chemical ontology

PubMed Central

2013-01-01

Background The Gene Ontology (GO) facilitates the description of the action of gene products in a biological context. Many GO terms refer to chemical entities that participate in biological processes. To facilitate accurate and consistent systems-wide biological representation, it is necessary to integrate the chemical view of these entities with the biological view of GO functions and processes. We describe a collaborative effort between the GO and the Chemical Entities of Biological Interest (ChEBI) ontology developers to ensure that the representation of chemicals in the GO is both internally consistent and in alignment with the chemical expertise captured in ChEBI. Results We have examined and integrated the ChEBI structural hierarchy into the GO resource through computationally-assisted manual curation of both GO and ChEBI. Our work has resulted in the creation of computable definitions of GO terms that contain fully defined semantic relationships to corresponding chemical terms in ChEBI. Conclusions The set of logical definitions using both the GO and ChEBI has already been used to automate aspects of GO development and has the potential to allow the integration of data across the domains of biology and chemistry. These logical definitions are available as an extended version of the ontology from http://purl.obolibrary.org/obo/go/extensions/go-plus.owl. PMID:23895341

Biological and physicochemical characterization of a serum- and xeno-free chemically defined cryopreservation procedure for adult human progenitor cells.

PubMed

Zeisberger, Steffen M; Schulz, Julia C; Mairhofer, Mario; Ponsaerts, Peter; Wouters, Guy; Doerr, Daniel; Katsen-Globa, Alisa; Ehrbar, Martin; Hescheler, Jurgen; Hoerstrup, Simon P; Zisch, Andreas H; Kolbus, Andrea; Zimmermann, Heiko

2011-01-01

While therapeutic cell transplantations using progenitor cells are increasingly evolving towards phase I and II clinical trials and chemically defined cell culture is established, standardization in biobanking is still in the stage of infancy. In this study, the EU FP6-funded CRYSTAL (CRYo-banking of Stem cells for human Therapeutic AppLication) consortium aimed to validate novel Standard Operating Procedures (SOPs) to perform and validate xeno-free and chemically defined cryopreservation of human progenitor cells and to reduce the amount of the potentially toxic cryoprotectant additive (CPA) dimethyl sulfoxide (DMSO). To achieve this goal, three human adult progenitor and stem cell populations-umbilical cord blood (UCB)-derived erythroid cells (UCB-ECs), UCB-derived endothelial colony forming cells (UCB-ECFCs), and adipose tissue (AT)-derived mesenchymal stromal cells (AT-MSCs)-were cryopreserved in chemically defined medium supplemented with 10% or 5% DMSO. Cell recovery, cell repopulation, and functionality were evaluated postthaw in comparison to cryopreservation in standard fetal bovine serum (FBS)-containing freezing medium. Even with a reduction of the DMSO CPA to 5%, postthaw cell count and viability assays indicated no overall significant difference versus standard cryomedium. Additionally, to compare cellular morphology/membrane integrity and ice crystal formation during cryopreservation, multiphoton laser-scanning cryomicroscopy (cryo-MPLSM) and scanning electron microscopy (SEM) were used. Neither cryo-MPLSM nor SEM indicated differences in membrane integrity for the tested cell populations under various conditions. Moreover, no influence was observed on functional properties of the cells following cryopreservation in chemically defined freezing medium, except for UCB-ECs, which showed a significantly reduced differentiation capacity after cryopreservation in chemically defined medium supplemented with 5% DMSO. In summary, these results demonstrate the feasibility and robustness of standardized xeno-free cryopreservation of different human progenitor cells and encourage their use even more in the field of tissue-engineering and regenerative medicine.

Preparing Synthetic Aβ in Different Aggregation States

PubMed Central

Stine, W. Blaine; Jungbauer, Lisa; Yu, Chunjiang; LaDu, Mary Jo

2013-01-01

This chapter outlines protocols that produce homogenous preparations of oligomeric and fibrillar amyloid -β peptide (Aβ). While there are several isoforms of this peptide, the 42 amino acid form is the focus because of its genetic and pathological link to Alzheimer’s disease (AD). Past decades of AD research highlight the dependence of Aβ42 function on its structural assembly state. Biochemical, cellular and in vivo studies of Aβ42 usually begin with purified peptide obtained by chemical synthesis or recombinant expression. The initial steps to solubilize and prepare these purified dry peptide stocks are critical to controlling the structural assembly of Aβ. To develop homogenous Aβ42 assemblies, we initially monomerize the peptide, erasing any “structural history” that could seed aggregation, by using a strong solvent. It is this starting material that has allowed us to define and optimize conditions that consistently produce homogenous solutions of soluble oligomeric and fibrillar Aβ42 assemblies. These preparations have been developed and characterized by using atomic force microscopy (AFM) to identify the structurally discrete species formed by Aβ42 under specific solution conditions. These preparations have been used extensively to demonstrate a variety of functional differences between oligomeric and fibrillar Aβ42. We also present a protocol for fluorescently labeling oligomeric Aβ42 that does not affect structure, as measured by AFM, or function, as measured by a cellular uptake assay. These reagents are critical experimental tools that allow for defining specific structure/function connections. PMID:20967580

Postsynthetic Tuning of Metal-Organic Frameworks for Targeted Applications.

PubMed

Islamoglu, Timur; Goswami, Subhadip; Li, Zhanyong; Howarth, Ashlee J; Farha, Omar K; Hupp, Joseph T

2017-04-18

Metal-organic frameworks (MOFs) are periodic, hybrid, atomically well-defined porous materials that typically form by self-assembly and consist of inorganic nodes (metal ions or clusters) and multitopic organic linkers. MOFs as a whole offer many intriguing properties, including ultrahigh porosity, tunable chemical functionality, and low density. These properties point to numerous potential applications, including gas storage, chemical separations, catalysis, light harvesting, and chemical sensing, to name a few. Reticular chemistry, or the linking of molecular building blocks into predetermined network structures, has been employed to synthesize thousands of MOFs. Given the vast library of candidate nodes and linkers, the number of potentially synthetically accessible MOFs is enormous. Nevertheless, a powerful complementary approach to obtain specific structures with desired chemical functionality is to modify known MOFs after synthesis. This approach is particularly useful when incorporation of particular chemical functionalities via direct synthesis is challenging or impossible. The challenges may stem from limited stability or solubility of precursors, unwanted secondary reactivity of precursors, or incompatibility of functional groups with the conditions needed for direct synthesis. MOFs can be postsynthetically modified by replacing the metal nodes and/or organic linkers or via functionalization of the metal nodes and/or organic linkers. Here we describe some of our efforts toward the development and application of postsynthetic strategies for imparting desired chemical functionalities in MOFs of known topology. The techniques include methods for functionalizing MOF nodes, i.e., solvent-assisted ligand incorporation (SALI) and atomic layer deposition in MOFs (AIM) as well as a method to replace structural linkers, termed solvent-assisted linker exchange (SALE), also known as postsynthethic exchange (PSE). For each functionalization strategy, we first describe its chemical basis along with the requirements for its successful implementation. We then present a small number of examples, with an emphasis on those that (a) convey the underlying concepts and/or (b) lead to functional structures (e.g., catalysts) that would be difficult or impossible to access via direct routes. The examples, however, are only illustrative, and a significant body of work exists from both our lab and others, especially for the SALE/PSE strategy. We refer readers to the papers cited and to the references therein. More exciting, in our view, will be new examples and new applications of the functionalization strategies-especially applications made possible by creatively combining the strategies. Underexplored (again, in our view) are implementations that impart electrical conductivity, enable increasingly selective chemical sensing, or facilitate cascade catalysis. It will be interesting to see where these strategies and others take this compelling field over the next few years.

Isothermal DNA origami folding: avoiding denaturing conditions for one-pot, hybrid-component annealing

NASA Astrophysics Data System (ADS)

Kopielski, Andreas; Schneider, Anne; Csáki, Andrea; Fritzsche, Wolfgang

2015-01-01

The DNA origami technique offers great potential for nanotechnology. Using biomolecular self-assembly, defined 2D and 3D nanoscale DNA structures can be realized. DNA origami allows the positioning of proteins, fluorophores or nanoparticles with an accuracy of a few nanometers and enables thereby novel nanoscale devices. Origami assembly usually includes a thermal denaturation step at 90 °C. Additional components used for nanoscale assembly (such as proteins) are often thermosensitive, and possibly damaged by such harsh conditions. They have therefore to be attached in an extra second step to avoid defects. To enable a streamlined one-step nanoscale synthesis - a so called one-pot folding - an adaptation of the folding procedures is required. Here we present a thermal optimization of this process for a 2D DNA rectangle-shaped origami resulting in an isothermal assembly protocol below 60 °C without thermal denaturation. Moreover, a room temperature protocol is presented using the chemical additive betaine, which is biocompatible in contrast to chemical denaturing approaches reported previously.The DNA origami technique offers great potential for nanotechnology. Using biomolecular self-assembly, defined 2D and 3D nanoscale DNA structures can be realized. DNA origami allows the positioning of proteins, fluorophores or nanoparticles with an accuracy of a few nanometers and enables thereby novel nanoscale devices. Origami assembly usually includes a thermal denaturation step at 90 °C. Additional components used for nanoscale assembly (such as proteins) are often thermosensitive, and possibly damaged by such harsh conditions. They have therefore to be attached in an extra second step to avoid defects. To enable a streamlined one-step nanoscale synthesis - a so called one-pot folding - an adaptation of the folding procedures is required. Here we present a thermal optimization of this process for a 2D DNA rectangle-shaped origami resulting in an isothermal assembly protocol below 60 °C without thermal denaturation. Moreover, a room temperature protocol is presented using the chemical additive betaine, which is biocompatible in contrast to chemical denaturing approaches reported previously. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr04176c

Cooperative catalysis: electron-rich Fe-H complexes and DMAP, a successful "joint venture" for ultrafast hydrogen production.

PubMed

Rommel, Susanne; Hettmanczyk, Lara; Klein, Johannes E M N; Plietker, Bernd

2014-08-01

A series of defined iron-hydrogen complexes was prepared in a straightforward one-pot approach. The structure and electronic properties of such complexes were investigated by means of quantum-chemical analysis. These new complexes were then applied in the dehydrogenative silylation of methanol. The complex (dppp)(CO)(NO)FeH showed a remarkable activity with a TOF of more than 600 000 h(-1) of pure hydrogen gas within seconds. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chiral pesticides: Identification, description, and environmental implications

USGS Publications Warehouse

Ulrich, Elin M.; Morrison, Candice N.; Goldsmith, Michael R.; Foreman, William T.

2012-01-01

Anthropogenic chemicals, including pesticides, are a major source of contamination and pollution in the environment. Pesticides have many positive uses: increased food production, decreased damage to crops and structures, reduced disease vector populations, and more. Nevertheless, pesticide exposure can pose risks to humans and the environment, so various mitigation strategies are exercised to make them safer, minimize their use, and reduce their unintended environment effects. One strategy that may help achieve these goals relies on the unique properties of chirality or molecular asymmetry. Some common terms related to chirality are defined in Table 1.

Fabrication of all-inorganic nanocrystal solids through matrix encapsulation of nanocrystal arrays.

PubMed

Kinder, Erich; Moroz, Pavel; Diederich, Geoffrey; Johnson, Alexa; Kirsanova, Maria; Nemchinov, Alexander; O'Connor, Timothy; Roth, Dan; Zamkov, Mikhail

2011-12-21

A general strategy for low-temperature processing of colloidal nanocrystals into all-inorganic films is reported. The present methodology goes beyond the traditional ligand-interlinking scheme and relies on encapsulation of morphologically defined nanocrystal arrays into a matrix of a wide-band gap semiconductor, which preserves optoelectronic properties of individual nanoparticles while rendering the nanocrystal film photoconductive. Fabricated solids exhibit excellent thermal stability, which is attributed to the heteroepitaxial structure of nanocrystal-matrix interfaces, and show compelling light-harvesting performance in prototype solar cells. © 2011 American Chemical Society

Calculating degree-based topological indices of dominating David derived networks

NASA Astrophysics Data System (ADS)

Ahmad, Muhammad Saeed; Nazeer, Waqas; Kang, Shin Min; Imran, Muhammad; Gao, Wei

2017-12-01

An important area of applied mathematics is the Chemical reaction network theory. The behavior of real world problems can be modeled by using this theory. Due to applications in theoretical chemistry and biochemistry, it has attracted researchers since its foundation. It also attracts pure mathematicians because it involves interesting mathematical structures. In this report, we compute newly defined topological indices, namely, Arithmetic-Geometric index (AG1 index), SK index, SK1 index, and SK2 index of the dominating David derived networks [1, 2, 3, 4, 5].

[Legal and management issues of public health requirements for swimming pools in Regione Toscana].

PubMed

Linguanti, Saverio; Totaro, Michele; Frendo, Lorenzo; Giorgi, Serena; Porretta, Andrea; Valentini, Paola; Baggiani, Angelo

2018-01-01

In this paper we describe the laws and rules applying to swimming pools. Authorization activity title for recreational swimming pools is regulated according to articles 80 and 86 of the TULPS R.D.n°773/1931. In Regione Toscana periodic management of the hygienic requirements for swimming pools is regulated by Regional Decree 54R/2015. It requires the evaluation of physical-chemical and microbiological indicators. The law applies to structural and organizational requirements of swimming pools as well as defines responsabilities of managers.

Structures Self-Assembled Through Directional Solidification

NASA Technical Reports Server (NTRS)

Dynys, Frederick W.; Sayir, Ali

2005-01-01

Nanotechnology has created a demand for new fabrication methods with an emphasis on simple, low-cost techniques. Directional solidification of eutectics (DSE) is an unconventional approach in comparison to low-temperature biomimetic approaches. A technical challenge for DSE is producing microstructural architectures on the nanometer scale. In both processes, the driving force is the minimization of Gibb's free energy. Selfassembly by biomimetic approaches depends on weak interaction forces between organic molecules to define the architectural structure. The architectural structure for solidification depends on strong chemical bonding between atoms. Constituents partition into atomic-level arrangements at the liquid-solid interface to form polyphase structures, and this atomic-level arrangement at the liquid-solid interface is controlled by atomic diffusion and total undercooling due to composition (diffusion), kinetics, and curvature of the boundary phases. Judicious selection of the materials system and control of the total undercooling are the keys to producing structures on the nanometer scale. The silicon-titanium silicide (Si-TiSi2) eutectic forms a rod structure under isothermal cooling conditions. At the NASA Glenn Research Center, directional solidification was employed along with a thermal gradient to promote uniform rods oriented with the thermal gradient. The preceding photomicrograph shows the typical transverse microstructure of a solidified Si-TiSi2 eutectic composition. The dark and light gray regions are Si and TiSi2, respectively. Preferred rod orientation along the thermal gradient was poor. The ordered TiSi2 rods have a narrow distribution in diameter of 2 to 3 m, as shown. The rod diameter showed a weak dependence on process conditions. Anisotropic etch behavior between different phases provides the opportunity to fabricate structures with high aspect ratios. The photomicrographs show the resulting microstructure after a wet chemical etch and a dry plasma etch. The wet chemical etches the silicon away, exposing the TiSi2 rods, whereas plasma etching preferentially etches the Si-TiSi2 interface to form a crater. The porous architectures are applicable to fabricating microdevices or creating templates for part fabrication. The porous rod structure can serve as a platform for fabricating microplasma devices for propulsion or microheat exchangers and for fabricating microfilters for miniatured chemical reactors. Although more work is required, self-assembly from DSE can have a role in microdevice fabrication.

SUBSTITUTION REACTIONS FOR THE DETOXIFICATION OF HAZARDOUS CHEMICALS

EPA Science Inventory

Chemical Treatment is one of several treatment techniques used for the remediation of toxic and hazardous chemicals. Chemical treatment in this report is defined as substitution of halogens by hydrogens for the conversion of halogenated organic toxicant into its native hydrocarb...

49 CFR 173.168 - Chemical oxygen generators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Chemical oxygen generators. 173.168 Section 173... Class 7 § 173.168 Chemical oxygen generators. An oxygen generator, chemical (defined in § 171.8 of this subchapter) may be transported only under the following conditions: (a) Approval. A chemical oxygen generator...

49 CFR 173.168 - Chemical oxygen generators.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Chemical oxygen generators. 173.168 Section 173... Class 7 § 173.168 Chemical oxygen generators. An oxygen generator, chemical (defined in § 171.8 of this subchapter) may be transported only under the following conditions: (a) Approval. A chemical oxygen generator...

14 CFR 25.1450 - Chemical oxygen generators.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Chemical oxygen generators. 25.1450 Section... oxygen generators. (a) For the purpose of this section, a chemical oxygen generator is defined as a device which produces oxygen by chemical reaction. (b) Each chemical oxygen generator must be designed...

49 CFR 173.168 - Chemical oxygen generators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Chemical oxygen generators. 173.168 Section 173... Class 7 § 173.168 Chemical oxygen generators. An oxygen generator, chemical (defined in § 171.8 of this subchapter) may be transported only under the following conditions: (a) Approval. A chemical oxygen generator...

14 CFR 25.1450 - Chemical oxygen generators.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Chemical oxygen generators. 25.1450 Section... oxygen generators. (a) For the purpose of this section, a chemical oxygen generator is defined as a device which produces oxygen by chemical reaction. (b) Each chemical oxygen generator must be designed...

49 CFR 173.168 - Chemical oxygen generators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Chemical oxygen generators. 173.168 Section 173... Class 7 § 173.168 Chemical oxygen generators. An oxygen generator, chemical (defined in § 171.8 of this subchapter) may be transported only under the following conditions: (a) Approval. A chemical oxygen generator...

49 CFR 173.168 - Chemical oxygen generators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Chemical oxygen generators. 173.168 Section 173... Class 7 § 173.168 Chemical oxygen generators. An oxygen generator, chemical (defined in § 171.8 of this subchapter) may be transported only under the following conditions: (a) Approval. A chemical oxygen generator...

14 CFR 25.1450 - Chemical oxygen generators.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Chemical oxygen generators. 25.1450 Section... oxygen generators. (a) For the purpose of this section, a chemical oxygen generator is defined as a device which produces oxygen by chemical reaction. (b) Each chemical oxygen generator must be designed...

Programmed folding of DNA origami structures through single-molecule force control.

PubMed

Bae, Wooli; Kim, Kipom; Min, Duyoung; Ryu, Je-Kyung; Hyeon, Changbong; Yoon, Tae-Young

2014-12-03

Despite the recent development in the design of DNA origami, its folding yet relies on thermal or chemical annealing methods. We here demonstrate mechanical folding of the DNA origami structure via a pathway that has not been accessible to thermal annealing. Using magnetic tweezers, we stretch a single scaffold DNA with mechanical tension to remove its secondary structures, followed by base pairing of the stretched DNA with staple strands. When the force is subsequently quenched, folding of the DNA nanostructure is completed through displacement between the bound staple strands. Each process in the mechanical folding is well defined and free from kinetic traps, enabling us to complete folding within 10 min. We also demonstrate parallel folding of DNA nanostructures through multiplexed manipulation of the scaffold DNAs. Our results suggest a path towards programmability of the folding pathway of DNA nanostructures.

Chemical potential and reaction electronic flux in symmetry controlled reactions.

PubMed

Vogt-Geisse, Stefan; Toro-Labbé, Alejandro

2016-07-15

In symmetry controlled reactions, orbital degeneracies among orbitals of different symmetries can occur along a reaction coordinate. In such case Koopmans' theorem and the finite difference approximation provide a chemical potential profile with nondifferentiable points. This results in an ill-defined reaction electronic flux (REF) profile, since it is defined as the derivative of the chemical potential with respect to the reaction coordinate. To overcome this deficiency, we propose a new way for the calculation of the chemical potential based on a many orbital approach, suitable for reactions in which symmetry is preserved. This new approach gives rise to a new descriptor: symmetry adapted chemical potential (SA-CP), which is the chemical potential corresponding to a given irreducible representation of a symmetry group. A corresponding symmetry adapted reaction electronic flux (SA-REF) is also obtained. Using this approach smooth chemical potential profiles and well defined REFs are achieved. An application of SA-CP and SA-REF is presented by studying the Cs enol-keto tautomerization of thioformic acid. Two SA-REFs are obtained, JA'(ξ) and JA'' (ξ). It is found that the tautomerization proceeds via an in-plane delocalized 3-center 4-electron O-H-S hypervalent bond which is predicted to exist only in the transition state (TS) region. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Calculation of NMR chemical shifts in organic solids: accounting for motional effects.

PubMed

Dumez, Jean-Nicolas; Pickard, Chris J

2009-03-14

NMR chemical shifts were calculated from first principles for well defined crystalline organic solids. These density functional theory calculations were carried out within the plane-wave pseudopotential framework, in which truly extended systems are implicitly considered. The influence of motional effects was assessed by averaging over vibrational modes or over snapshots taken from ab initio molecular dynamics simulations. It is observed that the zero-point correction to chemical shifts can be significant, and that thermal effects are particularly noticeable for shielding anisotropies and for a temperature-dependent chemical shift. This study provides insight into the development of highly accurate first principles calculations of chemical shifts in solids, highlighting the role of motional effects on well defined systems.

Structure and mechanism of action of the hydroxy-aryl-aldehyde class of IRE1 endoribonuclease inhibitors

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

Sanches, Mario; Duffy, Nicole M.; Talukdar, Manisha

2014-10-24

Endoplasmic reticulum (ER) stress activates the unfolded protein response and its dysfunction is linked to multiple diseases. The stress transducer IRE1α is a transmembrane kinase endoribonuclease (RNase) that cleaves mRNA substrates to re-establish ER homeostasis. Aromatic ring systems containing hydroxy–aldehyde moieties, termed hydroxy–aryl–aldehydes (HAA), selectively inhibit IRE1α RNase and thus represent a novel chemical series for therapeutic development. We solved crystal structures of murine IRE1α in complex with three HAA inhibitors. HAA inhibitors engage a shallow pocket at the RNase-active site through pi-stacking interactions with His910 and Phe889, an essential Schiff base with Lys907 and a hydrogen bond with Tyr892.more » Structure–activity studies and mutational analysis of contact residues define the optimal chemical space of inhibitors and validate the inhibitor-binding site. These studies lay the foundation for understanding both the biochemical and cellular functions of IRE1α using small molecule inhibitors and suggest new avenues for inhibitor design.« less

Single-Molecule Reaction Chemistry in Patterned Nanowells

PubMed Central

2016-01-01

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

Visualization and Phospholipid Identification (VaLID): online integrated search engine capable of identifying and visualizing glycerophospholipids with given mass

PubMed Central

Figeys, Daniel; Fai, Stephen; Bennett, Steffany A. L.

2013-01-01

Motivation: Establishing phospholipid identities in large lipidomic datasets is a labour-intensive process. Where genomics and proteomics capitalize on sequence-based signatures, glycerophospholipids lack easily definable molecular fingerprints. Carbon chain length, degree of unsaturation, linkage, and polar head group identity must be calculated from mass to charge (m/z) ratios under defined mass spectrometry (MS) conditions. Given increasing MS sensitivity, many m/z values are not represented in existing prediction engines. To address this need, Visualization and Phospholipid Identification is a web-based application that returns all theoretically possible phospholipids for any m/z value and MS condition. Visualization algorithms produce multiple chemical structure files for each species. Curated lipids detected by the Canadian Institutes of Health Research Training Program in Neurodegenerative Lipidomics are provided as high-resolution structures. Availability: VaLID is available through the Canadian Institutes of Health Research Training Program in Neurodegenerative Lipidomics resources web site at https://www.med.uottawa.ca/lipidomics/resources.html. Contacts: lipawrd@uottawa.ca Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:23162086

Solid state synthesis of chitosan and its unsaturated derivatives for laser microfabrication of 3D scaffolds

NASA Astrophysics Data System (ADS)

Akopova, T. A.; Demina, T. S.; Bagratashvili, V. N.; Bardakova, K. N.; Novikov, M. M.; Selezneva, I. I.; Istomin, A. V.; Svidchenko, E. A.; Cherkaev, G. V.; Surin, N. M.; Timashev, P. S.

