Application of Biologically Based Lumping To Investigate the Toxicokinetic Interactions of a Complex Gasoline Mixture.

PubMed

Jasper, Micah N; Martin, Sheppard A; Oshiro, Wendy M; Ford, Jermaine; Bushnell, Philip J; El-Masri, Hisham

2016-03-15

People are often exposed to complex mixtures of environmental chemicals such as gasoline, tobacco smoke, water contaminants, or food additives. We developed an approach that applies chemical lumping methods to complex mixtures, in this case gasoline, based on biologically relevant parameters used in physiologically based pharmacokinetic (PBPK) modeling. Inhalation exposures were performed with rats to evaluate the performance of our PBPK model and chemical lumping method. There were 109 chemicals identified and quantified in the vapor in the chamber. The time-course toxicokinetic profiles of 10 target chemicals were also determined from blood samples collected during and following the in vivo experiments. A general PBPK model was used to compare the experimental data to the simulated values of blood concentration for 10 target chemicals with various numbers of lumps, iteratively increasing from 0 to 99. Large reductions in simulation error were gained by incorporating enzymatic chemical interactions, in comparison to simulating the individual chemicals separately. The error was further reduced by lumping the 99 nontarget chemicals. The same biologically based lumping approach can be used to simplify any complex mixture with tens, hundreds, or thousands of constituents.

Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures.

PubMed

Bobb, Jennifer F; Valeri, Linda; Claus Henn, Birgit; Christiani, David C; Wright, Robert O; Mazumdar, Maitreyi; Godleski, John J; Coull, Brent A

2015-07-01

Because humans are invariably exposed to complex chemical mixtures, estimating the health effects of multi-pollutant exposures is of critical concern in environmental epidemiology, and to regulatory agencies such as the U.S. Environmental Protection Agency. However, most health effects studies focus on single agents or consider simple two-way interaction models, in part because we lack the statistical methodology to more realistically capture the complexity of mixed exposures. We introduce Bayesian kernel machine regression (BKMR) as a new approach to study mixtures, in which the health outcome is regressed on a flexible function of the mixture (e.g. air pollution or toxic waste) components that is specified using a kernel function. In high-dimensional settings, a novel hierarchical variable selection approach is incorporated to identify important mixture components and account for the correlated structure of the mixture. Simulation studies demonstrate the success of BKMR in estimating the exposure-response function and in identifying the individual components of the mixture responsible for health effects. We demonstrate the features of the method through epidemiology and toxicology applications. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Quantitative trace analysis of complex mixtures using SABRE hyperpolarization.

PubMed

Eshuis, Nan; van Weerdenburg, Bram J A; Feiters, Martin C; Rutjes, Floris P J T; Wijmenga, Sybren S; Tessari, Marco

2015-01-26

Signal amplification by reversible exchange (SABRE) is an emerging nuclear spin hyperpolarization technique that strongly enhances NMR signals of small molecules in solution. However, such signal enhancements have never been exploited for concentration determination, as the efficiency of SABRE can strongly vary between different substrates or even between nuclear spins in the same molecule. The first application of SABRE for the quantitative analysis of a complex mixture is now reported. Despite the inherent complexity of the system under investigation, which involves thousands of competing binding equilibria, analytes at concentrations in the low micromolar range could be quantified from single-scan SABRE spectra using a standard-addition approach. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nonparametric Fine Tuning of Mixtures: Application to Non-Life Insurance Claims Distribution Estimation

NASA Astrophysics Data System (ADS)

Sardet, Laure; Patilea, Valentin

When pricing a specific insurance premium, actuary needs to evaluate the claims cost distribution for the warranty. Traditional actuarial methods use parametric specifications to model claims distribution, like lognormal, Weibull and Pareto laws. Mixtures of such distributions allow to improve the flexibility of the parametric approach and seem to be quite well-adapted to capture the skewness, the long tails as well as the unobserved heterogeneity among the claims. In this paper, instead of looking for a finely tuned mixture with many components, we choose a parsimonious mixture modeling, typically a two or three-component mixture. Next, we use the mixture cumulative distribution function (CDF) to transform data into the unit interval where we apply a beta-kernel smoothing procedure. A bandwidth rule adapted to our methodology is proposed. Finally, the beta-kernel density estimate is back-transformed to recover an estimate of the original claims density. The beta-kernel smoothing provides an automatic fine-tuning of the parsimonious mixture and thus avoids inference in more complex mixture models with many parameters. We investigate the empirical performance of the new method in the estimation of the quantiles with simulated nonnegative data and the quantiles of the individual claims distribution in a non-life insurance application.

Mixture-based gatekeeping procedures in adaptive clinical trials.

PubMed

Kordzakhia, George; Dmitrienko, Alex; Ishida, Eiji

2018-01-01

Clinical trials with data-driven decision rules often pursue multiple clinical objectives such as the evaluation of several endpoints or several doses of an experimental treatment. These complex analysis strategies give rise to "multivariate" multiplicity problems with several components or sources of multiplicity. A general framework for defining gatekeeping procedures in clinical trials with adaptive multistage designs is proposed in this paper. The mixture method is applied to build a gatekeeping procedure at each stage and inferences at each decision point (interim or final analysis) are performed using the combination function approach. An advantage of utilizing the mixture method is that it enables powerful gatekeeping procedures applicable to a broad class of settings with complex logical relationships among the hypotheses of interest. Further, the combination function approach supports flexible data-driven decisions such as a decision to increase the sample size or remove a treatment arm. The paper concludes with a clinical trial example that illustrates the methodology by applying it to develop an adaptive two-stage design with a mixture-based gatekeeping procedure.

Paper SERS chromatography for detection of trace analytes in complex samples

NASA Astrophysics Data System (ADS)

Yu, Wei W.; White, Ian M.

2013-05-01

We report the application of paper SERS substrates for the detection of trace quantities of multiple analytes in a complex sample in the form of paper chromatography. Paper chromatography facilitates the separation of different analytes from a complex sample into distinct sections in the chromatogram, which can then be uniquely identified using SERS. As an example, the separation and quantitative detection of heroin in a highly fluorescent mixture is demonstrated. Paper SERS chromatography has obvious applications, including law enforcement, food safety, and border protection, and facilitates the rapid detection of chemical and biological threats at the point of sample.

Automatic NMR-Based Identification of Chemical Reaction Types in Mixtures of Co-Occurring Reactions

PubMed Central

Latino, Diogo A. R. S.; Aires-de-Sousa, João

2014-01-01

The combination of chemoinformatics approaches with NMR techniques and the increasing availability of data allow the resolution of problems far beyond the original application of NMR in structure elucidation/verification. The diversity of applications can range from process monitoring, metabolic profiling, authentication of products, to quality control. An application related to the automatic analysis of complex mixtures concerns mixtures of chemical reactions. We encoded mixtures of chemical reactions with the difference between the 1H NMR spectra of the products and the reactants. All the signals arising from all the reactants of the co-occurring reactions were taken together (a simulated spectrum of the mixture of reactants) and the same was done for products. The difference spectrum is taken as the representation of the mixture of chemical reactions. A data set of 181 chemical reactions was used, each reaction manually assigned to one of 6 types. From this dataset, we simulated mixtures where two reactions of different types would occur simultaneously. Automatic learning methods were trained to classify the reactions occurring in a mixture from the 1H NMR-based descriptor of the mixture. Unsupervised learning methods (self-organizing maps) produced a reasonable clustering of the mixtures by reaction type, and allowed the correct classification of 80% and 63% of the mixtures in two independent test sets of different similarity to the training set. With random forests (RF), the percentage of correct classifications was increased to 99% and 80% for the same test sets. The RF probability associated to the predictions yielded a robust indication of their reliability. This study demonstrates the possibility of applying machine learning methods to automatically identify types of co-occurring chemical reactions from NMR data. Using no explicit structural information about the reactions participants, reaction elucidation is performed without structure elucidation of the molecules in the mixtures. PMID:24551112

Automatic NMR-based identification of chemical reaction types in mixtures of co-occurring reactions.

PubMed

Latino, Diogo A R S; Aires-de-Sousa, João

2014-01-01

The combination of chemoinformatics approaches with NMR techniques and the increasing availability of data allow the resolution of problems far beyond the original application of NMR in structure elucidation/verification. The diversity of applications can range from process monitoring, metabolic profiling, authentication of products, to quality control. An application related to the automatic analysis of complex mixtures concerns mixtures of chemical reactions. We encoded mixtures of chemical reactions with the difference between the (1)H NMR spectra of the products and the reactants. All the signals arising from all the reactants of the co-occurring reactions were taken together (a simulated spectrum of the mixture of reactants) and the same was done for products. The difference spectrum is taken as the representation of the mixture of chemical reactions. A data set of 181 chemical reactions was used, each reaction manually assigned to one of 6 types. From this dataset, we simulated mixtures where two reactions of different types would occur simultaneously. Automatic learning methods were trained to classify the reactions occurring in a mixture from the (1)H NMR-based descriptor of the mixture. Unsupervised learning methods (self-organizing maps) produced a reasonable clustering of the mixtures by reaction type, and allowed the correct classification of 80% and 63% of the mixtures in two independent test sets of different similarity to the training set. With random forests (RF), the percentage of correct classifications was increased to 99% and 80% for the same test sets. The RF probability associated to the predictions yielded a robust indication of their reliability. This study demonstrates the possibility of applying machine learning methods to automatically identify types of co-occurring chemical reactions from NMR data. Using no explicit structural information about the reactions participants, reaction elucidation is performed without structure elucidation of the molecules in the mixtures.

Tandem mass spectrometry: analysis of complex mixtures

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

Singleton, K.E.

1985-01-01

Applications of tandem mass spectrometry (MS/MS) for the analysis of complex mixtures results in increased specificity and selectivity by using a variety of reagent gases in both negative and positive ion modes. Natural isotopic abundance ratios were examined in both simple and complex mixtures using parent, daughter and neutral loss scans. MS/MS was also used to discover new compounds. Daughter scans were used to identify seven new alkaloids in a cactus species. Three of these alkaloids were novel compounds, and included the first simple, fully aromatic isoquinoline alkaloids reported in Cactaceae. MS/MS was used to characterize the chemical reaction productsmore » of coal in studies designed to probe its macromolecular structure. Negative ion chemical ionization was utilized to study reaction products resulting from the oxidation of coal. Possible structural units in the precursor coal were predicted based on the reaction products identified, aliphatic and aromatic acids and their anhydrides. The MS/MS method was also used to characterize reaction products resulting from coal liquefaction and/or extraction. These studies illustrate the types of problems for which MS/MS is useful. Emphasis has been placed on characterization of complex mixtures by selecting experimental parameters which enhance the information obtained. The value of using MS/MS in conjunction with other analytical techniques as well as the chemical pretreatment is demonstrated.« less

Role of an Oxidant Mixture as Surface Modifier of Porous Silicon Microstructures Evaluated by Spectroscopic Ellipsometry

PubMed Central

Montiel-González, Zeuz; Escobar, Salvador; Nava, Rocío; del Río, J. Antonio; Tagüeña-Martínez, Julia

2016-01-01

Current research on porous silicon includes the construction of complex structures with luminescent and/or photonic properties. However, their preparation with both characteristics is still challenging. Recently, our group reported a possible method to achieve that by adding an oxidant mixture to the electrolyte used to produce porous silicon. This mixture can chemically modify their microstructure by changing the thickness and surface passivation of the pore walls. In this work, we prepared a series of samples (with and without oxidant mixture) and we evaluated the structural differences through their scanning electron micrographs and their optical properties determined by spectroscopic ellipsometry. The results showed that ellipsometry is sensitive to slight variations in the porous silicon structure, caused by changes in their preparation. The fitting process, based on models constructed from the features observed in the micrographs, allowed us to see that the mayor effect of the oxidant mixture is on samples of high porosity, where the surface oxidation strongly contributes to the skeleton thinning during the electrochemical etching. This suggests the existence of a porosity threshold for the action of the oxidant mixture. These results could have a significant impact on the design of complex porous silicon structures for different optoelectronic applications. PMID:27097767

Role of an Oxidant Mixture as Surface Modifier of Porous Silicon Microstructures Evaluated by Spectroscopic Ellipsometry.

PubMed

Montiel-González, Zeuz; Escobar, Salvador; Nava, Rocío; del Río, J Antonio; Tagüeña-Martínez, Julia

2016-04-21

Current research on porous silicon includes the construction of complex structures with luminescent and/or photonic properties. However, their preparation with both characteristics is still challenging. Recently, our group reported a possible method to achieve that by adding an oxidant mixture to the electrolyte used to produce porous silicon. This mixture can chemically modify their microstructure by changing the thickness and surface passivation of the pore walls. In this work, we prepared a series of samples (with and without oxidant mixture) and we evaluated the structural differences through their scanning electron micrographs and their optical properties determined by spectroscopic ellipsometry. The results showed that ellipsometry is sensitive to slight variations in the porous silicon structure, caused by changes in their preparation. The fitting process, based on models constructed from the features observed in the micrographs, allowed us to see that the mayor effect of the oxidant mixture is on samples of high porosity, where the surface oxidation strongly contributes to the skeleton thinning during the electrochemical etching. This suggests the existence of a porosity threshold for the action of the oxidant mixture. These results could have a significant impact on the design of complex porous silicon structures for different optoelectronic applications.

Monte Carlo simulations of mixtures involving ketones and aldehydes by a direct bubble pressure calculation.

PubMed

Ferrando, Nicolas; Lachet, Véronique; Boutin, Anne

2010-07-08

Ketone and aldehyde molecules are involved in a large variety of industrial applications. Because they are mainly present mixed with other compounds, the prediction of phase equilibrium of mixtures involving these classes of molecules is of first interest particularly to design and optimize separation processes. The main goal of this work is to propose a transferable force field for ketones and aldehydes that allows accurate molecular simulations of not only pure compounds but also complex mixtures. The proposed force field is based on the anisotropic united-atoms AUA4 potential developed for hydrocarbons, and it introduces only one new atom, the carbonyl oxygen. The Lennard-Jones parameters of this oxygen atom have been adjusted on saturated thermodynamic properties of both acetone and acetaldehyde. To simulate mixtures, Monte Carlo simulations are carried out in a specific pseudoensemble which allows a direct calculation of the bubble pressure. For polar mixtures involved in this study, we show that this approach is an interesting alternative to classical calculations in the isothermal-isobaric Gibbs ensemble. The pressure-composition diagrams of polar + polar and polar + nonpolar binary mixtures are well reproduced. Mutual solubilities as well as azeotrope location, if present, are accurately predicted without any empirical binary interaction parameters or readjustment. Such result highlights the transferability of the proposed force field, which is an essential feature toward the simulation of complex oxygenated mixtures of industrial interest.

Introduction to the special section on mixture modeling in personality assessment.

PubMed

Wright, Aidan G C; Hallquist, Michael N

2014-01-01

Latent variable models offer a conceptual and statistical framework for evaluating the underlying structure of psychological constructs, including personality and psychopathology. Complex structures that combine or compare categorical and dimensional latent variables can be accommodated using mixture modeling approaches, which provide a powerful framework for testing nuanced theories about psychological structure. This special series includes introductory primers on cross-sectional and longitudinal mixture modeling, in addition to empirical examples applying these techniques to real-world data collected in clinical settings. This group of articles is designed to introduce personality assessment scientists and practitioners to a general latent variable framework that we hope will stimulate new research and application of mixture models to the assessment of personality and its pathology.

Compositions containing borane or carborane cage compounds and related applications

DOEpatents

Bowen, III, Daniel E; Eastwood, Eric A

2013-05-28

Compositions comprising a polymer-containing matrix and a filler comprising a cage compound selected from borane cage compounds, carborane cage compounds, metal complexes thereof, residues thereof, mixtures thereof, and/or agglomerations thereof, where the cage compound is not covalently bound to the matrix polymer. Methods of making and applications for using such compositions are also disclosed.

Compositions containing borane or carborane cage compounds and related applications

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

Bowen, III, Daniel E; Eastwood, Eric A

2014-11-11

Compositions comprising a polymer-containing matrix and a filler comprising a cage compound selected from borane cage compounds, carborane cage compounds, metal complexes thereof, residues thereof, mixtures thereof, and/or agglomerations thereof, where the cage compound is not covalently bound to the matrix polymer. Methods of making and applications for using such compositions are also disclosed.

Compositions containing borane or carborane cage compounds and related applications

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

Bowen, III, Daniel E.; Eastwood, Eric A.

2015-09-15

Compositions comprising a polymer-containing matrix and a filler comprising a cage compound selected from borane cage compounds, carborane cage compounds, metal complexes thereof, residues thereof, mixtures thereof, and/or agglomerations thereof, where the cage compound is not covalently bound to the matrix polymer. Methods of making and applications for using such compositions are also disclosed.

Multidimensional profiling of components in complex mixtures of natural products for metabolic analysis, proof of concept: application to Quillaja saponins.

PubMed

Bankefors, Johan; Nord, Lars I; Kenne, Lennart

2010-02-01

A method for separation and detection of major and minor components in complex mixtures has been developed, utilising two-dimensional high-performance liquid chromatography (2D-HPLC) combined with electrospray ionisation ion-trap multiple-stage mass spectrometry (ESI-ITMS(n)). Chromatographic conditions were matched with mass spectrometric detection to maximise the number of components that could be separated. The described procedure has proven useful to discern several hundreds of saponin components when applied to Quillaja saponaria Molina bark extracts. The discrimination of each saponin component relies on the fact that three coordinates (x, y, z) for each component can be derived from the retention time of the two chromatographic steps (x, y) and the m/z-values from the multiple-stage mass spectrometry (z(n), n=1, 2, ...). Thus an improved graphical representation was obtained by combining retention times from the two-stage separation with +MS(1) (z(1)) and the additional structural information from the second mass stage +MS(2) (z(2), z(3)) corresponding to the main fragment ions. By this approach three-dimensional plots can be made that reveal both the chromatographic and structural properties of a specific mixture which can be useful in fingerprinting of complex mixtures. 2009 Elsevier B.V. All rights reserved.

Differential Attenuation of NMR Signals by Complementary Ion-Exchange Resin Beads for De Novo Analysis of Complex Metabolomics Mixtures.

PubMed

Zhang, Bo; Yuan, Jiaqi; Brüschweiler, Rafael

2017-07-12

A primary goal of metabolomics is the characterization of a potentially very large number of metabolites that are part of complex mixtures. Application to biofluids and tissue samples offers insights into biochemical metabolic pathways and their role in health and disease. 1D 1 H and 2D 13 C- 1 H HSQC NMR spectra are most commonly used for this purpose. They yield quantitative information about each proton of the mixture, but do not tell which protons belong to the same molecule. Interpretation requires the use of NMR spectral databases, which naturally limits these investigations to known metabolites. Here, a new method is presented that uses complementary ion exchange resin beads to differentially attenuate 2D NMR cross-peaks that belong to different metabolites. Based on their characteristic attenuation patterns, cross-peaks could be clustered and assigned to individual molecules, including unknown metabolites with multiple spin systems, as demonstrated for a metabolite model mixture and E. coli cell lysate. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical Mixtures and Epidemiologic Fundamentals for Risk Assessment Applications

EPA Science Inventory

Risk management options are increasingly being considered early in the risk assessment process to help scope the considerations and bound the inherent complexities related to potential exposures, risk and future clean-up decisions (including acceptable pollutant levels) related t...

Reflective Self-Metallizing Polyimide Films

NASA Technical Reports Server (NTRS)

Thompson, David W. (Inventor); Caplan, Maggie L. (Inventor); St.Clair, Anne (Inventor)

1997-01-01

A silver organic complex, such as silver acetate, is solubilized in a polyamic acid resin or soluble polyimide solution using a suitable solvent such as hexafluoroacetyl acetone. The mixture is stable and can be applied to both flat and contoured surfaces. Application can be performed by casting, dip-coating, spraying, or other suitable techniques. In addition, the mixture can be cast or extruded as a polyimide film which is not applied to an underlying substrate. Upon curing, a flexible silver coated polyimide film is produced.

Quantitative structural modeling on the wavelength interval (Δλ) in synchronous fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Samari, Fayezeh; Yousefinejad, Saeed

2017-11-01

Emission fluorescence spectroscopy has an extremely restricted scope of application to analyze of complex mixtures since its selectivity is reduced by the extensive spectral overlap. Synchronous fluorescence spectroscopy (SFS) is a technique enables us to analyze complex mixtures with overlapped emission and/or excitation spectra. The difference of excitation and emission wavelength of compounds (interval wavelength or Δλ) is an important characteristic in SFS. Thus a multi-parameter model was constructed to predict Δλ in 63 fluorescent compounds and the regression coefficient in training set, cross validation and test set were 0.88, 0.85 and 0.91 respectively. Furthermore, the applicability and validity of model were evaluated using different statistical methods such as y-scrambling and applicability domain. It was concluded that increasing average valence connectivity, number of Al2-NH functional group and Geary autocorrelation (lag 4) with electronegative weights can lead to increasing Δλ in the fluorescent compounds. The current study obtained an insight into the structural properties of compounds effective on their Δλ as an important parameter in SFS.

Pyrolysis Mass Spectrometry of Complex Organic Materials.

ERIC Educational Resources Information Center

Meuzelaar, Henk L. C.; And Others

1984-01-01

Illustrates the state of the art in pyrolysis mass spectrometry techniques through applications in: (1) structural determination and quality control of synthetic polymers; (2) quantitative analysis of polymer mixtures; (3) classification and structural characterization of fossil organic matter; and (4) nonsupervised numerical extraction of…

Evaluation of a High Intensity Focused Ultrasound-Immobilized Trypsin Digestion and 18O-Labeling Method for Quantitative Proteomics

PubMed Central

López-Ferrer, Daniel; Hixson, Kim K.; Smallwood, Heather; Squier, Thomas C.; Petritis, Konstantinos; Smith, Richard D.

2009-01-01

A new method that uses immobilized trypsin concomitant with ultrasonic irradiation results in ultra-rapid digestion and thorough 18O labeling for quantitative protein comparisons. The reproducible and highly efficient method provided effective digestions in <1 min with a minimized amount of enzyme required compared to traditional methods. This method was demonstrated for digestion of both simple and complex protein mixtures, including bovine serum albumin, a global proteome extract from the bacteria Shewanella oneidensis, and mouse plasma, as well as 18O labeling of such complex protein mixtures, which validated the application of this method for differential proteomic measurements. This approach is simple, reproducible, cost effective, rapid, and thus well-suited for automation. PMID:19555078

Acute and additive toxicity of ten photosystem-II herbicides to seagrass

NASA Astrophysics Data System (ADS)

Wilkinson, Adam D.; Collier, Catherine J.; Flores, Florita; Negri, Andrew P.

2015-11-01

Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (ΔF/Fm‧) by 50% at concentrations ranging from 3.5 μg l-1 (ametryn) to 132 μg l-1 (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ΔF/Fm‧.

Acute and additive toxicity of ten photosystem-II herbicides to seagrass

PubMed Central

Wilkinson, Adam D.; Collier, Catherine J.; Flores, Florita; Negri, Andrew P.

2015-01-01

Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (∆F/Fm′) by 50% at concentrations ranging from 3.5 μg l−1 (ametryn) to 132 μg l−1 (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ∆F/Fm′. PMID:26616444

Acute and additive toxicity of ten photosystem-II herbicides to seagrass.

PubMed

Wilkinson, Adam D; Collier, Catherine J; Flores, Florita; Negri, Andrew P

2015-11-30

Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (∆F/F(m)') by 50% at concentrations ranging from 3.5 μg l(-1) (ametryn) to 132 μg l(-1) (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ∆F/F(m)'.

The Umov effect in application to an optically thin two-component cloud of cosmic dust

NASA Astrophysics Data System (ADS)

Zubko, Evgenij; Videen, Gorden; Zubko, Nataliya; Shkuratov, Yuriy

2018-04-01

The Umov effect is an inverse correlation between linear polarization of the sunlight scattered by an object and its geometric albedo. The Umov effect has been observed in particulate surfaces, such as planetary regoliths, and recently it also was found in single-scattering small dust particles. Using numerical modeling, we study the Umov effect in a two-component mixture of small irregularly shaped particles. Such a complex chemical composition is suggested in cometary comae and other types of optically thin clouds of cosmic dust. We find that the two-component mixtures of small particles also reveal the Umov effect regardless of the chemical composition of their end-member components. The interrelation between log(Pmax) and log(A) in a two-component mixture of small irregularly shaped particles appears either in a straight linear form or in a slightly curved form. This curvature tends to decrease while the index n in a power-law size distribution r-n grows; at n > 2.5, the log(Pmax)-log(A) diagrams are almost straight linear in appearance. The curvature also noticeably decreases with the packing density of constituent material in irregularly shaped particles forming the mixture. That such a relation exists suggest the Umov effect may also be observed in more complex mixtures.

The Umov effect in application to an optically thin two-component cloud of cosmic dust

NASA Astrophysics Data System (ADS)

Zubko, Evgenij; Videen, Gorden; Zubko, Nataliya; Shkuratov, Yuriy

2018-07-01

The Umov effect is an inverse correlation between linear polarization of the sunlight scattered by an object and its geometric albedo. The Umov effect has been observed in particulate surfaces, such as planetary regoliths, and recently it also was found in single-scattering small dust particles. Using numerical modelling, we study the Umov effect in a two-component mixture of small irregularly shaped particles. Such a complex chemical composition is suggested in cometary comae and other types of optically thin clouds of cosmic dust. We find that the two-component mixtures of small particles also reveal the Umov effect regardless of the chemical composition of their end-member components. The interrelation between log(Pmax) and log(A) in a two-component mixture of small irregularly shaped particles appears either in a straight linear form or in a slightly curved form. This curvature tends to decrease while the index n in a power-law size distribution r-n grows; at n > 2.5, the log(Pmax)-log(A) diagrams are almost straight linear in appearance. The curvature also noticeably decreases with the packing density of constituent material in irregularly shaped particles forming the mixture. That such a relation exists suggests the Umov effect may also be observed in more complex mixtures.

UP-HILIC-MS/MS to Determine the Action Pattern of Penicillium sp. Dextranase.

PubMed

Yi, Lin; Sun, Xue; Du, Kenze; Ouyang, Yilan; Wu, Chengling; Xu, Naiyu; Linhardt, Robert J; Zhang, Zhenqing

2015-07-01

Investigation of the action pattern of enzymes acting on carbohydrates is challenging, as both the substrate and the digestion products are complex mixtures. Dextran and its enzyme-derived oligosaccharides are widely used for many industrial applications. In this work, a new method relying on ultra-performance hydrophilic interaction liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UP-HILIC-Q/TOF-MS/MS) was developed to analyze a complex mixture of dextran oligosaccharide products to determine the action pattern of dextranase. No derivatization of oligosaccharides was required and the impact of the α- and β-configurations of the native oligosaccharides on the chromatographic separation was eliminated. The 1→6, 1→3, 1→4 backbone linkages and the branch linkages of these oligosaccharides were all distinguished from diagnostic ions in their MS/MS spectra, including fragments corresponding to (0,2)A, (0,3)A, (0,4)A, B-H2O, (2,5)A, and (3,5)A. The sequences of the oligosaccharide products were similarly established. Thus, the complex oligosaccharide mixtures in dextran digestion products were profiled and identified using this method. The more enzyme-resistant structures in dextran were established using much less sample, labor, time, and uncertainty than in previous studies. This method provides an efficient, sensitive, and straightforward way to monitor the entire process of digestion, establish the action pattern of the dextranase from Penicillium sp., and to support the proper industrial application of dextranase.

UP-HILIC-MS/MS to Determine the Action Pattern of Penicillium sp. Dextranase

NASA Astrophysics Data System (ADS)

Yi, Lin; Sun, Xue; Du, Kenze; Ouyang, Yilan; Wu, Chengling; Xu, Naiyu; Linhardt, Robert J.; Zhang, Zhenqing

2015-07-01

Investigation of the action pattern of enzymes acting on carbohydrates is challenging, as both the substrate and the digestion products are complex mixtures. Dextran and its enzyme-derived oligosaccharides are widely used for many industrial applications. In this work, a new method relying on ultra-performance hydrophilic interaction liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UP-HILIC- Q/TOF-MS/MS) was developed to analyze a complex mixture of dextran oligosaccharide products to determine the action pattern of dextranase. No derivatization of oligosaccharides was required and the impact of the α- and β-configurations of the native oligosaccharides on the chromatographic separation was eliminated. The 1→6, 1→3, 1→4 backbone linkages and the branch linkages of these oligosaccharides were all distinguished from diagnostic ions in their MS/MS spectra, including fragments corresponding to 0,2A, 0,3A, 0,4A, B-H2O, 2,5A, and 3,5A. The sequences of the oligosaccharide products were similarly established. Thus, the complex oligosaccharide mixtures in dextran digestion products were profiled and identified using this method. The more enzyme-resistant structures in dextran were established using much less sample, labor, time, and uncertainty than in previous studies. This method provides an efficient, sensitive, and straightforward way to monitor the entire process of digestion, establish the action pattern of the dextranase from Penicillium sp., and to support the proper industrial application of dextranase.

DEMONSTRATION BULLETIN: HIGH VOLTAGE ELECTRON BEAM TECHNOLOGY - HIGH VOLTAGE ENVIRONMENTAL APPLICATIONS, INC.

EPA Science Inventory

The high energy electron beam irradiation technology is a low temperature method for destroying complex mixtures of hazardous organic chemicals in solutions containing solids. The system consists of a computer-automated, portable electron beam accelerator and a delivery system. T...

Ligand Fishing: A Remarkable Strategy for Discovering Bioactive Compounds from Complex Mixture of Natural Products.

PubMed

Zhuo, Rongjie; Liu, Hao; Liu, Ningning; Wang, Yi

2016-11-11

Identification of active compounds from natural products is a critical and challenging task in drug discovery pipelines. Besides commonly used bio-guided screening approaches, affinity selection strategy coupled with liquid chromatography or mass spectrometry, known as ligand fishing, has been gaining increasing interest from researchers. In this review, we summarized this emerging strategy and categorized those methods as off-line or on-line mode according to their features. The separation principles of ligand fishing were introduced based on distinct analytical techniques, including biochromatography, capillary electrophoresis, ultrafiltration, equilibrium dialysis, microdialysis, and magnetic beads. The applications of ligand fishing approaches in the discovery of lead compounds were reviewed. Most of ligand fishing methods display specificity, high efficiency, and require less sample pretreatment, which makes them especially suitable for screening active compounds from complex mixtures of natural products. We also summarized the applications of ligand fishing in the modernization of Traditional Chinese Medicine (TCM), and propose some perspectives of this remarkable technique.

Molecular dynamics study of thermodynamic stability and dynamics of [Li(glyme)]+ complex in lithium-glyme solvate ionic liquids

NASA Astrophysics Data System (ADS)

Shinoda, Wataru; Hatanaka, Yuta; Hirakawa, Masashi; Okazaki, Susumu; Tsuzuki, Seiji; Ueno, Kazuhide; Watanabe, Masayoshi

2018-05-01

Equimolar mixtures of glymes and organic lithium salts are known to produce solvate ionic liquids, in which the stability of the [Li(glyme)]+ complex plays an important role in determining the ionic dynamics. Since these mixtures have attractive physicochemical properties for application as electrolytes, it is important to understand the dependence of the stability of the [Li(glyme)]+ complex on the ion dynamics. A series of microsecond molecular dynamics simulations has been conducted to investigate the dynamic properties of these solvate ionic liquids. Successful solvate ionic liquids with high stability of the [Li(glyme)]+ complex have been shown to have enhanced ion dynamics. Li-glyme pair exchange rarely occurs: its characteristic time is longer than that of ion diffusion by one or two orders of magnitude. Li-glyme pair exchange most likely occurs through cluster formation involving multiple [Li(glyme)]+ pairs. In this process, multiple exchanges likely take place in a concerted manner without the production of energetically unfavorable free glyme or free Li+ ions.

METHODS AND TECHNIQUES FOR DEALING WITH THE UNIDENTIFIED FRACTION OF COMPLEX MIXTURES

EPA Science Inventory

For the vast majority of highly complex environmental mixtures to which humans are exposed, significant portions of the mixture are unidentified. Although toxicological data on the mixture itself are desired for risk assessment, such data, even on a similar mixture, are rarely a...

An innovative approach to sampling complex industrial emissions for use in animal toxicity tests: application to iron casting operations.

PubMed

Palmer, W G; Scholz, R C; Moorman, W J

1983-03-01

Sampling of complex mixtures of airborne contaminants for chronic animal toxicity tests often involves numerous sampling devices, requires extensive sampling time, and yields forms of collected materials unsuitable for administration to animals. A method is described which used a high volume, wet venturi scrubber for collection of respirable fractions of emissions from iron foundry casting operations. The construction and operation of the sampler are presented along with collection efficiency data and its application to the preparation of large quantities of samples to be administered to animals by intratracheal instillation.

(3, 2)D 1H, 13C BIRDr,X-HSQC-TOCSY for NMR structure elucidation of mixtures: application to complex carbohydrates.

PubMed

Brodaczewska, Natalia; Košťálová, Zuzana; Uhrín, Dušan

2018-02-01

Overlap of NMR signals is the major cause of difficulties associated with NMR structure elucidation of molecules contained in complex mixtures. A 2D homonuclear correlation spectroscopy in particular suffers from low dispersion of 1 H chemical shifts; larger dispersion of 13 C chemical shifts is often used to reduce this overlap, while still providing the proton-proton correlation information e.g. in the form of a 2D 1 H, 13 C HSQC-TOCSY experiment. For this methodology to work, 13 C chemical shift must be resolved. In case of 13 C chemical shifts overlap, 1 H chemical shifts can be used to achieve the desired resolution. The proposed (3, 2)D 1 H, 13 C BIRD r,X -HSQC-TOCSY experiment achieves this while preserving singlet character of cross peaks in the F 1 dimension. The required high-resolution in the 13 C dimension is thus retained, while the cross peak overlap occurring in a regular HSQC-TOCSY experiment is eliminated. The method is illustrated on the analysis of a complex carbohydrate mixture obtained by depolymerisation of a fucosylated chondroitin sulfate isolated from the body wall of the sea cucumber Holothuria forskali.

Reduction of chemical formulas from the isotopic peak distributions of high-resolution mass spectra.

PubMed

Roussis, Stilianos G; Proulx, Richard

2003-03-15

A method has been developed for the reduction of the chemical formulas of compounds in complex mixtures from the isotopic peak distributions of high-resolution mass spectra. The method is based on the principle that the observed isotopic peak distribution of a mixture of compounds is a linear combination of the isotopic peak distributions of the individual compounds in the mixture. All possible chemical formulas that meet specific criteria (e.g., type and number of atoms in structure, limits of unsaturation, etc.) are enumerated, and theoretical isotopic peak distributions are generated for each formula. The relative amount of each formula is obtained from the accurately measured isotopic peak distribution and the calculated isotopic peak distributions of all candidate formulas. The formulas of compounds in simple spectra, where peak components are fully resolved, are rapidly determined by direct comparison of the calculated and experimental isotopic peak distributions. The singular value decomposition linear algebra method is used to determine the contributions of compounds in complex spectra containing unresolved peak components. The principles of the approach and typical application examples are presented. The method is most useful for the characterization of complex spectra containing partially resolved peaks and structures with multiisotopic elements.

DEVELOPMENT OF A PASSIVE, IN SITU, INTEGRATIVE ...

EPA Pesticide Factsheets

Until recently, hydrophobic, bioconcentratable compounds have been the primary focus of most environmental organic contaminant investigations, There is an increasing realization that a holistic hazard assessment of complex environmental contaminant mixtures requires data on the concentrations of hydrophilic organic contaminants as well. This group of compounds includes a wide variety of chemicals, including potentially endocrine disrupting and estrogenic contaminants which have been shown to contribute to numerous abnormalities such as impaired reproduction in aquatic organisms exposed in environmental waters. To address this issue, we developed a passive, in situ, sampling device (the Polar Organic Chemical Integrative Sampler or POCIS) which integratively concentrates trace levels of complex mixtures of hydrophilic environmental contaminants, enables the determination of their time-weighted average water concentrations and provides a screening assessment of the toxicological significance of the complex mixture of waterborne contaminants. Using a prototype sampler (effective membrane sampling surface area = 18.2 cm 2) linear uptake of selected herbicides and pharmaceuticals was observed for up to 56 days. Estimation of the ambient water concentrations of chemicals of interest is achieved by using appropriate uptake models and determination of POCIS chemical sampling rates. The research focused on in the subtasks is the development and application of state-of

Transcriptional pathway and de novo network-based approaches to effects-based monitoring in the Great Lakes

EPA Science Inventory

Transcriptomics provides unique solutions for understanding the impact of complex mixtures and their components on aquatic systems. Here we describe the application of transcriptomics analysis of in situ fathead minnow exposures for assessing biological impacts of wastewater trea...

The perception of odor objects in everyday life: a review on the processing of odor mixtures

PubMed Central

Thomas-Danguin, Thierry; Sinding, Charlotte; Romagny, Sébastien; El Mountassir, Fouzia; Atanasova, Boriana; Le Berre, Elodie; Le Bon, Anne-Marie; Coureaud, Gérard

2014-01-01

Smelling monomolecular odors hardly ever occurs in everyday life, and the daily functioning of the sense of smell relies primarily on the processing of complex mixtures of volatiles that are present in the environment (e.g., emanating from food or conspecifics). Such processing allows for the instantaneous recognition and categorization of smells and also for the discrimination of odors among others to extract relevant information and to adapt efficiently in different contexts. The neurophysiological mechanisms underpinning this highly efficient analysis of complex mixtures of odorants is beginning to be unraveled and support the idea that olfaction, as vision and audition, relies on odor-objects encoding. This configural processing of odor mixtures, which is empirically subject to important applications in our societies (e.g., the art of perfumers, flavorists, and wine makers), has been scientifically studied only during the last decades. This processing depends on many individual factors, among which are the developmental stage, lifestyle, physiological and mood state, and cognitive skills; this processing also presents striking similarities between species. The present review gathers the recent findings, as observed in animals, healthy subjects, and/or individuals with affective disorders, supporting the perception of complex odor stimuli as odor objects. It also discusses peripheral to central processing, and cognitive and behavioral significance. Finally, this review highlights that the study of odor mixtures is an original window allowing for the investigation of daily olfaction and emphasizes the need for knowledge about the underlying biological processes, which appear to be crucial for our representation and adaptation to the chemical environment. PMID:24917831

A Statistical Approach for Judging Stability of Whole Mixture Chemical Composition over Time for Highly Complex Disinfection By-Product Mixtures from EPA's Four Lab Study

EPA Science Inventory

Chemical characterization of complex mixtures and assessment of stability over time of the characterized chemicals is crucial both to characterize exposure and to use data from one mixture as a surrogate for other similar mixtures. The chemical composition of test mixtures can va...

Environmentally relevant chemical mixtures of concern in waters of United States tributaries to the Great Lakes

USGS Publications Warehouse

Elliott, Sarah M.; Brigham, Mark E.; Kiesling, Richard L.; Schoenfuss, Heiko L.; Jorgenson, Zachary G.

2018-01-01

The North American Great Lakes are a vital natural resource that provide fish and wildlife habitat, as well as drinking water and waste assimilation services for millions of people. Tributaries to the Great Lakes receive chemical inputs from various point and nonpoint sources, and thus are expected to have complex mixtures of chemicals. However, our understanding of the co‐occurrence of specific chemicals in complex mixtures is limited. To better understand the occurrence of specific chemical mixtures in the US Great Lakes Basin, surface water from 24 US tributaries to the Laurentian Great Lakes was collected and analyzed for diverse suites of organic chemicals, primarily focused on chemicals of concern (e.g., pharmaceuticals, personal care products, fragrances). A total of 181 samples and 21 chemical classes were assessed for mixture compositions. Basin wide, 1664 mixtures occurred in at least 25% of sites. The most complex mixtures identified comprised 9 chemical classes and occurred in 58% of sampled tributaries. Pharmaceuticals typically occurred in complex mixtures, reflecting pharmaceutical‐use patterns and wastewater facility outfall influences. Fewer mixtures were identified at lake or lake‐influenced sites than at riverine sites. As mixture complexity increased, the probability of a specific mixture occurring more often than by chance greatly increased, highlighting the importance of understanding source contributions to the environment. This empirically based analysis of mixture composition and occurrence may be used to focus future sampling efforts or mixture toxicity assessments. 

Evaluation of the nephrotoxicity of complex mixtures containing organics and metals: advantages and disadvantages of the use of real-world complex mixtures.

PubMed

Simmons, J E; Yang, R S; Berman, E

1995-02-01

As part of a multidisciplinary health effects study, the nephrotoxicity of complex industrial waste mixtures was assessed. Adult, male Fischer 344 rats were gavaged with samples of complex industrial waste and nephrotoxicity evaluated 24 hr later. Of the 10 tested samples, 4 produced increased absolute or relative kidney weight, or both, coupled with a statistically significant alteration in at least one of the measured serum parameters (urea nitrogen (BUN), creatinine (CREAT), and BUN/CREAT ratio). Although the waste samples had been analyzed for a number of organic chemicals and 7 of the 10 samples were analyzed also for 12 elemental metals and metalloids, their nephrotoxicity was not readily predicted from the partial chemical characterization data. Because the chemical form or speciation of the metals was unknown, it was not possible to estimate their contribution to the observed biological response. Various experimental approaches, including use of real-world complex mixtures, chemically defined synthetic mixtures, and simple mixtures, will be necessary to adequately determine the potential human health risk from exposure to complex chemical mixtures.

Insight into Signal Response of Protein Ions in Native ESI-MS from the Analysis of Model Mixtures of Covalently Linked Protein Oligomers.

PubMed

Root, Katharina; Wittwer, Yves; Barylyuk, Konstantin; Anders, Ulrike; Zenobi, Renato

2017-09-01

Native ESI-MS is increasingly used for quantitative analysis of biomolecular interactions. In such analyses, peak intensity ratios measured in mass spectra are treated as abundance ratios of the respective molecules in solution. While signal intensities of similar-size analytes, such as a protein and its complex with a small molecule, can be directly compared, significant distortions of the peak ratio due to unequal signal response of analytes impede the application of this approach for large oligomeric biomolecular complexes. We use a model system based on concatenated maltose binding protein units (MBPn, n = 1, 2, 3) to systematically study the behavior of protein mixtures in ESI-MS. The MBP concatamers differ from each other only by their mass while the chemical composition and other properties remain identical. We used native ESI-MS to analyze model mixtures of MBP oligomers, including equimolar mixtures of two proteins, as well as binary mixtures containing different fractions of the individual components. Pronounced deviation from a linear dependence of the signal intensity with concentration was observed for all binary mixtures investigated. While equimolar mixtures showed linear signal dependence at low concentrations, distinct ion suppression was observed above 20 μM. We systematically studied factors that are most often used in the literature to explain the origin of suppression effects. Implications of this effect for quantifying protein-protein binding affinity by native ESI-MS are discussed in general and demonstrated for an example of an anti-MBP antibody with its ligand, MBP. Graphical Abstract ᅟ.

Considering the cumulative risk of mixtures of chemicals – A challenge for policy makers

PubMed Central

2012-01-01

Background The current paradigm for the assessment of the health risk of chemical substances focuses primarily on the effects of individual substances for determining the doses of toxicological concern in order to inform appropriately the regulatory process. These policy instruments place varying requirements on health and safety data of chemicals in the environment. REACH focuses on safety of individual substances; yet all the other facets of public health policy that relate to chemical stressors put emphasis on the effects of combined exposure to mixtures of chemical and physical agents. This emphasis brings about methodological problems linked to the complexity of the respective exposure pathways; the effect (more complex than simple additivity) of mixtures (the so-called 'cocktail effect'); dose extrapolation, i.e. the extrapolation of the validity of dose-response data to dose ranges that extend beyond the levels used for the derivation of the original dose-response relationship; the integrated use of toxicity data across species (including human clinical, epidemiological and biomonitoring data); and variation in inter-individual susceptibility associated with both genetic and environmental factors. Methods In this paper we give an overview of the main methodologies available today to estimate the human health risk of environmental chemical mixtures, ranging from dose addition to independent action, and from ignoring interactions among the mixture constituents to modelling their biological fate taking into account the biochemical interactions affecting both internal exposure and the toxic potency of the mixture. Results We discuss their applicability, possible options available to policy makers and the difficulties and potential pitfalls in implementing these methodologies in the frame of the currently existing policy framework in the European Union. Finally, we suggest a pragmatic solution for policy/regulatory action that would facilitate the evaluation of the health effects of chemical mixtures in the environment and consumer products. Conclusions One universally applicable methodology does not yet exist. Therefore, a pragmatic, tiered approach to regulatory risk assessment of chemical mixtures is suggested, encompassing (a) the use of dose addition to calculate a hazard index that takes into account interactions among mixture components; and (b) the use of the connectivity approach in data-rich situations to integrate mechanistic knowledge at different scales of biological organization. PMID:22759500

ALTERATION OF SOIL METAL CHEMISTRY AND PHYTOAVAILABILITY ASSOCIATED WITH BIOSOLIDS APPLICATION (ABSTRACT)

EPA Science Inventory

Biosolids are a complex mixture which contain both inorganic and organic adsorbents. Thus, addition of biosolids to soil not only increases the environmental loading of toxic metals (Cd, Zn, Cu, Ni, Pb, etc.) it alters the phytoavailability of these metals. This reduction in ph...

Application of the Attagene FACTORIAL™ assay to characterization of surface waters from a nationwide assessment of streams

EPA Science Inventory

Bioassays can be used to evaluate the integrated effects of complex mixtures from both known and unidentified contaminants present in environmental samples. However, such bio-monitoring approaches have typically focused only on one or a few pathways (e.g. estrogen receptor, andro...

A 3D smoothed particle hydrodynamics model for erosional dam-break floods

NASA Astrophysics Data System (ADS)

Amicarelli, Andrea; Kocak, Bozhana; Sibilla, Stefano; Grabe, Jürgen

2017-11-01

A mesh-less smoothed particle hydrodynamics (SPH) model for bed-load transport on erosional dam-break floods is presented. This mixture model describes both the liquid phase and the solid granular material. The model is validated on the results from several experiments on erosional dam breaks. A comparison between the present model and a 2-phase SPH model for geotechnical applications (Gadget Soil; TUHH) is performed. A demonstrative 3D erosional dam break on complex topography is investigated. The present 3D mixture model is characterised by: no tuning parameter for the mixture viscosity; consistency with the Kinetic Theory of Granular Flow; ability to reproduce the evolution of the free surface and the bed-load transport layer; applicability to practical problems in civil engineering. The numerical developments of this study are represented by a new SPH scheme for bed-load transport, which is implemented in the SPH code SPHERA v.8.0 (RSE SpA), distributed as FOSS on GitHub.

Application of ion exchange resin in floating drug delivery system.

PubMed

Upadhye, Abhijeet A; Ambike, Anshuman A; Mahadik, Kakasaheb R; Paradkar, Anant

2008-10-01

The purpose of this study was to explore the application of low-density ion exchange resin (IER) Tulsion(R) 344, for floating drug delivery system (FDDS), and study the effect of its particle size on rate of complexation, water uptake, drug release, and in situ complex formation. Batch method was used for the preparation of complexes, which were characterized by physical methods. Tablet containing resin with high degree of crosslinking showed buoyancy lag time (BLT) of 5-8 min. Decreasing the particle size of resin showed decrease in water uptake and drug release, with no significant effect on the rate of complexation and in situ complex formation for both preformed complexes (PCs) and physical mixtures (PMs). Thus, low-density and high degree of crosslinking of resin and water uptake may be the governing factor for controlling the initial release of tablet containing PMs but not in situ complex formation. However, further sustained release may be due to in situ complex formation.

COMPARATIVE TUMOR-INITIATING ACTIVITY OF COMPLEX MIXTURES FROM ENVIRONMENTAL PARTICULATE EMISSIONS ON SENCAR MOUSE SKIN

EPA Science Inventory

The value of the SENCAR mouse for testing tumorigenic properties of complex mixtures on mouse skin was studied. Seven complex mixtures were obtained as dichloromethane extracts of collected particulate emissions from three diesel-fueled automobiles, a heavy-duty diesel engine, a ...

Renewable Gasoline, Solvents, and Fuel Additives from 2,3-Butanediol.

PubMed

Harvey, Benjamin G; Merriman, Walter W; Quintana, Roxanne L

2016-07-21

2,3-Butanediol (2,3-BD) is a renewable alcohol that can be prepared in high yield from biomass sugars. 2,3-BD was selectively dehydrated in a solvent-free process to a complex mixture of 2-ethyl-2,4,5-trimethyl-1,3-dioxolanes and 4,5-dimethyl-2isopropyl dioxolanes with the heterogeneous acid catalyst Amberlyst-15. The purified dioxolane mixture exhibited an anti-knock index of 90.5, comparable to high octane gasoline, and a volumetric net heat of combustion 34 % higher than ethanol. The solubility of the dioxolane mixture in water was only 0.8 g per 100 mL, nearly an order of magnitude lower than the common gasoline oxygenate methyl tert-butyl ether. The dioxolane mixture has potential applications as a sustainable gasoline blending component, diesel oxygenate, and industrial solvent. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of Chemical Composition of Complex Disinfection Byproduct (DBP) Mixtures Produced by Different Treatment Methods - slides

EPA Science Inventory

Analyses of the chemical composition of complex DBP mixtures, produced by different drinking water treatment processes, are essential to generate toxicity data required for assessing their risks to humans. For mixture risk assessments, whole mixture toxicology studies generally a...

Comparison of Chemical Composition of Complex Disinfection Byproduct (DBP) Mixtures Produced by Different Treatment Methods

EPA Science Inventory

Analyses of the chemical composition of complex DBP mixtures, produced by different drinking water treatment processes, are essential to generate toxicity data required for assessing their risks to humans. For mixture risk assessments, whole mixture toxicology studies generally a...

General baseline toxicity QSAR for nonpolar, polar and ionisable chemicals and their mixtures in the bioluminescence inhibition assay with Aliivibrio fischeri.

PubMed

Escher, Beate I; Baumer, Andreas; Bittermann, Kai; Henneberger, Luise; König, Maria; Kühnert, Christin; Klüver, Nils

2017-03-22

The Microtox assay, a bioluminescence inhibition assay with the marine bacterium Aliivibrio fischeri, is one of the most popular bioassays for assessing the cytotoxicity of organic chemicals, mixtures and environmental samples. Most environmental chemicals act as baseline toxicants in this short-term screening assay, which is typically run with only 30 min of exposure duration. Numerous Quantitative Structure-Activity Relationships (QSARs) exist for the Microtox assay for nonpolar and polar narcosis. However, typical water pollutants, which have highly diverse structures covering a wide range of hydrophobicity and speciation from neutral to anionic and cationic, are often outside the applicability domain of these QSARs. To include all types of environmentally relevant organic pollutants we developed a general baseline toxicity QSAR using liposome-water distribution ratios as descriptors. Previous limitations in availability of experimental liposome-water partition constants were overcome by reliable prediction models based on polyparameter linear free energy relationships for neutral chemicals and the COSMOmic model for charged chemicals. With this QSAR and targeted mixture experiments we could demonstrate that ionisable chemicals fall in the applicability domain. Most investigated water pollutants acted as baseline toxicants in this bioassay, with the few outliers identified as uncouplers or reactive toxicants. The main limitation of the Microtox assay is that chemicals with a high melting point and/or high hydrophobicity were outside of the applicability domain because of their low water solubility. We quantitatively derived a solubility cut-off but also demonstrated with mixture experiments that chemicals inactive on their own can contribute to mixture toxicity, which is highly relevant for complex environmental mixtures, where these chemicals may be present at concentrations below the solubility cut-off.

DNA-Encoded Dynamic Combinatorial Chemical Libraries.

PubMed

Reddavide, Francesco V; Lin, Weilin; Lehnert, Sarah; Zhang, Yixin

2015-06-26

Dynamic combinatorial chemistry (DCC) explores the thermodynamic equilibrium of reversible reactions. Its application in the discovery of protein binders is largely limited by difficulties in the analysis of complex reaction mixtures. DNA-encoded chemical library (DECL) technology allows the selection of binders from a mixture of up to billions of different compounds; however, experimental results often show low a signal-to-noise ratio and poor correlation between enrichment factor and binding affinity. Herein we describe the design and application of DNA-encoded dynamic combinatorial chemical libraries (EDCCLs). Our experiments have shown that the EDCCL approach can be used not only to convert monovalent binders into high-affinity bivalent binders, but also to cause remarkably enhanced enrichment of potent bivalent binders by driving their in situ synthesis. We also demonstrate the application of EDCCLs in DNA-templated chemical reactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Generalized model of electromigration with 1:1 (analyte:selector) complexation stoichiometry: part II. Application to dual systems and experimental verification.

PubMed

Müllerová, Ludmila; Dubský, Pavel; Gaš, Bohuslav

2015-03-06

Interactions among analyte forms that undergo simultaneous dissociation/protonation and complexation with multiple selectors take the shape of a highly interconnected multi-equilibrium scheme. This makes it difficult to express the effective mobility of the analyte in these systems, which are often encountered in electrophoretical separations, unless a generalized model is introduced. In the first part of this series, we presented the theory of electromigration of a multivalent weakly acidic/basic/amphoteric analyte undergoing complexation with a mixture of an arbitrary number of selectors. In this work we demonstrate the validity of this concept experimentally. The theory leads to three useful perspectives, each of which is closely related to the one originally formulated for simpler systems. If pH, IS and the selector mixture composition are all kept constant, the system is treated as if only a single analyte form interacted with a single selector. If the pH changes at constant IS and mixture composition, the already well-established models of a weakly acidic/basic analyte interacting with a single selector can be employed. Varying the mixture composition at constant IS and pH leads to a situation where virtually a single analyte form interacts with a mixture of selectors. We show how to switch between the three perspectives in practice and confirm that they can be employed interchangeably according to the specific needs by measurements performed in single- and dual-selector systems at a pH where the analyte is fully dissociated, partly dissociated or fully protonated. Weak monoprotic analyte (R-flurbiprofen) and two selectors (native β-cyclodextrin and monovalent positively charged 6-monodeoxy-6-monoamino-β-cyclodextrin) serve as a model system. Copyright © 2015 Elsevier B.V. All rights reserved.

The Paralinear Oxidation of SiC in Combustion Environments

NASA Technical Reports Server (NTRS)

Opila, Elizabeth J.; Greenbauer-Seng, Leslie (Technical Monitor)

2000-01-01

SiC is proposed for structural applications in high pressure, high temperature. high gas velocity environments of turbine and rocket engines. These environments are typically composed of complex gas mixtures containing carbon dioxide, oxygen, water vapor, and nitrogen. It is known that the primary oxidant for SiC in these environments is water vapor.

Combined microplate-ABTS and HPLC-ABTS analysis of tomato and pepper extracts reveals synergetic and antagonist effects of their lipophilic antioxidative components.

PubMed

Le Grandois, Julie; Guffond, Delphine; Hamon, Erwann; Marchioni, Eric; Werner, Dalal

2017-05-15

The antioxidant capacity of 9 pure lipophilic compounds was examined by microplate-ABTS and HPLC-ABTS, using similar experimental conditions. Results obtained showed that HPLC-ABTS method can be used for a rapid determination of individual antioxidant capacity of compounds in standard solutions or complex mixtures. The application of both methods to real lipophilic extracts from tomato (Solanum lycopersicum L.), green and red peppers (Capsicum annuum) reveals possible interactions between antioxidants. Thus, synthetic mixtures of two compounds identified in tomato and peppers were measured using microplate-ABTS and HPLC-ABTS. Synergistic effects were observed between (β-carotene-capsanthin) (1:9) and (1:1), (α-tocopherol-capsanthin) (1:9), (lutein-lycopene) (9:1) and (capsanthin-δ-tocopherol) (9:1). On the contrary, antagonistic effects were observed for (lutein-δ-tocopherol) and (α-tocopherol-δ-tocopherol). The interactions observed with two-compound mixtures are not systematically observed in the natural lipophilic extracts from tomato, green and red peppers, probably since extracts are more complex and are susceptible to cause interferences. Copyright © 2016 Elsevier Ltd. All rights reserved.

Honeybees Learn Odour Mixtures via a Selection of Key Odorants

PubMed Central

Reinhard, Judith; Sinclair, Michael; Srinivasan, Mandyam V.; Claudianos, Charles

2010-01-01

Background The honeybee has to detect, process and learn numerous complex odours from her natural environment on a daily basis. Most of these odours are floral scents, which are mixtures of dozens of different odorants. To date, it is still unclear how the bee brain unravels the complex information contained in scent mixtures. Methodology/Principal Findings This study investigates learning of complex odour mixtures in honeybees using a simple olfactory conditioning procedure, the Proboscis-Extension-Reflex (PER) paradigm. Restrained honeybees were trained to three scent mixtures composed of 14 floral odorants each, and then tested with the individual odorants of each mixture. Bees did not respond to all odorants of a mixture equally: They responded well to a selection of key odorants, which were unique for each of the three scent mixtures. Bees showed less or very little response to the other odorants of the mixtures. The bees' response to mixtures composed of only the key odorants was as good as to the original mixtures of 14 odorants. A mixture composed of the other, non-key-odorants elicited a significantly lower response. Neither an odorant's volatility or molecular structure, nor learning efficiencies for individual odorants affected whether an odorant became a key odorant for a particular mixture. Odorant concentration had a positive effect, with odorants at high concentration likely to become key odorants. Conclusions/Significance Our study suggests that the brain processes complex scent mixtures by predominantly learning information from selected key odorants. Our observations on key odorant learning lend significant support to previous work on olfactory learning and mixture processing in honeybees. PMID:20161714

Application of headspace solid-phase microextraction (HS-SPME) and comprehensive two-dimensional gas chromatography (GC x GC) for the chemical profiling of volatile oils in complex herbal mixtures.

PubMed

Di, Xin; Shellie, Robert A; Marriott, Philip J; Huie, Carmen W

2004-04-01

The coupling of headspace solid-phase microextraction (HS-SPME) with comprehensive two-dimensional gas chromatography (GC x GC) was shown to be a powerful technique for the rapid sampling and analysis of volatile oils in complex herbal materials. When compared to one-dimensional (1-D) GC, the improved analytical capabilities of GC x GC in terms of increased detection sensitivity and separation power were demonstrated by using HS-SPME/GC x GC for the chemical profiling (fingerprinting) of essential/volatile oils contained in herbal materials of increasing analytical complexity. More than 20 marker compounds belonging to Panax quinquefolius (American ginseng) can be observed within the 2-D contour plots of ginseng itself, a mixture of ginseng and another important herb (P. quinquefolius/Radix angelicae sinensis), as well as a mixture of ginseng and three other herbs (P. quinquefolius /R. angelicae sinensis/R. astragali/R. rehmanniae preparata). Such analytical capabilities should be important towards the authentication and quality control of herbal products, which are receiving increasing attention as alternative medicines worldwide. In particular, the presence of Panax in the herb formulation could be readily identified through its specific peak pattern in the 2-D GC x GC plot.

Investigation of thermal and optical properties of some quartet mixed hydrogen-bonded liquid crystals

NASA Astrophysics Data System (ADS)

Okumuş, Mustafa

2017-11-01

In this study, the thermal and optical properties of quartet mixtures formed at different weight ratios (1:1:1:1 and 1.5:1:1:1) from liquid crystals 4-octyloxy-4‧-cyanobiphenyl (8OCB), 4-hexylbenzoic acid, 4-(octyloxy)benzoic acid and 4-(decyloxy)benzoic acid were investigated by differential scanning calorimeter (DSC) and polarized optic microscopy (POM). The phase transition temperatures of the novel quartet mixtures measured in the DSC experiments are in line with the POM experiments. The experimental results clearly show that the novel liquid crystal mixtures have displayed pure liquid crystalline properties. According to the phase diagram drawn from DSC results, the nematic range of the novel mixture at the eutectic point is larger than the nematic ranges of the components. The mesomorphic structures of produced homolog complex mixtures are found to be smectic and nematic phases. But the smectic phase cannot be observed in the novel complex 1.5:1:1:1 mixture during continuous cooling. The nematic range of the novel complex 1.5:1:1:1 mixture is bigger than the nematic range of the novel complex 1:1:1:1 mixture with increasing 8OCB. Also, the nematic-to-isotropic phase transition temperature decreases with increasing the weight ratio of 8OCB in the complex quartet mixture. Another interesting result is that the produced mixtures are to be like a medical cream at room temperatures. Furthermore, order parameter and thermal stability factor of the transitions are also calculated.

Detection of Potential TNA and RNA Nucleoside Precursors in a Prebiotic Mixture by Pure Shift Diffusion-Ordered NMR Spectroscopy

PubMed Central

Islam, Saidul; Aguilar, Juan A; Powner, Matthew W; Nilsson, Mathias; Morris, Gareth A; Sutherland, John D

2013-01-01

In the context of prebiotic chemistry, one of the characteristics of mixed nitrogenous-oxygenous chemistry is its propensity to give rise to highly complex reaction mixtures. There is therefore an urgent need to develop improved spectroscopic techniques if onerous chromatographic separations are to be avoided. One potential avenue is the combination of pure shift methodology, in which NMR spectra are measured with greatly improved resolution by suppressing multiplet structure, with diffusion-ordered spectroscopy, in which NMR signals from different species are distinguished through their different rates of diffusion. Such a combination has the added advantage of working with intact mixtures, allowing analyses to be carried out without perturbing mixtures in which chemical entities are part of a network of reactions in equilibrium. As part of a systems chemistry approach towards investigating the self-assembly of potentially prebiotic small molecules, we have analysed the complex mixture arising from mixing glycolaldehyde and cyanamide, in a first application of pure shift DOSY NMR to the characterisation of a partially unknown reaction composition. The work presented illustrates the potential of pure shift DOSY to be applied to chemistries that give rise to mixtures of compounds in which the NMR signal resolution is poor. The direct formation of potential RNA and TNA nucleoside precursors, amongst other adducts, was observed. These preliminary observations may have implications for the potentially prebiotic assembly chemistry of pyrimidine threonucleotides, and therefore of TNA, by using recently reported chemistries that yield the activated pyridimidine ribonucleotides. PMID:23371787

Evaluating the aquatic toxicity of complex organic chemical mixtures: lessons learned from polycyclic aromatic hydrocarbon and petroleum hydrocarbon case studies.

PubMed

Landrum, Peter F; Chapman, Peter M; Neff, Jerry; Page, David S

2012-04-01

Experimental designs for evaluating complex mixture toxicity in aquatic environments can be highly variable and, if not appropriate, can produce and have produced data that are difficult or impossible to interpret accurately. We build on and synthesize recent critical reviews of mixture toxicity using lessons learned from 4 case studies, ranging from binary to more complex mixtures of primarily polycyclic aromatic hydrocarbons and petroleum hydrocarbons, to provide guidance for evaluating the aquatic toxicity of complex mixtures of organic chemicals. Two fundamental requirements include establishing a dose-response relationship and determining the causative agent (or agents) of any observed toxicity. Meeting these 2 requirements involves ensuring appropriate exposure conditions and measurement endpoints, considering modifying factors (e.g., test conditions, test organism life stages and feeding behavior, chemical transformations, mixture dilutions, sorbing phases), and correctly interpreting dose-response relationships. Specific recommendations are provided. Copyright © 2011 SETAC.

Increasing solubility of red bell pepper carotenoids by complexation with 2-hydroxypropyl-β-cyclodextrin.

PubMed

de Lima Petito, Nicolly; da Silva Dias, Daiana; Costa, Valéria Gonçalves; Falcão, Deborah Quintanilha; de Lima Araujo, Kátia Gome

2016-10-01

Red bell pepper carotenoids were complexed with 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) in different mass ratios (1:4, 1:6, 1:8 and 1:10) through ultrasonic homogenization in order to increase carotenoid solubility and their use as natural pigment in food. Inclusion complexes, red bell pepper extract and physical mixtures were analyzed by DSC, FT-IR, (1)H NMR and DLS. Solubility assay was performed to identify the effect of complexation on the solubility of carotenoids. From characterization assays, results showed that inclusion process occurred for all tested ratios. Results for water solubility assays demonstrated clear differences between solubility index of inclusion complexes (8.06±2.59-16.55±4.40mg/mL) and physical mixtures (3.53±1.44-7.3±1.88mg/mL), while carotenoid extract was no water soluble, as expected. These results indicated that molecular inclusion of carotenoids in 2-HPβCD was efficient to enhance their solubility in water, enabling application of red bell pepper carotenoid as natural pigment and/or bioactive substances in food. Copyright © 2016 Elsevier Ltd. All rights reserved.

Isolation and genetic analysis of pure cells from forensic biological mixtures: The precision of a digital approach.

PubMed

Fontana, F; Rapone, C; Bregola, G; Aversa, R; de Meo, A; Signorini, G; Sergio, M; Ferrarini, A; Lanzellotto, R; Medoro, G; Giorgini, G; Manaresi, N; Berti, A

2017-07-01

Latest genotyping technologies allow to achieve a reliable genetic profile for the offender identification even from extremely minute biological evidence. The ultimate challenge occurs when genetic profiles need to be retrieved from a mixture, which is composed of biological material from two or more individuals. In this case, DNA profiling will often result in a complex genetic profile, which is then subject matter for statistical analysis. In principle, when more individuals contribute to a mixture with different biological fluids, their single genetic profiles can be obtained by separating the distinct cell types (e.g. epithelial cells, blood cells, sperm), prior to genotyping. Different approaches have been investigated for this purpose, such as fluorescent-activated cell sorting (FACS) or laser capture microdissection (LCM), but currently none of these methods can guarantee the complete separation of different type of cells present in a mixture. In other fields of application, such as oncology, DEPArray™ technology, an image-based, microfluidic digital sorter, has been widely proven to enable the separation of pure cells, with single-cell precision. This study investigates the applicability of DEPArray™ technology to forensic samples analysis, focusing on the resolution of the forensic mixture problem. For the first time, we report here the development of an application-specific DEPArray™ workflow enabling the detection and recovery of pure homogeneous cell pools from simulated blood/saliva and semen/saliva mixtures, providing full genetic match with genetic profiles of corresponding donors. In addition, we assess the performance of standard forensic methods for DNA quantitation and genotyping on low-count, DEPArray™-isolated cells, showing that pure, almost complete profiles can be obtained from as few as ten haploid cells. Finally, we explore the applicability in real casework samples, demonstrating that the described approach provides complete separation of cells with outstanding precision. In all examined cases, DEPArray™ technology proves to be a groundbreaking technology for the resolution of forensic biological mixtures, through the precise isolation of pure cells for an incontrovertible attribution of the obtained genetic profiles. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Establishment method of a mixture model and its practical application for transmission gears in an engineering vehicle

NASA Astrophysics Data System (ADS)

Wang, Jixin; Wang, Zhenyu; Yu, Xiangjun; Yao, Mingyao; Yao, Zongwei; Zhang, Erping

2012-09-01

Highly versatile machines, such as wheel loaders, forklifts, and mining haulers, are subject to many kinds of working conditions, as well as indefinite factors that lead to the complexity of the load. The load probability distribution function (PDF) of transmission gears has many distributions centers; thus, its PDF cannot be well represented by just a single-peak function. For the purpose of representing the distribution characteristics of the complicated phenomenon accurately, this paper proposes a novel method to establish a mixture model. Based on linear regression models and correlation coefficients, the proposed method can be used to automatically select the best-fitting function in the mixture model. Coefficient of determination, the mean square error, and the maximum deviation are chosen and then used as judging criteria to describe the fitting precision between the theoretical distribution and the corresponding histogram of the available load data. The applicability of this modeling method is illustrated by the field testing data of a wheel loader. Meanwhile, the load spectra based on the mixture model are compiled. The comparison results show that the mixture model is more suitable for the description of the load-distribution characteristics. The proposed research improves the flexibility and intelligence of modeling, reduces the statistical error and enhances the fitting accuracy, and the load spectra complied by this method can better reflect the actual load characteristic of the gear component.

