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Concept: Mixture

410

Plastic debris litters aquatic habitats globally, the majority of which is microscopic (< 1 mm), and is ingested by a large range of species. Risks associated with such small fragments come from the material itself and from chemical pollutants that sorb to it from surrounding water. Hazards associated with the complex mixture of plastic and accumulated pollutants are largely unknown. Here, we show that fish, exposed to a mixture of polyethylene with chemical pollutants sorbed from the marine environment, bioaccumulate these chemical pollutants and suffer liver toxicity and pathology. Fish fed virgin polyethylene fragments also show signs of stress, although less severe than fish fed marine polyethylene fragments. We provide baseline information regarding the bioaccumulation of chemicals and associated health effects from plastic ingestion in fish and demonstrate that future assessments should consider the complex mixture of the plastic material and their associated chemical pollutants.

Concepts: Chemical substance, Mixture, Toxicology, Pollution, Plastic, Chemical compound, Material, Ocean

210

California’s furniture flammability standard Technical Bulletin 117 (TB 117) is believed to be a major driver of chemical flame retardant (FR) use in residential furniture in the United States. With the phase-out of the polybrominated diphenyl ether (PBDE) FR mixture PentaBDE in 2005, alternative FRs are increasingly being used to meet TB 117; however, it was unclear which chemicals were being used and how frequently. To address this data gap, we collected and analyzed 102 samples of polyurethane foam from residential couches purchased in the United States from 1985 to 2010. Overall, we detected chemical flame retardants in 85% of the couches. In samples purchased prior to 2005 (n = 41) PBDEs associated with the PentaBDE mixture including BDEs 47, 99, and 100 (PentaBDE) were the most common FR detected (39%), followed by tris(1,3-dichloroisopropyl) phosphate (TDCPP; 24%), which is a suspected human carcinogen. In samples purchased in 2005 or later (n = 61) the most common FRs detected were TDCPP (52%) and components associated with the Firemaster550 (FM 550) mixture (18%). Since the 2005 phase-out of PentaBDE, the use of TDCPP increased significantly. In addition, a mixture of nonhalogenated organophosphate FRs that included triphenyl phosphate (TPP), tris(4-butylphenyl) phosphate (TBPP), and a mix of butylphenyl phosphate isomers were observed in 13% of the couch samples purchased in 2005 or later. Overall the prevalence of flame retardants (and PentaBDE) was higher in couches bought in California compared to elsewhere, although the difference was not quite significant (p = 0.054 for PentaBDE). The difference was greater before 2005 than after, suggesting that TB 117 is becoming a de facto standard across the U.S. We determined that the presence of a TB 117 label did predict the presence of a FR; however, lack of a label did not predict the absence of a flame retardant. Following the PentaBDE phase out, we also found an increased number of flame retardants on the market. Given these results, and the potential for human exposure to FRs, health studies should be conducted on the types of FRs identified here.

Concepts: United States, Mixture, Fire retardant, Flame retardant, Decabromodiphenyl ether, Polychlorinated biphenyl, Flame retardants, De facto

174

This paper describes the design of a new instrumental technique, Gas Chromatography Recomposition-Olfactometry (GC-R), that adapts the reconstitution technique used in flavor chemistry studies by extracting volatiles from a sample by headspace solid-phase microextraction (SPME), separating the extract on a capillary GC column, and recombining individual compounds selectively as they elute off of the column into a mixture for sensory analysis (Figure 1). Using the chromatogram of a mixture as a map, the GC-R instrument allows the operator to “cut apart” and recombine the components of the mixture at will, selecting compounds, peaks, or sections based on retention time to include or exclude in a reconstitution for sensory analysis. Selective recombination is accomplished with the installation of a Deans Switch directly in-line with the column, which directs compounds either to waste or to a cryotrap at the operator’s discretion. This enables the creation of, for example, aroma reconstitutions incorporating all of the volatiles in a sample, including instrumentally undetectable compounds as well those present at concentrations below sensory thresholds, thus correcting for the “reconstitution discrepancy” sometimes noted in flavor chemistry studies. Using only flowering lavender (Lavandula angustifola ‘Hidcote Blue’) as a source for volatiles, we used the instrument to build mixtures of subsets of lavender volatiles in-instrument and characterized their aroma qualities with a sensory panel. We showed evidence of additive, masking, and synergistic effects in these mixtures and of “lavender' aroma character as an emergent property of specific mixtures. This was accomplished without the need for chemical standards, reductive aroma models, or calculation of Odor Activity Values, and is broadly applicable to any aroma or flavor.