2015-07-01

Chitosans with various degrees of deacetylation and molecular weights and their allyl substituted derivatives were obtained through a solvent-free reaction under shear deformation in an extruder. Structure and physical-chemical analysis of the samples were carried out using nuclear magnetic resonance (NMR), ultraviolet (UV) and infrared radiation (IR) spectroscopy. Photosensitive materials based on the synthesized polymers were successfully used for microfabrication of 3D well-defined architectonic structures by laser stereolithography. Study on the metabolic activity of NCTC L929 cultured in the presence of the cured chitosan extracts indicates that the engineered biomaterials could support adhesion, spreading and growth of adherent-dependent cells, and thus could be considered as biocompatible scaffolds.

On the possible operation of natural laws in ecosystems.

PubMed

Woodley, Michael A

2007-01-01

In this manuscript, after a brief review of the history of typological thinking in the biological sciences from Transcendentalism to Structuralism, it is argued that natural Platonic laws may operate in ecosystems. This claim is based on two observations of law-like behaviour. Firstly, that adaptation towards specialization can be considered as a form of typological lineage degeneration, where specialized species are more vulnerable to environmental perturbation. And secondly, that the convergent recurrence of biological forms indicates that there exists a finite number of niches which in the abstract could be considered as ecological analogies to Denton's molecular Platonic moulds, operating as attractors and restricting the range of possible organismal body plans based on the physical and chemical gradients that partly define their hyper-structure.

Quantitative Survey and Structural Classification of Fracking Chemicals Reported in Unconventional Gas Exploitation

NASA Astrophysics Data System (ADS)

Elsner, Martin; Schreglmann, Kathrin

2015-04-01

Few technologies are being discussed in such controversial terms as hydraulic fracturing ("fracking") in the recovery of unconventional gas. Particular concern regards the chemicals that may return to the surface as a result of hydraulic fracturing. These are either "fracking chemicals" - chemicals that are injected together with the fracking fluid to optimize the fracturing performance or geogenic substances which may turn up during gas production, in the so-called produced water originating from the target formation. Knowledge about them is warranted for several reasons. (1) Monitoring. Air emissions are reported to arise from well drilling, the gas itself or condensate tanks. In addition, potential spills and accidents bear the danger of surface and shallow groundwater contaminations. Monitoring strategies are therefore warranted to screen for "indicator" substances of potential impacts. (2) Chemical Analysis. To meet these analytical demands, target substances must be defined so that adequate sampling approaches and analytical methods can be developed. (3) Transformation in the Subsurface. Identification and classification of fracking chemicals (aromatics vs. alcohols vs. acids, esters, etc.) is further important to assess the possibility of subsurface reactions which may potentially generate new, as yet unidentified transformation products. (4) Wastewater Treatment. For the same reason chemical knowledge is important for optimized wastewater treatment strategies. (5) Human and Ecosystem Health. Knowledge of the most frequent fracking chemicals is further essential for risk assessment (environmental behavior, toxicity) (6) Public Discussions. Finally, an overview of reported fracking chemicals can provide unbiased scientific into current public debates and enable critical reviews of Green Chemistry approaches. Presently, however, such information is not readily available. We aim to close this knowledge gap by providing a quantitative overview of chemical additives reported for use in hydraulic fracturing. For the years 2005-2009 it is based on the Waxman report, and for the years 2011-2013 it relies on the database FracFocus, where it makes use of the data extracted and provided by the website "SkyTruth". For the first time, we list fracking chemicals according to their chemical structure and functional groups, because these properties are important as a starting point for (i) the design of analytical methods, (ii) to assess environmental fate and (iii) to understand why a given chemical is used at a certain stage of the fracturing process and what possible alternatives exist.

Nickel containing CO dehydrogenases and hydrogenases.

PubMed

Ragsdale, S W

2000-01-01

The two redox catalysts described here can generate very low potential electrons in one direction and perform chemically difficult reductions in the other. The chemical transformations occur at unusual metal clusters. Spectroscopic, crystallographic, and kinetic analyses are converging on answers to how the metals in these clusters are arranged and how they are involved in the chemical and redox steps. The first structure of CO dehydrogenase, which will appear in the next year, will help define a firm chemical basis for future mechanistic studies. In the immediate future, we hope to learn whether the hydride intermediate in hydrogenase or the carbonyl intermediate in CO dehydrogenase bind to the Ni or Fe subsites in these heterometallic clusters. Or perhaps could they be bridged to two metals? Inter- and intramolecular wires have been proposed that connect the catalytic redox machine to proximal redox centers leading eventually to the ultimate redox partners. Elucidating the pathways of electron flow is a priority for the future. There is evidence for molecular channels delivering substrates to the active sites of these enzymes. In the next few years, these channels will be better defined. The products of CO2 and proton reduction are passed to the active sites of other enzymes and, in the case of H2, even passed from one organism to another. In the future, the mechanism of gas transfer will be uncovered. General principles of how these redox reactions are catalyzed are becoming lucid as the reactions are modeled theoretically and experimentally. Proton and CO2 reduction and the generation of C-C bonds from simple precursors are important reactions in industry. H2 could be the clean fuel of the future. Hopefully, the knowledge gained from studies of hydrogenase, CO dehydrogenase, and acetyl-CoA synthase can be used to improve life on earth.

Modular and Orthogonal Synthesis of Hybrid Polymers and Networks

PubMed Central

Liu, Shuang; Dicker, Kevin T.; Jia, Xinqiao

2015-01-01

Biomaterials scientists strive to develop polymeric materials with distinct chemical make-up, complex molecular architectures, robust mechanical properties and defined biological functions by drawing inspirations from biological systems. Salient features of biological designs include (1) repetitive presentation of basic motifs; and (2) efficient integration of diverse building blocks. Thus, an appealing approach to biomaterials synthesis is to combine synthetic and natural building blocks in a modular fashion employing novel chemical methods. Over the past decade, orthogonal chemistries have become powerful enabling tools for the modular synthesis of advanced biomaterials. These reactions require building blocks with complementary functionalities, occur under mild conditions in the presence of biological molecules and living cells and proceed with high yield and exceptional selectivity. These chemistries have facilitated the construction of complex polymers and networks in a step-growth fashion, allowing facile modulation of materials properties by simple variations of the building blocks. In this review, we first summarize features of several types of orthogonal chemistries. We then discuss recent progress in the synthesis of step growth linear polymers, dendrimers and networks that find application in drug delivery, 3D cell culture and tissue engineering. Overall, orthogonal reactions and modulular synthesis have not only minimized the steps needed for the desired chemical transformations but also maximized the diversity and functionality of the final products. The modular nature of the design, combined with the potential synergistic effect of the hybrid system, will likely result in novel hydrogel matrices with robust structures and defined functions. PMID:25572255

Recent Advances in the Chemical Biology of Nitroxyl (HNO) Detection and Generation

PubMed Central

Miao, Zhengrui; King, S. Bruce

2016-01-01

Nitroxyl or azanone (HNO) represents the redox-related (one electron reduced and protonated) relative of the well-known biological signaling molecule nitric oxide (NO). Despite the close structural similarity to NO, defined biological roles and endogenous formation of HNO remain unclear due to the high reactivity of HNO with itself, soft nucleophiles and transition metals. While significant work has been accomplished in terms of the physiology, biology and chemistry of HNO, important and clarifying work regarding HNO detection and formation has occurred within the last 10 years. This review summarizes advances in the areas of HNO detection and donation and their application to normal and pathological biology. Such chemical biological tools allow a deeper understanding of biological HNO formation and the role that HNO plays in a variety of physiological systems. PMID:27108951

Determination of an ensemble of structures representing the intermediate state of the bacterial immunity protein Im7.

PubMed

Gsponer, Joerg; Hopearuoho, Harri; Whittaker, Sara B-M; Spence, Graham R; Moore, Geoffrey R; Paci, Emanuele; Radford, Sheena E; Vendruscolo, Michele

2006-01-03

We present a detailed structural characterization of the intermediate state populated during the folding and unfolding of the bacterial immunity protein Im7. We achieve this result by incorporating a variety of experimental data available for this species in molecular dynamics simulations. First, we define the structure of the exchange-competent intermediate state of Im7 by using equilibrium hydrogen-exchange protection factors. Second, we use this ensemble to predict Phi-values and compare the results with the experimentally determined Phi-values of the kinetic refolding intermediate. Third, we predict chemical-shift measurements and compare them with the measured chemical shifts of a mutational variant of Im7 for which the kinetic folding intermediate is the most stable state populated at equilibrium. Remarkably, we found that the properties of the latter two species are predicted with high accuracy from the exchange-competent intermediate that we determined, suggesting that these three states are characterized by a similar architecture in which helices I, II, and IV are aligned in a native-like, but reorganized, manner. Furthermore, the structural ensemble that we obtained enabled us to rationalize the results of tryptophan fluorescence experiments in the WT protein and a series of mutational variants. The results show that the integration of diverse sets of experimental data at relatively low structural resolution is a powerful approach that can provide insights into the structural organization of this conformationally heterogeneous three-helix intermediate with unprecedented detail and highlight the importance of both native and non-native interactions in stabilizing its structure.

Finding Chemical Structures Corresponding to a Set of Coordinates in Chemical Descriptor Space.

PubMed

Miyao, Tomoyuki; Funatsu, Kimito

2017-08-01

When chemical structures are searched based on descriptor values, or descriptors are interpreted based on values, it is important that corresponding chemical structures actually exist. In order to consider the existence of chemical structures located in a specific region in the chemical space, we propose to search them inside training data domains (TDDs), which are dense areas of a training dataset in the chemical space. We investigated TDDs' features using diverse and local datasets, assuming that GDB11 is the chemical universe. These two analyses showed that considering TDDs gives higher chance of finding chemical structures than a random search-based method, and that novel chemical structures actually exist inside TDDs. In addition to those findings, we tested the hypothesis that chemical structures were distributed on the limited areas of chemical space. This hypothesis was confirmed by the fact that distances among chemical structures in several descriptor spaces were much shorter than those among randomly generated coordinates in the training data range. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

76 FR 1067 - Testing of Certain High Production Volume Chemicals; Second Group of Chemicals

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

... 2070-AD16 Testing of Certain High Production Volume Chemicals; Second Group of Chemicals AGENCY... processors of certain high production volume (HPV) chemical substances to conduct testing to obtain screening... potentially affected by this action if you manufacture (defined by statute to include import) or process any...

Cumulative effects of antiandrogenic chemical mixtures and their relevance to human health risk assessment

EPA Science Inventory

Toxicological studies of defined chemical mixtures assist human health risk assessment by establishing the manner by which chemicals interact with one another to induce an effect. This paper reviews how antiandrogenic chemical mixtures can alter reproductive tract development in ...

Merging Applicability Domains for in Silico Assessment of Chemical Mutagenicity

DTIC Science & Technology

2014-02-04

molecular fingerprints as descriptors for developing quantitative structure−activity relationship ( QSAR ) models and defining applicability domains with...used to define and quantify an applicability domain for either method. The importance of using applicability domains in QSAR modeling cannot be...domain from roughly 80% to 90%. These results indicated that the proposed QSAR protocol constituted a highly robust chemical mutagenicity prediction

Phytochemica: a platform to explore phytochemicals of medicinal plants.

PubMed

Pathania, Shivalika; Ramakrishnan, Sai Mukund; Bagler, Ganesh

2015-01-01

Plant-derived molecules (PDMs) are known to be a rich source of diverse scaffolds that could serve as the basis for rational drug design. Structured compilation of phytochemicals from traditional medicinal plants can facilitate prospection for novel PDMs and their analogs as therapeutic agents. Atropa belladonna, Catharanthus roseus, Heliotropium indicum, Picrorhiza kurroa and Podophyllum hexandrum are important Himalayan medicinal plants, reported to have immense therapeutic properties against various diseases. We present Phytochemica, a structured compilation of 963 PDMs from these plants, inclusive of their plant part source, chemical classification, IUPAC names, SMILES notations, physicochemical properties and 3-dimensional structures with associated references. Phytochemica is an exhaustive resource of natural molecules facilitating prospection for therapeutic molecules from medicinally important plants. It also offers refined search option to explore the neighbourhood of chemical space against ZINC database to identify analogs of natural molecules at user-defined cut-off. Availability of phytochemical structured dataset may enable their direct use in in silico drug discovery which will hasten the process of lead identification from natural products under proposed hypothesis, and may overcome urgent need for phytomedicines. Compilation and accessibility of indigenous phytochemicals and their derivatives can be a source of considerable advantage to research institutes as well as industries. home.iitj.ac.in/∼bagler/webservers/Phytochemica. © The Author(s) 2015. Published by Oxford University Press.

Identifying and designing chemicals with minimal acute aquatic toxicity.

PubMed

Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T; Zimmerman, Julie Beth

2015-05-19

Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure-activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical-chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard.

Contribution of hydrophobic effect to the sorption of phenanthrene, 9-phenanthrol and 9, 10-phenanthrenequinone on carbon nanotubes.

PubMed

Peng, Hongbo; Zhang, Di; Pan, Bo; Peng, Jinhui

2017-02-01

Polycyclic aromatic hydrocarbons (PAHs), with diverse sources and acute toxicity, are categorized as priority pollutants. Previous studies have stated that the hydrophobic effect controls PAH sorption, but no study has been conducted to quantify the exact contribution of the hydrophobic effect. Considering the well-defined structure of carbon nanotubes and their stable chemical composition in organic solvents, three multi-walled carbon nanotubes (MWCNTs) were selected as a model adsorbent. Phenanthrene (PHE) and its degradation intermediates 9-phenanthrol (PTR) and 9, 10-phenanthrenequinone (PQN) were used as model adsorbates. To quantify the contribution of the hydrophobic effect for these three chemicals, the effect of organic solvent (methanol and hexadecane) was investigated. Adsorption isotherms for PHE, PTR and PQN were well fitted by the Freundlich isotherm model. A positive relationship between adsorption affinities of these three chemicals and specific surface area (SSA) was observed in hexadecane but not in water or methanol. Other factors should be included other than SSA. Adsorption of PQN on MWCNTs with oxygen functional groups was higher than that on pristine MWCNTs due to π-π EDA interactions. The contribution of hydrophobic effect was 50%-85% for PHE, suggesting that hydrophobic effect was the predominant mechanism. This contribution was lower than 30% for PTR/PQN on functionalized MWCNTs. Hydrogen bonds control the adsorption of PTR, and π-π bonding interactions control PQN sorption after screening out the hydrophobic effect in hexadecane. Hydrophobic effect is the control mechanism for nonpolar chemicals, while functional groups of CNTs and solvent types control the adsorption of polar compounds. Extended work on quantifying the relationship between chemical structure and the contribution of the hydrophobic effect will provide a useful technique for PAH fate modeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization of Whole Grain Pasta: Integrating Physical, Chemical, Molecular, and Instrumental Sensory Approaches.

PubMed

Marti, Alessandra; Cattaneo, Stefano; Benedetti, Simona; Buratti, Susanna; Abbasi Parizad, Parisa; Masotti, Fabio; Iametti, Stefania; Pagani, Maria Ambrogina

2017-11-01

The consumption of whole-grain food-including pasta-has been increasing steadily. In the case of whole-grain pasta, given the many different producers, it seems important to have some objective parameters to define its overall quality. In this study, commercial whole-grain pasta samples representative of the Italian market have been characterized from both molecular and electronic-senses (electronic nose and electronic tongue) standpoint in order to provide a survey of the properties of different commercial samples. Only 1 pasta product showed very low levels of heat damage markers (furosine and pyrraline), suggesting that this sample underwent to low temperature dry treatment. In all samples, the furosine content was directly correlated to protein structural indices, since protein structure compactness increased with increasing levels of heat damage markers. Electronic senses were able to discriminate among pasta samples according to the intensity of heat treatment during the drying step. Pasta sample with low furosine content was discriminated by umami taste and by sensors responding to aliphatic and inorganic compounds. Data obtained with this multidisciplinary approach are meant to provide hints for identifying useful indices for pasta quality. As observed for semolina pasta, objective parameters based on heat-damage were best suited to define the overall quality of wholegrain pasta, almost independently of compositional differences among commercial samples. Drying treatments of different intensity also had an impact on instrumental sensory traits that may provide a reliable alternative to analytical determination of chemical markers of heat damage in all cases where there is a need for avoiding time-consuming procedures. © 2017 Institute of Food Technologists®.

Property Graph vs RDF Triple Store: A Comparison on Glycan Substructure Search

PubMed Central

Alocci, Davide; Mariethoz, Julien; Horlacher, Oliver; Bolleman, Jerven T.; Campbell, Matthew P.; Lisacek, Frederique

2015-01-01

Resource description framework (RDF) and Property Graph databases are emerging technologies that are used for storing graph-structured data. We compare these technologies through a molecular biology use case: glycan substructure search. Glycans are branched tree-like molecules composed of building blocks linked together by chemical bonds. The molecular structure of a glycan can be encoded into a direct acyclic graph where each node represents a building block and each edge serves as a chemical linkage between two building blocks. In this context, Graph databases are possible software solutions for storing glycan structures and Graph query languages, such as SPARQL and Cypher, can be used to perform a substructure search. Glycan substructure searching is an important feature for querying structure and experimental glycan databases and retrieving biologically meaningful data. This applies for example to identifying a region of the glycan recognised by a glycan binding protein (GBP). In this study, 19,404 glycan structures were selected from GlycomeDB (www.glycome-db.org) and modelled for being stored into a RDF triple store and a Property Graph. We then performed two different sets of searches and compared the query response times and the results from both technologies to assess performance and accuracy. The two implementations produced the same results, but interestingly we noted a difference in the query response times. Qualitative measures such as portability were also used to define further criteria for choosing the technology adapted to solving glycan substructure search and other comparable issues. PMID:26656740

Coupled near-field and far-field exposure assessment framework for chemicals in consumer products.

PubMed

Fantke, Peter; Ernstoff, Alexi S; Huang, Lei; Csiszar, Susan A; Jolliet, Olivier

2016-09-01

Humans can be exposed to chemicals in consumer products through product use and environmental emissions over the product life cycle. Exposure pathways are often complex, where chemicals can transfer directly from products to humans during use or exchange between various indoor and outdoor compartments until sub-fractions reach humans. To consistently evaluate exposure pathways along product life cycles, a flexible mass balance-based assessment framework is presented structuring multimedia chemical transfers in a matrix of direct inter-compartmental transfer fractions. By matrix inversion, we quantify cumulative multimedia transfer fractions and exposure pathway-specific product intake fractions defined as chemical mass taken in by humans per unit mass of chemical in a product. Combining product intake fractions with chemical mass in the product yields intake estimates for use in life cycle impact assessment and chemical alternatives assessment, or daily intake doses for use in risk-based assessment and high-throughput screening. Two illustrative examples of chemicals used in personal care products and flooring materials demonstrate how this matrix-based framework offers a consistent and efficient way to rapidly compare exposure pathways for adult and child users and for the general population. This framework constitutes a user-friendly approach to develop, compare and interpret multiple human exposure scenarios in a coupled system of near-field ('user' environment), far-field and human intake compartments, and helps understand the contribution of individual pathways to overall human exposure in various product application contexts to inform decisions in different science-policy fields for which exposure quantification is relevant. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

14 CFR 25.1450 - Chemical oxygen generators.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Chemical oxygen generators. 25.1450 Section... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Equipment Miscellaneous Equipment § 25.1450 Chemical oxygen generators. (a) For the purpose of this section, a chemical oxygen generator is defined as a...

14 CFR 25.1450 - Chemical oxygen generators.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Chemical oxygen generators. 25.1450 Section... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Equipment Miscellaneous Equipment § 25.1450 Chemical oxygen generators. (a) For the purpose of this section, a chemical oxygen generator is defined as a...

Application of a framework for extrapolating chemical effects ...

EPA Pesticide Factsheets

Cross-species extrapolation of toxicity data from limited surrogate test organisms to all wildlife with potential of chemical exposure remains a key challenge in ecological risk assessment. A number of factors affect extrapolation, including the chemical exposure, pharmacokinetics, life-stage, and pathway similarities/differences. Here we propose a framework using a tiered approach for species extrapolation that enables a transparent weight-of-evidence driven evaluation of pathway conservation (or lack thereof) in the context of adverse outcome pathways. Adverse outcome pathways describe the linkages from a molecular initiating event, defined as the chemical-biomolecule interaction, through subsequent key events leading to an adverse outcome of regulatory concern (e.g., mortality, reproductive dysfunction). Tier 1 of the extrapolation framework employs in silico evaluations of sequence and structural conservation of molecules (e.g., receptors, enzymes) associated with molecular initiating events or upstream key events. Such evaluations make use of available empirical and sequence data to assess taxonomic relevance. Tier 2 uses in vitro bioassays, such as enzyme inhibition/activation, competitive receptor binding, and transcriptional activation assays to explore functional conservation of pathways across taxa. Finally, Tier 3 provides a comparative analysis of in vivo responses between species utilizing well-established model organisms to assess departure from

Using Graph Indices for the Analysis and Comparison of Chemical Datasets.

PubMed

Fourches, Denis; Tropsha, Alexander

2013-10-01

In cheminformatics, compounds are represented as points in multidimensional space of chemical descriptors. When all pairs of points found within certain distance threshold in the original high dimensional chemistry space are connected by distance-labeled edges, the resulting data structure can be defined as Dataset Graph (DG). We show that, similarly to the conventional description of organic molecules, many graph indices can be computed for DGs as well. We demonstrate that chemical datasets can be effectively characterized and compared by computing simple graph indices such as the average vertex degree or Randic connectivity index. This approach is used to characterize and quantify the similarity between different datasets or subsets of the same dataset (e.g., training, test, and external validation sets used in QSAR modeling). The freely available ADDAGRA program has been implemented to build and visualize DGs. The approach proposed and discussed in this report could be further explored and utilized for different cheminformatics applications such as dataset diversification by acquiring external compounds, dataset processing prior to QSAR modeling, or (dis)similarity modeling of multiple datasets studied in chemical genomics applications. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enzymatic Specific Production and Chemical Functionalization of Phenylpropanone Platform Monomers from Lignin

PubMed Central

Hasegawa, Ryoichi; Kurosawa, Kanako; Maeda, Allyn H.; Koizumi, Toshio; Nishimura, Hiroshi; Okada, Hitomi; Qu, Chen; Saito, Kaori; Watanabe, Takashi; Hatada, Yuji

2016-01-01

Abstract Enzymatic catalysis is an ecofriendly strategy for the production of high‐value low‐molecular‐weight aromatic compounds from lignin. Although well‐definable aromatic monomers have been obtained from synthetic lignin‐model dimers, enzymatic‐selective synthesis of platform monomers from natural lignin has not been accomplished. In this study, we successfully achieved highly specific synthesis of aromatic monomers with a phenylpropane structure directly from natural lignin using a cascade reaction of β‐O‐4‐cleaving bacterial enzymes in one pot. Guaiacylhydroxylpropanone (GHP) and the GHP/syringylhydroxylpropanone (SHP) mixture are exclusive monomers from lignin isolated from softwood (Cryptomeria japonica) and hardwood (Eucalyptus globulus). The intermediate products in the enzymatic reactions show the capacity to accommodate highly heterologous substrates at the substrate‐binding sites of the enzymes. To demonstrate the applicability of GHP as a platform chemical for bio‐based industries, we chemically generate value‐added GHP derivatives for bio‐based polymers. Together with these chemical conversions for the valorization of lignin‐derived phenylpropanone monomers, the specific and enzymatic production of the monomers directly from natural lignin is expected to provide a new stream in “white biotechnology” for sustainable biorefineries. PMID:27878983

The effect of chemical modification on the physico-chemical characteristics of halloysite: FTIR, XRF, and XRD studies

NASA Astrophysics Data System (ADS)

Szczepanik, Beata; Słomkiewicz, Piotr; Garnuszek, Magdalena; Czech, Kamil; Banaś, Dariusz; Kubala-Kukuś, Aldona; Stabrawa, Ilona

2015-03-01

The effect of chemical modification of halloysite from a Polish strip mine "Dunino" on the chemical composition and structure of this clay mineral was studied using infrared spectroscopy (ATR FT-IR), wavelength dispersive X-ray fluorescence (WDXRF), and X-ray powder diffraction (XRPD) methods. The results obtained by the WDXRF technique confirm that the content of silica and alumina was the highest for bleached halloysite samples and the lowest for acid-treated halloysite. A higher content of Fe2O3 in comparison to halloysite samples coming from other countries was observed for raw halloysite samples. XRPD diffraction pattern obtained for raw halloysite confirmed the presence of halloysite, kaolinite, hematite, and calcite minerals in the sample. Bleaching the halloysite removes (or significantly reduces) the content of other minerals present in the raw halloysite. The FT-IR spectra of the studied halloysite samples show in the 3700-3600 cm-1 region well-defined hydroxyl stretching bands characteristic for the kaolin-group minerals and bands associated with the vibrations of the aluminium-silicon skeleton in the 1400-1000 cm-1 region. Modifying halloysite with 4-chloro-aniline causes successive incorporation of amine into the BH sample.