COMPONENT-BASED AND WHOLE-MIXTURE ASSESSMENTS IN ADDRESSING THE UNIDENTIFIED FRACTION OF COMPLEX MIXTURES: DRINKING WATER AS AN EXAMPLE

EPA Science Inventory

Component-Based and Whole-Mixtures Assessments in Addressing the Unidentified Fraction of Complex Mixtures: Drinking Water as an Example

J. E. Simmons; L. K. Teuschler; C. Gennings; T. F. Speth; S. D. Richardson; R. J. Miltner; M. G. Narotsky; K. D. Schenck; G. Rice

Liquid class predictor for liquid handling of complex mixtures

DOEpatents

Seglke, Brent W [San Ramon, CA; Lekin, Timothy P [Livermore, CA

2008-12-09

A method of establishing liquid classes of complex mixtures for liquid handling equipment. The mixtures are composed of components and the equipment has equipment parameters. The first step comprises preparing a response curve for the components. The next step comprises using the response curve to prepare a response indicator for the mixtures. The next step comprises deriving a model that relates the components and the mixtures to establish the liquid classes.

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

Quantitation of Phenol Levels in Oil of Wintergreen Using Gas Chromatography-Mass Spectrometry with Selected Ion Monitoring

ERIC Educational Resources Information Center

Sobel, Robert M.; Ballantine, David S.; Ryzhov, Victor

2005-01-01

Industrial application of gas chromatography-mass spectrometry (GC-MS) analysis is a powerful technique that could be used to elucidate components of a complex mixture while offering the benefits of high-precision quantitative analysis. The natural wintergreen oil is examined for its phenol concentration to determine the level of refining…

COMPLEX MIXTURES OF CHEMICAL CARCINOGENS: PRINCIPLES OF ACTION AND HUMAN CANCER

EPA Science Inventory

There is strong epidemiological evidence supported by experimental animal data that complex environmental mixtures pose a risk to human health producing increases in cancer incidence. Understanding the chemical and biological properties of these mixtures leads to a clearer unde...

Advanced statistical analysis of Raman spectroscopic data for the identification of body fluid traces: semen and blood mixtures.

PubMed

Sikirzhytski, Vitali; Sikirzhytskaya, Aliaksandra; Lednev, Igor K

2012-10-10

Conventional confirmatory biochemical tests used in the forensic analysis of body fluid traces found at a crime scene are destructive and not universal. Recently, we reported on the application of near-infrared (NIR) Raman microspectroscopy for non-destructive confirmatory identification of pure blood, saliva, semen, vaginal fluid and sweat. Here we expand the method to include dry mixtures of semen and blood. A classification algorithm was developed for differentiating pure body fluids and their mixtures. The classification methodology is based on an effective combination of Support Vector Machine (SVM) regression (data selection) and SVM Discriminant Analysis of preprocessed experimental Raman spectra collected using an automatic mapping of the sample. This extensive cross-validation of the obtained results demonstrated that the detection limit of the minor contributor is as low as a few percent. The developed methodology can be further expanded to any binary mixture of complex solutions, including but not limited to mixtures of other body fluids. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Thermo-Chemical Conversion of Microwave Activated Biomass Mixtures

NASA Astrophysics Data System (ADS)

Barmina, I.; Kolmickovs, A.; Valdmanis, R.; Vostrikovs, S.; Zake, M.

2018-05-01

Thermo-chemical conversion of microwave activated wheat straw mixtures with wood or peat pellets is studied experimentally with the aim to provide more effective application of wheat straw for heat energy production. Microwave pre-processing of straw pellets is used to provide a partial decomposition of the main constituents of straw and to activate the thermo-chemical conversion of wheat straw mixtures with wood or peat pellets. The experimental study includes complex measurements of the elemental composition of biomass pellets (wheat straw, wood, peat), DTG analysis of their thermal degradation, FTIR analysis of the composition of combustible volatiles entering the combustor, the flame temperature, the heat output of the device and composition of the products by comparing these characteristics for mixtures with unprocessed and mw pre-treated straw pellets. The results of experimental study confirm that mw pre-processing of straw activates the thermal decomposition of mixtures providing enhanced formation of combustible volatiles. This leads to improvement of the combustion conditions in the flame reaction zone, completing thus the combustion of volatiles, increasing the flame temperature, the heat output from the device, the produced heat energy per mass of burned mixture and decreasing at the same time the mass fraction of unburned volatiles in the products.

Supercritical fluid extraction. Principles and practice

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

McHugh, M.A.; Krukonis, V.J.

This book is a presentation of the fundamentals and application of super-critical fluid solvents (SCF). The authors cover virtually every facet of SCF technology: the history of SCF extraction, its underlying thermodynamic principles, process principles, industrial applications, and analysis of SCF research and development efforts. The thermodynamic principles governing SCF extraction are covered in depth. The often complex three-dimensional pressure-temperature composition (PTx) phase diagrams for SCF-solute mixtures are constructed in a coherent step-by-step manner using the more familiar two-dimensional Px diagrams. The experimental techniques used to obtain high pressure phase behavior information are described in detail and the advantages andmore » disadvantages of each technique are explained. Finally, the equations used to model SCF-solute mixtures are developed, and modeling results are presented to highlight the correlational strengths of a cubic equation of state.« less

The Gaseous Explosive Reaction : A Study of the Kinetics of Composite Fuels

NASA Technical Reports Server (NTRS)

Stevens, F W

1929-01-01

This report deals with the results of a series of studies of the kinetics of gaseous explosive reactions where the fuel under observation, instead of being a simple gas, is a known mixture of simple gases. In the practical application of the gaseous explosive reaction as a source of power in the gas engine, the fuels employed are composite, with characteristics that are apt to be due to the characteristics of their components and hence may be somewhat complex. The simplest problem that could be proposed in an investigation either of the thermodynamics or kinetics of the gaseous explosive reaction of a composite fuel would seem to be a separate study of the reaction characteristics of each component of the fuel and then a study of the reaction characteristics of the various known mixtures of those components forming composite fuels more and more complex. (author)

Optimization of the high-performance liquid chromatographic separation of a complex mixture containing urinary steroids, boldenone and bolasterone: application to urine samples.

PubMed

Gonzalo-Lumbreras, R; Izquierdo-Hornillos, R

2000-05-26

An HPLC separation of a complex mixture containing 13 urinary anabolics and corticoids, and boldenone and bolasterone (synthetic anabolics) has been carried out. The applied optimization method involved the use of binary, ternary and quaternary mobile phases containing acetonitrile, methanol or tetrahydrofuran as organic modifiers. The effect of different reversed-phase packings and temperature on the separation was studied. The optimum separation was achieved by using a water-acetonitrile (60:40, v/v) mobile phase in reversed-phase HPLC at 30 degrees C, allowing the separation of all the analytes in about 24 min. Calibration graphs were obtained using bolasterone or methyltestosterone as internal standards. Detection limits were in the range 0.012-0.107 microg ml(-1). The optimized separation was applied to the analysis, after liquid-liquid extraction, of human urine samples spiked with steroids.

Accelerated Gaussian mixture model and its application on image segmentation

NASA Astrophysics Data System (ADS)

Zhao, Jianhui; Zhang, Yuanyuan; Ding, Yihua; Long, Chengjiang; Yuan, Zhiyong; Zhang, Dengyi

2013-03-01

Gaussian mixture model (GMM) has been widely used for image segmentation in recent years due to its superior adaptability and simplicity of implementation. However, traditional GMM has the disadvantage of high computational complexity. In this paper an accelerated GMM is designed, for which the following approaches are adopted: establish the lookup table for Gaussian probability matrix to avoid the repetitive probability calculations on all pixels, employ the blocking detection method on each block of pixels to further decrease the complexity, change the structure of lookup table from 3D to 1D with more simple data type to reduce the space requirement. The accelerated GMM is applied on image segmentation with the help of OTSU method to decide the threshold value automatically. Our algorithm has been tested through image segmenting of flames and faces from a set of real pictures, and the experimental results prove its efficiency in segmentation precision and computational cost.

Real-time monitoring of enzyme-free strand displacement cascades by colorimetric assays

NASA Astrophysics Data System (ADS)

Duan, Ruixue; Wang, Boya; Hong, Fan; Zhang, Tianchi; Jia, Yongmei; Huang, Jiayu; Hakeem, Abdul; Liu, Nannan; Lou, Xiaoding; Xia, Fan

2015-03-01

The enzyme-free toehold-mediated strand displacement reaction has shown potential for building programmable DNA circuits, biosensors, molecular machines and chemical reaction networks. Here we report a simple colorimetric method using gold nanoparticles as signal generators for the real-time detection of the product of the strand displacement cascade. During the process the assembled gold nanoparticles can be separated, resulting in a color change of the solution. This assay can also be applied in complex mixtures, fetal bovine serum, and to detect single-base mismatches. These results suggest that this method could be of general utility to monitor more complex enzyme-free strand displacement reaction-based programmable systems or for further low-cost diagnostic applications.The enzyme-free toehold-mediated strand displacement reaction has shown potential for building programmable DNA circuits, biosensors, molecular machines and chemical reaction networks. Here we report a simple colorimetric method using gold nanoparticles as signal generators for the real-time detection of the product of the strand displacement cascade. During the process the assembled gold nanoparticles can be separated, resulting in a color change of the solution. This assay can also be applied in complex mixtures, fetal bovine serum, and to detect single-base mismatches. These results suggest that this method could be of general utility to monitor more complex enzyme-free strand displacement reaction-based programmable systems or for further low-cost diagnostic applications. Electronic supplementary information (ESI) available: Experimental procedures and analytical data are provided. See DOI: 10.1039/c5nr00697j

Analytic Complexity and Challenges in Identifying Mixtures of Exposures Associated with Phenotypes in the Exposome Era.

PubMed

Patel, Chirag J

2017-01-01

Mixtures, or combinations and interactions between multiple environmental exposures, are hypothesized to be causally linked with disease and health-related phenotypes. Established and emerging molecular measurement technologies to assay the exposome , the comprehensive battery of exposures encountered from birth to death, promise a new way of identifying mixtures in disease in the epidemiological setting. In this opinion, we describe the analytic complexity and challenges in identifying mixtures associated with phenotype and disease. Existing and emerging machine-learning methods and data analytic approaches (e.g., "environment-wide association studies" [EWASs]), as well as large cohorts may enhance possibilities to identify mixtures of correlated exposures associated with phenotypes; however, the analytic complexity of identifying mixtures is immense. If the exposome concept is realized, new analytical methods and large sample sizes will be required to ascertain how mixtures are associated with disease. The author recommends documenting prevalent correlated exposures and replicated main effects prior to identifying mixtures.

Mixtures of Berkson and classical covariate measurement error in the linear mixed model: Bias analysis and application to a study on ultrafine particles.

PubMed

Deffner, Veronika; Küchenhoff, Helmut; Breitner, Susanne; Schneider, Alexandra; Cyrys, Josef; Peters, Annette

2018-05-01

The ultrafine particle measurements in the Augsburger Umweltstudie, a panel study conducted in Augsburg, Germany, exhibit measurement error from various sources. Measurements of mobile devices show classical possibly individual-specific measurement error; Berkson-type error, which may also vary individually, occurs, if measurements of fixed monitoring stations are used. The combination of fixed site and individual exposure measurements results in a mixture of the two error types. We extended existing bias analysis approaches to linear mixed models with a complex error structure including individual-specific error components, autocorrelated errors, and a mixture of classical and Berkson error. Theoretical considerations and simulation results show, that autocorrelation may severely change the attenuation of the effect estimations. Furthermore, unbalanced designs and the inclusion of confounding variables influence the degree of attenuation. Bias correction with the method of moments using data with mixture measurement error partially yielded better results compared to the usage of incomplete data with classical error. Confidence intervals (CIs) based on the delta method achieved better coverage probabilities than those based on Bootstrap samples. Moreover, we present the application of these new methods to heart rate measurements within the Augsburger Umweltstudie: the corrected effect estimates were slightly higher than their naive equivalents. The substantial measurement error of ultrafine particle measurements has little impact on the results. The developed methodology is generally applicable to longitudinal data with measurement error. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solubility enhancement of miconazole nitrate: binary and ternary mixture approach.

PubMed

Rai, Vineet Kumar; Dwivedi, Harinath; Yadav, Narayan Prasad; Chanotiya, Chandan Singh; Saraf, Shubhini A

2014-08-01

Enhancement of aqueous solubility of very slightly soluble Miconazole Nitrate (MN) is required to widen its application from topical formulation to oral/mucoadhesive formulations. Aim of the present investigation was to enhance the aqueous solubility of MN using binary and ternary mixture approach. Binary mixtures such as solvent deposition, inclusion complexation and solid dispersion were adopted to enhance solubility using different polymers like lactose, beta-cyclodextrin (β-CD) and polyethylene-glycol 6000 (PEG 6000), respectively. Batches of binary mixtures with highest solubility enhancement potentials were further mixed to form ternary mixture by a simple kneading method. Drug polymer interaction and mixture morphology was studied using the Fourier transform infrared spectroscopy and the scanning electron microscopy, respectively along with their saturation solubility studies and drug release. An excellent solubility enhancement, i.e. up to 72 folds and 316 folds of MN was seen by binary and ternary mixture, respectively. Up to 99.5% drug was released in 2 h from the mixtures of MN and polymers. RESULTS revealed that solubility enhancement by binary mixtures is achieved due to surface modification and by increasing wettability of MN. Tremendous increase in solubility of MN by ternary mixture could possibly be due to blending of water soluble polymers, i.e. lactose and PEG 6000 with β-CD which was found to enhance the solubilizing nature of β-CD. Owing to the excellent solubility enhancement potential of ternary mixtures in enhancing MN solubility from 110.4 μg/ml to 57640.0 μg/ml, ternary mixture approach could prove to be promising in the development of oral/mucoadhesive formulations.

Plant constituents interfering with human sex hormone-binding globulin. Evaluation of a test method and its application to Urtica dioica root extracts.

PubMed

Gansser, D; Spiteller, G

1995-01-01

A test system is described, which allows the search for compounds interfering with human sex hormone-binding globulin (SHBG) even in complex plant extracts. The method has been evaluated and applied to Urtica dioica root extracts. The lignan secoisolariciresinol (5) as well as a mixture of isomeric (11 E)-9,10,13-trihydroxy-11-octadecenoic and (10 E)-9,12,13-trihydroxy-10-octadecenoic acids (3 and 4, resp.) were demonstrated to reduce binding activity of human SHBG. Methylation of the mixture of 3 and 4 increased its activity about 10-fold.

DetectTLC: Automated Reaction Mixture Screening Utilizing Quantitative Mass Spectrometry Image Feature

PubMed Central

Kaddi, Chanchala D.; Bennett, Rachel V.; Paine, Martin R. L.; Banks, Mitchel D.; Weber, Arthur L.; Fernández, Facundo M.; Wang, May D.

2016-01-01

Full characterization of complex reaction mixtures is necessary to understand mechanisms, optimize yields, and elucidate secondary reaction pathways. Molecular-level information for species in such mixtures can be readily obtained by coupling mass spectrometry imaging (MSI) with thin layer chromatography (TLC) separations. User-guided investigation of imaging data for mixture components with known m/z values is generally straightforward; however, spot detection for unknowns is highly tedious, and limits the applicability of MSI in conjunction with TLC. To accelerate imaging data mining, we developed DetectTLC, an approach that automatically identifies m/z values exhibiting TLC spot-like regions in MS molecular images. Furthermore, DetectTLC can also spatially match m/z values for spots acquired during alternating high and low collision-energy scans, pairing product ions with precursors to enhance structural identification. As an example, DetectTLC is applied to the identification and structural confirmation of unknown, yet significant, products of abiotic pyrazinone and aminopyrazine nucleoside analog synthesis. PMID:26508443

Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

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

Jarvis, Ian W.H., E-mail: Ian.Jarvis@ki.se; Bergvall, Christoffer, E-mail: Christoffer.Bergvall@anchem.su.se; Bottai, Matteo, E-mail: Matteo.Bottai@ki.se

2013-02-01

Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNAmore » damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs. -- Highlights: ► Benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP) and air PM PAH extracts were compared. ► Binary mixture of BP and DBP induced a more than additive DNA damage response. ► Air PM PAH extracts were more potent than toxicity equivalency factor estimates. ► Larger PAHs (> 4 rings) contribute more to the genotoxicity of PAHs in air PM. ► Chk1 is a sensitive marker for persistent activation of DNA damage signaling from PAH mixtures.« less

Broadband ion mobility deconvolution for rapid analysis of complex mixtures.

PubMed

Pettit, Michael E; Brantley, Matthew R; Donnarumma, Fabrizio; Murray, Kermit K; Solouki, Touradj

2018-05-04

High resolving power ion mobility (IM) allows for accurate characterization of complex mixtures in high-throughput IM mass spectrometry (IM-MS) experiments. We previously demonstrated that pure component IM-MS data can be extracted from IM unresolved post-IM/collision-induced dissociation (CID) MS data using automated ion mobility deconvolution (AIMD) software [Matthew Brantley, Behrooz Zekavat, Brett Harper, Rachel Mason, and Touradj Solouki, J. Am. Soc. Mass Spectrom., 2014, 25, 1810-1819]. In our previous reports, we utilized a quadrupole ion filter for m/z-isolation of IM unresolved monoisotopic species prior to post-IM/CID MS. Here, we utilize a broadband IM-MS deconvolution strategy to remove the m/z-isolation requirement for successful deconvolution of IM unresolved peaks. Broadband data collection has throughput and multiplexing advantages; hence, elimination of the ion isolation step reduces experimental run times and thus expands the applicability of AIMD to high-throughput bottom-up proteomics. We demonstrate broadband IM-MS deconvolution of two separate and unrelated pairs of IM unresolved isomers (viz., a pair of isomeric hexapeptides and a pair of isomeric trisaccharides) in a simulated complex mixture. Moreover, we show that broadband IM-MS deconvolution improves high-throughput bottom-up characterization of a proteolytic digest of rat brain tissue. To our knowledge, this manuscript is the first to report successful deconvolution of pure component IM and MS data from an IM-assisted data-independent analysis (DIA) or HDMSE dataset.

Elucidating complicated assembling systems in biology using size-and-shape analysis of sedimentation velocity data

PubMed Central

Chaton, Catherine T.

2017-01-01

Sedimentation velocity analytical ultracentrifugation (SV-AUC) has seen a resurgence in popularity as a technique for characterizing macromolecules and complexes in solution. SV-AUC is a particularly powerful tool for studying protein conformation, complex stoichiometry, and interacting systems in general. Deconvoluting velocity data to determine a sedimentation coefficient distribution c(s) allows for the study of either individual proteins or multi-component mixtures. The standard c(s) approach estimates molar masses of the sedimenting species based on determination of the frictional ratio (f/f0) from boundary shapes. The frictional ratio in this case is a weight-averaged parameter, which can lead to distortion of mass estimates and loss of information when attempting to analyze mixtures of macromolecules with different shapes. A two-dimensional extension of the c(s) analysis approach provides size-and-shape distributions that describe the data in terms of a sedimentation coefficient and frictional ratio grid. This allows for better resolution of species with very distinct shapes that may co-sediment and provides better molar mass determinations for multi-component mixtures. An example case is illustrated using globular and non-globular proteins of different masses with nearly identical sedimentation coefficients that could only be resolved using the size-and-shape distribution. Other applications of this analytical approach to complex biological systems are presented, focusing on proteins involved in the innate immune response to cytosolic microbial DNA. PMID:26412652

Novel chemometric strategy based on the application of artificial neural networks to crossed mixture design for the improvement of recombinant protein production in continuous culture.

PubMed

Didier, Caroline; Forno, Guillermina; Etcheverrigaray, Marina; Kratje, Ricardo; Goicoechea, Héctor

2009-09-21

The optimal blends of six compounds that should be present in culture media used in recombinant protein production were determined by means of artificial neural networks (ANN) coupled with crossed mixture experimental design. This combination constitutes a novel approach to develop a medium for cultivating genetically engineered mammalian cells. The compounds were collected in two mixtures of three elements each, and the experimental space was determined by a crossed mixture design. Empirical data from 51 experimental units were used in a multiresponse analysis to train artificial neural networks which satisfy different requirements, in order to define two new culture media (Medium 1 and Medium 2) to be used in a continuous biopharmaceutical production process. These media were tested in a bioreactor to produce a recombinant protein in CHO cells. Remarkably, for both predicted media all responses satisfied the predefined goals pursued during the analysis, except in the case of the specific growth rate (mu) observed for Medium 1. ANN analysis proved to be a suitable methodology to be used when dealing with complex experimental designs, as frequently occurs in the optimization of production processes in the biotechnology area. The present work is a new example of the use of ANN for the resolution of a complex, real life system, successfully employed in the context of a biopharmaceutical production process.

Evaluating the similarity of complex drinking-water disinfection by-product mixtures: overview of the issues.

PubMed

Rice, Glenn E; Teuschler, Linda K; Bull, Richard J; Simmons, Jane E; Feder, Paul I

2009-01-01

Humans are exposed daily to complex mixtures of environmental chemical contaminants, which arise as releases from sources such as engineering procedures, degradation processes, and emissions from mobile or stationary sources. When dose-response data are available for the actual environmental mixture to which individuals are exposed (i.e., the mixture of concern), these data provide the best information for dose-response assessment of the mixture. When suitable data on the mixture itself are not available, surrogate data might be used from a sufficiently similar mixture or a group of similar mixtures. Consequently, the determination of whether the mixture of concern is "sufficiently similar" to a tested mixture or a group of tested mixtures is central to the use of whole mixture methods. This article provides an overview for a series of companion articles whose purpose is to develop a set of biostatistical, chemical, and toxicological criteria and approaches for evaluating the similarity of drinking-water disinfection by-product (DBPs) complex mixtures. Together, the five articles in this series serve as a case study whose techniques will be relevant to assessing similarity for other classes of complex mixtures of environmental chemicals. Schenck et al. (2009) describe the chemistry and mutagenicity of a set of DBP mixtures concentrated from five different drinking-water treatment plants. Bull et al. (2009a, 2009b) describe how the variables that impact the formation of DBP affect the chemical composition and, subsequently, the expected toxicity of the mixture. Feder et al. (2009a, 2009b) evaluate the similarity of DBP mixture concentrates by applying two biostatistical approaches, principal components analysis, and a nonparametric "bootstrap" analysis. Important factors for determining sufficient similarity of DBP mixtures found in this research include disinfectant used; source water characteristics, including the concentrations of bromide and total organic carbon; concentrations and proportions of individual DBPs with known toxicity data on the same endpoint; magnitude of the unidentified fraction of total organic halides; similar toxicity outcomes for whole mixture testing (e.g., mutagenicity); and summary chemical measures such as total trihalomethanes, total haloacetic acids, total haloacetonitriles, and the levels of bromide incorporation in the DBP classes.

Subcritical Water Induced Complexation of Soy Protein and Rutin: Improved Interfacial Properties and Emulsion Stability.

PubMed

Chen, Xiao-Wei; Wang, Jin-Mei; Yang, Xiao-Quan; Qi, Jun-Ru; Hou, Jun-Jie

2016-09-01

Rutin is a common dietary flavonoid with important antioxidant and pharmacological activities. However, its application in the food industry is limited mainly because of its poor water solubility. The subcritical water (SW) treatment provides an efficient technique to solubilize and achieve the enrichment of rutin in soy protein isolate (SPI) by inducing their complexation. The physicochemical, interfacial, and emulsifying properties of the complex were investigated and compared to the mixtures. SW treatment had much enhanced rutin-combined capacity of SPI than that of conventional method, ascribing to the well-contacted for higher water solubility of rutin with stronger collision-induced hydrophobic interactions. Compared to the mixtures of rutin with proteins, the complex exhibited an excellent surface activity and improved the physical and oxidative stability of its stabilized emulsions. This improving effect could be attributed to the targeted accumulation of rutin at the oil-water interface accompanied by the adsorption of SPI resulting in the thicker interfacial layer, as evidenced by higher interfacial protein and rutin concentrations. This study provides a novel strategy for the design and enrichment of nanovehicle providing water-insoluble hydrophobic polyphenols for interfacial delivery in food emulsified systems. © 2016 Institute of Food Technologists®

Characterization of the Androgen-sensitive MDA-kb2 Cell Line for Assessing Complex Environmental Mixtures, Presentation

EPA Science Inventory

Synthetic and natural steroidal androgens and estrogens and many other non-steroidal endocrine-active compounds commonly occur as complex mixtures in aquatic environments. It is important to understand the potential interactive effects of these mixtures to properly assess their r...

Integrated Disinfection By-Products Research: Assessing Reproductive and Developmental Risks Posed by Complex Disinfection By-Product Mixtures

EPA Science Inventory

This article presents a toxicologically-based risk assessment strategy for identifying the individual components or fractions of a complex mixture that are associated with its toxicity. The strategy relies on conventional component-based mixtures risk approaches such as dose addi...

Evaluation of the efficiency of continuous wavelet transform as processing and preprocessing algorithm for resolution of overlapped signals in univariate and multivariate regression analyses; an application to ternary and quaternary mixtures

NASA Astrophysics Data System (ADS)

Hegazy, Maha A.; Lotfy, Hayam M.; Mowaka, Shereen; Mohamed, Ekram Hany

2016-07-01

Wavelets have been adapted for a vast number of signal-processing applications due to the amount of information that can be extracted from a signal. In this work, a comparative study on the efficiency of continuous wavelet transform (CWT) as a signal processing tool in univariate regression and a pre-processing tool in multivariate analysis using partial least square (CWT-PLS) was conducted. These were applied to complex spectral signals of ternary and quaternary mixtures. CWT-PLS method succeeded in the simultaneous determination of a quaternary mixture of drotaverine (DRO), caffeine (CAF), paracetamol (PAR) and p-aminophenol (PAP, the major impurity of paracetamol). While, the univariate CWT failed to simultaneously determine the quaternary mixture components and was able to determine only PAR and PAP, the ternary mixtures of DRO, CAF, and PAR and CAF, PAR, and PAP. During the calculations of CWT, different wavelet families were tested. The univariate CWT method was validated according to the ICH guidelines. While for the development of the CWT-PLS model a calibration set was prepared by means of an orthogonal experimental design and their absorption spectra were recorded and processed by CWT. The CWT-PLS model was constructed by regression between the wavelet coefficients and concentration matrices and validation was performed by both cross validation and external validation sets. Both methods were successfully applied for determination of the studied drugs in pharmaceutical formulations.

21 CFR 1310.13 - Exemption of chemical mixtures; application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Exemption of chemical mixtures; application. 1310... REPORTS OF LISTED CHEMICALS AND CERTAIN MACHINES § 1310.13 Exemption of chemical mixtures; application. (a... application of all or any part of the Act a chemical mixture consisting of two or more chemical components, at...

21 CFR 1310.13 - Exemption of chemical mixtures; application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Exemption of chemical mixtures; application. 1310... REPORTS OF LISTED CHEMICALS AND CERTAIN MACHINES § 1310.13 Exemption of chemical mixtures; application. (a... application of all or any part of the Act a chemical mixture consisting of two or more chemical components, at...

21 CFR 1310.13 - Exemption of chemical mixtures; application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Exemption of chemical mixtures; application. 1310... REPORTS OF LISTED CHEMICALS AND CERTAIN MACHINES § 1310.13 Exemption of chemical mixtures; application. (a... application of all or any part of the Act a chemical mixture consisting of two or more chemical components, at...

21 CFR 1310.13 - Exemption of chemical mixtures; application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Exemption of chemical mixtures; application. 1310... REPORTS OF LISTED CHEMICALS AND CERTAIN MACHINES § 1310.13 Exemption of chemical mixtures; application. (a... application of all or any part of the Act a chemical mixture consisting of two or more chemical components, at...

21 CFR 1310.13 - Exemption of chemical mixtures; application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Exemption of chemical mixtures; application. 1310... REPORTS OF LISTED CHEMICALS AND CERTAIN MACHINES § 1310.13 Exemption of chemical mixtures; application. (a... application of all or any part of the Act a chemical mixture consisting of two or more chemical components, at...

Seed Storage Proteins as a System for Teaching Protein Identification by Mass Spectrometry in Biochemistry Laboratory

ERIC Educational Resources Information Center

Wilson, Karl A.; Tan-Wilson, Anna

2013-01-01

Mass spectrometry (MS) has become an important tool in studying biological systems. One application is the identification of proteins and peptides by the matching of peptide and peptide fragment masses to the sequences of proteins in protein sequence databases. Often prior protein separation of complex protein mixtures by 2D-PAGE is needed,…

Comprehensive Metabolite Identification Strategy Using Multiple Two-Dimensional NMR Spectra of a Complex Mixture Implemented in the COLMARm Web Server

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

Bingol, Kerem; Li, Da-Wei; Zhang, Bo

Identification of metabolites in complex mixtures represents a key step in metabolomics. A new strategy is introduced, which is implemented in a new public web server, COLMARm, that permits the co-analysis of up to three 2D NMR spectra, namely 13C-1H HSQC, 1H-1H TOCSY, and 13C-1H HSQC-TOCSY for the comprehensive, accurate, and efficient performance of this task. The highly versatile and interactive nature of COLMARm permits its application to a wide range of metabolomics samples independent of the magnetic field. Database query is performed using the HSQC spectrum and the top metabolite hits are then validated against the TOCSY-type experiment(s) bymore » superimposing the expected cross-peaks on the mixture spectrum. In this way the user can directly accept or reject candidate metabolites by taking advantage of the complementary spectral information offered by these experiments and their different sensitivities. The power of COLMARm is demonstrated for a human serum sample uncovering the existence of 14 metabolites that hitherto were not identified by NMR.« less

Improving Toxicity Assessment of Pesticide Mixtures: The Use of Polar Passive Sampling Devices Extracts in Microalgae Toxicity Tests

PubMed Central

Kim Tiam, Sandra; Fauvelle, Vincent; Morin, Soizic; Mazzella, Nicolas

2016-01-01

Complexity of contaminants exposure needs to be taking in account for an appropriate evaluation of risks related to mixtures of pesticides released in the ecosystems. Toxicity assessment of such mixtures can be made through a variety of toxicity tests reflecting different level of biological complexity. This paper reviews the recent developments of passive sampling techniques for polar compounds, especially Polar Organic Chemical Integrative Samplers (POCIS) and Chemcatcher® and the principal assessment techniques using microalgae in laboratory experiments. The progresses permitted by the coupled use of such passive samplers and ecotoxicology testing as well as their limitations are presented. Case studies combining passive sampling devices (PSD) extracts and toxicity assessment toward microorganisms at different biological scales from single organisms to communities level are presented. These case studies, respectively, aimed (i) at characterizing the “toxic potential” of waters using dose-response curves, and (ii) at performing microcosm experiments with increased environmental realism in the toxicant exposure in term of cocktail composition and concentration. Finally perspectives and limitations of such approaches for future applications in the area of environmental risk assessment are discussed. PMID:27667986

Leidenfrost Phenomenon-assisted Thermal Desorption (LPTD) and Its Application to Open Ion Sources at Atmospheric Pressure Mass Spectrometry

NASA Astrophysics Data System (ADS)

Saha, Subhrakanti; Chen, Lee Chuin; Mandal, Mridul Kanti; Hiraoka, Kenzo

2013-03-01

This work describes the development and application of a new thermal desorption technique that makes use of the Leidenfrost phenomenon in open ion sources at atmospheric pressure for direct mass spectrometric detection of ultratrace levels of illicit, therapeutic, and stimulant drugs, toxicants, and peptides (molecular weight above 1 kDa) in their unaltered state from complex real world samples without or with minor sample pretreatment. A low temperature dielectric barrier discharge ion source was used throughout the experiments and the analytical figures of merit of this technique were investigated. Further, this desorption technique coupled with other ionization sources such as electrospray ionization (ESI) and dc corona discharge atmospheric pressure chemical ionization (APCI) in open atmosphere was also investigated. The use of the high-resolution `Exactive Orbitrap' mass spectrometer provided unambiguous identification of trace levels of the targeted compounds from complex mixtures and background noise; the limits of detection for various small organic molecules and peptides treated with this technique were at the level of parts per trillion and 10-9 M, respectively. The high sensitivity of the present technique is attributed to the spontaneous enrichment of analyte molecules during the slow evaporation of the solvent, as well as to the sequential desorption of molecules from complex mixtures based on their volatilities. This newly developed desorption technique is simple and fast, while molecular ions are observed as the major ions.

Cork-resin ablative insulation for complex surfaces and method for applying the same

NASA Technical Reports Server (NTRS)

Walker, H. M.; Sharpe, M. H.; Simpson, W. G. (Inventor)

1980-01-01

A method of applying cork-resin ablative insulation material to complex curved surfaces is disclosed. The material is prepared by mixing finely divided cork with a B-stage curable thermosetting resin, forming the resulting mixture into a block, B-stage curing the resin-containing block, and slicing the block into sheets. The B-stage cured sheet is shaped to conform to the surface being insulated, and further curing is then performed. Curing of the resins only to B-stage before shaping enables application of sheet material to complex curved surfaces and avoids limitations and disadvantages presented in handling of fully cured sheet material.

An Innovative Concept for Testing Rutting Susceptibility of Asphalt Mixture

NASA Astrophysics Data System (ADS)

Mohseni, Alaeddin; Azari, Haleh

Currently, flow number (FN) is being used for measuring permanent deformation resistance of asphalt mixtures. The provisional AASHTO TP 79-10 test method specifies the requirements of the FN test; however, there are undefined levels of test variables, such as temperature, axial stress, and confinement. Therefore, agreeable FN criteria that can reliably discriminate between various mixtures have not been established yet. As the asphalt industry continues to develop more sophisticated mixtures (Warm Mix, RAP and RAS), the FN value has failed to capture the true complexity of the asphalt mixtures. These shortcomings and the unpredictable testing time of the FN test have affected its usefulness for evaluating high temperature performance of asphalt mixtures. A new test procedure for evaluation of rutting susceptibility of asphalt mixtures is being proposed. The new procedure is conducted at one temperature and multiple stresses on the same replicate in three increments of 500 cycles, which only takes 33 minutes to complete. The property of the test is the permanent strain due to the last cycle of each test increment (Minimum Strain Rate, or MSR). A master curve is developed by plotting the MSR values versus parameter TP, which is a product of Temperature and Pressure. The MSR master curve represents the unit rutting damage (rut per axle) of asphalt mixtures at any stress and temperature and can be used in laboratory for material characterization, mix design verification, ranking of the mixtures, or for pavement design applications to predict rut depth for project climate and design traffic.

Mixture and odorant processing in the olfactory systems of insects: a comparative perspective.

PubMed

Clifford, Marie R; Riffell, Jeffrey A

2013-11-01

Natural olfactory stimuli are often complex mixtures of volatiles, of which the identities and ratios of constituents are important for odor-mediated behaviors. Despite this importance, the mechanism by which the olfactory system processes this complex information remains an area of active study. In this review, we describe recent progress in how odorants and mixtures are processed in the brain of insects. We use a comparative approach toward contrasting olfactory coding and the behavioral efficacy of mixtures in different insect species, and organize these topics around four sections: (1) Examples of the behavioral efficacy of odor mixtures and the olfactory environment; (2) mixture processing in the periphery; (3) mixture coding in the antennal lobe; and (4) evolutionary implications and adaptations for olfactory processing. We also include pertinent background information about the processing of individual odorants and comparative differences in wiring and anatomy, as these topics have been richly investigated and inform the processing of mixtures in the insect olfactory system. Finally, we describe exciting studies that have begun to elucidate the role of the processing of complex olfactory information in evolution and speciation.

Applications of space-electrophoresis in medicine. [for cellular separations in molecular biology

NASA Technical Reports Server (NTRS)

Bier, M.

1976-01-01

The nature of electrophoresis is reviewed and potential advances realizable in the field of biology and medicine from a space electrophoresis facility are examined. The ground-based applications of electrophoresis: (1) characterization of an ionized species; (2) determination of the quantitative composition of a complex mixture; and (3) isolation of the components of a mixture, separation achieved on the basis of the difference in transport rates is reviewed. The electrophoresis of living cells is considered, touching upon the following areas: the separation of T and B lymphocytes; the genetic influence on mouse lymphocyte mobilities; the abnormal production of specific and monoclonal immunoproteins; and the study of cancer. Schematic diagrams are presented of three types of electrophoresis apparatus: the column assembly for the static electrophoresis experiment on the Apollo-Soyuz mission, the continuous flow apparatus used in the same mission and a miniaturized electrophoresis apparatus.

THE GENOTOXICITY OF PRIORITY POLYCYCLIC AROMATIC HYDROCARBONS IN COMPLEX MIXTURES

EPA Science Inventory

Risk assessment of complex environmental samples suffers from difficulty in identifying toxic components, inadequacy of available toxicity data, and a paucity of knowledge about the behavior of geno(toxic) substances in complex mixtures. Lack of information about the behavior of ...

Accurate characterization of weak macromolecular interactions by titration of NMR residual dipolar couplings: application to the CD2AP SH3-C:ubiquitin complex.

PubMed

Ortega-Roldan, Jose Luis; Jensen, Malene Ringkjøbing; Brutscher, Bernhard; Azuaga, Ana I; Blackledge, Martin; van Nuland, Nico A J

2009-05-01

The description of the interactome represents one of key challenges remaining for structural biology. Physiologically important weak interactions, with dissociation constants above 100 muM, are remarkably common, but remain beyond the reach of most of structural biology. NMR spectroscopy, and in particular, residual dipolar couplings (RDCs) provide crucial conformational constraints on intermolecular orientation in molecular complexes, but the combination of free and bound contributions to the measured RDC seriously complicates their exploitation for weakly interacting partners. We develop a robust approach for the determination of weak complexes based on: (i) differential isotopic labeling of the partner proteins facilitating RDC measurement in both partners; (ii) measurement of RDC changes upon titration into different equilibrium mixtures of partially aligned free and complex forms of the proteins; (iii) novel analytical approaches to determine the effective alignment in all equilibrium mixtures; and (iv) extraction of precise RDCs for bound forms of both partner proteins. The approach is demonstrated for the determination of the three-dimensional structure of the weakly interacting CD2AP SH3-C:Ubiquitin complex (K(d) = 132 +/- 13 muM) and is shown, using cross-validation, to be highly precise. We expect this methodology to extend the remarkable and unique ability of NMR to study weak protein-protein complexes.

Accurate characterization of weak macromolecular interactions by titration of NMR residual dipolar couplings: application to the CD2AP SH3-C:ubiquitin complex

PubMed Central

Ortega-Roldan, Jose Luis; Jensen, Malene Ringkjøbing; Brutscher, Bernhard; Azuaga, Ana I.; Blackledge, Martin; van Nuland, Nico A. J.

2009-01-01

The description of the interactome represents one of key challenges remaining for structural biology. Physiologically important weak interactions, with dissociation constants above 100 μM, are remarkably common, but remain beyond the reach of most of structural biology. NMR spectroscopy, and in particular, residual dipolar couplings (RDCs) provide crucial conformational constraints on intermolecular orientation in molecular complexes, but the combination of free and bound contributions to the measured RDC seriously complicates their exploitation for weakly interacting partners. We develop a robust approach for the determination of weak complexes based on: (i) differential isotopic labeling of the partner proteins facilitating RDC measurement in both partners; (ii) measurement of RDC changes upon titration into different equilibrium mixtures of partially aligned free and complex forms of the proteins; (iii) novel analytical approaches to determine the effective alignment in all equilibrium mixtures; and (iv) extraction of precise RDCs for bound forms of both partner proteins. The approach is demonstrated for the determination of the three-dimensional structure of the weakly interacting CD2AP SH3-C:Ubiquitin complex (Kd = 132 ± 13 μM) and is shown, using cross-validation, to be highly precise. We expect this methodology to extend the remarkable and unique ability of NMR to study weak protein–protein complexes. PMID:19359362

Assessment of health effects in epidemiologic studies of air pollution.

PubMed Central

Samet, J M; Speizer, F E

1993-01-01

As we increasingly recognize the complexity of the pollutants in indoor and outdoor microenvironments, a broad array of inhaled mixtures has assumed scientific, public health, and regulatory importance. Few adverse effects of environmental pollutants are specific, that is, uniquely associated with a single agent; the adverse effects that might be considered in an investigation of the consequences of exposure to an inhaled complex mixture are generally nonspecific. In the context of this paper, we will refer to binary mixtures as complex, though we realize that a more precise definition of complexity would restrict the term to mixtures of three or more constituents. Their causes potentially include not only pollutant exposures through the medium of inhaled air but other environmental agents, such as infectious organisms and radiation, and inherent characteristics of the exposed persons, such as atopy. We review the outcome measures that have been used in epidemiologic studies of the health effects of single pollutants and complex mixtures. Some of these outcome measures have been carefully standardized, whereas others need similar standardization and modification to improve sensitivity and specificity for investigating the health effects of air pollution. PMID:8206024

Molecular identification of organic compounds in atmospheric complex mixtures and relationship to atmospheric chemistry and sources.

PubMed

Mazurek, Monica A

2002-12-01

This article describes a chemical characterization approach for complex organic compound mixtures associated with fine atmospheric particles of diameters less than 2.5 m (PM2.5). It relates molecular- and bulk-level chemical characteristics of the complex mixture to atmospheric chemistry and to emission sources. Overall, the analytical approach describes the organic complex mixtures in terms of a chemical mass balance (CMB). Here, the complex mixture is related to a bulk elemental measurement (total carbon) and is broken down systematically into functional groups and molecular compositions. The CMB and molecular-level information can be used to understand the sources of the atmospheric fine particles through conversion of chromatographic data and by incorporation into receptor-based CMB models. Once described and quantified within a mass balance framework, the chemical profiles for aerosol organic matter can be applied to existing air quality issues. Examples include understanding health effects of PM2.5 and defining and controlling key sources of anthropogenic fine particles. Overall, the organic aerosol compositional data provide chemical information needed for effective PM2.5 management.

Separation system suitability (3S): a new criterion of chromatogram classification in HPLC based on cross-evaluation of separation capacity/peak symmetry and its application to complex mixtures of anthraquinones.

PubMed

Nowik, Witold; Héron, Sylvie; Bonose, Myriam; Tchapla, Alain

2013-10-07

A comparison of chromatograms obtained in a series of separation conditions for a given complex mixture may be done with a series of chromatographic descriptors. In this study, we used two descriptors: the number of critical pairs and symmetry of peaks, further rescaled and converted to the corresponding critical pairs' coefficient (CPc) and symmetry coefficient (Sc). Considering the difficulty of appreciating global separation quality using CPc and Sc criteria separately, as their respective values are usually uncorrelated, a double-criteria cross-evaluation system was required. For that purpose we tested the commonly used multi-criteria decision-making method - Derringer's desirability function (D) - as well as the recently introduced sum of ranking differences (SRD). To facilitate the graphical comparison of both approaches, the desirability function (D) was used in the inverse form (Dinv). The advantages and drawbacks of both evaluation methods, especially the respective under- or over-evaluation of outliers, caused us to introduce a new ranking approach, separation system suitability (3S). The obtained suitability rankings for the three tested approaches (Dinv, SRD and 3S) are different; nevertheless, 3S appears to be the most balanced and the easiest to interpret as well. The approach developed for selection of suitable systems was applied to the problem of separation of complex mixtures through the analysis of a series of standards of anthraquinone derivatives. To judge the pertinence of this evaluation, a sample containing a number of natural anthraquinones extracted from the bark of Indian mulberry (Morinda citrifolia) was analysed. In conclusion, the proposed methodology for the cross-evaluation of the series of chromatograms using single specific descriptors (CPc and Sc) through a global composite descriptor (3S) significantly simplifies the decision that separation systems are the most suitable for the separation of complex target mixtures of compounds.

Identifying Complex Mixtures in the Environment with Cheminformatics and Non-targeted High Resolution Mass Spectrometry (SETAC NA Focused Topic Meeting : Risk Assessment of Chemical Mixtures)

EPA Science Inventory

Non-target high resolution mass spectrometry techniques combined with advanced cheminformatics offer huge potential for exploring complex mixtures in our environment – yet also offers plenty of challenges. Peak inventories of several non-target studies from within Europe reveal t...

Development of a ratiometric time-resolved luminescence sensor for pH based on lanthanide complexes.

PubMed

Liu, Mingjing; Ye, Zhiqiang; Xin, Chenglong; Yuan, Jingli

2013-01-25

Time-resolved luminescence bioassay technique using lanthanide complexes as luminescent probes/sensors has shown great utilities in clinical diagnostics and biotechnology discoveries. In this work, a novel terpyridine polyacid derivative that can form highly stable complexes with lanthanide ions in aqueous media, (4'-hydroxy-2,2':6',2''-terpyridine-6,6''-diyl) bis(methylenenitrilo) tetrakis(acetic acid) (HTTA), was designed and synthesized for developing time-resolved luminescence pH sensors based on its Eu(3+) and Tb(3+) complexes. The luminescence characterization results reveal that the luminescence intensity of HTTA-Eu(3+) is strongly dependent on the pH values in weakly acidic to neutral media (pK(a) = 5.8, pH 4.8-7.5), while that of HTTA-Tb(3+) is pH-independent. This unique luminescence response allows the mixture of HTTA-Eu(3+) and HTTA-Tb(3+) (the HTTA-Eu(3+)/Tb(3+) mixture) to be used as a ratiometric luminescence sensor for the time-resolved luminescence detection of pH with the intensity ratio of its Tb(3+) emission at 540 nm to its Eu(3+) emission at 610 nm, I(540 nm)/I(610 nm), as a signal. Moreover, the UV absorption spectrum changes of the HTTA-Eu(3+)/Tb(3+) mixture at different pHs (pH 4.0-7.0) also display a ratiometric response to the pH changes with the ratio of absorbance at 290 nm to that at 325 nm, A(290 nm)/A(325 nm), as a signal. This feature enables the HTTA-Eu(3+)/Tb(3+) mixture to have an additional function for the pH detection with the absorption spectrometry technique. For loading the complexes into the living cells, the acetoxymethyl ester of HTTA was synthesized and used for loading HTTA-Eu(3+) and HTTA-Tb(3+) into the cultured HeLa cells. The luminescence imaging results demonstrated the practical utility of the new sensor for the time-resolved luminescence cell imaging application. Copyright © 2012 Elsevier B.V. All rights reserved.

STRATEGIES TO IDENTIFY BIOACTIVE SUBSTANCES IN COMPLEX AIR POLLUTANT MIXTURES

EPA Science Inventory

Both indoor and outdoor air contains a very complex mixture of gas and particulate matter (PM) pollutants. The assessment of the role of each pollutant in the complex atmosphere in the induction of an associated health effect or a response can be difficult due to many factors, i...

Evaluation of the efficiency of continuous wavelet transform as processing and preprocessing algorithm for resolution of overlapped signals in univariate and multivariate regression analyses; an application to ternary and quaternary mixtures.

PubMed

Hegazy, Maha A; Lotfy, Hayam M; Mowaka, Shereen; Mohamed, Ekram Hany

2016-07-05

Wavelets have been adapted for a vast number of signal-processing applications due to the amount of information that can be extracted from a signal. In this work, a comparative study on the efficiency of continuous wavelet transform (CWT) as a signal processing tool in univariate regression and a pre-processing tool in multivariate analysis using partial least square (CWT-PLS) was conducted. These were applied to complex spectral signals of ternary and quaternary mixtures. CWT-PLS method succeeded in the simultaneous determination of a quaternary mixture of drotaverine (DRO), caffeine (CAF), paracetamol (PAR) and p-aminophenol (PAP, the major impurity of paracetamol). While, the univariate CWT failed to simultaneously determine the quaternary mixture components and was able to determine only PAR and PAP, the ternary mixtures of DRO, CAF, and PAR and CAF, PAR, and PAP. During the calculations of CWT, different wavelet families were tested. The univariate CWT method was validated according to the ICH guidelines. While for the development of the CWT-PLS model a calibration set was prepared by means of an orthogonal experimental design and their absorption spectra were recorded and processed by CWT. The CWT-PLS model was constructed by regression between the wavelet coefficients and concentration matrices and validation was performed by both cross validation and external validation sets. Both methods were successfully applied for determination of the studied drugs in pharmaceutical formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Complexation Effect on Redox Potential of Iron(III)-Iron(II) Couple: A Simple Potentiometric Experiment

ERIC Educational Resources Information Center

Rizvi, Masood Ahmad; Syed, Raashid Maqsood; Khan, Badruddin

2011-01-01

A titration curve with multiple inflection points results when a mixture of two or more reducing agents with sufficiently different reduction potentials are titrated. In this experiment iron(II) complexes are combined into a mixture of reducing agents and are oxidized to the corresponding iron(III) complexes. As all of the complexes involve the…

Combination of electrospray ionization, atmospheric pressure photoionization and laser desorption ionization Fourier transform ion cyclotronic resonance mass spectrometry for the investigation of complex mixtures - Application to the petroleomic analysis of bio-oils.

PubMed

Hertzog, Jasmine; Carré, Vincent; Le Brech, Yann; Mackay, Colin Logan; Dufour, Anthony; Mašek, Ondřej; Aubriet, Frédéric

2017-05-29

The comprehensive description of complex mixtures such as bio-oils is required to understand and improve the different processes involved during biological, environmental or industrial operation. In this context, we have to consider how different ionization sources can improve a non-targeted approach. Thus, the Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) has been coupled to electrospray ionization (ESI), laser desorption ionization (LDI) and atmospheric pressure photoionization (APPI) to characterize an oak pyrolysis bio-oil. Close to 90% of the all 4500 compound formulae has been attributed to C x H y O z with similar oxygen class compound distribution. Nevertheless, their relative abundance in respect with their double bound equivalent (DBE) value has evidenced significant differences depending on the ion source used. ESI has allowed compounds with low DBE but more oxygen atoms to be ionized. APPI has demonstrated the efficient ionization of less polar compounds (high DBE values and less oxygen atoms). The LDI behavior of bio-oils has been considered intermediate in terms of DBE and oxygen amounts but it has also been demonstrated that a significant part of the features are specifically detected by this ionization method. Thus, the complementarity of three different ionization sources has been successfully demonstrated for the exhaustive characterization by petroleomic approach of a complex mixture. Copyright © 2017 Elsevier B.V. All rights reserved.

Transferring mixtures of chemicals from sediment to a bioassay using silicone-based passive sampling and dosing.

PubMed

Mustajärvi, Lukas; Eriksson-Wiklund, Ann-Kristin; Gorokhova, Elena; Jahnke, Annika; Sobek, Anna

2017-11-15

Environmental mixtures of chemicals consist of a countless number of compounds with unknown identity and quantity. Yet, chemical regulation is mainly built around the assessment of single chemicals. Existing frameworks for assessing the toxicity of mixtures require that both the chemical composition and quantity are known. Quantitative analyses of the chemical composition of environmental mixtures are however extremely challenging and resource-demanding. Bioassays may therefore serve as a useful approach for investigating the combined toxicity of environmental mixtures of chemicals in a cost-efficient and holistic manner. In this study, an unknown environmental mixture of bioavailable semi-hydrophobic to hydrophobic chemicals was sampled from a contaminated sediment in a coastal Baltic Sea area using silicone polydimethylsiloxane (PDMS) as an equilibrium passive sampler. The chemical mixture was transferred to a PDMS-based passive dosing system, and its applicability was demonstrated using green algae Tetraselmis suecica in a cell viability assay. The proportion of dead cells increased significantly with increasing exposure level and in a dose-response manner. At an ambient concentration, the proportion of dead cells in the population was nearly doubled compared to the control; however, the difference was non-significant due to high inter-replicate variability and a low number of replicates. The validation of the test system regarding equilibrium sampling, loading efficiency into the passive dosing polymer, stability of the mixture composition, and low algal mortality in control treatments demonstrates that combining equilibrium passive sampling and passive dosing is a promising tool for investigating the toxicity of bioavailable semi-hydrophobic and hydrophobic chemicals in complex environmental mixtures.

Modeling the chemistry of complex petroleum mixtures.

PubMed Central

Quann, R J

1998-01-01

Determining the complete molecular composition of petroleum and its refined products is not feasible with current analytical techniques because of the astronomical number of molecular components. Modeling the composition and behavior of such complex mixtures in refinery processes has accordingly evolved along a simplifying concept called lumping. Lumping reduces the complexity of the problem to a manageable form by grouping the entire set of molecular components into a handful of lumps. This traditional approach does not have a molecular basis and therefore excludes important aspects of process chemistry and molecular property fundamentals from the model's formulation. A new approach called structure-oriented lumping has been developed to model the composition and chemistry of complex mixtures at a molecular level. The central concept is to represent an individual molecular or a set of closely related isomers as a mathematical construct of certain specific and repeating structural groups. A complex mixture such as petroleum can then be represented as thousands of distinct molecular components, each having a mathematical identity. This enables the automated construction of large complex reaction networks with tens of thousands of specific reactions for simulating the chemistry of complex mixtures. Further, the method provides a convenient framework for incorporating molecular physical property correlations, existing group contribution methods, molecular thermodynamic properties, and the structure--activity relationships of chemical kinetics in the development of models. PMID:9860903

Polysaccharide-derived mesoporous materials (Starbon®) for sustainable separation of complex mixtures.

PubMed

Zuin, Vânia G; Budarin, Vitaliy L; De Bruyn, Mario; Shuttleworth, Peter S; Hunt, Andrew J; Pluciennik, Camille; Borisova, Aleksandra; Dodson, Jennifer; Parker, Helen L; Clark, James H

2017-09-21

The recovery and separation of high value and low volume extractives are a considerable challenge for the commercial realisation of zero-waste biorefineries. Using solid-phase extractions (SPE) based on sustainable sorbents is a promising method to enable efficient, green and selective separation of these complex extractive mixtures. Mesoporous carbonaceous solids derived from renewable polysaccharides are ideal stationary phases due to their tuneable functionality and surface structure. In this study, the structure-separation relationships of thirteen polysaccharide-derived mesoporous materials and two modified types as sorbents for ten naturally-occurring bioactive phenolic compounds were investigated. For the first time, a comprehensive statistical analysis of the key molecular and surface properties influencing the recovery of these species was carried out. The obtained results show the possibility of developing tailored materials for purification, separation or extraction, depending on the molecular composition of the analyte. The wide versatility and application span of these polysaccharide-derived mesoporous materials offer new sustainable and inexpensive alternatives to traditional silica-based stationary phases.

Photolithography and Fluorescence Correlation Spectroscopy used to examine the rates of exchange in reverse micelle systems

NASA Astrophysics Data System (ADS)

Norris, Zach; Mawson, Cara; Johnson, Kyron; Kessler, Sarah; Rebecca, Anne; Wolf, Nathan; Lim, Michael; Nucci, Nathaniel

Reverse micelles are molecular complexes that encapsulate a nanoscale pool of water in a surfactant shell dissolved in non-polar solvent. These complexes have a wide range of applications, and in all cases, the degree to which reverse micelles (RM) exchange their contents is relevant for their use. Despite its importance, this aspect of RM behavior is poorly understood. Photolithography is employed here to create micro and nano scale fluidic systems in which mixing rates can be precisely measured using fluorescence correlation spectroscopy (FCS). Micro-channel patterns are etched using reactive ion etching process into a layer of silicon dioxide on crystalline silicon substrates. Solutions containing mixtures of reverse micelles, proteins, and fluorophores are placed into reservoirs in the patterns, while diffusion and exchange between RMs is monitored using a FCS system built from a modified confocal Raman spectrometer. Using this approach, the diffusion and exchange rates for RM systems are measured as a function of the components of the RM mixture. Funding provided by Rowan University.

Monolayers of derivatized poly(l-lysine)-grafted poly(ethylene glycol) on metal oxides as a class of biomolecular interfaces

PubMed Central

Ruiz-Taylor, L. A.; Martin, T. L.; Zaugg, F. G.; Witte, K.; Indermuhle, P.; Nock, S.; Wagner, P.

2001-01-01

We report on the design and characterization of a class of biomolecular interfaces based on derivatized poly(l-lysine)-grafted poly(ethylene glycol) copolymers adsorbed on negatively charged surfaces. As a model system, we synthesized biotin-derivatized poly(l-lysine)-grafted poly(ethylene glycol) copolymers, PLL-g-[(PEGm)(1−x) (PEG-biotin)x], where x varies from 0 to 1. Monolayers were produced on titanium dioxide substrates and characterized by x-ray photoelectron spectroscopy. The specific biorecognition properties of these biotinylated surfaces were investigated with the use of radiolabeled streptavidin alone and within complex protein mixtures. The PLL-g-PEG-biotin monolayers specifically capture streptavidin, even from a complex protein mixture, while still preventing nonspecific adsorption of other proteins. This streptavidin layer can subsequently capture biotinylated proteins. Finally, with the use of microfluidic networks and protein arraying, we demonstrate the potential of this class of biomolecular interfaces for applications based on protein patterning. PMID:11158560

Synthesis of 1,8-naphthyridines and their application in the development of anionic fluorogenic chemosensors.

PubMed

Nicoleti, Celso R; Garcia, Diogo N; da Silva, Luiz E; Begnini, Iêda M; Rebelo, Ricardo A; Joussef, Antonio C; Machado, Vanderlei G

2012-07-01

Two 1,8-naphthyridines were synthesized and found to be fluorescent in solution. These compounds were studied in the presence of Cu(+) and Cu(2+) ions and it was verified that the metal causes the quenching of their fluorescence emission, due to the formation of complexes between the naphthyridine and the metal. A displacement assay was carried out in a DMSO-water mixture with the addition of various anions to the solutions of the complexes, and it was observed that these systems have a high capacity to selectively detect cyanide.

Physicochemical properties of sorbents based on silica gel modified by 1-phenylazo-2-naphtholic complexes of transition metals

NASA Astrophysics Data System (ADS)

Makarycheva, A. I.; Slizhov, Yu. G.

2017-09-01

Gas chromatography sorbents based on Silokhrom C80 and modified by 1-phenylazo-2-naphtholic complexes of 3 d metals (Co(II), Ni(II), Cu(II)) are obtained. Their structural, chromatographic, and sorption characteristics are investigated. It is found that modifying them with 1-phenylazo-2-naphthols of transition metals has a considerable effect on the chromatographic polarity and selectivity of sorption materials. The prospects for the practical application of the obtained sorbents are demonstrated by experiments on the gas chromatographic separation of mixtures of different classes of organic compounds.

Identification of Major Histocompatibility Complex-Regulated Body Odorants by Statistical Analysis of a Comparative Gas Chromatography/Mass Spectrometry Experiment

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

Willse, Alan R.; Belcher, Ann; Preti, George

2005-04-15

Gas chromatography (GC), combined with mass spectrometry (MS) detection, is a powerful analytical technique that can be used to separate, quantify, and identify volatile compounds in complex mixtures. This paper examines the application of GC-MS in a comparative experiment to identify volatiles that differ in concentration between two groups. A complex mixture might comprise several hundred or even thousands of volatile compounds. Because their number and location in a chromatogram generally are unknown, and because components overlap in populous chromatograms, the statistical problems offer significant challenges beyond traditional two-group screening procedures. We describe a statistical procedure to compare two-dimensional GC-MSmore » profiles between groups, which entails (1) signal processing: baseline correction and peak detection in single ion chromatograms; (2) aligning chromatograms in time; (3) normalizing differences in overall signal intensities; and (4) detecting chromatographic regions that differ between groups. Compared to existing approaches, the proposed method is robust to errors made at earlier stages of analysis, such as missed peaks or slightly misaligned chromatograms. To illustrate the method, we identify differences in GC-MS chromatograms of ether-extracted urine collected from two nearly identical inbred groups of mice, to investigate the relationship between odor and genetics of the major histocompatibility complex.« less

MULTISUBSTRATE BIODEGRADATION KINETICS FOR BINARY AND COMPLEX MIXTURES OF POLYCYCLIC AROMATIC HYDROCARBONS

EPA Science Inventory

Biodegradation kinetics were studied for binary and complex mixtures of nine polycyclic aromatic hydrocarbons (PAHs): naphthalene, 1-methylnaphthalene, 2-methylnaphthalene, 2-ethylnaphthalene, phenanthrene, anthracene, pyrene, fluorene and fluoranthene. Discrepancies between the ...

Phenol removal pretreatment process

DOEpatents

Hames, Bonnie R.

2004-04-13

A process for removing phenols from an aqueous solution is provided, which comprises the steps of contacting a mixture comprising the solution and a metal oxide, forming a phenol metal oxide complex, and removing the complex from the mixture.

Capacity enhancement of aqueous borohydride fuels for hydrogen storage in liquids

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

Schubert, David; Neiner, Doinita; Bowden, Mark

2015-10-01

In this work we demonstrate enhanced hydrogen storage capacities through increased solubility of sodium borate product species in aqueous media achieved by adjusting the sodium (NaOH) to boron (B(OH) 3) ratio, i.e., M/B, to obtain a distribution of polyborate anions. For a 1:1 mole ratio of NaOH to B(OH) 3, M/B = 1, the ratio of the hydrolysis product formed from NaBH 4 hydrolysis, the sole borate species formed and observed by 11B NMR is sodium metaborate, NaB(OH) 4. When the ratio is 1:3 NaOH to B(OH) 3, M/B = 0.33, a mixture of borate anions is formed and observedmore » as a broad peak in the 11B NMR spectrum. The complex polyborate mixture yields a metastable solution that is difficult to crystallize. Given the enhanced solubility of the polyborate mixture formed when M/B = 0.33 it should follow that the hydrolysis of sodium octahydrotriborate, NaB 3H 8, can provide a greater storage capacity of hydrogen for fuel cell applications compared to sodium borohydride while maintaining a single phase. Accordingly, the hydrolysis of a 23 wt% NaB 3H 8 solution in water yields a solution having the same complex polyborate mixture as formed by mixing a 1:3 molar ratio of NaOH and B(OH) 3 and releases >8 eq of H 2. By optimizing the M/B ratio a complex mixture of soluble products, including B 3O 3(OH) 5 2-, B 4O 5(OH) 4 2-, B 3O 3(OH) 4-, B 5O 6(OH) 4- and B(OH) 3, can be maintained as a single liquid phase throughout the hydrogen release process. Consequently, hydrolysis of NaB 3H 8 can provide a 40% increase in H 2 storage density compared to the hydrolysis of NaBH 4 given the decreased solubility of sodium metaborate. The authors would like to thank Jim Sisco and Paul Osenar of Protonex Inc. for useful discussion regarding liquid hydrogen storage materials for portable power applications and the U.S. DoE Office of Energy Efficiency and Renewable Energy Fuel Cell Technologies Office for their continued interest in liquid hydrogen storage carriers. Pacific Northwest National Laboratory is a multi-program national laboratory operated for DOE by Battelle. The authors dedicate the work to the memory of Professor Sheldon Shore. His contributions to boron hydride chemistry set the foundation for many who have followed.« less

Leidenfrost phenomenon-assisted thermal desorption (LPTD) and its application to open ion sources at atmospheric pressure mass spectrometry.

PubMed

Saha, Subhrakanti; Chen, Lee Chuin; Mandal, Mridul Kanti; Hiraoka, Kenzo

2013-03-01

This work describes the development and application of a new thermal desorption technique that makes use of the Leidenfrost phenomenon in open ion sources at atmospheric pressure for direct mass spectrometric detection of ultratrace levels of illicit, therapeutic, and stimulant drugs, toxicants, and peptides (molecular weight above 1 kDa) in their unaltered state from complex real world samples without or with minor sample pretreatment. A low temperature dielectric barrier discharge ion source was used throughout the experiments and the analytical figures of merit of this technique were investigated. Further, this desorption technique coupled with other ionization sources such as electrospray ionization (ESI) and dc corona discharge atmospheric pressure chemical ionization (APCI) in open atmosphere was also investigated. The use of the high-resolution 'Exactive Orbitrap' mass spectrometer provided unambiguous identification of trace levels of the targeted compounds from complex mixtures and background noise; the limits of detection for various small organic molecules and peptides treated with this technique were at the level of parts per trillion and 10(-9) M, respectively. The high sensitivity of the present technique is attributed to the spontaneous enrichment of analyte molecules during the slow evaporation of the solvent, as well as to the sequential desorption of molecules from complex mixtures based on their volatilities. This newly developed desorption technique is simple and fast, while molecular ions are observed as the major ions.

Supercritical separation process for complex organic mixtures

DOEpatents

Chum, Helena L.; Filardo, Giuseppe

1990-01-01

A process is disclosed for separating low molecular weight components from complex aqueous organic mixtures. The process includes preparing a separation solution of supercritical carbon dioxide with an effective amount of an entrainer to modify the solvation power of the supercritical carbon dioxide and extract preselected low molecular weight components. The separation solution is maintained at a temperature of at least about 70.degree. C. and a pressure of at least about 1,500 psi. The separation solution is then contacted with the organic mixtures while maintaining the temperature and pressure as above until the mixtures and solution reach equilibrium to extract the preselected low molecular weight components from the organic mixtures. Finally, the entrainer/extracted components portion of the equilibrium mixture is isolated from the separation solution.

Rabbit Neonates and Human Adults Perceive a Blending 6-Component Odor Mixture in a Comparable Manner

PubMed Central

Sinding, Charlotte; Thomas-Danguin, Thierry; Chambault, Adeline; Béno, Noelle; Dosne, Thibaut; Chabanet, Claire; Schaal, Benoist; Coureaud, Gérard

2013-01-01

Young and adult mammals are constantly exposed to chemically complex stimuli. The olfactory system allows for a dual processing of relevant information from the environment either as single odorants in mixtures (elemental perception) or as mixtures of odorants as a whole (configural perception). However, it seems that human adults have certain limits in elemental perception of odor mixtures, as suggested by their inability to identify each odorant in mixtures of more than 4 components. Here, we explored some of these limits by evaluating the perception of three 6-odorant mixtures in human adults and newborn rabbits. Using free-sorting tasks in humans, we investigated the configural or elemental perception of these mixtures, or of 5-component sub-mixtures, or of the 6-odorant mixtures with modified odorants' proportion. In rabbit pups, the perception of the same mixtures was evaluated by measuring the orocephalic sucking response to the mixtures or their components after conditioning to one of these stimuli. The results revealed that one mixture, previously shown to carry the specific odor of red cordial in humans, was indeed configurally processed in humans and in rabbits while the two other 6-component mixtures were not. Moreover, in both species, such configural perception was specific not only to the 6 odorants included in the mixture but also to their respective proportion. Interestingly, rabbit neonates also responded to each odorant after conditioning to the red cordial mixture, which demonstrates their ability to perceive elements in addition to configuration in this complex mixture. Taken together, the results provide new insights related to the processing of relatively complex odor mixtures in mammals and the inter-species conservation of certain perceptual mechanisms; the results also revealed some differences in the expression of these capacities between species putatively linked to developmental and ecological constraints. PMID:23341948

Computer program for calculation of complex chemical equilibrium compositions and applications. Supplement 1: Transport properties

NASA Technical Reports Server (NTRS)

Gordon, S.; Mcbride, B.; Zeleznik, F. J.