Concepts: Mixture, Chromatography, High performance liquid chromatography, Analytical chemistry, Gas chromatography, Chemical compound, Solid phase microextraction, Separation process

164

Human artefacts in general are highly structured and often display ordering principles such as translational, reflectional or rotational symmetry. In contrast, human artefacts that are intended to appear random and non symmetrical are very rare. Furthermore, many studies show that humans find it extremely difficult to recognize or reproduce truly random patterns or sequences. Here, we attempt to model two-dimensional decorative spatial patterns produced by humans that show no obvious order. “Crazy quilts” represent a historically important style of quilt making that became popular in the 1870s, and lasted about 50 years. Crazy quilts are unusual because unlike most human artefacts, they are specifically intended to appear haphazard and unstructured. We evaluate the degree to which this intention was achieved by using statistical techniques of spatial point pattern analysis to compare crazy quilts with regular quilts from the same region and era and to evaluate the fit of various random distributions to these two quilt classes. We found that the two quilt categories exhibit fundamentally different spatial characteristics: The patch areas of crazy quilts derive from a continuous random distribution, while area distributions of regular quilts consist of Gaussian mixtures. These Gaussian mixtures derive from regular pattern motifs that are repeated and we suggest that such a mixture is a distinctive signature of human-made visual patterns. In contrast, the distribution found in crazy quilts is shared with many other naturally occurring spatial patterns. Centroids of patches in the two quilt classes are spaced differently and in general, crazy quilts but not regular quilts are well-fitted by a random Strauss process. These results indicate that, within the constraints of the quilt format, Victorian quilters indeed achieved their goal of generating random structures.

Concepts: Statistics, Symmetry, Mixture, Pattern, Rotational symmetry, Pattern matching, Quilting, Quilt

142

Concentration addition (CA) was proposed as a reasonable default approach for the ecological risk assessment of chemical mixtures. However, CA cannot predict the toxicity of mixture at some effect zones if not all components have definite effective concentrations at the given effect, such as some compounds induce hormesis. In this paper, we developed a new method for the toxicity prediction of various types of binary mixtures, an interpolation method based on the Delaunay triangulation (DT) and Voronoi tessellation (VT) as well as the training set of direct equipartition ray design (EquRay) mixtures, simply IDVequ. At first, the EquRay was employed to design the basic concentration compositions of five binary mixture rays. The toxic effects of single components and mixture rays at different times and various concentrations were determined by the time-dependent microplate toxicity analysis. Secondly, the concentration-toxicity data of the pure components and various mixture rays were acted as a training set. The DT triangles and VT polygons were constructed by various vertices of concentrations in the training set. The toxicities of unknown mixtures were predicted by the linear interpolation and natural neighbor interpolation of vertices. The IDVequ successfully predicted the toxicities of various types of binary mixtures.

Concepts: Chemical substance, Mixture, Chemical compound, Toxicity, Computational geometry, Delaunay triangulation, Voronoi diagram, CGAL

53

The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin - the latter with and without rapamycin, and two drugs previously examined: 17-α-estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously. 17-α-estradiol at a threefold higher dose robustly extended both median and maximal lifespan, but still only in males. The male-specific extension of median lifespan by NDGA was replicated at the original dose, and using doses threefold lower and higher. The effects of NDGA were dose dependent and male specific but without an effect on maximal lifespan. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit, based on historical comparison with earlier studies of rapamycin given alone. The α-glucosidase inhibitor, acarbose, at a concentration previously tested (1000 ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16 months. Neither fish oil nor UDCA extended lifespan. These results underscore the reproducibility of ITP longevity studies and illustrate the importance of identifying optimal doses in lifespan studies.