The CHEMDNER corpus of chemicals and drugs and its annotation principles.

PubMed

Krallinger, Martin; Rabal, Obdulia; Leitner, Florian; Vazquez, Miguel; Salgado, David; Lu, Zhiyong; Leaman, Robert; Lu, Yanan; Ji, Donghong; Lowe, Daniel M; Sayle, Roger A; Batista-Navarro, Riza Theresa; Rak, Rafal; Huber, Torsten; Rocktäschel, Tim; Matos, Sérgio; Campos, David; Tang, Buzhou; Xu, Hua; Munkhdalai, Tsendsuren; Ryu, Keun Ho; Ramanan, S V; Nathan, Senthil; Žitnik, Slavko; Bajec, Marko; Weber, Lutz; Irmer, Matthias; Akhondi, Saber A; Kors, Jan A; Xu, Shuo; An, Xin; Sikdar, Utpal Kumar; Ekbal, Asif; Yoshioka, Masaharu; Dieb, Thaer M; Choi, Miji; Verspoor, Karin; Khabsa, Madian; Giles, C Lee; Liu, Hongfang; Ravikumar, Komandur Elayavilli; Lamurias, Andre; Couto, Francisco M; Dai, Hong-Jie; Tsai, Richard Tzong-Han; Ata, Caglar; Can, Tolga; Usié, Anabel; Alves, Rui; Segura-Bedmar, Isabel; Martínez, Paloma; Oyarzabal, Julen; Valencia, Alfonso

2015-01-01

The automatic extraction of chemical information from text requires the recognition of chemical entity mentions as one of its key steps. When developing supervised named entity recognition (NER) systems, the availability of a large, manually annotated text corpus is desirable. Furthermore, large corpora permit the robust evaluation and comparison of different approaches that detect chemicals in documents. We present the CHEMDNER corpus, a collection of 10,000 PubMed abstracts that contain a total of 84,355 chemical entity mentions labeled manually by expert chemistry literature curators, following annotation guidelines specifically defined for this task. The abstracts of the CHEMDNER corpus were selected to be representative for all major chemical disciplines. Each of the chemical entity mentions was manually labeled according to its structure-associated chemical entity mention (SACEM) class: abbreviation, family, formula, identifier, multiple, systematic and trivial. The difficulty and consistency of tagging chemicals in text was measured using an agreement study between annotators, obtaining a percentage agreement of 91. For a subset of the CHEMDNER corpus (the test set of 3,000 abstracts) we provide not only the Gold Standard manual annotations, but also mentions automatically detected by the 26 teams that participated in the BioCreative IV CHEMDNER chemical mention recognition task. In addition, we release the CHEMDNER silver standard corpus of automatically extracted mentions from 17,000 randomly selected PubMed abstracts. A version of the CHEMDNER corpus in the BioC format has been generated as well. We propose a standard for required minimum information about entity annotations for the construction of domain specific corpora on chemical and drug entities. The CHEMDNER corpus and annotation guidelines are available at: http://www.biocreative.org/resources/biocreative-iv/chemdner-corpus/.

The CHEMDNER corpus of chemicals and drugs and its annotation principles

PubMed Central

2015-01-01

The automatic extraction of chemical information from text requires the recognition of chemical entity mentions as one of its key steps. When developing supervised named entity recognition (NER) systems, the availability of a large, manually annotated text corpus is desirable. Furthermore, large corpora permit the robust evaluation and comparison of different approaches that detect chemicals in documents. We present the CHEMDNER corpus, a collection of 10,000 PubMed abstracts that contain a total of 84,355 chemical entity mentions labeled manually by expert chemistry literature curators, following annotation guidelines specifically defined for this task. The abstracts of the CHEMDNER corpus were selected to be representative for all major chemical disciplines. Each of the chemical entity mentions was manually labeled according to its structure-associated chemical entity mention (SACEM) class: abbreviation, family, formula, identifier, multiple, systematic and trivial. The difficulty and consistency of tagging chemicals in text was measured using an agreement study between annotators, obtaining a percentage agreement of 91. For a subset of the CHEMDNER corpus (the test set of 3,000 abstracts) we provide not only the Gold Standard manual annotations, but also mentions automatically detected by the 26 teams that participated in the BioCreative IV CHEMDNER chemical mention recognition task. In addition, we release the CHEMDNER silver standard corpus of automatically extracted mentions from 17,000 randomly selected PubMed abstracts. A version of the CHEMDNER corpus in the BioC format has been generated as well. We propose a standard for required minimum information about entity annotations for the construction of domain specific corpora on chemical and drug entities. The CHEMDNER corpus and annotation guidelines are available at: http://www.biocreative.org/resources/biocreative-iv/chemdner-corpus/ PMID:25810773

An experimental and numerical study of diffusion flames in cross-flow and quiescent environment at smoke point condition

NASA Astrophysics Data System (ADS)

Goh, Sien Fong

An experimental and numerical study of a turbulent smoke point diffusion flame in a quiescent and cross-flow condition was performed. The fuel mass flow rate of a turbulent smoke point flame was determined at a quiescent condition and in cross-flow with velocity ranging from 2 to 4 m/s. This fuel mass flow rate is defined as the Critical Fuel Mass Flow Rate (CFMFR). At a fuel mass flow rate below the CFMFR the flame produces smoke. In the dilution study, an amount of inert gas (nitrogen) was added to the fuel stream to achieve the smoke point condition for ten different fractions of CFMFR. From this dilution study, three regions were defined, the chemically-dominated region, transition region, and momentum-dominated region. The first objective of this study was to determine the factors behind the distinction of these three regions. The second objective was to understand the effect of cross-flow velocity on the smoke point flame structure. The flame temperature, radiation, geometrical dimension of flame, velocity, and global emissions and in-flame species concentration were measured. The third objective was to study a numerical model that can simulate the turbulent smoke point flame structure. The dilution study showed that the flames in quiescent condition and in the 3.5 and 4 m/s cross-flow condition had the chemically-dominated region at 5% to 20% CFMFR, the transition region at 20% to 40% CFMFR, and the momentum-dominated region at 40% to 100% CFMFR. On the other hand, the flame in cross-flow of 2 to 3 m/s showed the chemically-dominated region at 5% to 10% CFMFR, the transition region at 10% to 30% CFMFR, and the momentum-dominated region at 30% to 100% CFMFR. The chemically-dominated flame had a sharp dual-peak structure for the flame temperature, CO2 and NO concentration profiles at 25% and 50% flame length. However, the momentum-dominated region flame exhibited a dual peak structure only at 25% flame length. The decrease of flow rate from 30% to 10% CFMFR showed an increase of flame length. The LII study showed that the soot concentration increased with the decrease of the turbulence intensity in the momentum dominated region (tested on the 100% and 60% CFMFR). The cross-flow velocity had a non-monotonic effects on the flame. The evidences could be observed from the flame length and the soot concentration results. The flame length showed a decrease when the cross-flow velocity increased from 2 to 3 m/s. The numerical model was fairly adequate in qualitatively predicting a smoke point turbulent diffusion flame structure in a cross-flow and quiescent condition. The model failed in the prediction of a laminar flame. The model showed a good agreement between experimental and numerical results for O 2 concentration and flame temperature. (Abstract shortened by UMI.)

COBRA: A Computational Brewing Application for Predicting the Molecular Composition of Organic Aerosols

PubMed Central

Fooshee, David R.; Nguyen, Tran B.; Nizkorodov, Sergey A.; Laskin, Julia; Laskin, Alexander; Baldi, Pierre

2012-01-01

Atmospheric organic aerosols (OA) represent a significant fraction of airborne particulate matter and can impact climate, visibility, and human health. These mixtures are difficult to characterize experimentally due to their complex and dynamic chemical composition. We introduce a novel Computational Brewing Application (COBRA) and apply it to modeling oligomerization chemistry stemming from condensation and addition reactions in OA formed by photooxidation of isoprene. COBRA uses two lists as input: a list of chemical structures comprising the molecular starting pool, and a list of rules defining potential reactions between molecules. Reactions are performed iteratively, with products of all previous iterations serving as reactants for the next. The simulation generated thousands of structures in the mass range of 120–500 Da, and correctly predicted ~70% of the individual OA constituents observed by high-resolution mass spectrometry. Select predicted structures were confirmed with tandem mass spectrometry. Esterification was shown to play the most significant role in oligomer formation, with hemiacetal formation less important, and aldol condensation insignificant. COBRA is not limited to atmospheric aerosol chemistry; it should be applicable to the prediction of reaction products in other complex mixtures for which reasonable reaction mechanisms and seed molecules can be supplied by experimental or theoretical methods. PMID:22568707

Advanced fabrication of Si nanowire FET structures by means of a parallel approach.

PubMed

Li, J; Pud, S; Mayer, D; Vitusevich, S

2014-07-11

In this paper we present fabricated Si nanowires (NWs) of different dimensions with enhanced electrical characteristics. The parallel fabrication process is based on nanoimprint lithography using high-quality molds, which facilitates the realization of 50 nm-wide NW field-effect transistors (FETs). The imprint molds were fabricated by using a wet chemical anisotropic etching process. The wet chemical etch results in well-defined vertical sidewalls with edge roughness (3σ) as small as 2 nm, which is about four times better compared with the roughness usually obtained for reactive-ion etching molds. The quality of the mold was studied using atomic force microscopy and scanning electron microscopy image data. The use of the high-quality mold leads to almost 100% yield during fabrication of Si NW FETs as well as to an exceptional quality of the surfaces of the devices produced. To characterize the Si NW FETs, we used noise spectroscopy as a powerful method for evaluating device performance and the reliability of structures with nanoscale dimensions. The Hooge parameter of fabricated FET structures exhibits an average value of 1.6 × 10(-3). This value reflects the high quality of Si NW FETs fabricated by means of a parallel approach that uses a nanoimprint mold and cost-efficient technology.

Marine Pharmacology in 2005-6: Antitumour and Cytotoxic Compounds

PubMed Central

Mayer, Alejandro M.S.; Gustafson, Kirk R.

2009-01-01

During 2005 and 2006, marine pharmacology research directed towards the discovery and development of novel antitumour agents was reported in 171 peer-reviewed articles. The purpose of this article is to present a structured review of the antitumour and cytotoxic properties of 136 marine natural products, many of which are novel compounds that belong to diverse structural classes, including polyketides, terpenes, steroids, and peptides. The organisms yielding these bioactive marine compounds included invertebrate animals, algae, fungi and bacteria. Antitumour pharmacological studies were conducted with 42 structurally defined marine natural products in a number of experimental and clinical models which further defined their mechanisms of action. Particularly potent in vitro cytotoxicity data generated with murine and human tumour cell lines was reported for 94 novel marine chemicals with as yet undetermined mechanisms of action. Noteworthy is the fact that marine anticancer research was sustained by a global collaborative effort, involving researchers from Australia, Belgium, Benin, Brazil, Canada, China, Egypt, France, Germany, India, Indonesia, Italy, Japan, Mexico, the Netherlands, New Zealand, Panama, the Philippines, Slovenia, South Korea, Spain, Sweden, Taiwan, Thailand, United Kingdom, and the United States. Finally, this 2005-6 overview of the marine pharmacology literature highlights the fact that the discovery of novel marine antitumour agents continued at the same active pace as during 1998-2004. PMID:18701274

Scientific evaluation of traditional Chinese medicine under DSHEA: a conundrum. Dietary Supplement Health and Education Act.

PubMed

Chang, J

1999-04-01

In the United States, traditional Chinese medicines (TCM) are currently sold as dietary supplements, as defined by The Dietary Supplement Health and Education Act (DSHEA). This legislation is unique to the United States and while "structure and function" claims are allowable under DSHEA, disease claims are not. The narrow definition, however, poses a challenge to designing appropriate clinical studies that can provide data for "structure and function" claim substantiation. The process of melding Chinese herbal medicines into the dietary supplement category is complex and there is a need to define a clinical trial paradigm carefully that addresses "structure and function claims" without sacrificing scientific rigor. It is frequently not recognized that TCM favors an amalgamation of several herbs to generate the putative clinical effect. Because of this historical multiherb approach, the reliance on retrospective data to support the potential health benefits of an herb extract has severe limitations. Notwithstanding the immense value of identifying the pharmacological activity of a TCM herb to a chemical suitable for pharmaceutical development, another approach to safe and efficacious herbal products is to develop a standardized herbal extract. This article highlights issues related to the latter approach and will discuss a research-based strategy that may be suitable for validating, in part, the putative health benefits of TCM.

Tuning the Magnetic and Electronic Properties of Iron(x )Silicon(1-x) Thin Films for Spintronics

NASA Astrophysics Data System (ADS)

Karel, Julie Elizabeth

This dissertation investigated the magnetic and electronic properties of a potentially better alternative: off-stoichimetry, bcc-like FexSi 1-x thin films (0.43800 K) and theoretically predicted high spin polarization (100%). However, little work has been done on off-stoichiometry FexSi1-x thin films (0.43

SCREENING INFORMATION DATA SETS (SIDS)

EPA Science Inventory

The Organization for Economic Cooperation and Development (OECD) is jointly investigating international high production volume (HPV) chemicals. These HPV chemicals are defined as chemicals produced in one OECD Member country in quantities above10,000 metric tons (22 million lbs) ...

ENVIRONMENTAL ENGINEERING AND ENDOCRINE DISRUPTING CHEMICALS

EPA Science Inventory

Endocrine disruptors are a class of chemicals of growing interest to the environmental community. USEPA's Risk Assessment Forum defined an endocrine disrupting chemical (EDC) as "an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elim...

Design and Control of Chemical Grouting : Volume 3 - Engineering Practice

DOT National Transportation Integrated Search

1983-04-01

Recent improvements in the engineering practice of chemical grouting have provided increased confidence in this method of ground modification. Designers can significantly improve the success of chemical grouting by defining their grouting program obj...

40 CFR 712.5 - Method of identification of substances for reporting purposes.

Code of Federal Regulations, 2010 CFR

2010-07-01

... substance in practice. (1) The chemical substance in aqueous solution. (2) The chemical substance containing... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT CHEMICAL INFORMATION RULES General Provisions § 712.5 Method of... otherwise required, respondents must report only about quantities of a chemical that is defined as a...

40 CFR 712.5 - Method of identification of substances for reporting purposes.

Code of Federal Regulations, 2011 CFR

2011-07-01

... substance in practice. (1) The chemical substance in aqueous solution. (2) The chemical substance containing... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT CHEMICAL INFORMATION RULES General Provisions § 712.5 Method of... otherwise required, respondents must report only about quantities of a chemical that is defined as a...

Cumulative effects of anti-androgenic chemical mixtures and their relevance to human health risk assessment

EPA Science Inventory

Kembra L. Howdeshell and L. Earl Gray, Jr.Toxicological studies of defined chemical mixtures assist human health risk assessment by characterizing the joint action of chemicals. This presentation will review the effects of anti-androgenic chemical mixtures on reproductive tract d...

40 CFR 700.43 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the PMN for the intermediate identifies the final product and describes the chemical reactions leading... chemical substance (each being assigned a separate PMN number by EPA) as a result of a prenotice agreement... chapter. Final product means a new chemical substance (as “new chemical substance” is defined in § 720.3...

40 CFR 700.43 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the PMN for the intermediate identifies the final product and describes the chemical reactions leading... chemical substance (each being assigned a separate PMN number by EPA) as a result of a prenotice agreement... chapter. Final product means a new chemical substance (as “new chemical substance” is defined in § 720.3...

40 CFR 700.43 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the PMN for the intermediate identifies the final product and describes the chemical reactions leading... chemical substance (each being assigned a separate PMN number by EPA) as a result of a prenotice agreement... chapter. Final product means a new chemical substance (as “new chemical substance” is defined in § 720.3...

40 CFR 700.43 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the PMN for the intermediate identifies the final product and describes the chemical reactions leading... chemical substance (each being assigned a separate PMN number by EPA) as a result of a prenotice agreement... chapter. Final product means a new chemical substance (as “new chemical substance” is defined in § 720.3...

40 CFR 700.43 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the PMN for the intermediate identifies the final product and describes the chemical reactions leading... chemical substance (each being assigned a separate PMN number by EPA) as a result of a prenotice agreement... chapter. Final product means a new chemical substance (as “new chemical substance” is defined in § 720.3...

3D freeform printing of silk fibroin.

PubMed

Rodriguez, Maria J; Dixon, Thomas A; Cohen, Eliad; Huang, Wenwen; Omenetto, Fiorenzo G; Kaplan, David L

2018-04-15

Freeform fabrication has emerged as a key direction in printing biologically-relevant materials and structures. With this emerging technology, complex structures with microscale resolution can be created in arbitrary geometries and without the limitations found in traditional bottom-up or top-down additive manufacturing methods. Recent advances in freeform printing have used the physical properties of microparticle-based granular gels as a medium for the submerged extrusion of bioinks. However, most of these techniques require post-processing or crosslinking for the removal of the printed structures (Miller et al., 2015; Jin et al., 2016) [1,2]. In this communication, we introduce a novel method for the one-step gelation of silk fibroin within a suspension of synthetic nanoclay (Laponite) and polyethylene glycol (PEG). Silk fibroin has been used as a biopolymer for bioprinting in several contexts, but chemical or enzymatic additives or bulking agents are needed to stabilize 3D structures. Our method requires no post-processing of printed structures and allows for in situ physical crosslinking of pure aqueous silk fibroin into arbitrary geometries produced through freeform 3D printing. 3D bioprinting has emerged as a technology that can produce biologically relevant structures in defined geometries with microscale resolution. Techniques for fabrication of free-standing structures by printing into granular gel media has been demonstrated previously, however, these methods require crosslinking agents and post-processing steps on printed structures. Our method utilizes one-step gelation of silk fibroin within a suspension of synthetic nanoclay (Laponite), with no need for additional crosslinking compounds or post processing of the material. This new method allows for in situ physical crosslinking of pure aqueous silk fibroin into defined geometries produced through freeform 3D printing. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Nanometer-Scale Chemistry of a Calcite Biomineralization Template: Implications for Skeletal Composition and Nucleation.

PubMed

Branson, Oscar; Bonnin, Elisa A; Perea, Daniel E; Spero, Howard J; Zhu, Zihua; Winters, Maria; Hönisch, Bärbel; Russell, Ann D; Fehrenbacher, Jennifer S; Gagnon, Alexander C

2016-11-15

Plankton, corals, and other organisms produce calcium carbonate skeletons that are integral to their survival, form a key component of the global carbon cycle, and record an archive of past oceanographic conditions in their geochemistry. A key aspect of the formation of these biominerals is the interaction between organic templating structures and mineral precipitation processes. Laboratory-based studies have shown that these atomic-scale processes can profoundly influence the architecture and composition of minerals, but their importance in calcifying organisms is poorly understood because it is difficult to measure the chemistry of in vivo biomineral interfaces at spatially relevant scales. Understanding the role of templates in biomineral nucleation, and their importance in skeletal geochemistry requires an integrated, multiscale approach, which can place atom-scale observations of organic-mineral interfaces within a broader structural and geochemical context. Here we map the chemistry of an embedded organic template structure within a carbonate skeleton of the foraminifera Orbulina universa using both atom probe tomography (APT), a 3D chemical imaging technique with Ångström-level spatial resolution, and time-of-flight secondary ionization mass spectrometry (ToF-SIMS), a 2D chemical imaging technique with submicron resolution. We quantitatively link these observations, revealing that the organic template in O. universa is uniquely enriched in both Na and Mg, and contributes to intraskeletal chemical heterogeneity. Our APT analyses reveal the cation composition of the organic surface, offering evidence to suggest that cations other than Ca 2+ , previously considered passive spectator ions in biomineral templating, may be important in defining the energetics of carbonate nucleation on organic templates.

Photon antibunching from a single lithographically defined InGaAs/GaAs quantum dot.

PubMed

Verma, V B; Stevens, Martin J; Silverman, K L; Dias, N L; Garg, A; Coleman, J J; Mirin, R P

2011-02-28

We demonstrate photon antibunching from a single lithographically defined quantum dot fabricated by electron beam lithography, wet chemical etching, and overgrowth of the barrier layers by metalorganic chemical vapor deposition. Measurement of the second-order autocorrelation function indicates g(2)(0)=0.395±0.030, below the 0.5 limit necessary for classification as a single photon source.

Correlating the vibrational spectra of structurally related molecules: A spectroscopic measure of similarity.

PubMed

Tao, Yunwen; Zou, Wenli; Cremer, Dieter; Kraka, Elfi

2018-03-05

Using catastrophe theory and the concept of a mutation path, an algorithm is developed that leads to the direct correlation of the normal vibrational modes of two structurally related molecules. The mutation path is defined by weighted incremental changes in mass and geometry of the molecules in question, which are successively applied to mutate a molecule into a structurally related molecule and thus continuously converting their normal vibrational spectra from one into the other. Correlation diagrams are generated that accurately relate the normal vibrational modes to each other by utilizing mode-mode overlap criteria and resolving allowed and avoided crossings of vibrational eigenstates. The limitations of normal mode correlation, however, foster the correlation of local vibrational modes, which offer a novel vibrational measure of similarity. It will be shown how this will open new avenues for chemical studies. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Unravelling the structural control of mississippi valley-type deposits and prospects in carbonate sequences of the Western Canada Sedimentary Basin

USGS Publications Warehouse

Pana, D.

2006-01-01

Re-examination of selected MVT outcrops and cores in the Interior Plains and Rocky Moun-tains of Alberta, corroborated with previous paragenetic, isotopic and structural data, suggests Laramide structural channelling of dolomitizing and mineralizing fluids into strained carbonate rocks. At Pine Point, extensional faults underlying the trends of MVT ore bodies and brittle faults overprinting the Great Slave Lake Shear Zone define apinnate fault geometry and appear to be kinematically linked. Chemical and isotopic characteristics of MVT parental fluids are consistent with seawater and brine convection within fault-confined verticalaquifers, strong water-basement rock interaction, metalleaching from the basement, and focused release of hydrothermal fluids within linear zones of strained carbonate caprocks. Zones of recurrent strain in the basement and a cap of carbonate strata constitute the critical criteria for MVTexploration target selection in the WCSB.

Structural Design Principle of Small-Molecule Organic Semiconductors for Metal-Free, Visible-Light-Promoted Photocatalysis.

PubMed

Wang, Lei; Huang, Wei; Li, Run; Gehrig, Dominik; Blom, Paul W M; Landfester, Katharina; Zhang, Kai A I

2016-08-08

Herein, we report on the structural design principle of small-molecule organic semiconductors as metal-free, pure organic and visible light-active photocatalysts. Two series of electron-donor and acceptor-type organic semiconductor molecules were synthesized to meet crucial requirements, such as 1) absorption range in the visible region, 2) sufficient photoredox potential, and 3) long lifetime of photogenerated excitons. The photocatalytic activity was demonstrated in the intermolecular C-H functionalization of electron-rich heteroaromates with malonate derivatives. A mechanistic study of the light-induced electron transport between the organic photocatalyst, substrate, and the sacrificial agent are described. With their tunable absorption range and defined energy-band structure, the small-molecule organic semiconductors could offer a new class of metal-free and visible light-active photocatalysts for chemical reactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

On the structure of contact binaries. I - The contact discontinuity

NASA Technical Reports Server (NTRS)

Shu, F. H.; Lubow, S. H.; Anderson, L.