1984-01-01

An addition to the computer program of NASA SP-273 is given that permits transport property calculations for the gaseous phase. Approximate mixture formulas are used to obtain viscosity and frozen thermal conductivity. Reaction thermal conductivity is obtained by the same method as in NASA TN D-7056. Transport properties for 154 gaseous species were selected for use with the program.

Effective Enrichment and Mass Spectrometry Analysis of Phosphopeptides Using Mesoporous Metal Oxide Nanomaterials

PubMed Central

Nelson, Cory A.; Szczech, Jeannine R.; Dooley, Chad J.; Xu, Qingge; Lawrence, Matthew J.; Zhu, Haoyue; Jin, Song; Ge, Ying

2010-01-01

Mass spectrometry (MS)-based phosphoproteomics remains challenging due to the low abundance of phosphoproteins and substoichiometric phosphorylation. This demands better methods to effectively enrich phosphoproteins/peptides prior to MS analysis. We have previously communicated the first use of mesoporous zirconium oxide (ZrO2) nanomaterials for effective phosphopeptide enrichment. Here we present the full report including the synthesis, characterization, and application of mesoporous titanium dioxide (TiO2), ZrO2, and hafnium oxide (HfO2) in phosphopeptide enrichment and MS analysis. Mesoporous ZrO2 and HfO2 are demonstrated to be superior to TiO2 for phosphopeptide enrichment from a complex mixture with high specificity (>99%), which could almost be considered as “a purification”, mainly because of the extremely large active surface area of mesoporous nanomaterials. A single enrichment and Fourier transform MS analysis of phosphopeptides digested from a complex mixture containing 7% of α-casein identified 21 out of 22 phosphorylation sites for α-casein. Moreover, the mesoporous ZrO2 and HfO2 can be reused after a simple solution regeneration procedure with comparable enrichment performance to that of fresh materials. Mesoporous ZrO2 and HfO2 nanomaterials hold great promise for applications in MS-based phosphoproteomics. PMID:20704311

OVERVIEW OF AN INTEGRATIVE SAMPLER FOR ...

EPA Pesticide Factsheets

Anthropogenic pollution is recognized as a global problem contributing to degradation of ecosystem quality, to loss of numerous plant and animal species, and to adverse impacts on human health. There is an increasing realization that a holistic hazard assessment of complex environmental contaminant mixtures requires data on the concentrations of hydrophilic organic contaminants as well. An approach to provide a time-weighted average (TWA) assessment is critical in understanding organism exposure to the complex mixture of pollutants present in the environment. A recently developed device, the polar organic chemical integrative sampler (POCIS), is designed to integratively sample the more polar waterborne organic chemicals. Laboratory trials and field deployments have demonstrated that the POCIS is very effective for sequestering hydrophilic chemicals such as antibiotics, hormones, other pharmaceutically derived chemicals, polar pesticides, surfactants, etc. Environmentally derived sample extracts from the integrative samplers are readily amenable for assays utilizing bio-indicator tests. An overview of the POCIS and selected environmental applications will be presented. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and

Using Big Data Analytics to Address Mixtures Exposure

EPA Science Inventory

The assessment of chemical mixtures is a complex issue for regulators and health scientists. We propose that assessing chemical co-occurrence patterns and prevalence rates is a relatively simple yet powerful approach in characterizing environmental mixtures and mixtures exposure...

Ground-Based Aerosol Measurements

EPA Science Inventory

Atmospheric particulate matter (PM) is a complex chemical mixture of liquid and solid particles suspended in air (Seinfeld and Pandis 2016). Measurements of this complex mixture form the basis of our knowledge regarding particle formation, source-receptor relationships, data to ...

Indoor air-assessment: Indoor concentrations of environmental carcinogens

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

Gold, K.W.; Naugle, D.F.; Berry, M.A.

1991-01-01

In the report, indoor concentration data are presented for the following general categories of air pollutants: radon-222, environmental tobacco smoke (ETS), asbestos, gas phase organic compounds, formaldehyde, polycyclic aromatic hydrocarbons (PAH), pesticides, and inorganic compounds. These pollutants are either known or suspect carcinogens (i.e., radon-222, asbestos) or more complex mixtures or classes of compounds which contain known or suspect carcinogens. Concentration data for individual carcinogenic compounds in complex mixtures are usually far from complete. The data presented for complex mixtures often include compounds which are not carcinogenic or for which data are insufficient to evaluate carcinogenicity. Their inclusion is justified,more » however, by the possibility that further work may show them to be carcinogens, cocarcinogens, initiators or promotors, or that they may be employed as markers (e.g., nicotine, acrolein) for the estimation of exposure to complex mixtures.« less

Application of a spectrally filtered probing light beam and RGB decomposition of microphotographs for flow registration of ultrasonically enhanced agglutination of erythrocytes

NASA Astrophysics Data System (ADS)

Doubrovski, V. A.; Ganilova, Yu. A.; Zabenkov, I. V.

2013-08-01

We propose a development of the flow microscopy method to increase the resolving power upon registration of erythrocyte agglutination. We experimentally show that the action of a ultrasonic standing wave on an agglutinating mixture blood-serum leads to the formation of so large erythrocytic immune complexes that it seems possible to propose a new two-wave optical method of registration of the process of erythrocyte agglutination using the RGB decomposition of microphotographs of the flow of the mixture under study. This approach increases the reliability of registration of erythrocyte agglutination and, consequently, increases the reliability of blood typing. Our results can be used in the development of instruments for automatic human blood typing.

Bioanalytical methods for food contaminant analysis.

PubMed

Van Emon, Jeanette M

2010-01-01

Foods are complex mixtures of lipids, carbohydrates, proteins, vitamins, organic compounds, and other naturally occurring substances. Sometimes added to this mixture are residues of pesticides, veterinary and human drugs, microbial toxins, preservatives, contaminants from food processing and packaging, and other residues. This milieu of compounds can pose difficulties in the analysis of food contaminants. There is an expanding need for rapid and cost-effective residue methods for difficult food matrixes to safeguard our food supply. Bioanalytical methods are established for many food contaminants such as mycotoxins and are the method of choice for many food allergens. Bioanalytical methods are often more cost-effective and sensitive than instrumental procedures. Recent developments in bioanalytical methods may provide more applications for their use in food analysis.

Engineering Escherichia coli coculture systems for the production of biochemical products.

PubMed

Zhang, Haoran; Pereira, Brian; Li, Zhengjun; Stephanopoulos, Gregory

2015-07-07

Engineering microbial consortia to express complex biosynthetic pathways efficiently for the production of valuable compounds is a promising approach for metabolic engineering and synthetic biology. Here, we report the design, optimization, and scale-up of an Escherichia coli-E. coli coculture that successfully overcomes fundamental microbial production limitations, such as high-level intermediate secretion and low-efficiency sugar mixture utilization. For the production of the important chemical cis,cis-muconic acid, we show that the coculture approach achieves a production yield of 0.35 g/g from a glucose/xylose mixture, which is significantly higher than reported in previous reports. By efficiently producing another compound, 4-hydroxybenzoic acid, we also demonstrate that the approach is generally applicable for biosynthesis of other important industrial products.

Complex mixtures, complex responses: Assessing pharmaceutical mixtures using field and laboratory approaches

USGS Publications Warehouse

Schoenfuss, Heiko L.; Furlong, Edward T.; Phillips, Patrick J.; Scott, Tia-Marie; Kolpin, Dana W.; Cetkovic-Cvrlje, Marina; Lesteberg, Kelsey E.; Rearick, Daniel C.

2016-01-01

Pharmaceuticals are present in low concentrations (<100 ng/L) in most municipal wastewater effluents but may be elevated locally because of factors such as input from pharmaceutical formulation facilities. Using existing concentration data, the authors assessed pharmaceuticals in laboratory exposures of fathead minnows (Pimephales promelas) and added environmental complexity through effluent exposures. In the laboratory, larval and mature minnows were exposed to a simple opioid mixture (hydrocodone, methadone, and oxycodone), an opioid agonist (tramadol), a muscle relaxant (methocarbamol), a simple antidepressant mixture (fluoxetine, paroxetine, venlafaxine), a sleep aid (temazepam), or a complex mixture of all compounds. Larval minnow response to effluent exposure was not consistent. The 2010 exposures resulted in shorter exposed minnow larvae, whereas the larvae exposed in 2012 exhibited altered escape behavior. Mature minnows exhibited altered hepatosomatic indices, with the strongest effects in females and in mixture exposures. In addition, laboratory-exposed, mature male minnows exposed to all pharmaceuticals (except the selective serotonin reuptake inhibitor mixture) defended nest sites less rigorously than fish in the control group. Tramadol or antidepressant mixture exposure resulted in increased splenic T lymphocytes. Only male minnows exposed to whole effluent responded with increased plasma vitellogenin concentrations. Female minnows exposed to pharmaceuticals (except the opioid mixture) had larger livers, likely as a compensatory result of greater prominence of vacuoles in liver hepatocytes. The observed alteration of apical endpoints central to sustaining fish populations confirms that effluents containing waste streams from pharmaceutical formulation facilities can adversely impact fish populations but that the effects may not be temporally consistent. The present study highlights the importance of including diverse biological endpoints spanning levels of biological organization and life stages when assessing contaminant interactions.

Transcriptional responses to complex mixtures - A review

EPA Science Inventory

Exposure of people to hazardous compounds is primarily through complex environmental mixtures, those that occur through media such as air, soil, water, food, cigarette smoke, and combustion emissions. Microarray technology offers the ability to query the entire genome after expos...

Fact or artifact: the representativeness of ESI-MS for complex natural organic mixtures.

PubMed

Novotny, Nicole R; Capley, Erin N; Stenson, Alexandra C

2014-04-01

Because mass spectrometers provide their own dispersion and resolution of analytes, electrospray ionization mass spectrometry (ESI-MS) has become a workhorse for the characterization of complex mixtures from aerosols to crude oil. Unfortunately, ESI mass spectra commonly contain multimers, adducts and fragments. For the characterization of complex mixtures of unknown initial composition, this presents a significant concern. Mixed-multimer formation could potentially lead to results that bare no resemblance to the original mixture. Conversely, ESI-MS has continually reflected subtle differences between natural organic matter mixtures that are in agreement with prediction or theory. Knowing the real limitations of the technique is therefore critical to avoiding both over-interpretation and unwarranted skepticism. Here, data were collected on four mass spectrometers under a battery of conditions. Results indicate that formation of unrepresentative ions cannot entirely be ruled out, but non-covalent multimers do not appear to make a major contribution to typical natural organic matter spectra based on collision-induced dissociation results. Multimers also appear notably reduced when a cooling gas is present in the accumulation region of the mass spectrometer. For less complex mixtures, the choice of spray solvent can make a difference, but generally spectrum cleanliness (i.e. representativeness) comes at the price of increased selectivity. Copyright © 2014 John Wiley & Sons, Ltd.

Supercritical separation process for complex organic mixtures

DOEpatents

Chum, H.L.; Filardo, G.

1990-10-23

A process is disclosed for separating low molecular weight components from complex aqueous organic mixtures. The process includes preparing a separation solution of supercritical carbon dioxide with an effective amount of an entrainer to modify the solvation power of the supercritical carbon dioxide and extract preselected low molecular weight components. The separation solution is maintained at a temperature of at least about 70 C and a pressure of at least about 1,500 psi. The separation solution is then contacted with the organic mixtures while maintaining the temperature and pressure as above until the mixtures and solution reach equilibrium to extract the preselected low molecular weight components from the organic mixtures. Finally, the entrainer/extracted components portion of the equilibrium mixture is isolated from the separation solution. 1 fig.

Toward the Rational Use of Exposure Information in Mixtures Toxicology

EPA Science Inventory

Of all the disciplines of toxicology, perhaps none is as dependent on exposure information as Mixtures Toxicology. Identifying real world mixtures and replicating them in the laboratory (or in silico) is critical to understanding their risks. Complex mixtures such as cigarett...

Highly-Complex Environmentally-Realistic Mixtures: Challenges and Advances

EPA Science Inventory

The difficulties involved in design, conduct, analysis and interpretation of defmed mixtures experiments and use of the resulting data in risk assessment are now wellknown to the toxicology, risk assessment and risk management communities. The arena of highly-complex environment...

Constituent bioconcentration in rainbow trout exposed to a complex chemical mixture

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

Linder, G.; Bergman, H.L.; Meyer, J.S.

1984-09-01

Classically, aquatic contaminant fate models predicting a chemical's bioconcentration factor (BCF) are based upon single-compound derived models, yet such BCF predictions may deviate from observed BCFs when physicochemical interactions or biological responses to complex chemical mixture exposures are not adequately considered in the predictive model. Rainbow trout were exposed to oil-shale retort waters. Such a study was designed to model the potential biological effects precluded by exposure to complex chemical mixtures such as solid waste leachates, agricultural runoff, and industrial process waste waters. Chromatographic analysis of aqueous and nonaqueous liquid-liquid reservoir components yielded differences in mixed extraction solvent HPLC profilesmore » of whole fish exposed for 1 and 3 weeks to the highest dilution of the complex chemical mixture when compared to their corresponding control, yet subsequent whole fish extractions at 6, 9, 12, and 15 weeks into exposure demonstrated no qualitative differences between control and exposed fish. Liver extractions and deproteinized bile samples from exposed fish were qualitatively different than their corresponding controls. These findings support the projected NOEC of 0.0045% dilution, even though the differences in bioconcentration profiles suggest hazard assessment strategies may be useful in evaluating environmental fate processes associated with complex chemical mixtures. 12 references, 4 figures, 2 tables.« less

Co-assembly in chitosan-surfactant mixtures: thermodynamics, structures, interfacial properties and applications.

PubMed

Chiappisi, Leonardo; Gradzielski, Michael

2015-06-01

In this review, different aspects characterizing chitosan-surfactant mixtures are summarized and compared. Chitosan is a bioderived cationic polysaccharide that finds wide-ranged applications in various field, e.g., medical or food industry, in which synergistic effects with surfactant can play a fundamental role. In particular, the behavior of chitosan interacting with strong and weak anionic, nonionic as well as cationic surfactants is reviewed. We put a focus on oppositely charged systems, as they exhibit the most interesting features. In that context, we discuss the thermodynamic description of the interaction and in particular the structural changes as they occur as a function of the mixed systems and external parameters. Moreover, peculiar properties of chitosan coated phospholipid vesicles are summarized. Finally, their co-assembly at interfaces is briefly reviewed. Despite the behavior of the mentioned systems might strongly differ, resulting in a high variety of properties, few general rules can be pointed out which improve the understanding of such complex systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Stepped MS(All) Relied Transition (SMART): An approach to rapidly determine optimal multiple reaction monitoring mass spectrometry parameters for small molecules.

PubMed

Ye, Hui; Zhu, Lin; Wang, Lin; Liu, Huiying; Zhang, Jun; Wu, Mengqiu; Wang, Guangji; Hao, Haiping

2016-02-11

Multiple reaction monitoring (MRM) is a universal approach for quantitative analysis because of its high specificity and sensitivity. Nevertheless, optimization of MRM parameters remains as a time and labor-intensive task particularly in multiplexed quantitative analysis of small molecules in complex mixtures. In this study, we have developed an approach named Stepped MS(All) Relied Transition (SMART) to predict the optimal MRM parameters of small molecules. SMART requires firstly a rapid and high-throughput analysis of samples using a Stepped MS(All) technique (sMS(All)) on a Q-TOF, which consists of serial MS(All) events acquired from low CE to gradually stepped-up CE values in a cycle. The optimal CE values can then be determined by comparing the extracted ion chromatograms for the ion pairs of interest among serial scans. The SMART-predicted parameters were found to agree well with the parameters optimized on a triple quadrupole from the same vendor using a mixture of standards. The parameters optimized on a triple quadrupole from a different vendor was also employed for comparison, and found to be linearly correlated with the SMART-predicted parameters, suggesting the potential applications of the SMART approach among different instrumental platforms. This approach was further validated by applying to simultaneous quantification of 31 herbal components in the plasma of rats treated with a herbal prescription. Because the sMS(All) acquisition can be accomplished in a single run for multiple components independent of standards, the SMART approach are expected to find its wide application in the multiplexed quantitative analysis of complex mixtures. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization and comparison of lidocaine-tetracaine and lidocaine-camphor eutectic mixtures based on their crystallization and hydrogen-bonding abilities.

PubMed

Gala, Urvi; Chuong, Monica C; Varanasi, Ravi; Chauhan, Harsh

2015-06-01

Eutectic mixtures formed between active pharmaceutical ingredients and/or excipients provide vast scope for pharmaceutical applications. This study aimed at the exploration of the crystallization abilities of two eutectic mixtures (EM) i.e., lidocaine-tetracaine and lidocaine-camphor (1:1 w/w). Thermogravimetric analysis (TGA) for degradation behavior whereas modulated temperature differential scanning calorimetry (MTDSC) set in first heating, cooling, and second heating cycles, was used to qualitatively analyze the complex exothermic and endothermic thermal transitions. Raman microspectroscopy characterized vibrational information specific to chemical bonds. Prepared EMs were left at room temperature for 24 h to visually examine their crystallization potentials. The degradation of lidocaine, tetracaine, camphor, lidocaine-tetracaine EM, and lidocaine-camphor EM began at 196.56, 163.82, 76.86, 146.01, and 42.72°C, respectively, which indicated that eutectic mixtures are less thermostable compared to their individual components. The MTDSC showed crystallization peaks for lidocaine, tetracaine, and camphor at 31.86, 29.36, and 174.02°C, respectively (n = 3). When studying the eutectic mixture, no crystallization peak was observed in the lidocaine-tetracaine EM, but a lidocaine-camphor EM crystallization peak was present at 18.81°C. Crystallization occurred in lidocaine-camphor EM after being kept at room temperature for 24 h, but not in lidocaine-tetracaine EM. Certain peak shifts were observed in Raman spectra which indicated possible interactions of eutectic mixture components, when a eutectic mixture was formed. We found that if the components forming a eutectic mixture have crystallization peaks close to each other and have sufficient hydrogen-bonding capability, then their eutectic mixture is least likely to crystallize out (as seen in lidocaine-tetracaine EM) or vice versa (lidocaine-camphor EM).

Metagenomic Assembly: Overview, Challenges and Applications

PubMed Central

Ghurye, Jay S.; Cepeda-Espinoza, Victoria; Pop, Mihai

2016-01-01

Advances in sequencing technologies have led to the increased use of high throughput sequencing in characterizing the microbial communities associated with our bodies and our environment. Critical to the analysis of the resulting data are sequence assembly algorithms able to reconstruct genes and organisms from complex mixtures. Metagenomic assembly involves new computational challenges due to the specific characteristics of the metagenomic data. In this survey, we focus on major algorithmic approaches for genome and metagenome assembly, and discuss the new challenges and opportunities afforded by this new field. We also review several applications of metagenome assembly in addressing interesting biological problems. PMID:27698619

Para-hydrogen induced polarization of Si-29 NMR resonances as a potentially useful tool for analytical applications.

PubMed

Ellena, Silvano; Viale, Alessandra; Gobetto, Roberto; Aime, Silvio

2012-08-01

Para-hydrogen-induced polarization effects have been observed in the (29)Si NMR spectra of trimethylsilyl para-hydrogenated molecules. The high signal enhancements and the long T(1) values observed for the (29)Si hyperpolarized resonances point toward the possibility of using (29)Si for hyperpolarization applications. A method for the discrimination of multiple compounds and/or complex mixtures of hydroxylic compounds (such as steroids), consisting of the silylization of alcoholic functionalities with an unsaturated silylalkyl moiety and subsequent reaction with para-H(2), is proposed. Copyright © 2012 John Wiley & Sons, Ltd.

Insights into aquatic toxicities of the antibiotics oxytetracycline and ciprofloxacin in the presence of metal: complexation versus mixture.

PubMed

Zhang, Yu; Cai, Xiyun; Lang, Xianming; Qiao, Xianliang; Li, Xuehua; Chen, Jingwen

2012-07-01

Co-contamination of ligand-like antibiotics (e.g., tetracyclines and quinolones) and heavy metals prevails in the environment, and thus the complexation between them is involved in environmental risks of antibiotics. To understand toxicological significance of the complex, effects of metal coordination on antibiotics' toxicity were investigated. The complexation of two antibiotics, oxytetracycline and ciprofloxacin, with three heavy metals, copper, zinc, and cadmium, was verified by spectroscopic techniques. The antibiotics bound metals via multiple coordination sites and rendered a mixture of various complexation speciations. Toxicity analysis indicated that metal coordination did modify the toxicity of the antibiotics and that antibiotic, metal, and their complex acted primarily as concentration addition. Comparison of EC(50) values revealed that the complex commonly was highest toxic and predominately correlated in toxicity to the mixture. Finally, environmental scenario analysis demonstrated that ignoring complexation would improperly classify environmental risks of the antibiotics. Copyright © 2012 Elsevier Ltd. All rights reserved.

NUTS and BOLTS: Applications of Fluorescence Detected Sedimentation

PubMed Central

Kroe, Rachel R.; Laue, Thomas M.

2008-01-01

Analytical ultracentrifugation is a widely used method for characterizing the solution behavior of macromolecules. However, the two commonly used detectors (absorbance and interference) impose some fundamental restrictions on the concentrations and complexity of the solutions that can be analyzed. The recent addition of a fluorescence detector for the XL-I analytical ultracentrifuge (AU-FDS) enables two different types of sedimentation experiments. First, the AU-FDS can detect picomolar concentrations of labeled solutes allowing the characterization of very dilute solutions of macromolecules, applications we call Normal Use Tracer Sedimentation (NUTS). The great sensitivity of NUTS analysis allows the characterization of small quantities of materials and high affinity interactions. Second, AU-FDS allows characterization of trace quantities of labeled molecules in solutions containing high concentrations and complex mixtures of unlabeled molecules, applications we call Biological On Line Tracer Sedimentation (BOLTS). The discrimination of BOLTS enables the size distribution of a labeled macromolecule to be determined in biological milieu such as cell lysates and serum. Examples are presented that embody features of both NUTS and BOLTS applications, along with our observations on these applications. PMID:19103145

Single-Scan Multidimensional NMR Analysis of Mixtures at Sub-Millimolar Concentrations by using SABRE Hyperpolarization.

PubMed

Daniele, Valeria; Legrand, François-Xavier; Berthault, Patrick; Dumez, Jean-Nicolas; Huber, Gaspard

2015-11-16

Signal amplification by reversible exchange (SABRE) is a promising method to increase the sensitivity of nuclear magnetic resonance (NMR) experiments. However, SABRE-enhanced (1)H NMR signals are short lived, and SABRE is often used to record 1D NMR spectra only. When the sample of interest is a complex mixture, this results in severe overlaps for (1)H spectra. In addition, the use of a co-substrate, whose signals may obscure the (1) H spectra, is currently the most efficient way to lower the detection limit of SABRE experiments. Here, we describe an approach to obtain clean, SABRE-hyperpolarized 2D (1)H NMR spectra of mixtures of small molecules at sub-millimolar concentrations in a single scan. The method relies on the use of para-hydrogen together with a deuterated co-substrate for hyperpolarization and ultrafast 2D NMR for acquisition. It is applicable to all substrates that can be polarized with SABRE. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimization of homonuclear 2D NMR for fast quantitative analysis: application to tropine-nortropine mixtures.

PubMed

Giraudeau, Patrick; Guignard, Nadia; Hillion, Emilie; Baguet, Evelyne; Akoka, Serge

2007-03-12

Quantitative analysis by (1)H NMR is often hampered by heavily overlapping signals that may occur for complex mixtures, especially those containing similar compounds. Bidimensional homonuclear NMR spectroscopy can overcome this difficulty. A thorough review of acquisition and post-processing parameters was carried out to obtain accurate and precise, quantitative 2D J-resolved and DQF-COSY spectra in a much reduced time, thus limiting the spectrometer instabilities in the course of time. The number of t(1) increments was reduced as much as possible, and standard deviation was improved by optimization of spectral width, number of transients, phase cycling and apodization function. Localized polynomial baseline corrections were applied to the relevant chemical shift areas. Our method was applied to tropine-nortropine mixtures. Quantitative J-resolved spectra were obtained in less than 3 min and quantitative DQF-COSY spectra in 12 min, with an accuracy of 3% for J-spectroscopy and 2% for DQF-COSY, and a standard deviation smaller than 1%.

Effects of non-condensable gas on the dynamic oscillations of cavitation bubbles

NASA Astrophysics Data System (ADS)

Zhang, Yuning

2016-11-01

Cavitation is an essential topic of multiphase flow with a broad range of applications. Generally, there exists non-condensable gas in the liquid and a complex vapor/gas mixture bubble will be formed. A rigorous prediction of the dynamic behavior of the aforementioned mixture bubble is essential for the development of a complete cavitation model. In the present paper, effects of non-condensable gas on the dynamic oscillations of the vapor/gas mixture bubble are numerically investigated in great detail. For the completeness, a large parameter zone (e.g. bubble radius, frequency and ratio between gas and vapor) is investigated with many demonstrating examples. The mechanisms of mass diffusion are categorized into different groups with their characteristics and dominated regions given. Influences of non-condensable gas on the wave propagation (e.g. wave speed and attenuation) in the bubbly liquids are also briefly discussed. Specifically, the minimum wave speed is quantitatively predicted in order to close the pressure-density coupling relationship usually employed for the cavitation modelling. Finally, the application of the present finding on the development of cavitation model is demonstrated with a brief discussion of its influence on the cavitation dynamics. This work was financially supported by the National Natural Science Foundation of China (Project No.: 51506051).

Evaluating porewater polycyclic aromatic hydrocarbon-related toxicity at a contaminated sediment site using a spiked field-sediment approach.

PubMed

Hartzell, Sharon E; Unger, Michael A; Vadas, George G; Yonkos, Lance T

2018-03-01

Although the complexity of contaminant mixtures in sediments can confound the identification of causative agents of adverse biological response, understanding the contaminant(s) of primary concern at impacted sites is critical to sound environmental management and remediation. In the present study, a stock mixture of 18 polycyclic aromatic hydrocarbon (PAH) compounds was prepared to reflect the variety and relative proportions of PAHs measured in surface sediment samples collected from discrete areas of a historically contaminated industrial estuary. This site-specific PAH stock mixture was spiked into nontoxic in-system and out-of-system field-collected reference sediments in dilution series spanning the range of previously measured total PAH concentrations from the region. Spiked sediments were evaluated in 10-d Leptocheirus plumulosus tests to determine whether toxicity in laboratory-created PAH concentrations was similar to the toxicity found in field-collected samples with equivalent PAH concentrations. The results show that toxicity of contaminated sediments was not explained by PAH exposure, while indicating that toxicity in spiked in-system (fine grain, high total organic carbon [TOC]) and out-of-system (course grain, low TOC) sediments was better explained by porewater PAH concentrations, measured using an antibody-based biosensor that quantified 3- to 5-ring PAHs, than total sediment PAH concentrations. The study demonstrates the application of site-specific spiking experiments to evaluate sediment toxicity at sites with complex mixtures of multiple contaminant classes and the utility of the PAH biosensor for rapid sediment-independent porewater PAH analysis. Environ Toxicol Chem 2018;37:893-902. © 2017 SETAC. © 2017 SETAC.

Capillary electrophoresis for aluminum ion speciation: Optimized separation conditions for complex polycation mixtures.

PubMed

Ouadah, Nesrine; Moire, Claudine; Brothier, Fabien; Kuntz, Jean-François; Deschaume, Olivier; Bartic, Carmen; Cottet, Hervé

2018-06-01

Aluminum chlorohydrates (ACH) are used in numerous applications and commercial products on a global scale including water treatment, catalysis or antiperspirants. They are complex mixtures of water soluble aluminum polycations of different degrees of polymerization, that are difficult to separate and quantify due to their susceptibility to depolymerize in solution when placed out of equilibrium, which is inherent to any separation process. We recently achieved the first capillary electrophoresis separation and characterization of ACH oligomers using 4-morpholineethanesulfonic acid (MES) as background electrolyte counter-ion. MES stabilizes the separated ACH oligomers during the electrophoretic process leading to highly repeatable and fast separations. In this work, the separation of ACH oligomers was further studied and perfected by varying the ionic strength, MES concentration and pH of the background electrolyte. Complex electrophoretic behavior is reported for the separation of Al 13 , Al 30 and Na + ions according to these experimental parameters. The transformation of the electropherograms in effective mobility scale and the use of the slope-plot approach are used to better understand the observed changes in selectivity/resolution. Optimal conditions (700 mM MES at 25 mM ionic strength containing 0.1 mM didodecyldimethylammonium bromide for dynamic capillary coating, pH 4.8) obtained for the separation of ACH oligomers are used for the baseline separation of samples difficult to analyze with other methods, including different molecular, aggregated and colloidal forms of aluminum from the Al 13 , Al 30 and Na + mixture, validating the rationale of the approach. Copyright © 2018. Published by Elsevier B.V.

Rapid Quadrupole-Time-of-Flight Mass Spectrometry Method Quantifies Oxygen-Rich Lignin Compound in Complex Mixtures

NASA Astrophysics Data System (ADS)

Boes, Kelsey S.; Roberts, Michael S.; Vinueza, Nelson R.

2018-03-01

Complex mixture analysis is a costly and time-consuming task facing researchers with foci as varied as food science and fuel analysis. When faced with the task of quantifying oxygen-rich bio-oil molecules in a complex diesel mixture, we asked whether complex mixtures could be qualitatively and quantitatively analyzed on a single mass spectrometer with mid-range resolving power without the use of lengthy separations. To answer this question, we developed and evaluated a quantitation method that eliminated chromatography steps and expanded the use of quadrupole-time-of-flight mass spectrometry from primarily qualitative to quantitative as well. To account for mixture complexity, the method employed an ionization dopant, targeted tandem mass spectrometry, and an internal standard. This combination of three techniques achieved reliable quantitation of oxygen-rich eugenol in diesel from 300 to 2500 ng/mL with sufficient linearity (R2 = 0.97 ± 0.01) and excellent accuracy (percent error = 0% ± 5). To understand the limitations of the method, it was compared to quantitation attained on a triple quadrupole mass spectrometer, the gold standard for quantitation. The triple quadrupole quantified eugenol from 50 to 2500 ng/mL with stronger linearity (R2 = 0.996 ± 0.003) than the quadrupole-time-of-flight and comparable accuracy (percent error = 4% ± 5). This demonstrates that a quadrupole-time-of-flight can be used for not only qualitative analysis but also targeted quantitation of oxygen-rich lignin molecules in complex mixtures without extensive sample preparation. The rapid and cost-effective method presented here offers new possibilities for bio-oil research, including: (1) allowing for bio-oil studies that demand repetitive analysis as process parameters are changed and (2) making this research accessible to more laboratories. [Figure not available: see fulltext.

Rapid Quadrupole-Time-of-Flight Mass Spectrometry Method Quantifies Oxygen-Rich Lignin Compound in Complex Mixtures

NASA Astrophysics Data System (ADS)

Boes, Kelsey S.; Roberts, Michael S.; Vinueza, Nelson R.

2017-12-01

Complex mixture analysis is a costly and time-consuming task facing researchers with foci as varied as food science and fuel analysis. When faced with the task of quantifying oxygen-rich bio-oil molecules in a complex diesel mixture, we asked whether complex mixtures could be qualitatively and quantitatively analyzed on a single mass spectrometer with mid-range resolving power without the use of lengthy separations. To answer this question, we developed and evaluated a quantitation method that eliminated chromatography steps and expanded the use of quadrupole-time-of-flight mass spectrometry from primarily qualitative to quantitative as well. To account for mixture complexity, the method employed an ionization dopant, targeted tandem mass spectrometry, and an internal standard. This combination of three techniques achieved reliable quantitation of oxygen-rich eugenol in diesel from 300 to 2500 ng/mL with sufficient linearity (R2 = 0.97 ± 0.01) and excellent accuracy (percent error = 0% ± 5). To understand the limitations of the method, it was compared to quantitation attained on a triple quadrupole mass spectrometer, the gold standard for quantitation. The triple quadrupole quantified eugenol from 50 to 2500 ng/mL with stronger linearity (R2 = 0.996 ± 0.003) than the quadrupole-time-of-flight and comparable accuracy (percent error = 4% ± 5). This demonstrates that a quadrupole-time-of-flight can be used for not only qualitative analysis but also targeted quantitation of oxygen-rich lignin molecules in complex mixtures without extensive sample preparation. The rapid and cost-effective method presented here offers new possibilities for bio-oil research, including: (1) allowing for bio-oil studies that demand repetitive analysis as process parameters are changed and (2) making this research accessible to more laboratories. [Figure not available: see fulltext.

Rapid Quadrupole-Time-of-Flight Mass Spectrometry Method Quantifies Oxygen-Rich Lignin Compound in Complex Mixtures.

PubMed

Boes, Kelsey S; Roberts, Michael S; Vinueza, Nelson R

2018-03-01

Complex mixture analysis is a costly and time-consuming task facing researchers with foci as varied as food science and fuel analysis. When faced with the task of quantifying oxygen-rich bio-oil molecules in a complex diesel mixture, we asked whether complex mixtures could be qualitatively and quantitatively analyzed on a single mass spectrometer with mid-range resolving power without the use of lengthy separations. To answer this question, we developed and evaluated a quantitation method that eliminated chromatography steps and expanded the use of quadrupole-time-of-flight mass spectrometry from primarily qualitative to quantitative as well. To account for mixture complexity, the method employed an ionization dopant, targeted tandem mass spectrometry, and an internal standard. This combination of three techniques achieved reliable quantitation of oxygen-rich eugenol in diesel from 300 to 2500 ng/mL with sufficient linearity (R 2 = 0.97 ± 0.01) and excellent accuracy (percent error = 0% ± 5). To understand the limitations of the method, it was compared to quantitation attained on a triple quadrupole mass spectrometer, the gold standard for quantitation. The triple quadrupole quantified eugenol from 50 to 2500 ng/mL with stronger linearity (R 2 = 0.996 ± 0.003) than the quadrupole-time-of-flight and comparable accuracy (percent error = 4% ± 5). This demonstrates that a quadrupole-time-of-flight can be used for not only qualitative analysis but also targeted quantitation of oxygen-rich lignin molecules in complex mixtures without extensive sample preparation. The rapid and cost-effective method presented here offers new possibilities for bio-oil research, including: (1) allowing for bio-oil studies that demand repetitive analysis as process parameters are changed and (2) making this research accessible to more laboratories. Graphical Abstract ᅟ.

Understanding the human health effects of chemical mixtures.

PubMed Central

Carpenter, David O; Arcaro, Kathleen; Spink, David C

2002-01-01

Most research on the effects of chemicals on biologic systems is conducted on one chemical at a time. However, in the real world people are exposed to mixtures, not single chemicals. Although various substances may have totally independent actions, in many cases two substances may act at the same site in ways that can be either additive or nonadditive. Many even more complex interactions may occur if two chemicals act at different but related targets. In the extreme case there may be synergistic effects, in which case the effects of two substances together are greater than the sum of either effect alone. In reality, most persons are exposed to many chemicals, not just one or two, and therefore the effects of a chemical mixture are extremely complex and may differ for each mixture depending on the chemical composition. This complexity is a major reason why mixtures have not been well studied. In this review we attempt to illustrate some of the principles and approaches that can be used to study effects of mixtures. By the nature of the state of the science, this discussion is more a presentation of what we do not know than of what we do know about mixtures. We approach the study of mixtures at three levels, using specific examples. First, we discuss several human diseases in relation to a variety of environmental agents believed to influence the development and progression of the disease. We present results of selected cellular and animal studies in which simple mixtures have been investigated. Finally, we discuss some of the effects of mixtures at a molecular level. PMID:11834461

Synergistic effect of ATP for RuvA-RuvB-Holliday junction DNA complex formation.

PubMed

Iwasa, Takuma; Han, Yong-Woon; Hiramatsu, Ryo; Yokota, Hiroaki; Nakao, Kimiko; Yokokawa, Ryuji; Ono, Teruo; Harada, Yoshie

2015-12-14

The Escherichia coli RuvB hexameric ring motor proteins, together with RuvAs, promote branch migration of Holliday junction DNA. Zero mode waveguides (ZMWs) constitute of nanosized holes and enable the visualization of a single fluorescent molecule under micromolar order of the molecules, which is applicable to characterize the formation of RuvA-RuvB-Holliday junction DNA complex. In this study, we used ZMWs and counted the number of RuvBs binding to RuvA-Holliday junction DNA complex. Our data demonstrated that different nucleotide analogs increased the amount of Cy5-RuvBs binding to RuvA-Holliday junction DNA complex in the following order: no nucleotide, ADP, ATPγS, and mixture of ADP and ATPγS. These results suggest that not only ATP binding to RuvB but also ATP hydrolysis by RuvB facilitates a stable RuvA-RuvB-Holliday junction DNA complex formation.

Identification of hybrid node and link communities in complex networks

PubMed Central

He, Dongxiao; Jin, Di; Chen, Zheng; Zhang, Weixiong

2015-01-01

Identifying communities in complex networks is an effective means for analyzing complex systems, with applications in diverse areas such as social science, engineering, biology and medicine. Finding communities of nodes and finding communities of links are two popular schemes for network analysis. These schemes, however, have inherent drawbacks and are inadequate to capture complex organizational structures in real networks. We introduce a new scheme and an effective approach for identifying complex mixture structures of node and link communities, called hybrid node-link communities. A central piece of our approach is a probabilistic model that accommodates node, link and hybrid node-link communities. Our extensive experiments on various real-world networks, including a large protein-protein interaction network and a large network of semantically associated words, illustrated that the scheme for hybrid communities is superior in revealing network characteristics. Moreover, the new approach outperformed the existing methods for finding node or link communities separately. PMID:25728010

Identification of hybrid node and link communities in complex networks.

PubMed

He, Dongxiao; Jin, Di; Chen, Zheng; Zhang, Weixiong

2015-03-02

Identifying communities in complex networks is an effective means for analyzing complex systems, with applications in diverse areas such as social science, engineering, biology and medicine. Finding communities of nodes and finding communities of links are two popular schemes for network analysis. These schemes, however, have inherent drawbacks and are inadequate to capture complex organizational structures in real networks. We introduce a new scheme and an effective approach for identifying complex mixture structures of node and link communities, called hybrid node-link communities. A central piece of our approach is a probabilistic model that accommodates node, link and hybrid node-link communities. Our extensive experiments on various real-world networks, including a large protein-protein interaction network and a large network of semantically associated words, illustrated that the scheme for hybrid communities is superior in revealing network characteristics. Moreover, the new approach outperformed the existing methods for finding node or link communities separately.

Identification of hybrid node and link communities in complex networks

NASA Astrophysics Data System (ADS)

He, Dongxiao; Jin, Di; Chen, Zheng; Zhang, Weixiong

2015-03-01

Identifying communities in complex networks is an effective means for analyzing complex systems, with applications in diverse areas such as social science, engineering, biology and medicine. Finding communities of nodes and finding communities of links are two popular schemes for network analysis. These schemes, however, have inherent drawbacks and are inadequate to capture complex organizational structures in real networks. We introduce a new scheme and an effective approach for identifying complex mixture structures of node and link communities, called hybrid node-link communities. A central piece of our approach is a probabilistic model that accommodates node, link and hybrid node-link communities. Our extensive experiments on various real-world networks, including a large protein-protein interaction network and a large network of semantically associated words, illustrated that the scheme for hybrid communities is superior in revealing network characteristics. Moreover, the new approach outperformed the existing methods for finding node or link communities separately.

Alternative Enzymes Lead to Improvements in Sequence Coverage and PTM Analysis

PubMed Central

Hooper, Kyle; Rosenblatt, Michael; Urh, Marjeta; Saveliev, Sergei; Hosfield, Chris; Kobs, Gary; Ford, Michael; Jones, Richard; Amunugama, Ravi; Allen, David; Brazas, Robert

2013-01-01

The profiling of proteins using biological mass spectrometry (bottom up proteomics) most commonly requires trypsin. Trypsin is advantageous in that it produces peptides of optimal charge and size. However, for applications in which the proteins under investigation are part of a complex mixture or not isolated at high levels (i.e. low ng from an immunoprecipitation), sequence coverage is rarely complete. In addition, we have found that in several cases, like phosphorylation, acetylation, and methylation, alternative proteases are required to prepare peptides suitable for MS detection. This poster will provide specific examples which demonstrate this observation. For example, the application of a combined Trypsin/ Lys-C mixture reduces the number of missed cleavages by more than 3-fold producing samples with lower CV's (for biological replicates). The mixture is also well-suited for the complete proteolysis of hydrophobic, compact proteins. The addition of chymotrypsin and elastase has been found to be useful for identifying phosphorylation sites on proteins, especially on sequences where the site of phosphorylation inhibits trypsin (i.e. proximal to K or R). Many epigenetic applications have focused on histone modifications, like lysine acetylation and arginine methylation. Alternative proteases like Asp-N, Glu-C, and chymotrypsin have been especially useful given the fact that the modified K and R residues are resistant to c-terminal cleavage by trypsin. Finally, in the case of serum profiling, the addition of the endoglycosidase, PNGase F has been found to improve sequence coverage due to the removal of N-linked glycans.

Characterization of the Androgen-sensitive MDA-kb2 Cell Line for Assessing Complex Environmental Mixtures

EPA Science Inventory

Complex mixtures of synthetic and natural androgens and estrogens, and many other non-steroidal components are commonly released to the aquatic environment from anthropogenic sources. It is important to understand the potential interactive (i.e., additive, synergistic, antagonist...

Diagnostic Assessment of the Ecological Risk of EDCs in Complex Mixtures

EPA Science Inventory

Although it is important to be able to forecast the potential endocrine toxicity of chemical mixtures that could enter aquatic environments, in many instances there is a need to determine possible effects of endocrine-active chemicals already present in complex environmental mixt...

SOLUBILITY, SORPTION AND TRANSPORT OF HYDROPHOBIC ORGANIC CHEMICALS IN COMPLEX MIXTURES

EPA Science Inventory

The research summarized in this report focuses on the effects which organic cosolvents have on the sorption and mobility of organic contaminants. This work was initiated In an effort to improve our understanding of the environmental consequences associated with complex mixtur...

Assessing chemical exposure and ecological impacts of environmental surface waters using cell culture-based metabolomic

EPA Science Inventory

Waste water treatment plants (WWTPs), as well as industrial and agricultural operations release complex mixtures of anthropogenic chemicals that negatively affect surface water quality. Previous studies have shown that exposure to such complex chemical mixtures can produce adver...

DIRECT AND PHOTOACTIVATED TOXICITY OF A COMPLEX PETROLEUM MIXTURE: A COMPARISON OF SOLUBILIZATION METHODS

EPA Science Inventory

This work addresses several issues associated with the toxicity of a complex petroleum mixture (combined kerosene/diesel and crude oil), including developmental effects and early lifestage mortality, method of solubilization, and potential photo-activated and photo-modified toxic...

Application of hierarchical Bayesian unmixing models in river sediment source apportionment

NASA Astrophysics Data System (ADS)

Blake, Will; Smith, Hugh; Navas, Ana; Bodé, Samuel; Goddard, Rupert; Zou Kuzyk, Zou; Lennard, Amy; Lobb, David; Owens, Phil; Palazon, Leticia; Petticrew, Ellen; Gaspar, Leticia; Stock, Brian; Boeckx, Pacsal; Semmens, Brice

2016-04-01

Fingerprinting and unmixing concepts are used widely across environmental disciplines for forensic evaluation of pollutant sources. In aquatic and marine systems, this includes tracking the source of organic and inorganic pollutants in water and linking problem sediment to soil erosion and land use sources. It is, however, the particular complexity of ecological systems that has driven creation of the most sophisticated mixing models, primarily to (i) evaluate diet composition in complex ecological food webs, (ii) inform population structure and (iii) explore animal movement. In the context of the new hierarchical Bayesian unmixing model, MIXSIAR, developed to characterise intra-population niche variation in ecological systems, we evaluate the linkage between ecological 'prey' and 'consumer' concepts and river basin sediment 'source' and sediment 'mixtures' to exemplify the value of ecological modelling tools to river basin science. Recent studies have outlined advantages presented by Bayesian unmixing approaches in handling complex source and mixture datasets while dealing appropriately with uncertainty in parameter probability distributions. MixSIAR is unique in that it allows individual fixed and random effects associated with mixture hierarchy, i.e. factors that might exert an influence on model outcome for mixture groups, to be explored within the source-receptor framework. This offers new and powerful ways of interpreting river basin apportionment data. In this contribution, key components of the model are evaluated in the context of common experimental designs for sediment fingerprinting studies namely simple, nested and distributed catchment sampling programmes. Illustrative examples using geochemical and compound specific stable isotope datasets are presented and used to discuss best practice with specific attention to (1) the tracer selection process, (2) incorporation of fixed effects relating to sample timeframe and sediment type in the modelling process, (3) deriving and using informative priors in sediment fingerprinting context and (4) transparency of the process and replication of model results by other users.

Formulation of electroclinic, ferroelectric and antiferroelectric liquid crystal mixtures suitable for display devices

NASA Astrophysics Data System (ADS)

Debnath, Asim; Goswami, Debarghya; Mandal, Pradip Kumar

2018-04-01

Most of the liquid crystal display (LCD) devices starting from simplest wrist watches or calculators to complex laptops or flat TV sets are based on nematics. Although a tremendous improvement in the quality of display as well as reduction of manufacturing cost has taken place over the years, there are many issues which the LC industry is trying hard to address. Ferroelectric liquid crystals (FLC) are of current interest in the LCD industry since among various other advantages FLC based displays have micro-second order switching compared to milli-second order switching in nematic based displays. To meet the market demand much effort has been made to optimize the physical parameters of FLCs, such as temperature range, spontaneous polarization (PS), helical pitch (p), switching time (τ), tilt angle (θ) and rotational viscosity (γ). Multicomponent mixtures are, therefore, formulated to optimize all the required properties for practical applications since no single FLC compound can satisfy the above requirements. To the best of our knowledge electroclinic, ferroelectric and antiferroelectric liquid crystal mixtures have been formulated first time by any Indian group which have properties suitable for FLC based display devices and at par with mixtures used in the industry.

Integrating Mass Spectrometry of Intact Protein Complexes into Structural Proteomics

PubMed Central

Hyung, Suk-Joon; Ruotolo, Brandon T.

2013-01-01

Summary Mass spectrometry analysis of intact protein complexes has emerged as an established technology for assessing the composition and connectivity within dynamic, heterogeneous multiprotein complexes at low concentrations and in the context of mixtures. As this technology continues to move forward, one of the main challenges is to integrate the information content of such intact protein complex measurements with other mass spectrometry approaches in structural biology. Methods such as H/D exchange, oxidative foot-printing, chemical cross-linking, affinity purification, and ion mobility separation add complementary information that allows access to every level of protein structure and organization. Here, we survey the structural information that can be retrieved by such experiments, demonstrate the applicability of integrative mass spectrometry approaches in structural proteomics, and look to the future to explore upcoming innovations in this rapidly-advancing area. PMID:22611037

Development and validation of a multi-locus DNA metabarcoding method to identify endangered species in complex samples

PubMed Central

Arulandhu, Alfred J.; Staats, Martijn; Hagelaar, Rico; Voorhuijzen, Marleen M.; Prins, Theo W.; Scholtens, Ingrid; Costessi, Adalberto; Duijsings, Danny; Rechenmann, François; Gaspar, Frédéric B.; Barreto Crespo, Maria Teresa; Holst-Jensen, Arne; Birck, Matthew; Burns, Malcolm; Haynes, Edward; Hochegger, Rupert; Klingl, Alexander; Lundberg, Lisa; Natale, Chiara; Niekamp, Hauke; Perri, Elena; Barbante, Alessandra; Rosec, Jean-Philippe; Seyfarth, Ralf; Sovová, Tereza; Van Moorleghem, Christoff; van Ruth, Saskia; Peelen, Tamara

2017-01-01

Abstract DNA metabarcoding provides great potential for species identification in complex samples such as food supplements and traditional medicines. Such a method would aid Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) enforcement officers to combat wildlife crime by preventing illegal trade of endangered plant and animal species. The objective of this research was to develop a multi-locus DNA metabarcoding method for forensic wildlife species identification and to evaluate the applicability and reproducibility of this approach across different laboratories. A DNA metabarcoding method was developed that makes use of 12 DNA barcode markers that have demonstrated universal applicability across a wide range of plant and animal taxa and that facilitate the identification of species in samples containing degraded DNA. The DNA metabarcoding method was developed based on Illumina MiSeq amplicon sequencing of well-defined experimental mixtures, for which a bioinformatics pipeline with user-friendly web-interface was developed. The performance of the DNA metabarcoding method was assessed in an international validation trial by 16 laboratories, in which the method was found to be highly reproducible and sensitive enough to identify species present in a mixture at 1% dry weight content. The advanced multi-locus DNA metabarcoding method assessed in this study provides reliable and detailed data on the composition of complex food products, including information on the presence of CITES-listed species. The method can provide improved resolution for species identification, while verifying species with multiple DNA barcodes contributes to an enhanced quality assurance. PMID:29020743

Development and validation of a multi-locus DNA metabarcoding method to identify endangered species in complex samples.

PubMed

Arulandhu, Alfred J; Staats, Martijn; Hagelaar, Rico; Voorhuijzen, Marleen M; Prins, Theo W; Scholtens, Ingrid; Costessi, Adalberto; Duijsings, Danny; Rechenmann, François; Gaspar, Frédéric B; Barreto Crespo, Maria Teresa; Holst-Jensen, Arne; Birck, Matthew; Burns, Malcolm; Haynes, Edward; Hochegger, Rupert; Klingl, Alexander; Lundberg, Lisa; Natale, Chiara; Niekamp, Hauke; Perri, Elena; Barbante, Alessandra; Rosec, Jean-Philippe; Seyfarth, Ralf; Sovová, Tereza; Van Moorleghem, Christoff; van Ruth, Saskia; Peelen, Tamara; Kok, Esther

2017-10-01

DNA metabarcoding provides great potential for species identification in complex samples such as food supplements and traditional medicines. Such a method would aid Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) enforcement officers to combat wildlife crime by preventing illegal trade of endangered plant and animal species. The objective of this research was to develop a multi-locus DNA metabarcoding method for forensic wildlife species identification and to evaluate the applicability and reproducibility of this approach across different laboratories. A DNA metabarcoding method was developed that makes use of 12 DNA barcode markers that have demonstrated universal applicability across a wide range of plant and animal taxa and that facilitate the identification of species in samples containing degraded DNA. The DNA metabarcoding method was developed based on Illumina MiSeq amplicon sequencing of well-defined experimental mixtures, for which a bioinformatics pipeline with user-friendly web-interface was developed. The performance of the DNA metabarcoding method was assessed in an international validation trial by 16 laboratories, in which the method was found to be highly reproducible and sensitive enough to identify species present in a mixture at 1% dry weight content. The advanced multi-locus DNA metabarcoding method assessed in this study provides reliable and detailed data on the composition of complex food products, including information on the presence of CITES-listed species. The method can provide improved resolution for species identification, while verifying species with multiple DNA barcodes contributes to an enhanced quality assurance. © The Authors 2017. Published by Oxford University Press.

Understanding and exploiting the phase behavior of mixtures of oppositely charged polymers and surfactants in water.

PubMed

Piculell, Lennart

2013-08-20

Complexes of oppositely charged polymers and surfactants (OCPS) in water come in many varieties, including liquid-crystalline materials, soluble complexes, structured nanoparticles, and water-insoluble surface layers. The range of available structures and properties increases even further with the addition of other amphiphilic substances that may enter, or even dissolve, the complexes, depending on the nature of the additive. Simple operations may change the properties of OCPS systems dramatically. For instance, dilution with water can induce a phase separation in an initially stable OCPS solution. More complicated processes, involving chemical reactions, can be used to either create or disintegrate OCPS particles or surface layers. The richness of their properties has made OCPS mixtures ubiquitous in everyday household products, such as shampoos and laundry detergents, and also attractive ingredients in the design of new types of responsive particles, surfaces, and delivery agents of potential use in future applications. A challenge for the rational design of an OCPS system is, however, to obtain a good fundamental understanding of how to select molecular shapes and sizes and how to tune the hydrophobic and electrostatic interactions such that the desired properties are obtained. Recent studies of OCPS phase equilibria, using a strategy where the minimum number of components is always used to address a particular question, have brought out general rules and trends that can be used for such a rational design. Those fundamental studies are reviewed here, together with more application-oriented studies where fundamental learning has been put to use.

Engineering Escherichia coli coculture systems for the production of biochemical products

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

Zhang, Haoran; Pereira, Brian; Li, Zhengjun

Engineering microbial consortia to express complex biosynthetic pathways efficiently for the production of valuable compounds is a promising approach for metabolic engineering and synthetic biology. Here, we report the design, optimization, and scale-up of an Escherichia coli-E. coli coculture that successfully overcomes fundamental microbial production limitations, such as high-level intermediate secretion and low-efficiency sugar mixture utilization. For the production of the important chemical cis,cis-muconic acid, we show that the coculture approach achieves a production yield of 0.35 g/g from a glucose/xylose mixture, which is significantly higher than reported in previous reports. Furthermore, by efficiently producing another compound, 4-hydroxybenzoic acid, wemore » also demonstrate that the approach is generally applicable for biosynthesis of other important industrial products.« less

Patterned surfaces in the drying of films composed of water, polymer, and alcohol

NASA Astrophysics Data System (ADS)

Fichot, Julie; Heyd, Rodolphe; Josserand, Christophe; Chourpa, Igor; Gombart, Emilie; Tranchant, Jean-Francois; Saboungi, Marie-Louise

2012-12-01

A study of the complex drying dynamics of polymeric mixtures with optical microscopy and gravimetric measurement is presented. Droplet formation is observed, followed by a collapse that leads to the residual craters in the dried film. The process is followed in situ under well-defined temperature and hygrometric conditions to determine the origin and nature of these droplets and craters. The drying process is usually completed within 1 h. The observations are explained using a simple diffusion model based on experimental results collected from mass and optical measurements as well as Raman confocal microspectrometry. Although the specific polymeric mixtures used here are of interest to the cosmetic industry, the general conclusions reached can apply to other polymeric aqueous solutions with applications to commercial and artistic painting.

Engineering Escherichia coli coculture systems for the production of biochemical products

DOE PAGES

Zhang, Haoran; Pereira, Brian; Li, Zhengjun; ...

2015-06-25

Engineering microbial consortia to express complex biosynthetic pathways efficiently for the production of valuable compounds is a promising approach for metabolic engineering and synthetic biology. Here, we report the design, optimization, and scale-up of an Escherichia coli-E. coli coculture that successfully overcomes fundamental microbial production limitations, such as high-level intermediate secretion and low-efficiency sugar mixture utilization. For the production of the important chemical cis,cis-muconic acid, we show that the coculture approach achieves a production yield of 0.35 g/g from a glucose/xylose mixture, which is significantly higher than reported in previous reports. Furthermore, by efficiently producing another compound, 4-hydroxybenzoic acid, wemore » also demonstrate that the approach is generally applicable for biosynthesis of other important industrial products.« less

Decoding 2D-PAGE complex maps: relevance to proteomics.

PubMed

Pietrogrande, Maria Chiara; Marchetti, Nicola; Dondi, Francesco; Righetti, Pier Giorgio

2006-03-20

This review describes two mathematical approaches useful for decoding the complex signal of 2D-PAGE maps of protein mixtures. These methods are helpful for interpreting the large amount of data of each 2D-PAGE map by extracting all the analytical information hidden therein by spot overlapping. Here the basic theory and application to 2D-PAGE maps are reviewed: the means for extracting information from the experimental data and their relevance to proteomics are discussed. One method is based on the quantitative theory of statistical model of peak overlapping (SMO) using the spot experimental data (intensity and spatial coordinates). The second method is based on the study of the 2D-autocovariance function (2D-ACVF) computed on the experimental digitised map. They are two independent methods that are able to extract equal and complementary information from the 2D-PAGE map. Both methods permit to obtain fundamental information on the sample complexity and the separation performance and to single out ordered patterns present in spot positions: the availability of two independent procedures to compute the same separation parameters is a powerful tool to estimate the reliability of the obtained results. The SMO procedure is an unique tool to quantitatively estimate the degree of spot overlapping present in the map, while the 2D-ACVF method is particularly powerful in simply singling out the presence of order in the spot position from the complexity of the whole 2D map, i.e., spot trains. The procedures were validated by extensive numerical computation on computer-generated maps describing experimental 2D-PAGE gels of protein mixtures. Their applicability to real samples was tested on reference maps obtained from literature sources. The review describes the most relevant information for proteomics: sample complexity, separation performance, overlapping extent, identification of spot trains related to post-translational modifications (PTMs).

Packing optimization for automated generation of complex system's initial configurations for molecular dynamics and docking.

PubMed

Martínez, José Mario; Martínez, Leandro

2003-05-01

Molecular Dynamics is a powerful methodology for the comprehension at molecular level of many chemical and biochemical systems. The theories and techniques developed for structural and thermodynamic analyses are well established, and many software packages are available. However, designing starting configurations for dynamics can be cumbersome. Easily generated regular lattices can be used when simple liquids or mixtures are studied. However, for complex mixtures, polymer solutions or solid adsorbed liquids (for example) this approach is inefficient, and it turns out to be very hard to obtain an adequate coordinate file. In this article, the problem of obtaining an adequate initial configuration is treated as a "packing" problem and solved by an optimization procedure. The initial configuration is chosen in such a way that the minimum distance between atoms of different molecules is greater than a fixed tolerance. The optimization uses a well-known algorithm for box-constrained minimization. Applications are given for biomolecule solvation, many-component mixtures, and interfaces. This approach can reduce the work of designing starting configurations from days or weeks to few minutes or hours, in an automated fashion. Packing optimization is also shown to be a powerful methodology for space search in docking of small ligands to proteins. This is demonstrated by docking of the thyroid hormone to its nuclear receptor. Copyright 2003 Wiley Periodicals, Inc. J Comput Chem 24: 819-825, 2003

Application of the Attagene FACTORIAL™ assay to ...

EPA Pesticide Factsheets

Bioassays can be used to evaluate the integrated effects of complex mixtures from both known and unidentified contaminants present in environmental samples. However, such bio-monitoring approaches have typically focused only on one or a few pathways (e.g. estrogen receptor, androgen receptor) despite the fact that the chemicals in a mixture may exhibit a range of biological activities. High-throughput screening approaches that can rapidly assess samples for a broad diversity of biological activities offer a means to provide a more comprehensive characterization of complex mixtures. The Attagene FactorialTM platform is a high-throughput, cell based assay utilized by US EPA’s ToxCast Program, which provides high-content assessment of over 90 different gene regulatory pathways and all 48 human nuclear receptors (NRs). This assay has previously been used in a preliminary screening of surface water extracts from sites across the Great Lakes. In the current study, surface waters samples from 38 sites were collected, extracted, and screened through the Factorial assay as part of a USGS nationwide stream assessment. All samples were evaluated in a six point, 3-fold dilution series and analyzed using the ToxCast Data Pipeline (TCPL) to generate dose-response curves and corresponding half-maximal activity concentration (AC50) estimates. A total of 27 assay endpoints responded to extracts from one or more sites, with up to 14 assays active for a single extract. The four

Application of the high throughput Attagene Factorial TM ...

EPA Pesticide Factsheets

Bioassays can be employed to evaluate the integrated effects of complex mixtures of both known and unidentified contaminants present in environmental samples. However, such methods have typically focused on one or a few pathways despite the fact that the chemicals in a mixture may exhibit a wide range of activities. High throughput toxicology approaches that can rapidly screen samples for a broad diversity of biological activities offer a means to provide a more comprehensive characterization of complex mixtures. To test this concept, twenty-four ambient water samples were collected, extracted, and screened for their ability to interact with or modulate over 80 different transcription factors using the Attagene FactorialTM platform utilized by the US EPA’s ToxCast Program. Samples evaluated included 10 water samples collected in varying proximity to a wastewater discharge into the St. Louis River, MN; water collected at five sites along a gradient centered on a wastewater discharge into the Maumee River, Ohio, USA; and eight samples collected in association with a nation-wide USGS surface streams study. For samples collected along the St. Louis River, the greatest number of biological activities were observed at locations closest to wastewater discharge with up to 13 endpoints responding. The Maumee River showed a gradient response in the number of observed activities, ranging from three positive responses observed far upstream of a wastewater discharge to 10

A multimodal imaging workflow to visualize metal mixtures in the human placenta and explore colocalization with biological response markers.

PubMed

Niedzwiecki, Megan M; Austin, Christine; Remark, Romain; Merad, Miriam; Gnjatic, Sacha; Estrada-Gutierrez, Guadalupe; Espejel-Nuñez, Aurora; Borboa-Olivares, Hector; Guzman-Huerta, Mario; Wright, Rosalind J; Wright, Robert O; Arora, Manish

2016-04-01

Fetal exposure to essential and toxic metals can influence life-long health trajectories. The placenta regulates chemical transmission from maternal circulation to the fetus and itself exhibits a complex response to environmental stressors. The placenta can thus be a useful matrix to monitor metal exposures and stress responses in utero, but strategies to explore the biologic effects of metal mixtures in this organ are not well-developed. In this proof-of-concept study, we used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to measure the distributions of multiple metals in placental tissue from a low-birth-weight pregnancy, and we developed an approach to identify the components of metal mixtures that colocalized with biological response markers. Our novel workflow, which includes custom-developed software tools and algorithms for spatial outlier identification and background subtraction in multidimensional elemental image stacks, enables rapid image processing and seamless integration of data from elemental imaging and immunohistochemistry. Using quantitative spatial statistics, we identified distinct patterns of metal accumulation at sites of inflammation. Broadly, our multiplexed approach can be used to explore the mechanisms mediating complex metal exposures and biologic responses within placentae and other tissue types. Our LA-ICP-MS image processing workflow can be accessed through our interactive R Shiny application 'shinyImaging', which is available at or through our laboratory's website, .

Metallic elements in fossil fuel combustion products: amounts and form of emissions and evaluation of carcinogenicity and mutagenicity.

PubMed

Vouk, V B; Piver, W T

1983-01-01

Metallic elements contained in coal, oil and gasoline are mobilized by combustion processes and may be emitted into the atmosphere, mainly as components of submicron particles. The information about the amounts, composition and form of metal compounds is reviewed for some fuels and combustion processes. Since metal compounds are always contained in urban air pollutants, they have to be considered whenever an evaluation of biological impact of air pollutants is made. The value of currently used bioassays for the evaluation of the role of trace metal compounds, either as major biologically active components or as modifiers of biological effects of organic compounds is assessed. The whole animal bioassays for carcinogenicity do not seem to be an appropriate approach. They are costly, time-consuming and not easily amenable to the testing of complex mixtures. Some problems related to the application and interpretation of short-term bioassays are considered, and the usefulness of such bioassays for the evaluation of trace metal components contained in complex air pollution mixtures is examined.

Fluorescence life-time imaging and steady state polarization for examining binding of fluorophores to gold nanoparticles.

PubMed

Schwartz, Shmulik; Fixler, Dror; Popovtzer, Rachela; Shefi, Orit

2015-11-01

Nanocomposites as multifunctional agents are capable of combing imaging and cell biology technologies. The conventional methods used for validation of the conjugation process of nanoparticles (NPs) to fluorescent molecules such as spectroscopy analysis and surface potential measurements, are not sufficient. In this paper we present a new and highly sensitive procedure that uses the combination of (1) fluorescence spectrum, (2) fluorescence lifetime, and (3) steady state fluorescence polarization measurements. We characterize and analyze gold NPs with Lucifer yellow (LY) surface coating as a model. We demonstrate the ability to differentiate between LY-GNP (the conjugated complex) and a mixture of coated NP and free dyes. We suggest the approach for neuroscience applications where LY is used for detecting and labeling cells, studying morphology and intracellular communications. Histograms of Fluorescence lifetime imaging (FLIM) of free LY dye (Left) in comparison to the conjugated dye to gold nanoparticles, LY-GNP (Middle) enable the differentiation between LY-GNP (the conjugated complex) and a mixture of coated NP and free dyes (Right). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Crystallization using reverse micelles and water-in-oil microemulsion systems: the highly selective tool for the purification of organic compounds from complex mixtures.

PubMed

Kljajic, Alen; Bester-Rogac, Marija; Klobcar, Andrej; Zupet, Rok; Pejovnik, Stane

2013-02-01

The active pharmaceutical ingredient orlistat is usually manufactured using a semi-synthetic procedure, producing crude product and complex mixtures of highly related impurities with minimal side-chain structure variability. It is therefore crucial for the overall success of industrial/pharmaceutical application to develop an effective purification process. In this communication, we present the newly developed water-in-oil reversed micelles and microemulsion system-based crystallization process. Physiochemical properties of the presented crystallization media were varied through surfactants and water composition, and the impact on efficiency was measured through final variation of these two parameters. Using precisely defined properties of the dispersed water phase in crystallization media, a highly efficient separation process in terms of selectivity and yield was developed. Small-angle X-ray scattering, high-performance liquid chromatography, mass spectrometry, and scanning electron microscopy were used to monitor and analyze the separation processes and orlistat products obtained. Typical process characteristics, especially selectivity and yield in regard to reference examples, were compared and discussed. Copyright © 2012 Wiley Periodicals, Inc.

Monitoring of protease catalyzed reactions by quantitative MALDI MS using metal labeling.

PubMed

Gregorius, Barbara; Jakoby, Thomas; Schaumlöffel, Dirk; Tholey, Andreas

2013-05-21

Quantitative mass spectrometry is a powerful tool for the determination of enzyme activities as it does not require labeled substrates and simultaneously allows for the identification of reaction products. However, major restrictions are the limited number of samples which can be measured in parallel due to the need for isotope labeled internal standards. Here we describe the use of metal labeling of peptides for the setup of multiplexed enzyme activity assays. After proteolytic reaction, using the protease trypsin, remaining substrates and peptide products formed in the reaction were labeled with metal chelators complexing rare earth metal ions. Labeled peptides were quantified with high accuracy and over a wide dynamic range (at least 2 orders of magnitude) using MALDI MS in case of simple peptide mixtures or by LC-MALDI MS for complex substrate mixtures and used for the monitoring of time-dependent product formation and substrate consumption. Due to multiplexing capabilities and accuracy, the presented approach will be useful for the determination of enzyme activities with a wide range of biochemical and biotechnological applications.