Concepts: Male, Female, Gender, Dose, Sex, Mixture, Gamete, Hermaphrodite

40

Our society is increasingly relying on the digitized, aggregated opinions of others to make decisions. We therefore designed and analyzed a large-scale randomized experiment on a social news aggregation Web site to investigate whether knowledge of such aggregates distorts decision-making. Prior ratings created significant bias in individual rating behavior, and positive and negative social influences created asymmetric herding effects. Whereas negative social influence inspired users to correct manipulated ratings, positive social influence increased the likelihood of positive ratings by 32% and created accumulating positive herding that increased final ratings by 25% on average. This positive herding was topic-dependent and affected by whether individuals were viewing the opinions of friends or enemies. A mixture of changing opinion and greater turnout under both manipulations together with a natural tendency to up-vote on the site combined to create the herding effects. Such findings will help interpret collective judgment accurately and avoid social influence bias in collective intelligence in the future.

Concepts: Critical thinking, Future, Sociology, Aggregate, Mixture, Individual, Social influence, Opinion

34

Exosomes are nanoscale extracellular vesicles that play an important role in many biological processes, including intercellular communications, antigen presentation, and the transport of proteins, RNA, and other molecules. Recently there has been significant interest in exosome-related fundamental research, seeking new exosome-based biomarkers for health monitoring and disease diagnoses. Here, we report a separation method based on acoustofluidics (i.e., the integration of acoustics and microfluidics) to isolate exosomes directly from whole blood in a label-free and contact-free manner. This acoustofluidic platform consists of two modules: a microscale cell-removal module that first removes larger blood components, followed by extracellular vesicle subgroup separation in the exosome-isolation module. In the cell-removal module, we demonstrate the isolation of 110-nm particles from a mixture of micro- and nanosized particles with a yield greater than 99%. In the exosome-isolation module, we isolate exosomes from an extracellular vesicle mixture with a purity of 98.4%. Integrating the two acoustofluidic modules onto a single chip, we isolated exosomes from whole blood with a blood cell removal rate of over 99.999%. With its ability to perform rapid, biocompatible, label-free, contact-free, and continuous-flow exosome isolation, the integrated acoustofluidic device offers a unique approach to investigate the role of exosomes in the onset and progression of human diseases with potential applications in health monitoring, medical diagnosis, targeted drug delivery, and personalized medicine.

Concepts: Immune system, Protein, Medicine, Disease, Blood, Mixture, Blood plasma, Separation process

28

Viruses are a cause of significant health problem worldwide, especially in the developing nations. Due to different anthropological activities, human populations are exposed to different viral pathogens, many of which emerge as outbreaks. In such situations, discovery of novel viruses is utmost important for deciding prevention and treatment strategies. Since last century, a number of different virus discovery methods, based on cell culture inoculation, sequence-independent PCR have been used for identification of a variety of viruses. However, the recent emergence and commercial availability of next-generation sequencers (NGS) has entirely changed the field of virus discovery. These massively parallel sequencing platforms can sequence a mixture of genetic materials from a very heterogeneous mix, with high sensitivity. Moreover, these platforms work in a sequence-independent manner, making them ideal tools for virus discovery. However, for their application in clinics, sample preparation or enrichment is necessary to detect low abundance virus populations. A number of techniques have also been developed for enrichment or viral nucleic acids. In this manuscript, we review the evolution of sequencing; NGS technologies available today as well as widely used virus enrichment technologies. We also discuss the challenges associated with their applications in the clinical virus discovery.

Concepts: DNA, Genetics, Virus, Vaccination, Nucleic acid, Mixture, Virology, Computer virus

28

A new generation of designer solvents emerged in the last decade as promising green media for multiple applications, including separation processes: the low-transition-temperature mixtures (LTTMs). They can be prepared by mixing natural high-melting-point starting materials, which form a liquid by hydrogen-bond interactions. Among them, deep-eutectic solvents (DESs) were presented as promising alternatives to conventional ionic liquids (ILs). Some limitations of ILs are overcome by LTTMs, which are cheap and easy to prepare from natural and readily available starting materials, biodegradable, and renewable.

Concepts: Chemical substance, Mixture, Analytical chemistry, Solvent, Ionic liquid, Distillation, Separation process, Deep eutectic solvent