1976-01-01

The problem of the interior structure of contact binaries is reviewed, and a simple resolution of the difficulties which plague the theory is suggested. It is proposed that contact binaries contain a contact discontinuity between the lower surface of the common envelope and the Roche lobe of the cooler star. This discontinuity is maintained against thermal diffusion by fluid flow, and the transition layer is thin to the extent that the dynamical time scale is short in comparison with the thermal time scale. The idealization that the transition layer has infinitesimal thickness allows a simple formulation of the structure equations which are closed by appropriate jump conditions across the discontinuity. The further imposition of the standard boundary conditions suffices to define a unique model for the system once the chemical composition, the masses of the two stars, and the orbital separation are specified.

Information generation and processing systems that regulate periodontal structure and function.

PubMed

Bartold, P Mark; McCulloch, Christopher A

2013-10-01

The periodontium is a very dynamic organ that responds rapidly to mechanical and chemical stimuli. It is very complex in that it is composed of two hard tissues (cementum and bone) and two soft connective tissues (periodontal ligament and gingiva). Together these tissues are defined by the molecules expressed by the resident periodontal cells in each compartment and this determines not only the structure and function of the periodontium but also how it responds to infection and inflammation. The biological activity of these molecules is tightly regulated in time and space to preserve tissue homeostasis, influence inflammatory responses and participate in tissue regeneration. In this issue of Periodontology 2000 we explore new experimental approaches and data sets which help to understand the molecules and cells that regulate tissue form and structure in health, disease and regeneration. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Designing cooperatively folded abiotic uni- and multimolecular helix bundles

NASA Astrophysics Data System (ADS)

de, Soumen; Chi, Bo; Granier, Thierry; Qi, Ting; Maurizot, Victor; Huc, Ivan

2018-01-01

Abiotic foldamers, that is foldamers that have backbones chemically remote from peptidic and nucleotidic skeletons, may give access to shapes and functions different to those of peptides and nucleotides. However, design methodologies towards abiotic tertiary and quaternary structures are yet to be developed. Here we report rationally designed interactional patterns to guide the folding and assembly of abiotic helix bundles. Computational design facilitated the introduction of hydrogen-bonding functionalities at defined locations on the aromatic amide backbones that promote cooperative folding into helix-turn-helix motifs in organic solvents. The hydrogen-bond-directed aggregation of helices not linked by a turn unit produced several thermodynamically and kinetically stable homochiral dimeric and trimeric bundles with structures that are distinct from the designed helix-turn-helix. Relative helix orientation within the bundles may be changed from parallel to tilted on subtle solvent variations. Altogether, these results prefigure the richness and uniqueness of abiotic tertiary structure behaviour.

Microwave plasma chemical synthesis of nanocrystalline carbon film structures and study their properties

NASA Astrophysics Data System (ADS)

Bushuev, N.; Yafarov, R.; Timoshenkov, V.; Orlov, S.; Starykh, D.

2015-08-01

The self-organization effect of diamond nanocrystals in polymer-graphite and carbon films is detected. The carbon materials deposition was carried from ethanol vapors out at low pressure using a highly non-equilibrium microwave plasma. Deposition processes of carbon film structures (diamond, graphite, graphene) is defined. Deposition processes of nanocrystalline structures containing diamond and graphite phases in different volume ratios is identified. The solid film was obtained under different conditions of microwave plasma chemical synthesis. We investigated the electrical properties of the nanocrystalline carbon films and identified it's from various factors. Influence of diamond-graphite film deposition mode in non-equilibrium microwave plasma at low pressure on emission characteristics was established. This effect is justified using the cluster model of the structure of amorphous carbon. It was shown that the reduction of bound hydrogen in carbon structures leads to a decrease in the threshold electric field of emission from 20-30 V/m to 5 V/m. Reducing the operating voltage field emission can improve mechanical stability of the synthesized film diamond-graphite emitters. Current density emission at least 20 A/cm2 was obtained. Nanocrystalline carbon film materials can be used to create a variety of functional elements in micro- and nanoelectronics and photonics such as cold electron source for emission in vacuum devices, photonic devices, cathodoluminescent flat display, highly efficient white light sources. The obtained graphene carbon net structure (with a net size about 6 μm) may be used for the manufacture of large-area transparent electrode for solar cells and cathodoluminescent light sources

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.

Conformational Plasticity of the Influenza A M2 Transmembrane Helix in Lipid Bilayers Under Varying pH, Drug Binding and Membrane Thickness

PubMed Central

Hu, Fanghao; Luo, Wenbin; Cady, Sarah D.; Hong, Mei

2010-01-01

Membrane proteins change their conformations to respond to environmental cues, thus conformational plasticity is important for function. The influenza A M2 protein forms an acid-activated proton channel important for the virus lifecycle. Here we have used solid-state NMR spectroscopy to examine the conformational plasticity of membrane-bound transmembrane domain of M2 (M2TM). 13C and 15N chemical shifts indicate coupled conformational changes of several pore-facing residues due to changes in bilayer thickness, drug binding and pH. The structural changes are attributed to the formation of a well-defined helical kink at G34 in the drug-bound state and in thick lipid bilayers, non-ideal backbone conformation of the secondary-gate residue V27 in the presence of drug, and non-ideal conformation of the proton-sensing residue H37 at high pH. The chemical shifts constrained the (ϕ, ψ) torsion angles for three basis states, the equilibrium among which explains the multiple resonances per site in the NMR spectra under different combinations of bilayer thickness, drug binding and pH conditions. Thus, conformational plasticity is important for the proton conduction and inhibition of M2TM. The study illustrates the utility of NMR chemical shifts for probing the structural plasticity and folding of membrane proteins. PMID:20883664

Surface reactions of ethanol over UO 2(100) thin film

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

S. D. Senanayake; Mudiyanselage, K.; Burrell, A. K.

2015-10-08

The study of the reactions of oxygenates on well-defined oxide surfaces is important for the fundamental understanding of heterogeneous chemical pathways that are influenced by atomic geometry, electronic structure, and chemical composition. In this work, an ordered uranium oxide thin film surface terminated in the (100) orientation is prepared on a LaAlO 3 substrate and studied for its reactivity with a C-2 oxygenate, ethanol (CH 3CH 2OH). With the use of synchrotron X-ray photoelectron spectroscopy (XPS), we have probed the adsorption and desorption processes observed in the valence band, C 1s, O 1s, and U 4f to investigate the bondingmore » mode, surface composition, electronic structure, and probable chemical changes to the stoichiometric-UO 2(100) [smooth-UO 2(100)] and Ar +-sputtered UO 2(100) [rough-UO 2(100)] surfaces. Unlike UO 2(111) single crystal and UO 2 thin film, Ar-ion-sputtering of this UO 2(100) did not result in noticeable reduction of U cations. Upon ethanol adsorption (saturation occurred at 0.5 ML), only the ethoxy (CH 3CH 2O –) species is formed on smooth-UO 2(100) whereas initially formed ethoxy species are partially oxidized to surface acetate (CH3COO–) on the Ar +-sputtered UO 2(100) surface. Furthermore, all ethoxy and acetate species are removed from the surface between 600 and 700 K.« less

[Chemical and physical characteristics and toxicology of man-made mineral fibers].

PubMed

Foà, V; Basilico, S

1999-01-01

The evidence for the adverse health effects following exposure to asbestos (i.e. fibrogenic and carcinogenic effect) has prompted widespread removal of asbestos-containing materials and led to banning of asbestos internationally (in Italy, DPR 257/1992), resulting in the increased use of substitutes composed of both naturally occurring and synthetic materials, including man made mineral fibres (MMMFs) and man made organic fibres (MMOF). MMMFs represent a family of synthetic, inorganic vitreous substances derived primarily from glass, rock, slag, or clay. MMMFs are further divided into two categories: 1) man made vitreous fibres (MMVFs), further divided as follows: a) fibrous glass, including mainly continuous filament, special purpose fibres; and microfibres. The materials are typically composed of oxides of silicon, calcium, sodium, potassium, aluminum, and boron. b) Mineral wool, including glass wool, rock wool (derived from magma rock) and slag wool (made from molten slag produced in metallurgical processes such as the production of iron, steel, or copper). The main components of rock wool and slag wool are oxides of silicon, calcium, magnesium, aluminum, and iron. 2) Refractory/ceramic fibres, amorphous or partially crystalline materials made from kaolin clay or oxides of aluminum, silicon or other metal oxides (i.e. oxides of zirconium and yttrium). Less commonly, refractory fibres are also made from non-oxide refractory materials such as silicon carbide, silicon nitride, or boron nitride. Industrial production of MMVFs began in the second half of the 19th century, while ceramic fibres production began more recently, in the early 1970s. Major uses of MMMFs include thermal, acoustic and aerospace insulation, fire proofing, reinforcing material in plastics, cement and textile, optic fibres, air and liquid filtration, friction products, refractory coatings. Serious questions have been raised about health implications of MMMFs. Suspicion about the possible occurrence of adverse effects following exposure to MMMFs arises mainly from some similarities of MMMFs with asbestos (fibrous aspects, inhalability, chemical composition, free radical formation). The fibre characteristics that have been identified as crucial in influencing the pathogenesis of fibre-related adverse respiratory effects can be mainly divided into two groups: fibre dimension, and chemical composition and structure. Fibre dimension plays a determining role in conditioning penetration in the lung. In a broad sense, the term "respirable" means "capable of being carried by breath into the respiratory system". For regulatory purposes, "respirable fibres" (i.e. RFP) are defined in most countries following WHO criteria: length > 5 microns, diameter < 3 microns, length/diameter > 3. MMMFs are generally produced as fibres of diameter higher than asbestos, and too large in diameter to be respirable. Moreover, due to the production process, they are structurally amorphous. Since MMMFs have no crystalline domains, they also have no clearly defined structural faults and they fracture transversely, and randomly. Fragments that are too large to be taken up by macrophages can be resolved in the lung by a leaching--or dissolution--process which leads to a progressive reduction of particle length. In contrast, when abraded, asbestos tends to split longitudinally into new, fine, straight fibres: these fibrils are of much smaller diameter, more respirable, and consequently more hazardous than parent fibres. Fibre chemical composition plays a determining role in conditioning the higher or lower biological activity, durability, biopersistence, and biodegradability. The term "biological activity" means reactivity or ability to interact (possibly due to formation of active oxygen species, identified as a crucial step in the mechanism of action) with biological structures and tissues. Fibre "durability" is strictly related to its solubility. It can be defined as the ability to resist

Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.

PubMed

Matthews, Edwin J; Kruhlak, Naomi L; Weaver, James L; Benz, R Daniel; Contrera, Joseph F

2004-12-01

The FDA's Spontaneous Reporting System (SRS) database contains over 1.5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects. We have linked the trade names of the drugs to 1861 generic names and retrieved molecular structures for each chemical to obtain a set of 1515 organic chemicals that are suitable for modeling with commercially available QSAR software packages. ADR report data for 631 of these compounds were extracted and pooled for the first five years that each drug was marketed. Patient exposure was estimated during this period using pharmaceutical shipping units obtained from IMS Health. Significant drug effects were identified using a Reporting Index (RI), where RI = (# ADR reports / # shipping units) x 1,000,000. MCASE/MC4PC software was used to identify the optimal conditions for defining a significant adverse effect finding. Results suggest that a significant effect in our database is characterized by > or = 4 ADR reports and > or = 20,000 shipping units during five years of marketing, and an RI > or = 4.0. Furthermore, for a test chemical to be evaluated as active it must contain a statistically significant molecular structural alert, called a decision alert, in two or more toxicologically related endpoints. We also report the use of a composite module, which pools observations from two or more toxicologically related COSTAR term endpoints to provide signal enhancement for detecting adverse effects.

New approach for producing chemical templates over large area by Molecular Transfer Printing

NASA Astrophysics Data System (ADS)

Inoue, Takejiro; Janes, Dustin; Ren, Jiaxing; Willson, Grant; Ellison, Christopher; Nealey, Paul

2014-03-01

Fabrication of well-defined chemically patterned surfaces is crucially important to the development of next generation microprocessors, hard disk memory devices, photonic/plasmonic devices, separation membranes, and biological microarrays. One promising patterning method in these fields is Molecular Transfer Printing (MTP), which replicates chemical patterns with feature dimensions of the order of 10nm utilizing a master template defined by the microphase separated domains of a block copolymer thin film. The total transfer printing area achievable by MTP has so far been limited by the contact area between two rigid substrates. Therefore, strategies to make conformal contact between substrates could be practically useful because a single lithographically-defined starting pattern could be used to fabricate many replicates by a low-cost process. Here we show a new approach that utilizes a chemically deposited SiN layer and a liquid conformal layer to enable transfer printing of chemical patterns upon thermal annealing over large, continuous areas. We anticipate that our process could be integrated into Step and Flash Imprint Lithography (SFIL) tools to achieve conformal layer thicknesses thin and uniform enough to permit pattern transfer through a dry-etch protocol.

Fabrication of Gold-coated 3-D Woodpile Structures for Mid-IR Thermal Emitters

NASA Astrophysics Data System (ADS)

Li, Shengkai; Moridani, Amir; Kothari, Rohit; Lee, Jae-Hwang; Watkins, James

3-D metallic woodpile nanostructures possess enhancements in thermal radiation that are both wavelength and polarization specific and are promising for thermal-optical devices for various applications including thermal photovoltaics, self-cooling devices, and chemical and bio-sensors. However, current fabrication techniques for such structures are limited by slow speed, small area capability, the need for expensive facilities and, in general, are not suitable for high-throughput mass production. Here we demonstrate a new strategy for the fabrication of 3D metallic woodpile structures. Well-defined TiO2 woodpile structures were fabricated using a layer-by-layer nanoimprint method using TiO2 nanoparticle ink dispersions. The TiO2 woodpile was then coated with a high purity, conformal gold film via reactive deposition in supercritical carbon dioxide. The final gold-coated woodpile structures exhibit strong spectral and polarization specific thermal emission enhancements. The fabrication method demonstrated here is promising for high-throughput, low-cost preparation of 3D metallic woodpile structures and other 3D nanostructures. Center for Hierarchical Manufacturing, NSF.

The fluid mechanics of thrombus formation

NASA Technical Reports Server (NTRS)

1972-01-01

Experimental data are presented for the growth of thrombi (blood clots) in a stagnation point flow of fresh blood. Thrombus shape, size and structure are shown to depend on local flow conditions. The evolution of a thrombus is described in terms of a physical model that includes platelet diffusion, a platelet aggregation mechanism, and diffusion and convection of the chemical species responsible for aggregation. Diffusion-controlled and convection-controlled regimes are defined by flow parameters and thrombus location, and the characteristic growth pattern in each regime is explained. Quantitative comparisons with an approximate theoretical model are presented, and a more general model is formulated.

Factors Affecting Exocellular Polysaccharide Production by Lactobacillus delbrueckii subsp. bulgaricus Grown in a Chemically Defined Medium†

PubMed Central

Petry, Sandrine; Furlan, Sylviane; Crepeau, Marie-Jeanne; Cerning, Jutta; Desmazeaud, Michel

2000-01-01

We developed a chemically defined medium (CDM) containing lactose or glucose as the carbon source that supports growth and exopolysaccharide (EPS) production of two strains of Lactobacillus delbrueckii subsp. bulgaricus. The factors found to affect EPS production in this medium were oxygen, pH, temperature, and medium constituents, such as orotic acid and the carbon source. EPS production was greatest during the stationary phase. Composition analysis of EPS isolated at different growth phases and produced under different fermentation conditions (varying carbon source or pH) revealed that the component sugars were the same. The EPS from strain L. delbrueckii subsp. bulgaricus CNRZ 1187 contained galactose and glucose, and that of strain L. delbrueckii subsp. bulgaricus CNRZ 416 contained galactose, glucose, and rhamnose. However, the relative proportions of the individual monosaccharides differed, suggesting that repeating unit structures can vary according to specific medium alterations. Under pH-controlled fermentation conditions, L. delbrueckii subsp. bulgaricus strains produced as much EPS in the CDM as in milk. Furthermore, the relative proportions of individual monosaccharides of EPS produced in pH-controlled CDM or in milk were very similar. The CDM we developed may be a useful model and an alternative to milk in studies of EPS production. PMID:10919802

Composition, Chemistry, and Climate of the Atmosphere. 2: Mean properties of the atmosphere

NASA Technical Reports Server (NTRS)

Singh, Hanwant B. (Editor); Salstein, David A.

1994-01-01

The atmosphere can be defined as the relatively thin gaseous envelope surrounding the entire planet Earth. It possesses a number of properties related to its physical state and chemical composition, and it undergoes a variety of internal processes and external interactions that can either maintain or alter these properties. Whereas descriptions of the atmosphere's chemical properties form much of the remaining chapters of this book, the present chapter will highlight the atmosphere's gases, and these define its temperature structure. In contrast, the larger-scale motions comprise the winds, the global organization of which is often referred to as the general circulation. The framework of the dynamical and thermodynamical laws, including the three principles of conversation of mass, momentum, and energy, are fundamental in describing both the internal processes of the atmosphere and its external interactions. The atmosphere is not a closed system, because it exchanges all three of these internally conservative quantities across the atmosphere's boundary below and receives input from regions outside it. Thus surface fluxes of moisture, momentum, and heat occur to and from the underlying ocean and land. The atmosphere exchanges very little mass and momentum with space, though it absorbs directly a portion of the solar radiational energy received from above.

Limiting factors for carbon based chemical double layer capacitors

NASA Technical Reports Server (NTRS)

Rose, M. Frank; Johnson, C.; Owens, T.; Stevens, B.

1993-01-01

The Chemical Double Layer (CDL) capacitor improves energy storage density dramatically when compared with conventional electrolytic capacitors. When compared to batteries, the CDL Capacitor is much less energy dense; however, the power density is orders of magnitude better. As a result, CDL-battery combinations present an interesting pulse power system with many potential applications. Due to the nature of the CDL it is inherently a low voltage device. The applications of the CDL can be tailored to auxiliary energy and burst mode storages which require fast charge/discharge cycles. Typical of the applications envisioned are power system backup, directed energy weapons concepts, electric automobiles, and electric actuators. In this paper, we will discuss some of the general characteristics of carbon-based CDL technology describing the structure, performance parameters, and methods of construction. Further, analytical and experimental results which define the state of the art are presented and described in terms of impact on applications.

First principles view on chemical compound space: Gaining rigorous atomistic control of molecular properties

DOE PAGES

von Lilienfeld, O. Anatole

2013-02-26

A well-defined notion of chemical compound space (CCS) is essential for gaining rigorous control of properties through variation of elemental composition and atomic configurations. Here, we give an introduction to an atomistic first principles perspective on CCS. First, CCS is discussed in terms of variational nuclear charges in the context of conceptual density functional and molecular grand-canonical ensemble theory. Thereafter, we revisit the notion of compound pairs, related to each other via “alchemical” interpolations involving fractional nuclear charges in the electronic Hamiltonian. We address Taylor expansions in CCS, property nonlinearity, improved predictions using reference compound pairs, and the ounce-of-gold prizemore » challenge to linearize CCS. Finally, we turn to machine learning of analytical structure property relationships in CCS. Here, these relationships correspond to inferred, rather than derived through variational principle, solutions of the electronic Schrödinger equation.« less

Chemical profile and anti-leishmanial activity of three Ecuadorian propolis samples from Quito, Guayaquil and Cotacachi regions.

PubMed

Cuesta-Rubio, Osmany; Campo Fernández, Mercedes; Márquez Hernández, Ingrid; Jaramillo, Carmita Gladys Jaramillo; González, Victor Hugo; Montes De Oca Porto, Rodny; Marrero Delange, David; Monzote Fidalgo, Lianet; Piccinelli, Anna Lisa; Campone, Luca; Rastrelli, Luca

2017-07-01

Three propolis samples were collected from different regions of Ecuador (Quito, Guayaquil and Cotacachi) and their methanolic extracts were prepared. Preliminary information supplied by TLC and NMR data, allowed us to define two main types of propolis: Cotacachi propoli sample (CPS), rich in flavonoids and Quito and Guayaquil samples (QPS and GPS) containing triterpenic alcohols and acetyl triterpenes as the main constituents. Two different approaches based on RP-HPLC preparative procedure and NMR structural determination (CPS) and GC-MS analysis (QPS and GPS) were successfully used for the chemical characterization of their major compounds. All three propolis extracts were able to inhibit Leishmania amazonensis growth but propolis sample rich in flavonoids was the most active (IC 50 =17.1±1.7μg/mL). In the literature this is the first study on propolis from Ecuador. Copyright © 2017. Published by Elsevier B.V.

Laboratory glassware rack for seismic safety

NASA Technical Reports Server (NTRS)

Cohen, M. M. (Inventor)

1985-01-01

A rack for laboratory bottles and jars for chemicals and medicines has been designed to provide the maximum strength and security to the glassware in the event of a significant earthquake. The rack preferably is rectangular and may be made of a variety of chemically resistant materials including polypropylene, polycarbonate, and stainless steel. It comprises a first plurality of parallel vertical walls, and a second plurality of parallel vertical walls, perpendicular to the first. These intersecting vertical walls comprise a self-supporting structure without a bottom which sits on four legs. The top surface of the rack is formed by the top edges of all the vertical walls, which are not parallel but are skewed in three dimensions. These top edges form a grid matrix having a number of intersections of the vertical walls which define a number of rectangular compartments having varying widths and lengths and varying heights.

Diagnosis of middle atmosphere chemistry-dynamics interactions

NASA Astrophysics Data System (ADS)

Zhu, X.; Swartz, W. H.; Garcia, R. R.; Chartier, A.; Yee, J. H.; Yue, J.

2017-12-01

We apply the recently developed middle atmosphere climate feedback-response analysis method (MCFRAM) to diagnosing the temperature variations associated with chemistry-dynamics interactions in the middle atmosphere. By using output fields from the Whole Atmosphere Community Climate Model (WACCM) coupled with the measurements, we identify and isolate the distinctive characteristics of different components in the observed temperature variations. Both the temperature trends associated with the anthropogenic forcing and temperature changes associated with natural and internal feedback processes are quantified based on MCFRAM defined partial temperature changes corresponding to localized radiative heating, non-localized chemical heating, eddy transport, and transport by the mean meridional circulation of energy and chemical species. In addition, the temperature responses to variations of CO2, O3, and solar flux have distinctly different spatial structures that can be systematically categorized by the eigenmodes of the generalized damping matrix derived from MCFRAM.

Nonequilibrium phase transitions in cuprates observed by ultrafast electron crystallography.

PubMed

Gedik, Nuh; Yang, Ding-Shyue; Logvenov, Gennady; Bozovic, Ivan; Zewail, Ahmed H

2007-04-20

Nonequilibrium phase transitions, which are defined by the formation of macroscopic transient domains, are optically dark and cannot be observed through conventional temperature- or pressure-change studies. We have directly determined the structural dynamics of such a nonequilibrium phase transition in a cuprate superconductor. Ultrafast electron crystallography with the use of a tilted optical geometry technique afforded the necessary atomic-scale spatial and temporal resolutions. The observed transient behavior displays a notable "structural isosbestic" point and a threshold effect for the dependence of c-axis expansion (Deltac) on fluence (F), with Deltac/F = 0.02 angstrom/(millijoule per square centimeter). This threshold for photon doping occurs at approximately 0.12 photons per copper site, which is unexpectedly close to the density (per site) of chemically doped carriers needed to induce superconductivity.

Atomic and Ionic Radii of Elements 1-96.