Metallic elements in fossil fuel combustion products: amounts and form of emissions and evaluation of carcinogenicity and mutagenicity.

PubMed Central

Vouk, V B; Piver, W T

1983-01-01

Metallic elements contained in coal, oil and gasoline are mobilized by combustion processes and may be emitted into the atmosphere, mainly as components of submicron particles. The information about the amounts, composition and form of metal compounds is reviewed for some fuels and combustion processes. Since metal compounds are always contained in urban air pollutants, they have to be considered whenever an evaluation of biological impact of air pollutants is made. The value of currently used bioassays for the evaluation of the role of trace metal compounds, either as major biologically active components or as modifiers of biological effects of organic compounds is assessed. The whole animal bioassays for carcinogenicity do not seem to be an appropriate approach. They are costly, time-consuming and not easily amenable to the testing of complex mixtures. Some problems related to the application and interpretation of short-term bioassays are considered, and the usefulness of such bioassays for the evaluation of trace metal components contained in complex air pollution mixtures is examined. PMID:6337825

Evaluating the Similarity of Complex Drinking-Water Disinfection By-Product Mixtures: Overview of the Issues

EPA Science Inventory

The Presentation describes the advantages and challenges of working with Whole Mixtures, discusses an exploratory approach for evaluating sufficient similarity, and challenges of applying such approaches to other environmental mixtures.

Differential effects of a complex organochlorine mixture on the proliferation of breast cancer cell lines

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

Aube, Michel, E-mail: 4aubem@videotron.ca; Larochelle, Christian, E-mail: christian.larochelle@inspq.qc.ca; Ayotte, Pierre, E-mail: pierre.ayotte@inspq.qc.ca

2011-04-15

Organochlorine compounds (OCs) are a group of persistent chemicals that accumulate in fatty tissues with age. Although OCs has been tested individually for their capacity to induce breast cancer cell proliferation, few studies examined the effect of complex mixtures that comprise compounds frequently detected in the serum of women. We constituted such an OC mixture containing 15 different components in environmentally relevant proportions and assessed its proliferative effects in four breast cancer cell lines (MCF-7, T47D, CAMA-1, MDAMB231) and in non-cancerous CV-1 cells. We also determined the capacity of the mixture to modulate cell cycle stage of breast cancer cellsmore » and to induce estrogenic and antiandrogenic effects using gene reporter assays. We observed that low concentrations of the mixture (100x10{sup 3} and 50x10{sup 3} dilutions) stimulated the proliferation of MCF-7 cells while higher concentrations (10x10{sup 3} and 5x10{sup 3} dilutions) had the opposite effect. In contrast, the mixture inhibited the proliferation of non-hormone-dependent cell lines. The mixture significantly increased the number of MCF-7 cells entering the S phase, an effect that was blocked by the antiestrogen ICI 182,780. Low concentrations of the mixture also caused an increase in CAMA-1 cell proliferation but only in the presence estradiol and dihydrotestosterone (p<0.05 at the 50x10{sup 3} dilution). DDT analogs and polychlorinated biphenyls all had the capacity to stimulate the proliferation of CAMA-1 cells in the presence of sex steroids. Reporter gene assays further revealed that the mixture and several of its constituents (DDT analogs, aldrin, dieldrin, {beta}-hexachlorocyclohexane, toxaphene) induced estrogenic effects, whereas the mixture and several components (DDT analogs, aldrin, dieldrin and PCBs) inhibited the androgen signaling pathway. Our results indicate that the complex OC mixture increases the proliferation of MCF-7 cells due to its estrogenic potential. The proliferative effect of the mixture on CAMA-1 cells in the presence of sex steroids appears mostly due to the antiandrogenic properties of p,p'-DDE, a major constituent of the mixture. Other mixtures of contaminants that include emerging compounds of interest such as brominated flame retardants and perfluoroalkyl compounds should be tested for their capacity to induce breast cancer cell proliferation. - Research highlights: {yields} We studied effects of a complex organochlorine mixture on breast cancer cell growth. {yields} Weak xenoestrogens in the mixture stimulated the proliferation of MCF-7 cells. {yields} Antiandrogens increased the proliferation CAMA-1 cells grown with sex steroids. {yields} High concentrations of the mixture decreased the proliferation of all cell lines.« less

The Precise Measurement of Vapor-Liquid Equilibrium Properties of the CO2/Isopentane Binary Mixture, and Fitted Parameters for a Helmholtz Energy Mixture Model

NASA Astrophysics Data System (ADS)

Miyamoto, H.; Shoji, Y.; Akasaka, R.; Lemmon, E. W.

2017-10-01

Natural working fluid mixtures, including combinations of CO2, hydrocarbons, water, and ammonia, are expected to have applications in energy conversion processes such as heat pumps and organic Rankine cycles. However, the available literature data, much of which were published between 1975 and 1992, do not incorporate the recommendations of the Guide to the Expression of Uncertainty in Measurement. Therefore, new and more reliable thermodynamic property measurements obtained with state-of-the-art technology are required. The goal of the present study was to obtain accurate vapor-liquid equilibrium (VLE) properties for complex mixtures based on two different gases with significant variations in their boiling points. Precise VLE data were measured with a recirculation-type apparatus with a 380 cm3 equilibration cell and two windows allowing observation of the phase behavior. This cell was equipped with recirculating and expansion loops that were immersed in temperature-controlled liquid and air baths, respectively. Following equilibration, the composition of the sample in each loop was ascertained by gas chromatography. VLE data were acquired for CO2/ethanol and CO2/isopentane binary mixtures within the temperature range from 300 K to 330 K and at pressures up to 7 MPa. These data were used to fit interaction parameters in a Helmholtz energy mixture model. Comparisons were made with the available literature data and values calculated by thermodynamic property models.

A Molecular Dynamics Study of Single-Walled Carbon Nanotubes (SWCNTs) Dispersed in Bile Salt Surfactants

NASA Astrophysics Data System (ADS)

Phelan, Frederick, Jr.; Sun, Huai

2014-03-01

Single-walled carbon nanotubes (SWNCTs) are materials with structural, electronic and optical properties that make them attractive for a myriad of advanced technology applications. A practical barrier to their use is that SWCNT synthesis techniques produce heterogeneous mixtures of varying lengths and chirality, whereas applications generally require tubes with narrow size distributions and individual type. Most separation techniques currently in use to obtain monodisperse tube fractions rely on dispersion of these materials in aqueous solution using surfactants. The dispersion process results in a mixture of colloidal structures in which individual tubes are dispersed and contained in a surfactant shell. Understanding the structure and properties of the SWCNT-surfactant complex at the molecular level, and how this is affected by chirality, is key to understanding and improving separations processes. In this study, we use molecular dynamics (MD) simulations to study the structure and properties of SWCNT-surfactant colloidal complexes. We tested a number of methods and protocols in order to build an accurate model for simulating SWCNT systems for a variety of bile salt surfactants as well as anionic co-surfactants, components that are widely used and important in experimental separation studies at NIST. The custom force field parameters used here will be stored in WebFF, a Web-hosted smart force-field repository for polymeric and organic materials being developed at NIST for the Materials Genome Initiative.

Application of diffusion-edited and solvent suppression ¹H-NMR to the direct analysis of markers in valerian-hop liquid herbal products.

PubMed

Prieto, Jose M; Mellinas-Gomez, Maria; Zloh, Mire

2016-01-01

The rising trend to consume herbal products for the treatment and/or prevention of minor ailments together with their chemical and pharmacological complexity means there is an urgent need to develop new approaches to their quality and stability. This work looks at the application of one-dimensional diffusion-edited (1)H-NMR spectroscopy (1D DOSY) and (1)H-NMR with suppression of the ethanol and water signals to the characterisation of quality and stability markers in multi-component herbal medicines/food supplements. The experiments were performed with commercial tinctures of Valeriana officinalis L. (valerian), expired and non-expired, as well as its combination with Hummulus lupulus L. (hops), which is one of the most popular blends of relaxant herbs. These techniques did not require purification or evaporation of components for the qualitative analysis of the mixture, but only the addition of D2 O and TSP. The best diagnostic signals were found at δ 7 ppm (H-11, valerenic acid), δ 4.2 ppm (H-1, hydroxyvalerenic acid) and δ 1.5-1.8 ppm (methyl groups in prenylated moieties, α-acids/prenylated flavones). This work concludes on the potential value of 1D DOSY (1)H-NMR to provide additional assurance of quality in complex natural mixtures. Copyright © 2016 John Wiley & Sons, Ltd.

Intermolecular forces in acetonitrile + ethanol binary liquid mixtures

NASA Astrophysics Data System (ADS)

Elangovan, A.; Shanmugam, R.; Arivazhagan, G.; Mahendraprabu, A.; Karthick, N. K.

2015-10-01

FTIR spectral measurements have been carried out on the binary mixtures of acetonitrile with ethanol at 1:0 (acetonitrile:ethanol), 1:1, 1:2, 1:3 and 0:1 at room temperature. DFT and isosurface calculations have been performed. The acetonitrile + ethanol binary mixtures consist of 1:1, 1:2, 1:3 and 1:4 complexes formed through both the red and blue shifting H-bonds. Inter as well as intra molecular forces are found to exist in 1:3 and 1:4 complexes.

Combining Toxicological and Chemical Characterization of Complex Mixtures to Understand the Impact of the Unknown Fraction

EPA Science Inventory

Toxicological assessment of adverse health outcomes associated with exposure to complex mixtures provides an integrated response of the organism (or in vitro test system) that accounts for additivity among the components (both dose and response) as well as any greater than or les...

In Vitro Assays for Assessment of Androgenic and Estrogenic Activity of Defined Mixtures and Complex Environmental Samples

EPA Science Inventory

Point sources of endocrine active compounds to aquatic environments such as waste water treatment plants, pulp and paper mills, and animal feeding operations invariably contain complex mixtures of chemicals. The current study investigates the use of targeted in vitro assays des...

In vitro assays for assessment of androgenic and estrogenic activity of defined mixtures and complex environment samples

EPA Science Inventory

Point sources of potentially endocrine active compounds to aquatic environments such as waste water treatment plants, pulp and paper mills, and animal feeding operations invariably contain complex mixtures of chemicals. The current study investigates the use of targeted in vitro ...

Integrating multiple lines of evidence to assess biological hazards of complex mixtures: A case study in the Maumee River

EPA Science Inventory

Product Description:Due to technological improvements, increasing numbers of chemical contaminants are being detected in surface waters nation-wide, including the Great Lakes. Methods are needed to understand what impact these complex mixtures of contaminants can have on aquatic ...

The Developmental Effects Of A Municipal Wastewater Effluent On The Northern Leopard Frog, Rana pipiens

EPA Science Inventory

Wastewater effluents are complex mixtures containing a variety of anthropogenic compounds, many of which are known endocrine disruptors. In order to characterize the development and behavorial effects of such a complex mixture, northern leopard frogs, Rana pipiens, were e...

THE POWER TO DETECT A DIFFERENCE: DETERMINING SAMPLE SIZE REQUIREMENTS FOR EVALUATION OF REPRODUCTIVE/DEVELOPMENTAL EFFECTS FROM EXPOSURE TO COMPLEX MIXTURES OF DISINFECTION BYPRODUCTS

EPA Science Inventory

Toxicological assessment of environmentally-realistic complex mixtures of drinking-water disinfection byproducts (DBPs) are needed to address concerns raised by some epidemiological studies showing associations between exposure to chemically disinfected water and adverse reproduc...

In vitro assays for assessment of androgenic and estrogenic activity in defined mixtures and complex environmental samples

EPA Science Inventory

Eflluents from sources such as waste water treatment plants and animal feeding operations invariably contain complex mixtures of chemicals. Recent research on effluent from cattle feeding operations in the US have linked morphological alterations in fish with in vitro androgenic ...

Ground-Based Aerosol Measurements | Science Inventory ...

EPA Pesticide Factsheets

Atmospheric particulate matter (PM) is a complex chemical mixture of liquid and solid particles suspended in air (Seinfeld and Pandis 2016). Measurements of this complex mixture form the basis of our knowledge regarding particle formation, source-receptor relationships, data to test and verify complex air quality models, and how PM impacts human health, visibility, global warming, and ecological systems (EPA 2009). Historically, PM samples have been collected on filters or other substrates with subsequent chemical analysis in the laboratory and this is still the major approach for routine networks (Chow 2005; Solomon et al. 2014) as well as in research studies. In this approach, air, at a specified flow rate and time period, is typically drawn through an inlet, usually a size selective inlet, and then drawn through filters, 1 INTRODUCTION Atmospheric particulate matter (PM) is a complex chemical mixture of liquid and solid particles suspended in air (Seinfeld and Pandis 2016). Measurements of this complex mixture form the basis of our knowledge regarding particle formation, source-receptor relationships, data to test and verify complex air quality models, and how PM impacts human health, visibility, global warming, and ecological systems (EPA 2009). Historically, PM samples have been collected on filters or other substrates with subsequent chemical analysis in the laboratory and this is still the major approach for routine networks (Chow 2005; Solomo

Mixture effects in samples of multiple contaminants - An inter-laboratory study with manifold bioassays.

PubMed

Altenburger, Rolf; Scholze, Martin; Busch, Wibke; Escher, Beate I; Jakobs, Gianina; Krauss, Martin; Krüger, Janet; Neale, Peta A; Ait-Aissa, Selim; Almeida, Ana Catarina; Seiler, Thomas-Benjamin; Brion, François; Hilscherová, Klára; Hollert, Henner; Novák, Jiří; Schlichting, Rita; Serra, Hélène; Shao, Ying; Tindall, Andrew; Tolefsen, Knut-Erik; Umbuzeiro, Gisela; Williams, Tim D; Kortenkamp, Andreas

2018-05-01

Chemicals in the environment occur in mixtures rather than as individual entities. Environmental quality monitoring thus faces the challenge to comprehensively assess a multitude of contaminants and potential adverse effects. Effect-based methods have been suggested as complements to chemical analytical characterisation of complex pollution patterns. The regularly observed discrepancy between chemical and biological assessments of adverse effects due to contaminants in the field may be either due to unidentified contaminants or result from interactions of compounds in mixtures. Here, we present an interlaboratory study where individual compounds and their mixtures were investigated by extensive concentration-effect analysis using 19 different bioassays. The assay panel consisted of 5 whole organism assays measuring apical effects and 14 cell- and organism-based bioassays with more specific effect observations. Twelve organic water pollutants of diverse structure and unique known modes of action were studied individually and as mixtures mirroring exposure scenarios in freshwaters. We compared the observed mixture effects against component-based mixture effect predictions derived from additivity expectations (assumption of non-interaction). Most of the assays detected the mixture response of the active components as predicted even against a background of other inactive contaminants. When none of the mixture components showed any activity by themselves then the mixture also was without effects. The mixture effects observed using apical endpoints fell in the middle of a prediction window defined by the additivity predictions for concentration addition and independent action, reflecting well the diversity of the anticipated modes of action. In one case, an unexpectedly reduced solubility of one of the mixture components led to mixture responses that fell short of the predictions of both additivity mixture models. The majority of the specific cell- and organism-based endpoints produced mixture responses in agreement with the additivity expectation of concentration addition. Exceptionally, expected (additive) mixture response did not occur due to masking effects such as general toxicity from other compounds. Generally, deviations from an additivity expectation could be explained due to experimental factors, specific limitations of the effect endpoint or masking side effects such as cytotoxicity in in vitro assays. The majority of bioassays were able to quantitatively detect the predicted non-interactive, additive combined effect of the specifically bioactive compounds against a background of complex mixture of other chemicals in the sample. This supports the use of a combination of chemical and bioanalytical monitoring tools for the identification of chemicals that drive a specific mixture effect. Furthermore, we demonstrated that a panel of bioassays can provide a diverse profile of effect responses to a complex contaminated sample. This could be extended towards representing mixture adverse outcome pathways. Our findings support the ongoing development of bioanalytical tools for (i) compiling comprehensive effect-based batteries for water quality assessment, (ii) designing tailored surveillance methods to safeguard specific water uses, and (iii) devising strategies for effect-based diagnosis of complex contamination. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Analytical Application of Flow Immunosensor in Detection of Thyroxine and Triiodothyronine in Serum.

PubMed

Wani, Tanveer A; Zargar, Seema; Majid, Salma; Darwish, Ibrahim A

2016-11-01

In this study, an immunosensor based on kinetic exclusion analysis (KinExA) was used for thyroxine (T4) and triiodothyronine (T3) estimation. A KinExA™ 3200 instrument was used for this analysis, which is an automated flow fluorimeter designed to separate free unbound antibody binding sites in reaction mixtures of antibody, antigen, and antibody-antigen complex. A T3-BSA- and T4-BSA-coated polymethyl methacrylate (PMMA) bead microcolumn is generated inside the flow cell of the instrument. A sample mixture containing T3 and T4 with their respective monoclonal antibodies and their complexes are drawn past the microbead column. The unbound T3 or T4 monoclonal antibody binding sites are captured by their respective T3 and T4 antigens coated on the PMMA beads as bovine serum albumin conjugates. Fluorescently labeled secondary antibodies bind to the T3 or T4 antigen-antibody complex to generate fluorescence intensity for analysis. The limit of detection for the T3 and T4 assays was found to be 0.06 and 1.9 ng mL -1 with acceptable precision values. The convenience of the automated KinExA format may be valuable in medical diagnostic laboratories.

A competitive binding model predicts the response of mammalian olfactory receptors to mixtures

NASA Astrophysics Data System (ADS)

Singh, Vijay; Murphy, Nicolle; Mainland, Joel; Balasubramanian, Vijay

Most natural odors are complex mixtures of many odorants, but due to the large number of possible mixtures only a small fraction can be studied experimentally. To get a realistic understanding of the olfactory system we need methods to predict responses to complex mixtures from single odorant responses. Focusing on mammalian olfactory receptors (ORs in mouse and human), we propose a simple biophysical model for odor-receptor interactions where only one odor molecule can bind to a receptor at a time. The resulting competition for occupancy of the receptor accounts for the experimentally observed nonlinear mixture responses. We first fit a dose-response relationship to individual odor responses and then use those parameters in a competitive binding model to predict mixture responses. With no additional parameters, the model predicts responses of 15 (of 18 tested) receptors to within 10 - 30 % of the observed values, for mixtures with 2, 3 and 12 odorants chosen from a panel of 30. Extensions of our basic model with odorant interactions lead to additional nonlinearities observed in mixture response like suppression, cooperativity, and overshadowing. Our model provides a systematic framework for characterizing and parameterizing such mixing nonlinearities from mixture response data.

Widom Lines in Binary Mixtures of Supercritical Fluids.

PubMed

Raju, Muralikrishna; Banuti, Daniel T; Ma, Peter C; Ihme, Matthias

2017-06-08

Recent experiments on pure fluids have identified distinct liquid-like and gas-like regimes even under supercritical conditions. The supercritical liquid-gas transition is marked by maxima in response functions that define a line emanating from the critical point, referred to as Widom line. However, the structure of analogous state transitions in mixtures of supercritical fluids has not been determined, and it is not clear whether a Widom line can be identified for binary mixtures. Here, we present first evidence for the existence of multiple Widom lines in binary mixtures from molecular dynamics simulations. By considering mixtures of noble gases, we show that, depending on the phase behavior, mixtures transition from a liquid-like to a gas-like regime via distinctly different pathways, leading to phase relationships of surprising complexity and variety. Specifically, we show that miscible binary mixtures have behavior analogous to a pure fluid and the supercritical state space is characterized by a single liquid-gas transition. In contrast, immiscible binary mixture undergo a phase separation in which the clusters transition separately at different temperatures, resulting in multiple distinct Widom lines. The presence of this unique transition behavior emphasizes the complexity of the supercritical state to be expected in high-order mixtures of practical relevance.

Composition, distribution, and potential toxicity of organochlorine mixtures in bed sediments of streams

USGS Publications Warehouse

Phillips, Patrick J.; Nowell, Lisa H.; Gilliom, Robert J.; Nakagaki, Naomi; Murray, Karen; VanAlstyne, Carolyn

2010-01-01

Mixtures of organochlorine compounds have the potential for additive or interactive toxicity to organisms exposed in the stream. This study uses a variety of methods to identify mixtures and a modified concentration-addition approach to estimate their potential toxicity at 845 stream sites across the United States sampled between 1992 and 2001 for organochlorine pesticides and polychlorinated biphenyls (PCBs) in bed sediment. Principal-component (PC) analysis identified five PCs that account for 77% of the total variance in 14 organochlorine compounds in the original dataset. The five PCs represent: (1) chlordane-related compounds and dieldrin; (2) p,p′-DDT and its degradates; (3) o,p′-DDT and its degradates; (4) the pesticide degradates oxychlordane and heptachlor epoxide; and (5) PCBs. The PC analysis grouped compounds that have similar chemical structure (such as parent compound and degradate), common origin (in the same technical pesticide mixture), and(or) similar relation of concentrations to land use. For example, the highest concentrations of chlordane compounds and dieldrin occurred at urban sites, reflecting past use of parent pesticides for termite control. Two approaches to characterizing mixtures—PC-based mixtures and unique mixtures—were applied to all 299 samples with a detection of two or more organochlorine compounds. PC-based mixtures are defined by the presence (in the sample) of one or more compounds associated with that PC. Unique mixtures are defined as a specific combination of two or more compounds detected in a sample, regardless of how many other compounds were also detected in that sample. The simplest PC-based mixtures (containing compounds from 1 or 2 PCs) commonly occurred in a variety of land use settings. Complex mixtures (containing compounds from 3 or more PCs) were most common in samples from urban and mixed/urban sites, especially in the Northeast, reflecting high concentrations of multiple chlordane, dieldrin, DDT-related compounds, and(or) PCBs. The most commonly occurring unique mixture (p,p′-DDE, p,p′-DDD) occurred in both simple and complex PC-based mixtures, and at both urban and agricultural sites. Mean Probable Effect Concentration Quotients (PEC-Q) values, which estimate the potential toxicity of organochlorine contaminant mixtures, were highest for complex mixtures. Mean PEC-Q values were highest for urban sites in the Northeast, followed by mixed/urban sites in the Northeast and agricultural sites in cotton growing areas. These results demonstrate that the PEC-Q approach can be used in combination with PC-based and unique mixture analyses to relate potential aquatic toxicity of contaminant mixtures to mixture complexity, land use, and other surrogates for contaminant sources.

Bioactive and biocompatible pieces of HA/sol-gel glass mixtures obtained by the gel-casting method.

PubMed

Padilla, S; Sánchez-Salcedo, S; Vallet-Regí, M

2005-10-01

Hydroxyapatite (HA)/glass mixtures have shown a faster bioactive behaviour than HA itself. On the other hand, the gel-casting method is a simple and reproducible colloidal method to produce ceramic pieces with complex shapes. In this work, pieces of HA/glass mixtures were prepared by the gel-casting method. A study for obtaining concentrated slurries of these mixtures is reported; the bioactivity and biocompatibility of the obtained pieces have been studied also. The influence of pH, dispersant concentration, the content and milling of glass, and the way to prepare the suspensions were investigated. The lowest viscosity and better rheological properties were achieved with the lowest glass content, when the glass was added after the dispersion of the HA powder and when the glass was not milled after calcination. Fluid suspensions with a high solid content (50 vol.%) could be prepared and well-shaped pieces were obtained from these slurries. These pieces showed in vitro bioactive behavior in simulated body fluid; additionally, the proliferation and spreading assays with osteoblastic cells (HOS) showed that the pieces are biocompatible. The results obtained indicate that the gel-casting of HA/glass mixtures produces bioactive and biocompatible pieces with the required shapes. Therefore, these materials could be good candidates for clinical applications and scaffolds for tissue engineering. (c) 2005 Wiley Periodicals, Inc.

Analysis of the improvement of selenite retention in smectite by adding alumina nanoparticles.

PubMed

Mayordomo, Natalia; Alonso, Ursula; Missana, Tiziana

2016-12-01

Smectite clay is used as barrier for hazardous waste retention and confinement. It is a powerful material to retain cations, but less effective for retaining anionic species like selenite. This study shows that the addition of a small percentage of γ-Al 2 O 3 nanoparticles to smectite significantly improves selenite sorption. γ-Al 2 O 3 nanoparticles provide high surface area and positively charged surface sites within a wide range of pH, since their point of zero charge is at pH8-9. An addition of 20wt% of γ-Al 2 O 3 to smectite is sufficient to approach the sorption capacity of pure alumina. To analyze the sorption behavior of the smectite/oxide mixtures, a nonelectrostatic surface complexation model was considered, accounting for the surface complexation of HSeO 3 - and SeO 3 2- , the anion competition, and the formation of surface ternary complexes with major cations present in the solution. Selenite sorption in mixtures was satisfactorily described with the surface parameters and complexation constants defined for the pure systems, accounting only for the mixture weight fractions. Sorption in mixtures was additive despite the particle heteroaggregation observed in previous stability studies carried out on smectite/γ-Al 2 O 3 mixtures. Copyright © 2016 Elsevier B.V. All rights reserved.

Mathematical biodescriptors of proteomics maps: background and applications.

PubMed

Basak, Subhash C; Gute, Brian D

2008-05-01

This article reviews recent developments in the formulation and application of biodescriptors to characterize proteomics maps. Such biodescriptors can be derived by applying techniques from discrete mathematics (graph theory, linear algebra and information theory). This review focuses on the development of biodescriptors for proteomics maps derived from 2D gel electrophoresis. Preliminary results demonstrated that such descriptors have a reasonable ability to differentiate between proteomics patterns that result from exposure to closely related individual chemicals and complex mixtures, such as the jet fuel JP-8. Further research is required to evaluate the utility of these proteomics-based biodescriptors for drug discovery and predictive toxicology.

Proteomics-based compositional analysis of complex cellulase-hemicellulase mixtures.

PubMed

Chundawat, Shishir P S; Lipton, Mary S; Purvine, Samuel O; Uppugundla, Nirmal; Gao, Dahai; Balan, Venkatesh; Dale, Bruce E

2011-10-07

Efficient deconstruction of cellulosic biomass to fermentable sugars for fuel and chemical production is accomplished by a complex mixture of cellulases, hemicellulases, and accessory enzymes (e.g., >50 extracellular proteins). Cellulolytic enzyme mixtures, produced industrially mostly using fungi like Trichoderma reesei, are poorly characterized in terms of their protein composition and its correlation to hydrolytic activity on cellulosic biomass. The secretomes of commercial glycosyl hydrolase-producing microbes was explored using a proteomics approach with high-throughput quantification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Here, we show that proteomics-based spectral counting approach is a reasonably accurate and rapid analytical technique that can be used to determine protein composition of complex glycosyl hydrolase mixtures that also correlates with the specific activity of individual enzymes present within the mixture. For example, a strong linear correlation was seen between Avicelase activity and total cellobiohydrolase content. Reliable, quantitative and cheaper analytical methods that provide insight into the cellulosic biomass degrading fungal and bacterial secretomes would lead to further improvements toward commercialization of plant biomass-derived fuels and chemicals.

The Blue-Shift of Photoluminescence Spectra of Zinc Complexes of 8-Hydroxyquinoline by Addition of ZnO Nanoparticles

NASA Astrophysics Data System (ADS)

Keshmiri, Laleh; Elahi, Seyed Mohammad; Jafari, Mohammad Reza; Jafari, Fatemeh; Parhizgar, Sara Sadat

2018-02-01

In this research, an organo-metallic complex based on zinc ions (Znq2), which can be used in organic light-emitting diodes, was investigated. Nanoparticles of ZnO were produced and added to the Znq2 complex. By means of x-ray diffraction, the structure of Znq2 complex and ZnO nanoparticles and the energy levels of them were determined from cyclic-voltammetry analysis. From thermal gravimetric studies, it was found that the complexes have a high thermal stability in the air atmosphere. The purity of samples was confirmed by Fourier transform infrared spectroscopy. The maximum intensity of the photoluminescence spectrum of Znq2 occurred at 565 nm and showed a blue shift to 511 nm by adding ZnO nanoparticles to the Znq2 complex. The optical and electrical properties of the Znq2 and the mixture of Znq2 and ZnO nano powders were studied in order to find any possible applications in organic light emitting devices.

Exploring the Fate of Nitrogen Heterocycles in Complex Prebiotic Mixtures

NASA Technical Reports Server (NTRS)

Smith, Karen E.; Callahan, Michael P.; Cleaves, Henderson J.; Dworkin, Jason P.; House, Christopher H.

2011-01-01

A long standing question in the field of prebiotic chemistry is the origin of the genetic macromolecules DNA and RNA. DNA and RNA have very complex structures with repeating subunits of nucleotides, which are composed of nucleobases (nitrogen heterocycles) connected to sugar-phosphate. Due to the instability of some nucleobases (e.g. cytosine), difficulty of synthesis and instability of D-ribose, and the likely scarcity of polyphosphates necessary for the modern nucleotides, alternative nucleotides have been proposed for constructing the first genetic material. Thus, we have begun to investigate the chemistry of nitrogen heterocycles in plausible, complex prebiotic mixtures in an effort to identify robust reactions and potential alternative nucleotides. We have taken a complex prebiotic mixture produced by a spark discharge acting on a gas mixture of N2, CO2, CH4, and H2, and reacted it with four nitrogen heterocycles: uracil, 5-hydroxymethyluracil, guanine, and isoxanthopterin (2-amino-4,7-dihydroxypteridine). The products of the reaction between the spark mixture and each nitrogen heterocycle were characterized by liquid chromatography coupled to UV spectroscopy and Orbitrap mass spectrometry. We found that the reaction between the spark mixtUl'e and isoxanthopterin formed one major product, which was a cyanide adduct. 5-hydroxymethyluracil also reacted with the spark mixture to form a cyanide adduct, uracil-5-acetonitrile, which has been synthesized previously by reacting HCN with S-hydroxymethyluracil. Unlike isoxanthopterin, the chromatogram of the 5-hydroxymethyluracil reaction was much more complex with multiple products including spark-modified dimers. Additionally, we observed that HMU readily self-polymerizes in solution to a variety of oligomers consistent with those suggested by Cleaves. Guanine and uracil, the biological nucleobases, did not react with the spark mixture, even at high temperature (100 C). This suggests that there are alternative nucleobases which are more reactive under prebiotic conditions and may have been involved in producing precursor nucleotides.

Fast 2D NMR Spectroscopy for In vivo Monitoring of Bacterial Metabolism in Complex Mixtures.

PubMed

Dass, Rupashree; Grudzia Ż, Katarzyna; Ishikawa, Takao; Nowakowski, Michał; Dȩbowska, Renata; Kazimierczuk, Krzysztof

2017-01-01

The biological toolbox is full of techniques developed originally for analytical chemistry. Among them, spectroscopic experiments are very important source of atomic-level structural information. Nuclear magnetic resonance (NMR) spectroscopy, although very advanced in chemical and biophysical applications, has been used in microbiology only in a limited manner. So far, mostly one-dimensional 1 H experiments have been reported in studies of bacterial metabolism monitored in situ . However, low spectral resolution and limited information on molecular topology limits the usability of these methods. These problems are particularly evident in the case of complex mixtures, where spectral peaks originating from many compounds overlap and make the interpretation of changes in a spectrum difficult or even impossible. Often a suite of two-dimensional (2D) NMR experiments is used to improve resolution and extract structural information from internuclear correlations. However, for dynamically changing sample, like bacterial culture, the time-consuming sampling of so-called indirect time dimensions in 2D experiments is inefficient. Here, we propose the technique known from analytical chemistry and structural biology of proteins, i.e., time-resolved non-uniform sampling. The method allows application of 2D (and multi-D) experiments in the case of quickly varying samples. The indirect dimension here is sparsely sampled resulting in significant reduction of experimental time. Compared to conventional approach based on a series of 1D measurements, this method provides extraordinary resolution and is a real-time approach to process monitoring. In this study, we demonstrate the usability of the method on a sample of Escherichia coli culture affected by ampicillin and on a sample of Propionibacterium acnes , an acne causing bacterium, mixed with a dose of face tonic, which is a complicated, multi-component mixture providing complex NMR spectrum. Through our experiments we determine the exact concentration and time at which the anti-bacterial agents affect the bacterial metabolism. We show, that it is worth to extend the NMR toolbox for microbiology by including techniques of 2D z-TOCSY, for total "fingerprinting" of a sample and 2D 13 C-edited HSQC to monitor changes in concentration of metabolites in selected metabolic pathways.

ORD'S FOUR LAB STUDY: TOXICOLOGICAL AND CHEMICAL EVALUATION OF COMPLEX MIXTURES OF DRINKING WATER DISINFECTION BY-PRODUCTS

EPA Science Inventory

Disinfectants used in the production of drinking water react with naturally occurring organic and inorganic material in the source water to produce disinfection by-products (DBPs). Humans are exposed daily to a complex mixture of DBPs via oral, dermal, and inhalation routes. To ...

ION COMPOSITION ELUCIDATION (ICE): A HIGH RESOLUTION MASS SPECTROMETRIC TECHNIQUE FOR IDENTIFYING COMPOUNDS IN COMPLEX MIXTURES

EPA Science Inventory

When tentatively identifying compounds in complex mixtures using mass spectral libraries, multiple matches or no plausible matches due to a high level of chemical noise or interferences can occur. Worse yet, most analytes are not in the libraries. In each case, Ion Composition El...

Fast sodium ionic conduction in Na2B10H10-Na2B12H12 pseudo-binary complex hydride and application to a bulk-type all-solid-state battery

NASA Astrophysics Data System (ADS)

Yoshida, Koji; Sato, Toyoto; Unemoto, Atsushi; Matsuo, Motoaki; Ikeshoji, Tamio; Udovic, Terrence J.; Orimo, Shin-ichi

2017-03-01

In the present work, we developed highly sodium-ion conductive Na2B10H10-Na2B12H12 pseudo-binary complex hydride via mechanically ball-milling admixtures of the pure Na2B10H10 and Na2B12H12 components. Both of these components show a monoclinic phase at room temperature, but ball-milled mixtures partially stabilized highly ion-conductive, disordered cubic phases, whose fraction and favored structural symmetry (body-centered cubic or face-centered cubic) depended on the conditions of mechanical ball-milling and molar ratio of the component compounds. First-principles molecular-dynamics simulations demonstrated that the total energy of the closo-borane mixtures and pure materials is quite close, helping to explain the observed stabilization of the mixed compounds. The ionic conductivity of the closo-borane mixtures appeared to be correlated with the fraction of the body-centered-cubic phase, exhibiting a maximum at a molar ratio of Na2B10H10:Na2B12H12 = 1:3. A conductivity as high as log(σ/S cm-1) = -3.5 was observed for the above ratio at 303 K, being approximately 2-3 orders of magnitude higher than that of either pure material. A bulk-type all-solid-state sodium-ion battery with a closo-borane-mixture electrolyte, sodium-metal negative-electrode, and TiS2 positive-electrode demonstrated a high specific capacity, close to the theoretical value of NaTiS2 formation and a stable discharge/charge cycling for at least eleven cycles, with a high discharge capacity retention ratio above 91% from the second cycle.

Optical trapping for complex fluid microfluidics

NASA Astrophysics Data System (ADS)

Vestad, Tor; Oakey, John; Marr, David W. M.

2004-10-01

Many proposed applications of microfluidics involve the manipulation of complex fluid mixtures such as blood or bacterial suspensions. To sort and handle the constituent particles within these suspensions, we have developed a miniaturized automated cell sorter using optical traps. This microfluidic cell sorter offers the potential to perform chip-top microbiology more rapidly and with less associated hardware and preparation time than other techniques currently available. To realize the potential of this technology in practical clinical and consumer lab-on-a-chip devices however, microscale control of not only particulates but also the fluid phase must be achieved. To address this, we have developed a mechanical fluid control scheme that integrates well with our optical separations approach. We demonstrate here a combined technique, one that employs both mechanical actuation and optical trapping for the precise control of complex suspensions. This approach enables both cell and particle separations as well as the subsequent fluid control required for the completion of complex analyses.

Real-time monitoring of enzyme-free strand displacement cascades by colorimetric assays.

PubMed

Duan, Ruixue; Wang, Boya; Hong, Fan; Zhang, Tianchi; Jia, Yongmei; Huang, Jiayu; Hakeem, Abdul; Liu, Nannan; Lou, Xiaoding; Xia, Fan

2015-03-19

The enzyme-free toehold-mediated strand displacement reaction has shown potential for building programmable DNA circuits, biosensors, molecular machines and chemical reaction networks. Here we report a simple colorimetric method using gold nanoparticles as signal generators for the real-time detection of the product of the strand displacement cascade. During the process the assembled gold nanoparticles can be separated, resulting in a color change of the solution. This assay can also be applied in complex mixtures, fetal bovine serum, and to detect single-base mismatches. These results suggest that this method could be of general utility to monitor more complex enzyme-free strand displacement reaction-based programmable systems or for further low-cost diagnostic applications.

Lifetimes and stabilities of familiar explosives molecular adduct complexes during ion mobility measurements

PubMed Central

McKenzie, Alan; DeBord, John Daniel; Ridgeway, Mark; Park, Melvin; Eiceman, Gary; Fernandez-Lima, Francisco

2015-01-01

Trapped ion mobility spectrometry coupled to mass spectrometry (TIMS-MS) was utilized for the separation and identification of familiar explosives in complex mixtures. For the first time, molecular adduct complex lifetimes, relative stability, binding energies and candidate structures are reported for familiar explosives. Experimental and theoretical results showed that the adduct size and reactivity, complex binding energy and the explosive structure tailors the stability of the molecular adduct complex. TIMS flexibility to adapt the mobility separation as a function of the molecular adduct complex stability (i.e., short or long IMS experiments / low or high IMS resolution) permits targeted measurements of explosives in complex mixtures with higher confidence levels. PMID:26153567

Polymer gel electrolytes for application in aluminum deposition and rechargeable aluminum ion batteries

DOE PAGES

Sun, Xiao -Guang; Fang, Youxing; Jiang, Xueguang; ...

2015-10-22

Polymer gel electrolyte using AlCl3 complexed acrylamide as functional monomer and ionic liquids based on acidic mixture of 1-ethyl-3-methylimidazolium chloride (EMImCl) and AlCl 3 as plasticizer has been successfully prepared for the first time by free radical polymerization. Aluminum deposition is successfully obtained with a polymer gel membrane contianing 80 wt% ionic liquid. As a result, the polymer gel membranes are also good candidates for rechargeable aluminum ion batteries.

A Study on Reactive Ion Etching of Barium Strontium Titanate Films Using Mixtures of Argon (Ar), Carbon Tetrafluoride (CF4), and Sulfur Hexafluoride (SF6)

DTIC Science & Technology

2014-07-01

BST) is a complex oxide material with ferroic properties which has been considered for applications ranging from non-volatile memory to microwave...utilizing self-aligned etching to create metal-insulator-metal (MIM) varactors . As part of this method we employed reactive ion etching (RIE) to remove BST...of BST removed vs. etch time for Ar:SF6. .........................................................4 Figure 3. SEM cross-section of varactor showing

Development of a Magnetic Microbead Affinity Selection Screen (MagMASS) Using Mass Spectrometry for Ligands to the Retinoid X Receptor-α

NASA Astrophysics Data System (ADS)

Rush, Michael D.; Walker, Elisabeth M.; Prehna, Gerd; Burton, Tristesse; van Breemen, Richard B.

2017-03-01

To overcome limiting factors in mass spectrometry-based screening methods such as automation while still facilitating the screening of complex mixtures such as botanical extracts, magnetic microbead affinity selection screening (MagMASS) was developed. The screening process involves immobilization of a target protein on a magnetic microbead using a variety of possible chemistries, incubation with mixtures of molecules containing possible ligands, a washing step that removes non-bound compounds while a magnetic field retains the beads in the microtiter well, and an organic solvent release step followed by LC-MS analysis. Using retinoid X receptor-α (RXRα) as an example, which is a nuclear receptor and target for anti-inflammation therapy as well as cancer treatment and prevention, a MagMASS assay was developed and compared with an existing screening assay, pulsed ultrafiltration (PUF)-MS. Optimization of MagMASS involved evaluation of multiple protein constructs and several magnetic bead immobilization chemistries. The full-length RXRα construct immobilized with amylose beads provided optimum results. Additional enhancements of MagMASS were the application of 96-well plates to enable automation, use of UHPLC instead of HPLC for faster MS analyses, and application of metabolomics software for faster, automated data analysis. Performance of MagMASS was demonstrated using mixtures of synthetic compounds and known ligands spiked into botanical extracts.

Statistical Modeling of Single Target Cell Encapsulation

PubMed Central

Moon, SangJun; Ceyhan, Elvan; Gurkan, Umut Atakan; Demirci, Utkan

2011-01-01

High throughput drop-on-demand systems for separation and encapsulation of individual target cells from heterogeneous mixtures of multiple cell types is an emerging method in biotechnology that has broad applications in tissue engineering and regenerative medicine, genomics, and cryobiology. However, cell encapsulation in droplets is a random process that is hard to control. Statistical models can provide an understanding of the underlying processes and estimation of the relevant parameters, and enable reliable and repeatable control over the encapsulation of cells in droplets during the isolation process with high confidence level. We have modeled and experimentally verified a microdroplet-based cell encapsulation process for various combinations of cell loading and target cell concentrations. Here, we explain theoretically and validate experimentally a model to isolate and pattern single target cells from heterogeneous mixtures without using complex peripheral systems. PMID:21814548

Stationary-phase optimized selectivity liquid chromatography: development of a linear gradient prediction algorithm.

PubMed

De Beer, Maarten; Lynen, Fréderic; Chen, Kai; Ferguson, Paul; Hanna-Brown, Melissa; Sandra, Pat

2010-03-01

Stationary-phase optimized selectivity liquid chromatography (SOS-LC) is a tool in reversed-phase LC (RP-LC) to optimize the selectivity for a given separation by combining stationary phases in a multisegment column. The presently (commercially) available SOS-LC optimization procedure and algorithm are only applicable to isocratic analyses. Step gradient SOS-LC has been developed, but this is still not very elegant for the analysis of complex mixtures composed of components covering a broad hydrophobicity range. A linear gradient prediction algorithm has been developed allowing one to apply SOS-LC as a generic RP-LC optimization method. The algorithm allows operation in isocratic, stepwise, and linear gradient run modes. The features of SOS-LC in the linear gradient mode are demonstrated by means of a mixture of 13 steroids, whereby baseline separation is predicted and experimentally demonstrated.

Environment applications for ion mobility spectrometry

NASA Technical Reports Server (NTRS)

Ritchie, Robert K.; Rudolph, Andreas

1995-01-01

The detection of environmentally important polychlorinated aromatics by ion mobility spectrometry (IMS) was investigated. Single polychlorinated biphenyl (PCB) isomers (congeners) having five or more chlorine atoms were reliably detected in isooctane solution at levels of 35 ng with a Barringer IONSCAN ion mobility spectrometer operating in negative mode; limits of detection (LOD) were extrapolated to be in the low ng region. Mixtures of up to four PCB congeners, showing characteristic multiple peaks, and complex commercial mixtures of PCBs (Aroclors) were also detected. Detection of Aroclors in transformer oil was suppressed by the presence of the antioxidant BHT (2,6-di-t-butyl4-methylphenol) in the oil. The wood preservative pentachlorophenol (PCP) was easily detected in recycled wood shavings at levels of 52 ppm with the IONSCAN; the LOD was extrapolated to be in the low ppm region.

Gaussian mixtures on tensor fields for segmentation: applications to medical imaging.

PubMed

de Luis-García, Rodrigo; Westin, Carl-Fredrik; Alberola-López, Carlos

2011-01-01

In this paper, we introduce a new approach for tensor field segmentation based on the definition of mixtures of Gaussians on tensors as a statistical model. Working over the well-known Geodesic Active Regions segmentation framework, this scheme presents several interesting advantages. First, it yields a more flexible model than the use of a single Gaussian distribution, which enables the method to better adapt to the complexity of the data. Second, it can work directly on tensor-valued images or, through a parallel scheme that processes independently the intensity and the local structure tensor, on scalar textured images. Two different applications have been considered to show the suitability of the proposed method for medical imaging segmentation. First, we address DT-MRI segmentation on a dataset of 32 volumes, showing a successful segmentation of the corpus callosum and favourable comparisons with related approaches in the literature. Second, the segmentation of bones from hand radiographs is studied, and a complete automatic-semiautomatic approach has been developed that makes use of anatomical prior knowledge to produce accurate segmentation results. Copyright © 2010 Elsevier Ltd. All rights reserved.

Comprehensive evaluation of direct injection mass spectrometry for the quantitative profiling of volatiles in food samples

PubMed Central

2016-01-01

Although qualitative strategies based on direct injection mass spectrometry (DIMS) have recently emerged as an alternative for the rapid classification of food samples, the potential of these approaches in quantitative tasks has scarcely been addressed to date. In this paper, the applicability of different multivariate regression procedures to data collected by DIMS from simulated mixtures has been evaluated. The most relevant factors affecting quantitation, such as random noise, the number of calibration samples, type of validation, mixture complexity and similarity of mass spectra, were also considered and comprehensively discussed. Based on the conclusions drawn from simulated data, and as an example of application, experimental mass spectral fingerprints collected by direct thermal desorption coupled to mass spectrometry were used for the quantitation of major volatiles in Thymus zygis subsp. zygis chemotypes. The results obtained, validated with the direct thermal desorption coupled to gas chromatography–mass spectrometry method here used as a reference, show the potential of DIMS approaches for the fast and precise quantitative profiling of volatiles in foods. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644978

Overview of online two-dimensional liquid chromatography based on cell membrane chromatography for screening target components from traditional Chinese medicines.

PubMed

Muhammad, Saqib; Han, Shengli; Xie, Xiaoyu; Wang, Sicen; Aziz, Muhammad Majid

2017-01-01

Cell membrane chromatography is a simple, specific, and time-saving technique for studying drug-receptor interactions, screening of active components from complex mixtures, and quality control of traditional Chinese medicines. However, the short column life, low sensitivity, low column efficiency (so cannot resolve satisfactorily mixture of compounds), low peak capacity, and inefficient in structure identification were bottleneck in its application. Combinations of cell membrane chromatography with multidimensional chromatography such as two-dimensional liquid chromatography and high sensitivity detectors like mass have significantly reduced many of the above-mentioned shortcomings. This paper provides an overview of the current advances in online two-dimensional-based cell membrane chromatography for screening target components from traditional Chinese medicines with particular emphasis on the instrumentation, preparation of cell membrane stationary phase, advantages, and disadvantages compared to alternative approaches. The last section of the review summarizes the applications of the online two-dimensional high-performance liquid chromatography based cell membrane chromatography reported since its emergence to date (2010-June 2016). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Application of complex macromolecular architectures for advanced microelectronic materials.

PubMed

Hedrick, James L; Magbitang, Teddie; Connor, Eric F; Glauser, Thierry; Volksen, Willi; Hawker, Craig J; Lee, Victor Y; Miller, Robert D

2002-08-02

The distinctive features of well-defined, three-dimensional macromolecules with topologies designed to enhance solubility and amplify end-group functionality facilitated nanophase morphologies in mixtures with organosilicates and ultimately nanoporous organosilicate networks. Novel macromolecular architectures including dendritic and star-shaped polymers and organic nanoparticles were prepared by a modular approach from several libraries of building blocks including various generations of dendritic initiators and dendrons, selectively placed to amplify functionality and/or arm number, coupled with living polymerization techniques. Mixtures of an organosilicate and the macromolecular template were deposited, cured, and the phase separation of the organic component, organized the vitrifying organosilicate into nanostructures. Removal of the sacrificial macromolecular template, also denoted as porogen, by thermolysis, yielded the desired nanoporous organosilicate, and the size scale of phase separation was strongly dependent on the chain topology. These materials were designed for use as interlayer, ultra-low dielectric insulators for on-chip applications with dielectric constant values as low as 1.5. The porogen design, chemistry and role of polymer architecture on hybrid and pore morphology will be emphasized.

Accelerated High-Resolution Differential Ion Mobility Separations Using Hydrogen

PubMed Central

Shvartsburg, Alexandre A.; Smith, Richard D.

2011-01-01

The resolving power of differential ion mobility spectrometry (FAIMS) was dramatically increased recently by carrier gases comprising up to 75% He or various vapors, enabling many new applications. However, the need for resolution of complex mixtures is virtually open-ended and many topical analyses demand yet finer separations. Also, the resolving power gains are often at the expense of speed, in particular making high-resolution FAIMS incompatible with online liquid-phase separations. Here, we report FAIMS employing hydrogen, specifically in mixtures with N2 containing up to 90% H2. Such compositions raise the mobilities of all ions and thus the resolving power beyond that previously feasible, while avoiding the electrical breakdown inevitable in He-rich mixtures. The increases in resolving power and ensuing peak resolution are especially significant at H2 fractions above ~50%. Higher resolution can be exchanged for acceleration of the analyses by up to ~4 times, at least. For more mobile species such as multiply-charged peptides, this exchange is presently forced by the constraints of existing FAIMS devices, but future designs optimized for H2 should consistently improve resolution for all analytes. PMID:22074292

NAPL source zone depletion model and its application to railroad-tank-car spills.

PubMed

Marruffo, Amanda; Yoon, Hongkyu; Schaeffer, David J; Barkan, Christopher P L; Saat, Mohd Rapik; Werth, Charles J

2012-01-01

We developed a new semi-analytical source zone depletion model (SZDM) for multicomponent light nonaqueous phase liquids (LNAPLs) and incorporated this into an existing screening model for estimating cleanup times for chemical spills from railroad tank cars that previously considered only single-component LNAPLs. Results from the SZDM compare favorably to those from a three-dimensional numerical model, and from another semi-analytical model that does not consider source zone depletion. The model was used to evaluate groundwater contamination and cleanup times for four complex mixtures of concern in the railroad industry. Among the petroleum hydrocarbon mixtures considered, the cleanup time of diesel fuel was much longer than E95, gasoline, and crude oil. This is mainly due to the high fraction of low solubility components in diesel fuel. The results demonstrate that the updated screening model with the newly developed SZDM is computationally efficient, and provides valuable comparisons of cleanup times that can be used in assessing the health and financial risk associated with chemical mixture spills from railroad-tank-car accidents. © 2011, The Author(s). Ground Water © 2011, National Ground Water Association.

The application of computer modeling to health effect research

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

Yang, R.S.H.

1996-12-31

In the United States, estimates show that more than 30,000 hazardous waste disposal sites exist, not including military installations, U.S. Department of Energy nuclear facilities, and hundreds and thousands of underground fuel storage tanks; these sites undoubtedly have their own respective hazardous waste chemical problems. When so many sites contain hazardous chemicals, how does one study the health effects of the chemicals at these sites? There could be many different answers, but none would be perfect. For an area as complex and difficult as the study of chemical mixtures associated with hazardous waste disposal sites, there are no perfect approachesmore » and protocols. Human exposure to chemicals, be it environmental or occupational, is rarely, if ever, limited to a single chemical. Therefore, it is essential that we consider multiple chemical effects and interactions in our risk assessment process. Systematic toxicity testing of chemical mixtures in the environment or workplace that uses conventional toxicology methodologies is highly impractical because of the immense numbers of mixtures involved. For example, about 600,000 chemicals are being used in our society. Just considering binary chemical mixtures, this means that there could be 600,000 x 599,999/2 = 359,999,400,000 pairs of chemicals. Assuming that only one in a million of these pairs of chemicals acts synergistically or has other toxicologic interactions, there would still be 359,999 binary chemical mixtures possessing toxicologic interactions. Moreover, toxicologic interactions undoubtedly exist among chemical mixtures with three or more component chemicals; the number of possible combinations for these latter mixtures is almost infinite. These are astronomically large numbers with respect to systematic toxicity testing. 22 refs., 5 figs., 1 tab.« less

Toxicity of natural mixtures of organic pollutants in temperate and polar marine phytoplankton.

PubMed

Echeveste, Pedro; Galbán-Malagón, Cristóbal; Dachs, Jordi; Berrojalbiz, Naiara; Agustí, Susana

2016-11-15

Semivolatile and persistent organic pollutants (POPs) undergo atmospheric transport before being deposited to the oceans, where they partition to phytoplankton organic matter. The goal of this study was to determine the toxicity of naturally occurring complex mixtures of organic pollutants to temperate and polar phytoplankton communities from the Mediterranean Sea, the North East (NE) Atlantic, and Southern Oceans. The cell abundance of the different phytoplankton groups, chlorophyll a concentrations, viability of the cells, and growth and decay constants were monitored in response to addition of a range of concentrations of mixtures of organic pollutants obtained from seawater extracts. Almost all of the phytoplankton groups were significantly affected by the complex mixtures of non-polar and polar organic pollutants, with toxicity being greater for these mixtures than for single POPs or simple POP mixtures. Cocktails' toxicity arose at concentrations as low as tenfold the field oceanic levels, probably due to a higher chemical activity of the mixture than of simple POPs mixtures. Overall, smaller cells were the most affected, although Mediterranean picophytoplankton was significantly more tolerant to non-polar POPs than picophytoplankton from the Atlantic Ocean or the Bellingshausen Sea microphytoplankton. Copyright © 2016 Elsevier B.V. All rights reserved.

SELECTIVE CHANGES IN BRAIN PROTEIN KINASE C ISOFORMS FOLLOWING DEVELOPMENTAL EXPOSURE TO A PCB MIXTURE.

EPA Science Inventory

Introduction
Polychlorinated biphenyls (PCBs) offer a unique model to understand the major issues related to complex environmental mixtures. These environmental pollutants are ubiquitous, persistent, bioaccumulate in human body through the food chain, and exist as mixtures of ...

Method of analysis of polymerizable monomeric species in a complex mixture

DOEpatents

Hermes, Robert E

2014-03-18

Method of selective quantitation of a polymerizable monomeric species in a well spacer fluid, said method comprising the steps of adding at least one solvent having a refractive index of less than about 1.33 to a sample of the complex mixture to produce a solvent phase, and measuring the refractive index of the solvent phase.

NATURE OF UNRESOLVED COMPLEX MIXTURE IN SIZE-DISTRIBUTED EMISSIONS FROM RESIDENTIAL WOOD COMBUSTION AS MEASURED BY THERMAL DESORPTION-GAS CHROMATOGRAPHY-MASS SPECTROMETRY

EPA Science Inventory

In this study, the unresolved complex mixture (UCM) in size resolved fine aerosol emissions from residential wood combustion (RWC) is examined. The aerosols are sorted by size in an electrical low-pressure impactor (ELPI) and subsequently analyzed by thermal desorbtion/gas chroma...

76 FR 31824 - Chemical Mixtures Containing Listed Forms of Phosphorus and Change in Application Process

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

... 1117-AA66 Chemical Mixtures Containing Listed Forms of Phosphorus and Change in Application Process... establish those chemical mixtures containing red phosphorus or hypophosphorous acid and its salts (hereinafter ``regulated phosphorus'') that shall automatically qualify for exemption from the [[Page 31825...

Process for removing cadmium from scrap metal

DOEpatents

Kronberg, J.W.

1995-04-11

A process is described for the recovery of a metal, in particular, cadmium contained in scrap, in a stable form. The process comprises the steps of mixing the cadmium-containing scrap with an ammonium carbonate solution, preferably at least a stoichiometric amount of ammonium carbonate, and/or free ammonia, and an oxidizing agent to form a first mixture so that the cadmium will react with the ammonium carbonate to form a water-soluble ammine complex; evaporating the first mixture so that ammine complex dissociates from the first mixture leaving carbonate ions to react with the cadmium and form a second mixture that includes cadmium carbonate; optionally adding water to the second mixture to form a third mixture; adjusting the pH of the third mixture to the acid range whereby the cadmium carbonate will dissolve; and adding at least a stoichiometric amount of sulfide, preferably in the form of hydrogen sulfide or an aqueous ammonium sulfide solution, to the third mixture to precipitate cadmium sulfide. This mixture of sulfide is then preferably digested by heating to facilitate precipitation of large particles of cadmium sulfide. The scrap may be divided by shredding or breaking up to expose additional surface area. Finally, the precipitated cadmium sulfide can be mixed with glass formers and vitrified for permanent disposal. 2 figures.

Process for removing cadmium from scrap metal

DOEpatents

Kronberg, J.W.

1994-01-01

A process for the recovery of a metal, in particular, cadmium contained in scrap, in a stable form. The process comprises the steps of mixing the cadmium-containing scrap with an ammonium carbonate solution, preferably at least a stoichiometric amount of ammonium carbonate, and/or free ammonia, and an oxidizing agent to form a first mixture so that the cadmium will react with the ammonium carbonate to form a water-soluble ammine complex; evaporating the first mixture so that ammine complex dissociates from the first mixture leaving carbonate ions to react with the cadmium and form a second mixture that includes cadmium carbonate; optionally adding water to the second mixture to form a third mixture; adjusting the pH of the third mixture to the acid range whereby the cadmium carbonate will dissolve; and adding at least a stoichiometric amount of sulfide, preferably in the form of hydrogen sulfide or an aqueous ammonium sulfide solution, to the third mixture to precipitate cadmium sulfide. This mixture of sulfide is then preferably digested by heating to facilitate precipitation of large particles of cadmium sulfide. The scrap may be divided by shredding or breaking up to exposure additional surface area. Finally, the precipitated cadmium sulfide can be mixed with glass formers and vitrified for permanent disposal.

Process for removing cadmium from scrap metal

DOEpatents

Kronberg, James W.

1995-01-01

A process for the recovery of a metal, in particular, cadmium contained in scrap, in a stable form. The process comprises the steps of mixing the cadmium-containing scrap with an ammonium carbonate solution, preferably at least a stoichiometric amount of ammonium carbonate, and/or free ammonia, and an oxidizing agent to form a first mixture so that the cadmium will react with the ammonium carbonate to form a water-soluble ammine complex; evaporating the first mixture so that ammine complex dissociates from the first mixture leaving carbonate ions to react with the cadmium and form a second mixture that includes cadmium carbonate; optionally adding water to the second mixture to form a third mixture; adjusting the pH of the third mixture to the acid range whereby the cadmium carbonate will dissolve; and adding at least a stoichiometric amount of sulfide, preferably in the form of hydrogen sulfide or an aqueous ammonium sulfide solution, to the third mixture to precipitate cadmium sulfide. This mixture of sulfide is then preferably digested by heating to facilitate precipitation of large particles of cadmium sulfide. The scrap may be divided by shredding or breaking up to expose additional surface area. Finally, the precipitated cadmium sulfide can be mixed with glass formers and vitrified for permanent disposal.

Quantification of acidic compounds in complex biomass-derived streams

DOE PAGES

Karp, Eric M.; Nimlos, Claire T.; Deutch, Steve; ...

2016-05-10

Biomass-derived streams that contain acidic compounds from the degradation of lignin and polysaccharides (e.g. black liquor, pyrolysis oil, pyrolytic lignin, etc.) are chemically complex solutions prone to instability and degradation during analysis, making quantification of compounds within them challenging. Here we present a robust analytical method to quantify acidic compounds in complex biomass-derived mixtures using ion exchange, sample reconstitution in pyridine and derivatization with BSTFA. The procedure is based on an earlier method originally reported for kraft black liquors and, in this work, is applied to identify and quantify a large slate of acidic compounds in corn stover derived alkalinemore » pretreatment liquor (APL) as a function of pretreatment severity. Analysis of the samples is conducted with GCxGC-TOFMS to achieve good resolution of the components within the complex mixture. The results reveal the dominant low molecular weight components and their concentrations as a function of pretreatment severity. Application of this method is also demonstrated in the context of lignin conversion technologies by applying it to track the microbial conversion of an APL substrate. Here as well excellent results are achieved, and the appearance and disappearance of compounds is observed in agreement with the known metabolic pathways of two bacteria, indicating the sample integrity was maintained throughout analysis. Finally, it is shown that this method applies more generally to lignin-rich materials by demonstrating its usefulness in analysis of pyrolysis oil and pyrolytic lignin.« less

Gallium metal affinity capture tandem mass spectrometry for the selective detection of phosphopeptides in complex mixtures

PubMed Central

Blacken, Grady R.; Sadílek, Martin; Tureček, František

2008-01-01

Metal affinity capture tandem mass spectrometry (MAC-MSMS) is evaluated in a comparative study of a lysine-derived nitrilotriacetic acid (Nα, Nα-bis-(carboxymethyl)lysine, LysNTA) and an aspartic-acid-related iminodiacetic acid (N-(4-aminobutyl)aspartic acid, AspIDA) as selective phosphopeptide detection reagents. Both LysNTA and AspIDA spontaneously form ternary complexes with GaIII and phosphorylated amino acids and phosphopeptides upon mixing in solution. Collision-induced dissociation of positive complex ions produced by electrospray produces common fragments (LysNTA + H)+ or (AspIDA + H)+ at m/z 263 and 205, respectively. MSMS precursor scans using these fragments as reporter ions allow one to selectively detect multiple charge states of phosphopeptides in mixtures. It follows from this comparative study that LysNTA is superior to AspIDA in detecting phosphopeptides, possibly because of the higher coordination number and greater stability constant for GaIII – phosphopeptide complexation of the former reagent. In a continuing development of MAC-MSMS for proteomics applications, we demonstrate its utility in a post-column reaction format. Using a simple post-column-reaction ‘T’ and syringe pump to deliver our chelating reagents, α-casein tryptic phosphopeptides can be selectively analyzed from a solution containing a twofold molar excess of bovine serum albumin. The MAC-MSMS method is shown to be superior to the commonly used neutral loss scan for the common loss of phosphoric acid. PMID:18265438

Aqueous two-phase extraction of nickel dimethylglyoximato complex and its application to spectrophotometric determination of nickel in stainless steel.

PubMed

Yoshikuni, Nobutaka; Baba, Takayuki; Tsunoda, Natsuki; Oguma, Koichi

2005-03-31

A polyethylene glycol (PEG)-based aqueous two-phase system has been established for the extraction of Ni-dimethylglyoximato complex. Appropriate amounts of PEG solution and solid (NH(4))(2)SO(4) were added to the Ni-dimethylglyoximato complex which had been formed in the presence of sodium tartrate and K(2)S(2)O(8) at pH 12 in a separatory funnel and shaken vigorously for about 1min. The mixture was allowed to stand for 10min and then the absorbance of the extracted complex in the upper PEG-rich phase was measured at 470nm. Beer's law was obeyed over the range of 0.26-2.1ppm Ni. The proposed extraction method has been applied to the determination of Ni in steel. A steel sample was decomposed with an appropriate acid mixture. An aliquot of the sample solution was taken, treated with H(3)PO(4) and most of the iron and copper were removed by hydroxide precipitation using solid BaCO(3) to control the pH of the sample solution in advance of the extraction of Ni. The analytical results obtained for Ni in steel certified reference material JSS 650-10 (The Japan Iron and Steel Federation), BCS 323 (Bureau of Analysed Samples Ltd.) and NIST SRM 361 and 362 (National Institute of Standards and Technology) were in good agreement with certified values.

Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by lipid emulsions for improved treatment of cancer

PubMed Central

Zhang, Bo; Song, Yunmei; Wang, Tianqi; Yang, Shaomei; Zhang, Jing; Liu, Yongjun; Zhang, Na; Garg, Sanjay

2017-01-01

Combinational nanomedicine is becoming a topic of much interest in cancer therapy, although its translation into the clinic remains extremely challenging. One of the main obstacles lies in the difficulty to efficiently co-deliver immiscible hydrophilic/hydrophobic drugs into tumor sites. The aim of this study was to develop co-loaded lipid emulsions (LEs) to co-deliver immiscible hydrophilic/hydrophobic drugs to improve cancer therapy and to explore the co-delivery abilities between co-loaded LEs and mixture formulation. Multiple oxaliplatin/irinotecan drug–phospholipid complexes (DPCs) were formulated. Co-loaded LEs were prepared using DPC technique to efficiently encapsulate both drugs. Co-loaded LEs exhibited uniform particle size distribution, desired stability and synchronous release profiles in both drugs. Co-loaded LEs demonstrated superior anti-tumor activity compared with the simple solution mixture and the mixture of single-loaded LEs. Furthermore, co-loaded nanocarriers could co-deliver both drugs into the same cells more efficiently and exhibited the optimized synergistic effect. These results indicate that co-loaded LEs could be a desired formulation for enhanced cancer therapy with potential application prospects. The comparison between co-loaded LEs and mixture formulation is significant for pharmaceutical designs aimed at co-delivery of multiple drugs. PMID:28435264

Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by lipid emulsions for improved treatment of cancer.

PubMed

Zhang, Bo; Song, Yunmei; Wang, Tianqi; Yang, Shaomei; Zhang, Jing; Liu, Yongjun; Zhang, Na; Garg, Sanjay

2017-01-01

Combinational nanomedicine is becoming a topic of much interest in cancer therapy, although its translation into the clinic remains extremely challenging. One of the main obstacles lies in the difficulty to efficiently co-deliver immiscible hydrophilic/hydrophobic drugs into tumor sites. The aim of this study was to develop co-loaded lipid emulsions (LEs) to co-deliver immiscible hydrophilic/hydrophobic drugs to improve cancer therapy and to explore the co-delivery abilities between co-loaded LEs and mixture formulation. Multiple oxaliplatin/irinotecan drug-phospholipid complexes (DPCs) were formulated. Co-loaded LEs were prepared using DPC technique to efficiently encapsulate both drugs. Co-loaded LEs exhibited uniform particle size distribution, desired stability and synchronous release profiles in both drugs. Co-loaded LEs demonstrated superior anti-tumor activity compared with the simple solution mixture and the mixture of single-loaded LEs. Furthermore, co-loaded nanocarriers could co-deliver both drugs into the same cells more efficiently and exhibited the optimized synergistic effect. These results indicate that co-loaded LEs could be a desired formulation for enhanced cancer therapy with potential application prospects. The comparison between co-loaded LEs and mixture formulation is significant for pharmaceutical designs aimed at co-delivery of multiple drugs.