PubMed

Rahm, Martin; Hoffmann, Roald; Ashcroft, N W

2016-10-04

Atomic and cationic radii have been calculated for the first 96 elements, together with selected anionic radii. The metric adopted is the average distance from the nucleus where the electron density falls to 0.001 electrons per bohr(3) , following earlier work by Boyd. Our radii are derived using relativistic all-electron density functional theory calculations, close to the basis set limit. They offer a systematic quantitative measure of the sizes of non-interacting atoms, commonly invoked in the rationalization of chemical bonding, structure, and different properties. Remarkably, the atomic radii as defined in this way correlate well with van der Waals radii derived from crystal structures. A rationalization for trends and exceptions in those correlations is provided. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Friebel, Daniel

In situ x-ray absorption spectroscopy (XAS) at the Pt L{sub 3} edge is a useful probe for Pt-O interactions at polymer electrolyte membrane fuel cell (PEMFC) cathodes. We show that XAS using the high energy resolution fluorescence detection (HERFD) mode, applied to a well-defined monolayer Pt/Rh(111) sample where the bulk penetrating hard x-rays probe only surface Pt atoms, provides a unique sensitivity to structure and chemical bonding at the Pt-electrolyte interface. Ab initio multiple-scattering calculations using the FEFF8 code and complementary extended x-ray absorption fine structure (EXAFS) results indicate that the commonly observed large increase of the white-line at highmore » electrochemical potentials on PEMFC cathodes originates from platinum oxide formation, whereas previously proposed chemisorbed oxygen-containing species merely give rise to subtle spectral changes.« less

Structure-activity relationship study of vitamin k derivatives yields highly potent neuroprotective agents.

PubMed

Josey, Benjamin J; Inks, Elizabeth S; Wen, Xuejun; Chou, C James

2013-02-14

Historically known for its role in blood coagulation and bone formation, vitamin K (VK) has begun to emerge as an important nutrient for brain function. While VK involvement in the brain has not been fully explored, it is well-known that oxidative stress plays a critical role in neurodegenerative diseases. It was recently reported that VK protects neurons and oligodendrocytes from oxidative injury and rescues Drosophila from mitochondrial defects associated with Parkinson's disease. In this study, we take a chemical approach to define the optimal and minimum pharmacophore responsible for the neuroprotective effects of VK. In doing so, we have developed a series of potent VK analogues with favorable drug characteristics that provide full protection at nanomolar concentrations in a well-defined model of neuronal oxidative stress. Additionally, we have characterized key cellular responses and biomarkers consistent with the compounds' ability to rescue cells from oxidative stress induced cell death.

Web-based resources for mass-spectrometry-based metabolomics: a user's guide.

PubMed

Tohge, Takayuki; Fernie, Alisdair R

2009-03-01

In recent years, a plethora of web-based tools aimed at supporting mass-spectrometry-based metabolite profiling and metabolomics applications have appeared. Given the huge hurdles presented by the chemical diversity and dynamic range of the metabolites present in the plant kingdom, profiling the levels of a broad range of metabolites is highly challenging. Given the scale and costs involved in defining the plant metabolome, it is imperative that data are effectively shared between laboratories pursuing this goal. However, ensuring accurate comparison of samples run on the same machine within the same laboratory, let alone cross-machine and cross-laboratory comparisons, requires both careful experimentation and data interpretation. In this review, we present an overview of currently available software that aids either in peak identification or in the related field of peak alignment as well as those with utility in defining structural information of compounds and metabolic pathways.

The landscape ecology and microbiota of the human nose, mouth and throat

PubMed Central

Proctor, Diana M.; Relman, David A.

2017-01-01

Landscape ecology examines the relationships between the spatial arrangement of different landforms and the processes that give rise to spatial and temporal patterns in local community structure. These relationships that underlie the patterns of the microbial communities that inhabit the human body, and in particular, those of the nose, mouth and throat, deserve greater attention. Important questions include what defines the size of a population (i.e., ‘patch’) in a given body site; what defines the boundaries of distinct patches within a single body site, and where and over what spatial scales within a body site are gradients detected. This review looks at the landscape ecology in the upper respiratory tract and mouth, and seeks greater clarity about the physiological factors, whether immunological, chemical or physical, that govern microbial community composition and function, and the ecological traits that underlie health and disease. PMID:28407480

Directed assembly of bio-inspired hierarchical materials with controlled nanofibrillar architectures

NASA Astrophysics Data System (ADS)

Tseng, Peter; Napier, Bradley; Zhao, Siwei; Mitropoulos, Alexander N.; Applegate, Matthew B.; Marelli, Benedetto; Kaplan, David L.; Omenetto, Fiorenzo G.

2017-05-01

In natural systems, directed self-assembly of structural proteins produces complex, hierarchical materials that exhibit a unique combination of mechanical, chemical and transport properties. This controlled process covers dimensions ranging from the nano- to the macroscale. Such materials are desirable to synthesize integrated and adaptive materials and systems. We describe a bio-inspired process to generate hierarchically defined structures with multiscale morphology by using regenerated silk fibroin. The combination of protein self-assembly and microscale mechanical constraints is used to form oriented, porous nanofibrillar networks within predesigned macroscopic structures. This approach allows us to predefine the mechanical and physical properties of these materials, achieved by the definition of gradients in nano- to macroscale order. We fabricate centimetre-scale material geometries including anchors, cables, lattices and webs, as well as functional materials with structure-dependent strength and anisotropic thermal transport. Finally, multiple three-dimensional geometries and doped nanofibrillar constructs are presented to illustrate the facile integration of synthetic and natural additives to form functional, interactive, hierarchical networks.

Rapid prototyping of microstructures in polydimethylsiloxane (PDMS) by direct UV-lithography.

PubMed

Scharnweber, Tim; Truckenmüller, Roman; Schneider, Andrea M; Welle, Alexander; Reinhardt, Martina; Giselbrecht, Stefan

2011-04-07

Microstructuring of polydimethylsiloxane (PDMS) is a key step for many lab-on-a-chip (LOC) applications. In general, the structure is generated by casting the liquid prepolymer against a master. The production of the master in turn calls for special equipment and know how. Furthermore, a given master only allows the reproduction of the defined structure. We report on a simple, cheap and practical method to produce microstructures in already cured PDMS by direct UV-lithography followed by chemical development. Due to the available options during the lithographic process like multiple exposures, the method offers a high design flexibility granting easy access to complex and stepped structures. Furthermore, no master is needed and the use of pre-cured PDMS allows processing at ambient (light) conditions. Features down to approximately 5 µm and a depth of 10 µm can be realised. As a proof of principle, we demonstrate the feasibility of the process by applying the structures to various established soft lithography techniques.

Unraveling the Structural Modifications in Lignin of Arundo donax Linn. during Acid-Enhanced Ionic Liquid Pretreatment.

PubMed

You, Tingting; Zhang, Liming; Guo, Siqin; Shao, Lupeng; Xu, Feng

2015-12-23

Solid acid-enhanced ionic liquid (IL) pretreatment is of paramount importance for boosting the yield of sugars from biomass cost-effectively and environmentally friendly. To unravel the chemical and supramolecular structural changes of lignin after pretreatment, IL-acid lignin (ILAL) and subsequent residual cellulolytic enzyme lignin (RCEL) were isolated from Arundo donax Linn. The structural features were compared with those of the corresponding milled wood lignin (MWL). Results indicated that the pretreatment caused loss of β-O-4', β-β', β-1' linkages and formation of condensed structures in lignin. A preferential breakdown of G-type lignin may have occurred, evidenced by an increased S/G ratio revealed by 2D HSQC NMR analysis. It was determined that the depolymerization of β-O-4' linkage, lignin recondensation, and cleavage of ferulate-lignin ether linkages took place. Moreover, a simulation module was first developed to define morphological changes in lignin based on AFM and TEM analyses. Briefly, tree branch like aggregates was destroyed to monodisperse particles.

Film processing investigation. [improved chemical mixing system

NASA Technical Reports Server (NTRS)

Kelly, J. L.

1972-01-01

The present operational chemical mixing system for the Photographic Technology Division is evaluated, and the limitations are defined in terms of meeting the present and programmed chemical supply and delivery requirements. A major redesign of the entire chemical mixing, storage, analysis, and supply system is recommended. Other requirements for immediate and future implementations are presented.

46 CFR 188.10-7 - Chemical stores.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Chemical stores. 188.10-7 Section 188.10-7 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-7 Chemical stores. This term means those chemicals intended for use in the performance of the vessel's scientific activities and is further defined...

46 CFR 188.10-7 - Chemical stores.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Chemical stores. 188.10-7 Section 188.10-7 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-7 Chemical stores. This term means those chemicals intended for use in the performance of the vessel's scientific activities and is further defined...

21 CFR 1300.02 - Definitions relating to listed chemicals.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Definitions relating to listed chemicals. 1300.02....02 Definitions relating to listed chemicals. (a) Any term not defined in this part shall have the... international transaction in a listed chemical by— (i) Negotiating contracts; (ii) Serving as an agent or...

Protecting Children from Chemical Exposure: Social Work and U.S. Social Welfare Policy.

ERIC Educational Resources Information Center

Rogge, Mary E.; Combs-Orme, Terri

2003-01-01

Defines chemical contamination and reviews data regarding the ubiquity of toxic chemicals. Describes major risk pathways to fetuses and children at different developmental stages and discusses evidence regarding exposure and harm to children from chemical contamination. Reviews the roles for social workers in protecting current and future…

21 CFR 1300.02 - Definitions relating to listed chemicals.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Definitions relating to listed chemicals. 1300.02....02 Definitions relating to listed chemicals. (a) Any term not defined in this part shall have the... respect to the sale or purchase of a scheduled listed chemical product, means a sale or purchase for...

46 CFR 188.10-7 - Chemical stores.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false Chemical stores. 188.10-7 Section 188.10-7 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-7 Chemical stores. This term means those chemicals intended for use in the performance of the vessel's scientific activities and is further defined...

46 CFR 188.10-7 - Chemical stores.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false Chemical stores. 188.10-7 Section 188.10-7 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-7 Chemical stores. This term means those chemicals intended for use in the performance of the vessel's scientific activities and is further defined...

21 CFR 1300.02 - Definitions relating to listed chemicals.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Definitions relating to listed chemicals. 1300.02....02 Definitions relating to listed chemicals. (a) Any term not defined in this part shall have the... respect to the sale or purchase of a scheduled listed chemical product, means a sale or purchase for...

21 CFR 1300.02 - Definitions relating to listed chemicals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Definitions relating to listed chemicals. 1300.02....02 Definitions relating to listed chemicals. (a) Any term not defined in this part shall have the... respect to the sale or purchase of a scheduled listed chemical product, means a sale or purchase for...

46 CFR 188.10-7 - Chemical stores.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false Chemical stores. 188.10-7 Section 188.10-7 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-7 Chemical stores. This term means those chemicals intended for use in the performance of the vessel's scientific activities and is further defined...

X-ray excited Auger transitions of Pu compounds

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

Nelson, Art J., E-mail: nelson63@llnl.gov; Grant, William K.; Stanford, Jeff A.

2015-05-15

X-ray excited Pu core–valence–valence and core–core–valence Auger line-shapes were used in combination with the Pu 4f photoelectron peaks to characterize differences in the oxidation state and local electronic structure for Pu compounds. The evolution of the Pu 4f core-level chemical shift as a function of sputtering depth profiling and hydrogen exposure at ambient temperature was quantified. The combination of the core–valence–valence Auger peak energies with the associated chemical shift of the Pu 4f photoelectron line defines the Auger parameter and results in a reliable method for definitively determining oxidation states independent of binding energy calibration. Results show that PuO{sub 2},more » Pu{sub 2}O{sub 3}, PuH{sub 2.7}, and Pu have definitive Auger line-shapes. These data were used to produce a chemical state (Wagner) plot for select plutonium oxides. This Wagner plot allowed us to distinguish between the trivalent hydride and the trivalent oxide, which cannot be differentiated by the Pu 4f binding energy alone.« less

Sensing in tissue bioreactors

NASA Astrophysics Data System (ADS)

Rolfe, P.

2006-03-01

Specialized sensing and measurement instruments are under development to aid the controlled culture of cells in bioreactors for the fabrication of biological tissues. Precisely defined physical and chemical conditions are needed for the correct culture of the many cell-tissue types now being studied, including chondrocytes (cartilage), vascular endothelial cells and smooth muscle cells (blood vessels), fibroblasts, hepatocytes (liver) and receptor neurones. Cell and tissue culture processes are dynamic and therefore, optimal control requires monitoring of the key process variables. Chemical and physical sensing is approached in this paper with the aim of enabling automatic optimal control, based on classical cell growth models, to be achieved. Non-invasive sensing is performed via the bioreactor wall, invasive sensing with probes placed inside the cell culture chamber and indirect monitoring using analysis within a shunt or a sampling chamber. Electroanalytical and photonics-based systems are described. Chemical sensing for gases, ions, metabolites, certain hormones and proteins, is under development. Spectroscopic analysis of the culture medium is used for measurement of glucose and for proteins that are markers of cell biosynthetic behaviour. Optical interrogation of cells and tissues is also investigated for structural analysis based on scatter.

Principles and applications of laser-induced liquid-phase jet-chemical etching

NASA Astrophysics Data System (ADS)

Stephen, Andreas; Metev, Simeon; Vollertsen, Frank

2003-11-01

In this treatment method laser radiation, which is guided from a coaxially expanding liquid jet-stream, locally initiates a thermochemical etching reaction on a metal surface, which leads to selective material removal at high resolution and quality of the treated surface as well as low thermal influence on the workpiece. Electrochemical investigations were performed under focused laser irradiation using a cw-Nd:YAG laser with a maximum power of 15 W and a simultaneous impact of the liquid jet-stream consisting of phosphoric acid with a maximum flow rate of 20 m/s. The time resolved measurements of the electrical potential difference against an electrochemical reference electrode were correlated with the specific processing parameters and corresponding etch rates to identify processing conditions for temporally stable and enhanced chemical etching reactions. Applications of laser-induced liquid-phase jet-chemical etching in the field of sensor technology, micromechanics and micrmoulding technology are presented. This includes the microstructuring of thin film systems, cutting of foils of shape memory alloys or the generation of structures with defined shape in bulk material.

From flower to honey bouquet: possible markers for the botanical origin of Robinia honey.

PubMed

Aronne, Giovanna; Giovanetti, Manuela; Sacchi, Raffaele; De Micco, Veronica

2014-01-01

Flowers are complex structures devoted to pollinator attraction, through visual as well as chemical signals. As bees collect nectar on flowers to produce honey, some aspects of floral chemistry are transferred to honey, making chemical markers an important technique to identify the botanical and geographical origins of honey. We applied a new approach that considers the simultaneous analysis of different floral parts (petals, stamens + pistils, calyxes + nectarines, and nectar) and the corresponding unifloral honey. We collected fresh flowers of Robinia pseudoacacia L. (black locust), selected five samples of Robinia honey from different geographical origins, applied SPME-GC/MS for volatile analyses, and defined the chemical contribution added by different floral parts to the honey final bouquet. Our results show that honey blends products from nectar as well as other flower parts. Comparing honey and flower profiles, we detected compounds coming directly from flower parts but not present in the nectar, such as hotrienol and β-pinene. These may turn out to be of special interest when selecting floral markers for the botanical origin of honey.

Chemically defined medium and Caenorhabditis elegans

NASA Technical Reports Server (NTRS)

Szewczyk, Nathaniel J.; Kozak, Elena; Conley, Catharine A.

2003-01-01

BACKGROUND: C. elegans has been established as a powerful genetic system. Use of a chemically defined medium (C. elegans Maintenance Medium (CeMM)) now allows standardization and systematic manipulation of the nutrients that animals receive. Liquid cultivation allows automated culturing and experimentation and should be of use in large-scale growth and screening of animals. RESULTS: We find that CeMM is versatile and culturing is simple. CeMM can be used in a solid or liquid state, it can be stored unused for at least a year, unattended actively growing cultures may be maintained longer than with standard techniques, and standard C. elegans protocols work well with animals grown in defined medium. We also find that there are caveats to using defined medium. Animals in defined medium grow more slowly than on standard medium, appear to display adaptation to the defined medium, and display altered growth rates as they change the composition of the defined medium. CONCLUSIONS: As was suggested with the introduction of C. elegans as a potential genetic system, use of defined medium with C. elegans should prove a powerful tool.

Functional micro/nanostructures: simple synthesis and application in sensors, fuel cells, and gene delivery.

PubMed

Guo, Shaojun; Wang, Erkang

2011-07-19

In order to develop new, high technology devices for a variety of applications, researchers would like to better control the structure and function of micro/nanomaterials through an understanding of the role of size, shape, architecture, composition, hybridization, molecular engineering, assembly, and microstructure. However, researchers continue to face great challenges in the construction of well-defined micro/nanomaterials with diverse morphologies. At the same time, the research interface where micro/nanomaterials meet electrochemistry, analytical chemistry, biomedicine, and other fields provides rich opportunities to reveal new chemical, physical, and biological properties of micro/nanomaterials and to uncover many new functions and applications of these materials. In this Account, we describe our recent progress in the construction of novel inorganic and polymer nanostructures formed through different simple strategies. Our synthetic strategies include wet-chemical and electrochemical methods for the controlled production of inorganic and polymer nanomaterials with well-defined morphologies. These methods are both facile and reliable, allowing us to produce high-quality micro/nanostructures, such as nanoplates, micro/nanoflowers, monodisperse micro/nanoparticles, nanowires, nanobelts, and polyhedron and even diverse hybrid structures. We implemented a series of approaches to address the challenges in the preparation of new functional micro/nanomaterials for a variety of important applications This Account also highlights new or enhanced applications of certain micro/nanomaterials in sensing applications. We singled out analytical techniques that take advantage of particular properties of micro/nanomaterials. Then by rationally tailoring experimental parameters, we readily and selectively obtained different types of micro/nanomaterials with novel morphologies with high performance in applications such as electrochemical sensors, electrochemiluminescent sensors, gene delivery agents, and fuel cell catalysts. We expect that micro/nanomaterials with unique structural characteristics, properties, and functions will attract increasing research interest and will lead to new opportunities in various fields of research.

Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a chemically defined (HGM) medium

PubMed Central

1996-01-01

Mature adult parenchymal hepatocytes, typically of restricted capacity to proliferate in culture, can now enter into clonal growth under the influence of hepatocyte growth factor (scatter factor) (HGF/SF), epidermal growth factor (EGF), and transforming growth factor alpha (TGFalpha) in the presence of a new chemically defined medium (HGM). The expanding populations of hepatocytes lose expression of hepatocyte specific genes (albumin, cytochrome P450 IIB1), acquire expression of markers expressed by bile duct epithelium (cytokeratin 19), produce TGFalpha and acidic FGF and assume a very simplified morphologic phenotype by electron microscopy. A major change associated with this transition is the decrease in ratio between transcription factors C/EBPalpha and C/EBPbeta, as well as the emergence in the proliferating hepatocytes of transcription factors AP1, NFkappaB. The liver associated transcription factors HNFI, HNF3, and HNF4 are preserved throughout this process. After population expansion and clonal growth, the proliferating hepatocytes can return to mature hepatocyte phenotype in the presence of EHS gel (Matrigel). This includes complete restoration of electron microscopic structure and albumin expression. The hepatocyte cultures however can instead be induced to form acinar/ductular structures akin to bile ductules (in the presence of HGF/SF and type I collagen). These transformations affect the entire population of the hepatocytes and occur even when DNA synthesis is inhibited. Similar acinar/ductular structures are seen in embryonic liver when HGF/SF and its receptor are expressed at high levels. These findings strongly support the hypothesis that mature hepatocytes can function as or be a source of bipotential facultative hepatic stem cells (hepatoblasts). These studies also provide evidence for the growth factor and matrix signals that govern these complex phenotypic transitions of facultative stem cells which are crucial for recovery from acute and chronic liver injury. PMID:8601590

Protein structure refinement using a quantum mechanics-based chemical shielding predictor.

PubMed

Bratholm, Lars A; Jensen, Jan H

2017-03-01

The accurate prediction of protein chemical shifts using a quantum mechanics (QM)-based method has been the subject of intense research for more than 20 years but so far empirical methods for chemical shift prediction have proven more accurate. In this paper we show that a QM-based predictor of a protein backbone and CB chemical shifts (ProCS15, PeerJ , 2016, 3, e1344) is of comparable accuracy to empirical chemical shift predictors after chemical shift-based structural refinement that removes small structural errors. We present a method by which quantum chemistry based predictions of isotropic chemical shielding values (ProCS15) can be used to refine protein structures using Markov Chain Monte Carlo (MCMC) simulations, relating the chemical shielding values to the experimental chemical shifts probabilistically. Two kinds of MCMC structural refinement simulations were performed using force field geometry optimized X-ray structures as starting points: simulated annealing of the starting structure and constant temperature MCMC simulation followed by simulated annealing of a representative ensemble structure. Annealing of the CHARMM structure changes the CA-RMSD by an average of 0.4 Å but lowers the chemical shift RMSD by 1.0 and 0.7 ppm for CA and N. Conformational averaging has a relatively small effect (0.1-0.2 ppm) on the overall agreement with carbon chemical shifts but lowers the error for nitrogen chemical shifts by 0.4 ppm. If an amino acid specific offset is included the ProCS15 predicted chemical shifts have RMSD values relative to experiments that are comparable to popular empirical chemical shift predictors. The annealed representative ensemble structures differ in CA-RMSD relative to the initial structures by an average of 2.0 Å, with >2.0 Å difference for six proteins. In four of the cases, the largest structural differences arise in structurally flexible regions of the protein as determined by NMR, and in the remaining two cases, the large structural change may be due to force field deficiencies. The overall accuracy of the empirical methods are slightly improved by annealing the CHARMM structure with ProCS15, which may suggest that the minor structural changes introduced by ProCS15-based annealing improves the accuracy of the protein structures. Having established that QM-based chemical shift prediction can deliver the same accuracy as empirical shift predictors we hope this can help increase the accuracy of related approaches such as QM/MM or linear scaling approaches or interpreting protein structural dynamics from QM-derived chemical shift.

Designing molecular complexes using free-energy derivatives from liquid-state integral equation theory

NASA Astrophysics Data System (ADS)

Mrugalla, Florian; Kast, Stefan M.

2016-09-01

Complex formation between molecules in solution is the key process by which molecular interactions are translated into functional systems. These processes are governed by the binding or free energy of association which depends on both direct molecular interactions and the solvation contribution. A design goal frequently addressed in pharmaceutical sciences is the optimization of chemical properties of the complex partners in the sense of minimizing their binding free energy with respect to a change in chemical structure. Here, we demonstrate that liquid-state theory in the form of the solute-solute equation of the reference interaction site model provides all necessary information for such a task with high efficiency. In particular, computing derivatives of the potential of mean force (PMF), which defines the free-energy surface of complex formation, with respect to potential parameters can be viewed as a means to define a direction in chemical space toward better binders. We illustrate the methodology in the benchmark case of alkali ion binding to the crown ether 18-crown-6 in aqueous solution. In order to examine the validity of the underlying solute-solute theory, we first compare PMFs computed by different approaches, including explicit free-energy molecular dynamics simulations as a reference. Predictions of an optimally binding ion radius based on free-energy derivatives are then shown to yield consistent results for different ion parameter sets and to compare well with earlier, orders-of-magnitude more costly explicit simulation results. This proof-of-principle study, therefore, demonstrates the potential of liquid-state theory for molecular design problems.

Designing molecular complexes using free-energy derivatives from liquid-state integral equation theory.

PubMed

Mrugalla, Florian; Kast, Stefan M

2016-09-01

Complex formation between molecules in solution is the key process by which molecular interactions are translated into functional systems. These processes are governed by the binding or free energy of association which depends on both direct molecular interactions and the solvation contribution. A design goal frequently addressed in pharmaceutical sciences is the optimization of chemical properties of the complex partners in the sense of minimizing their binding free energy with respect to a change in chemical structure. Here, we demonstrate that liquid-state theory in the form of the solute-solute equation of the reference interaction site model provides all necessary information for such a task with high efficiency. In particular, computing derivatives of the potential of mean force (PMF), which defines the free-energy surface of complex formation, with respect to potential parameters can be viewed as a means to define a direction in chemical space toward better binders. We illustrate the methodology in the benchmark case of alkali ion binding to the crown ether 18-crown-6 in aqueous solution. In order to examine the validity of the underlying solute-solute theory, we first compare PMFs computed by different approaches, including explicit free-energy molecular dynamics simulations as a reference. Predictions of an optimally binding ion radius based on free-energy derivatives are then shown to yield consistent results for different ion parameter sets and to compare well with earlier, orders-of-magnitude more costly explicit simulation results. This proof-of-principle study, therefore, demonstrates the potential of liquid-state theory for molecular design problems.