Molecular investigation on the binding of Cd(II) by the binary mixtures of montmorillonite with two bacterial species

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

Du, Huihui; Qu, ChenChen; Liu, Jing

Bacteria and phyllosilicate commonly coexist in the natural environment, producing various bacteria–clay complexes that are capable of immobilizing heavy metals, such as cadmium, via adsorption. However, the molecular binding mechanisms of heavy metals on these complex aggregates still remain poorly understood. This study investigated Cd adsorption on Gram-positive B. subtilis, Gram-negative P. putida and their binary mixtures with montmorillonite (Mont) using the Cd K-edge x-ray absorption spectroscopy (XAS) and isothermal titration calorimetry (ITC). We observed a lower adsorptive capacity for P. putida than B. subtilis, whereas P. putida–Mont and B. subtilis–Mont mixtures showed nearly identical Cd adsorption behaviors. EXAFS fitsmore » and ITC measurements demonstrated more phosphoryl binding of Cd in P. putida. The decreased coordination of C atoms around Cd and the reduced adsorption enthalpies and entropies for the binary mixtures compared to that for individual bacteria suggested that the bidentate Cd-carboxyl complexes in pure bacteria systems were probably transformed into monodentate complexes that acted as ionic bridging structure between bacteria and motmorillonite. This study clarified the binding mechanism of Cd at the bacteria–phyllosilicate interfaces from a molecular and thermodynamic view, which has an environmental significance for predicting the chemical behavior of trace elements in complex mineral–organic systems.« less

Hidden drivers of low-dose pharmaceutical pollutant mixtures revealed by the novel GSA-QHTS screening method

PubMed Central

Rodea-Palomares, Ismael; Gonzalez-Pleiter, Miguel; Gonzalo, Soledad; Rosal, Roberto; Leganes, Francisco; Sabater, Sergi; Casellas, Maria; Muñoz-Carpena, Rafael; Fernández-Piñas, Francisca

2016-01-01

The ecological impacts of emerging pollutants such as pharmaceuticals are not well understood. The lack of experimental approaches for the identification of pollutant effects in realistic settings (that is, low doses, complex mixtures, and variable environmental conditions) supports the widespread perception that these effects are often unpredictable. To address this, we developed a novel screening method (GSA-QHTS) that couples the computational power of global sensitivity analysis (GSA) with the experimental efficiency of quantitative high-throughput screening (QHTS). We present a case study where GSA-QHTS allowed for the identification of the main pharmaceutical pollutants (and their interactions), driving biological effects of low-dose complex mixtures at the microbial population level. The QHTS experiments involved the integrated analysis of nearly 2700 observations from an array of 180 unique low-dose mixtures, representing the most complex and data-rich experimental mixture effect assessment of main pharmaceutical pollutants to date. An ecological scaling-up experiment confirmed that this subset of pollutants also affects typical freshwater microbial community assemblages. Contrary to our expectations and challenging established scientific opinion, the bioactivity of the mixtures was not predicted by the null mixture models, and the main drivers that were identified by GSA-QHTS were overlooked by the current effect assessment scheme. Our results suggest that current chemical effect assessment methods overlook a substantial number of ecologically dangerous chemical pollutants and introduce a new operational framework for their systematic identification. PMID:27617294

Short-term bioassay of complex organic mixtures. Part II. Mutagenicity testing

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

Epler, J.L.; Clark, B.R.; Ho, C.

1978-01-01

The feasibility of using short-term mutagenicity assays to predict the potential biohazard of various crude and complex test materials has been examined in a coupled chemical and biological approach. The principal focus of the research has involved the preliminary chemical characterizatiion and preparation for bioassay, followed by testing in the Salmonella histidine reversion assay system. The mutagenicity tests are intended to act as predictors of profound long-range health effects such as mutagenesis and/or carcinogenesis; act as a mechanism to rapidly isolate and identify a hazardous agent in a complex mixture; and function as a measure of biological activity correlating baselinemore » data with changes in process conditions. Since complex mixtures can be fractionated and approached in these short-term assays, information reflecting on the actual compounds responsible for the biological effect may be accumulated.« less

ANALYSIS OF FUNCTIONAL EFFECTS OF A MIXTURE OF FIVE PESTICIDES USING A RAY DESIGN

EPA Science Inventory

Abstract
The protection of human health from the adverse effects of cumulative environmental exposure to chemical mixtures is an important issue. Of particular interest is the potential detection and characterization of interaction among chemicals in complex mixtures. R...

Hydroxyl group as IR probe to detect the structure of ionic liquid-acetonitrile mixtures

NASA Astrophysics Data System (ADS)

Xu, Jing; Deng, Geng; Zhou, Yu; Ashraf, Hamad; Yu, Zhi-Wu

2018-06-01

Task-specific ionic liquids (ILs) are those with functional groups introduced in the cations or anions of ILs to bring about specific properties for various tasks. In this work, the hydrogen bonding interactions between a hydroxyl functionalized IL 1-(2-hydroxylethyl)-3-methylimidazolium tetrafluoroborate ([C2OHMIM][BF4]) and acetonitrile were investigated in detail by infrared spectroscopy, excess spectroscopy, two-dimensional correlation spectroscopy, combined with hydrogen nuclear magnetic resonance and density functional theory calculations (DFT). The hydroxyl group rather than C2sbnd H is found to be the main interaction site in the cation. And the ν(Osbnd H) is more sensitive than v(C-Hs) to the environment, which has been taken as an intrinsic probe to reflect the structural change of IL. Examining the region of ν(Osbnd H), by combining excess spectroscopy and DFT calculation, a number of species were identified in the mixtures. Other than the hydrogen bond between a cation and an anion, the hydroxyl group allows the formation of a hydrogen bond between two like-charged cations. The Osbnd H⋯O hydrogen bonding interactions in the hydroxyl-mediated cation-cation complexes are cooperative, while Osbnd H⋯F and C2sbnd H⋯F hydrogen bonding interactions in cation-anion complexes are anti-cooperative. These in-depth studies on the properties of the ionic liquid-acetonitrile mixtures may shed light on exploring their applications as mixed solvents and understanding the nature of doubly ionic hydrogen bonds.

Simultaneous quantification of Aroclor mixtures in soil samples by gas chromatography/mass spectrometry with solid phase microextraction using partial least-squares regression.

PubMed

Zhang, Mengliang; Harrington, Peter de B

2015-01-01

Multivariate partial least-squares (PLS) method was applied to the quantification of two complex polychlorinated biphenyls (PCBs) commercial mixtures, Aroclor 1254 and 1260, in a soil matrix. PCBs in soil samples were extracted by headspace solid phase microextraction (SPME) and determined by gas chromatography/mass spectrometry (GC/MS). Decachlorinated biphenyl (deca-CB) was used as internal standard. After the baseline correction was applied, four data representations including extracted ion chromatograms (EIC) for Aroclor 1254, EIC for Aroclor 1260, EIC for both Aroclors and two-way data sets were constructed for PLS-1 and PLS-2 calibrations and evaluated with respect to quantitative prediction accuracy. The PLS model was optimized with respect to the number of latent variables using cross validation of the calibration data set. The validation of the method was performed with certified soil samples and real field soil samples and the predicted concentrations for both Aroclors using EIC data sets agreed with the certified values. The linear range of the method was from 10μgkg(-1) to 1000μgkg(-1) for both Aroclor 1254 and 1260 in soil matrices and the detection limit was 4μgkg(-1) for Aroclor 1254 and 6μgkg(-1) for Aroclor 1260. This holistic approach for the determination of mixtures of complex samples has broad application to environmental forensics and modeling. Copyright © 2014 Elsevier Ltd. All rights reserved.

Simultaneous separation of inorganic anions and metal-citrate complexes on a zwitterionic stationary phase with on-column complexation.

PubMed

Nesterenko, Ekaterina P; Nesterenko, Pavel N; Paull, Brett

2008-12-05

The retention and separation selectivity of inorganic anions and on-column derivatised negatively charged citrate or oxalate metal complexes on reversed-phase stationary phases dynamically coated with N-(dodecyl-N,N-dimethylammonio)undecanoate (DDMAU) has been investigated. The retention mechanism for the metal-citrate complexes was predominantly anion exchange, although the amphoteric/zwitterionic nature of the stationary phase coating undoubtedly also contributed to the unusual separation selectivity shown. A mixture of 10 inorganic anions and metal cations was achieved using a 20 cm monolithic DDMAU modified column and a 1 mM citrate eluent, pH 4.0, flow rate equal to 0.8 mL/min. Selectivity was found to be strongly pH dependent, allowing additional scope for manipulation of solute retention, and thus application to complex samples. This is illustrated with the analysis of an acidic mine drainage sample with a range of inorganic anions and transition metal cations, varying significantly in their concentrations levels.

Protein complex purification from Thermoplasma acidophilum using a phage display library.

PubMed

Hubert, Agnes; Mitani, Yasuo; Tamura, Tomohiro; Boicu, Marius; Nagy, István

2014-03-01

We developed a novel protein complex isolation method using a single-chain variable fragment (scFv) based phage display library in a two-step purification procedure. We adapted the antibody-based phage display technology which has been developed for single target proteins to a protein mixture containing about 300 proteins, mostly subunits of Thermoplasma acidophilum complexes. T. acidophilum protein specific phages were selected and corresponding scFvs were expressed in Escherichia coli. E. coli cell lysate containing the expressed His-tagged scFv specific against one antigen protein and T. acidophilum crude cell lysate containing intact target protein complexes were mixed, incubated and subjected to protein purification using affinity and size exclusion chromatography steps. This method was confirmed to isolate intact particles of thermosome and proteasome suitable for electron microscopy analysis and provides a novel protein complex isolation strategy applicable to organisms where no genetic tools are available. Copyright © 2013 Elsevier B.V. All rights reserved.

Hydrogen-related complexes in Li-diffused ZnO single crystals

NASA Astrophysics Data System (ADS)

Corolewski, Caleb D.; Parmar, Narendra S.; Lynn, Kelvin G.; McCluskey, Matthew D.

2016-07-01

Zinc oxide (ZnO) is a wide band gap semiconductor and a potential candidate for next generation white solid state lighting applications. In this work, hydrogen-related complexes in lithium diffused ZnO single crystals were studied. In addition to the well-known Li-OH complex, several other hydrogen defects were observed. When a mixture of Li2O and ZnO is used as the dopant source, zinc vacancies are suppressed and the bulk Li concentration is very high (>1019 cm-3). In that case, the predominant hydrogen complex has a vibrational frequency of 3677 cm-1, attributed to surface O-H species. When Li2CO3 is used, a structured blue luminescence band and O-H mode at 3327 cm-1 are observed at 10 K. These observations, along with positron annihilation measurements, suggest a zinc vacancy-hydrogen complex, with an acceptor level ˜0.3 eV above the valence-band maximum. This relatively shallow acceptor could be beneficial for p-type ZnO.

Models of chromatin spatial organisation in the cell nucleus

NASA Astrophysics Data System (ADS)

Nicodemi, Mario

2014-03-01

In the cell nucleus chromosomes have a complex architecture serving vital functional purposes. Recent experiments have started unveiling the interaction map of DNA sites genome-wide, revealing different levels of organisation at different scales. The principles, though, which orchestrate such a complex 3D structure remain still mysterious. I will overview the scenario emerging from some classical polymer physics models of the general aspect of chromatin spatial organisation. The available experimental data, which can be rationalised in a single framework, support a picture where chromatin is a complex mixture of differently folded regions, self-organised across spatial scales according to basic physical mechanisms. I will also discuss applications to specific DNA loci, e.g. the HoxB locus, where models informed with biological details, and tested against targeted experiments, can help identifying the determinants of folding.

Equilibration of a polycation - anionic surfactant mixture at the water/vapor interface.

PubMed

Akanno, Andrew; Guzmán, Eduardo; Fernández-Peña, Laura; Llamas, Sara; Ortega, Francisco; Rubio, Ramon Gonzalez

2018-06-01

The adsorption of concentrated poly(diallyldimethylammonium chloride) (PDADMAC) - sodium lauryl ether sulfate (SLES) mixtures at the water / vapor interface has been studied by different surface tension techniques and dilational visco-elasticity measurements. This work tries to shed light on the way in which the formation of polyelectrolyte - surfactant complexes in the bulk affects to the interfacial properties of mixtures formed by a polycation and an oppositely charged surfactant. The results are discussed in terms of a two-step adsorption-equilibration of PDADMAC - SLES complexes at the interface, with the initial stages involving the diffusion of kinetically trapped aggregates formed in the bulk to the interface followed by the dissociation and spreading of such aggregates at the interface. This latter process becomes the main contribution to the surface tension decrease. This work helps on the understanding of the most fundamental bases of the physico-chemical behavior of concentrated polyelectrolyte - surfactant mixtures which present complex bulk and interfacial interactions with interest in both basic and applied sciences.

NGS-based likelihood ratio for identifying contributors in two- and three-person DNA mixtures.

PubMed

Chan Mun Wei, Joshua; Zhao, Zicheng; Li, Shuai Cheng; Ng, Yen Kaow

2018-06-01

DNA fingerprinting, also known as DNA profiling, serves as a standard procedure in forensics to identify a person by the short tandem repeat (STR) loci in their DNA. By comparing the STR loci between DNA samples, practitioners can calculate a probability of match to identity the contributors of a DNA mixture. Most existing methods are based on 13 core STR loci which were identified by the Federal Bureau of Investigation (FBI). Analyses based on these loci of DNA mixture for forensic purposes are highly variable in procedures, and suffer from subjectivity as well as bias in complex mixture interpretation. With the emergence of next-generation sequencing (NGS) technologies, the sequencing of billions of DNA molecules can be parallelized, thus greatly increasing throughput and reducing the associated costs. This allows the creation of new techniques that incorporate more loci to enable complex mixture interpretation. In this paper, we propose a computation for likelihood ratio that uses NGS (next generation sequencing) data for DNA testing on mixed samples. We have applied the method to 4480 simulated DNA mixtures, which consist of various mixture proportions of 8 unrelated whole-genome sequencing data. The results confirm the feasibility of utilizing NGS data in DNA mixture interpretations. We observed an average likelihood ratio as high as 285,978 for two-person mixtures. Using our method, all 224 identity tests for two-person mixtures and three-person mixtures were correctly identified. Copyright © 2018 Elsevier Ltd. All rights reserved.

CHANGES IN NUCLEAR TRANSCRIPTION FACTORS IN RAT HIPPOCAMPUS AND CEREBELLUM FOLLOWING DEVELOPMENTAL EXPOSURE TO A COMMERCIAL PCB MIXTURE.

EPA Science Inventory

Polychlorinated biphenyls (PCBs) offer a unique model to understand the major issues related to complex environmental mixtures. These pollutants are ubiquitous and exist as mixtures of several congeners in the environment. Human exposures to PCBs are associated with a variety of ...

CHANGES IN HIPPOCAMPAL SPINE DENSITY AND PROTEIN KINASE C ISOFORMS FOLLOWING DEVELOPMENTAL EXPOSURE TO A MIXTURE OF PERSISTENT CHEMICALS.

EPA Science Inventory

Polychlorinated biphenyls (PCBs) offer a unique model to understand the major issues related to complex environmental mixtures of persistent chemicals. These pollutants are ubiquitous, persistent, bioaccumulate in human body through the food chain, and exist as mixtures of severa...

In-vitro activity of taurolidine on single species and a multispecies population associated with periodontitis.

PubMed

Zollinger, Lilly; Schnyder, Simone; Nietzsche, Sandor; Sculean, Anton; Eick, Sigrun

2015-04-01

The antimicrobial activity of taurolidine was compared with minocycline against microbial species associated with periodontitis (four single strains and a 12-species mixture). Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs), killing as well as activities on established and forming single-species biofilms and a 12-species biofilm were determined. The MICs of taurolidine against single species were always 0.31 mg/ml, the MBCs were 0.64 mg/ml. The used mixed microbiota was less sensitive to taurolidine, MIC and the MBC was 2.5 mg/ml. The strains and the mixture were completely killed by 2.5 mg/ml taurolidine, whereas 256 μg/ml minocycline reduced the bacterial counts of the mixture by 5 log10 colony forming units (cfu). Coating the surface with 10 mg/ml taurolidine or 256 μg/ml minocycline prevented completely biofilm formation of Porphyromonas gingivalis ATCC 33277 but not of Aggregatibacter actinomycetemcomitans Y4 and the mixture. On 4.5 d old biofilms, taurolidine acted concentration dependent with a reduction by 5 log10 cfu (P. gingivalis ATCC 33277) and 7 log10 cfu (A. actinomycetemcomitans Y4) when applying 10 mg/ml. Minocycline decreased the cfu counts by 1-2 log10 cfu independent of the used concentration. The reduction of the cfu counts in the 4.5 d old multi-species biofilms was about 3 log10 cfu after application of any minocycline concentration and after using 10 mg/ml taurolidine. Taurolidine is active against species associated with periodontitis, even within biofilms. Nevertheless a complete elimination of complex biofilms by taurolidine seems to be impossible and underlines the importance of a mechanical removal of biofilms prior to application of taurolidine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Method for milling and drilling glass

NASA Technical Reports Server (NTRS)

Rice, S. H. (Inventor)

1980-01-01

A process for machining glass by placing a rotating carbide working surface under minimum pressure against an area of glass to be worked is described. Concurrently the region between the working surface and the area of glass is wet with a lubricant consisting essentially of a petroleum carrier, a complex mixture of esters and a complex mixture of naturally occurring aromatic oils.

Pacific Northwest Laboratory annual report for 1984 to the DOE Office of Energy Research. Part 1. Biomedical sciences

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

Felton, D.L.

1985-02-01

Research progress is reported in the following areas: (1) evaluation of possible health effects among nuclear workers; (2) dose-effect relationship studies of carcinogenesis from both nuclear materials and complex mixtures; (3) microbial mutagenesis studies with 6-aminochrysene and benzo(a)pyrene in coal-derived complex mixtures; and (4) a variety of studies relating to noncarcinogenic and nonmutagenic endpoints, including teratology, perinatal studies and studies to determine absorption, metabolism, and doses to critical tissues and organs of coal-derived mixtures and radionuclides. Items have been individually abstracted for the data base. (ACR)

A low-cost gradient system for high-performance liquid chromatography. Quantitation of complex pharmaceutical raw materials.

PubMed

Erni, F; Frei, R W

1976-09-29

A device is described that makes use of an eight-port motor valve to generate step gradients on the low-pressure side of a piston pump with a low dead volume. Such a gradient device with an automatic control unit, which also permits repetition of previous steps, can be built for about half the cost of a gradient system with two pumps. Applications of this gradient unit to the separation of complex mixtures of glycosides and alkaloids are discussed and compared with separations systems using two high-pressure pumps. The gradients that are used on reversed-phase material with solvent mixtures of water and completely miscible organic solvents are suitable for quantitative routine control of pharmaceutical products. The reproducibility of retention data is excellent over several months and, with the use of loop injectors, major components can be determined quantitatively with a reproducibility of better than 2% (relative standard deviation). The step gradient selector valve can also be used as an introduction system for very large sample volumes. Up to 11 can be injected and samples with concentrations of less than 1 ppb can be determined with good reproducibilities.

Accomplishing simple, solubility-based separations of rare earth elements with complexes bearing size-sensitive molecular apertures

PubMed Central

Bogart, Justin A.; Cole, Bren E.; Boreen, Michael A.; Lippincott, Connor A.; Manor, Brian C.; Carroll, Patrick J.; Schelter, Eric J.

2016-01-01

Rare earth (RE) metals are critical components of electronic materials and permanent magnets. Recycling of consumer materials is a promising new source of rare REs. To incentivize recycling, there is a clear need for the development of simple methods for targeted separations of mixtures of RE metal salts. Metal complexes of a tripodal hydroxylaminato ligand, TriNOx3–, featured a size-sensitive aperture formed of its three η2-(N,O) ligand arms. Exposure of cations in the aperture induced a self-associative equilibrium comprising RE(TriNOx)THF and [RE(TriNOx)]2 species. Differences in the equilibrium constants Kdimer for early and late metals enabled simple separations through leaching. Separations were performed on RE1/RE2 mixtures, where RE1 = La–Sm and RE2 = Gd–Lu, with emphasis on Eu/Y separations for potential applications in the recycling of phosphor waste from compact fluorescent light bulbs. Using the leaching method, separations factors approaching 2,000 were obtained for early–late RE combinations. Following solvent optimization, >95% pure samples of Eu were obtained with a 67% recovery for the technologically relevant Eu/Y separation. PMID:27956636

Accomplishing simple, solubility-based separations of rare earth elements with complexes bearing size-sensitive molecular apertures.

PubMed

Bogart, Justin A; Cole, Bren E; Boreen, Michael A; Lippincott, Connor A; Manor, Brian C; Carroll, Patrick J; Schelter, Eric J

2016-12-27

Rare earth (RE) metals are critical components of electronic materials and permanent magnets. Recycling of consumer materials is a promising new source of rare REs. To incentivize recycling, there is a clear need for the development of simple methods for targeted separations of mixtures of RE metal salts. Metal complexes of a tripodal hydroxylaminato ligand, TriNOx 3- , featured a size-sensitive aperture formed of its three η 2 -(N,O) ligand arms. Exposure of cations in the aperture induced a self-associative equilibrium comprising RE(TriNOx)THF and [RE(TriNOx)] 2 species. Differences in the equilibrium constants K dimer for early and late metals enabled simple separations through leaching. Separations were performed on RE1/RE2 mixtures, where RE1 = La-Sm and RE2 = Gd-Lu, with emphasis on Eu/Y separations for potential applications in the recycling of phosphor waste from compact fluorescent light bulbs. Using the leaching method, separations factors approaching 2,000 were obtained for early-late RE combinations. Following solvent optimization, >95% pure samples of Eu were obtained with a 67% recovery for the technologically relevant Eu/Y separation.

Qualitative and quantitative assessment of unresolved complex mixture in PM2.5 of Bakersfield, CA

NASA Astrophysics Data System (ADS)

Nallathamby, Punith Dev; Lewandowski, Michael; Jaoui, Mohammed; Offenberg, John H.; Kleindienst, Tadeusz E.; Rubitschun, Caitlin; Surratt, Jason D.; Usenko, Sascha; Sheesley, Rebecca J.

2014-12-01

The 2010 CalNex (California Nexus) field experiment offered an opportunity for detailed characterization of atmospheric particulate carbon composition and sources in Bakersfield, CA. In the current study, the authors describe and employ a new protocol for reporting unresolved complex mixture (UCM) in over 30 daily samples. The Bakersfield, CA site has significant contribution from UCM, 2.9 ± 2.2% of the daily OC, which makes it an ideal first application. The new protocol reports two UCM peaks for Bakersfield with unique mean vapor pressure, retention time, mass spectra and daily ambient concentration trends. The first UCM peak, UCM-A, was comprised of semi-volatile compounds including alkanes, alkenes, and alkynes, with a mean vapor pressure of 2E-04 Torr and medium to heavy-duty diesel exhaust as a likely source. The second UCM peak, UCM-B, was comprised of linear, branched, and cyclic alkanes, with a mean vapor pressure of 1E-08 Torr. UCM-B had strong similarities to UCM in the NIST Standard Reference Material 1649b (urban dust) and to previously reported, detailed UCM for a representative Bakersfield sample, with possible sources including: motor vehicle exhaust, agricultural activities, and construction activities.

Electrophoresis-mass spectrometry probe

DOEpatents

Andresen, Brian D.; Fought, Eric R.

1987-01-01

The invention involves a new technique for the separation of complex mixtures of chemicals, which utilizes a unique interface probe for conventional mass spectrometers which allows the electrophoretically separated compounds to be analyzed in real-time by a mass spectrometer. This new chemical analysis interface, which couples electrophoresis with mass spectrometry, allows complex mixtures to be analyzed very rapidly, with much greater specificity, and with greater sensitivity. The interface or probe provides a means whereby large and/or polar molecules in complex mixtures to be completely characterized. The preferred embodiment of the probe utilizes a double capillary tip which allows the probe tip to be continually wetted by the buffer, which provides for increased heat dissipation, and results in a continually operating interface which is more durable and electronically stable than the illustrated single capillary tip probe interface.

Quantitative carbon detector for enhanced detection of molecules in foods, pharmaceuticals, cosmetics, flavors, and fuels.

PubMed

Beach, Connor A; Krumm, Christoph; Spanjers, Charles S; Maduskar, Saurabh; Jones, Andrew J; Dauenhauer, Paul J

2016-03-07

Analysis of trace compounds, such as pesticides and other contaminants, within consumer products, fuels, and the environment requires quantification of increasingly complex mixtures of difficult-to-quantify compounds. Many compounds of interest are non-volatile and exhibit poor response in current gas chromatography and flame ionization systems. Here we show the reaction of trimethylsilylated chemical analytes to methane using a quantitative carbon detector (QCD; the Polyarc™ reactor) within a gas chromatograph (GC), thereby enabling enhanced detection (up to 10×) of highly functionalized compounds including carbohydrates, acids, drugs, flavorants, and pesticides. Analysis of a complex mixture of compounds shows that the GC-QCD method exhibits faster and more accurate analysis of complex mixtures commonly encountered in everyday products and the environment.

[Assessment of antibacterial efficacy of ozone therapy in treatment of caries at the white spot stage].

PubMed

Makeeva, I M; Turkina, A Yu; Margaryan, E G; Paramonov, Yu O; Polyakova, M A

Effect on cariogenic flora is the key toremineralizing therapy efficacy in treatment of initial caries (at the white spot stage). Ozone in dentistry is used as a highly effective antibacterial agent. Treatment of white spot lesions with the ozone-air mixture leads to significant increase of efficacy in non-invasive treatment of initial caries. clinical and microbiological assessment of antibacterial efficacy of ozone therapy in treatment of caries at the white spot stage. The trial recruited 86 patients for non-invasive treatment of caries at the white spot stage which included the complex of professional oral hygiene, medicamental treatment of white spot lesions with hydrogen peroxide 3% and chlorhexidinedigluconate 0,2%, treatment with the ozone-air mixture and application of hydroxyapatite Са2+. Material for microbiological study was received before the treatment, after the complex of professional oral hygiene and medicamental treatment of white spot lesions conducted as well as after the treatment with the ozone-air mixture. Before the treatment up to 16 kinds of microorganisms on the surface of white spot lesion were detected with the following shares: S. mutans (19.9%), S. salivarius (15.1%), S. epidermidis (8.7%), S. mitis (6.5%), Lactobacillus (6.5%) and different kinds of staphylococci (10.8%). After the complex of professional oral hygiene and medicamental treatment conducted decrease in number of cariogenic microorganisms was indicated as follows: S. mutans - from 1·105 to 1·104, S. salivarius - from 1·107 to 1·106, S. epidermidis - from 1·105 to 1·104, S. mitis - from 1·104 to 1·103, Lactobacillus - from 1·104 tо 1·103. After the treatment of tooth enamel with the ozone-air mixture increase in microorganisms was not observed. The efficacy of ozone on cariogenic microorganisms exceeds significantly the efficacy of 3% hydrogen peroxide and 0,2% chlorhexidinedigluconate. It is strongly advisable to include ozone in protocol of non-invasive treatment of initial dental caries.

Lagged kernel machine regression for identifying time windows of susceptibility to exposures of complex mixtures.

PubMed

Liu, Shelley H; Bobb, Jennifer F; Lee, Kyu Ha; Gennings, Chris; Claus Henn, Birgit; Bellinger, David; Austin, Christine; Schnaas, Lourdes; Tellez-Rojo, Martha M; Hu, Howard; Wright, Robert O; Arora, Manish; Coull, Brent A

2018-07-01

The impact of neurotoxic chemical mixtures on children's health is a critical public health concern. It is well known that during early life, toxic exposures may impact cognitive function during critical time intervals of increased vulnerability, known as windows of susceptibility. Knowledge on time windows of susceptibility can help inform treatment and prevention strategies, as chemical mixtures may affect a developmental process that is operating at a specific life phase. There are several statistical challenges in estimating the health effects of time-varying exposures to multi-pollutant mixtures, such as: multi-collinearity among the exposures both within time points and across time points, and complex exposure-response relationships. To address these concerns, we develop a flexible statistical method, called lagged kernel machine regression (LKMR). LKMR identifies critical exposure windows of chemical mixtures, and accounts for complex non-linear and non-additive effects of the mixture at any given exposure window. Specifically, LKMR estimates how the effects of a mixture of exposures change with the exposure time window using a Bayesian formulation of a grouped, fused lasso penalty within a kernel machine regression (KMR) framework. A simulation study demonstrates the performance of LKMR under realistic exposure-response scenarios, and demonstrates large gains over approaches that consider each time window separately, particularly when serial correlation among the time-varying exposures is high. Furthermore, LKMR demonstrates gains over another approach that inputs all time-specific chemical concentrations together into a single KMR. We apply LKMR to estimate associations between neurodevelopment and metal mixtures in Early Life Exposures in Mexico and Neurotoxicology, a prospective cohort study of child health in Mexico City.

Hollow silica microspheres for buoyancy-assisted separation of infectious pathogens from stool.

PubMed

Weigum, Shannon E; Xiang, Lichen; Osta, Erica; Li, Linying; López, Gabriel P

2016-09-30

Separation of cells and microorganisms from complex biological mixtures is a critical first step in many analytical applications ranging from clinical diagnostics to environmental monitoring for food and waterborne contaminants. Yet, existing techniques for cell separation are plagued by high reagent and/or instrumentation costs that limit their use in many remote or resource-poor settings, such as field clinics or developing countries. We developed an innovative approach to isolate infectious pathogens from biological fluids using buoyant hollow silica microspheres that function as "molecular buoys" for affinity-based target capture and separation by floatation. In this process, antibody functionalized glass microspheres are mixed with a complex biological sample, such as stool. When mixing is stopped, the target-bound, low-density microspheres float to the air/liquid surface, which simultaneously isolates and concentrates the target analytes from the sample matrix. The microspheres are highly tunable in terms of size, density, and surface functionality for targeting diverse analytes with separation times of ≤2min in viscous solutions. We have applied the molecular buoy technique for isolation of a protozoan parasite that causes diarrheal illness, Cryptosporidium, directly from stool with separation efficiencies over 90% and low non-specific binding. This low-cost method for phenotypic cell/pathogen separation from complex mixtures is expected to have widespread use in clinical diagnostics as well as basic research. Copyright © 2016 Elsevier B.V. All rights reserved.

Dielectric constant of liquid alkanes and hydrocarbon mixtures

NASA Technical Reports Server (NTRS)

Sen, A. D.; Anicich, V. G.; Arakelian, T.

1992-01-01

The complex dielectric constants of n-alkanes with two to seven carbon atoms have been measured. The measurements were conducted using a slotted-line technique at 1.2 GHz and at atmospheric pressure. The temperature was varied from the melting point to the boiling point of the respective alkanes. The real part of the dielectric constant was found to decrease with increasing temperature and correlate with the change in the molar volume. An upper limit to all the loss tangents was established at 0.001. The complex dielectric constants of a few mixtures of liquid alkanes were also measured at room temperature. For a pentane-octane mixture the real part of the dielectric constant could be explained by the Clausius-Mosotti theory. For the mixtures of n-hexane-ethylacetate and n-hexane-acetone the real part of the dielectric constants could be explained by the Onsager theory extended to mixtures. The dielectric constant of the n-hexane-acetone mixture displayed deviations from the Onsager theory at the highest fractions of acetone. The dipole moments of ethylacetate and acetone were determined for dilute mixtures using the Onsager theory and were found to be in agreement with their accepted gas-phase values. The loss tangents of the mixtures exhibited a linear relationship with the volume fraction for low concentrations of the polar liquids.

Dielectric properties of benzylamine in 1,2,6-hexanetriol mixture using time domain reflectometry technique

NASA Astrophysics Data System (ADS)

Swami, M. B.; Hudge, P. G.; Pawar, V. P.

The dielectric properties of binary mixtures of benzylamine-1,2,6-hexantriol mixtures at different volume fractions of 1,2,6-hexanetriol have been measured using Time Domain Reflectometry (TDR) technique in the frequency range of 10 MHz to 30 GHz. Complex permittivity spectra were fitted using Havriliak-Negami equation. By using least square fit method the dielectric parameters such as static dielectric constant (ɛ0), dielectric constant at high frequency (ɛ∞), relaxation time τ (ps) and relaxation distribution parameter (β) were extracted from complex permittivity spectra at 25∘C. The intramolecular interaction of different molecules has been discussed using the Kirkwood correlation factor, Bruggeman factor. The Kirkwood correlation factor (gf) and effective Kirkwood correlation factor (geff) indicate the dipole ordering of the binary mixtures.

Quantitative, equal carbon response HSQC experiment, QEC-HSQC

NASA Astrophysics Data System (ADS)

Mäkelä, Valtteri; Helminen, Jussi; Kilpeläinen, Ilkka; Heikkinen, Sami

2016-10-01

Quantitative NMR has become increasingly useful and popular in recent years, with many new and emerging applications in metabolomics, quality control, reaction monitoring and other types of mixture analysis. While sensitive and simple to acquire, the low resolving power of 1D 1H NMR spectra can be a limiting factor when analyzing complex mixtures. This drawback can be solved by observing a different type of nuclei offering improved resolution or with multidimensional experiments, such as HSQC. In this paper, we present a novel Quantitative, Equal Carbon HSQC (QEC-HSQC) experiment providing an equal response across different type of carbons regardless of the number of attached protons, in addition to an uniform response over a wide range of 1JCH couplings. This enables rapid quantification and integration over multiple signals without the need for complete resonance assignments and simplifies the integration of overlapping signals.

Dynamics and universal scaling law in geometrically-controlled sessile drop evaporation

PubMed Central

Sáenz, P. J.; Wray, A. W.; Che, Z.; Matar, O. K.; Valluri, P.; Kim, J.; Sefiane, K.

2017-01-01

The evaporation of a liquid drop on a solid substrate is a remarkably common phenomenon. Yet, the complexity of the underlying mechanisms has constrained previous studies to spherically symmetric configurations. Here we investigate well-defined, non-spherical evaporating drops of pure liquids and binary mixtures. We deduce a universal scaling law for the evaporation rate valid for any shape and demonstrate that more curved regions lead to preferential localized depositions in particle-laden drops. Furthermore, geometry induces well-defined flow structures within the drop that change according to the driving mechanism. In the case of binary mixtures, geometry dictates the spatial segregation of the more volatile component as it is depleted. Our results suggest that the drop geometry can be exploited to prescribe the particle deposition and evaporative dynamics of pure drops and the mixing characteristics of multicomponent drops, which may be of interest to a wide range of industrial and scientific applications. PMID:28294114

Dynamics and universal scaling law in geometrically-controlled sessile drop evaporation.

PubMed

Sáenz, P J; Wray, A W; Che, Z; Matar, O K; Valluri, P; Kim, J; Sefiane, K

2017-03-15

The evaporation of a liquid drop on a solid substrate is a remarkably common phenomenon. Yet, the complexity of the underlying mechanisms has constrained previous studies to spherically symmetric configurations. Here we investigate well-defined, non-spherical evaporating drops of pure liquids and binary mixtures. We deduce a universal scaling law for the evaporation rate valid for any shape and demonstrate that more curved regions lead to preferential localized depositions in particle-laden drops. Furthermore, geometry induces well-defined flow structures within the drop that change according to the driving mechanism. In the case of binary mixtures, geometry dictates the spatial segregation of the more volatile component as it is depleted. Our results suggest that the drop geometry can be exploited to prescribe the particle deposition and evaporative dynamics of pure drops and the mixing characteristics of multicomponent drops, which may be of interest to a wide range of industrial and scientific applications.

Latent log-linear models for handwritten digit classification.

PubMed

Deselaers, Thomas; Gass, Tobias; Heigold, Georg; Ney, Hermann

2012-06-01

We present latent log-linear models, an extension of log-linear models incorporating latent variables, and we propose two applications thereof: log-linear mixture models and image deformation-aware log-linear models. The resulting models are fully discriminative, can be trained efficiently, and the model complexity can be controlled. Log-linear mixture models offer additional flexibility within the log-linear modeling framework. Unlike previous approaches, the image deformation-aware model directly considers image deformations and allows for a discriminative training of the deformation parameters. Both are trained using alternating optimization. For certain variants, convergence to a stationary point is guaranteed and, in practice, even variants without this guarantee converge and find models that perform well. We tune the methods on the USPS data set and evaluate on the MNIST data set, demonstrating the generalization capabilities of our proposed models. Our models, although using significantly fewer parameters, are able to obtain competitive results with models proposed in the literature.

Estimation of yohimbine base in complex mixtures by quantitative HPTLC application.

PubMed

Adel-Kader, Maged Saad; Alwahebi, Naif Wahebi Hamadan; Alam, Prawez

2017-01-01

The indole alkaloid Yohimbine has been used for over two centuries in the treatment of erectly dysfunction. Several formulations containing yohimbine salts, yohimbe bark power or extract are marketed worldwide. Determination of the amount of yohimbine in such formulation is a challenging task due to their complex nature. Extraction followed by acid-base purification resulted in a relatively pure alkaloids containing fractions. The exact amounts of yohimbine free base in different formulations were determined by densitometric HPTLC validated methods using silica gel TLC plates. Standard curve for yohimbine was generated using yohimbine hydrochloride subjected to the same acid-base treatment as the used samples. All formulations found to contain yohimbine though some with less concentration than the labeled amount.

Enhanced Antimicrobial Activity Of Antibiotics Mixed With Metal Nanoparticles

NASA Astrophysics Data System (ADS)

Kumar, Sandeep; Kumar, Neeraj; Bhanjana, Gaurav; Thakur, Rajesh; Dilbaghi, Neeraj

2011-12-01

Current producers of antimicrobial technology have a long lasting, environmentally safe, non-leaching, water soluble solution that will eventually replace all poisons and heavy metals. The transition metal ions inevitably exist as metal complexes in biological systems by interaction with the numerous molecules possessing groupings capable of complexation or chelation. Nanoparticles of metal oxides offer a wide variety of potential applications in medicine due to the unprecedented advances in nanobiotechnology research. the bacterial action of antibiotics like penicillin, erythryomycin, ampicillin, streptomycin, kanamycin etc. and that of a mixture of antibiotics and metal and metal oxide nanoparticles like zinc oxide, zirconium, silver and gold on microbes was examined by the agar-well-diffusion method, enumeration of colony-forming units (CFU) and turbidimetry.

A comparison of complexation of Li+ ion with macrocyclic ligands 15-crown-5 and 12-crown-4 in binary nitromethane-acetonitrile mixtures by using lithium-7 NMR technique and ab initio calculation.

PubMed

Alizadeh, Nina

2011-01-01

Lithium-7 NMR measurements were used to investigate the stoichiometry and stability of Li+ complexes with 15-crown-5 (15C5), benzo-15-crown-5 (B15C5), dibenzo-15-crown-5 (DB15C5) and 12-crown-4 (12C4) in a number of nitromethane (NM)-acetonitrile (AN) binary mixtures. In all cases, the exchange between the free and complexed lithium ion was fast on the NMR time scale and a single population average resonance was observed. While all crown ethers form 1:1 complexes with Li+ ion in the binary mixtures used, both 1:1 and 2:1 (sandwich) complexes were observed between lithium ion and 12C4 in pure nitromethane solution. Stepwise formation constants of the 1:1 and 2:1 (ligand/metal) complexes were evaluated from computer fitting of the NMR-mole ratio data to equations which relate the observed metal ion chemical shifts to formation constants. There is an inverse linear relationship between the logarithms of the stability constants and the mole fraction of acetonitrile in the solvent mixtures. The stability order of the 1:1 complexes was found to be 15C5·Li+>B15C5·Li+>DB15C5·Li+>12C4·Li+. The optimized structures of the free ligands and their 1:1 and 2:1 complexes with Li+ ion were predicted by ab initio theoretical calculations using the Gaussian 98 software, and the results are discussed. Copyright © 2010 Elsevier B.V. All rights reserved.

High-performance liquid chromatography/high-resolution multiple stage tandem mass spectrometry using negative-ion-mode hydroxide-doped electrospray ionization for the characterization of lignin degradation products.

PubMed

Owen, Benjamin C; Haupert, Laura J; Jarrell, Tiffany M; Marcum, Christopher L; Parsell, Trenton H; Abu-Omar, Mahdi M; Bozell, Joseph J; Black, Stuart K; Kenttämaa, Hilkka I

2012-07-17

In the search for a replacement for fossil fuel and the valuable chemicals currently obtained from crude oil, lignocellulosic biomass has become a promising candidate as an alternative biorenewable source for crude oil. Hence, many research efforts focus on the extraction, degradation, and catalytic transformation of lignin, hemicellulose, and cellulose. Unfortunately, these processes result in the production of very complex mixtures. Further, while methods have been developed for the analysis of mixtures of oligosaccharides, this is not true for the complex mixtures generated upon degradation of lignin. For example, high-performance liquid chromatography/multiple stage tandem mass spectrometry (HPLC/MS(n)), a tool proven to be invaluable in the analysis of complex mixtures derived from many other biopolymers, such as proteins and DNA, has not been implemented for lignin degradation products. In this study, we have developed an HPLC separation method for lignin degradation products that is amenable to negative-ion-mode electrospray ionization (ESI doped with NaOH), the best method identified thus far for ionization of lignin-related model compounds without fragmentation. The separated and ionized compounds are then analyzed by MS(3) experiments to obtain detailed structural information while simultaneously performing high-resolution measurements to determine their elemental compositions in the two parts of a commercial linear quadrupole ion trap/Fourier-transform ion cyclotron resonance mass spectrometer. A lignin degradation product mixture was analyzed using this method, and molecular structures were proposed for some components. This methodology significantly improves the ability to analyze complex product mixtures that result from degraded lignin.

Introducing Students to Gas Chromatography-Mass Spectrometry Analysis and Determination of Kerosene Components in a Complex Mixture

ERIC Educational Resources Information Center

Pacot, Giselle Mae M.; Lee, Lyn May; Chin, Sung-Tong; Marriott, Philip J.

2016-01-01

Gas chromatography-mass spectrometry (GC-MS) and GC-tandem MS (GC-MS/MS) are useful in many separation and characterization procedures. GC-MS is now a common tool in industry and research, and increasingly, GC-MS/MS is applied to the measurement of trace components in complex mixtures. This report describes an upper-level undergraduate experiment…

Modeling of Complex Mixtures: JP-8 Toxicokinetics

DTIC Science & Technology

2008-10-01

generic tissue compartments in which we have combined diffusion limitation and deep tissue (global tissue model). We also applied a QSAR approach for...SUBJECT TERMS jet fuel, JP-8, PBPK modeling, complex mixtures, nonane, decane, naphthalene, QSAR , alternative fuels 16. SECURITY CLASSIFICATION OF...necessary, to apply to the interaction of specific compounds with specific tissues. We have also applied a QSAR approach for estimating blood and tissue

The Control of Orbital Mixing in Ruthenium Complexes Containing Quinone Related Ligands

DTIC Science & Technology

1991-04-04

and sodium, respectively. Tetrabutylammonium perchlorate (TBAP) and tetrabutylammonium hexafluorophosphate (Kodak; TBAH) were recrystallized from...solution. Lithium perchlorate trihydrate (0.036 g; 0.23 mmol) in methanol (2 mL) was added to the hot reaction mixture. The mixture was cooled to room...and lithium aluminum hydride suspension in THF (this required the use of the 4,5-dimethylated orthophenylenediamine complex for solubility reasons

OFFICE OF RESEARCH AND DEVELOPMENT'S FOUR LAB STUDY: TOXICOLOGICCAL AND CHEMICAL EVALUATION OF COMPLEX MIXTURES OF DISINFECTION BY-PRODUCTS (DBPS) AND QUALITY ASSURANCE ACTIVITIES FOR A LARGE U. S. EPA MULTILABORATORY STUDY

EPA Science Inventory

Office of Research and Development's Four Lab Study: Toxicological and Chemical Evaluation of Complex Mixtures of Disinfection By-Products (DBPs), and Quality Assurance Activities for a Large U.S. EPA Multilaboratoty Study

Thomas J. Hughes, Project and QA Manager, Expe...

Pharmacokinetic Modeling of JP-8 Jet Fuel Components: II. A Conceptual Framework

DTIC Science & Technology

2003-12-01

example, a single type of (simple) binary interaction between 300 components would require the specification of some 105 interaction coefficients . One...individual substances, via binary mechanisms, is enough to predict the interactions present in the mixture. Secondly, complex mixtures can often be...approximated as pseudo- binary systems, consisting of the compound of interest plus a single interacting complex vehicle with well-defined, composite

Sorption and desorption of selected non-steroidal anti-inflammatory drugs in an agricultural loam-textured soil.

PubMed

Zhang, Y; Price, G W; Jamieson, R; Burton, D; Khosravi, K

2017-05-01

Non-steroidal, anti-inflammatory drugs (NSAIDs) are widely used pharmaceutical products with analgesic and anti-inflammatory effects that are consistently detected in municipal wastewater systems and in municipal biosolids. Land application of biosolids and irrigation with reclaimed wastewater introduces these compounds into agricultural environments, which is an emerging issue of concern for ecosystem health. In this study, the sorption-desorption behaviour of four commonly consumed NSAIDs, including naproxen (NPX), ibuprofen (IBU), ketoprofen (KTF), and diclofenac (DCF), was examined in a loam textured soil exposed to either an individual-compound or a mixture of the four NSAIDs. The proportion of NSAIDs adsorbed to the soil in the mixture-compound system was 72%, 55%, 50% and 45%, for diclofenac, naproxen, ketoprofen, and ibuprofen, respectively, and differed slightly from the individual compound adsorption. Diclofenac displayed strong sorption and low desorption in both the individual-compound and mixture-compound systems. Naproxen and ibuprofen exhibited significant differences between the adsorption isotherms of the individual-compound and mixture-compound systems. Results of this study highlight differences in the sorption behaviour of NSAIDs, when present as mixtures, possibly through multilayer bonding effects or complexation with cationic metals or organo-clays from the soil. Soil organic matter (SOM) may have played a role in determining some of the interactions between the compounds but other factors associated with the mixture-compound system, such as cation bridging or multilayer cooperative adsorption. Desorption data suggests that the mechanisms involved in binding NSAIDs to the soil surface are also influence by the presence of other compounds in a mixture. A reduction in desorption was observed for all four NSAIDs in the mixture-compound system relative to the individual-compound system, but were greatest for naproxen and ibuprofen. The sorption-desorption hysteresis increased for naproxen and ibuprofen in the mixture-compound system. This study suggests that cooperative adsorption plays a role in the interaction of NSAIDs when present as mixtures rather than as individual compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preparation, physicochemical characterization and release behavior of the inclusion complex of trans-anethole and β-cyclodextrin.

PubMed

Zhang, Wenwen; Li, Xinying; Yu, Taocheng; Yuan, Lun; Rao, Gang; Li, Defu; Mu, Changdao

2015-08-01

Trans-anethole (AT) has a variety of antimicrobial properties and is widely used as food functional ingredient. However, the applications of AT are limited due to its low water solubility, strong odor and low physicochemical stability. Therefore, the aim of this work was to encapsulate AT with β-cyclodextrin (β-CD) for obtaining inclusion complex by co-precipitation method. The measurements effectively confirmed the formation of inclusion complex between AT and β-CD. The results showed that the inclusion complex presented new solid crystalline phases and was more thermally stable than the physical mixture and β-CD. The phase solubility study showed that the aqueous solubility of AT was increased by being included in β-CD. The calculated stability constant of inclusion complex was 1195M -1 , indicating the strong interaction between AT and β-CD. Furthermore, the release study suggested that β-CD provided the protection for AT against evaporation. The release behavior of AT from the inclusion complex was controlled. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Agrawal, Rakesh

This project sought and successfully answered two big challenges facing the creation of low-energy, cost-effective, zeotropic multi-component distillation processes: first, identification of an efficient search space that includes all the useful distillation configurations and no undesired configurations; second, development of an algorithm to search the space efficiently and generate an array of low-energy options for industrial multi-component mixtures. Such mixtures are found in large-scale chemical and petroleum plants. Commercialization of our results was addressed by building a user interface allowing practical application of our methods for industrial problems by anyone with basic knowledge of distillation for a given problem. Wemore » also provided our algorithm to a major U.S. Chemical Company for use by the practitioners. The successful execution of this program has provided methods and algorithms at the disposal of process engineers to readily generate low-energy solutions for a large class of multicomponent distillation problems in a typical chemical and petrochemical plant. In a petrochemical complex, the distillation trains within crude oil processing, hydrotreating units containing alkylation, isomerization, reformer, LPG (liquefied petroleum gas) and NGL (natural gas liquids) processing units can benefit from our results. Effluents from naphtha crackers and ethane-propane crackers typically contain mixtures of methane, ethylene, ethane, propylene, propane, butane and heavier hydrocarbons. We have shown that our systematic search method with a more complete search space, along with the optimization algorithm, has a potential to yield low-energy distillation configurations for all such applications with energy savings up to 50%.« less

A Flexible Method for Multi-Material Decomposition of Dual-Energy CT Images.

PubMed

Mendonca, Paulo R S; Lamb, Peter; Sahani, Dushyant V

2014-01-01

The ability of dual-energy computed-tomographic (CT) systems to determine the concentration of constituent materials in a mixture, known as material decomposition, is the basis for many of dual-energy CT's clinical applications. However, the complex composition of tissues and organs in the human body poses a challenge for many material decomposition methods, which assume the presence of only two, or at most three, materials in the mixture. We developed a flexible, model-based method that extends dual-energy CT's core material decomposition capability to handle more complex situations, in which it is necessary to disambiguate among and quantify the concentration of a larger number of materials. The proposed method, named multi-material decomposition (MMD), was used to develop two image analysis algorithms. The first was virtual unenhancement (VUE), which digitally removes the effect of contrast agents from contrast-enhanced dual-energy CT exams. VUE has the ability to reduce patient dose and improve clinical workflow, and can be used in a number of clinical applications such as CT urography and CT angiography. The second algorithm developed was liver-fat quantification (LFQ), which accurately quantifies the fat concentration in the liver from dual-energy CT exams. LFQ can form the basis of a clinical application targeting the diagnosis and treatment of fatty liver disease. Using image data collected from a cohort consisting of 50 patients and from phantoms, the application of MMD to VUE and LFQ yielded quantitatively accurate results when compared against gold standards. Furthermore, consistent results were obtained across all phases of imaging (contrast-free and contrast-enhanced). This is of particular importance since most clinical protocols for abdominal imaging with CT call for multi-phase imaging. We conclude that MMD can successfully form the basis of a number of dual-energy CT image analysis algorithms, and has the potential to improve the clinical utility of dual-energy CT in disease management.

Methods for Converter Sludge Dehydration Intensification

NASA Astrophysics Data System (ADS)

Vakhromeev, M. I.; Moreva, Y. A.; Starkova, L. G.

2017-11-01

The article considers the intensification methods for converter sludge dehydration exemplified by the sludges of the Oxygen Converter Workshop (OCW) of the Open Joint-Stock Company “Magnitogorsk Iron and Steel Works” (MMK, OJSC), one of the largest metallurgical companies in the Southern Urals. Converter sludges can contain up to 45-70% of ferrum [21] which is interesting in terms of their use as an addition to a sinter-feed mixture. Sludge intensifies the sintering process. It positively influences pelletizing and fusion mixture melting dynamics at sintering. Over the period of the converter sludge dehydration complex operation at the OCW, MMK, OJSC, it was revealed that processing results in obtaining of high humidity sludge. It causes sludge freezing during the winter period, thus, its transportation involves extra costs for sludge warming up. To resolve the above-mentioned problem, the following works were performed in 2016: - experimental studies of how the application of the low-molecular anionic flocculate “SEURVEY” FL-3 influences sludge humidity reduction. - experimental studies of how the filtering press process operation parameters influence sludge humidity reduction. The new flocculate application didn't lower the dehydrated sludge humidity (the objective was the humidity of not more than 15%). Basing upon the conducted research results, we can make a conclusion that putting into operation the sewage water reactant treatment technology with the use of “SEURVEY”, FL-3 (H-10) is not recommended. The research of the influence the filtering press process parameters have on the dehydration process intensification demonstrated that reaching of the obtained residue humidity value lower than 15% is possible under the reduction of the filtering press chamber depths to 30 mm and with the application of additional operation “Residue drying” with compressed air. This way of the sludge dehydration problem resolving at filtering presses of the converter sludge dehydration complex of the OCW, MMK, OJSC, can be recommended for application.

Thermodynamics, interfacial pressure isotherms and dilational rheology of mixed protein-surfactant adsorption layers.

PubMed

Fainerman, V B; Aksenenko, E V; Krägel, J; Miller, R

2016-07-01

Proteins and their mixtures with surfactants are widely used in many applications. The knowledge of their solution bulk behavior and its impact on the properties of interfacial layers made great progress in the recent years. Different mechanisms apply to the formation process of protein/surfactant complexes for ionic and non-ionic surfactants, which are governed mainly by electrostatic and hydrophobic interactions. The surface activity of these complexes is often remarkably different from that of the individual protein and has to be considered in respective theoretical models. At very low protein concentration, small amounts of added surfactants can change the surface activity of proteins remarkably, even though no strongly interfacial active complexes are observed. Also small added amounts of non-ionic surfactants change the surface activity of proteins in the range of small bulk concentrations or surface coverages. The modeling of the equilibrium adsorption behavior of proteins and their mixtures with surfactants has reached a rather high level. These models are suitable also to describe the high frequency limits of the dilational viscoelasticity of the interfacial layers. Depending on the nature of the protein/surfactant interactions and the changes in the interfacial layer composition rather complex dilational viscoelasticities can be observed and described by the available models. The differences in the interfacial behavior, often observed in literature for studies using different experimental methods, are at least partially explained by a depletion of proteins, surfactants and their complexes in the range of low concentrations. A correction of these depletion effects typically provides good agreement between the data obtained with different methods, such as drop and bubble profile tensiometry. Copyright © 2015 Elsevier B.V. All rights reserved.

Determinants of Whether or not Mixtures of Disinfection By-products are Similar

EPA Science Inventory

This project summary and its related publications provide information on the development of chemical, toxicological and statistical criteria for determining the sufficient similarity of complex chemical mixtures.

A guide for effective anatomical vascularization studies: useful ex vivo methods for both CT and MRI imaging before dissection.

PubMed

Renard, Yohann; Hossu, Gabriela; Chen, Bailiang; Krebs, Marine; Labrousse, Marc; Perez, Manuela

2018-01-01

The objective of this study was to develop a simple and useful injection protocol for imaging cadaveric vascularization and dissection. Mixtures of contrast agent and cast product should provide adequate contrast for two types of ex vivo imaging (MRI and CT) and should harden to allow gross dissection of the injected structures. We tested the most popular contrast agents and cast products, and selected the optimal mixture composition based on their availability and ease of use. All mixtures were first tested in vitro to adjust dilution parameters of each contrast agent and to fine-tune MR imaging acquisition sequences. Mixtures were then injected in 24 pig livers and one human pancreas for MR and computed tomography (CT) imaging before anatomical dissection. Colorized latex, gadobutrol and barite mixture met the above objective. Mixtures composed of copper sulfate (CuSO 4 ) gadoxetic acid (for MRI) and iodine (for CT) gave an inhomogeneous signal or extravasation of the contrast agent. Agar did not harden sufficiently for gross dissection but appears useful for CT and magnetic resonance imaging (MRI) studies without dissection. Silicone was very hard to inject but achieved the goals of the study. Resin is particularly difficult to use but could replace latex as an alternative for corrosion instead of dissection. This injection protocol allows CT and MRI images to be obtained of cadaveric vascularization and anatomical casts in the same anatomic specimen. Post-imaging processing software allow easy 3D reconstruction of complex anatomical structures using this technique. Applications are numerous, e.g. surgical training, teaching methods, postmortem anatomic studies, pathologic studies, and forensic diagnoses. © 2017 Anatomical Society.

Kinetic behavior of Fe(o,o-EDDHA)-humic substance mixtures in several soil components and in calcareous soils.

PubMed

Cerdán, Mar; Alcañiz, Sara; Juárez, Margarita; Jordá, Juana D; Bermúdez, Dolores

2007-10-31

Ferric ethylenediamine- N, N'-bis-(o-hydroxyphenylacetic)acid chelate (Fe(o, o-EDDHA)) is one of the most effective Fe fertilizers in calcareous soils. However, humic substances are occasionally combined with iron chelates in drip irrigation systems in order to lower costs. The reactivity of iron chelate-humic substance mixtures in several soil components and in calcareous soils was investigated through interaction tests, and their behavior was compared to the application of iron chelates and humic substances separately. Two commercial humic substances and two Fe(o, o-EDDHA) chelates (one synthesized in the laboratory and one commercial) were used to prepare iron chelate-humic substance mixtures at 50% (w/w). Various soil components (calcium carbonate, gibbsite, amorphous iron oxide, hematite, tenorite, zincite, amorphous Mn oxide, and peat) and three calcareous soils were shaken for 15 days with the mixtures and with iron chelate and humic substance solutions. The kinetic behavior of Fe(o, o-EDDHA) and Fe non-(o,o-EDDHA) (Fe bonded to (o,p-EDDHA) and other polycondensated ligands) and of the different nutrients solubilized after the interaction assay was determined. The results showed that the mixtures did not significantly reduce the retention of Fe(o, o-EDDHA) and Fe non-(o,o-EDDHA) in the soil components and the calcareous soils compared to the iron chelate solutions, but they did produce changes in the retention rate. Moreover, the competition between humic substances and synthetic chelating agents for complexing metal cations limited the effectiveness of the mixtures to mobilize nutrients from the substrates. The presence of Fe(o, p-EDDHA) and other byproducts in the commercial iron chelate had an important effect on the evolution of Fe(o, o-EDDHA) and the nutrient solubilization process.

High-performance liquid chromatography coupled with post-column dual-bioactivity assay for simultaneous screening of xanthine oxidase inhibitors and free radical scavengers from complex mixture.

PubMed

Li, D Q; Zhao, J; Li, S P

2014-06-06

Xanthine oxidase (XO) can catalyze hypoxanthine and xanthine to generate uric acid and reactive oxygen species (ROS), including superoxide anion radical (O₂(•-)) and hydrogen peroxide. XO inhibitors and free radical scavengers are beneficial to the treatment of gout and many related diseases. In the present study, an on-line high-performance liquid chromatography (HPLC) coupled with post-column dual-bioactivity assay was established and successfully applied to simultaneously screening of XO inhibitors and free radical scavengers from a complex mixture, Oroxylum indicum extract. The integrated system of HPLC separation, bioactivity screening and mass spectrometry identification was proved to be simple and effective for rapid and sensitive screening of individual bioactive compounds in complex mixtures. Copyright © 2014 Elsevier B.V. All rights reserved.

Electrophoresis-mass spectrometry probe

DOEpatents

Andresen, B.D.; Fought, E.R.

1987-11-10

The invention involves a new technique for the separation of complex mixtures of chemicals, which utilizes a unique interface probe for conventional mass spectrometers which allows the electrophoretically separated compounds to be analyzed in real-time by a mass spectrometer. This new chemical analysis interface, which couples electrophoresis with mass spectrometry, allows complex mixtures to be analyzed very rapidly, with much greater specificity, and with greater sensitivity. The interface or probe provides a means whereby large and/or polar molecules in complex mixtures to be completely characterized. The preferred embodiment of the probe utilizes a double capillary tip which allows the probe tip to be continually wetted by the buffer, which provides for increased heat dissipation, and results in a continually operating interface which is more durable and electronically stable than the illustrated single capillary tip probe interface. 8 figs.

Advanced instrumental methods for analyzing organics in solid waste: The use of gas chromatography/matrix isolation infrared spectroscopy (GC/MIIR) and supercritical fluid chromatography (SFC) for waste characterization

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

Raphaelian, L.A.; Boparai, A.S.; Schneider, J.F.

1987-01-01

Objectives of this research project were: (1) to enhance the capabilities of analyzing the complex mixtures found in coal wastes by using gas chromatography/matrix isolation infrared spectroscopy (GC/MIIR); (2) to separate, by supercritical fluid chromatography (SFC), the complex mixtures found in coal wastes into a few, less-complex mixtures so that analysis by gas chromatography (GC/MS) and GC/MIIR would be simplified. Preliminary results are presented for the mass spectra and infrared spectra of xylene isomers, gas chromatogram of 12 C/sub 2/-Napthalenes, averaged IR spectrum and a comparison of matrix isolation with light-pipe infrared spectra. A SFC chromatogram of polynuclear aromatic hydrocarbonsmore » is also presented. 2 refs., 5 figs.« less

Differential gene expression patterns in developing sexually dimorphic rat brain regions exposed to antiandrogenic, estrogenic, or complex endocrine disruptor mixtures: glutamatergic synapses as target.

PubMed

Lichtensteiger, Walter; Bassetti-Gaille, Catherine; Faass, Oliver; Axelstad, Marta; Boberg, Julie; Christiansen, Sofie; Rehrauer, Hubert; Georgijevic, Jelena Kühn; Hass, Ulla; Kortenkamp, Andreas; Schlumpf, Margret

2015-04-01

The study addressed the question whether gene expression patterns induced by different mixtures of endocrine disrupting chemicals (EDCs) administered in a higher dose range, corresponding to 450×, 200×, and 100× high-end human exposure levels, could be characterized in developing brain with respect to endocrine activity of mixture components, and which developmental processes were preferentially targeted. Three EDC mixtures, A-Mix (anti-androgenic mixture) with 8 antiandrogenic chemicals (di-n-butylphthalate, diethylhexylphthalate, vinclozolin, prochloraz, procymidone, linuron, epoxiconazole, and DDE), E-Mix (estrogenic mixture) with 4 estrogenic chemicals (bisphenol A, 4-methylbenzylidene camphor, 2-ethylhexyl 4-methoxycinnamate, and butylparaben), a complex mixture, AEP-Mix, containing the components of A-Mix and E-Mix plus paracetamol, and paracetamol alone, were administered by oral gavage to rat dams from gestation day 7 until weaning. General developmental endpoints were not affected by EDC mixtures or paracetamol. Gene expression was analyzed on postnatal day 6, during sexual brain differentiation, by exon microarray in medial preoptic area in the high-dose group, and by real-time RT-PCR in medial preoptic area and ventromedial hypothalamus in all dose groups. Expression patterns were mixture, sex, and region specific. Effects of the analgesic drug paracetamol, which exhibits antiandrogenic activity in peripheral systems, differed from those of A-Mix. All mixtures had a strong, mixture-specific impact on genes encoding for components of excitatory glutamatergic synapses and genes controlling migration and pathfinding of glutamatergic and GABAergic neurons, as well as genes linked with increased risk of autism spectrum disorders. Because development of glutamatergic synapses is regulated by sex steroids also in hippocampus, this may represent a general target of ECD mixtures.

Toxicity interactions between manganese (Mn) and lead (Pb) or cadmium (Cd) in a model organism the nematode C. elegans.

PubMed

Lu, Cailing; Svoboda, Kurt R; Lenz, Kade A; Pattison, Claire; Ma, Hongbo

2018-06-01

Manganese (Mn) is considered as an emerging metal contaminant in the environment. However, its potential interactions with companying toxic metals and the associated mixture effects are largely unknown. Here, we investigated the toxicity interactions between Mn and two commonly seen co-occurring toxic metals, Pb and Cd, in a model organism the nematode Caenorhabditis elegans. The acute lethal toxicity of mixtures of Mn+Pb and Mn+Cd were first assessed using a toxic unit model. Multiple toxicity endpoints including reproduction, lifespan, stress response, and neurotoxicity were then examined to evaluate the mixture effects at sublethal concentrations. Stress response was assessed using a daf-16::GFP transgenic strain that expresses GFP under the control of DAF-16 promotor. Neurotoxicity was assessed using a dat-1::GFP transgenic strain that expresses GFP in dopaminergic neurons. The mixture of Mn+Pb induced a more-than-additive (synergistic) lethal toxicity in the worm whereas the mixture of Mn+Cd induced a less-than-additive (antagonistic) toxicity. Mixture effects on sublethal toxicity showed more complex patterns and were dependent on the toxicity endpoints as well as the modes of toxic action of the metals. The mixture of Mn+Pb induced additive effects on both reproduction and lifespan, whereas the mixture of Mn+Cd induced additive effects on lifespan but not reproduction. Both mixtures seemed to induce additive effects on stress response and neurotoxicity, although a quantitative assessment was not possible due to the single concentrations used in mixture tests. Our findings demonstrate the complexity of metal interactions and the associated mixture effects. Assessment of metal mixture toxicity should take into consideration the unique property of individual metals, their potential toxicity mechanisms, and the toxicity endpoints examined.

Probing the mer- to fac-isomerization of tris-cyclometallated homo- and heteroleptic (C,N)3 iridium(III) complexes.

PubMed

McDonald, Aidan R; Lutz, Martin; von Chrzanowski, Lars S; van Klink, Gerard P M; Spek, Anthony L; van Koten, Gerard

2008-08-04

We have developed techniques which allow for covalent tethering, via a "hetero" cyclometallating ligand, of heteroleptic tris-cyclometallated iridium(III) complexes to polymeric supports (for application in light-emitting diode technologies). This involved the selective synthesis and thorough characterization of heteroleptic [Ir(C,N) 2(C',N')] tris-cyclometallated iridium(III) complexes. Furthermore, the synthesis and characterization of heteroleptic [Ir(C,N) 2OR] complexes is presented. Under standard thermal conditions for the synthesis of the facial ( fac) isomer of tris-cyclometallated complexes, it was not possible to synthesize pure heteroleptic complexes of the form [Ir(C,N) 2(C',N')]. Instead, a mixture of homo- and heteroleptic complexes was acquired. It was found that a stepwise procedure involving the synthesis of a pure meridonial ( mer) isomer followed by photochemical isomerization of this mer to the fac isomer was necessary to synthesize pure fac-[Ir(C,N) 2(C',N')] complexes. Under thermal isomerization conditions, the conversion of mer-[Ir(C,N) 2(C',N')] to fac-[Ir(C,N) 2(C',N')] was also not a clean reaction, with again a mixture of homo- and heteroleptic complexes acquired. An investigation into the thermal mer to fac isomerization of both homo- and heteroleptic tris-cyclometallated complexes is presented. It was found that the process is an alcohol-catalyzed reaction with the formation of an iridium alkoxide [Ir(C,N) 2OR] intermediate in the isomerization process. This catalyzed reaction can be carried out between 50 and 100 degrees C, the first such example of low-temperature mer-fac thermal isomerization. We have synthesized analogous complexes and have shown that they do indeed react so as to give fac-tris-cyclometallated products. A detailed explanation of the intermediates (and all of their stereoisomers, in particular when systems of the generic formula [M(a,b) 2(a',b')] are synthesized) formed in the mer to fac isomerization process is presented, including how the formed intermediates react further, and the stereoisomeric products they yield.

Enzyme-coupled nanoparticles-assisted laser desorption ionization mass spectrometry for searching for low-mass inhibitors of enzymes in complex mixtures.

PubMed

Salwiński, Aleksander; Da Silva, David; Delépée, Raphaël; Maunit, Benoît

2014-04-01

In this report, enzyme-coupled magnetic nanoparticles (EMPs) were shown to be an effective affinity-based tool for finding specific interactions between enzymatic targets and the low-mass molecules in complex mixtures using classic MALDI-TOF apparatus. EMPs used in this work act as nonorganic matrix enabling ionization of small molecules without any interference in the low-mass range (enzyme-coupled nanoparticles-assisted laser desorption ionization MS, ENALDI MS) and simultaneously carry the superficial specific binding sites to capture inhibitors present in a studied mixture. We evaluated ENALDI approach in two complementary variations: 'ion fading' (IF-ENALDI), based on superficial adsorption of inhibitors and 'ion hunting' (IH-ENALDI), based on selective pre-concentration of inhibitors. IF-ENALDI was applied for two sets of enzyme-inhibitor pairs: tyrosinase-glabridin and trypsin-leupeptin and for the real plant sample: Sparrmannia discolor leaf and stem methanol extract. The efficacy of IH-ENALDI was shown for the pair of trypsin-leupeptin. Both ENALDI approaches pose an alternative for bioassay-guided fractionation, the common method for finding inhibitors in the complex mixtures.