Constitutional dynamic chemistry: bridge from supramolecular chemistry to adaptive chemistry.

PubMed

Lehn, Jean-Marie

2012-01-01

Supramolecular chemistry aims at implementing highly complex chemical systems from molecular components held together by non-covalent intermolecular forces and effecting molecular recognition, catalysis and transport processes. A further step consists in the investigation of chemical systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined functional supramolecular architectures by self-assembly from their components, thus behaving as programmed chemical systems. Supramolecular chemistry is intrinsically a dynamic chemistry in view of the lability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when the molecular entity contains covalent bonds that may form and break reversibility, so as to allow a continuous change in constitution by reorganization and exchange of building blocks. These features define a Constitutional Dynamic Chemistry (CDC) on both the molecular and supramolecular levels.CDC introduces a paradigm shift with respect to constitutionally static chemistry. The latter relies on design for the generation of a target entity, whereas CDC takes advantage of dynamic diversity to allow variation and selection. The implementation of selection in chemistry introduces a fundamental change in outlook. Whereas self-organization by design strives to achieve full control over the output molecular or supramolecular entity by explicit programming, self-organization with selection operates on dynamic constitutional diversity in response to either internal or external factors to achieve adaptation.The merging of the features: -information and programmability, -dynamics and reversibility, -constitution and structural diversity, points to the emergence of adaptive and evolutive chemistry, towards a chemistry of complex matter.

Ordered Nanostructures Made Using Chaperonin Polypeptides

NASA Technical Reports Server (NTRS)

Trent, Jonathan; McMillan, Robert; Paavola, Chad; Mogul, Rakesh; Kagawa, Hiromi

2004-01-01

A recently invented method of fabricating periodic or otherwise ordered nanostructures involves the use of chaperonin polypeptides. The method is intended to serve as a potentially superior and less expensive alternative to conventional lithographic methods for use in the patterning steps of the fabrication of diverse objects characterized by features of the order of nanometers. Typical examples of such objects include arrays of quantum dots that would serve as the functional building blocks of future advanced electronic and photonic devices. A chaperonin is a double-ring protein structure having a molecular weight of about 60 plus or minus 5 kilodaltons. In nature, chaperonins are ubiquitous, essential, subcellular structures. Each natural chaperonin molecule comprises 14, 16, or 18 protein subunits, arranged as two stacked rings approximately 16 to 18 nm tall by approximately 15 to 17 nm wide, the exact dimensions depending on the biological species in which it originates. The natural role of chaperonins is unknown, but they are believed to aid in the correct folding of other proteins, by enclosing unfolded proteins and preventing nonspecific aggregation during assembly. What makes chaperonins useful for the purpose of the present method is that under the proper conditions, chaperonin rings assemble themselves into higher-order structures. This method exploits such higher-order structures to define nanoscale devices. The higher-order structures are tailored partly by choice of chemical and physical conditions for assembly and partly by using chaperonins that have been mutated. The mutations are made by established biochemical techniques. The assembly of chaperonin polypeptides into such structures as rings, tubes, filaments, and sheets (two-dimensional crystals) can be regulated chemically. Rings, tubes, and filaments of some chaperonin polypeptides can, for example, function as nano vessels if they are able to absorb, retain, protect, and release gases or chemical reagents, including reagents of medical or pharmaceutical interest. Chemical reagents can be bound in, or released from, such structures under suitable controlled conditions. In an example of a contemplated application, a two-dimensional crystal of chaperonin polypeptides would be formed on a surface of an inorganic substrate and used to form a planar array of nanoparticles or quantum dots. Through genetic engineering of the organisms used to manufacture the chaperonins, specific sites on the chaperonin molecules and, thus, on the two-dimensional crystals can be chemically modified to react in a specific manner so as to favor the deposition of the material of the desired nanoparticles or quantum dots. A mutation that introduces a cysteine residue at the desired sites on a chaperonin of Sulfolobus shibatae was used to form planar arrays of gold nanoparticles (see figure).

Detailed Chemical Composition of Condensed Tannins via Quantitative (31)P NMR and HSQC Analyses: Acacia catechu, Schinopsis balansae, and Acacia mearnsii.

PubMed

Crestini, Claudia; Lange, Heiko; Bianchetti, Giulia

2016-09-23

The chemical composition of Acacia catechu, Schinopsis balansae, and Acacia mearnsii proanthocyanidins has been determined using a novel analytical approach that rests on the concerted use of quantitative (31)P NMR and two-dimensional heteronuclear NMR spectroscopy. This approach has offered significant detailed information regarding the structure and purity of these complex and often elusive proanthocyanidins. More specifically, rings A, B, and C of their flavan-3-ol units show well-defined and resolved absorbance regions in both the quantitative (31)P NMR and HSQC spectra. By integrating each of these regions in the (31)P NMR spectra, it is possible to identify the oxygenation patterns of the flavan-3-ol units. At the same time it is possible to acquire a fingerprint of the proanthocyanidin sample and evaluate its purity via the HSQC information. This analytical approach is suitable for both the purified natural product proanthocyanidins and their commercial analogues. Overall, this effort demonstrates the power of the concerted use of these two NMR techniques for the structural elucidation of natural products containing labile hydroxy protons and a carbon framework that can be traced out via HSQC.

Fluorophore labeling of a cell-penetrating peptide induces differential effects on its cellular distribution and affects cell viability.

PubMed

Birch, Ditlev; Christensen, Malene Vinther; Staerk, Dan; Franzyk, Henrik; Nielsen, Hanne Mørck

2017-12-01

Cell-penetrating peptides constitute efficient delivery vectors, and studies of their uptake and mechanism of translocation typically involve fluorophore-labeled conjugates. In the present study, the influence of a number of specific fluorophores on the physico-chemical properties and uptake-related characteristics of penetratin were studied. An array of seven fluorophores belonging to distinct structural classes was examined, and the impact of fluorophore labeling on intracellular distribution and cytotoxicity was correlated to the physico-chemical properties of the conjugates. Exposure of several mammalian cell types to fluorophore-penetratin conjugates revealed a strong structure-dependent reduction in viability (1.5- to 20-fold lower IC 50 values as compared to those of non-labeled penetratin). Also, the degree of less severe effects on membrane integrity, as well as intracellular distribution patterns differed among the conjugates. Overall, neutral hydrophobic fluorophores or negatively charged fluorophores conferred less cytotoxicity as compared to the effect exerted by positively charged, hydrophobic fluorophores. The latter conjugates, however, exhibited less membrane association and more clearly defined intracellular distribution patterns. Thus, selection of the appropriate flurophore is critical. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical Fate of a Metamorphic Inducer in Larvae-like Buds of the Cnidarian Cassiopea andromeda.

PubMed

Fleck, J

1998-02-01

Larvae-like vegetative buds of the scyphozoan Cassiopea andromeda metamorphose into polyps in the presence of oligopeptides that have a well-defined primary structure. Buds were incubated with the hexapeptide 14C-dansyl-GPGGPA, a representative inducer. Autoradiography of longitudinal sections of these buds revealed rapid internalization of peptide by the buds. Silver grain density was highest in the pre-pedal disc region (or aboral knob) of metamorphosing buds. Larvae and buds sporadically explore their habitat with this aboral knob, searching for a suitable solid substrate to which irreversible attachment will be made. Buds were incubated for 3, 8, or 16 h with 14C-dansyl-GPGGPA, then homogenized and the supernatants analyzed to determine the chemical fate of the inducer. The signal molecule was shown to be partly degraded to 14C-dansyl-GP, partly to 14C-dansyl-G, and in part still present in its original structure. These cleavage products were also found in the surrounding medium after an incubation time of 8 h with 14C-dansyl-GPGGPA, but did not induce metamorphosis. This study suggests that exposure of metamorphosis-inducing peptides to buds of Cassiopea andromeda results in signal termination.

Well-defined protein-polymer conjugates--synthesis and potential applications.

PubMed

Thordarson, Pall; Le Droumaguet, Benjamin; Velonia, Kelly

2006-11-01

During the last decades, numerous studies have focused on combining the unique catalytic/functional properties and structural characteristics of proteins and enzymes with those of synthetic molecules and macromolecules. The aim of such multidisciplinary studies is to improve the properties of the natural component, combine them with those of the synthetic, and create novel biomaterials in the nanometer scale. The specific coupling of polymers onto the protein structures has proved to be one of the most straightforward and applicable approaches in that sense. In this article, we focus on the synthetic pathways that have or can be utilized to specifically couple proteins to polymers. The different categories of well-defined protein-polymer conjugates and the effect of the polymer on the protein function are discussed. Studies have shown that the specific conjugation of a synthetic polymer to a protein conveys its physico-chemical properties and, therefore, modifies the biodistribution and solubility of the protein, making it in certain cases soluble and active in organic solvents. An overview of the applications derived from such bioconjugates in the pharmaceutical industry, biocatalysis, and supramolecular nanobiotechnology is presented at the final part of the article.

Curriculum Assessment as a Direct Tool in ABET Outcomes Assessment in a Chemical Engineering Programme

ERIC Educational Resources Information Center

Abu-Jdayil, Basim; Al-Attar, Hazim

2010-01-01

The chemical engineering programme at the United Arab Emirates University is designed to fulfil the Accreditation Board for Engineering and Technology (ABET) (A-K) EC2000 criteria. The Department of Chemical & Petroleum Engineering has established a well-defined process for outcomes assessment for the chemical engineering programme in order to…

Defining the relationship between individuals’ aggregate and maximum source-specific exposures

EPA Science Inventory

The concepts of aggregate and source-specific exposures play an important role in chemical risk management. The concepts of aggregate and source-specific exposures play an important role in chemical risk management. Aggregate exposure to a chemical refers to combined exposures fr...

Differentiating Left- and Right-Handed Carbon Nanotubes by DNA.

PubMed

Ao, Geyou; Streit, Jason K; Fagan, Jeffrey A; Zheng, Ming

2016-12-28

New structural characteristics emerge when solid-state crystals are constructed in lower dimensions. This is exemplified by single-wall carbon nanotubes, which exhibit a degree of freedom in handedness and a multitude of helicities that give rise to three distinct types of electronic structures: metals, quasi-metals, and semiconductors. Here we report the use of intrinsically chiral single-stranded DNA to achieve simultaneous handedness and helicity control for all three types of nanotubes. We apply polymer aqueous two-phase systems to select special DNA-wrapped carbon nanotubes, each of which we argue must have an ordered DNA structure that binds to a nanotube of defined handedness and helicity and resembles a well-folded biomacromolecule with innate stereoselectivity. We have screened over 300 short single-stranded DNA sequences with palindrome symmetry, leading to the selection of more than 20 distinct carbon nanotube structures that have defined helicity and handedness and cover the entire chiral angle range and all three electronic types. The mechanism of handedness selection is illustrated by a DNA sequence that adopts two distinct folds on a pair of (6,5) nanotube enantiomers, rendering them large differences in fluorescence intensity and chemical reactivity. This result establishes a first example of functionally distinguishable left- and right-handed carbon nanotubes. Taken together, our work demonstrates highly efficient enantiomer differentiation by DNA and offers a first comprehensive solution to achieve simultaneous handedness and helicity control for all three electronic types of carbon nanotubes.

Celecoxib Encapsulation in β-Casein Micelles: Structure, Interactions, and Conformation.

PubMed

Turovsky, Tanya; Khalfin, Rafail; Kababya, Shifi; Schmidt, Asher; Barenholz, Yechezkel; Danino, Dganit

2015-07-07

β-Casein is a 24 kDa natural protein that has an open conformation and almost no folded or secondary structure, and thus is classified as an intrinsically unstructured protein. At neutral pH, β-casein has an amphiphilic character. Therefore, in contrast to most unstructured proteins that remain monomeric in solution, β-casein self-assembles into well-defined core-shell micelles. We recently developed these micelles as potential carriers for oral administration of poorly water-soluble pharmaceuticals, using celecoxib as a model drug. Herein we present deep and precise insight into the physicochemical characteristics of the protein-drug formulation, both in bulk solution and in dry form, emphasizing drug conformation, packing properties and aggregation state. In addition, the formulation is extensively studied in terms of structure and morphology, protein/drug interactions and physical stability. Particularly, NMR measurements indicated strong drug-protein interactions and noncrystalline drug conformation, which is expected to improve drug solubility and bioavailability. Small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM) were combined for nanostructural characterization, proving that drug-protein interactions lead to well-defined spheroidal micelles that become puffier and denser upon drug loading. Dynamice light scattering (DLS), turbidity measurements, and visual observations complemented the analysis for determining formulation structure, interactions, and stability. Additionally, it was shown that the loaded micelles retain their properties through freeze-drying and rehydration, providing long-term physical and chemical stability. Altogether, the formulation seems greatly promising for oral drug delivery.

Differentiating Left- and Right-handed Carbon Nanotubes by DNA

NASA Astrophysics Data System (ADS)

Zheng, Ming

New structural characteristics emerge when solid-state crystals are constructed in lower dimensions. This is exemplified by single-wall carbon nanotubes, which exhibit a degree of freedom in handedness, and a multitude of helicity that gives rise to three distinct types of electronic structures - metals, quasi-metals, and semiconductors. Here, we report the use of intrinsically chiral single-stranded DNA to achieve simultaneous handedness and helicity control for all three types of nanotubes. We apply polymer aqueous two-phase systems to select special DNA-wrapped carbon nanotubes, each of which we argue must have an ordered DNA structure bound to a nanotube of defined handedness and helicity, resembling a well-folded biomacromolecule with innate stereo-selectivity. We have screened over 300 short single-stranded DNA sequences with palindrome symmetry, leading to the selection of more than 20 distinct carbon nanotube structures that have defined helicity and handedness and cover the entire chiral angle range and all three electronic types. The mechanism of handedness selection is illustrated by a DNA sequence that adopts two distinct folds on a pair of (6,5) nanotube enantiomers, respectively, rendering them large differences in fluorescence intensity and chemical reactivity. This result establishes a first example of functionally distinguishable left- and right-handed carbon nanotubes. Taken together, our work demonstrates highly efficient enantiomer differentiation by DNA, and offers a first comprehensive solution to achieve simultaneous handedness and helicity control for all three electronic types of carbon nanotubes. .

Cheminformatics Analysis of EPA ToxCast Chemical Libraries ...

EPA Pesticide Factsheets

An important goal of toxicology research is the development of robust methods that use in vitro and chemical structure information to predict in vivo toxicity endpoints. The US EPA ToxCast program is addressing this goal using ~600 in vitro assays to create bioactivity profiles on a set of 320 compounds, mostly pesticide actives, that have well characterized in vivo toxicity. These 320 compounds (EPA-320 set evaluated in Phase I of ToxCast) are a subset of a much larger set of ~10,000 candidates that are of interest to the EPA (called here EPA-10K). Predictive models of in vivo toxicity are being constructed from the in vitro assay data on the EPA-320 chemical set. These models require validation on additional chemicals prior to wide acceptance, and this will be carried out by evaluating compounds from EPA-10K in Phase II of ToxCast. We have used cheminformatics approaches including clustering, data visualization, and QSAR to develop models for EPA-320 that could help prioritizing EPA-10K validation chemicals. Both chemical descriptors, as well as calculated physicochemical properties have been used. Compounds from EPA-10K are prioritized based on their similarity to EPA-320 using different similarity metrics, with similarity thresholds defining the domain of applicability for the predictive models built for EPA-320 set. In addition, prioritized lists of compounds of increasing dissimilarity from the EPA-320 have been produced, to test the ability of the EPA-320

The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap.

PubMed

Brown, Jeffrey W; Bullitt, Esther; Sriswasdi, Sira; Harper, Sandra; Speicher, David W; McKnight, C James

2015-06-01

The primary, secondary, and tertiary structures of spectrin are reasonably well defined, but the structural basis for the known dramatic molecular shape change, whereby the molecular length can increase three-fold, is not understood. In this study, we combine previously reported biochemical and high-resolution crystallographic data with structural mass spectroscopy and electron microscopic data to derive a detailed, experimentally-supported quaternary structure of the spectrin heterotetramer. In addition to explaining spectrin's physiological resting length of ~55-65 nm, our model provides a mechanism by which spectrin is able to undergo a seamless three-fold extension while remaining a linear filament, an experimentally observed property. According to the proposed model, spectrin's quaternary structure and mechanism of extension is similar to a Chinese Finger Trap: at shorter molecular lengths spectrin is a hollow cylinder that extends by increasing the pitch of each spectrin repeat, which decreases the internal diameter. We validated our model with electron microscopy, which demonstrated that, as predicted, spectrin is hollow at its biological resting length of ~55-65 nm. The model is further supported by zero-length chemical crosslink data indicative of an approximately 90 degree bend between adjacent spectrin repeats. The domain-domain interactions in our model are entirely consistent with those present in the prototypical linear antiparallel heterotetramer as well as recently reported inter-strand chemical crosslinks. The model is consistent with all known physical properties of spectrin, and upon full extension our Chinese Finger Trap Model reduces to the ~180-200 nm molecular model currently in common use.

Thermodynamic Analysis of Compatibility of Several Reinforcement Materials with Beta Phase NiAl Alloys

NASA Technical Reports Server (NTRS)

Misra, Ajay K.

1988-01-01

Chemical compatibility of several reinforcement materials with beta phase NiAl alloys within the concentration range 40 to 50 at. percent Al have been analyzed from thermodynamic considerations at 1373 and 1573 K. The reinforcement materials considered in this study include carbides, borides, oxides, nitrides, beryllides, and silicides. Thermodynamic data for NiAl alloys have been reviewed and activity of Ni and Al in the beta phase have been derived at 1373 and 1573 K. Criteria for chemical compatibility between the reinforcement material and the matrix have been defined and several chemically compatible reinforcement materials have been defined.

Protein structure refinement using a quantum mechanics-based chemical shielding predictor† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc04344e Click here for additional data file.

PubMed Central

2017-01-01

The accurate prediction of protein chemical shifts using a quantum mechanics (QM)-based method has been the subject of intense research for more than 20 years but so far empirical methods for chemical shift prediction have proven more accurate. In this paper we show that a QM-based predictor of a protein backbone and CB chemical shifts (ProCS15, PeerJ, 2016, 3, e1344) is of comparable accuracy to empirical chemical shift predictors after chemical shift-based structural refinement that removes small structural errors. We present a method by which quantum chemistry based predictions of isotropic chemical shielding values (ProCS15) can be used to refine protein structures using Markov Chain Monte Carlo (MCMC) simulations, relating the chemical shielding values to the experimental chemical shifts probabilistically. Two kinds of MCMC structural refinement simulations were performed using force field geometry optimized X-ray structures as starting points: simulated annealing of the starting structure and constant temperature MCMC simulation followed by simulated annealing of a representative ensemble structure. Annealing of the CHARMM structure changes the CA-RMSD by an average of 0.4 Å but lowers the chemical shift RMSD by 1.0 and 0.7 ppm for CA and N. Conformational averaging has a relatively small effect (0.1–0.2 ppm) on the overall agreement with carbon chemical shifts but lowers the error for nitrogen chemical shifts by 0.4 ppm. If an amino acid specific offset is included the ProCS15 predicted chemical shifts have RMSD values relative to experiments that are comparable to popular empirical chemical shift predictors. The annealed representative ensemble structures differ in CA-RMSD relative to the initial structures by an average of 2.0 Å, with >2.0 Å difference for six proteins. In four of the cases, the largest structural differences arise in structurally flexible regions of the protein as determined by NMR, and in the remaining two cases, the large structural change may be due to force field deficiencies. The overall accuracy of the empirical methods are slightly improved by annealing the CHARMM structure with ProCS15, which may suggest that the minor structural changes introduced by ProCS15-based annealing improves the accuracy of the protein structures. Having established that QM-based chemical shift prediction can deliver the same accuracy as empirical shift predictors we hope this can help increase the accuracy of related approaches such as QM/MM or linear scaling approaches or interpreting protein structural dynamics from QM-derived chemical shift. PMID:28451325

The Relevance of Marine Chemical Ecology to Plankton and Ecosystem Function: An Emerging Field

PubMed Central

Ianora, Adrianna; Bentley, Matthew G.; Caldwell, Gary S.; Casotti, Raffaella; Cembella, Allan D.; Engström-Öst, Jonna; Halsband, Claudia; Sonnenschein, Eva; Legrand, Catherine; Llewellyn, Carole A.; Paldavičienë, Aistë; Pilkaityte, Renata; Pohnert, Georg; Razinkovas, Arturas; Romano, Giovanna; Tillmann, Urban; Vaiciute, Diana

2011-01-01

Marine chemical ecology comprises the study of the production and interaction of bioactive molecules affecting organism behavior and function. Here we focus on bioactive compounds and interactions associated with phytoplankton, particularly bloom-forming diatoms, prymnesiophytes and dinoflagellates. Planktonic bioactive metabolites are structurally and functionally diverse and some may have multiple simultaneous functions including roles in chemical defense (antipredator, allelopathic and antibacterial compounds), and/or cell-to-cell signaling (e.g., polyunsaturated aldehydes (PUAs) of diatoms). Among inducible chemical defenses in response to grazing, there is high species-specific variability in the effects on grazers, ranging from severe physical incapacitation and/or death to no apparent physiological response, depending on predator susceptibility and detoxification capability. Most bioactive compounds are present in very low concentrations, in both the producing organism and the surrounding aqueous medium. Furthermore, bioactivity may be subject to synergistic interactions with other natural and anthropogenic environmental toxicants. Most, if not all phycotoxins are classic secondary metabolites, but many other bioactive metabolites are simple molecules derived from primary metabolism (e.g., PUAs in diatoms, dimethylsulfoniopropionate (DMSP) in prymnesiophytes). Producing cells do not seem to suffer physiological impact due to their synthesis. Functional genome sequence data and gene expression analysis will provide insights into regulatory and metabolic pathways in producer organisms, as well as identification of mechanisms of action in target organisms. Understanding chemical ecological responses to environmental triggers and chemically-mediated species interactions will help define crucial chemical and molecular processes that help maintain biodiversity and ecosystem functionality. PMID:22131962

Systems Biology Approach Reveals a Calcium-Dependent Mechanism for Basal Toxicity in Daphnia magna.

PubMed

Antczak, Philipp; White, Thomas A; Giri, Anirudha; Michelangeli, Francesco; Viant, Mark R; Cronin, Mark T D; Vulpe, Chris; Falciani, Francesco

2015-09-15

The expanding diversity and ever increasing amounts of man-made chemicals discharged to the environment pose largely unknown hazards to ecosystem and human health. The concept of adverse outcome pathways (AOPs) emerged as a comprehensive framework for risk assessment. However, the limited mechanistic information available for most chemicals and a lack of biological pathway annotation in many species represent significant challenges to effective implementation of this approach. Here, a systems level, multistep modeling strategy demonstrates how to integrate information on chemical structure with mechanistic insight from genomic studies, and phenotypic effects to define a putative adverse outcome pathway. Results indicated that transcriptional changes indicative of intracellular calcium mobilization were significantly overrepresented in Daphnia magna (DM) exposed to sublethal doses of presumed narcotic chemicals with log Kow ≥ 1.8. Treatment of DM with a calcium ATPase pump inhibitor substantially recapitulated the common transcriptional changes. We hypothesize that calcium mobilization is a potential key molecular initiating event in DM basal (narcosis) toxicity. Heart beat rate analysis and metabolome analysis indicated sublethal effects consistent with perturbations of calcium preceding overt acute toxicity. Together, the results indicate that altered calcium homeostasis may be a key early event in basal toxicity or narcosis induced by lipophilic compounds.

Raman Enhancement Effect on Thin GaSe Flake and Its Thickness Dependence

NASA Astrophysics Data System (ADS)

Quan, Lin; Song, Yuqing; Zhang, Guanghui; Wu, Yukun; Jin, Ke; Ding, Huaiyi; Pan, Nan; Luo, Yi; Wang, Xiaoping

Chemical enhancement is one of the important mechanisms in surface-enhanced Raman spectroscopy, however, its origin is still under debate. Two dimensional (2D) layered material is thought to be a strong candidate to investigate the chemical mechanism of Raman enhancement because it has flat surface, well defined structure and without the interference of electromagnetic enhancement. Herein we report the systematic studies of Raman enhancement effect on the gallium selenide (GaSe) flake by using copper phthalocyanine (CuPc) molecule as a probe. It is found that the Raman signal of CuPc on the monolayer GaSe can be significantly increased by one order of magnitude than that on the SiO2/Si substrate. Meanwhile, the enhancement effect is found to decrease with increasing the thickness of GaSe flake. The origin of the Raman enhancement is attributed to the chemical mechanism resulted from the charge transfer between the GaSe flake and the detected molecules. The supposition is further verified by the investigation of Raman enhancement effect of CuPc with different thicknesses on the GaSe flake. Our work will shed more light on the understanding of the chemical mechanism for Raman enhancement and expand more practical applications of GaSe.