Cellular Binding of Anionic Nanoparticles is Inhibited by Serum Proteins Independent of Nanoparticle Composition.

PubMed

Fleischer, Candace C; Kumar, Umesh; Payne, Christine K

2013-09-01

Nanoparticles used in biological applications encounter a complex mixture of extracellular proteins. Adsorption of these proteins on the nanoparticle surface results in the formation of a "protein corona," which can dominate the interaction of the nanoparticle with the cellular environment. The goal of this research was to determine how nanoparticle composition and surface modification affect the cellular binding of protein-nanoparticle complexes. We examined the cellular binding of a collection of commonly used anionic nanoparticles: quantum dots, colloidal gold nanoparticles, and low-density lipoprotein particles, in the presence and absence of extracellular proteins. These experiments have the advantage of comparing different nanoparticles under identical conditions. Using a combination of fluorescence and dark field microscopy, flow cytometry, and spectroscopy, we find that cellular binding of these anionic nanoparticles is inhibited by serum proteins independent of nanoparticle composition or surface modification. We expect these results will aid in the design of nanoparticles for in vivo applications.

OXIDATIVE DNA DAMAGE FROM POTASSIUM BROMATE EXPOSURE IN LONG-EVANS RATS IS NOT ENHANCED BY A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS

EPA Science Inventory

Public drinking water treated with chemical disinfectants contains a complex mixture of disinfection by-products (DBPs) for which the relative toxicity of the mixtures needs to be characterized to accurately assess risk. Potassium bromate (KBrO3) is a by-product from ozonation of...

Historical and biochemical aspects of a seventeenth century gold-based aurum vitae recipe.

PubMed

Rubbiani, Riccardo; Wahrig, Bettina; Ott, Ingo

2014-08-01

The medicinal chemistry and biomedical applications of gold complexes have been intensively studied over the last decades. Some complexes have been used for the treatment of rheumatoid arthritis, and a considerable number of new metallodrug candidates have been developed as new anticancer drugs and anti-infectives. However, the therapeutic use of gold and its complexes goes back to ancient times and was also of great importance for alchemists until the modern age. In this report, we give an overview of the alchemic medicine between the sixteenth and the early eighteenth century and describe the cytotoxicity and thioredoxin reductase (TrxR) inhibition of a typical "aurum vitae" medicine, which was prepared according to a recipe by Bartholomäus Kretschmar from the seventeenth century. "Aurum vitae" consists of a mixture of gold, mercury and antimony complexes and shows the expected cytotoxic and TrxR inhibitory properties providing some rationale for therapeutic effects of this kind of historical medicinal preparation.

Degradation of pesticides in biobeds: the effect of concentration and pesticide mixtures.

PubMed

Fogg, Paul; Boxall, Alistair B A; Walker, Allan

2003-08-27

Biobeds aim to create an environment whereby any pesticide spills are retained and then degraded, thus reducing the potential for surface or groundwater contamination. Biobeds may receive high concentrations of relatively complex mixtures of pesticides. The effects of concentration and pesticide interaction on degradation rate were therefore investigated. At concentrations up to 20 times the maximum recommended application rate for isoproturon and chlorothalonil, the rate of degradation in topsoil and biomix decreased with increasing concentration. With the exception of isoproturon at concentrations above 11 mg kg(-1), degradation was quicker in biomix (a composted mixture of topsoil, compost, and wheat straw) than in topsoil. One possible explanation for faster isoproturon degradation in topsoil as compared to biomix may be that previous treatments of isoproturon applied to the field soil as part of normal agricultural practices had resulted in proliferation of microbial communities specifically adapted to use isoproturon as an energy source. Such microbial adaptation could enhance the performance of a biobed. Studies with a mixture of isoproturon and chlorothalonil showed that interactions between pesticides are possible. In biomix, the degradation of either isoproturon or chlorothalonil was unaffected by the presence of the other pesticide, whereas in topsoil, isoproturon DT(50) values increased from 18.5 to 71.5 days in the presence of chlorothalonil. These studies suggest that biobeds appear capable of treating high concentrations of more than one pesticide.

Application of the target lipid model and passive samplers to characterize the toxicity of bioavailable organics in oil sands process-affected water.

PubMed

Redman, Aaron D; Parkerton, Thomas F; Butler, Josh David; Letinski, Daniel J; Frank, Richard A; Hewitt, L Mark; Bartlett, Adrienne J; Gillis, Patricia Leigh; Marentette, Julie R; Parrott, Joanne L; Hughes, Sarah A; Guest, Rodney; Bekele, Asfaw; Zhang, Kun; Morandi, Garrett; Wiseman, Steve B; Giesy, John P

2018-06-14

Oil sand operations in Alberta, Canada will eventually include returning treated process-affected waters to the environment. Organic constituents in oil sand process-affected water (OSPW) represent complex mixtures of nonionic and ionic (e.g. naphthenic acids) compounds, and compositions can vary spatially and temporally, which has impeded development of water quality benchmarks. To address this challenge, it was hypothesized that solid phase microextraction fibers coated with polydimethylsiloxane (PDMS) could be used as a biomimetic extraction (BE) to measure bioavailable organics in OSPW. Organic constituents of OSPW were assumed to contribute additively to toxicity, and partitioning to PDMS was assumed to be predictive of accumulation in target lipids, which were the presumed site of action. This method was tested using toxicity data for individual model compounds, defined mixtures, and organic mixtures extracted from OSPW. Toxicity was correlated with BE data, which supports the use of this method in hazard assessments of acute lethality to aquatic organisms. A species sensitivity distribution (SSD), based on target lipid model and BE values, was similar to SSDs based on residues in tissues for both nonionic and ionic organics. BE was shown to be an analytical tool that accounts for bioaccumulation of organic compound mixtures from which toxicity can be predicted, with the potential to aid in the development of water quality guidelines.

Quantification of Complex Polycyclic Aromatic Hydrocarbon Mixtures in Standard Reference Materials Using GC×GC/ToF-MS

PubMed Central

Manzano, Carlos; Hoh, Eunha; Massey Simonich, Staci L.

2014-01-01

This research is the first to quantify complex PAH mixtures in NIST SRMs using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/ToF-MS), with and without extract cleanup, and reports previously unidentified PAH isomers in the NIST SRMs. We tested a novel, high orthogonality GC column combination (LC-50×NSP-35), as well as with a commonly used column combination (Rtx-5ms×Rxi-17) for the quantification of a complex mixture of 85 different PAHs, including parent (PAHs), alkyl- (MPAHs), nitro- (NPAHs), oxy- (OPAHs), thio- (SPAHs), bromo- (BrPAHs), and chloro-PAHs (ClPAHs) in extracts from two standard reference materials: NIST SRM1650b (diesel particulate matter), with cleanup and NIST SRM1975 (diesel particulate extract), with and without extract cleanup. The LC-50×NSP-35 column combination resulted in an average absolute percent difference of 33.8%, 62.2% and 30.8% compared to the NIST certified PAH concentrations for NIST SRM1650b, NIST SRM1975 with cleanup and NIST SRM1975 without cleanup, while the Rtx-5ms×Rxi-17 resulted in an absolute percent difference of 38.6%, 67.2% and 79.6% for NIST SRM1650b, NIST SRM1975 with cleanup and NIST SRM1975 without cleanup, respectively. This GC×GC/ToF-MS method increases the number of PAHs detected and quantified in complex environmental extracts using a single chromatographic run. Without clean-up, 7 additional compounds were detected and quantified in NIST SRM1975 using the LC-50×NSP-35 column combination. These results suggest that the use of the LC-50×NSP-35 column combination in GC×GC/ToF-MS not only results in better chromatographic resolution and greater orthogonality for the separation of complex PAH mixtures, but can also be used for the accurate quantification of complex PAH mixtures in environmental extracts without cleanup. PMID:23932031

Predicting herbicide mixture effects on multiple algal species using mixture toxicity models.

PubMed

Nagai, Takashi

2017-10-01

The validity of the application of mixture toxicity models, concentration addition and independent action, to a species sensitivity distribution (SSD) for calculation of a multisubstance potentially affected fraction was examined in laboratory experiments. Toxicity assays of herbicide mixtures using 5 species of periphytic algae were conducted. Two mixture experiments were designed: a mixture of 5 herbicides with similar modes of action and a mixture of 5 herbicides with dissimilar modes of action, corresponding to the assumptions of the concentration addition and independent action models, respectively. Experimentally obtained mixture effects on 5 algal species were converted to the fraction of affected (>50% effect on growth rate) species. The predictive ability of the concentration addition and independent action models with direct application to SSD depended on the mode of action of chemicals. That is, prediction was better for the concentration addition model than the independent action model for the mixture of herbicides with similar modes of action. In contrast, prediction was better for the independent action model than the concentration addition model for the mixture of herbicides with dissimilar modes of action. Thus, the concentration addition and independent action models could be applied to SSD in the same manner as for a single-species effect. The present study to validate the application of the concentration addition and independent action models to SSD supports the usefulness of the multisubstance potentially affected fraction as the index of ecological risk. Environ Toxicol Chem 2017;36:2624-2630. © 2017 SETAC. © 2017 SETAC.

The influence of water-ethanol mixture on the thermodynamics of complex formation between 18-crown-6 ether and L-phenylalanine

NASA Astrophysics Data System (ADS)

Usacheva, T. R.; Sharnin, V. A.; Chernov, I. V.; Matteoli, E.; Terekhova, I. V.; Kumeev, R. S.

2012-08-01

The influence of water-ethanol mixture composition on the complex formation between 18-crown-6 ether and L-phenylalanine was studied by titration calorimetry at Т = 298.15 K. The standard thermodynamic parameters (ΔrGо, ΔrHо, ТΔrSо) of formation of [Phe18C6] molecular complex were calculated from data obtained by means of the microcalorimetric system TAM III (TA Instruments, USA) at X(EtOH) = 0.0/0.6 mol fraction. The stability of [Phe18C6] and the mechanism of complexation in water were investigated using the 1Н and 13С NMR spectroscopy. The increase of EtOH concentration results in an increase of the complex stability and of the exothermicity of complexation.

The noninvasive mouse ear swelling assay. II. Testing the contact sensitizing potency of fragrances.

PubMed

Thorne, P S; Hawk, C; Kaliszewski, S D; Guiney, P D

1991-11-01

The noninvasive mouse ear swelling assay (MESA) for contact allergy testing was evaluated using fragrance components and complex fragrance mixtures. The test materials represented weak sensitizers and nonsensitizers. Two versions of the MESA were investigated. Both were noninvasive and utilized only topical abdominal dosing and ear challenge with single applications in BALB/cBy mice. The vit A MESA differed from the regular MESA only in that mice were maintained on a diet with 17-fold higher levels of vitamin A (vit A) acetate beginning 3 weeks prior to induction. Sensitization reactions were determined by measuring the mean increase in ear swelling over baseline at 24, 48 and 72 hr postexposure. Irritation dose-response curves facilitated choosing a high nonirritating challenge dose. Sensitization dose-response curves were developed for cinnamaldehyde (CINN) and a complex fragrance mixture, F-16. From these curves, the SD50 was determined. This value represents the dose which sensitized half the animals and serves to rank the potency of compounds for allergic contact dermatitis and to compare values among different assays. The SD50 for CINN was 21.6% while the SD50vit A for F-16 was 26.6%. The other fragrance, isoeugenol (ISOE), and fragrance mixtures, F-07 and F-22, were also found to be weak sensitizers in the MESA and vit A MESA. The results in the MESA for CINN and ISOE were in the range observed with guinea pig test protocols but showed that the MESA was more sensitive than human test protocols. Two of the fragrance mixtures tested in the MESA gave comparable results in the Buehler guinea pig assay. However, the third (F-22) was negative in the Buehler assay and the MESA, but positive in the vit A MESA. The results of this work with weak sensitizers and the companion study (Thorne et al., 1991) with potent sensitizers at low doses illustrate that the noninvasive MESA is as sensitive as many standard guinea pig assays. In addition, it is easier and much less expensive to perform. The vit A MESA has the sensitivity and predictive power needed to test compounds and mixtures for contact sensitizing potency.

Distribution of rhodopin and spirilloxanthin between LH1 and LH2 complexes when incorporating carotenoid mixture into the membrane of purple sulfur bacterium Allochromatium minutissimum in vitro.

PubMed

Bolshakov, M A; Ashikhmin, A A; Makhneva, Z K; Moskalenko, A A

2016-11-01

Carotenoid mixture enriched by rhodopin and spirilloxanthin was incorporated in LH2 and LH1 complexes from Allochromatium (Alc.) minutissimum in vitro. The maximum incorporating level was ~95%. Rhodopin (56.4%) and spirilloxanthin (13.8%) were incorporated into the LH1 complex, in contrast to the control complex, which contained primarily spirilloxanthin (66.8%). After incorporating, the LH2 complex contained rhodopin (66.7%) and didehydrorhodopin (14.6%), which was close to their content in the control (67.4 and 20.5%, respectively). Thus, it was shown that carotenoids from the total pool are not selectively incorporated into LH2 and LH1 complexes in vitro in the proportion corresponding to the carotenoid content in the complexes in vivo.

Improved thermal-stability and mechanical properties of type I collagen by crosslinking with casein, keratin and soy protein isolate using transglutaminase.

PubMed

Wu, Xiaomeng; Liu, Yaowei; Liu, Anjun; Wang, Wenhang

2017-05-01

The inferior thermal- stability of collagen hinders its extensive application in food industry, including edible packaging. To improve the thermal- stability and mechanical properties of collagen, we attempted to crosslink collagen with some proteins possessing excellent thermal stability (i. e., casein, keratin and soy protein isolate (SPI)). Observed from the SDS- PAGE and particle size distribution, some complexes with higher molecule weight and relative bigger size particle occurred in the protein mixture, especially after TGase crosslinking. Importantly, the crosslinking greatly improved the thermal- stable property of protein complex, especially that of the collagen- casein complex judged from differential scanning calorimetric (DSC). Moreover, the crosslinking enhanced the mechanical properties of the combined films in terms of tensile strength (TS) and elongation at break (EAB). Also, some obvious differences in morphology of proteins before and after TGase crosslinking were observed by scanning electron microscopy (SEM). These impacts of TGase crosslinking with heat- resistant proteins on collagen features were associated with the conformational changes of the protein complex analyzed by Fourier transform infrared spectroscopy (FTIR). In conclusion, TGase crosslinking with higher thermally stable proteins could be an effective method to contribute to collagen' application in food packaging field. Copyright © 2017 Elsevier B.V. All rights reserved.

Intestinal Permeability of β-Lapachone and Its Cyclodextrin Complexes and Physical Mixtures.

PubMed

Mangas-Sanjuan, Victor; Gutiérrez-Nieto, Jorge; Echezarreta-López, Magdalena; González-Álvarez, Isabel; González-Álvarez, Marta; Casabó, Vicente-Germán; Bermejo, Marival; Landin, Mariana

2016-12-01

β-Lapachone (βLAP) is a promising, poorly soluble, antitumoral drug. βLAP combination with cyclodextrins (CDs) improves its solubility and dissolution but there is not enough information about the impact of cyclodextrins on βLAP intestinal permeability. The objectives of this work were to characterize βLAP intestinal permeability and to elucidate cyclodextrins effect on the dissolution properties and on the intestinal permeability. The final goal was to evaluate CDs influence on the oral absorption of βLAP. Binary systems (physical mixtures and inclusion complexes) including βLAP and CDs (β-cyclodextrin: βCD, random-methyl-β-cyclodextrin: RMβCD and sulfobutylether-β-cyclodextrin: SBEβCD) have been prepared and analysed by differential scanning calorimetry. βLAP (and its combinations with CDs) absorption rate coefficients and effective permeability values have been determined in vitro in MDCK or MDCK-Mdr1 monolayers and in situ in rat by a closed loop perfusion technique. DSC results confirmed the formation of the inclusion complexes. βLAP-CDs inclusion complexes improve drug solubility and dissolution rate in comparison with physical mixtures. βLAP presented a high permeability value which can provide complete oral absorption. Its oral absorption is limited by its low solubility and dissolution rate. Cyclodextrin (both as physical mixtures and inclusion complexes) showed a positive effect on the intestinal permeability of βLAP. Complexation with CDs does not reduce βLAP intestinal permeability in spite of the potential negative effect of the reduction in free fraction of the drug. The use of RMβCD or SBEβCD inclusion complexes could benefit βLAP oral absorption by enhancing its solubility, dissolution rate and permeability.

Evaluation of the Orbitrap Mass Spectrometer for the Molecular Fingerprinting Analysis of Natural Dissolved Organic Matter.

PubMed

Hawkes, Jeffrey A; Dittmar, Thorsten; Patriarca, Claudia; Tranvik, Lars; Bergquist, Jonas

2016-08-02

We investigated the application of the LTQ-Orbitrap mass spectrometer (LTQ-Velos Pro, Thermo Fisher) for resolving complex mixtures of natural aquatic dissolved organic matter (DOM) and compared this technique to the more established state-of-the-art technique, Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS, Bruker Daltonics), in terms of the distribution of molecular masses detected and the reproducibility of the results collected. The Orbitrap was capable of excellent reproducibility: Bray-Curtis dissimilarity between duplicate measurements was 2.85 ± 0.42% (mean ± standard deviation). The Orbitrap was also capable of the detection of most major ionizable organic molecules in typical aquatic mixtures, with the exception of most sulfur and phosphorus containing masses. This result signifies that the Orbitrap is an appropriate technique for the investigation of very subtle biogeochemical processing of bulk DOM. The lower costs (purchase and maintenance) and wider availability of Orbitrap mass spectrometers in university departments means that the tools necessary for research into DOM processing at the molecular level should be accessible to a much wider group of scientists than before. The main disadvantage of the technique is that substantially fewer molecular formulas can be resolved from a complex mixture (roughly one third as many), meaning some loss of information. In balance, most biogeochemical studies that aim at molecularly fingerprinting the source of natural DOM could be satisfactorily carried out with Orbitrap mass spectrometry. For more targeted metabolomic studies where individual compounds are traced through natural systems, FTICR-MS remains advantageous.

Application of quality by design concept to develop a dual gradient elution stability-indicating method for cloxacillin forced degradation studies using combined mixture-process variable models.

PubMed

Zhang, Xia; Hu, Changqin

2017-09-08

Penicillins are typical of complex ionic samples which likely contain large number of degradation-related impurities (DRIs) with different polarities and charge properties. It is often a challenge to develop selective and robust high performance liquid chromatography (HPLC) methods for the efficient separation of all DRIs. In this study, an analytical quality by design (AQbD) approach was proposed for stability-indicating method development of cloxacillin. The structures, retention and UV characteristics rules of penicillins and their impurities were summarized and served as useful prior knowledge. Through quality risk assessment and screen design, 3 critical process parameters (CPPs) were defined, including 2 mixture variables (MVs) and 1 process variable (PV). A combined mixture-process variable (MPV) design was conducted to evaluate the 3 CPPs simultaneously and a response surface methodology (RSM) was used to achieve the optimal experiment parameters. A dual gradient elution was performed to change buffer pH, mobile-phase type and strength simultaneously. The design spaces (DSs) was evaluated using Monte Carlo simulation to give their possibility of meeting the specifications of CQAs. A Plackett-Burman design was performed to test the robustness around the working points and to decide the normal operating ranges (NORs). Finally, validation was performed following International Conference on Harmonisation (ICH) guidelines. To our knowledge, this is the first study of using MPV design and dual gradient elution to develop HPLC methods and improve separations for complex ionic samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular insights into early stage aggregation of di-Fmoc-L-lysine in binary mixture of organic solvent and water

NASA Astrophysics Data System (ADS)

Huda, Md Masrul; Rai, Neeraj

Molecular gels are relatively new class of soft materials, which are formed by the supramolecular aggregation of low molecular weight gelators (LMWGs) in organic solvents and/or water. Hierarchical self-assembly of small gelator molecules lead to three-dimensional complex fibrillar networks, which restricts the flow of solvents and results in viscous solid like materials or gels. These gels have drawn significant attentions for their potential applications for drug delivery, tissue engineering, materials for sensors etc. As of now, self-assembly of gelator molecules into one-dimensional fibers is not well understood, although that is very important to design new gelators for desired applications. Here, we present molecular dynamics study that provides molecular level insight into early stage aggregation of selected gelator, di-Fmoc-L-lysine in binary mixture of organic solvent and water. We will present the role of different functional groups of gelator molecule such as aromatic ring, amide, and carboxylic group on aggregation. We will also present the effect of concentrations of gelator and solvent on self-assembly of gelators. This study has captured helical fiber growth and branching of fiber, which is in good agreement with experimental observations.

Lipase immobilization for catalytic applications obtained using fumed silica deposited with MAPLE technique

NASA Astrophysics Data System (ADS)

Bloisi, Francesco; Califano, Valeria; Perretta, Giuseppe; Nasti, Libera; Aronne, Antonio; Di Girolamo, Rocco; Auriemma, Finizia; De Rosa, Claudio; Vicari, Luciano R. M.

2016-06-01

Lipases are enzymes used for catalyzing reactions of acylglycerides in biodiesel production from lipids, where enzyme immobilization on a substrate is required. Silica nanoparticles in different morphologies and configurations are currently used in conjunction with biological molecules for drug delivery and catalysis applications, but up to date their use for triglycerides has been limited by the large size of long-chain lipid molecules. Matrix assisted pulsed laser evaporation (MAPLE), a laser deposition technique using a frozen solution/suspension as a target, is widely used for deposition of biomaterials and other delicate molecules. We have carried out a MAPLE deposition starting from a frozen mixture containing fumed silica and lipase in water. Deposition parameters were chosen in order to increase surface roughness and to promote the formation of complex structures. Both the target (a frozen thickened mixture of nanoparticles/catalyst in water) and the deposition configuration (a small target to substrate distance) are unusual and have been adopted in order to increase surface contact of catalyst and to facilitate access to long-chain molecules. The resulting innovative film morphology (fumed silica/lipase cluster level aggregation) and the lipase functionality (for catalytic biodiesel production) have been studied by FESEM, FTIR and transesterification tests.

Headgroup interactions and ion flotation efficiency in mixtures of a chelating surfactant, different foaming agents, and divalent metal ions.

PubMed

Svanedal, Ida; Boija, Susanne; Norgren, Magnus; Edlund, Håkan

2014-06-10

The correlation between interaction parameters and ion flotation efficiency in mixtures of chelating surfactant metal complexes and different foaming agents was investigated. We have recently shown that chelating surfactant 2-dodecyldiethylenetriaminepentaacetic acid (4-C12-DTPA) forms strong coordination complexes with divalent metal ions, and this can be utilized in ion flotation. Interaction parameters for mixed micelles and mixed monolayer formation for Mg(2+) and Ni(2+) complexes with the chelating surfactant 4-C12-DTPA and different foaming agents were calculated by Rubingh's regular solution theory. Parameters for the calculations were extracted from surface tension measurements and NMR diffusometry. The effects of metal ion coordination on the interactions between 4-C12-DTPA and the foaming agents could be linked to a previously established difference in coordination chemistry between the examined metal ions. As can be expected from mixtures of amphoteric surfactants, the interactions were strongly pH-dependent. Strong correlation was found between interaction parameter β(σ) for mixed monolayer formation and the phase-transfer efficiency of Ni(2+) complexes with 4-C12-DTPA during flotation in a customized flotation cell. In a mixture of Cu(2+) and Zn(2+), the significant difference in conditional stability constants (log K) between the metal complexes was utilized to selectively recover the metal complex with the highest log K (Cu(2+)) by ion flotation. Flotation experiments in an excess concentration of metal ions confirmed the coordination of more than one metal ion to the headgroup of 4-C12-DTPA.

Bioanalytical Methods for Food Contaminant Analysis

EPA Science Inventory

Foods are complex mixtures of lipids, carbohydrates, proteins, vitamins, organic compounds and other naturally occurring compounds. Sometimes added to this mixture are residues of pesticides, veterinary and human drugs, microbial toxins, preservatives, contaminants from food proc...

Study of oil-water partitioning of a chemical dispersant using an acute bioassay with marine crustaceans

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

Wells, P.G.; Abernethy, S.; Mackay, D.

1982-01-01

The toxicity of seawater dispersions of a chemical dispersant to two marine crustaceans was investigated in the presence and absence of various quantities of a non-toxic mineral oil. From the results and a physical-chemical partitioning analysis, a limiting value of the oil-water partition coefficient of the toxic compounds is deduced suggesting that essentially all of the toxic compounds in the dispersant will partition into solution in water following dispersant application to an oil spill. This conclusion simplifies interpretation and prediction of the toxic effects of a dispersed oil spill. The combined bioassay-partitioning procedure may have applications to the study ofmore » the toxicity of other complex mixtures such as industrial effluents.« less

Potential role of bromelain in clinical and therapeutic applications

PubMed Central

Rathnavelu, Vidhya; Alitheen, Noorjahan Banu; Sohila, Subramaniam; Kanagesan, Samikannu; Ramesh, Rajendran

2016-01-01

Pineapple has been used as part of traditional folk medicine since ancient times and it continues to be present in various herbal preparations. Bromelain is a complex mixture of protease extracted from the fruit or stem of the pineapple plant. Although the complete molecular mechanism of action of bromelain has not been completely identified, bromelain gained universal acceptability as a phytotherapeutic agent due to its history of safe use and lack of side effects. Bromelain is widely administered for its well-recognized properties, such as its anti-inflammatory, antithrombotic and fibrinolytic affects, anticancer activity and immunomodulatory effects, in addition to being a wound healing and circulatory improvement agent. The current review describes the promising clinical applications and therapeutic properties of bromelain. PMID:27602208

Effects of Polar Bear and Killer Whale Derived Contaminant Cocktails on Marine Mammal Immunity.

PubMed

Desforges, Jean-Pierre; Levin, Milton; Jasperse, Lindsay; De Guise, Sylvain; Eulaers, Igor; Letcher, Robert J; Acquarone, Mario; Nordøy, Erling; Folkow, Lars P; Hammer Jensen, Trine; Grøndahl, Carsten; Bertelsen, Mads F; St Leger, Judy; Almunia, Javier; Sonne, Christian; Dietz, Rune

2017-10-03

Most controlled toxicity studies use single chemical exposures that do not represent the real world situation of complex mixtures of known and unknown natural and anthropogenic substances. In the present study, complex contaminant cocktails derived from the blubber of polar bears (PB; Ursus maritimus) and killer whales (KW; Orcinus orca) were used for in vitro concentration-response experiments with PB, cetacean and seal spp. immune cells to evaluate the effect of realistic contaminant mixtures on various immune functions. Cytotoxic effects of the PB cocktail occurred at lower concentrations than the KW cocktail (1 vs 16 μg/mL), likely due to differences in contaminant profiles in the mixtures derived from the adipose of each species. Similarly, significant reduction of lymphocyte proliferation occurred at much lower exposures in the PB cocktail (EC 50 : 0.94 vs 6.06 μg/mL; P < 0.01), whereas the KW cocktail caused a much faster decline in proliferation (slope: 2.9 vs 1.7; P = 0.04). Only the KW cocktail modulated natural killer (NK) cell activity and neutrophil and monocyte phagocytosis in a concentration- and species-dependent manner. No clear sensitivity differences emerged when comparing cetaceans, seals and PB. Our results showing lower effect levels for complex mixtures relative to single compounds suggest that previous risk assessments underestimate the effects of real world contaminant exposure on immunity. Our results using blubber-derived contaminant cocktails add realism to in vitro exposure experiments and confirm the immunotoxic risk marine mammals face from exposure to complex mixtures of environmental contaminants.

Solid-phase microextraction low temperature plasma mass spectrometry for the direct and rapid analysis of chemical warfare simulants in complex mixtures.

PubMed

Dumlao, Morphy C; Jeffress, Laura E; Gooding, J Justin; Donald, William A

2016-06-21

Solid-phase microextraction (SPME) is directly integrated with low temperature plasma ionisation mass spectrometry to rapidly detect organophosphate chemical warfare agent simulants and their hydrolysis products in chemical mixtures, including urine. In this sampling and ionization method, the fibre serves: (i) to extract molecules from their native environment, and (ii) as the ionization electrode that is used to desorb and ionize molecules directly from the SPME surface. By use of a custom fabricated SPME fibre consisting of a stainless steel needle coated with a Linde Type A (LTA) zeolitic microporous material and low temperature plasma mass spectrometry, protonated dimethyl methylphosphonate (DMMP), diethyl ethylphosphonate (DEEP) and pinacolyl methylphosphonic acid (PinMPA) can be detected at less than 100 ppb directly in water and urine. Organophosphates were not readily detected by this approach using an uncoated needle in negative control experiments. The use of the LTA coating significantly outperformed the use of a high alumina Zeolite Socony Mobil-5 (ZSM-5) coating of comparable thickness that is significantly less polar than LTA. By conditioning the LTA probe by immersion in an aqueous CuSO4 solution, the ion abundance for protonated DMMP increased by more than 300% compared to that obtained without any conditioning. Sample recovery values were between 96 and 100% for each analyte. The detection of chemical warfare agent analogues and hydrolysis products required less than 2 min per sample. A key advantage of this sampling and ionization method is that analyte ions can be directly and rapidly sampled from chemical mixtures, such as urine and seawater, without sample preparation or chromatography for sensitive detection by mass spectrometry. This ion source should prove beneficial for portable mass spectrometry applications because relatively low detection limits can be obtained without the use of compressed gases, fluid pumps, and lasers. Moreover, the ion source is compact, can be powered with a 10 V battery, and is tolerant of complex mixtures.

The equilibrium constant of complex formation in solution: A study utilizing a dielectric constant method

NASA Astrophysics Data System (ADS)

Loh, C. W.

1980-03-01

A method was developed for determining equilibrium constants, heat of reaction, and change in free energy and entropy during a 1:1 complex formation in solutions. The measurements were carried out on ternary systems containing two interacting solutes in an inert solvent. The procedures was applied to the investigation of hydrogen bond complex formations in two mixtures systems, phenol and pyridine in carbon tetrachloride, and 4, 5, 6, 7-tetrachloro-2-trifluoromethylbenzimidazole (TTFB) and alkyl acetate in styrene. The first mixture system was studied in order to compare the results with those obtained by other methods. Results for the second mixture system indicated strong association between molecules of TTFB and alkyl acetate and suggested that the blocking of valinomycin-mediated bilayer membrane conductance by substituted benzimidazoles was due to competition for a limited number of adsorption sites on the membrane surface.

Study of complex permittivity spectra of binary mixtures of 2-chloroaniline and methanol in frequency range 10 KHz to 2 MHz at different temperatures

NASA Astrophysics Data System (ADS)

Shah, N. S.; Vankar, H. P.; Rana, V. A.

2017-05-01

The complex relative dielectric function ɛ*(ω)=ɛ'-jɛ″ of the binary mixture of 2-chloroaniline(2-CA) and methanol (MeOH) were measured using precision LCR meter in the frequency range of 10 KHz to 2 MHz The measurements were carried out at eight different temperatures and five different concentrations of 2-CA and MeOH. The loss tangent peaks were observed in the studied frequency range for all the binary mixtures. From the loss tangent peaks electrode polarization relaxation time were evaluated. In the plot of real part of complex permittivity against frequency, at different temperatures for 2-CA (54.54%) + MeOH (45.45%) and 2-CA (27.27%) + MeOH (72.72%)and 100% MeOH systems permittivity inversion effect was observed.

State of research: environmental pathways and food chain transfer.

PubMed Central

Vaughan, B E

1984-01-01

Data on the chemistry of biologically active components of petroleum, synthetic fuel oils, certain metal elements and pesticides provide valuable generic information needed for predicting the long-term fate of buried waste constituents and their likelihood of entering food chains. Components of such complex mixtures partition between solid and solution phases, influencing their mobility, volatility and susceptibility to microbial transformation. Estimating health hazards from indirect exposures to organic chemicals involves an ecosystem's approach to understanding the unique behavior of complex mixtures. Metabolism by microbial organisms fundamentally alters these complex mixtures as they move through food chains. Pathway modeling of organic chemicals must consider the nature and magnitude of food chain transfers to predict biological risk where metabolites may become more toxic than the parent compound. To obtain predictions, major areas are identified where data acquisition is essential to extend our radiological modeling experience to the field of organic chemical contamination. PMID:6428875

An assessment of the information content of likelihood ratios derived from complex mixtures.

PubMed

Marsden, Clare D; Rudin, Norah; Inman, Keith; Lohmueller, Kirk E

2016-05-01

With the increasing sensitivity of DNA typing methodologies, as well as increasing awareness by law enforcement of the perceived capabilities of DNA typing, complex mixtures consisting of DNA from two or more contributors are increasingly being encountered. However, insufficient research has been conducted to characterize the ability to distinguish a true contributor (TC) from a known non-contributor (KNC) in these complex samples, and under what specific conditions. In order to investigate this question, sets of six 15-locus Caucasian genotype profiles were simulated and used to create mixtures containing 2-5 contributors. Likelihood ratios were computed for various situations, including varying numbers of contributors and unknowns in the evidence profile, as well as comparisons of the evidence profile to TCs and KNCs. This work was intended to illustrate the best-case scenario, in which all alleles from the TC were detected in the simulated evidence samples. Therefore the possibility of drop-out was not modeled in this study. The computer program DNAMIX was then used to compute LRs comparing the evidence profile to TCs and KNCs. This resulted in 140,000 LRs for each of the two scenarios. These complex mixture simulations show that, even when all alleles are detected (i.e. no drop-out), TCs can generate LRs less than 1 across a 15-locus profile. However, this outcome was rare, 7 of 140,000 replicates (0.005%), and associated only with mixtures comprising 5 contributors in which the numerator hypothesis includes one or more unknown contributors. For KNCs, LRs were found to be greater than 1 in a small number of replicates (75 of 140,000 replicates, or 0.05%). These replicates were limited to 4 and 5 person mixtures with 1 or more unknowns in the numerator. Only 5 of these 75 replicates (0.004%) yielded an LR greater than 1,000. Thus, overall, these results imply that the weight of evidence that can be derived from complex mixtures containing up to 5 contributors, under a scenario in which no drop-out is required to explain any of the contributors, is remarkably high. This is a useful benchmark result on top of which to layer the effects of additional factors, such as drop-out, peak height, and other variables. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Energetic lanthanide complexes: coordination chemistry and explosives applications

NASA Astrophysics Data System (ADS)

Manner, V. W.; Barker, B. J.; Sanders, V. E.; Laintz, K. E.; Scott, B. L.; Preston, D. N.; Sandstrom, M.; Reardon, B. L.

2014-05-01

Metals are generally added to organic molecular explosives in a heterogeneous composite to improve overall heat and energy release. In order to avoid creating a mixture that can vary in homogeneity, energetic organic molecules can be directly bonded to high molecular weight metals, forming a single metal complex with Angstrom-scale separation between the metal and the explosive. To probe the relationship between the structural properties of metal complexes and explosive performance, a new series of energetic lanthanide complexes has been prepared using energetic ligands such as NTO (5-nitro-2,4-dihydro-1,2,4-triazole-3-one). These are the first examples of lanthanide NTO complexes where no water is coordinated to the metal, demonstrating novel control of the coordination environment. The complexes have been characterized by X-ray crystallography, NMR and IR spectroscopies, photoluminescence, and sensitivity testing. The structural and energetic properties are discussed in the context of enhanced blast effects and detection. Cheetah calculations have been performed to fine-tune physical properties, creating a systematic method for producing explosives with 'tailor made' characteristics. These new complexes will be benchmarks for further study in the field of metalized high explosives.

Energetic Lanthanide Complexes: Coordination Chemistry and Explosives Applications

NASA Astrophysics Data System (ADS)

Manner, Virginia; Barker, Beau; Sanders, Eric; Laintz, Kenneth; Scott, Brian; Preston, Daniel; Sandstrom, Mary; Reardon, Bettina

2013-06-01

Metals are generally added to organic molecular explosives in a heterogeneous composite to improve overall heat and energy release. In order to avoid creating a mixture that can vary in homogeneity, energetic organic molecules can be directly bonded to high molecular weight metals, forming a single metal complex with Angstrom-scale separation between the metal and the explosive. To probe the relationship between the structural properties of metal complexes and explosive performance, a new series of energetic lanthanide complexes has been prepared using energetic ligands such as NTO (5-nitro-2,4-dihydro-1,2,4-triazole-3-one). These are the first examples of lanthanide NTO complexes where no water is coordinated to the metal, demonstrating novel control of the coordination environment. The complexes have been characterized by X-ray crystallography, NMR and IR spectroscopies, photoluminescence, and sensitivity testing. The structural and energetic properties are discussed in the context of enhanced blast effects and detection. Cheetah calculations have been performed to fine-tune physical properties, creating a systematic method for producing explosives with ``tailor made'' characteristics. These new complexes will be benchmarks for further study in the field of metalized high explosives.

EDCs Mixtures: A Stealthy Hazard for Human Health?

PubMed

Ribeiro, Edna; Ladeira, Carina; Viegas, Susana

2017-02-07

Endocrine disrupting chemicals (EDCs) are exogenous chemicals that may occur naturally (e.g., phytoestrogens), while others are industrial substances and plasticizers commonly utilized worldwide to which human exposure, particularly at low-doses, is omnipresent, persistent and occurs in complex mixtures. EDCs can interfere with/or mimic estrogenic hormones and, consequently, can simultaneously trigger diverse signaling pathways which result in diverse and divergent biological responses. Additionally, EDCs can also bioaccumulate in lipid compartments of the organism forming a mixed "body burden" of contaminants. Although the independent action of chemicals has been considered the main principle in EDCs mixture toxicity, recent studies have demonstrated that numerous effects cannot be predicted when analyzing single compounds independently. Co-exposure to these agents, particularly in critical windows of exposure, may induce hazardous health effects potentially associated with a complex "body burden" of different origins. Here, we performed an exhaustive review of the available literature regarding EDCs mixtures exposure, toxicity mechanisms and effects, particularly at the most vulnerable human life stages. Although the assessment of potential risks to human health due to exposure to EDCs mixtures is a major topic for consumer safety, information regarding effective mixtures effects is still scarce.

Peptide Identification by Database Search of Mixture Tandem Mass Spectra*

PubMed Central

Wang, Jian; Bourne, Philip E.; Bandeira, Nuno

2011-01-01

In high-throughput proteomics the development of computational methods and novel experimental strategies often rely on each other. In certain areas, mass spectrometry methods for data acquisition are ahead of computational methods to interpret the resulting tandem mass spectra. Particularly, although there are numerous situations in which a mixture tandem mass spectrum can contain fragment ions from two or more peptides, nearly all database search tools still make the assumption that each tandem mass spectrum comes from one peptide. Common examples include mixture spectra from co-eluting peptides in complex samples, spectra generated from data-independent acquisition methods, and spectra from peptides with complex post-translational modifications. We propose a new database search tool (MixDB) that is able to identify mixture tandem mass spectra from more than one peptide. We show that peptides can be reliably identified with up to 95% accuracy from mixture spectra while considering only a 0.01% of all possible peptide pairs (four orders of magnitude speedup). Comparison with current database search methods indicates that our approach has better or comparable sensitivity and precision at identifying single-peptide spectra while simultaneously being able to identify 38% more peptides from mixture spectra at significantly higher precision. PMID:21862760

EDCs Mixtures: A Stealthy Hazard for Human Health?

PubMed Central

Ribeiro, Edna; Ladeira, Carina; Viegas, Susana

2017-01-01

Endocrine disrupting chemicals (EDCs) are exogenous chemicals that may occur naturally (e.g., phytoestrogens), while others are industrial substances and plasticizers commonly utilized worldwide to which human exposure, particularly at low-doses, is omnipresent, persistent and occurs in complex mixtures. EDCs can interfere with/or mimic estrogenic hormones and, consequently, can simultaneously trigger diverse signaling pathways which result in diverse and divergent biological responses. Additionally, EDCs can also bioaccumulate in lipid compartments of the organism forming a mixed “body burden” of contaminants. Although the independent action of chemicals has been considered the main principle in EDCs mixture toxicity, recent studies have demonstrated that numerous effects cannot be predicted when analyzing single compounds independently. Co-exposure to these agents, particularly in critical windows of exposure, may induce hazardous health effects potentially associated with a complex “body burden” of different origins. Here, we performed an exhaustive review of the available literature regarding EDCs mixtures exposure, toxicity mechanisms and effects, particularly at the most vulnerable human life stages. Although the assessment of potential risks to human health due to exposure to EDCs mixtures is a major topic for consumer safety, information regarding effective mixtures effects is still scarce. PMID:29051438

Hydrogen-related complexes in Li-diffused ZnO single crystals

DOE PAGES

Corolewski, Caleb D.; Parmar, Narendra S.; Lynn, Kelvin G.; ...

2016-07-21

Zinc oxide (ZnO) is a wide band gap semiconductor and a potential candidate for next generation white solid state lighting applications. In this work, hydrogen-related complexes in lithium diffused ZnO single crystals were studied. In addition to the well-known Li-OH complex, several other hydrogen defects were observed. When a mixture of Li 2O and ZnO is used as the dopant source, zinc vacancies are suppressed and the bulk Li concentration is very high (>10 19 cm -3). In that case, the predominant hydrogen complex has a vibrational frequency of 3677 cm -1, attributed to surface O-H species. When Li 2COmore » 3 is used, a structured blue luminescence band and O-H mode at 3327 cm -1 are observed at 10K. These observations, along with positron annihilation measurements, suggest a zinc vacancy–hydrogen complex, with an acceptor level 0.3 eV above the valence-band maximum. In conclusion, this relatively shallow acceptor could be beneficial for p-type ZnO.« less

Sound stream segregation: a neuromorphic approach to solve the “cocktail party problem” in real-time

PubMed Central

Thakur, Chetan Singh; Wang, Runchun M.; Afshar, Saeed; Hamilton, Tara J.; Tapson, Jonathan C.; Shamma, Shihab A.; van Schaik, André

2015-01-01

The human auditory system has the ability to segregate complex auditory scenes into a foreground component and a background, allowing us to listen to specific speech sounds from a mixture of sounds. Selective attention plays a crucial role in this process, colloquially known as the “cocktail party effect.” It has not been possible to build a machine that can emulate this human ability in real-time. Here, we have developed a framework for the implementation of a neuromorphic sound segregation algorithm in a Field Programmable Gate Array (FPGA). This algorithm is based on the principles of temporal coherence and uses an attention signal to separate a target sound stream from background noise. Temporal coherence implies that auditory features belonging to the same sound source are coherently modulated and evoke highly correlated neural response patterns. The basis for this form of sound segregation is that responses from pairs of channels that are strongly positively correlated belong to the same stream, while channels that are uncorrelated or anti-correlated belong to different streams. In our framework, we have used a neuromorphic cochlea as a frontend sound analyser to extract spatial information of the sound input, which then passes through band pass filters that extract the sound envelope at various modulation rates. Further stages include feature extraction and mask generation, which is finally used to reconstruct the targeted sound. Using sample tonal and speech mixtures, we show that our FPGA architecture is able to segregate sound sources in real-time. The accuracy of segregation is indicated by the high signal-to-noise ratio (SNR) of the segregated stream (90, 77, and 55 dB for simple tone, complex tone, and speech, respectively) as compared to the SNR of the mixture waveform (0 dB). This system may be easily extended for the segregation of complex speech signals, and may thus find various applications in electronic devices such as for sound segregation and speech recognition. PMID:26388721

Sound stream segregation: a neuromorphic approach to solve the "cocktail party problem" in real-time.

PubMed

Thakur, Chetan Singh; Wang, Runchun M; Afshar, Saeed; Hamilton, Tara J; Tapson, Jonathan C; Shamma, Shihab A; van Schaik, André

2015-01-01

The human auditory system has the ability to segregate complex auditory scenes into a foreground component and a background, allowing us to listen to specific speech sounds from a mixture of sounds. Selective attention plays a crucial role in this process, colloquially known as the "cocktail party effect." It has not been possible to build a machine that can emulate this human ability in real-time. Here, we have developed a framework for the implementation of a neuromorphic sound segregation algorithm in a Field Programmable Gate Array (FPGA). This algorithm is based on the principles of temporal coherence and uses an attention signal to separate a target sound stream from background noise. Temporal coherence implies that auditory features belonging to the same sound source are coherently modulated and evoke highly correlated neural response patterns. The basis for this form of sound segregation is that responses from pairs of channels that are strongly positively correlated belong to the same stream, while channels that are uncorrelated or anti-correlated belong to different streams. In our framework, we have used a neuromorphic cochlea as a frontend sound analyser to extract spatial information of the sound input, which then passes through band pass filters that extract the sound envelope at various modulation rates. Further stages include feature extraction and mask generation, which is finally used to reconstruct the targeted sound. Using sample tonal and speech mixtures, we show that our FPGA architecture is able to segregate sound sources in real-time. The accuracy of segregation is indicated by the high signal-to-noise ratio (SNR) of the segregated stream (90, 77, and 55 dB for simple tone, complex tone, and speech, respectively) as compared to the SNR of the mixture waveform (0 dB). This system may be easily extended for the segregation of complex speech signals, and may thus find various applications in electronic devices such as for sound segregation and speech recognition.

A Experimental Study of the Growth of Laser Spark and Electric Spark Ignited Flame Kernels.

NASA Astrophysics Data System (ADS)

Ho, Chi Ming

1995-01-01

Better ignition sources are constantly in demand for enhancing the spark ignition in practical applications such as automotive and liquid rocket engines. In response to this practical challenge, the present experimental study was conducted with the major objective to obtain a better understanding on how spark formation and hence spark characteristics affect the flame kernel growth. Two laser sparks and one electric spark were studied in air, propane-air, propane -air-nitrogen, methane-air, and methane-oxygen mixtures that were initially at ambient pressure and temperature. The growth of the kernels was monitored by imaging the kernels with shadowgraph systems, and by imaging the planar laser -induced fluorescence of the hydroxyl radicals inside the kernels. Characteristic dimensions and kernel structures were obtained from these images. Since different energy transfer mechanisms are involved in the formation of a laser spark as compared to that of an electric spark; a laser spark is insensitive to changes in mixture ratio and mixture type, while an electric spark is sensitive to changes in both. The detailed structures of the kernels in air and propane-air mixtures primarily depend on the spark characteristics. But the combustion heat released rapidly in methane-oxygen mixtures significantly modifies the kernel structure. Uneven spark energy distribution causes remarkably asymmetric kernel structure. The breakdown energy of a spark creates a blast wave that shows good agreement with the numerical point blast solution, and a succeeding complex spark-induced flow that agrees reasonably well with a simple puff model. The transient growth rates of the propane-air, propane-air -nitrogen, and methane-air flame kernels can be interpreted in terms of spark effects, flame stretch, and preferential diffusion. For a given mixture, a spark with higher breakdown energy produces a greater and longer-lasting enhancing effect on the kernel growth rate. By comparing the growth rates of the appropriate mixtures, the positive and negative effects of preferential diffusion and flame stretch on the developing flame are clearly demonstrated.

Spectroscopic Case-Based Studies in a Flipped Quantum Mechanics Course

NASA Astrophysics Data System (ADS)

Shipman, Steven

2015-06-01

Students in a flipped Quantum Mechanics course were expected to apply their knowledge of spectroscopy to a variety of case studies involving complex mixtures of chemicals. They used simulated data, prepared in advance by the instructor, to determine the major chemical constituents of complex mixtures. Students were required to request the appropriate data in order to ultimately make plausible guesses about the composition of the mixtures, allowing them ownership over the discovery process. This talk will describe how these activities worked in practice, give caveats for instructors who wish to adopt them in the future, and discuss how the results of these exercises can be used for both formative and summative assessment.

Toxicity of pesticide and fertilizer mixtures simulating corn production to eggs of snapping turtles (Chelydra serpentina).

PubMed

de Solla, Shane Raymond; Martin, Pamela Anne; Mikoda, Paul

2011-09-15

Many reptiles oviposit in soils associated with agricultural landscapes. We evaluated the toxicity of a pesticide and fertilizer regime similar to those used in corn production in Ontario on the survivorship of exposed snapping turtle (Chelydra serpentina) eggs. The herbicides atrazine, dimethenamid, and glyphosate, the pyrethroid insecticide tefluthrin, and the fertilizer ammonia, were applied to clean soil, both as partial mixtures within chemical classes, as well as complete mixtures. Eggs were incubated in the soil in a garden plot in which these mixtures were applied at a typical field application rate, and higher rates. Otherwise, the eggs were unmanipulated and were subject to ambient temperature and weather conditions. Eggs were also exposed at male producing temperatures in the laboratory in covered bins in the same soil, where there was less opportunity for loss through volatilization or leaching. Egg mortality was 100% at 10× the typical field application rate of the complete mixture, both with and without tefluthrin. At typical field application rates, hatching success ranged between 91.7 and 95.8%. Eggs exposed only to herbicides were not negatively affected at any application rates. Although fertilizer treatments at typical field application rates did not affect eggs, mortality was remarkably higher at three times this rate, and 100% at higher rates. The frequency of deformities of hatchlings was elevated at the highest application rate of the insecticide tefluthrin. The majority of the toxicity of the mixture was not due to the herbicides or insecticide, but was due to the ammonia fertilizer. At typical field application rates, the chemical regime associated with corn production does not appear to have any detrimental impacts upon turtle egg development; however toxicity dramatically increases if this threshold is passed. Copyright © 2011. Published by Elsevier B.V.

Use of Activity-Based Probes to Develop High Throughput Screening Assays That Can Be Performed in Complex Cell Extracts

PubMed Central

Deu, Edgar; Yang, Zhimou; Wang, Flora; Klemba, Michael; Bogyo, Matthew

2010-01-01

Background High throughput screening (HTS) is one of the primary tools used to identify novel enzyme inhibitors. However, its applicability is generally restricted to targets that can either be expressed recombinantly or purified in large quantities. Methodology and Principal Findings Here, we described a method to use activity-based probes (ABPs) to identify substrates that are sufficiently selective to allow HTS in complex biological samples. Because ABPs label their target enzymes through the formation of a permanent covalent bond, we can correlate labeling of target enzymes in a complex mixture with inhibition of turnover of a substrate in that same mixture. Thus, substrate specificity can be determined and substrates with sufficiently high selectivity for HTS can be identified. In this study, we demonstrate this method by using an ABP for dipeptidyl aminopeptidases to identify (Pro-Arg)2-Rhodamine as a specific substrate for DPAP1 in Plasmodium falciparum lysates and Cathepsin C in rat liver extracts. We then used this substrate to develop highly sensitive HTS assays (Z’>0.8) that are suitable for use in screening large collections of small molecules (i.e >300,000) for inhibitors of these proteases. Finally, we demonstrate that it is possible to use broad-spectrum ABPs to identify target-specific substrates. Conclusions We believe that this approach will have value for many enzymatic systems where access to large amounts of active enzyme is problematic. PMID:20700487

Signal Partitioning Algorithm for Highly Efficient Gaussian Mixture Modeling in Mass Spectrometry

PubMed Central

Polanski, Andrzej; Marczyk, Michal; Pietrowska, Monika; Widlak, Piotr; Polanska, Joanna

2015-01-01

Mixture - modeling of mass spectra is an approach with many potential applications including peak detection and quantification, smoothing, de-noising, feature extraction and spectral signal compression. However, existing algorithms do not allow for automated analyses of whole spectra. Therefore, despite highlighting potential advantages of mixture modeling of mass spectra of peptide/protein mixtures and some preliminary results presented in several papers, the mixture modeling approach was so far not developed to the stage enabling systematic comparisons with existing software packages for proteomic mass spectra analyses. In this paper we present an efficient algorithm for Gaussian mixture modeling of proteomic mass spectra of different types (e.g., MALDI-ToF profiling, MALDI-IMS). The main idea is automated partitioning of protein mass spectral signal into fragments. The obtained fragments are separately decomposed into Gaussian mixture models. The parameters of the mixture models of fragments are then aggregated to form the mixture model of the whole spectrum. We compare the elaborated algorithm to existing algorithms for peak detection and we demonstrate improvements of peak detection efficiency obtained by using Gaussian mixture modeling. We also show applications of the elaborated algorithm to real proteomic datasets of low and high resolution. PMID:26230717

CuInS2/ZnS QD-ferroelectric liquid crystal mixtures for faster electro-optical devices and their energy storage aspects

NASA Astrophysics Data System (ADS)

Singh, Dharmendra Pratap; Vimal, Tripti; Mange, Yatin J.; Varia, Mahesh C.; Nann, Thomas; Pandey, K. K.; Manohar, Rajiv; Douali, Redouane

2018-01-01

CuInS2/ZnS core/shell quantum dots (CIS/ZnS QDs) dispersed ferroelectric liquid crystal (FLC) mixtures have been characterized for their application in electro-optical devices, energy storage, and solar cells. Physical properties of the CIS/ZnS QD-FLC (ferroelectric liquid crystal) mixtures have also been investigated with varying QD concentrations in order to optimize the critical concentration of QDs in mixtures. The presence of QDs breaks the geometrical symmetry in the FLC matrix, which results in a change in the physical properties of the mixtures. We observed the reduced values of primary and secondary order parameters (tilt angle and spontaneous polarization, respectively) for mixtures, which also depend on the concentration of QDs. The reduction of spontaneous polarization in QDs-FLC mixtures is attributed to the adverse role of flexoelectric contribution in the mixtures. The 92% faster electro-optic response and enhanced capacitance indicate the possible application of these mixtures in electro-optical devices and solar cells. Photoluminescence emission of pure FLC and QDs-FLC mixtures has been thermally tailored, which is explained by suitable models.

Genetic barcoding with fluorescent proteins for multiplexed applications.

PubMed

Smurthwaite, Cameron A; Williams, Wesley; Fetsko, Alexandra; Abbadessa, Darin; Stolp, Zachary D; Reed, Connor W; Dharmawan, Andre; Wolkowicz, Roland

2015-04-14

Fluorescent proteins, fluorescent dyes and fluorophores in general have revolutionized the field of molecular cell biology. In particular, the discovery of fluorescent proteins and their genes have enabled the engineering of protein fusions for localization, the analysis of transcriptional activation and translation of proteins of interest, or the general tracking of individual cells and cell populations. The use of fluorescent protein genes in combination with retroviral technology has further allowed the expression of these proteins in mammalian cells in a stable and reliable manner. Shown here is how one can utilize these genes to give cells within a population of cells their own biosignature. As the biosignature is achieved with retroviral technology, cells are barcoded 'indefinitely'. As such, they can be individually tracked within a mixture of barcoded cells and utilized in more complex biological applications. The tracking of distinct populations in a mixture of cells is ideal for multiplexed applications such as discovery of drugs against a multitude of targets or the activation profile of different promoters. The protocol describes how to elegantly develop and amplify barcoded mammalian cells with distinct genetic fluorescent markers, and how to use several markers at once or one marker at different intensities. Finally, the protocol describes how the cells can be further utilized in combination with cell-based assays to increase the power of analysis through multiplexing.

Application of a multivariate analysis method for non-target screening detection of persistent transformation products during the cork boiling wastewater treatment.

PubMed

Ponce-Robles, L; Oller, I; Agüera, A; Trinidad-Lozano, M J; Yuste, F J; Malato, S; Perez-Estrada, L A

2018-08-15

Cork boiling wastewater is a very complex mixture of naturally occurring compounds leached and partially oxidized during the boiling cycles. The effluent generated is recalcitrant and could cause a significant environmental impact. Moreover, if this untreated industrial wastewater enters a municipal wastewater treatment plant it could hamper or reduce the efficiency of most activated sludge degradation processes. Despite the efforts to treat the cork boiling wastewater for reusing purposes, is still not well-known how safe these compounds (original compounds and oxidation by-products) will be. The purpose of this work was to apply an HPLC-high resolution mass spectrometry method and subsequent non-target screening using a multivariate analysis method (PCA), to explore relationships between samples (treatments) and spectral features (masses or compounds) that could indicate changes in formation, degradation or polarity, during coagulation/flocculation (C/F) and photo-Fenton (PhF). Although, most of the signal intensities were reduced after the treatment line, 16 and 4 new peaks were detected to be formed after C/F and PhF processes respectively. The use of this non-target approach showed to be an effective strategy to explore, classify and detect transformation products during the treatment of an unknown complex mixture. Copyright © 2018 Elsevier B.V. All rights reserved.

Molecular Dynamics Study of Surfactant Self-Assembly on Single-Walled Carbon Nanotubes (SWCNTs)

NASA Astrophysics Data System (ADS)

Phelan, Frederick, Jr.

2015-03-01

Single-walled carbon nanotubes (SWNCTs) are materials with structural, electronic and optical properties that make them attractive for a myriad of advanced technology applications. Increased adaptation of these materials requires advancement in separation techniques which enables them to be sorted with increased reliability into monodisperse fractions with respect to length and chirality. Most separation techniques currently in use rely on dispersion of tubes in aqueous solution using surfactants. This results in a colloidal mixture in which tubes are packed and individually dispersed in a surfactant shell. Understanding the structure and properties of the SWCNT-surfactant complex at the molecular level, and how this is affected by chirality, will help to improve separations processes. In this work, we study the structure and properties of SWCNT-surfactant colloidal complexes using all-atom molecular dynamics. Self-assembled structures are computed for a number of combinations SWCNT/surfactant, and also, co-surfactant mixtures for the bile salt surfactant sodium deoxycholate (DOC) and the anionic surfactant sodium dodecyl sulfate (SDS). From the radial distribution function we estimate the size of the SWCNT hydration layer, and use that information to compute the buoyant densities of unfilled tubes for a number of concentrations. Estimates of the change in hydrodynamic radius with increased surfactant packing and the binding energies of the individual surfactants are also obtained.

High resolution separations of charge variants and disulfide isomers of monoclonal antibodies and antibody drug conjugates using ultra-high voltage capillary electrophoresis with high electric field strength.

PubMed

Henley, W Hampton; He, Yan; Mellors, J Scott; Batz, Nicholas G; Ramsey, J Michael; Jorgenson, James W

2017-11-10

Ultra-high voltage capillary electrophoresis with high electric field strength has been applied to the separation of the charge variants, drug conjugates, and disulfide isomers of monoclonal antibodies. Samples composed of many closely related species are difficult to resolve and quantify using traditional analytical instrumentation. High performance instrumentation can often save considerable time and effort otherwise spent on extensive method development. Ideally, the resolution obtained for a given CE buffer system scales with the square root of the applied voltage. Currently available commercial CE instrumentation is limited to an applied voltage of approximately 30kV and a maximum electric field strength of 1kV/cm due to design limitations. The instrumentation described here is capable of safely applying potentials of at least 120kV with electric field strengths over 2000V/cm, potentially doubling the resolution of the best conventional CE buffer/capillary systems while decreasing analysis time in some applications. Separations of these complex mixtures using this new instrumentation demonstrate the potential of ultra-high voltage CE to identify the presence of previously unresolved components and to reduce analysis time for complex mixtures of antibody variants and drug conjugates. Copyright © 2017 Elsevier B.V. All rights reserved.

Monoclonal antibody to trivalent chromium chelate complex and its application to measurement of the total chromium concentration.

PubMed

Sasaki, Kazuhiro; Oguma, Shinichi; Namiki, Yukie; Ohmura, Naoya

2009-05-15

Isothiocyanobenzyl group-appended ethylenediamine tetraacetic acid (EDTA) was used to covalently couple Cr(III) x EDTA to keyhole limpet hemocyanin for use as an immunogen. An obtained monoclonal antibody (RD3G4) bound to Cr(III) x EDTA with an equilibrium dissociation constant (K(d)) of 9.7 nM, which was 100-fold tighter than the K(d)s for the other tested EDTA-metal complex. In particular, there was an over 2000-fold affinity difference between Cr(III) x EDTA and Fe(III) x EDTA, although the ion radius of trivalent chromium (0.76 A) was quite close to that of ferric ion (0.79 A). Hexavalent chromium could be detected by the antibody after being reduced into trivalent form. An immunoassay format showed an IC50 of 87 nM for hexavalent chromium, with a detection limit of 30 nM (1.6 microg/L). Therefore, the addition of reducing agents to the mixture of tri- and hexavalent chromium allows determination of the total chromium concentration by the immunoassay. Hexavalent chromium could be isolated from trivalent chromium by an anion-exchange column, and thus, the concentration of hexavalent chromium in tri- and hexa- mixture can also be estimated by the immunoassay.

Optical monitoring of gases with cholesteric liquid crystals.

PubMed

Han, Yang; Pacheco, Katherine; Bastiaansen, Cees W M; Broer, Dirk J; Sijbesma, Rint P

2010-03-10

A new approach to optical monitors for gases is introduced using cholesteric liquid crystals doped with reactive chiral compounds. The approach is based on cholesteric pitch length changes caused by a change in helical twisting power (HTP) of the chiral dopants upon reaction with the analyte. The concept is demonstrated for monitoring carbon dioxide via reversible carbamate formation and for oxygen using the irreversible oxidation of a chiral dithiol to a disulfide. Monitoring of CO(2) was achieved by doping a commercial cholesteric liquid crystalline mixture (E7) with 1.6% mol of the 1:1 complex of an optically pure diamine with a TADDOL derivative. Upon exposure to carbon dioxide, the reflection band of a thin film of the mixture shifted from 637 to 495 nm as a consequence of dissociation of the complex after carbamate formation of the diamine. An O(2) monitor was obtained by doping E7 with a chiral binaphthyl dithiol derivative and a nonresponsive codopant. The reflection band of the oxygen monitor film changed from 542 to 600 nm, due to the conformational change accompanying oxidation of the dithiol to disulfide. These monitoring mechanisms hold promise for application in smart packaging, where carbon dioxide and oxygen are of special interest because of their roles in food preservation.

Local and systemic toxicity of JP-8 from cutaneous exposures.

PubMed

McDougal, James N; Rogers, James V

2004-04-01

Jet propellant-8 (JP-8) jet fuel is a version of commercial jet fuel, Jet A, and is a complex mixture of primarily aliphatic (but also aromatic) hydrocarbons that varies in composition from batch to batch. There is potential for dermal exposure to jet fuels with personnel involved in aircraft refueling and maintenance operations as well as ground personnel. Cutaneous exposures have the potential to cause skin irritation, sensitization or skin cancer. JP-8 has been shown to be irritating and causes molecular changes in the skin of laboratory animals. The mechanisms of some of these effects have been investigated in intact skin and cultured skin cells. Hydrocarbons have also been shown to cause skin cancer with repeated application to the skin. Additionally, there is concern about systemic toxicity from dermal exposures to jet fuels, such as JP-8. Assessing risks from systemic absorption of hydrocarbon components is complex because most of the components are present in the mixture in small quantities (less than 1%). The effect of the fuel as a vehicle, different rates of penetration through the skin and different target organ toxicities all complicate the assessment of the hazards of cutaneous exposures. The purpose of this manuscript is to review studies of local and systemic toxicity of JP-8.

Evaluation of capillary zone electrophoresis for the quality control of complex biologic samples: Application to snake venoms.

PubMed

Kpaibe, André P S; Ben-Ameur, Randa; Coussot, Gaëlle; Ladner, Yoann; Montels, Jérôme; Ake, Michèle; Perrin, Catherine

2017-08-01

Snake venoms constitute a very promising resource for the development of new medicines. They are mainly composed of very complex peptide and protein mixtures, which composition may vary significantly from batch to batch. This latter consideration is a challenge for routine quality control (QC) in the pharmaceutical industry. In this paper, we report the use of capillary zone electrophoresis for the development of an analytical fingerprint methodology to assess the quality of snake venoms. The analytical fingerprint concept is being widely used for the QC of herbal drugs but rarely for venoms QC so far. CZE was chosen for its intrinsic efficiency in the separation of protein and peptide mixtures. The analytical fingerprint methodology was first developed and evaluated for a particular snake venom, Lachesis muta. Optimal analysis conditions required the use of PDADMAC capillary coating to avoid protein and peptide adsorption. Same analytical conditions were then applied to other snake venom species. Different electrophoretic profiles were obtained for each venom. Excellent repeatability and intermediate precision was observed for each batch. Analysis of different batches of the same species revealed inherent qualitative and quantitative composition variations of the venoms between individuals. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antioxidant capacity of pure compounds and complex mixtures evaluated by the ORAC-pyrogallol red assay in the presence of Triton X-100 micelles.

PubMed

Romero, Max; Rojano, Benjamin; Mella-Raipán, Jaime; Pessoa-Mahana, Carlos David; Lissi, Eduardo; López-Alarcón, Camilo

2010-09-01

The protective effect of different antioxidants and complex mixtures on the consumption of pyrogallol red (PGR) induced by peroxyl radicals was studied in the absence and presence of Triton X-100 micelles. The presence of micelles decreased significantly the protection of PGR afforded by lipophilic antioxidants (β-carotene, octyl gallate), while no effect of micelles was observed for hydrophilic antioxidants such as Trolox, caffeic acid, gallic acid, and ascorbic acid. In the presence of complex mixtures a clear effect of Triton X-100 micelles was also observed in the protection afforded by wines, tea infusions, and seed extracts of Eugenia jambolana and Myrciaria cauliflora. On the other hand, no effect of micelles was observed for orange juice and pulp fruit extracts. The ORAC (Oxygen Radical Absorbance Capacity) index was evaluated in the absence (ORAC-PGR) and presence of Triton X-100 micelles (ORAC-PGR(MIC)). Triton X-100 micelles affect ORAC-PGR values of antioxidants in a lipophilicity-dependent way. From the obtained results, we conclude that ORAC-PGR and ORAC-PGR(MIC) assays could be considered as an alternative to estimate the antioxidant ability (ORAC-PGR) and to infer the association to Triton X-100 micelles (ORAC-PGR/ORAC-PGR(MIC)) of pure antioxidants and their complex mixtures.

Potential of Laboratory Execution Systems (LESs) to Simplify the Application of Business Process Management Systems (BPMSs) in Laboratory Automation.

PubMed

Neubert, Sebastian; Göde, Bernd; Gu, Xiangyu; Stoll, Norbert; Thurow, Kerstin

2017-04-01

Modern business process management (BPM) is increasingly interesting for laboratory automation. End-to-end workflow automation and improved top-level systems integration for information technology (IT) and automation systems are especially prominent objectives. With the ISO Standard Business Process Model and Notation (BPMN) 2.X, a system-independent and interdisciplinary accepted graphical process control notation is provided, allowing process analysis, while also being executable. The transfer of BPM solutions to structured laboratory automation places novel demands, for example, concerning the real-time-critical process and systems integration. The article discusses the potential of laboratory execution systems (LESs) for an easier implementation of the business process management system (BPMS) in hierarchical laboratory automation. In particular, complex application scenarios, including long process chains based on, for example, several distributed automation islands and mobile laboratory robots for a material transport, are difficult to handle in BPMSs. The presented approach deals with the displacement of workflow control tasks into life science specialized LESs, the reduction of numerous different interfaces between BPMSs and subsystems, and the simplification of complex process modelings. Thus, the integration effort for complex laboratory workflows can be significantly reduced for strictly structured automation solutions. An example application, consisting of a mixture of manual and automated subprocesses, is demonstrated by the presented BPMS-LES approach.

Generation of two-dimensional binary mixtures in complex plasmas

NASA Astrophysics Data System (ADS)

Wieben, Frank; Block, Dietmar

2016-10-01

Complex plasmas are an excellent model system for strong coupling phenomena. Under certain conditions the dust particles immersed into the plasma form crystals which can be analyzed in terms of structure and dynamics. Previous experiments focussed mostly on monodisperse particle systems whereas dusty plasmas in nature and technology are polydisperse. Thus, a first and important step towards experiments in polydisperse systems are binary mixtures. Recent experiments on binary mixtures under microgravity conditions observed a phase separation of particle species with different radii even for small size disparities. This contradicts several numerical studies of 2D binary mixtures. Therefore, dedicated experiments are required to gain more insight into the physics of polydisperse systems. In this contribution first ground based experiments on two-dimensional binary mixtures are presented. Particular attention is paid to the requirements for the generation of such systems which involve the consideration of the temporal evolution of the particle properties. Furthermore, the structure of these two-component crystals is analyzed and compared to simulations. This work was supported by the Deutsche Forschungsgemeinschaft DFG in the framework of the SFB TR24 Greifswald Kiel, Project A3b.

Solubility Limits in Lennard-Jones Mixtures: Effects of Disparate Molecule Geometries.

PubMed

Dyer, Kippi M; Perkyns, John S; Pettitt, B Montgomery

2015-07-23

In order to better understand general effects of the size and energy disparities between macromolecules and solvent molecules in solution, especially for macromolecular constructs self-assembled from smaller molecules, we use the first- and second-order exact bridge diagram extensions of the HNC integral equation theory to investigate single-component, binary, ternary, and quaternary mixtures of Lennard-Jones fluids. For pure fluids, we find that the HNCH3 bridge function integral equation (i.e., exact to third order in density) is necessary to quantitatively predict the pure gas and pure liquid sides of the coexistence region of the phase diagram of the Lennard-Jones fluid. For the mixtures, we find that the HNCH2 bridge function integral equation is sufficient to qualitatively predict solubility in the binary, ternary, and quaternary mixtures, up to the nominal solubility limit. The results, as limiting cases, should be useful to several problems, including accurate phase diagram predictions for complex mixtures, design of self-assembling nanostructures via solvent controls, and the solvent contributions to the conformational behavior of macromolecules in complex fluids.

Scale Mixture Models with Applications to Bayesian Inference

NASA Astrophysics Data System (ADS)

Qin, Zhaohui S.; Damien, Paul; Walker, Stephen

2003-11-01

Scale mixtures of uniform distributions are used to model non-normal data in time series and econometrics in a Bayesian framework. Heteroscedastic and skewed data models are also tackled using scale mixture of uniform distributions.

INTEGRATED DISINFECTION BY-PRODUCTS (DBP) MIXTURES RESEARCH: GENE EXPRESSION ALTERATIONS IN PRIMARY RAT HEPATOCYTE CULTURES EXPOSED TO DBP MIXTURES FORMED BY CHLORINATION AND OZONATION/POSTCHLORINATION

EPA Science Inventory

What is the study?
This study was designed to provide data on the in vitro toxicity of water concentrates containing complex mixtures of DBPs. Rat hepatocytes in primary culture were exposed for 24 hr to full strength, 1:10 or 1:20 dilutions of chlorination or ozonation/chl...

Decoding DNA labels by melting curve analysis using real-time PCR.

PubMed

Balog, József A; Fehér, Liliána Z; Puskás, László G

2017-12-01

Synthetic DNA has been used as an authentication code for a diverse number of applications. However, existing decoding approaches are based on either DNA sequencing or the determination of DNA length variations. Here, we present a simple alternative protocol for labeling different objects using a small number of short DNA sequences that differ in their melting points. Code amplification and decoding can be done in two steps using quantitative PCR (qPCR). To obtain a DNA barcode with high complexity, we defined 8 template groups, each having 4 different DNA templates, yielding 158 (>2.5 billion) combinations of different individual melting temperature (Tm) values and corresponding ID codes. The reproducibility and specificity of the decoding was confirmed by using the most complex template mixture, which had 32 different products in 8 groups with different Tm values. The industrial applicability of our protocol was also demonstrated by labeling a drone with an oil-based paint containing a predefined DNA code, which was then successfully decoded. The method presented here consists of a simple code system based on a small number of synthetic DNA sequences and a cost-effective, rapid decoding protocol using a few qPCR reactions, enabling a wide range of authentication applications.

NIRP Core Software Suite v. 1.0

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

Whitener, Dustin Heath; Folz, Wesley; Vo, Duong

The NIRP Core Software Suite is a core set of code that supports multiple applications. It includes miscellaneous base code for data objects, mathematic equations, and user interface components; and the framework includes several fully-developed software applications that exist as stand-alone tools to compliment other applications. The stand-alone tools are described below. Analyst Manager: An application to manage contact information for people (analysts) that use the software products. This information is often included in generated reports and may be used to identify the owners of calculations. Radionuclide Viewer: An application for viewing the DCFPAK radiological data. Compliments the Mixture Managermore » tool. Mixture Manager: An application to create and manage radionuclides mixtures that are commonly used in other applications. High Explosive Manager: An application to manage explosives and their properties. Chart Viewer: An application to view charts of data (e.g. meteorology charts). Other applications may use this framework to create charts specific to their data needs.« less

Fast sparse Raman spectral unmixing for chemical fingerprinting and quantification

NASA Astrophysics Data System (ADS)

Yaghoobi, Mehrdad; Wu, Di; Clewes, Rhea J.; Davies, Mike E.

2016-10-01

Raman spectroscopy is a well-established spectroscopic method for the detection of condensed phase chemicals. It is based on scattered light from exposure of a target material to a narrowband laser beam. The information generated enables presumptive identification from measuring correlation with library spectra. Whilst this approach is successful in identification of chemical information of samples with one component, it is more difficult to apply to spectral mixtures. The capability of handling spectral mixtures is crucial for defence and security applications as hazardous materials may be present as mixtures due to the presence of degradation, interferents or precursors. A novel method for spectral unmixing is proposed here. Most modern decomposition techniques are based on the sparse decomposition of mixture and the application of extra constraints to preserve the sum of concentrations. These methods have often been proposed for passive spectroscopy, where spectral baseline correction is not required. Most successful methods are computationally expensive, e.g. convex optimisation and Bayesian approaches. We present a novel low complexity sparsity based method to decompose the spectra using a reference library of spectra. It can be implemented on a hand-held spectrometer in near to real-time. The algorithm is based on iteratively subtracting the contribution of selected spectra and updating the contribution of each spectrum. The core algorithm is called fast non-negative orthogonal matching pursuit, which has been proposed by the authors in the context of nonnegative sparse representations. The iteration terminates when the maximum number of expected chemicals has been found or the residual spectrum has a negligible energy, i.e. in the order of the noise level. A backtracking step removes the least contributing spectrum from the list of detected chemicals and reports it as an alternative component. This feature is particularly useful in detection of chemicals with small contributions, which are normally not detected. The proposed algorithm is easily reconfigurable to include new library entries and optional preferential threat searches in the presence of predetermined threat indicators. Under Ministry of Defence funding, we have demonstrated the algorithm for fingerprinting and rough quantification of the concentration of chemical mixtures using a set of reference spectral mixtures. In our experiments, the algorithm successfully managed to detect the chemicals with concentrations below 10 percent. The running time of the algorithm is in the order of one second, using a single core of a desktop computer.

Eco-friendly porous concrete using bottom ash aggregate for marine ranch application.

PubMed

Lee, Byung Jae; Prabhu, G Ganesh; Lee, Bong Chun; Kim, Yun Yong

2016-03-01

This article presents the test results of an investigation carried out on the reuse of coal bottom ash aggregate as a substitute material for coarse aggregate in porous concrete production for marine ranch applications. The experimental parameters were the rate of bottom ash aggregate substitution (30%, 50% and 100%) and the target void ratio (15%, 20% and 25%). The cement-coated granular fertiliser was substituted into a bottom ash aggregate concrete mixture to improve marine ranch applications. The results of leaching tests revealed that the bottom ash aggregate has only a negligible amount of the ten deleterious substances specified in the Ministry of Environment - Enforcement Regulation of the Waste Management Act of Republic Korea. The large amount of bubbles/air gaps in the bottom ash aggregate increased the voids of the concrete mixtures in all target void ratios, and decreased the compressive strength of the porous concrete mixture; however, the mixture substituted with 30% and 10% of bottom ash aggregate and granular fertiliser, respectively, showed an equal strength to the control mixture. The sea water resistibility of the bottom ash aggregate substituted mixture was relatively equal to that of the control mixture, and also showed a great deal of improvement in the degree of marine organism adhesion compared with the control mixture. No fatality of fish was observed in the fish toxicity test, which suggested that bottom ash aggregate was a harmless material and that the combination of bottom ash aggregate and granular fertiliser with substitution rates of 30% and 10%, respectively, can be effectively used in porous concrete production for marine ranch application. © The Author(s) 2015.

The application of reduced absorption cross section on the identification of the compounds with similar function-groups

NASA Astrophysics Data System (ADS)

Yu, Fei; Zuo, Jian; Mu, Kai-jun; Zhang, Zhen-wei; Zhang, Liang-liang; Zhang, Lei-wei; Zhang, Cun-lin

2013-08-01

Terahertz spectroscopy is a powerful tool for materials investigation. The low frequency vibrations were usually investigated by means of absorption coefficient regardless of the refractive index. It leads to the disregard of some inherent low-frequency vibrational information of the chemical compounds. Moreover, due to the scattering inside the sample, there are some distortions of the absorption features, so that the absorption dependent material identification is not valid enough. Here, a statistical parameter named reduced absorption cross section (RACS) is introduced. This can not only help us investigate the molecular dynamics but also distinguish one chemical compound with another which has similar function-groups. Experiments are carried out on L-Tyrosine and L-Phenylalanine and the different mass ratios of their mixtures as an example of the application of RACS. The results come out that the RACS spectrum of L-Tyrosine and L-Phenylalanine reserve the spectral fingerprint information of absorption spectrum. The log plot of RACSs of the two amino acids show power-law behavior σR(~ν) ~ (ν~α), and there is a linear relation between the wavenumber and the RACS in the double logarithmic plot. The exponents α, at the same time, are the slopes of the RACS curves in the double logarithmic plot. The big differences of the exponents α between the two amino acids and their mixtures can be seen visually from the slopes of the RACS curves. So we can use RACS analytical method to distinguish some complex compounds with similar function-groups and mixtures from another which has similar absorption peaks in THz region.

Equivalent electron fluence for space qualification of shallow junction heteroface GaAs solar cells

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Stock, L. V.

1984-01-01

It is desirable to perform qualification tests prior to deployment of solar cells in space power applications. Such test procedures are complicated by the complex mixture of differing radiation components in space which are difficult to simulate in ground test facilities. Although it has been shown that an equivalent electron fluence ratio cannot be uniquely defined for monoenergetic proton exposure of GaAs shallow junction cells, an equivalent electron fluence test can be defined for common spectral components of protons found in space. Equivalent electron fluence levels for the geosynchronous environment are presented.

Continuous flow immobilized enzyme reactor-tandem mass spectrometry for screening of AChE inhibitors in complex mixtures.

PubMed

Forsberg, Erica M; Green, James R A; Brennan, John D

2011-07-01

A method is described for identifying bioactive compounds in complex mixtures based on the use of capillary-scale monolithic enzyme-reactor columns for rapid screening of enzyme activity. A two-channel nanoLC system was used to continuously infuse substrate coupled with automated injections of substrate/small molecule mixtures, optionally containing the chromogenic Ellman reagent, through sol-gel derived acetylcholinesterase (AChE) doped monolithic columns. This is the first report of AChE encapsulated in monolithic silica for use as an immobilized enzyme reactor (IMER), and the first use of such IMERs for mixture screening. AChE IMER columns were optimized to allow rapid functional screening of compound mixtures based on changes in the product absorbance or the ratio of mass spectrometric peaks for product and substrate ions in the eluent. The assay had robust performance and produced a Z' factor of 0.77 in the presence of 2% (v/v) DMSO. A series of 52 mixtures consisting of 1040 compounds from the Canadian Compound Collection of bioactives was screened and two known inhibitors, physostigmine and 9-aminoacridine, were identified from active mixtures by manual deconvolution. The activity of the compounds was confirmed using the enzyme reactor format, which allowed determination of both IC(50) and K(I) values. Screening results were found to correlate well with a recently published fluorescence-based microarray screening assay for AChE inhibitors.

Adsorption of hydrophobin/β-casein mixtures at the solid-liquid interface.

PubMed

Tucker, I M; Petkov, J T; Penfold, J; Thomas, R K; Cox, A R; Hedges, N

2016-09-15

The adsorption behaviour of mixtures of the proteins β-casein and hydrophobin at the hydrophilic solid-liquid surface have been studied by neutron reflectivity. The results of measurements from sequential adsorption and co-adsorption from solution are contrasted. The adsorption properties of protein mixtures are important for a wide range of applications. Because of competing factors the adsorption behaviour of protein mixtures at interfaces is often difficult to predict. This is particularly true for mixtures containing hydrophobin as hydrophobin possesses some unusual surface properties. At β-casein concentrations ⩾0.1wt% β-casein largely displaces a pre-adsorbed layer of hydrophobin at the interface, similar to that observed in hydrophobin-surfactant mixtures. In the composition and concentration range studied here for the co-adsorption of β-casein-hydrophobin mixtures the adsorption is dominated by the β-casein adsorption. The results provide an important insight into how the competitive adsorption in protein mixtures of hydrophobin and β-casein can impact upon the modification of solid surface properties and the potential for a wide range of colloid stabilisation applications. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative Chemistry and Toxicity of Diesel and Biomass Combustion Emissions

EPA Science Inventory

Air pollution includes a complex mixture of carbonaceous gases and particles emitted from multiple anthropogenic, biogenic, and biomass burning sources, and also includes secondary organic components that form during atmospheric aging of these emissions. Exposure to these mixture...

EXPERIMENTS AT THE INTERFACE OF CARBON PARTICLE CHEMISTRY AND TOXCIOLOGY

EPA Science Inventory

Air pollution includes a complex mixture of carbonaceous gases and particles emitted from multiple anthropogenic, biogenic, and biomass burning sources, and also includes secondary organic components that form during atmospheric aging of these emissions. Exposure to these mixture...

A view at the interface between particle chemistry and toxicology

EPA Science Inventory

Air pollution includes a complex mixture of carbonaceous gases and particles emitted from multiple anthropogenic, biogenic, and biomass burning sources, and also includes secondary organic components that form during atmospheric aging of these emissions. Exposure to these mixture...

A rapid analytical method to quantify complex organohalogen contaminant mixtures in large samples of high lipid mammalian tissues.

PubMed

Desforges, Jean-Pierre; Eulaers, Igor; Periard, Luke; Sonne, Christian; Dietz, Rune; Letcher, Robert J

2017-06-01

In vitro investigations of the health impact of individual chemical compounds have traditionally been used in risk assessments. However, humans and wildlife are exposed to a plethora of potentially harmful chemicals, including organohalogen contaminants (OHCs). An alternative exposure approach to individual or simple mixtures of synthetic OHCs is to isolate the complex mixture present in free-ranging wildlife, often non-destructively sampled from lipid rich adipose. High concentration stock volumes required for in vitro investigations do, however, pose a great analytical challenge to extract sufficient amounts of complex OHC cocktails. Here we describe a novel method to easily, rapidly and efficiently extract an environmentally accumulated and therefore relevant contaminant cocktail from large (10-50 g) marine mammal blubber samples. We demonstrate that lipid freeze-filtration with acetonitrile removes up to 97% of blubber lipids, with minimal effect on the efficiency of OHC recovery. Sample extracts after freeze-filtration were further processed to remove residual trace lipids via high-pressure gel permeation chromatography and solid phase extraction. Average recoveries of OHCs from triplicate analysis of killer whale (Orcinus orca), polar bear (Ursus maritimus) and pilot whale (Globicephala spp.) blubber standard reference material (NIST SRM-1945) ranged from 68 to 80%, 54-92% and 58-145%, respectively, for 13 C-enriched internal standards of six polychlorinated biphenyl congeners, 16 organochlorine pesticides and four brominated flame retardants. This approach to rapidly generate OHC mixtures shows great potential for experimental exposures using complex contaminant mixtures, research or monitoring driven contaminant quantification in biological samples, as well as the untargeted identification of emerging contaminants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inclusion complexes of yellow bell pepper pigments with β-cyclodextrin: preparation, characterisation and application as food natural colorant.

PubMed

Lobo, Francine Albernaz Tf; Silva, Vitoria; Domingues, Josiane; Rodrigues, Silvana; Costa, Valéria; Falcão, Deborah; de Lima Araújo, Kátia G

2018-05-01

This work aimed to prepare inclusion complexes using yellow bell pepper pigments and β-cyclodextrin by two different procedures (method A, ultrasonic homogenisation; method B, kneading), to characterise them and evaluate their colour stability in an isotonic beverage model. The extract/β-cyclodextrin ratio was 1:2 for both inclusion methodologies evaluated. The formed extract-β-cyclodextrin complexes and a physical mixture of extract and β-cyclodextrin were evaluated by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Both methodologies resulted in good complex yield and inclusion efficiency. The colour indices L* (lightness), a* (green/red) and b* (blue/yellow) of isotonic drinks added with the complexes were measured during storage under irradiance (1400 lx) and in the absence of light at temperatures between 25 and 31 °C for 21 days. The complex obtained by inclusion method B promoted better colour protection for the beverage compared with the use of the crude extract, showing that the molecular inclusion of yellow bell pepper carotenoids can provide good results for that purpose. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Metal-assisted in situ formation of a tridentate acetylacetone ligand for complexation of fac-Re(CO)3+ for radiopharmaceutical applications.

PubMed

Benny, Paul D; Fugate, Glenn A; Barden, Adam O; Morley, Jennifer E; Silva-Lopez, Elsa; Twamley, Brendan

2008-04-07

Reaction of [NEt4]2[ReBr3(CO)3] with 2,4-pentanedione (acac) yields a complex of the type fac-Re(acac)(OH2)(CO)3 (1) under aqueous conditions. 1 was further reacted with a monodentate ligand (pyridine) to yield a fac-Re(acac)(pyridine)(CO)3 complex (2). Complex 1 was found to react with primary amines to generate a Schiff base (imine) in aqueous solutions. When a mixed-nitrogen donor bidentate ligand, 2-(2-aminoethyl)pyridine, that has different coordination affinities for fac-Re(acac)(OH2)(CO)3 was utilized, a unique tridentate ligand was formed in situ utilizing a metal-assisted Schiff base formation to yield a complex fac-Re(CO)3(3[(2-phenylethyl)imino]-2-pentanone) (3). Tridentate ligand formation was found to occur only with the Re-coordinated acac ligand. Reactions of acac with fac-Re(CO)3Br(2-(2-aminoethyl)pyridine) (4) or a mixture of [NEt4]2[ReBr3(CO)3], acac, and 2-(2-aminoethyl)pyridine did not yield the formation of complex 3 in water.

A Mechanistic Design Approach for Graphite Nanoplatelet (GNP) Reinforced Asphalt Mixtures for Low-Temperature Applications

DOT National Transportation Integrated Search

2018-01-01

This report explores the application of a discrete computational model for predicting the fracture behavior of asphalt mixtures at low temperatures based on the results of simple laboratory experiments. In this discrete element model, coarse aggregat...

Headspace versus direct immersion solid phase microextraction in complex matrixes: investigation of analyte behavior in multicomponent mixtures.

PubMed

Gionfriddo, Emanuela; Souza-Silva, Érica A; Pawliszyn, Janusz

2015-08-18

This work aims to investigate the behavior of analytes in complex mixtures and matrixes with the use of solid-phase microextraction (SPME). Various factors that influence analyte uptake such as coating chemistry, extraction mode, the physicochemical properties of analytes, and matrix complexity were considered. At first, an aqueous system containing analytes bearing different hydrophobicities, molecular weights, and chemical functionalities was investigated by using commercially available liquid and solid porous coatings. The differences in the mass transfer mechanisms resulted in a more pronounced occurrence of coating saturation in headspace mode. Contrariwise, direct immersion extraction minimizes the occurrence of artifacts related to coating saturation and provides enhanced extraction of polar compounds. In addition, matrix-compatible PDMS-modified solid coatings, characterized by a new morphology that avoids coating fouling, were compared to their nonmodified analogues. The obtained results indicate that PDMS-modified coatings reduce artifacts associated with coating saturation, even in headspace mode. This factor, coupled to their matrix compatibility, make the use of direct SPME very practical as a quantification approach and the best choice for metabolomics studies where wide coverage is intended. To further understand the influence on analyte uptake on a system where additional interactions occur due to matrix components, ex vivo and in vivo sampling conditions were simulated using a starch matrix model, with the aim of mimicking plant-derived materials. Our results corroborate the fact that matrix handling can affect analyte/matrix equilibria, with consequent release of high concentrations of previously bound hydrophobic compounds, potentially leading to coating saturation. Direct immersion SPME limited the occurrence of the artifacts, which confirms the suitability of SPME for in vivo applications. These findings shed light into the implementation of in vivo SPME strategies in quantitative metabolomics studies of complex plant-based systems.

High affinity ligands from in vitro selection: Complex targets

PubMed Central

Morris, Kevin N.; Jensen, Kirk B.; Julin, Carol M.; Weil, Michael; Gold, Larry

1998-01-01

Human red blood cell membranes were used as a model system to determine if the systematic evolution of ligands by exponential enrichment (SELEX) methodology, an in vitro protocol for isolating high-affinity oligonucleotides that bind specifically to virtually any single protein, could be used with a complex mixture of potential targets. Ligands to multiple targets were generated simultaneously during the selection process, and the binding affinities of these ligands for their targets are comparable to those found in similar experiments against pure targets. A secondary selection scheme, deconvolution-SELEX, facilitates rapid isolation of the ligands to targets of special interest within the mixture. SELEX provides high-affinity compounds for multiple targets in a mixture and might allow a means for dissecting complex biological systems. PMID:9501188

Less common applications of simulated moving bed chromatography in the pharmaceutical industry.

PubMed

Huthmann, E; Juza, M

2005-10-21

Simulated moving bed (SMB) chromatography is often perceived in the pharmaceutical industry as chromatographic method for separating binary mixtures, like racemates. However, SMB can also be used for unbalanced separations, i.e. binary mixtures of varying compositions and multi-component mixtures. These less common application modes of isocratic SMB chromatography are exemplified for four different compounds (racemates and diastereomers) and discussed in view of the so-called 'triangle theory' from an industrial perspective.

Nontargeted diagnostic ion network analysis (NINA): A software to streamline the analytical workflow for untargeted characterization of natural medicines.

PubMed

Ye, Hui; Zhu, Lin; Sun, Di; Luo, Xiaozhuo; Lu, Gaoyuan; Wang, Hong; Wang, Jing; Cao, Guoxiu; Xiao, Wei; Wang, Zhenzhong; Wang, Guangji; Hao, Haiping

2016-11-30

The characterization of herbal prescriptions serves as a foundation for quality control and regulation of herbal medicines. Previously, the characterization of herbal chemicals from natural medicines often relied on the analysis of signature fragment ions from the acquired tandem mass spectrometry (MS/MS) spectra with prior knowledge of the herbal species present in the herbal prescriptions of interest. Nevertheless, such an approach is often limited to target components, and it risks missing the critical components that we have no prior knowledge of. We previously reported a "diagnostic ion-guided network bridging" strategy. It is a generally applicable and robust approach to analyze unknown substances from complex mixtures in an untargeted manner. In this study, we have developed a standalone software named "Nontargeted Diagnostic Ion Network Analysis (NINA)" with a graphical user interface based on a strategy for post-acquisition data analysis. NINA allows one to rapidly determine the nontargeted diagnostic ions (NIs) by summarizing all of the fragment ions shared by the precursors from the acquired MS/MS spectra. A NI-guided network using bridging components that possess two or more NIs can then be established via NINA. With such a network, we could sequentially identify the structures of all the NIs once a single compound has been identified de novo. The structures of NIs can then be used as "priori" knowledge to narrow the candidates containing the sub-structure of the corresponding NI from the database hits. Subsequently, we applied the NINA software to the characterization of a model herbal prescription, Re-Du-Ning injection, and rapidly identified 56 herbal chemicals from the prescription using an ultra-performance liquid chromatography quadrupole time-of-flight system in the negative mode with no knowledge of the herbal species or herbal chemicals in the mixture. Therefore, we believe the applications of NINA will greatly facilitate the characterization of complex mixtures, such as natural medicines, especially when no advance information is available. In addition to herbal medicines, the NINA-based workflow will also benefit many other fields, such as environmental analysis, nutritional science, and forensic analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Chemometric comparison of polychlorinated biphenyl residues and toxicologically active polychlorinated biphenyl congeners in the eggs of Forster's Terns (Sterna fosteri)

USGS Publications Warehouse

Schwartz, Ted R.; Stalling, David L.

1991-01-01

The separation and characterization of complex mixtures of polychlorinated biphenyls (PCBs) is approached from the perspective of a problem in chemometrics. A technique for quantitative determination of PCB congeners is described as well as an enrichment technique designed to isolate only those congener residues which induce mixed aryl hydrocarbon hydroxylase enzyme activity. A congener-specific procedure is utilized for the determination of PCBs in whichn-alkyl trichloroacetates are used as retention index marker compounds. Retention indices are reproducible in the range of ±0.05 to ±0.7 depending on the specific congener. A laboratory data base system developed to aid in the editing and quantitation of data generated from capillary gas chromatography was employed to quantitate chromatographic data. Data base management was provided by computer programs written in VAX-DSM (Digital Standard MUMPS) for the VAX-DEC (Digital Equipment Corp.) family of computers.In the chemometric evaluation of these complex chromatographic profiles, data are viewed from a single analysis as a point in multi-dimensional space. Principal Components Analysis was used to obtain a representation of the data in a lower dimensional space. Two-and three-dimensional proections based on sample scores from the principal components models were used to visualize the behavior of Aroclor® mixtures. These models can be used to determine if new sample profiles may be represented by Aroclor profiles. Concentrations of individual congeners of a given chlorine substitution may be summed to form homologue concentration. However, the use of homologue concentrations in classification studies with environmental samples can lead to erroneous conclusions about sample similarity. Chemometric applications are discussed for evaluation of Aroclor mixture analysis and compositional description of environmental residues of PCBs in eggs of Forster's terns (Sterna fosteri) collected from colonies near Lake Poygan and Green Bay, Wisconsin. The application of chemometrics is extended to the comparison of: a) Aroclors and PCB-containing environmental samples; to b) fractions of Aroclors and of environmental samples that have been enriched in congeners which induce mixed aryl hydrocarbon hydroxylase enzyme activity.

A review of the occurrence, analyses, toxicity, and biodegradation of naphthenic acids.

PubMed

Clemente, Joyce S; Fedorak, Phillip M

2005-07-01

Naphthenic acids occur naturally in crude oils and in oil sands bitumens. They are toxic components in refinery wastewaters and in oil sands extraction waters. In addition, there are many industrial uses for naphthenic acids, so there is a potential for their release to the environment from a variety of activities. Studies have shown that naphthenic acids are susceptible to biodegradation, which decreases their concentration and reduces toxicity. This is a complex group of carboxylic acids with the general formula CnH(2n+Z)O2, where n indicates the carbon number and Z specifies the hydrogen deficiency resulting from ring formation. Measuring the concentrations of naphthenic acids in environmental samples and determining the chemical composition of a naphthenic acids mixture are huge analytical challenges. However, new analytical methods are being applied to these problems and progress is being made to better understand this mixture of chemically similar compounds. This paper reviews a variety of analytical methods and their application to assessing biodegradation of naphthenic acids.

Penicillium subrubescens is a promising alternative for Aspergillus niger in enzymatic plant biomass saccharification.

PubMed

Mäkelä, Miia R; Mansouri, Sadegh; Wiebenga, Ad; Rytioja, Johanna; de Vries, Ronald P; Hildén, Kristiina S

2016-12-25

In industrial applications, efficient mixtures of polysaccharide-degrading enzymes are needed to convert plant biomass into fermentable sugars. Most of the commercially produced lignocellulolytic enzymes are from a limited number of filamentous fungi, such as Trichoderma and Aspergillus species. In contrast, the plant biomass-degrading capacity of Penicillia has been less explored. We performed growth profiling of several Penicillia on diverse plant biomass-related substrates demonstrating the capacity particularly of Penicillium subrubescens to degrade crude lignocellulose feedstock, as well as polysaccharides, and metabolise their monomeric components. We focussed on the lignocellulolytic potential of P. subrubescens FBCC1632, which produced a variable set of (hemi-)cellulolytic activities on plant biomass substrates with activity levels comparable to those of Aspergillus niger. The good ability of the extracellular enzyme mixtures produced by P. subrubescens to saccharify complex plant biomasses, wheat bran and sugar beet pulp, indicated a high potential for this strain as a producer of industrial enzyme cocktails. Copyright © 2016 Elsevier B.V. All rights reserved.

Equalizer technology--Equal rights for disparate beads.

PubMed

Keidel, Eva-Maria; Ribitsch, Doris; Lottspeich, Friedrich

2010-06-01

One major limitation in proteomics is the detection and analysis of low-abundant proteins, i.e. in plasma. Several years ago, a technique to selectively enrich the relative concentration of low-abundant proteins was introduced by Boschetti and co-workers. It is based on a specific and saturable interaction of proteins to a high diversity of binding sites, realized by a hexapeptide library coupled to beads. This technology was commercialized as Equalizer beads or ProteoMiner. However, during application of ProteoMiner beads to plasma samples unexpected results questioned the proposed mode of action. Therefore, ProteoMiner beads were compared with chromatographic beads exhibiting completely different surface chemistry. Sepabeads FP-OD400 octadecyl, FP-DA400 diethylamine, FP-BU400 butyl, FP-HG400 hydroxyl and EXE056 epoxy were used. The results show that ProteoMiner or the different Sepabeads behave surprisingly similarly in the separation of complex protein mixtures. ProteoMiner beads interact with protein mixtures according to a general hydrophobic binding mechanism, where diversity in surface ligands plays only a negligible role.

Multivariate Analysis of Electron Detachment Dissociation and Infrared Multiphoton Dissociation Mass Spectra of Heparan Sulfate Tetrasaccharides Differing Only in Hexuronic acid Stereochemistry

NASA Astrophysics Data System (ADS)

Oh, Han Bin; Leach, Franklin E.; Arungundram, Sailaja; Al-Mafraji, Kanar; Venot, Andre; Boons, Geert-Jan; Amster, I. Jonathan

2011-03-01

The structural characterization of glycosaminoglycan (GAG) carbohydrates by mass spectrometry has been a long-standing analytical challenge due to the inherent heterogeneity of these biomolecules, specifically polydispersity, variability in sulfation, and hexuronic acid stereochemistry. Recent advances in tandem mass spectrometry methods employing threshold and electron-based ion activation have resulted in the ability to determine the location of the labile sulfate modification as well as assign the stereochemistry of hexuronic acid residues. To facilitate the analysis of complex electron detachment dissociation (EDD) spectra, principal component analysis (PCA) is employed to differentiate the hexuronic acid stereochemistry of four synthetic GAG epimers whose EDD spectra are nearly identical upon visual inspection. For comparison, PCA is also applied to infrared multiphoton dissociation spectra (IRMPD) of the examined epimers. To assess the applicability of multivariate methods in GAG mixture analysis, PCA is utilized to identify the relative content of two epimers in a binary mixture.

Algorithms for GPU-based molecular dynamics simulations of complex fluids: Applications to water, mixtures, and liquid crystals.

PubMed

Kazachenko, Sergey; Giovinazzo, Mark; Hall, Kyle Wm; Cann, Natalie M

2015-09-15

A custom code for molecular dynamics simulations has been designed to run on CUDA-enabled NVIDIA graphics processing units (GPUs). The double-precision code simulates multicomponent fluids, with intramolecular and intermolecular forces, coarse-grained and atomistic models, holonomic constraints, Nosé-Hoover thermostats, and the generation of distribution functions. Algorithms to compute Lennard-Jones and Gay-Berne interactions, and the electrostatic force using Ewald summations, are discussed. A neighbor list is introduced to improve scaling with respect to system size. Three test systems are examined: SPC/E water; an n-hexane/2-propanol mixture; and a liquid crystal mesogen, 2-(4-butyloxyphenyl)-5-octyloxypyrimidine. Code performance is analyzed for each system. With one GPU, a 33-119 fold increase in performance is achieved compared with the serial code while the use of two GPUs leads to a 69-287 fold improvement and three GPUs yield a 101-377 fold speedup. © 2015 Wiley Periodicals, Inc.

Mutual diffusion coefficients of heptane isomers in nitrogen: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Chae, Kyungchan; Violi, Angela

2011-01-01

The accurate knowledge of transport properties of pure and mixture fluids is essential for the design of various chemical and mechanical systems that include fluxes of mass, momentum, and energy. In this study we determine the mutual diffusion coefficients of mixtures composed of heptane isomers and nitrogen using molecular dynamics (MD) simulations with fully atomistic intermolecular potential parameters, in conjunction with the Green-Kubo formula. The computed results were compared with the values obtained using the Chapman-Enskog (C-E) equation with Lennard-Jones (LJ) potential parameters derived from the correlations of state values: MD simulations predict a maximum difference of 6% among isomers while the C-E equation presents that of 3% in the mutual diffusion coefficients in the temperature range 500-1000 K. The comparison of two approaches implies that the corresponding state principle can be applied to the models, which are only weakly affected by the anisotropy of the interaction potentials and the large uncertainty will be included in its application for complex polyatomic molecules. The MD simulations successfully address the pure effects of molecular structure among isomers on mutual diffusion coefficients by revealing that the differences of the total mutual diffusion coefficients for the six mixtures are caused mainly by heptane isomers. The cross interaction potential parameters, collision diameter σ _{12}, and potential energy well depth \\varepsilon _{12} of heptane isomers and nitrogen mixtures were also computed from the mutual diffusion coefficients.

Laboratory Scale Experiments and Numerical Modeling of Cosolvent flushing of NAPL Mixtures in Saturated Porous Media

NASA Astrophysics Data System (ADS)

Agaoglu, B.; Scheytt, T. J.; Copty, N. K.

2011-12-01

This study examines the mechanistic processes governing multiphase flow of a water-cosolvent-NAPL system in saturated porous media. Laboratory batch and column flushing experiments were conducted to determine the equilibrium properties of pure NAPL and synthetically prepared NAPL mixtures as well as NAPL recovery mechanisms for different water-ethanol contents. The effect of contact time was investigated by considering different steady and intermittent flow velocities. A modified version of multiphase flow simulator (UTCHEM) was used to compare the multiphase model simulations with the column experiment results. The effect of employing different grid geometries (1D, 2D, 3D), heterogeneity and different initial NAPL saturation configurations were also examined in the model. It is shown that the change in velocity affects the mass transfer rate between phases as well as the ultimate NAPL recovery percentage. The experiments with slow flow rate flushing of pure NAPL and the 3D UTCHEM simulations gave similar effluent concentrations and NAPL cumulative recoveries. The results were less consistent for fast non-equilibrium flow conditions. The dissolution process from the NAPL mixture into the water-ethanol flushing solutions was found to be more complex than dissolution expressions incorporated in the numerical model. The dissolution rate of individual organic compounds (namely Toluene and Benzene) from a mixture NAPL into the ethanol-water flushing solution is found not to correlate with their equilibrium solubility values.The implications of this controlled experimental and modeling study on field cosolvent remediation applications are discussed.

Sensitivity of the immature rat uterotrophic assay to mixtures of estrogens.

PubMed Central

Tinwell, Helen; Ashby, John

2004-01-01

We have evaluated whether mixtures of estrogens, present in the mix at doses that are individually inactive in the immature rat uterotrophic assay, can give a uterotrophic response. Seven chemicals were evaluated: nonylphenol, bisphenol A (BPA), methoxychlor, genistein (GEN), estradiol, diethylstilbestrol, and ethinyl estradiol. Dose responses in the uterotrophic assay were constructed for each chemical. The first series of experiments involved evaluating binary mixtures of BPA and GEN at dose levels that gave moderate uterotrophic responses when tested individually. The mixtures generally showed an intermediate or reduced uterotrophic effect compared with when the components of the mixture were tested alone at the dose used in the mixture. The next series of experiments used a multicomponent (complex) mixture of all seven chemicals evaluated at doses that gave either weakly positive or inactive uterotrophic responses when tested individually in the assay. Doses that were nominally equi-uterotrophic ranged over approximately six orders of magnitude for the seven chemicals. Doses of agents that gave a weak uterotrophic response when tested individually gave a marginally enhanced positive response in the assay when tested combined as a mixture. Doses of agents that gave a negative uterotrophic response when tested individually gave a positive response when tested as a mixture. These data indicate that a variety of different estrogen receptor (ER) agonists, present individually at subeffective doses, can act simultaneously to evoke an ER-regulated response. However, translating these findings into the process of environmental hazard assessment will be difficult. The simple addition of the observed, or predicted, activities for the components of a mixture is confirmed here to be inappropriate and to overestimate the actual effect induced by the mixture. Equally, isobole analysis is only suitable for two- or three-component mixtures, and concentration addition requires access to dose-response data and EC50 values (concentration giving 50% of the maximum response) for the individual components of the mixture--requirements that will rarely be fulfilled for complex environmental samples. Given these uncertainties, we conclude that it may be most expedient to select and bioassay whole environmental mixtures of potential concern. PMID:15064164

General Blending Models for Data From Mixture Experiments

PubMed Central

Brown, L.; Donev, A. N.; Bissett, A. C.

2015-01-01

We propose a new class of models providing a powerful unification and extension of existing statistical methodology for analysis of data obtained in mixture experiments. These models, which integrate models proposed by Scheffé and Becker, extend considerably the range of mixture component effects that may be described. They become complex when the studied phenomenon requires it, but remain simple whenever possible. This article has supplementary material online. PMID:26681812

Miscibility, chain packing, and hydration of 1-palmitoyl-2-oleoyl phosphatidylcholine and other lipids in surface phases.

PubMed

Smaby, J M; Brockman, H L

1985-11-01

The miscibility of 1-palmitoyl-2-oleoyl phosphatidylcholine with triolein, 1,2-diolein, 1,3-diolein, 1(3)-monoolein, oleyl alcohol, methyl oleate, oleic acid, and oleyl cyanide (18:1 lipids) was studied at the argon-water interface. The isothermal phase diagrams for the mixtures at 24 degrees were characterized by two compositional regions. At the limit of miscibility with lower mol fractions of 18:1 lipid, the surface pressure was composition-independent, but above a mixture-specific stoichiometry, surface pressure at the limit of miscibility was composition-dependent. From the two-dimensional phase rule, it was determined that at low mol fractions of 18:1 lipids, the surface consisted of phospholipid and a preferred packing array or complex of phospholipid and 18:1 lipid, whereas, above the stoichiometry of the complex, the surface phase consisted of complex and excess 18:1 lipids. In both regions of the phase diagram, mixing along the phase boundary was apparently ideal allowing application of an equation of state described earlier (J. M. Smaby and H. L. Brockman, 1984, Biochemistry, 23:3312-3316). From such analysis, apparent partial molecular areas and hydrations for phospholipid, complex, and 18:1 lipid were obtained. Comparison of these calculated parameters for the complexed and uncomplexed states shows that the aliphatic moieties behave independently of polar head group. The transition of each 18:1 chain to the complexed state involves the loss of about one interfacial water molecule and its corresponding area. For 18:1 lipids with more than one chain another two water molecules per additional chain are present in both states but contribute little to molecular area. In contrast to 18:1 lipids, the phospholipid area and hydration change little upon complexation. The uniformity of chain packing and hydration behavior among 18:1 lipid species contrasts with complex stoichiometries that vary from 0.04 to 0.65. This suggests that the stoichiometry of the preferred packing array is determined by interactions involving the more polar moieties of the 18:1 lipids and the phospholipid.

Tributyltin synergizes with 20-hydroxyecdysone to produce endocrine toxicity.

PubMed

Wang, Ying H; Kwon, Gwijun; Li, Hong; Leblanc, Gerald A

2011-09-01

One of the great challenges facing modern toxicology is in predicting the hazard associated with chemical mixtures. The development of effective means of predicting the toxicity of chemical mixtures requires an understanding of how chemicals interact to produce nonadditive outcomes (e.g., synergy). We hypothesized that tributyltin would elicit toxicity in daphnids (Daphnia magna) by exaggerating physiological responses to 20-hydroxyecdysone signaling via synergistic activation of the retinoid X receptor (RXR):ecdysteroid receptor (EcR) complex. Using reporter gene assays, we demonstrated that RXR, alone, is activated by a variety of ligands including tributyltin, whereas RXR:EcR heterodimers were not activated by tributyltin. However, tributyltin, in combination with the daphnid EcR ligand 20-hydroxyecdysone, caused concentration-dependent, synergistic activation of the RXR:EcR reporter. Electrophoretic mobility shift assays revealed that tributyltin did not enhance the activity of 20-hydroxyecdysone by increasing binding of the receptor complex to a DR-4 DNA-binding site. Exposure of daphnids to elevated concentrations of 20-hydroxyecdysone caused premature and incomplete ecdysis resulting in death. Tributyltin exaggerated this effect of exogenous 20-hydroxyecdysone. Further, exposure of daphnids to tributyltin enhanced the inductive effects of 20-hydroxyecdysone on expression of the 20-hydroxyecdysone-inducible gene HR3. Continuous, prolonged exposure of maternal daphnids to concentrations of tributyltin resulted in mortality concurrent with molting. Taken together, these results demonstrate that xenobiotics, such as tributyltin, can interact with RXR to influence gene expression regulated by the heterodimeric partner to RXR. The result of such interactions can be toxicity due to inappropriate or exaggerated hormonal signaling. The application of the in vitro/in vivo approach used in this study is discussed in relation to modeling of nonadditive interactions among constituents of chemical mixtures.

Research and Guidance on Drinking Water Contaminant Mixtures

EPA Science Inventory

Accurate assessment of potential human health risk(s) from multiple-route exposures to multiple chemicals in drinking water is needed because of widespread daily exposure to this complex mixture. Hundreds of chemicals have been identified in drinking water with the mix of chemic...

Effects of Photochemically-Aged Atmospheres on Allergic Responses in Mice

EPA Science Inventory

Although air pollution is a complex mixture consisting of multiple gaseous and particulate components, current regulations and research approaches often focus on single pollutants. To better assess the impact of air pollution mixtures on respiratory health, we investigated the ef...

Label-free and amplified quantitation of proteins in complex mixtures using diffractive optics technology.

PubMed

Cleverley, Steve; Chen, Irene; Houle, Jean-François

2010-01-15

Immunoaffinity approaches remain invaluable tools for characterization and quantitation of biopolymers. Their application in separation science is often limited due to the challenges of immunoassay development. Typical end-point immunoassays require time consuming and labor-intensive approaches for optimization. Real-time label-free analysis using diffractive optics technology (dot) helps guide a very effective iterative process for rapid immunoassay development. Both label-free and amplified approaches can be used throughout feasibility testing and ultimately in the final assay, providing a robust platform for biopolymer analysis over a very broad dynamic range. We demonstrate the use of dot in rapidly developing assays for quantitating (1) human IgG in complex media, (2) a fusion protein in production media and (3) protein A contamination in purified immunoglobulin preparations. 2009 Elsevier B.V. All rights reserved.

A framework for the use of single-chemical transcriptomics data in predicting the hazards associated with complex mixtures of polycyclic aromatic hydrocarbons.

PubMed

Labib, Sarah; Williams, Andrew; Kuo, Byron; Yauk, Carole L; White, Paul A; Halappanavar, Sabina

2017-07-01

The assumption of additivity applied in the risk assessment of environmental mixtures containing carcinogenic polycyclic aromatic hydrocarbons (PAHs) was investigated using transcriptomics. MutaTMMouse were gavaged for 28 days with three doses of eight individual PAHs, two defined mixtures of PAHs, or coal tar, an environmentally ubiquitous complex mixture of PAHs. Microarrays were used to identify differentially expressed genes (DEGs) in lung tissue collected 3 days post-exposure. Cancer-related pathways perturbed by the individual or mixtures of PAHs were identified, and dose-response modeling of the DEGs was conducted to calculate gene/pathway benchmark doses (BMDs). Individual PAH-induced pathway perturbations (the median gene expression changes for all genes in a pathway relative to controls) and pathway BMDs were applied to models of additivity [i.e., concentration addition (CA), generalized concentration addition (GCA), and independent action (IA)] to generate predicted pathway-specific dose-response curves for each PAH mixture. The predicted and observed pathway dose-response curves were compared to assess the sensitivity of different additivity models. Transcriptomics-based additivity calculation showed that IA accurately predicted the pathway perturbations induced by all mixtures of PAHs. CA did not support the additivity assumption for the defined mixtures; however, GCA improved the CA predictions. Moreover, pathway BMDs derived for coal tar were comparable to BMDs derived from previously published coal tar-induced mouse lung tumor incidence data. These results suggest that in the absence of tumor incidence data, individual chemical-induced transcriptomics changes associated with cancer can be used to investigate the assumption of additivity and to predict the carcinogenic potential of a mixture.

Complexation behavior of oppositely charged polyelectrolytes: Effect of charge distribution

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

Zhao, Mingtian; Li, Baohui, E-mail: dliang@pku.edu.cn, E-mail: baohui@nankai.edu.cn; Zhou, Jihan

Complexation behavior of oppositely charged polyelectrolytes in a solution is investigated using a combination of computer simulations and experiments, focusing on the influence of polyelectrolyte charge distributions along the chains on the structure of the polyelectrolyte complexes. The simulations are performed using Monte Carlo with the replica-exchange algorithm for three model systems where each system is composed of a mixture of two types of oppositely charged model polyelectrolyte chains (EGEG){sub 5}/(KGKG){sub 5}, (EEGG){sub 5}/(KKGG){sub 5}, and (EEGG){sub 5}/(KGKG){sub 5}, in a solution including explicit solvent molecules. Among the three model systems, only the charge distributions along the chains are notmore » identical. Thermodynamic quantities are calculated as a function of temperature (or ionic strength), and the microscopic structures of complexes are examined. It is found that the three systems have different transition temperatures, and form complexes with different sizes, structures, and densities at a given temperature. Complex microscopic structures with an alternating arrangement of one monolayer of E/K monomers and one monolayer of G monomers, with one bilayer of E and K monomers and one bilayer of G monomers, and with a mixture of monolayer and bilayer of E/K monomers in a box shape and a trilayer of G monomers inside the box are obtained for the three mixture systems, respectively. The experiments are carried out for three systems where each is composed of a mixture of two types of oppositely charged peptide chains. Each peptide chain is composed of Lysine (K) and glycine (G) or glutamate (E) and G, in solution, and the chain length and amino acid sequences, and hence the charge distribution, are precisely controlled, and all of them are identical with those for the corresponding model chain. The complexation behavior and complex structures are characterized through laser light scattering and atomic force microscopy measurements. The order of the apparent weight-averaged molar mass and the order of density of complexes observed from the three experimental systems are qualitatively in agreement with those predicted from the simulations.« less

AN OVERVIEW OF THE DEVELOPMENT, STATUS, AND APPLICATION OF EQUILIBRIUM PARTITIONING SEDIMENT BENCHMARKS FOR PAH MIXTURES

EPA Science Inventory

This article provides an overview of the development, theoretical basis, regulatory status, and application of the U.S. Environmental Protection Agency's (USEPA's)< Equilibrium Partitioning Sediment Benchmarks (ESBs) for PAH mixtures. ESBs are compared to other sediment quality g...

Biochemometrics for Natural Products Research: Comparison of Data Analysis Approaches and Application to Identification of Bioactive Compounds.

PubMed

Kellogg, Joshua J; Todd, Daniel A; Egan, Joseph M; Raja, Huzefa A; Oberlies, Nicholas H; Kvalheim, Olav M; Cech, Nadja B

2016-02-26

A central challenge of natural products research is assigning bioactive compounds from complex mixtures. The gold standard approach to address this challenge, bioassay-guided fractionation, is often biased toward abundant, rather than bioactive, mixture components. This study evaluated the combination of bioassay-guided fractionation with untargeted metabolite profiling to improve active component identification early in the fractionation process. Key to this methodology was statistical modeling of the integrated biological and chemical data sets (biochemometric analysis). Three data analysis approaches for biochemometric analysis were compared, namely, partial least-squares loading vectors, S-plots, and the selectivity ratio. Extracts from the endophytic fungi Alternaria sp. and Pyrenochaeta sp. with antimicrobial activity against Staphylococcus aureus served as test cases. Biochemometric analysis incorporating the selectivity ratio performed best in identifying bioactive ions from these extracts early in the fractionation process, yielding altersetin (3, MIC 0.23 μg/mL) and macrosphelide A (4, MIC 75 μg/mL) as antibacterial constituents from Alternaria sp. and Pyrenochaeta sp., respectively. This study demonstrates the potential of biochemometrics coupled with bioassay-guided fractionation to identify bioactive mixture components. A benefit of this approach is the ability to integrate multiple stages of fractionation and bioassay data into a single analysis.

Carboxylic acid functional group analysis using constant neutral loss scanning-mass spectrometry.

PubMed

Dron, Julien; Eyglunent, Gregory; Temime-Roussel, Brice; Marchand, Nicolas; Wortham, Henri

2007-12-12

The present study describes the development of a new analytical technique for the functional group determination of the carboxylic moiety using atmospheric pressure chemical ionization-mass spectrometry (APCI-MS/MS) operated in the constant neutral loss scanning (CNLS) mode. Carboxylic groups were first derivatized into their corresponding methyl esters by reacting with BF3/methanol mix and the reaction mixture was then directly injected into the APCI chamber. The loss of methanol (m/z = 32 amu) resulting from the fragmentation of the protonated methyl esters was then monitored. Applying this method together with a statistical approach to reference mixtures containing 31 different carboxylic acids at randomly calculated concentrations demonstrated its suitability for quantitative functional group measurements with relative standard deviations below 15% and a detection limit of 0.005 mmol L(-1). Its applicability to environmental matrices was also shown through the determination of carboxylic acid concentrations inside atmospheric aerosol samples. To the best of our knowledge, it is the first time that the tandem mass spectrometry was successfully applied to functional group analysis, offering great perspectives in the characterization of complex mixtures which are prevailing in the field of environmental analysis as well as in the understanding of the chemical processes occurring in these matrices.

Bile acids: analysis in biological fluids and tissues

PubMed Central

Griffiths, William J.; Sjövall, Jan

2010-01-01

The formation of bile acids/bile alcohols is of major importance for the maintenance of cholesterol homeostasis. Besides their functions in lipid absorption, bile acids/bile alcohols are regulatory molecules for a number of metabolic processes. Their effects are structure-dependent, and numerous metabolic conversions result in a complex mixture of biologically active and inactive forms. Advanced methods are required to characterize and quantify individual bile acids in these mixtures. A combination of such analyses with analyses of the proteome will be required for a better understanding of mechanisms of action and nature of endogenous ligands. Mass spectrometry is the basic detection technique for effluents from chromatographic columns. Capillary liquid chromatography-mass spectrometry with electrospray ionization provides the highest sensitivity in metabolome analysis. Classical gas chromatography-mass spectrometry is less sensitive but offers extensive structure-dependent fragmentation increasing the specificity in analyses of isobaric isomers of unconjugated bile acids. Depending on the nature of the bile acid/bile alcohol mixture and the range of concentration of individuals, different sample preparation sequences, from simple extractions to group separations and derivatizations, are applicable. We review the methods currently available for the analysis of bile acids in biological fluids and tissues, with emphasis on the combination of liquid and gas phase chromatography with mass spectrometry. PMID:20008121

Chirality-sensitive microwave spectroscopy - application to terpene molecules

NASA Astrophysics Data System (ADS)

Schnell, Melanie

Most molecules of biochemical relevance are chiral. Even though the physical properties of two enantiomers are nearly identical, they might exhibit completely different biochemical effects, such as different odor in the case of carvone. In nature and as products of chemical syntheses, chiral molecules often exist in mixtures with other chiral molecules. The analysis of these complex mixtures to identify the molecular components, to determine which enantiomers are present, and to measure the enantiomeric excesses (ee) is still one of the challenging and very important tasks of analytical chemistry. We recently experimentally demonstrated a new method of differentiating enantiomeric pairs of chiral molecules in the gas phase. It is based on broadband rotational spectroscopy and is a three-wave mixing process that involves a closed cycle of three rotational transitions. The phase of the acquired signal bares the signature of the enantiomer, as it depends upon the product of the transition dipole moments. Furthermore, because the signal amplitude is proportional to the ee, this technique allows not only for determining which enantiomer is in excess, but also by how much. A unique advantage of our technique is that it can also be applied to mixtures of chiral molecules, even when the molecules are very similar. In my lecture, I will introduce the technique and give an update on the recent developments.

NMR/MS Translator for the Enhanced Simultaneous Analysis of Metabolomics Mixtures by NMR Spectroscopy and Mass Spectrometry: Application to Human Urine.

PubMed

Bingol, Kerem; Brüschweiler, Rafael

2015-06-05

A novel metabolite identification strategy is presented for the combined NMR/MS analysis of complex metabolite mixtures. The approach first identifies metabolite candidates from 1D or 2D NMR spectra by NMR database query, which is followed by the determination of the masses (m/z) of their possible ions, adducts, fragments, and characteristic isotope distributions. The expected m/z ratios are then compared with the MS(1) spectrum for the direct assignment of those signals of the mass spectrum that contain information about the same metabolites as the NMR spectra. In this way, the mass spectrum can be assigned with very high confidence, and it provides at the same time validation of the NMR-derived metabolites. The method was first demonstrated on a model mixture, and it was then applied to human urine collected from a pool of healthy individuals. A number of metabolites could be detected that had not been reported previously, further extending the list of known urine metabolites. The new analysis approach, which is termed NMR/MS Translator, is fully automated and takes only a few seconds on a computer workstation. NMR/MS Translator synergistically uses the power of NMR and MS, enhancing the accuracy and efficiency of the identification of those metabolites compiled in databases.

Methods for compressible multiphase flows and their applications

NASA Astrophysics Data System (ADS)

Kim, H.; Choe, Y.; Kim, H.; Min, D.; Kim, C.

2018-06-01

This paper presents an efficient and robust numerical framework to deal with multiphase real-fluid flows and their broad spectrum of engineering applications. A homogeneous mixture model incorporated with a real-fluid equation of state and a phase change model is considered to calculate complex multiphase problems. As robust and accurate numerical methods to handle multiphase shocks and phase interfaces over a wide range of flow speeds, the AUSMPW+_N and RoeM_N schemes with a system preconditioning method are presented. These methods are assessed by extensive validation problems with various types of equation of state and phase change models. Representative realistic multiphase phenomena, including the flow inside a thermal vapor compressor, pressurization in a cryogenic tank, and unsteady cavitating flow around a wedge, are then investigated as application problems. With appropriate physical modeling followed by robust and accurate numerical treatments, compressible multiphase flow physics such as phase changes, shock discontinuities, and their interactions are well captured, confirming the suitability of the proposed numerical framework to wide engineering applications.

The role of phospholipid as a solubility- and permeability-enhancing excipient for the improved delivery of the bioactive phytoconstituents of Bacopa monnieri.

PubMed

Saoji, Suprit D; Dave, Vivek S; Dhore, Pradip W; Bobde, Yamini S; Mack, Connor; Gupta, Deepak; Raut, Nishikant A

2017-10-15

In an attempt to improve the solubility and permeability of Standardized Bacopa Extract (SBE), a complexation approach based on phospholipid was employed. A solvent evaporation method was used to prepare the SBE-phospholipid complex (Bacopa Naturosome, BN). The formulation and process variables were optimized using a central-composite design. The formation of BN was confirmed by photomicroscopy, Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD). The saturation solubility, the in-vitro dissolution, and the ex-vivo permeability studies were used for the functional evaluation of the prepared complex. BN exhibited a significantly higher aqueous solubility compared to the pure SBE (20-fold), or the physical mixture of SBE and the phospholipid (13-fold). Similarly, the in-vitro dissolution revealed a significantly higher efficiency of the prepared complex (BN) in releasing the SBE (>97%) in comparison to the pure SCE (~42%), or the physical mixture (~47%). The ex-vivo permeation studies showed that the prepared BN significantly improved the permeation of SBE (>90%), compared to the pure SBE (~21%), or the physical mixture (~24%). Drug-phospholipid complexation may thus be a promising strategy for solubility enhancement of bioactive phytoconstituents. Copyright © 2016 Elsevier B.V. All rights reserved.

Solid phase excitation-emission fluorescence method for the classification of complex substances: Cortex Phellodendri and other traditional Chinese medicines as examples.

PubMed

Gu, Yao; Ni, Yongnian; Kokot, Serge

2012-09-13

A novel, simple and direct fluorescence method for analysis of complex substances and their potential substitutes has been researched and developed. Measurements involved excitation and emission (EEM) fluorescence spectra of powdered, complex, medicinal herbs, Cortex Phellodendri Chinensis (CPC) and the similar Cortex Phellodendri Amurensis (CPA); these substances were compared and discriminated from each other and the potentially adulterated samples (Caulis mahoniae (CM) and David poplar bark (DPB)). Different chemometrics methods were applied for resolution of the complex spectra, and the excitation spectra were found to be the most informative; only the rank-ordering PROMETHEE method was able to classify the samples with single ingredients (CPA, CPC, CM) or those with binary mixtures (CPA/CPC, CPA/CM, CPC/CM). Interestingly, it was essential to use the geometrical analysis for interactive aid (GAIA) display for a full understanding of the classification results. However, these two methods, like the other chemometrics models, were unable to classify composite spectral matrices consisting of data from samples of single ingredients and binary mixtures; this suggested that the excitation spectra of the different samples were very similar. However, the method is useful for classification of single-ingredient samples and, separately, their binary mixtures; it may also be applied for similar classification work with other complex substances.

Enabling the identification, quantification, and characterization of organics in complex mixtures to understand atmospheric aerosols

NASA Astrophysics Data System (ADS)

Isaacman, Gabriel Avram

Particles in the atmosphere are known to have negative health effects and important but highly uncertain impacts on global and regional climate. A majority of this particulate matter is formed through atmospheric oxidation of naturally and anthropogenically emitted gases to yield highly oxygenated secondary organic aerosol (SOA), an amalgamation of thousands of individual chemical compounds. However, comprehensive analysis of SOA composition has been stymied by its complexity and lack of available measurement techniques. In this work, novel instrumentation, analysis methods, and conceptual frameworks are introduced for chemically characterizing atmospherically relevant mixtures and ambient aerosols, providing a fundamentally new level of detailed knowledge on their structures, chemical properties, and identification of their components. This chemical information is used to gain insights into the formation, transformation and oxidation of organic aerosols. Biogenic and anthropogenic mixtures are observed in this work to yield incredible complexity upon oxidation, producing over 100 separable compounds from a single precursor. As a first step toward unraveling this complexity, a method was developed for measuring the polarity and volatility of individual compounds in a complex mixture using two-dimensional gas chromatography, which is demonstrated in Chapter 2 for describing the oxidation of SOA formed from a biogenic compound (longifolene: C15H24). Several major products and tens of substantial minor products were produced, but none could be identified by traditional methods or have ever been isolated and studied in the laboratory. A major realization of this work was that soft ionization mass spectrometry could be used to identify the molecular mass and formula of these unidentified compounds, a major step toward a comprehensive description of complex mixtures. This was achieved by coupling gas chromatography to high resolution time-of-flight mass spectrometry with vacuum ultraviolet (VUV) photo-ionization. Chapters 3 and 4 describe this new analytical technique and its initial application to determine the structures of unknown compounds and formerly unresolvable mixtures, including a complete description of the chemical composition of two common petroleum products related to anthropogenic emissions: diesel fuel and motor oil. The distribution of hydrocarbon isomers in these mixtures - found to be mostly of branched, cyclic, and saturated -- is described with unprecedented detail. Instead of measuring average bulk aerosol properties, the methods developed and applied in this work directly measure the polarity, volatility, and structure of individual components to allow a mechanistic understanding of oxidation processes. Novel characterizations of these complex mixtures are used to elucidate the role of structure and functionality in particle-phase oxidation, including in Chapter 4 the first measurements of relative reaction rates in a complex hydrocarbon particle. Molecular structure is observed to influence particle-phase oxidation in unexpected and important ways, with cyclization decreasing reaction rates by ~30% and branching increasing reaction rates by ~20-50%. The observed structural dependence is proposed to result in compositional changes in anthropogenic organic aerosol downwind of urban areas, which has been confirmed in subsequent work by applying the techniques described here. Measurement of organic aerosol components is extended to ambient environments through the development of instrumentation with the unprecedented capability to measure hourly concentrations and gas/particle partitioning of individual highly oxygenated organic compounds in the atmosphere. Chapters 5 and 6 describe development of new procedures and hardware for the calibration and analysis of oxygenates using the Semi-Volatile Thermal desorption Aerosol Gas chromatograph (SV-TAG), a custom instrument for in situ quantification of gas- and particle-phase organic compounds in the atmosphere. High time resolution measurement of oxygenated compounds is achieved through a reproducible and quantitative methodology for in situ "derivatization" -- replacing highly polar functional groups that cannot be analyzed by traditional gas chromatography with less polar groups. Implementation of a two-channel sampling system for the simultaneous collection of particle-phase and total gas-plus-particle phase samples allows for the first direct measurements of gas/particle partitioning in the atmosphere, significantly advancing the study of atmospheric composition and variability, as well as the processes governing condensation and re-volatilization. This work presents the first in situ measurements of a large suite of highly oxygenated biogenic oxidation products in both the gas- and particle-phase. Isoprene, the most ubiquitous biogenic emission, oxidizes to form 2-methyltetrols and C5 alkene triols, while α-pinene, the most common monoterpene, forms pinic, pinonic, hydroxyglutaric, and other acids. These compounds are reported in Chapter 7 with unprecedented time resolution and are shown for the first time to have a large gas-phase component, contrary to typical assumptions. Hourly comparisons of these products with anthropogenic aerosol components elucidate the interaction of human and natural emissions at two rural sites: the southeastern, U.S. and Amazonia, Brazil. Anthropogenic influence on SOA formation is proposed to occur through the increase in liquid water caused by anthropogenic sulfate. Furthermore, these unparalleled observations of gas/particle partitioning of biogenic oxidation products demonstrate that partitioning of oxygenates is unexpectedly independent of volatility: many volatile, highly oxygenated compounds have a large particle-phase component that is poorly described by traditional models. These novel conclusions are reached in part by applying the new frameworks developed in previous chapters to understand the properties of unidentified compounds, demonstrating the importance of detailed characterization of atmospheric organic mixtures. Comprehensive analysis of anthropogenic and biogenic emissions and oxidation product mixtures is coupled in this work with high time-resolution measurement of individual organic components to yield significant insights into the transformations of organic aerosols. Oxidation chemistry is observed in both laboratory and field settings to depend on molecular properties, volatility, and atmospheric composition. However, this work demonstrates that these complex processes can be understood through the quantification of individual known and unidentified compounds, combined with their classification into descriptive frameworks.

Computational Docking of the Isomers of Nonylphenol to the Ligand Binding Domain of the Estrogen Receptor

EPA Science Inventory

Nonylphenols are environmentally persistent endocrine disrupting chemicals. They exist in the environment as complex mixtures containing many nonylphenol isomers. Environmental mixtures of nonylphenols, along with a few single isomers have been tested for their capacity to inte...

Quantitative structure - mesothelioma Potency Model Optimization for Complex Mixtures of Elongated Particles in Rat Pleura

EPA Science Inventory

Cancer potencies of mineral and synthetic elongated particle (EP) mixtures, including fibers from asbestos, are influenced by changes in fiber dose composition, bioavailability and biodurability in combination with relevant cytotoxic dose-response relationships. A unique and com...

Biologically-Based Lumping Methodology (BBLM) To Investigate Toxicological Interactions of Complex Chemical Mixtures

EPA Science Inventory

Many cases of environmental contamination result in concurrent or sequential exposure to more than one chemical. Limitations of available resources prevent experimental toxicology from providing health risk information about all the possible mixtures to which humans or other spec...

Proteomic analysis of a model fish species exposed to individual pesticides and a binary mixture

EPA Science Inventory

Aquatic organisms are often exposed to multiple pesticides simultaneously. Due to the relatively poor characterization of mixture constituent interactions and the potential for highly complex exposure scenarios, there is considerable uncertainty in understanding the toxicity of m...

PHOTOCHEMICAL PRODUCTS IN URBAN MIXTURES ENHANCE INFLAMMATORY RESPONSES IN LUNG CELLS

EPA Science Inventory

Complex urban air mixtures that realistically mimic urban smog can be generated for investigating adverse health effects. "Smog chambers" have been used for over 30 yr to conduct experiments for developing and testing photochemical models that predict ambient ozone (O(3)) concent...

Chloramination of Concentrated Drinking Water for Disinfection Byproduct Mixtures Creation- Indianapolis

EPA Science Inventory

Complex mixtures of disinfection by-products (DBPs) are formed when the disinfectant oxidizes constituents (e.g., natural organic matter (NOM) and organic pollutants) found in the source water. Since 1974, over 600 DBPs have been identified in drinking water. Despite intense iden...

Synergism and antagonism in extracting local anesthetics from aqueous media with mixtures of solvents

NASA Astrophysics Data System (ADS)

Sukhanov, P. T.; Chibisova, T. V.; Korenman, Ya. I.

2014-12-01

The extraction of local anesthetics from aqueous media with mixtures of solvent is examined and its synergistic and antagonistic effects are determined. Synergism parameters, separation factors, constants for the formation of anesthetic complexes, and solvate numbers are calculated.

Effects of Isoprene- and Toluene-Generated Smog on Allergic Inflammation in Mice

EPA Science Inventory

Reactions of organic compounds with nitric oxide (NO) and sunlight produce complex mixtures of pollutants including secondary organic aerosol (SOA), ozone (O3), nitrogen dioxide (NO2), and reactive aldehydes. The health effects of these photochemical smog mixtures in susceptible ...

Quantitative Trait Loci (QTL)-Guided Metabolic Engineering of a Complex Trait.