Choreographing an enzyme’s dance

PubMed Central

Villali, Janice; Kern, Dorothee

2010-01-01

While ground state structures combined with chemical tools and enzyme kinetics deliver useful information on possible chemical mechanisms of enzyme catalysis, they do not unravel the finely balanced energy inventory to explain the impressive rate enhancement of enzymes. For this goal, a complete description of enzyme catalysis in the form of an energy landscape is needed. Since the rate of catalysis is determined by the climb over a sequence of energy barriers, we focus here on the critical question of transition pathways. A combination of time-resolved NMR and simulation deliver a glimpse into how proteins can so efficiently move within the ensemble of the native conformations while avoiding unfolding during that journey. The loss of energy due to breakage of native contacts is compensated by non-native transient hydrogen bonds during the transition thereby “holding on” to the energy until the new native contacts form that define the alternate functional state. The use of kinetic isotope effects (KIE) to study the chemical step show that coordinated atomic fluctuations of the protein component dictate the probability of “correct” distance and orientation, due to its extreme sensitivity to distance. The examples here stress the point that highly choreographed conformational sampling together with chemical integrity is a prerequisite for efficient enzyme catalysis. PMID:20822946

A realistic molecular model of cement hydrates.

PubMed

Pellenq, Roland J-M; Kushima, Akihiro; Shahsavari, Rouzbeh; Van Vliet, Krystyn J; Buehler, Markus J; Yip, Sidney; Ulm, Franz-Josef

2009-09-22

Despite decades of studies of calcium-silicate-hydrate (C-S-H), the structurally complex binder phase of concrete, the interplay between chemical composition and density remains essentially unexplored. Together these characteristics of C-S-H define and modulate the physical and mechanical properties of this "liquid stone" gel phase. With the recent determination of the calcium/silicon (C/S = 1.7) ratio and the density of the C-S-H particle (2.6 g/cm(3)) by neutron scattering measurements, there is new urgency to the challenge of explaining these essential properties. Here we propose a molecular model of C-S-H based on a bottom-up atomistic simulation approach that considers only the chemical specificity of the system as the overriding constraint. By allowing for short silica chains distributed as monomers, dimers, and pentamers, this C-S-H archetype of a molecular description of interacting CaO, SiO2, and H2O units provides not only realistic values of the C/S ratio and the density computed by grand canonical Monte Carlo simulation of water adsorption at 300 K. The model, with a chemical composition of (CaO)(1.65)(SiO2)(H2O)(1.75), also predicts other essential structural features and fundamental physical properties amenable to experimental validation, which suggest that the C-S-H gel structure includes both glass-like short-range order and crystalline features of the mineral tobermorite. Additionally, we probe the mechanical stiffness, strength, and hydrolytic shear response of our molecular model, as compared to experimentally measured properties of C-S-H. The latter results illustrate the prospect of treating cement on equal footing with metals and ceramics in the current application of mechanism-based models and multiscale simulations to study inelastic deformation and cracking.

Structural and tribometric characterization of biomimetically inspired synthetic "insect adhesives"

PubMed Central

Speidel, Matthias W; Kleemeier, Malte; Hartwig, Andreas; Rischka, Klaus; Ellermann, Angelika; Daniels, Rolf

2017-01-01

Background: Based on previous chemical analyses of insect tarsal adhesives, we prepared 12 heterogeneous synthetic emulsions mimicking the polar/non-polar principle, analysed their microscopical structure and tested their adhesive, frictional, and rheological properties. Results: The prepared emulsions varied in their consistency from solid rubber-like, over soft elastic, to fluid (watery or oily). With droplet sizes >100 nm, all the emulsions belonged to the common type of macroemulsions. The emulsions of the first generation generally showed broader droplet-size ranges compared with the second generation, especially when less defined components such as petrolatum or waxes were present in the lipophilic fraction of the first generation of emulsions. Some of the prepared emulsions showed a yield point and were Bingham fluids. Tribometric adhesion was tested via probe tack tests. Compared with the "second generation" (containing less viscous components), the "first generation" emulsions were much more adhesive (31–93 mN), a finding attributable to their highly viscous components, i.e., wax, petrolatum, gelatin and poly(vinyl alcohol). In the second generation emulsions, we attained much lower adhesivenesses, ranging between 1–18 mN. The adhesive performance was drastically reduced in the emulsions that contained albumin as the protein component or that lacked protein. Tribometric shear tests were performed at moderate normal loads. Our measured friction forces (4–93 mN in the first and 0.1–5.8 mN in the second generation emulsions) were comparatively low. Differences in shear performance were related to the chemical composition and emulsion structure. Conclusion: By varying their chemical composition, synthetic heterogeneous adhesive emulsions can be adjusted to have diverse consistencies and are able to mimic certain rheological and tribological properties of natural tarsal insect adhesives. PMID:28144564

Nanometer-Scale Chemistry of a Calcite Biomineralization Template: Implications for Skeletal Composition and Nucleation

PubMed Central

Bonnin, Elisa A.; Perea, Daniel E.; Spero, Howard J.; Zhu, Zihua; Winters, Maria; Hönisch, Bärbel; Russell, Ann D.; Fehrenbacher, Jennifer S.; Gagnon, Alexander C.

2016-01-01

Plankton, corals, and other organisms produce calcium carbonate skeletons that are integral to their survival, form a key component of the global carbon cycle, and record an archive of past oceanographic conditions in their geochemistry. A key aspect of the formation of these biominerals is the interaction between organic templating structures and mineral precipitation processes. Laboratory-based studies have shown that these atomic-scale processes can profoundly influence the architecture and composition of minerals, but their importance in calcifying organisms is poorly understood because it is difficult to measure the chemistry of in vivo biomineral interfaces at spatially relevant scales. Understanding the role of templates in biomineral nucleation, and their importance in skeletal geochemistry requires an integrated, multiscale approach, which can place atom-scale observations of organic-mineral interfaces within a broader structural and geochemical context. Here we map the chemistry of an embedded organic template structure within a carbonate skeleton of the foraminifera Orbulina universa using both atom probe tomography (APT), a 3D chemical imaging technique with Ångström-level spatial resolution, and time-of-flight secondary ionization mass spectrometry (ToF-SIMS), a 2D chemical imaging technique with submicron resolution. We quantitatively link these observations, revealing that the organic template in O. universa is uniquely enriched in both Na and Mg, and contributes to intraskeletal chemical heterogeneity. Our APT analyses reveal the cation composition of the organic surface, offering evidence to suggest that cations other than Ca2+, previously considered passive spectator ions in biomineral templating, may be important in defining the energetics of carbonate nucleation on organic templates. PMID:27794119

Determination of contact maps in proteins: A combination of structural and chemical approaches

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

Wołek, Karol; Cieplak, Marek, E-mail: mc@ifpan.edu.pl; Gómez-Sicilia, Àngel

2015-12-28

Contact map selection is a crucial step in structure-based molecular dynamics modelling of proteins. The map can be determined in many different ways. We focus on the methods in which residues are represented as clusters of effective spheres. One contact map, denoted as overlap (OV), is based on the overlap of such spheres. Another contact map, named Contacts of Structural Units (CSU), involves the geometry in a different way and, in addition, brings chemical considerations into account. We develop a variant of the CSU approach in which we also incorporate Coulombic effects such as formation of the ionic bridges andmore » destabilization of possible links through repulsion. In this way, the most essential and well defined contacts are identified. The resulting residue-residue contact map, dubbed repulsive CSU (rCSU), is more sound in its physico-chemical justification than CSU. It also provides a clear prescription for validity of an inter-residual contact: the number of attractive atomic contacts should be larger than the number of repulsive ones — a feature that is not present in CSU. However, both of these maps do not correlate well with the experimental data on protein stretching. Thus, we propose to use rCSU together with the OV map. We find that the combined map, denoted as OV+rCSU, performs better than OV. In most situations, OV and OV+rCSU yield comparable folding properties but for some proteins rCSU provides contacts which improve folding in a substantial way. We discuss the likely residue-specificity of the rCSU contacts. Finally, we make comparisons to the recently proposed shadow contact map, which is derived from different principles.« less

The Toxicity Data Landscape for Environmental Chemicals

PubMed Central

Judson, Richard; Richard, Ann; Dix, David J.; Houck, Keith; Martin, Matthew; Kavlock, Robert; Dellarco, Vicki; Henry, Tala; Holderman, Todd; Sayre, Philip; Tan, Shirlee; Carpenter, Thomas; Smith, Edwin

2009-01-01

Objective Thousands of chemicals are in common use, but only a portion of them have undergone significant toxicologic evaluation, leading to the need to prioritize the remainder for targeted testing. To address this issue, the U.S. Environmental Protection Agency (EPA) and other organizations are developing chemical screening and prioritization programs. As part of these efforts, it is important to catalog, from widely dispersed sources, the toxicology information that is available. The main objective of this analysis is to define a list of environmental chemicals that are candidates for the U.S. EPA screening and prioritization process, and to catalog the available toxicology information. Data sources We are developing ACToR (Aggregated Computational Toxicology Resource), which combines information for hundreds of thousands of chemicals from > 200 public sources, including the U.S. EPA, National Institutes of Health, Food and Drug Administration, corresponding agencies in Canada, Europe, and Japan, and academic sources. Data extraction ACToR contains chemical structure information; physical–chemical properties; in vitro assay data; tabular in vivo data; summary toxicology calls (e.g., a statement that a chemical is considered to be a human carcinogen); and links to online toxicology summaries. Here, we use data from ACToR to assess the toxicity data landscape for environmental chemicals. Data synthesis We show results for a set of 9,912 environmental chemicals being considered for analysis as part of the U.S. EPA ToxCast screening and prioritization program. These include high-and medium-production-volume chemicals, pesticide active and inert ingredients, and drinking water contaminants. Conclusions Approximately two-thirds of these chemicals have at least limited toxicity summaries available. About one-quarter have been assessed in at least one highly curated toxicology evaluation database such as the U.S. EPA Toxicology Reference Database, U.S. EPA Integrated Risk Information System, and the National Toxicology Program. PMID:19479008

Backbone-only restraints for fast determination of the protein fold: The role of paramagnetism-based restraints. Cytochrome b562 as an example

NASA Astrophysics Data System (ADS)

Banci, Lucia; Bertini, Ivano; Felli, Isabella C.; Sarrou, Josephine

2005-02-01

CH α residual dipolar couplings (Δ rdc's) were measured for the oxidized cytochrome b562 from Escherichia coli as a result of its partial self-orientation in high magnetic fields due to the anisotropy of the overall magnetic susceptibility tensor. Both the low spin iron (III) heme and the four-helix bundle fold contribute to the magnetic anisotropy tensor. CH α Δ rdc's, which span a larger range than the analogous NH values (already available in the literature) sample large space variations at variance with NH Δ rdc's, which are largely isooriented within α helices. The whole structure is now significantly refined with the chemical shift index and CH α Δ rdc's. The latter are particularly useful also in defining the molecular magnetic anisotropy parameters. It is shown here that the backbone folding can be conveniently and accurately determined using backbone restraints only, which include NOEs, hydrogen bonds, residual dipolar couplings, pseudocontact shifts, and chemical shift index. All these restraints are easily and quickly determined from the backbone assignment. The calculated backbone structure is comparable to that obtained by using also side chain restraint. Furthermore, the structure obtained with backbone only restraints is, in its whole, very similar to that obtained with the complete set of restraints. The paramagnetism based restraints are shown to be absolutely relevant, especially for Δ rdc's.

CHEMICAL STRUCTURE INDEXING OF TOXICITY DATA ON ...

EPA Pesticide Factsheets

Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives that are accelerating the pace of this transformation, with particular reference to toxicology-related chemical information. Chemical content annotators, structure locator services, large structure/data aggregator web sites, structure browsers, International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) codes, toxicity data models and public chemical/biological activity profiling initiatives are all playing a role in overcoming barriers to the integration of toxicity data, and are bringing researchers closer to the reality of a mineable chemical Semantic Web. An example of this integration of data is provided by the collaboration among researchers involved with the Distributed Structure-Searchable Toxicity (DSSTox) project, the Carcinogenic Potency Project, projects at the National Cancer Institute and the PubChem database. Standardizing chemical structure annotation of public toxicity databases

Representational Competence in Chemistry: A Comparison between Students with Different Levels of Understanding of Basic Chemical Concepts and Chemical Representations

ERIC Educational Resources Information Center

Sim, Joong Hiong; Daniel, Esther Gnanamalar Sarojini

2014-01-01

Representational competence is defined as "skills in interpreting and using representations". This study attempted to compare students' of high, medium, and low levels of understanding of (1) basic chemical concepts, and (2) chemical representations, in their representational competence. A total of 411 Form 4 science students (mean age =…

Chemically Defined Medium and Caenorhabditis elegans: A Powerful Approach

NASA Technical Reports Server (NTRS)

Szewczyk, N. J.; Kozak, E.; Conley, C. A.

2003-01-01

C. elegans has been established as a powerful genetic system. Growth in a chemically defined medium (C. elegans Maintenance Medium (CeMM)) now allows standardization and systematic manipulation of the nutrients that animals receive. Liquid cultivation allows automated culturing and experimentation and should be of me in large-scale growth and screening of animals. Here we present our initial results from developing culture systems with CeMM. We find that CeMM is versatile and culturing is simple. CeMM can be used in a solid or liquid state, it can be stored unused for at least a year, unattended actively growing cultures may be maintained longer than with standard techniques, and standard C. elegans protocols work well with animals grown in defined medium. We also find that there are caveats of using defined medium. Animals in defined medium grow more slowly than on standard medium, appear to display adaptation to the defined medium, and display altered growth rates as they change defined medium composition. As was suggested with the introduction of C. elegans as a potential genetic system, use of defined medium with C. elegans should prove a powerful tool.

Is an ecosystem services-based approach developed for setting specific protection goals for plant protection products applicable to other chemicals?

PubMed

Maltby, Lorraine; Jackson, Mathew; Whale, Graham; Brown, A Ross; Hamer, Mick; Solga, Andreas; Kabouw, Patrick; Woods, Richard; Marshall, Stuart

2017-02-15

Clearly defined protection goals specifying what to protect, where and when, are required for designing scientifically sound risk assessments and effective risk management of chemicals. Environmental protection goals specified in EU legislation are defined in general terms, resulting in uncertainty in how to achieve them. In 2010, the European Food Safety Authority (EFSA) published a framework to identify more specific protection goals based on ecosystem services potentially affected by plant protection products. But how applicable is this framework to chemicals with different emission scenarios and receptor ecosystems? Four case studies used to address this question were: (i) oil refinery waste water exposure in estuarine environments; (ii) oil dispersant exposure in aquatic environments; (iii) down the drain chemicals exposure in a wide range of ecosystems (terrestrial and aquatic); (iv) persistent organic pollutant exposure in remote (pristine) Arctic environments. A four-step process was followed to identify ecosystems and services potentially impacted by chemical emissions and to define specific protection goals. Case studies demonstrated that, in principle, the ecosystem services concept and the EFSA framework can be applied to derive specific protection goals for a broad range of chemical exposure scenarios. By identifying key habitats and ecosystem services of concern, the approach offers the potential for greater spatial and temporal resolution, together with increased environmental relevance, in chemical risk assessments. With modifications including improved clarity on terminology/definitions and further development/refinement of the key concepts, we believe the principles of the EFSA framework could provide a methodical approach to the identification and prioritization of ecosystems, ecosystem services and the service providing units that are most at risk from chemical exposure. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Impact of Chemical Proportions on the Acute Neurotoxicity of a Mixture of Seven Carbamates in Rats

EPA Science Inventory

Environmental exposures generally involve multiple chemicals and pathways, and statistical methodologies now exist to evaluate interactions among any number of chemicals in defined mixtures. N-methyl carbamate pesticides are presumed to act through a common mode of action, that i...

High-throughput exposure modeling to support prioritization of chemicals in personal care products

EPA Science Inventory

We demonstrate the application of a high-throughput modeling framework to estimate exposure to chemicals used in personal care products (PCPs). As a basis for estimating exposure, we use the product intake fraction (PiF), defined as the mass of chemical taken by an individual or ...

Solving the scalability issue in quantum-based refinement: Q|R#1.

PubMed

Zheng, Min; Moriarty, Nigel W; Xu, Yanting; Reimers, Jeffrey R; Afonine, Pavel V; Waller, Mark P

2017-12-01

Accurately refining biomacromolecules using a quantum-chemical method is challenging because the cost of a quantum-chemical calculation scales approximately as n m , where n is the number of atoms and m (≥3) is based on the quantum method of choice. This fundamental problem means that quantum-chemical calculations become intractable when the size of the system requires more computational resources than are available. In the development of the software package called Q|R, this issue is referred to as Q|R#1. A divide-and-conquer approach has been developed that fragments the atomic model into small manageable pieces in order to solve Q|R#1. Firstly, the atomic model of a crystal structure is analyzed to detect noncovalent interactions between residues, and the results of the analysis are represented as an interaction graph. Secondly, a graph-clustering algorithm is used to partition the interaction graph into a set of clusters in such a way as to minimize disruption to the noncovalent interaction network. Thirdly, the environment surrounding each individual cluster is analyzed and any residue that is interacting with a particular cluster is assigned to the buffer region of that particular cluster. A fragment is defined as a cluster plus its buffer region. The gradients for all atoms from each of the fragments are computed, and only the gradients from each cluster are combined to create the total gradients. A quantum-based refinement is carried out using the total gradients as chemical restraints. In order to validate this interaction graph-based fragmentation approach in Q|R, the entire atomic model of an amyloid cross-β spine crystal structure (PDB entry 2oNA) was refined.

From precision polymers to complex materials and systems

NASA Astrophysics Data System (ADS)

Lutz, Jean-François; Lehn, Jean-Marie; Meijer, E. W.; Matyjaszewski, Krzysztof

2016-05-01

Complex chemical systems, such as living biological matter, are highly organized structures based on discrete molecules in constant dynamic interactions. These natural materials can evolve and adapt to their environment. By contrast, man-made materials exhibit simpler properties. In this Review, we highlight that most of the necessary elements for the development of more complex synthetic matter are available today. Using modern strategies, such as controlled radical polymerizations, supramolecular polymerizations or stepwise synthesis, polymers with precisely controlled molecular structures can be synthesized. Moreover, such tailored polymers can be folded or self-assembled into defined nanoscale morphologies. These self-organized macromolecular objects can be at thermal equilibrium or can be driven out of equilibrium. Recently, in the latter case, interesting dynamic materials have been developed. However, this is just a start, and more complex adaptive materials are anticipated.

A systematic investigation of the preparation and properties of composite carbon molecular sieves containing inorganic oxides

NASA Technical Reports Server (NTRS)

Foley, Henry C.

1990-01-01

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

The Development of High-Density Vertical Silicon Nanowires and Their Application in a Heterojunction Diode.

PubMed

Chang, Wen-Chung; Su, Sheng-Chien; Wu, Chia-Ching

2016-06-30

Vertically aligned p-type silicon nanowire (SiNW) arrays were fabricated through metal-assisted chemical etching (MACE) of Si wafers. An indium tin oxide/indium zinc oxide/silicon nanowire (ITO/IZO/SiNW) heterojunction diode was formed by depositing ITO and IZO thin films on the vertically aligned SiNW arrays. The structural and electrical properties of the resulting ITO/IZO/SiNW heterojunction diode were characterized by field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and current-voltage (I-V) measurements. Nonlinear and rectifying I-V properties confirmed that a heterojunction diode was successfully formed in the ITO/IZO/SiNW structure. The diode had a well-defined rectifying behavior, with a rectification ratio of 550.7 at 3 V and a turn-on voltage of 2.53 V under dark conditions.

Controlled Release from Recombinant Polymers

PubMed Central

Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

2014-01-01

Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed. PMID:24956486

Synthetic approaches to aromatic belts: building up strain in macrocyclic polyarenes.

PubMed

Eisenberg, David; Shenhar, Roy; Rabinovitz, Mordecai

2010-08-01

This tutorial review discusses synthetic strategies towards aromatic belts, defined here as double-stranded conjugated macrocycles, such as [n]cyclacenes, [n]cyclophenacenes, Schlüter belt, and Vögtle belt. Their appeal stems, firstly, from the unique nature of their conjugation, having p orbitals oriented radially rather than perpendicular to the plane of the macrocycle. Secondly, as aromatic belts are model compounds of carbon nanotubes of different chiralities, a synthetic strategy towards the buildup of structural strain in these compounds could finally open a route towards rational chemical synthesis of carbon nanotubes. The elusiveness of these compounds has stimulated fascinating and ingenious synthetic strategies over the last decades. The various strategies are classified here by their approach to the buildup of structural strain, which is the main obstacle in the preparation of these curved polyarenes.

In situ X-ray probing reveals fingerprints of surface platinum oxide.

PubMed

Friebel, Daniel; Miller, Daniel J; O'Grady, Christopher P; Anniyev, Toyli; Bargar, John; Bergmann, Uwe; Ogasawara, Hirohito; Wikfeldt, Kjartan Thor; Pettersson, Lars G M; Nilsson, Anders

2011-01-07

In situ X-ray absorption spectroscopy (XAS) at the Pt L(3) edge is a useful probe for Pt-O interactions at polymer electrolyte membrane fuel cell (PEMFC) cathodes. We show that XAS using the high energy resolution fluorescence detection (HERFD) mode, applied to a well-defined monolayer Pt/Rh(111) sample where the bulk penetrating hard X-rays probe only surface Pt atoms, provides a unique sensitivity to structure and chemical bonding at the Pt-electrolyte interface. Ab initio multiple-scattering calculations using the FEFF code and complementary extended X-ray absorption fine structure (EXAFS) results indicate that the commonly observed large increase of the white-line at high electrochemical potentials on PEMFC cathodes originates from platinum oxide formation, whereas previously proposed chemisorbed oxygen-containing species merely give rise to subtle spectral changes.

Development of methodology for identification the nature of the polyphenolic extracts by FTIR associated with multivariate analysis

NASA Astrophysics Data System (ADS)

Grasel, Fábio dos Santos; Ferrão, Marco Flôres; Wolf, Carlos Rodolfo

2016-01-01

Tannins are polyphenolic compounds of complex structures formed by secondary metabolism in several plants. These polyphenolic compounds have different applications, such as drugs, anti-corrosion agents, flocculants, and tanning agents. This study analyses six different type of polyphenolic extracts by Fourier transform infrared spectroscopy (FTIR) combined with multivariate analysis. Through both principal component analysis (PCA) and hierarchical cluster analysis (HCA), we observed well-defined separation between condensed (quebracho and black wattle) and hydrolysable (valonea, chestnut, myrobalan, and tara) tannins. For hydrolysable tannins, it was also possible to observe the formation of two different subgroups between samples of chestnut and valonea and between samples of tara and myrobalan. Among all samples analysed, the chestnut and valonea showed the greatest similarity, indicating that these extracts contain equivalent chemical compositions and structure and, therefore, similar properties.