PubMed

Maurer, Matthew J; Sutardja, Lawrence; Pinel, Dominic; Bauer, Stefan; Muehlbauer, Amanda L; Ames, Tyler D; Skerker, Jeffrey M; Arkin, Adam P

2017-03-17

Engineering complex phenotypes for industrial and synthetic biology applications is difficult and often confounds rational design. Bioethanol production from lignocellulosic feedstocks is a complex trait that requires multiple host systems to utilize, detoxify, and metabolize a mixture of sugars and inhibitors present in plant hydrolysates. Here, we demonstrate an integrated approach to discovering and optimizing host factors that impact fitness of Saccharomyces cerevisiae during fermentation of a Miscanthus x giganteus plant hydrolysate. We first used high-resolution Quantitative Trait Loci (QTL) mapping and systematic bulk Reciprocal Hemizygosity Analysis (bRHA) to discover 17 loci that differentiate hydrolysate tolerance between an industrially related (JAY291) and a laboratory (S288C) strain. We then used this data to identify a subset of favorable allelic loci that were most amenable for strain engineering. Guided by this "genetic blueprint", and using a dual-guide Cas9-based method to efficiently perform multikilobase locus replacements, we engineered an S288C-derived strain with superior hydrolysate tolerance than JAY291. Our methods should be generalizable to engineering any complex trait in S. cerevisiae, as well as other organisms.

Prebiotic selection and assembly of proteinogenic amino acids and natural nucleotides from complex mixtures

NASA Astrophysics Data System (ADS)

Islam, Saidul; Bučar, Dejan-Krešimir; Powner, Matthew W.

2017-06-01

A central problem for the prebiotic synthesis of biological amino acids and nucleotides is to avoid the concomitant synthesis of undesired or irrelevant by-products. Additionally, multistep pathways require mechanisms that enable the sequential addition of reactants and purification of intermediates that are consistent with reasonable geochemical scenarios. Here, we show that 2-aminothiazole reacts selectively with two- and three-carbon sugars (glycolaldehyde and glyceraldehyde, respectively), which results in their accumulation and purification as stable crystalline aminals. This permits ribonucleotide synthesis, even from complex sugar mixtures. Remarkably, aminal formation also overcomes the thermodynamically favoured isomerization of glyceraldehyde into dihydroxyacetone because only the aminal of glyceraldehyde separates from the equilibrating mixture. Finally, we show that aminal formation provides a novel pathway to amino acids that avoids the synthesis of the non-proteinogenic α,α-disubstituted analogues. The common physicochemical mechanism that controls the proteinogenic amino acid and ribonucleotide assembly from prebiotic mixtures suggests that these essential classes of metabolite had a unified chemical origin.

Comparative Analysis of Stress Induced Gene Expression in Caenorhabditis elegans following Exposure to Environmental and Lab Reconstituted Complex Metal Mixture

PubMed Central

Kumar, Ranjeet; Pradhan, Ajay; Khan, Faisal Ahmad; Lindström, Pia; Ragnvaldsson, Daniel; Ivarsson, Per; Olsson, Per-Erik; Jass, Jana

2015-01-01

Metals are essential for many physiological processes and are ubiquitously present in the environment. However, high metal concentrations can be harmful to organisms and lead to physiological stress and diseases. The accumulation of transition metals in the environment due to either natural processes or anthropogenic activities such as mining results in the contamination of water and soil environments. The present study used Caenorhabditis elegans to evaluate gene expression as an indicator of physiological response, following exposure to water collected from three different locations downstream of a Swedish mining site and a lab reconstituted metal mixture. Our results indicated that the reconstituted metal mixture exerted a direct stress response in C. elegans whereas the environmental waters elicited either a diminished or abrogated response. This suggests that it is not sufficient to use the biological effects observed from laboratory mixtures to extrapolate the effects observed in complex aquatic environments and apply this to risk assessment and intervention. PMID:26168046

Biomarkers of Cytotoxic, Genotoxic and Apoptotic Effects in Cyprinus carpio Exposed to Complex Mixture of Contaminants from Hospital Effluents.

PubMed

Olvera-Néstor, Corina G; Morales-Avila, Enrique; Gómez-Olivan, Leobardo M; Galár-Martínez, Marcela; García-Medina, Sandra; Neri-Cruz, Nadia

2016-03-01

Hospital wastewater is an important source of emerging contaminants. Recent studies emphasize the importance of assessing the effects of mixtures of contaminants rather than environmental risk of their individual components, as well as the determination of intrinsic toxicity of wastewater. Mixtures of pollutants has possible interactions that have notable environmental side effects. The aim of this study is an attempt to characterize biomarkers in Cyprinus carpio related to the exposure to a complex mixture of contaminants found in hospital wastewater. Results of a particular hospital effluent show the presence of traces of heavy metals, high chlorine concentration and emerging contaminants such as non-steroidal anti-inflammatory drugs. The LC50 was of 5.49 % at 96 h. The cytotoxic, genotoxic and apoptotic biomarkers increase when fishes were exposed to wastewater (1/10 CL50) from hospital wastewater. This study emphasizes the importance of identifying and quantifying the effects of contaminants as pharmaceuticals, disinfectants and surfactants in order to design and implement an ecotoxicological plan.

HPLC-Chip/MS Technology in Proteomic Profiling

NASA Astrophysics Data System (ADS)

Vollmer, Martin; van de Goor, Tom

HPLC-chip/MS is a novel nanoflow analytical technology conducted on a microfabricated chip that allows for highly efficient HPLC separation and superior sensitive MS detection of complex proteomic mixtures. This is possible through on-chip preconcentration and separation with fluidic connection made automatically in a leak-tight fashion. Minimum precolumn and postcolumn peak dispersion and uncompromised ease of use result in compounds eluting in bands of only a few nanoliters. The chip is fabricated out of bio-inert polyimide-containing channels and integrated chip structures, such as an electrospray emitter, columns, and frits manufactured by laser ablation technology. Meanwhile, a variety of HPLC-chips differing in design and stationary phase are commercially available, which provide a comprehensive solution for applications in proteomics, glycomics, biomarker, and pharmaceutical discovery. The HPLC-chip can also be easily integrated into a multidimensional separation workflow where different orthogonal separation techniques are combined to solve a highly complex separation problems. In this chapter, we describe in detail the methodological chip usage and functionality and its application in the elucidation of the protein profile of human nucleoli.

Nano-Assemblies of Modified Cyclodextrins and Their Complexes with Guest Molecules: Incorporation in Nanostructured Membranes and Amphiphile Nanoarchitectonics Design

PubMed Central

Zerkoune, Leïla; Angelova, Angelina; Lesieur, Sylviane

2014-01-01

A variety of cyclodextrin-based molecular structures, with substitutions of either primary or secondary faces of the natural oligosaccharide macrocycles of α-, β-, or γ-cyclodextrins, have been designed towards innovative applications of self-assembled cyclodextrin nanomaterials. Amphiphilic cyclodextrins have been obtained by chemical or enzymatic modifications of their macrocycles using phospholipidyl, peptidolipidyl, cholesteryl, and oligo(ethylene oxide) anchors as well as variable numbers of grafted hydrophobic hydrocarbon or fluorinated chains. These novel compounds may self-assemble in an aqueous medium into different types of supramolecular nanoassemblies (vesicles, micelles, nanorods, nanospheres, and other kinds of nanoparticles and liquid crystalline structures). This review discusses the supramolecular nanoarchitectures, which can be formed by amphiphilic cyclodextrin derivatives in mixtures with other molecules (phospholipids, surfactants, and olygonucleotides). Biomedical applications are foreseen for nanoencapsulation of drug molecules in the hydrophobic interchain volumes and nanocavities of the amphiphilic cyclodextrins (serving as drug carriers or pharmaceutical excipients), anticancer phototherapy, gene delivery, as well as for protection of instable active ingredients through inclusion complexation in nanostructured media. PMID:28344245

Protonation of Different Goethite Surfaces - Unified Models for NaNO3 and NaCl Media.

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

Lutzenkirchen, Johannes; Boily, Jean F.; Gunneriusson, Lars

2008-01-01

Acid-base titration data for two goethites samples in sodium nitrate and sodium chloride media are discussed. The data are modelled based on various surface complexation models in the framework of the MUlti SIte Complexation (MUSIC) model. Various assumptions with respect to the goethite morphology are considered in determining the site density of the surface functional groups. The results from the various model applications are not statistically significant in terms of goodness of fit. More importantly, various published assumptions with respect to the goethite morphology (i.e. the contributions of different crystal planes and their repercussions on the “overall” site densities ofmore » the various surface functional groups) do not significantly affect the final model parameters. The simultaneous fit of the chloride and nitrate data results in electrolyte binding constants, which are applicable over a wide range of electrolyte concentrations including mixtures of chloride and nitrate. Model parameters for the high surface area goethite sample are in excellent agreement with parameters that were independently obtained by another group on different goethite titration data sets.« less

Statistical mixture design and multivariate analysis of inkjet printed a-WO3/TiO2/WOX electrochromic films.

PubMed

Wojcik, Pawel Jerzy; Pereira, Luís; Martins, Rodrigo; Fortunato, Elvira

2014-01-13

An efficient mathematical strategy in the field of solution processed electrochromic (EC) films is outlined as a combination of an experimental work, modeling, and information extraction from massive computational data via statistical software. Design of Experiment (DOE) was used for statistical multivariate analysis and prediction of mixtures through a multiple regression model, as well as the optimization of a five-component sol-gel precursor subjected to complex constraints. This approach significantly reduces the number of experiments to be realized, from 162 in the full factorial (L=3) and 72 in the extreme vertices (D=2) approach down to only 30 runs, while still maintaining a high accuracy of the analysis. By carrying out a finite number of experiments, the empirical modeling in this study shows reasonably good prediction ability in terms of the overall EC performance. An optimized ink formulation was employed in a prototype of a passive EC matrix fabricated in order to test and trial this optically active material system together with a solid-state electrolyte for the prospective application in EC displays. Coupling of DOE with chromogenic material formulation shows the potential to maximize the capabilities of these systems and ensures increased productivity in many potential solution-processed electrochemical applications.

Prospective power calculations for the Four Lab study of a multigenerational reproductive/developmental toxicity rodent bioassay using a complex mixture of disinfection by-products in the low-response region.

PubMed

Dingus, Cheryl A; Teuschler, Linda K; Rice, Glenn E; Simmons, Jane Ellen; Narotsky, Michael G

2011-10-01

In complex mixture toxicology, there is growing emphasis on testing environmentally representative doses that improve the relevance of results for health risk assessment, but are typically much lower than those used in traditional toxicology studies. Traditional experimental designs with typical sample sizes may have insufficient statistical power to detect effects caused by environmentally relevant doses. Proper study design, with adequate statistical power, is critical to ensuring that experimental results are useful for environmental health risk assessment. Studies with environmentally realistic complex mixtures have practical constraints on sample concentration factor and sample volume as well as the number of animals that can be accommodated. This article describes methodology for calculation of statistical power for non-independent observations for a multigenerational rodent reproductive/developmental bioassay. The use of the methodology is illustrated using the U.S. EPA's Four Lab study in which rodents were exposed to chlorinated water concentrates containing complex mixtures of drinking water disinfection by-products. Possible experimental designs included two single-block designs and a two-block design. Considering the possible study designs and constraints, a design of two blocks of 100 females with a 40:60 ratio of control:treated animals and a significance level of 0.05 yielded maximum prospective power (~90%) to detect pup weight decreases, while providing the most power to detect increased prenatal loss.

Prospective Power Calculations for the Four Lab Study of A Multigenerational Reproductive/Developmental Toxicity Rodent Bioassay Using A Complex Mixture of Disinfection By-Products in the Low-Response Region

PubMed Central

Dingus, Cheryl A.; Teuschler, Linda K.; Rice, Glenn E.; Simmons, Jane Ellen; Narotsky, Michael G.

2011-01-01

In complex mixture toxicology, there is growing emphasis on testing environmentally representative doses that improve the relevance of results for health risk assessment, but are typically much lower than those used in traditional toxicology studies. Traditional experimental designs with typical sample sizes may have insufficient statistical power to detect effects caused by environmentally relevant doses. Proper study design, with adequate statistical power, is critical to ensuring that experimental results are useful for environmental health risk assessment. Studies with environmentally realistic complex mixtures have practical constraints on sample concentration factor and sample volume as well as the number of animals that can be accommodated. This article describes methodology for calculation of statistical power for non-independent observations for a multigenerational rodent reproductive/developmental bioassay. The use of the methodology is illustrated using the U.S. EPA’s Four Lab study in which rodents were exposed to chlorinated water concentrates containing complex mixtures of drinking water disinfection by-products. Possible experimental designs included two single-block designs and a two-block design. Considering the possible study designs and constraints, a design of two blocks of 100 females with a 40:60 ratio of control:treated animals and a significance level of 0.05 yielded maximum prospective power (~90%) to detect pup weight decreases, while providing the most power to detect increased prenatal loss. PMID:22073030

21 CFR 1310.09 - Temporary exemption from registration.

Code of Federal Regulations, 2010 CFR

2010-04-01

... manufacture, distribute, import, or export regulated iodine, including regulated iodine chemical mixtures... a chemical mixture containing iodine on or before August 31, 2007. The exemption will remain in... distributes, imports, or exports a chemical mixture containing iodine whose application for exemption is...

75 FR 36306 - Chemical Mixtures Containing Listed Forms of Phosphorus and Change in Application Process

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-25

... 1117-AA66 Chemical Mixtures Containing Listed Forms of Phosphorus and Change in Application Process... phosphorus, white phosphorus (also known as yellow phosphorus), or hypophosphorous acid and its salts (hereinafter ``regulated phosphorus'') that shall automatically qualify for exemption from the Controlled...

Evaluation of the Microhaplotypes panel for DNA mixture analyses.

PubMed

Chen, Peng; Yin, Caiyong; Li, Zheng; Pu, Yan; Yu, Youjia; Zhao, Peng; Chen, Dexin; Liang, Weibo; Zhang, Lin; Chen, Feng

2018-05-12

The identification of a suspect in a DNA mixture typed with the standard short tandem repeat polymorphism (STR) kits has faced challenges. Several improved methods or technologies have been introduced to address this issue. However, some complex situations in the process remain elusive. In the present study, we presented a panel of 26 tiny microhaplotypes, each generating a relatively high (>3.0) effective number of alleles (A e ) and possessing low (<50 bp) sequence lengths. The average A e and heterozygosity values among the 9 populations of 26 microhaps were in ranges from 2.60 to 4.54 and 0.59 to 0.96, respectively. Power of discrimination and power of exclusion values were ranged from 0.49 to 0.87 and 0.29 to 0.94, respectively. Significant positive correlations have been found between A e values and heterozygosity (r = 0.43, p = 0.02) or power of discrimination values (r = 0.55, p = 0.003), respectively. The cumulative probability of detecting a mixture of two unrelated individuals could reach 0.9999998 when using a panel of 26 microhaps with A e  = 3. We further tested the panel by using massively parallel sequencing, and 14 out of 26 microhaps were successfully genotyped in a single multiplex system. 60 unrelated Chinese Han individuals and 2 artificially prepared samples mixed by two unrelated contributors (in duplicate, ie. 4 mixtures) were sequenced. Approximately 32.14% of the 14 loci presented three or four alleles in the two mixtures. The likelihood ratio values to cognizance the mixtures' contributor were in a range from 1.95 × 10 6 to 1.10 × 10 7 . The results demonstrated that the present panel could offer a valuable complementary tool in forensic applications. Copyright © 2018 Elsevier B.V. All rights reserved.

BioMOL: a computer-assisted biological modeling tool for complex chemical mixtures and biological processes at the molecular level.

PubMed Central

Klein, Michael T; Hou, Gang; Quann, Richard J; Wei, Wei; Liao, Kai H; Yang, Raymond S H; Campain, Julie A; Mazurek, Monica A; Broadbelt, Linda J

2002-01-01

A chemical engineering approach for the rigorous construction, solution, and optimization of detailed kinetic models for biological processes is described. This modeling capability addresses the required technical components of detailed kinetic modeling, namely, the modeling of reactant structure and composition, the building of the reaction network, the organization of model parameters, the solution of the kinetic model, and the optimization of the model. Even though this modeling approach has enjoyed successful application in the petroleum industry, its application to biomedical research has just begun. We propose to expand the horizons on classic pharmacokinetics and physiologically based pharmacokinetics (PBPK), where human or animal bodies were often described by a few compartments, by integrating PBPK with reaction network modeling described in this article. If one draws a parallel between an oil refinery, where the application of this modeling approach has been very successful, and a human body, the individual processing units in the oil refinery may be considered equivalent to the vital organs of the human body. Even though the cell or organ may be much more complicated, the complex biochemical reaction networks in each organ may be similarly modeled and linked in much the same way as the modeling of the entire oil refinery through linkage of the individual processing units. The integrated chemical engineering software package described in this article, BioMOL, denotes the biological application of molecular-oriented lumping. BioMOL can build a detailed model in 1-1,000 CPU sec using standard desktop hardware. The models solve and optimize using standard and widely available hardware and software and can be presented in the context of a user-friendly interface. We believe this is an engineering tool with great promise in its application to complex biological reaction networks. PMID:12634134

The glatiramoid class of immunomodulator drugs.

PubMed

Varkony, Haim; Weinstein, Vera; Klinger, Ety; Sterling, Jeffrey; Cooperman, Helena; Komlosh, Turi; Ladkani, David; Schwartz, Rivka

2009-03-01

Glatiramer acetate (GA) is a complex heterogenous mixture of polypeptides with immunomodulatory activity approved for treatment of relapsing-remitting multiple sclerosis. GA is the first, and was until recently, the only member of the glatiramoids, a family of synthetic copolymer mixtures comprising the four amino acids, L-glutamic acid, L-alanine, L-lysine and L-tyrosine, in a defined molar ratio. Another glatiramoid, protiramer, was recently evaluated in preclinical studies and in two small Phase II clinical trials with relapsing-remitting multiple sclerosis patients. Due to the complexity and heterogeneity of GA and other glatiramoids, the clinically active epitopes within the mixture cannot be identified and the consistency of polypeptide sequences within the mixture is dependent on a tightly controlled manufacturing process. Although no two glatiramoids can be proved identical, it is possible to differentiate among members of the glatiramoid class using analytical methods and immunological and biological markers. Even slight differences in the distribution of molecular masses or in the composition of antigenic polypeptide sequences among glatiramoids can significantly influence their efficacy, toxicity and immunogenicity profiles. Experience with GA may be instructive regarding important safety and efficacy considerations for new glatiramoid mixtures now in development.

Adaptation of aeronautical engines to high altitude flying

NASA Technical Reports Server (NTRS)

Kutzbach, K

1923-01-01

Issues and techniques relative to the adaptation of aircraft engines to high altitude flight are discussed. Covered here are the limits of engine output, modifications and characteristics of high altitude engines, the influence of air density on the proportions of fuel mixtures, methods of varying the proportions of fuel mixtures, the automatic prevention of fuel waste, and the design and application of air pressure regulators to high altitude flying. Summary: 1. Limits of engine output. 2. High altitude engines. 3. Influence of air density on proportions of mixture. 4. Methods of varying proportions of mixture. 5. Automatic prevention of fuel waste. 6. Design and application of air pressure regulators to high altitude flying.

An experimental evaluation of two nonazeotropic refrigerant mixtures in a water-to-water breadboard heat pump

NASA Astrophysics Data System (ADS)

Kauffeld, Michael; Mulroy, William; McLinden, Mark; Didion, David

1990-02-01

As part of the Department of Energy/Oak Ridge National Laboratory Building Equipment Research program, the National Institute of Standards and Technology constructed an experimental, easily reconfigurable, water-to-water, breadboard heat pump apparatus in order to compare pure R22 to nonazeotropic refrigerant mixtures. Performance of the heat pump charged with a range of compositions of the binary mixtures R22/RI14 and R13/R12 were compared to R22. The advantage claimed for mixtures in this application is improved thermodynamic efficiency as a result of gliding refrigerant temperatures in the evaporator and condenser in low lift, high glide applications typical of air conditioning.

Application of Recycled Ceramic Aggregates for the Production of Mineral-Asphalt Mixtures.

PubMed

Andrzejuk, Wojciech; Barnat-Hunek, Danuta; Siddique, Rafat; Zegardło, Bartosz; Łagód, Grzegorz

2018-04-24

This paper describes a method of designing and producing innovative mineral⁻asphalt mixtures, which utilize waste aggregate from the recycling of sanitary ceramics. The work presents the basic properties of the ceramic material, the investigation concerning the microstructure of the aggregate obtained from the grinding of waste, and a comparison with the images obtained for the aggregates usually employed in mineral⁻asphalt mixtures. The mixtures were designed for the application in the wearing course. Four series of mixtures were prepared. In the first and second, the ceramic aggregate constituted a partial substitute for dolomite, whereas in the third, we substituted granodiorite, and the fourth series contained only dolomite. The mixtures were examined for the content of soluble binder, the bulk density of samples, the presence of voids, the space filled with binder, and the susceptibility to water and frost corrosion. The obtained results were compared with the standard requirements. The microstructure as well as the contact zone in the considered mineral⁻asphalt mixtures are presented based on research conducted by means of a scanning electron microscope (SEM).

Application of Recycled Ceramic Aggregates for the Production of Mineral-Asphalt Mixtures

PubMed Central

Andrzejuk, Wojciech; Barnat-Hunek, Danuta; Siddique, Rafat; Zegardło, Bartosz; Łagód, Grzegorz

2018-01-01

This paper describes a method of designing and producing innovative mineral–asphalt mixtures, which utilize waste aggregate from the recycling of sanitary ceramics. The work presents the basic properties of the ceramic material, the investigation concerning the microstructure of the aggregate obtained from the grinding of waste, and a comparison with the images obtained for the aggregates usually employed in mineral–asphalt mixtures. The mixtures were designed for the application in the wearing course. Four series of mixtures were prepared. In the first and second, the ceramic aggregate constituted a partial substitute for dolomite, whereas in the third, we substituted granodiorite, and the fourth series contained only dolomite. The mixtures were examined for the content of soluble binder, the bulk density of samples, the presence of voids, the space filled with binder, and the susceptibility to water and frost corrosion. The obtained results were compared with the standard requirements. The microstructure as well as the contact zone in the considered mineral–asphalt mixtures are presented based on research conducted by means of a scanning electron microscope (SEM). PMID:29695115

Estimation of value at risk and conditional value at risk using normal mixture distributions model

NASA Astrophysics Data System (ADS)

Kamaruzzaman, Zetty Ain; Isa, Zaidi

2013-04-01

Normal mixture distributions model has been successfully applied in financial time series analysis. In this paper, we estimate the return distribution, value at risk (VaR) and conditional value at risk (CVaR) for monthly and weekly rates of returns for FTSE Bursa Malaysia Kuala Lumpur Composite Index (FBMKLCI) from July 1990 until July 2010 using the two component univariate normal mixture distributions model. First, we present the application of normal mixture distributions model in empirical finance where we fit our real data. Second, we present the application of normal mixture distributions model in risk analysis where we apply the normal mixture distributions model to evaluate the value at risk (VaR) and conditional value at risk (CVaR) with model validation for both risk measures. The empirical results provide evidence that using the two components normal mixture distributions model can fit the data well and can perform better in estimating value at risk (VaR) and conditional value at risk (CVaR) where it can capture the stylized facts of non-normality and leptokurtosis in returns distribution.

Complex formation and vectorization of a phosphorothioate oligonucleotide with an amphipathic leucine- and lysine-rich peptide: study at molecular and cellular levels.

PubMed

Boukhalfa-Heniche, Fatima-Zohra; Hernández, Belén; Gaillard, Stéphane; Coïc, Yves-Marie; Huynh-Dinh, Tam; Lecouvey, Marc; Seksek, Olivier; Ghomi, Mahmoud

2004-04-15

Optical spectroscopic techniques such as CD, Raman scattering, and fluorescence imaging allowed us to analyze the complex formation and vectorization of a single-stranded 20-mer phosphorothioate oligodeoxynucleotide with a 15-mer amphipathic peptide at molecular and cellular levels. Different solvent mixtures (methanol and water) and molecular ratios of peptide/oligodeoxynucleotide complexes were tested in order to overcome the problems related to solubility. Optimal conditions for both spectroscopic and cellular experiments were obtained with the molecular ratio peptide/oligodeoxynucleotide equal to 21:4, corresponding to a 7:5 ratio for their respective +/- charge ratio. At the molecular level, CD and Raman spectra were consistent with a alpha-helix conformation of the peptide in water or in a methanol-water mixture. The presence of methanol increased considerably the solubility of the peptide without altering its alpha-helix conformation, as evidenced by CD and Raman spectroscopies. UV absorption melting profile of the oligodeoxynucleotide gave rise to a flat melting profile, corresponding to its random structure in solution. Raman spectra of oligodeoxynucleotide/peptide complexes could only be studied in methanol/water mixture solutions. Drastic changes observed in Raman spectra have undoubtedly shown: (a) the perturbation occurred in the peptide secondary structure, and (b) possible interaction between the lysine residues of the peptide and the oligodeoxynucleotide. At the cellular level, the complex was prepared in a mixture of 10% methanol and 90% cell medium. Cellular uptake in optimal conditions for the oligodeoxynucleotide delivery with low cytotoxicity was controlled by fluorescence imaging allowing to specifically locate the compacted oligonucleotide labeled with fluorescein at its 5'-terminus with the peptide into human glioma cells after 1 h of incubation at 37 degrees C. Copyright 2004 Wiley Periodicals, Inc.

Band-selective excited ultrahigh resolution PSYCHE-TOCSY: fast screening of organic molecules and complex mixtures.

PubMed

Kakita, Veera Mohana Rao; Vemulapalli, Sahithya Phani Babu; Bharatam, Jagadeesh

2016-04-01

Precise assignments of (1) H atomic sites and establishment of their through-bond COSY or TOCSY connectivity are crucial for molecular structural characterization by using (1) H NMR spectroscopy. However, this exercise is often hampered by signal overlap, primarily because of (1) H-(1) H scalar coupling multiplets, even at typical high magnetic fields. The recent developments in homodecoupling strategies for effectively suppressing the coupling multiplets into nice singlets (pure-shift), particularly, Morris's advanced broadband pure-shift yielded by chirp excitation (PSYCHE) decoupling and ultrahigh resolution PSYCHE-TOCSY schemes, have shown new possibilities for unambiguous structural elucidation of complex organic molecules. The superior broadband PSYCHE-TOCSY exhibits enhanced performance over the earlier TOCSY methods, which however warrants prolonged experimental times due to the requirement of large number of dwell increments along the indirect dimension. Herein, we present fast and band-selective analog of the broadband PSYCHE-TOCSY, which is useful for analyzing complex organic molecules that exhibit characteristic yet crowded spectral regions. The simple pulse scheme relies on band-selective excitation (BSE) followed by PSYCHE homodecoupling in the indirect dimension. The BSE-PSYCHE-TOCSY has been exemplified for Estradiol and a complex carbohydrate mixture comprised of six constituents of closely comparable molecular weights. The experimental times are greatly reduced viz., ~20 fold for Estradiol and ~10 fold for carbohydrate mixture, with respect to the broadband PSYCHE-TOCSY. Furthermore, unlike the earlier homonuclear band-selective decoupling, the BSE-PSYCHE-decoupling provides fully decoupled pure-shift spectra for all the individual chemical sites within the excited band. The BSE-PSYCHE-TOCSY is expected to have significant potential for quick screening of complex organic molecules and mixtures at ultrahigh resolution. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Quantitative structure - mesothelioma potency model optimization for complex mixtures of elongated particles in rat pleura: A retrospective study

EPA Science Inventory

Cancer potencies of mineral and synthetic elongated particle (EP) mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. A unique and compreh...

METHODOLOGICAL ISSUES IN HUMAN EXPOSURE STUDIES OF LOW LEVEL SOLVENT MIXTURES

EPA Science Inventory

The design of appropriate studies to assess the sensory irritant and neurobehavioral-effects of exposure to complex VOC mixtures poses a variety of methodological challenges, particularly at the low levels found in new buildings. or instance, Otto et al (1989) exposed subjects to...

CONCENTRATION AND TREATMENT OF DRINKING WATERS IN THE FOUR LAB STUDY

EPA Science Inventory

The purpose of the four lab study was to address concerns related to potential health effects from exposure to complex mixtures of DBPs that cannot be addressed directly from toxicological studies of individual disinfection by-products (DBPs) or simple DBP mixtures. In order to ...

INTEGRATED DISINFECTION BYPRODUCTS MIXTURES RESEARCH: COMPREHENSIVE CHARACTERIZATION OF WATER CONCENTRATES PREPARED FROM CHLORINATED AND OZONATED/POSTCHLORINATED DRINKING WATER

EPA Science Inventory

This article describes the disinfection byproduct (DBP) characterization portion of a series of experiments designed for comprehensive chemical and toxicological evaluation of two drinking water concentrates containing highly complex mixtures of DBP. This project, called the Four...

Assessment of wastewater treatment plant effluent on fish reproduction utilizing the adverse outcome pathway conceptual framework

EPA Science Inventory

Wastewater treatment plant (WWTP) effluents are a known contributor of chemical mixture inputs into the environment. Whole effluent testing guidelines were developed to screen these complex mixtures for acute toxicity. However, efficient and cost-effective approaches for screenin...

Surface complexation modeling of Cu(II) adsorption on mixtures of hydrous ferric oxide and kaolinite

PubMed Central

Lund, Tracy J; Koretsky, Carla M; Landry, Christopher J; Schaller, Melinda S; Das, Soumya

2008-01-01

Background The application of surface complexation models (SCMs) to natural sediments and soils is hindered by a lack of consistent models and data for large suites of metals and minerals of interest. Furthermore, the surface complexation approach has mostly been developed and tested for single solid systems. Few studies have extended the SCM approach to systems containing multiple solids. Results Cu adsorption was measured on pure hydrous ferric oxide (HFO), pure kaolinite (from two sources) and in systems containing mixtures of HFO and kaolinite over a wide range of pH, ionic strength, sorbate/sorbent ratios and, for the mixed solid systems, using a range of kaolinite/HFO ratios. Cu adsorption data measured for the HFO and kaolinite systems was used to derive diffuse layer surface complexation models (DLMs) describing Cu adsorption. Cu adsorption on HFO is reasonably well described using a 1-site or 2-site DLM. Adsorption of Cu on kaolinite could be described using a simple 1-site DLM with formation of a monodentate Cu complex on a variable charge surface site. However, for consistency with models derived for weaker sorbing cations, a 2-site DLM with a variable charge and a permanent charge site was also developed. Conclusion Component additivity predictions of speciation in mixed mineral systems based on DLM parameters derived for the pure mineral systems were in good agreement with measured data. Discrepancies between the model predictions and measured data were similar to those observed for the calibrated pure mineral systems. The results suggest that quantifying specific interactions between HFO and kaolinite in speciation models may not be necessary. However, before the component additivity approach can be applied to natural sediments and soils, the effects of aging must be further studied and methods must be developed to estimate reactive surface areas of solid constituents in natural samples. PMID:18783619

Liquid-liquid phase separation in atmospheric aerosol particles: dependence on organic functionalities and mixture complexity

NASA Astrophysics Data System (ADS)

Song, M.; Marcolli, C.; Krieger, U. K.; Zuend, A.; Peter, T.

2012-04-01

In the troposphere, aerosol particles undergo phase transitions such as deliquescence and efflorescence during humidity cycles (Marcolli and Krieger, 2006). In addition, interactions between organic and inorganic compounds lead to liquid-liquid phase separation (LLPS) (Ciobanu et al., 2009). Recent studies on a limited number of model systems have shown that oxygen-to-carbon ratios (O:C) of the organic aerosol fraction might be a good predictor for LLPS in mixed organic/ammonium sulfate (AS) particles (Bertram et al., 2011; Song et al., 2011). However, in order to corroborate this hypothesis experiments with an organic fraction that consists of a higher number of components with different O:C ratios and functional groups are needed. In order to determine the influence of O:C ratio, the specific organic functionalities and the mixture complexity on LLPS, we subjected organic/AS particles deposited on a hydrophobically coated substrate to relative humidity (RH) cycles and observed phase changes using optical microscopy and micro-Raman spectroscopy. To determine the influence of mixture complexity, we mixed together up to 10 organic compounds. We also prepared mixtures that were rich in different types of functional groups like polyols, aromatics and dicarboxylic acids which were identified from field measurements. We screened for a miscibility gap by varying the organic-to-inorganic ratio from 2:1 to 1:6. AS in the investigated single particles effloresced at 27 - 50 %RH and deliquesced at 72 - 79 %RH during humidity cycles. The occurrence of LLPS is determined to a high degree by the O:C of the organics: there was no LLPS for mixtures with O:C > 0.8 and there was always LLPS for mixtures with O:C < 0.57. In the range in between, we observed a dependence on the specific functional groups: a high share of aromatic functionalities shifts the range of O:C for which LLPS occurs to lower values. A correlation was also found for the onset RH of LLPS as a function of O:C. We did not find any dependence of LLPS on the complexity of the mixture. Overall, the RH range of coexistence of two liquid phases depends in first place on the O:C ratio of the particles and in second place also on the specific organic functionalities.

Binding of the respiratory chain inhibitor ametoctradin to the mitochondrial bc1 complex.

PubMed

Fehr, Marcus; Wolf, Antje; Stammler, Gerd

2016-03-01

Ametoctradin is an agricultural fungicide that inhibits the mitochondrial bc1 complex of oomycetes. The bc1 complex has two quinone binding sites that can be addressed by inhibitors. Depending on their binding sites and binding modes, the inhibitors show different degrees of cross-resistance that need to be considered when designing spray programmes for agricultural fungicides. The binding site of ametoctradin was unknown. Cross-resistance analyses, the reduction of isolated Pythium sp. bc1 complex in the presence of different inhibitors and molecular modelling studies were used to analyse the binding site and binding mode of ametoctradin. All three approaches provide data supporting the argument that ametoctradin binds to the Pythium bc1 complex similarly to stigmatellin. The binding mode of ametoctradin differs from other agricultural fungicides such as cyazofamid and the strobilurins. This explains the lack of cross-resistance with strobilurins and related inhibitors, where resistance is mainly caused by G143A amino acid exchange. Accordingly, mixtures or alternating applications of these fungicides and ametoctradin can help to minimise the risk of the emergence of new resistant isolates. © 2015 Society of Chemical Industry.

Chemical Mixtures Health Risk Assessment of Environmental Contaminants: Concepts, Methods, Applications

EPA Science Inventory

This problems-based, introductory workshop focuses on methods to assess health risks posed by exposures to chemical mixtures in the environment. Chemical mixtures health risk assessment methods continue to be developed and evolve to address concerns over health risks from multic...

Chemical Mixtures Health Risk Assessment of Environmental Contaminants: Concepts, Methods, And Applications

EPA Science Inventory

This problems-based, introductory workshop focuses on methods to assess health risks posed by exposures to chemical mixtures in the environment. Chemical mixtures health risk assessment methods continue to be developed and evolve to address concerns over health risks from multic...

Fast and Scalable Gaussian Process Modeling with Applications to Astronomical Time Series

NASA Astrophysics Data System (ADS)

Foreman-Mackey, Daniel; Agol, Eric; Ambikasaran, Sivaram; Angus, Ruth

2017-12-01

The growing field of large-scale time domain astronomy requires methods for probabilistic data analysis that are computationally tractable, even with large data sets. Gaussian processes (GPs) are a popular class of models used for this purpose, but since the computational cost scales, in general, as the cube of the number of data points, their application has been limited to small data sets. In this paper, we present a novel method for GPs modeling in one dimension where the computational requirements scale linearly with the size of the data set. We demonstrate the method by applying it to simulated and real astronomical time series data sets. These demonstrations are examples of probabilistic inference of stellar rotation periods, asteroseismic oscillation spectra, and transiting planet parameters. The method exploits structure in the problem when the covariance function is expressed as a mixture of complex exponentials, without requiring evenly spaced observations or uniform noise. This form of covariance arises naturally when the process is a mixture of stochastically driven damped harmonic oscillators—providing a physical motivation for and interpretation of this choice—but we also demonstrate that it can be a useful effective model in some other cases. We present a mathematical description of the method and compare it to existing scalable GP methods. The method is fast and interpretable, with a range of potential applications within astronomical data analysis and beyond. We provide well-tested and documented open-source implementations of this method in C++, Python, and Julia.

The Urtica dioica Agglutinin Is a Complex Mixture of Isolectins 1

PubMed Central

Van Damme, Els J. M.; Broekaert, Willem F.; Peumans, Willy J.

1988-01-01

Rhizomes of stinging nettle (Urtica dioica) contain a complex mixture of isolectins. Ion exchange chromatography with a high resolution fast protein liquid chromatography system revealed six isoforms which exhibit identical agglutination properties and carbohydrate-binding specificity and in addition have the same molecular structure and virtually identical biochemical properties. However, since the U. dioica agglutinin isolectins differ definitely with respect to their amino acid composition, it is likely that at least some of them are different polypeptides coded for by different genes. Images Fig. 3 PMID:16665952

Systematic developmental neurotoxicity assessment of a representative PAH Superfund mixture using zebrafish

DOE PAGES

Geier, Mitra C.; James Minick, D.; Truong, Lisa; ...

2018-04-01

Superfund sites often consist of complex mixtures of polycyclic aromatic hydrocarbons (PAHs). It is widely recognized that PAHs pose risks to human and environmental health, but the risks posed by exposure to PAH mixtures are unclear. Here, we constructed an environmentally relevant PAH mixture with the top 10 most prevalent PAHs (SM10) from a Superfund site derived from environmental passive sampling data. Using the zebrafish model, we measured body burden at 48 hours post fertilization (hpf) and evaluated the developmental and neurotoxicity of SM10 and the 10 individual constituents at 24 hours post fertilization (hpf) and 5 days post fertilizationmore » (dpf). Zebrafish embryos were exposed from 6 to 120 hpf to (1) the SM10 mixture, (2) a variety of individual PAHs: pyrene, fluoranthene, retene, benzo[a]anthracene, chrysene, naphthalene, acenaphthene, phenanthrene, fluorene, and 2-methylnaphthalene. We demonstrated that SM10 and only 3 of the individual PAHs were developmentally toxic. Subsequently, we constructed and exposed developing zebrafish to two sub-mixtures: SM3 (comprised of 3 of the developmentally toxicity PAHs) and SM7 (7 non-developmentally toxic PAHs). We found that the SM3 toxicity profile was similar to SM10, and SM7 unexpectedly elicited developmental toxicity unlike that seen with its individual components. The results demonstrated that the overall developmental toxicity in the mixtures could be explained using the general concentration addition model. To determine if exposures activated the AHR pathway, spatial expression of CYP1A was evaluated in the 10 individual PAHs and the 3 mixtures at 5 dpf. Results showed activation of AHR in the liver and vasculature for the mixtures and some individual PAHs. Embryos exposed to SM10 during development and raised in chemical-free water into adulthood exhibited decreased learning and responses to startle stimulus indicating that developmental SM10 exposures affect neurobehavior. Collectively, these results exemplify the utility of zebrafish to investigate the developmental and neurotoxicity of complex mixtures.« less

Systematic developmental neurotoxicity assessment of a representative PAH Superfund mixture using zebrafish

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

Geier, Mitra C.; James Minick, D.; Truong, Lisa

Superfund sites often consist of complex mixtures of polycyclic aromatic hydrocarbons (PAHs). It is widely recognized that PAHs pose risks to human and environmental health, but the risks posed by exposure to PAH mixtures are unclear. Here, we constructed an environmentally relevant PAH mixture with the top 10 most prevalent PAHs (SM10) from a Superfund site derived from environmental passive sampling data. Using the zebrafish model, we measured body burden at 48 hours post fertilization (hpf) and evaluated the developmental and neurotoxicity of SM10 and the 10 individual constituents at 24 hours post fertilization (hpf) and 5 days post fertilizationmore » (dpf). Zebrafish embryos were exposed from 6 to 120 hpf to (1) the SM10 mixture, (2) a variety of individual PAHs: pyrene, fluoranthene, retene, benzo[a]anthracene, chrysene, naphthalene, acenaphthene, phenanthrene, fluorene, and 2-methylnaphthalene. We demonstrated that SM10 and only 3 of the individual PAHs were developmentally toxic. Subsequently, we constructed and exposed developing zebrafish to two sub-mixtures: SM3 (comprised of 3 of the developmentally toxicity PAHs) and SM7 (7 non-developmentally toxic PAHs). We found that the SM3 toxicity profile was similar to SM10, and SM7 unexpectedly elicited developmental toxicity unlike that seen with its individual components. The results demonstrated that the overall developmental toxicity in the mixtures could be explained using the general concentration addition model. To determine if exposures activated the AHR pathway, spatial expression of CYP1A was evaluated in the 10 individual PAHs and the 3 mixtures at 5 dpf. Results showed activation of AHR in the liver and vasculature for the mixtures and some individual PAHs. Embryos exposed to SM10 during development and raised in chemical-free water into adulthood exhibited decreased learning and responses to startle stimulus indicating that developmental SM10 exposures affect neurobehavior. Collectively, these results exemplify the utility of zebrafish to investigate the developmental and neurotoxicity of complex mixtures.« less

Utility of controlled human exposure studies for assessing the health effects of complex mixtures and indoor air pollutants.

PubMed Central

McDonnell, W F

1993-01-01

The study of health effects induced by exposure to mixtures of pollutants is a complex task. The purpose of this paper is to identify areas of research in which the conduct of human controlled exposure (clinical) studies may contribute to better understanding health effects of exposure to indoor air and other mixtures. The strengths and weaknesses of clinical studies in general are reviewed, as well as examples from the literature of approaches that have been used. Human chamber studies play an important role alongside epidemiologic and animal toxicologic studies in such research. Human chamber studies are limited with regard to assessing chronic effects, rare effects, or effects from long-duration exposures but are powerful in assessing acute, reversible effects from short-duration exposures in humans. The areas in which human chamber studies are most likely to contribute include identification of effects or markers of effects for exposure to a given pollutant or mix of pollutants; direct dose-response assessment of effects for individual compounds and mixtures of set composition; identification of individual compounds responsible for the effects of a mixture; study of the joint effects of a binary mixture; development of markers of acute exposure for particular compounds; development of outcome measurements to be used in the field; and identification, characterization, and testing of sensitive subpopulations. PMID:8206031

Characterization of a nose-only inhalation exposure system for hydrocarbon mixtures and jet fuels.

PubMed

Martin, Sheppard A; Tremblay, Raphael T; Brunson, Kristyn F; Kendrick, Christine; Fisher, Jeffrey W

2010-04-01

A directed-flow nose-only inhalation exposure system was constructed to support development of physiologically based pharmacokinetic (PBPK) models for complex hydrocarbon mixtures, such as jet fuels. Due to the complex nature of the aerosol and vapor-phase hydrocarbon exposures, care was taken to investigate the chamber hydrocarbon stability, vapor and aerosol droplet compositions, and droplet size distribution. Two-generation systems for aerosolizing fuel and hydrocarbons were compared and characterized for use with either jet fuels or a simple mixture of eight hydrocarbons. Total hydrocarbon concentration was monitored via online gas chromatography (GC). Aerosol/vapor (A/V) ratios, and total and individual hydrocarbon concentrations, were determined using adsorbent tubes analyzed by thermal desorption-gas chromatography-mass spectrometry (TDS-GC-MS). Droplet size distribution was assessed via seven-stage cascade impactor. Droplet mass median aerodynamic diameter (MMAD) was between 1 and 3 mum, depending on the generator and mixture utilized. A/V hydrocarbon concentrations ranged from approximately 200 to 1300 mg/m(3), with between 20% and 80% aerosol content, depending on the mixture. The aerosolized hydrocarbon mixtures remained stable during the 4-h exposure periods, with coefficients of variation (CV) of less than 10% for the total hydrocarbon concentrations. There was greater variability in the measurement of individual hydrocarbons in the A-V phase. In conclusion, modern analytical chemistry instruments allow for improved descriptions of inhalation exposures of rodents to aerosolized fuel.

Study of decolorisation of binary dye mixture by response surface methodology.

PubMed

Khamparia, Shraddha; Jaspal, Dipika

2017-10-01

Decolorisation of a complex mixture of two different classes of textile dyes Direct Red 81 (DR81) and Rhodamine B (RHB), simulating one of the most important condition in real textile effluent was investigated onto deoiled Argemone Mexicana seeds (A. Mexicana). The adsorption behaviour of DR81 and RHB dyes was simultaneously analyzed in the mixture using derivative spectrophotometric method. Central composite design (CCD) was employed for designing the experiments for this complex binary mixture where significance of important parameters and possible interactions were analyzed by response surface methodology (RSM). Maximum adsorption of DR81 and RHB by A. Mexicana was obtained at 53 °C after 63.33 min with 0.1 g of adsorbent and 8 × 10 -6  M DR81, 12 × 10 -6  M RHB with composite desirability of 0.99. The predicted values for percentage removal of dyes from the mixture were in good agreement with the experimental values with R 2 > 96% for both the dyes. CCD superimposed RSM confirmed that presence of different dyes in a solution created a competition for the adsorbent sites and hence interaction of dyes was one of the most important factor to be studied to simulate the real effluent. The adsorbent showed remarkable adsorption capacities for both the dyes in the mixture. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simultaneous resonant enhanced multiphoton ionization and electron avalanche ionization in gas mixtures

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

Shneider, Mikhail N.; Zhang Zhili; Miles, Richard B.

2008-07-15

Resonant enhanced multiphoton ionization (REMPI) and electron avalanche ionization (EAI) are measured simultaneously in Ar:Xe mixtures at different partial pressures of mixture components. A simple theory for combined REMPI+EAI in gas mixture is developed. It is shown that the REMPI electrons seed the avalanche process, and thus the avalanche process amplifies the REMPI signal. Possible applications are discussed.

Computational estimation of errors generated by lumping of physiologically-based pharmacokinetic (PBPK) interaction models of inhaled complex chemical mixtures

EPA Science Inventory

Many cases of environmental contamination result in concurrent or sequential exposure to more than one chemical. However, limitations of available resources make it unlikely that experimental toxicology will provide health risk information about all the possible mixtures to which...

ELECTROSTATIC PRECIPITATION AN AN ALTERNATIVE METHOD FOR /IN VITRO/ EXPOSURES TO MIXTURES OF GASES AND PARTICLES

EPA Science Inventory

There is an increasing interest in examining complex urban air pollution mixtures that include both particulate and gaseous components. Conventional methodologies are unable to expose lung cells in vitro simultaneously to both particulate and gaseous pollutants that are being for...

Conceptual Model for Assessing Criteria Air Pollutants in a Multipollutant Context: A Modified Adverse Outcome Pathway Approach

EPA Science Inventory

Background: Air pollution consists of a complex mixture of particulate and gaseous components. Individual criteria and other hazardous air pollutants have been linked to adverse respiratory and cardiovascular health outcomes. However, assessing risk of air pollutant mixtures is d...

From the lab bench: Mixtures of grasses and legumes; a good or bad thing?

USDA-ARS?s Scientific Manuscript database

A column was written to discuss the advantages of complex mixtures of grasses and legumes. Historically, Kentucky pastures have been primarily composed of toxic endophyte-infected tall fescue, but Kentucky bluegrass and other grasses are presently encroaching tall fescue pastures. These other gras...

Gene Expression Responses in Male Fathead Minnows Exposed to Binary Mixtures of an Estrogen and Antiestrogen

EPA Science Inventory

Aquatic organisms are continuously exposed to complex mixtures of chemicals, many of which can interfere with their endocrine system, resulting in impaired reproduction, development or survival, among others. In order to analyze the effects and mechanisms of action of estrogen...

Chloraminated Concentrated Drinking Water for Disinfection Byproduct Mixtures Research: Evaluating Free Chlorine Contact Times

EPA Science Inventory

Complex mixtures of disinfection by-products (DBPs) are formed when the disinfectant oxidizes constituents (e.g., natural organic matter (NOM) and organic pollutants) present in the source water. Since 1974, over 600 DBPs have been identified in drinking water, yet a large portio...

Mixture Modeling: Applications in Educational Psychology

ERIC Educational Resources Information Center

Harring, Jeffrey R.; Hodis, Flaviu A.

2016-01-01

Model-based clustering methods, commonly referred to as finite mixture modeling, have been applied to a wide variety of cross-sectional and longitudinal data to account for heterogeneity in population characteristics. In this article, we elucidate 2 such approaches: growth mixture modeling and latent profile analysis. Both techniques are…

Chemical Mixtures Health Risk Assessment of Environmental Contaminants: Concepts, Methods, Applications: Handbook

EPA Science Inventory

This problems-based, half-day, introductory workshop focuses on methods to assess health risks posed by exposures to chemical mixtures in the environment. Chemical mixtures health risk assessment methods continue to be developed and evolve to address concerns over health risks f...

NEUROTOXICOLOGICAL AND STATISTICAL ANALYSES OF A MIXTURE OF FIVE ORGANOPHOSPHORUS PESTICIDES USING A RAY DESIGN.

EPA Science Inventory

Pesticide application patterns generally result in exposure to mixtures instead of single chemicals. Of particular importance in the estimation of pesticide mixture risks is the detection and characterization of their interactions. This research tested for interaction(s) in a mix...

Determining the Partial Pressure of Volatile Components via Substrate-Integrated Hollow Waveguide Infrared Spectroscopy with Integrated Microfluidics.

PubMed

Kokoric, Vjekoslav; Theisen, Johannes; Wilk, Andreas; Penisson, Christophe; Bernard, Gabriel; Mizaikoff, Boris; Gabriel, Jean-Christophe P

2018-04-03

A microfluidic system combined with substrate-integrated hollow waveguide (iHWG) vapor phase infrared spectroscopy has been developed for evaluating the chemical activity of volatile compounds dissolved in complex fluids. Chemical activity is an important yet rarely exploited parameter in process analysis and control. Access to chemical activity parameters enables systematic studies on phase diagrams of complex fluids, the detection of aggregation processes, etc. The instrumental approach developed herein uniquely enables controlled evaporation/permeation from a sample solution into a hollow waveguide structure and the analysis of the partial pressures of volatile constituents. For the example of a binary system, it was shown that the chemical activity may be deduced from partial pressure measurements at thermodynamic equilibrium conditions. The combined microfluidic-iHWG midinfrared sensor system (μFLUID-IR) allows the realization of such studies in the absence of any perturbations provoked by sampling operations, which is unavoidable using state-of-the-art analytical techniques such as headspace gas chromatography. For demonstration purposes, a water/ethanol mixture was investigated, and the derived data was cross-validated with established literature values at different mixture ratios. Next to perturbation-free measurements, a response time of the sensor <150 s ( t 90 ) at a recovery time <300 s ( t recovery ) has been achieved, which substantiates the utility of μFLUID-IR for future process analysis-and-control applications.

Computational Evaluation of Mg–Salen Compounds as Subsurface Fluid Tracers: Molecular Dynamics Simulations in Toluene–Water Mixtures and Clay Mineral Nanopores

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

Greathouse, Jeffery A.; Boyle, Timothy J.; Kemp, Richard A.

Molecular tracers that can be selectively placed underground and uniquely identified at the surface using simple on-site spectroscopic methods would significantly enhance subsurface fluid monitoring capabilities. To ensure their widespread utility, the solubility of these tracers must be easily tuned to oil- or water-wet conditions as well as reducing or eliminating their propensity to adsorb onto subsurface rock and/or mineral phases. In this work, molecular dynamics simulations were used to investigate the relative solubilities and mineral surface adsorption properties of three candidate tracer compounds comprising Mg–salen derivatives of varying degrees of hydrophilic character. Simulations in water–toluene liquid mixtures indicate thatmore » the partitioning of each Mg–salen compound relative to the interface is strongly influenced by the degree of hydrophobicity of the compound. Simulations of these complexes in fluid-filled mineral nanopores containing neutral (kaolinite) and negatively charged (montmorillonite) mineral surfaces reveal that adsorption tendencies depend upon a variety of parameters, including tracer chemical properties, mineral surface type, and solvent type (water or toluene). Simulation snapshots and averaged density profiles reveal insight into the solvation and adsorption mechanisms that control the partitioning of these complexes in mixed liquid phases and nanopore environments. As a result, this work demonstrates the utility of molecular simulation in the design and screening of molecular tracers for use in subsurface applications.« less

Computational Evaluation of Mg–Salen Compounds as Subsurface Fluid Tracers: Molecular Dynamics Simulations in Toluene–Water Mixtures and Clay Mineral Nanopores

DOE PAGES

Greathouse, Jeffery A.; Boyle, Timothy J.; Kemp, Richard A.

2018-04-11

Molecular tracers that can be selectively placed underground and uniquely identified at the surface using simple on-site spectroscopic methods would significantly enhance subsurface fluid monitoring capabilities. To ensure their widespread utility, the solubility of these tracers must be easily tuned to oil- or water-wet conditions as well as reducing or eliminating their propensity to adsorb onto subsurface rock and/or mineral phases. In this work, molecular dynamics simulations were used to investigate the relative solubilities and mineral surface adsorption properties of three candidate tracer compounds comprising Mg–salen derivatives of varying degrees of hydrophilic character. Simulations in water–toluene liquid mixtures indicate thatmore » the partitioning of each Mg–salen compound relative to the interface is strongly influenced by the degree of hydrophobicity of the compound. Simulations of these complexes in fluid-filled mineral nanopores containing neutral (kaolinite) and negatively charged (montmorillonite) mineral surfaces reveal that adsorption tendencies depend upon a variety of parameters, including tracer chemical properties, mineral surface type, and solvent type (water or toluene). Simulation snapshots and averaged density profiles reveal insight into the solvation and adsorption mechanisms that control the partitioning of these complexes in mixed liquid phases and nanopore environments. As a result, this work demonstrates the utility of molecular simulation in the design and screening of molecular tracers for use in subsurface applications.« less

Selective chromogenic and fluorogenic peptide substrates for the assay of cysteine peptidases in complex mixtures.

PubMed

Semashko, Tatiana A; Vorotnikova, Elena A; Sharikova, Valeriya F; Vinokurov, Konstantin S; Smirnova, Yulia A; Dunaevsky, Yakov E; Belozersky, Mikhail A; Oppert, Brenda; Elpidina, Elena N; Filippova, Irina Y

2014-03-15

This study describes the design, synthesis, and use of selective peptide substrates for cysteine peptidases of the C1 papain family, important in many biological processes. The structure of the newly synthesized substrates is Glp-Xaa-Ala-Y (where Glp=pyroglutamyl; Xaa=Phe or Val; and Y=pNA [p-nitroanilide], AMC [4-amino-7-methylcoumaride], or AFC [4-amino-7-trifluoromethyl-coumaride]). Substrates were synthesized enzymatically to guarantee selectivity of the reaction and optical purity of the target compounds, simplifying the scheme of synthesis and isolation of products. The hydrolysis of the synthesized substrates was evaluated by C1 cysteine peptidases from different organisms and with different functions, including plant enzymes papain, bromelain, ficin, and mammalian lysosomal cathepsins B and L. The new substrates were selective for C1 cysteine peptidases and were not hydrolyzed by serine, aspartic, or metallo peptidases. We demonstrated an application of the selectivity of the synthesized substrates during the chromatographic separation of a multicomponent set of digestive peptidases from a beetle, Tenebrio molitor. Used in combination with the cysteine peptidase inhibitor E-64, these substrates were able to differentiate cysteine peptidases from peptidases of other classes in midgut extracts from T. molitor larvae and larvae of the genus Tribolium; thus, they are useful in the analysis of complex mixtures containing peptidases from different classes. Published by Elsevier Inc.

INVESTIGATION AND OPTIMIZATION OF TITRIMETRIC AND SPECTROPHOTOMETRIC METHODS FOR THE ASSAY OF FLUNARIZINE DIHYDROCHLORIDE USING IN SITU BROMINE.

PubMed

Prashanth, Kudige Nagaraj; Swamy, Nagaraju; Basavaiah, Kanakapura

2016-01-01

Three indirect methods for the assay of flunarizine dihydrochloride (FNH) in bulk drug and commercial formulation based on titrimetric and spectrophotometric techniques using bromate-bromide mixture are described. In titrimetry, a measured excess of bromate-bromide mixture is added to an acidified solution of FNH and the unreacted bromine is determined iodometrically (method A). Spectrophotometry involves the addition of a known excess of bromate-bromide mixture to FNH in acid medium followed by estimation of unreacted bromine by its reaction with excess iodide and the liberated iodine (I₃⁻) is either measured at 370 nm (method B) or liberated iodine reacted with starch followed by the measurement of the blue colored starch-iodide complex at 575 run (method C). Titrimetric method is applicable over the range 4.5-30.0 mg FNH (method A), and the reaction stoichiometry is found to be 1:2 (FNH:KBrO₃). The spectrophotometric methods are applicable over the concentration ranges 0.8-16.0 µg/mL and 0.4-8.0 µg/mL FNH for method B and method C, respectively. The molar absorptivities are calculated to be 2.83 x 10⁴ and 4.96 x 10⁴ L mol⁻¹cm⁻¹ for method B and method C, respectively, and the corresponding Sandell sensitivity values are 0.0168 and 0.0096 µg cm⁻². The proposed methods have been applied successfully for the determination of FNH in pure form and in its dosage form and the results were compared with those of a literature method by applying the Student's t-test and F-test.

Applicability of Separation Potentials to Determining the Parameters of Cascade Efficiency in Enrichment of Ternary Mixtures

NASA Astrophysics Data System (ADS)

Palkin, V. A.; Igoshin, I. S.

2017-01-01

The separation potentials suggested by various researchers for separating multicomponent isotopic mixtures are considered. An estimation of their applicability to determining the parameters of the efficiency of enrichment of a ternary mixture in a cascade with an optimum scheme of connection of stages made up of elements with three takeoffs is carried out. The separation potential most precisely characterizing the separative power and other efficiency parameters of stages and cascade schemes has been selected based on the results of the estimation made.

Densities of some molten fluoride salt mixtures suitable for heat storage in space power applications

NASA Technical Reports Server (NTRS)

Misra, Ajay K.

1988-01-01

Liquid densities were determined for a number of fluoride salt mixtures suitable for heat storage in space power applications, using a procedure that consisted of measuring the loss of weight of an inert bob in the melt. The density apparatus was calibrated with pure LiF and NaF at different temperatures. Density data for safe binary and ternary fluoride salt eutectics and congruently melting intermediate compounds are presented. In addition, a comparison was made between the volumetric heat storage capacity of different salt mixtures.

Mixture Distribution Latent State-Trait Analysis: Basic Ideas and Applications

ERIC Educational Resources Information Center

Courvoisier, Delphine S.; Eid, Michael; Nussbeck, Fridtjof W.

2007-01-01

Extensions of latent state-trait models for continuous observed variables to mixture latent state-trait models with and without covariates of change are presented that can separate individuals differing in their occasion-specific variability. An empirical application to the repeated measurement of mood states (N = 501) revealed that a model with 2…

Method of separating short half-life radionuclides from a mixture of radionuclides

DOEpatents

Bray, Lane A.; Ryan, Jack L.

1999-01-01

The present invention is a method of removing an impurity of plutonium, lead or a combination thereof from a mixture of radionuclides that contains the impurity and at least one parent radionuclide. The method has the steps of (a) insuring that the mixture is a hydrochloric acid mixture; (b) oxidizing the acidic mixture and specifically oxidizing the impurity to its highest oxidation state; and (c) passing the oxidized mixture through a chloride form anion exchange column whereupon the oxidized impurity absorbs to the chloride form anion exchange column and the 22.sup.9 Th or 2.sup.27 Ac "cow" radionuclide passes through the chloride form anion exchange column. The plutonium is removed for the purpose of obtaining other alpha emitting radionuclides in a highly purified form suitable for medical therapy. In addition to plutonium; lead, iron, cobalt, copper, uranium, and other metallic cations that form chloride anionic complexes that may be present in the mixture; are removed from the mixture on the chloride form anion exchange column.

Method of separating short half-life radionuclides from a mixture of radionuclides

DOEpatents

Bray, L.A.; Ryan, J.L.

1999-03-23

The present invention is a method of removing an impurity of plutonium, lead or a combination thereof from a mixture of radionuclides that contains the impurity and at least one parent radionuclide. The method has the steps of (a) insuring that the mixture is a hydrochloric acid mixture; (b) oxidizing the acidic mixture and specifically oxidizing the impurity to its highest oxidation state; and (c) passing the oxidized mixture through a chloride form anion exchange column whereupon the oxidized impurity absorbs to the chloride form anion exchange column and the {sup 229}Th or {sup 227}Ac ``cow`` radionuclide passes through the chloride form anion exchange column. The plutonium is removed for the purpose of obtaining other alpha emitting radionuclides in a highly purified form suitable for medical therapy. In addition to plutonium, lead, iron, cobalt, copper, uranium, and other metallic cations that form chloride anionic complexes that may be present in the mixture are removed from the mixture on the chloride form anion exchange column. 8 figs.

A mixture gatekeeping procedure based on the Hommel test for clinical trial applications.

PubMed

Brechenmacher, Thomas; Xu, Jane; Dmitrienko, Alex; Tamhane, Ajit C

2011-07-01

When conducting clinical trials with hierarchically ordered objectives, it is essential to use multiplicity adjustment methods that control the familywise error rate in the strong sense while taking into account the logical relations among the null hypotheses. This paper proposes a gatekeeping procedure based on the Hommel (1988) test, which offers power advantages compared to other p value-based tests proposed in the literature. A general description of the procedure is given and details are presented on how it can be applied to complex clinical trial designs. Two clinical trial examples are given to illustrate the methodology developed in the paper.

Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation

PubMed Central

McKay, Craig S.; Finn, M.G.

2014-01-01

The selective chemical modification of biological molecules drives a good portion of modern drug development and fundamental biological research. While a few early examples of reactions that engage amine and thiol groups on proteins helped establish the value of such processes, the development of reactions that avoid most biological molecules so as to achieve selectivity in desired bond-forming events has revolutionized the field. We provide an update on recent developments in bioorthogonal chemistry that highlights key advances in reaction rates, biocompatibility, and applications. While not exhaustive, we hope this summary allows the reader to appreciate the rich continuing development of good chemistry that operates in the biological setting. PMID:25237856

Method for oxygen reduction in a uranium-recovery process. [US DOE patent application

DOEpatents

Hurst, F.J.; Brown, G.M.; Posey, F.A.

1981-11-04

An improvement in effecting uranium recovery from phosphoric acid solutions is provided by sparging dissolved oxygen contained in solutions and solvents used in a reductive stripping stage with an effective volume of a nonoxidizing gas before the introduction of the solutions and solvents into the stage. Effective volumes of nonoxidizing gases, selected from the group consisting of argon, carbon dioxide, carbon monoxide, helium, hydrogen, nitrogen, sulfur dioxide, and mixtures thereof, displace oxygen from the solutions and solvents thereby reduce deleterious effects of oxygen such as excessive consumption of elemental or ferrous iron and accumulation of complex iron phosphates or cruds.

Two-step ion-exchange chromatographic purification combined with reversed-phase chromatography to isolate C-peptide for mass spectrometric analysis.

PubMed

Kabytaev, Kuanysh; Durairaj, Anita; Shin, Dmitriy; Rohlfing, Curt L; Connolly, Shawn; Little, Randie R; Stoyanov, Alexander V

2016-02-01

A liquid chromatography with mass spectrometry on-line platform that includes the orthogonal techniques of ion exchange and reversed phase chromatography is applied for C-peptide analysis. Additional improvement is achieved by the subsequent application of cation- and anion-exchange purification steps that allow for isolating components that have their isoelectric points in a narrow pH range before final reversed-phase mass spectrometry analysis. The utility of this approach for isolating fractions in the desired "pI window" for profiling complex mixtures is discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Health Impacts of Estrogens in the Environment, Considering Complex Mixture Effects

PubMed Central

Filby, Amy L.; Neuparth, Teresa; Thorpe, Karen L.; Owen, Richard; Galloway, Tamara S.; Tyler, Charles R.

2007-01-01

Background Environmental estrogens in wastewater treatment work (WwTW) effluents are well established as the principal cause of reproductive disruption in wild fish populations, but their possible role in the wider health effects of effluents has not been established. Objectives We assessed the contribution of estrogens to adverse health effects induced in a model fish species by exposure to WwTW effluents and compared effects of an estrogen alone and as part of a complex mixture (i.e., spiked into effluent). Methods Growth, genotoxic, immunotoxic, metabolic, and endocrine (feminized) responses were compared in fathead minnows (Pimephales promelas) exposed for 21 days to a potent estrogenic effluent, a weakly estrogenic effluent before and after spiking with a steroidal estrogen [17α-ethinyl-estradiol (EE2)], and to EE2 alone. Results In addition to endocrine disruption, effluent exposure induced genotoxic damage, modulated immune function, and altered metabolism; many of these effects were elicited in a sex-specific manner and were proportional to the estrogenic potencies of the effluents. A key finding was that some of the responses to EE2 were modified when it was present in a complex mixture (i.e., spiked into effluent), suggesting that mixture effects may not be easily modeled for effluent discharges or when the chemicals impact on a diverse array of biological axes. Conclusion These data reveal a clear link between estrogens present in effluents and diverse, adverse, and sex-related health impacts. Our findings also highlight the need for an improved understanding of interactive effects of chemical toxicants on biological systems for understanding health effects of environmental mixtures. PMID:18087587

A rapid, ideal, and eco-friendlier protocol for quantifying proline.

PubMed

Shabnam, Nisha; Tripathi, Indu; Sharmila, P; Pardha-Saradhi, P

2016-11-01

Proline, a stress marker, is routinely quantified by a protocol that essentially uses hazardous toluene. Negative impacts of toluene on human health prompted us to develop a reliable alternate protocol for proline quantification. Absorbance of the proline-ninhydrin condensation product formed by reaction of proline with ninhydrin at 100 °C in the reaction mixture was significantly higher than that recorded after its transfer to toluene, revealing that toluene lowers sensitivity of this assay. λ max of the proline-ninhydrin complex in the reaction mixture and toluene were 508 and 513 nm, respectively. Ninhydrin in glacial acetic acid yielded higher quantity of the proline-ninhydrin condensation product compared to ninhydrin in mixture of glacial acetic acid and H 3 PO 4 , indicating negative impact of H 3 PO 4 on proline quantification. Further, maximum yield of the proline-ninhydrin complex with ninhydrin in glacial acetic acid and ninhydrin in mixture of glacial acetic acid and H 3 PO 4 was achieved within 30 and 60 min, respectively. This revealed that H 3 PO 4 has negative impact on the reaction rate and quantity of the proline-ninhydrin complex formed. In brief, our proline quantification protocol involves reaction of a 1-ml proline sample with 2 ml of 1.25 % ninhydrin in glacial acetic acid at 100 °C for 30 min, followed by recording absorbance of the proline-ninhydrin condensation product in the reaction mixture itself at 508 nm. Amongst proline quantification protocols known till date, our protocol is the most simple, rapid, reliable, cost-effective, and eco-friendlier.