Carbohydrate Cluster Microarrays Fabricated on 3-Dimensional Dendrimeric Platforms for Functional Glycomics Exploration

PubMed Central

Zhou, Xichun; Turchi, Craig; Wang, Denong

2009-01-01

We reported here a novel, ready-to-use bioarray platform and methodology for construction of sensitive carbohydrate cluster microarrays. This technology utilizes a 3-dimensional (3-D) poly(amidoamine) starburst dendrimer monolayer assembled on glass surface, which is functionalized with terminal aminooxy and hydrazide groups for site-specific coupling of carbohydrates. A wide range of saccharides, including monosaccharides, oligosaccharides and polysaccharides of diverse structures, are applicable for the 3-D bioarray platform without prior chemical derivatization. The process of carbohydrate coupling is effectively accelerated by microwave radiation energy. The carbohydrate concentration required for microarray fabrication is substantially reduced using this technology. Importantly, this bioarray platform presents sugar chains in defined orientation and cluster configurations. It is, thus, uniquely useful for exploration of the structural and conformational diversities of glyco-epitope and their functional properties. PMID:19791771

A study of the propagation, dynamics, and extinguishment of cellular flames using microgravity techniques

NASA Technical Reports Server (NTRS)

Ronney, Paul D.

1989-01-01

The characteristics of premixed gas flames in mixtures with low Lewis numbers, free of natural convection effects, were investigated and found to be dominated by diffusive-thermal instabilities. For sufficiently reactive mixtures, cellular structures resulting from these instabilities were observed and found to spawn new cells in regular patterns. For less reactive mixtures, cells formed shortly after ignition but did not spawn new cells; instead these cells evolved into a flame structure composed of stationary, apparently stable spherical flamelets. As a result of these phenomena, well-defined flammability limits were not observed. The experimental results are found to be in qualitative agreement with a simple analytical model based on the interaction of heat release due to chemical reaction, differential diffusion of thermal energy and mass, flame front curvature, and heat losses due to gas radiation.

Nanotechnology in the Chemical Industry - Opportunities and Challenges

NASA Astrophysics Data System (ADS)

Qiu Zhao, Qian; Boxman, Arthur; Chowdhry, Uma

2003-12-01

The traditional chemical industry has become a largely mature industry with many commodity products based on established technologies. Therefore, new product and market opportunities will more likely come from speciality chemicals, and from new functionalities obtained from new processing technologies as well as new microstructure control methodologies. It is a well-known fact that in addition to its molecular structure, the microstructure of a material is key to determining its properties. Controlling structures at the micro- and nano-levels is therefore essential to new discoveries. For this article, we define nanotechnology as the controlled manipulation of nanomaterials with at least one dimension less than 100nm. Nanotechnology is emerging as one of the principal areas of investigation that is integrating chemistry and materials science, and in some cases integrating these with biology to create new and yet undiscovered properties that can be exploited to gain new market opportunities. In this article market opportunities for nanotechnology will be presented from an industrial perspective covering electronic, biomedical, performance materials, and consumer products. Manufacturing technology challenges will be identified, including operations ranging from particle formation, coating, dispersion, to characterization, modeling, and simulation. Finally, a nanotechnology innovation roadmap is proposed wherein the interplay between the development of nanoscale building blocks, product design, process design, and value chain integration is identified. A suggestion is made for an R&D model combining market pull and technology push as a way to quickly exploit the advantages in nanotechnology and translate these into customer benefits.

A comparative study of physico-chemical properties of CBD and SILAR grown ZnO thin films

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

Jambure, S.B.; Patil, S.J.; Deshpande, A.R.

2014-01-01

Graphical abstract: Schematic model indicating ZnO nanorods by CBD (Z{sub 1}) and nanograins by SILAR (Z{sub 2}). - Highlights: • Simple methods for the synthesis of ZnO thin films. • Comparative study of physico-chemical properties of ZnO thin films prepared by CBD and SILAR methods. • CBD outperforms SILAR method. - Abstract: In the present work, nanocrystalline zinc oxide (ZnO) thin films have been successfully deposited onto glass substrates by simple and economical chemical bath deposition (CBD) and successive ionic layer adsorption reaction (SILAR) methods. These films were further characterized for their structural, optical, surface morphological and wettability properties. Themore » X-ray diffraction (XRD) patterns for both CBD and SILAR deposited ZnO thin films reveal the highly crystalline hexagonal wurtzite structure. From optical studies, band gaps obtained are 2.9 and 3.0 eV for CBD and SILAR deposited thin films, respectively. The scanning electron microscope (SEM) patterns show growth of well defined randomly oriented nanorods and nanograins on the CBD and SILAR deposited samples, respectively. The resistivity of CBD deposited films (10{sup 2} Ω cm) is lower than that of SILAR deposited films (10{sup 5} Ω cm). Surface wettability studies show hydrophobic nature for both films. From the above results it can be concluded that CBD grown ZnO thin films show better properties as compared to SILAR method.« less

Rapid and reliable protein structure determination via chemical shift threading.

PubMed

Hafsa, Noor E; Berjanskii, Mark V; Arndt, David; Wishart, David S

2018-01-01

Protein structure determination using nuclear magnetic resonance (NMR) spectroscopy can be both time-consuming and labor intensive. Here we demonstrate how chemical shift threading can permit rapid, robust, and accurate protein structure determination using only chemical shift data. Threading is a relatively old bioinformatics technique that uses a combination of sequence information and predicted (or experimentally acquired) low-resolution structural data to generate high-resolution 3D protein structures. The key motivations behind using NMR chemical shifts for protein threading lie in the fact that they are easy to measure, they are available prior to 3D structure determination, and they contain vital structural information. The method we have developed uses not only sequence and chemical shift similarity but also chemical shift-derived secondary structure, shift-derived super-secondary structure, and shift-derived accessible surface area to generate a high quality protein structure regardless of the sequence similarity (or lack thereof) to a known structure already in the PDB. The method (called E-Thrifty) was found to be very fast (often < 10 min/structure) and to significantly outperform other shift-based or threading-based structure determination methods (in terms of top template model accuracy)-with an average TM-score performance of 0.68 (vs. 0.50-0.62 for other methods). Coupled with recent developments in chemical shift refinement, these results suggest that protein structure determination, using only NMR chemical shifts, is becoming increasingly practical and reliable. E-Thrifty is available as a web server at http://ethrifty.ca .

Complex Chemical Reaction Networks from Heuristics-Aided Quantum Chemistry.

PubMed

Rappoport, Dmitrij; Galvin, Cooper J; Zubarev, Dmitry Yu; Aspuru-Guzik, Alán

2014-03-11

While structures and reactivities of many small molecules can be computed efficiently and accurately using quantum chemical methods, heuristic approaches remain essential for modeling complex structures and large-scale chemical systems. Here, we present a heuristics-aided quantum chemical methodology applicable to complex chemical reaction networks such as those arising in cell metabolism and prebiotic chemistry. Chemical heuristics offer an expedient way of traversing high-dimensional reactive potential energy surfaces and are combined here with quantum chemical structure optimizations, which yield the structures and energies of the reaction intermediates and products. Application of heuristics-aided quantum chemical methodology to the formose reaction reproduces the experimentally observed reaction products, major reaction pathways, and autocatalytic cycles.

An Unusual Conformational Isomer of Verrucosidin Backbone from a Hydrothermal Vent Fungus, Penicillium sp. Y-50-10.

PubMed

Pan, Chengqian; Shi, Yutong; Auckloo, Bibi Nazia; Chen, Xuegang; Chen, Chen-Tung Arthur; Tao, Xinyi; Wu, Bin

2016-08-18

A new verrucosidin derivative, methyl isoverrucosidinol (1), was isolated from the marine fungus Penicillium sp. Y-50-10, dwelling in sulfur rich sediment in the Kueishantao hydrothermal vents off Taiwan. The structure was established by spectroscopic means including HRMS and 2D-NMR spectroscopic analysis. The absolute configuration was defined mainly by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Among hitherto known compounds with a verrucosidine backbone isolated from natural resource, compound 1 represents the first example of a new conformational isomer of its skeleton, exhibiting antibiotic activity against Bacillus subtilis with MIC value 32 μg/mL.

[3,3]-Sigmatropic rearrangements: recent applications in the total synthesis of natural products†

PubMed Central

Ilardi, Elizabeth A.; Stivala, Craig E.

2014-01-01

Among the fundamental chemical transformations in organic synthesis, the [3,3]-sigmatropic rearrangement occupies a unique position as a powerful, reliable, and well-defined method for the stereoselective construction of carbon–carbon or carbon–heteroatom bonds. While many other reactions can unite two subunits and create a new bond, the strengths of sigmatropic rearrangements derive from their ability to enable structural reorganization with unmatched build-up of complexity. Recent applications that illustrate [3,3]-sigmatropic processes as a key concept in the synthesis of complex natural products are described in this tutorial review, covering literature from about 2001 through early 2009. PMID:19847347

Electronic passivation of n- and p-type GaAs using chemical vapor deposited GaS

NASA Technical Reports Server (NTRS)

Tabib-Azar, Massood; Kang, Soon; Macinnes, Andrew N.; Power, Michael B.; Barron, Andrew R.; Jenkins, Phillip P.; Hepp, Aloysius F.

1993-01-01

We report on the electronic passivation of n- and p-type GaAs using CVD cubic GaS. Au/GaS/GaAs-fabricated metal-insulator-semiconductor (MIS) structures exhibit classical high-frequency capacitor vs voltage (C-V) behavior with well-defined accumulation and inversion regions. Using high- and low-frequency C-V, the interface trap densities of about 10 exp 11/eV per sq cm on both n- and p-type GaAs are determined. The electronic condition of GaS/GaAs interface did not show any deterioration after a six week time period.

Cellular structures with interconnected microchannels

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

Shaefer, Robert Shahram; Ghoniem, Nasr M.; Williams, Brian

A method for fabricating a cellular tritium breeder component includes obtaining a reticulated carbon foam skeleton comprising a network of interconnected ligaments. The foam skeleton is then melt-infiltrated with a tritium breeder material, for example, lithium zirconate or lithium titanate. The foam skeleton is then removed to define a cellular breeder component having a network of interconnected tritium purge channels. In an embodiment the ligaments of the foam skeleton are enlarged by adding carbon using chemical vapor infiltration (CVI) prior to melt-infiltration. In an embodiment the foam skeleton is coated with a refractory material, for example, tungsten, prior to meltmore » infiltration.« less

Evaluation of Selected Chemical Processes for Production of Low-cost Silicon, Phase 3

NASA Technical Reports Server (NTRS)

Blocher, J. M.; Browning, M. F.

1979-01-01

Refinements of the design of the 50 MT/year Experimental Process System Development Unit were made and competitive bids were received from mechanical, electrical, and structural contractors. Bids on most of the equipment were received and cataloged. Emergency procedures were defined to counter a variety of contingencies disclosed in operations and safety reviews. Experimental work with an electrolytic cell for zinc chloride disclosed no significant increase in power efficiency by steps taken to increase electrolyte circulation. On the basis of materials compatibility and permeability tests, 310 stainless steel was chosen for the shell of the fluidized-bed reactor and SiC-coated graphite for the liner.

Effect of the Polymeric Stabilizer in the Aqueous Phase Fischer-Tropsch Synthesis Catalyzed by Colloidal Cobalt Nanocatalysts

PubMed Central

Delgado, Jorge A.; Claver, Carmen; Castillón, Sergio; Curulla-Ferré, Daniel; Godard, Cyril

2017-01-01

A series of small and well defined cobalt nanoparticles were synthesized by the chemical reduction of cobalt salts in water using NaBH4 as a reducing agent and using various polymeric stabilizers. The obtained nanocatalysts of similar mean diameters (ca. 2.6 nm) were fully characterized and tested in the aqueous phase Fischer-Tropsch Synthesis (AFTS). Interestingly, the nature and structure of the stabilizers used during the synthesis of the CoNPs affected the reduction degree of cobalt and the B-doping of these NPs and consequently, influenced the performance of these nanocatalysts in AFTS. PMID:28336892

Relationship between chemical structure and rat repellency

USGS Publications Warehouse

Bellack, E.; DeWitt, J.B.; Treichler, R.

1953-01-01

Repellent activity is defined as the activity of a compound in preventing consumption of, or gnawing attacks upon, foodstuffs or articles containing or treated with the candidate substance. Data are presented on repellency indices of 2700 compounds, and it is shown that repellency is associated with specific functional groups attached to alkyl, aryl, or heterocyclic nuclei. Functional groups containing nitrogen, sulfur or halogens are most active, with amines, imides, thiocyanates and thiocarbamates forming some of the most active classes. Activity of any functional group may be affected by molecular weight, unsaturation, or spatial configuration of the nucleus, or by the presence of additional substituent groups.

2D nanomaterials assembled from sequence-defined molecules

DOE PAGES

Mu, Peng; Zhou, Guangwen; Chen, Chun-Long

2017-10-21

Two dimensional (2D) nanomaterials have attracted broad interest owing to their unique physical and chemical properties with potential applications in electronics, chemistry, biology, medicine and pharmaceutics. Due to the current limitations of traditional 2D nanomaterials (e.g., graphene and graphene oxide) in tuning surface chemistry and compositions, 2D nanomaterials assembled from sequence-defined molecules (e.g., DNAs, proteins, peptides and peptoids) have recently been developed. They represent an emerging class of 2D nanomaterials with attractive physical and chemical properties. Here, we summarize the recent progress in the synthesis and applications of this type of sequence-defined 2D nanomaterials. We also discuss the challenges andmore » opportunities in this new field.« less

2D nanomaterials assembled from sequence-defined molecules

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

Mu, Peng; Zhou, Guangwen; Chen, Chun-Long

Two dimensional (2D) nanomaterials have attracted broad interest owing to their unique physical and chemical properties with potential applications in electronics, chemistry, biology, medicine and pharmaceutics. Due to the current limitations of traditional 2D nanomaterials (e.g., graphene and graphene oxide) in tuning surface chemistry and compositions, 2D nanomaterials assembled from sequence-defined molecules (e.g., DNAs, proteins, peptides and peptoids) have recently been developed. They represent an emerging class of 2D nanomaterials with attractive physical and chemical properties. Here, we summarize the recent progress in the synthesis and applications of this type of sequence-defined 2D nanomaterials. We also discuss the challenges andmore » opportunities in this new field.« less

Predicting Odor Pleasantness from Odorant Structure: Pleasantness as a Reflection of the Physical World

DTIC Science & Technology

2009-11-01

34 ( Engen , 1982). We next reduced the dimensionality of physico- chemical properties, and identified a primary axis of physico- chemical space. This axis...words, there is no scientist or perfumer who can predict the smell of a novel molecule by its physico- chemical structure, or the physico- chemical ...structure of a novel smell. Understanding this link between physico- chemical structure and percept has been elusive because the percept is in large

Ionizable side chains at catalytic active sites of enzymes.

PubMed

Jimenez-Morales, David; Liang, Jie; Eisenberg, Bob

2012-05-01

Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1,072 Å(3). The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes.

Ionizable Side Chains at Catalytic Active Sites of Enzymes

PubMed Central

Jimenez-Morales, David; Liang, Jie

2012-01-01

Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1072 Å3. The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes. PMID:22484856

Spectroscopic study of a DNA brush synthesized in situ by surface initiated enzymatic polymerization.

PubMed

Khan, M Nuruzzaman; Tjong, Vinalia; Chilkoti, Ashutosh; Zharnikov, Michael

2013-08-29

We used a combination of synchrotron-based X-ray photoelectron spectroscopy (XPS) and angle-resolved near-edge X-ray absorption fine structure (NEXAFS) spectroscopy to study the chemical integrity, purity, and possible internal alignment of single-strand (ss) adenine deoxynucleotide (poly(A)) DNA brushes. The brushes were synthesized by surface-initiated enzymatic polymerization (SIEP) on a 25-mer of adenine self-assembled monolayer (SAM) on gold (A25-SH), wherein the terminal 3'-OH of the A25-SH serve as the initiation sites for SIEP of poly(A). XPS and NEXAFS spectra of poly(A) brushes were found to be almost identical to those of A25-SH initiator, with no unambiguous traces of contamination. Apart from the well-defined chemical integrity and contamination-free character, the brushes were found to have a high degree of orientational order, with an upright orientation of individual strands, despite their large thickness up to ~55 nm, that corresponds to a chain length of at least several hundred nucleotides for individual ssDNA molecules. The orientational order exhibited by these poly(A) DNA brushes, mediated presumably by base stacking, was found to be independent of the brush thickness as long as the packing density was high enough. The well-defined character and orientational ordering of the ssDNA brushes make them a potentially promising system for different applications.

A novel approach: chemical relational databases, and the role of the ISSCAN database on assessing chemical carcinogenicity.

PubMed

Benigni, Romualdo; Bossa, Cecilia; Richard, Ann M; Yang, Chihae

2008-01-01

Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as "look-up-tables" of existing data, and most often did not contain chemical structures. Concepts and technologies originated from the structure-activity relationships science have provided powerful tools to create new types of databases, where the effective linkage of chemical toxicity with chemical structure can facilitate and greatly enhance data gathering and hypothesis generation, by permitting: a) exploration across both chemical and biological domains; and b) structure-searchability through the data. This paper reviews the main public databases, together with the progress in the field of chemical relational databases, and presents the ISSCAN database on experimental chemical carcinogens.

ACToR Chemical Structure processing using Open Source ...

EPA Pesticide Factsheets

ACToR (Aggregated Computational Toxicology Resource) is a centralized database repository developed by the National Center for Computational Toxicology (NCCT) at the U.S. Environmental Protection Agency (EPA). Free and open source tools were used to compile toxicity data from over 1,950 public sources. ACToR contains chemical structure information and toxicological data for over 558,000 unique chemicals. The database primarily includes data from NCCT research programs, in vivo toxicity data from ToxRef, human exposure data from ExpoCast, high-throughput screening data from ToxCast and high quality chemical structure information from the EPA DSSTox program. The DSSTox database is a chemical structure inventory for the NCCT programs and currently has about 16,000 unique structures. Included are also data from PubChem, ChemSpider, USDA, FDA, NIH and several other public data sources. ACToR has been a resource to various international and national research groups. Most of our recent efforts on ACToR are focused on improving the structural identifiers and Physico-Chemical properties of the chemicals in the database. Organizing this huge collection of data and improving the chemical structure quality of the database has posed some major challenges. Workflows have been developed to process structures, calculate chemical properties and identify relationships between CAS numbers. The Structure processing workflow integrates web services (PubChem and NIH NCI Cactus) to d

Chemical profiling: A tool to decipher the structure and organisation of illicit drug markets: An 8-year study in Western Switzerland.

PubMed

Broséus, Julian; Baechler, Simon; Gentile, Natacha; Esseiva, Pierre

2016-09-01

Illicit drug analyses usually focus on the identification and quantitation of questioned material to support the judicial process. In parallel, more and more laboratories develop physical and chemical profiling methods in a forensic intelligence perspective. The analysis of large databases resulting from this approach enables not only to draw tactical and operational intelligence, but may also contribute to the strategic overview of drugs markets. In Western Switzerland, the chemical analysis of illicit drug seizures is centralised in a laboratory hosted by the University of Lausanne. For over 8 years, this laboratory has analysed 5875 cocaine and 2728 heroin specimens, coming from respectively 1138 and 614 seizures operated by police and border guards or customs. Chemical (major and minor alkaloids, purity, cutting agents, chemical class), physical (packaging and appearance) as well as circumstantial (criminal case number, mass of drug seized, date and place of seizure) information are collated in a dedicated database for each specimen. The study capitalises on this extended database and defines several indicators to characterise the structure of drugs markets, to follow-up on their evolution and to compare cocaine and heroin markets. Relational, spatial, temporal and quantitative analyses of data reveal the emergence and importance of distribution networks. They enable to evaluate the cross-jurisdictional character of drug trafficking and the observation time of drug batches, as well as the quantity of drugs entering the market every year. Results highlight the stable nature of drugs markets over the years despite the very dynamic flows of distribution and consumption. This research work illustrates how the systematic analysis of forensic data may elicit knowledge on criminal activities at a strategic level. In combination with information from other sources, such knowledge can help to devise intelligence-based preventive and repressive measures and to discuss the impact of countermeasures. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Expedite random structure searching using objects from Wyckoff positions

NASA Astrophysics Data System (ADS)

Wang, Shu-Wei; Hsing, Cheng-Rong; Wei, Ching-Ming

2018-02-01

Random structure searching has been proved to be a powerful approach to search and find the global minimum and the metastable structures. A true random sampling is in principle needed yet it would be highly time-consuming and/or practically impossible to find the global minimum for the complicated systems in their high-dimensional configuration space. Thus the implementations of reasonable constraints, such as adopting system symmetries to reduce the independent dimension in structural space and/or imposing chemical information to reach and relax into low-energy regions, are the most essential issues in the approach. In this paper, we propose the concept of "object" which is either an atom or composed of a set of atoms (such as molecules or carbonates) carrying a symmetry defined by one of the Wyckoff positions of space group and through this process it allows the searching of global minimum for a complicated system to be confined in a greatly reduced structural space and becomes accessible in practice. We examined several representative materials, including Cd3As2 crystal, solid methanol, high-pressure carbonates (FeCO3), and Si(111)-7 × 7 reconstructed surface, to demonstrate the power and the advantages of using "object" concept in random structure searching.

Nanostructured polymer brushes.

PubMed

Schmelmer, Ursula; Paul, Anne; Küller, Alexander; Steenackers, Marin; Ulman, Abraham; Grunze, Michael; Gölzhäuser, Armin; Jordan, Rainer

2007-03-01

Nanopatterned polymer brushes with sub-50-nm resolution were prepared by a combination of electron-beam chemical lithography (EBCL) of self-assembled monolayers (SAMs) and surface-initiated photopolymerization (SIPP). As a further development of our previous work, selective EBCL was performed with a highly focused electron beam and not via a mask, to region-selectively convert a SAM of 4'-nitro-1,1'-biphenyl-4-thiol to defined areas of crosslinked 4'-amino-1,1'-biphenyl-4-thiol. These "written" structures were then used to prepare surface-bonded, asymmetric, azo initiator sites of 4'-azomethylmalonodinitrile-1,1'-biphenyl-4-thiol. In the presence of bulk styrene, SIPP amplified the primary structures of line widths from 500 to 10 nm to polystyrene structures of line widths 530 nm down to approximately 45 nm at a brush height of 10 or 7 nm, respectively, as measured by scanning electron microscopy and atomic force microscopy (AFM). The relative position of individual structures was within a tolerance of a few nanometers, as verified by AFM. At line-to-line spacings down to 50-70 nm, individual polymer brush structures are still observable. Below this threshold, neighboring structures merge due to chain overlap.

Automated extraction of chemical structure information from digital raster images

PubMed Central

Park, Jungkap; Rosania, Gus R; Shedden, Kerby A; Nguyen, Mandee; Lyu, Naesung; Saitou, Kazuhiro

2009-01-01

Background To search for chemical structures in research articles, diagrams or text representing molecules need to be translated to a standard chemical file format compatible with cheminformatic search engines. Nevertheless, chemical information contained in research articles is often referenced as analog diagrams of chemical structures embedded in digital raster images. To automate analog-to-digital conversion of chemical structure diagrams in scientific research articles, several software systems have been developed. But their algorithmic performance and utility in cheminformatic research have not been investigated. Results This paper aims to provide critical reviews for these systems and also report our recent development of ChemReader – a fully automated tool for extracting chemical structure diagrams in research articles and converting them into standard, searchable chemical file formats. Basic algorithms for recognizing lines and letters representing bonds and atoms in chemical structure diagrams can be independently run in sequence from a graphical user interface-and the algorithm parameters can be readily changed-to facilitate additional development specifically tailored to a chemical database annotation scheme. Compared with existing software programs such as OSRA, Kekule, and CLiDE, our results indicate that ChemReader outperforms other software systems on several sets of sample images from diverse sources in terms of the rate of correct outputs and the accuracy on extracting molecular substructure patterns. Conclusion The availability of ChemReader as a cheminformatic tool for extracting chemical structure information from digital raster images allows research and development groups to enrich their chemical structure databases by annotating the entries with published research articles. Based on its stable performance and high accuracy, ChemReader may be sufficiently accurate for annotating the chemical database with links to scientific research articles. PMID:19196483

Teaching Structural Formulas in Chemistry: How Students Relate Structural Formulas to the Solubility of Substances.

ERIC Educational Resources Information Center

Goedhart, Martin; van Duin, Yvonne

Structural formulas give professional chemists information about physical and chemical properties of corresponding compounds. In chemistry education at secondary schools, structural formulas are introduced in the context of chemical bonding. Structural formulas are not introduced as representations of the properties of chemical compounds. This…