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Sample records for heterogeneous ribonuclear proteins

  1. Mechanistic Control of Carcinoembryonic Antigen-related Cell Adhesion Molecule-1 (CEACAM1) Splice Isoforms by the Heterogeneous Nuclear Ribonuclear Proteins hnRNP L, hnRNP A1, and hnRNP M*

    PubMed Central

    Dery, Kenneth J.; Gaur, Shikha; Gencheva, Marieta; Yen, Yun; Shively, John E.; Gaur, Rajesh K.

    2011-01-01

    Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is expressed in a variety of cell types and is implicated in carcinogenesis. Alternative splicing of CEACAM1 pre-mRNA generates two cytoplasmic domain splice variants characterized by the inclusion (L-isoform) or exclusion (S-isoform) of exon 7. Here we show that the alternative splicing of CEACAM1 pre-mRNA is regulated by novel cis elements residing in exon 7. We report the presence of three exon regulatory elements that lead to the inclusion or exclusion of exon 7 CEACAM1 mRNA in ZR75 breast cancer cells. Heterologous splicing reporter assays demonstrated that the maintenance of authentic alternative splicing mechanisms were independent of the CEACAM1 intron sequence context. We show that forced expression of these exon regulatory elements could alter CEACAM1 splicing in HEK-293 cells. Using RNA affinity chromatography, three members of the heterogeneous nuclear ribonucleoprotein family (hnRNP L, hnRNP A1, and hnRNP M) were identified. RNA immunoprecipitation of hnRNP L and hnRNP A1 revealed a binding motif located central and 3′ to exon 7, respectively. Depletion of hnRNP A1 or L by RNAi in HEK-293 cells promoted exon 7 inclusion, whereas overexpression led to exclusion of the variable exon. By contrast, overexpression of hnRNP M showed exon 7 inclusion and production of CEACAM1-L mRNA. Finally, stress-induced cytoplasmic accumulation of hnRNP A1 in MDA-MB-468 cells dynamically alters the CEACAM1-S:CEACAM1:L ratio in favor of the l-isoform. Thus, we have elucidated the molecular factors that control the mechanism of splice-site recognition in the alternative splicing regulation of CEACAM1. PMID:21398516

  2. A putative role of ribonuclear inclusions and MBNL1 in the impairment of gallbladder smooth muscle contractility with cholelithiasis in myotonic dystrophy type 1.

    PubMed

    Cardani, R; Mancinelli, E; Saino, G; Bonavina, L; Meola, G

    2008-08-01

    Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder caused by expansion of unstable trinucleotide (CTG) repeats at 3' untranslated region of the DMPK gene on chromosome 19q13.3. Mutant transcripts are retained in muscle nuclei as ribonuclear inclusions and interact with RNA-binding proteins, such as muscleblind-like protein 1 (MBNL1), leading to a reduction in their activity. The reduced MBNL1 activity has been associated to skeletal and cardiac muscle dysfunction. However, other organs and systems may be involved. It has been reported that 25-50% of DM1 patients have abdominal symptoms due to cholelithiasis or gallstones. Since impaired gallbladder motility plays an important role in gallstones formation, we have analyzed by FISH combined with MBNL1-immunofluorescence, the gallbladder obtained from a woman affected by DM1 who required a cholecystectomy at the age of 30. Gallbladders obtained from two no-DM1 subjects have been used as controls. Ribonuclear inclusions and MBNL1 foci accumulate and colocalize in nuclei of DM1 gallbladder smooth muscle cells. On the contrary, no ribonuclear inclusions are detectable in cell nuclei of control gallbladders and MBNL1 is uniformly distributed in smooth muscle cell nuclei. These results suggest that nuclear accumulation of MBNL1 and ribonuclear inclusions may have a direct adverse effect on gallbladder smooth muscle contractility and thus contribute to gallstones formation in DM1 patients.

  3. Suppression of conformational heterogeneity at a protein-protein interface.

    PubMed

    Deis, Lindsay N; Wu, Qinglin; Wang, You; Qi, Yang; Daniels, Kyle G; Zhou, Pei; Oas, Terrence G

    2015-07-21

    Staphylococcal protein A (SpA) is an important virulence factor from Staphylococcus aureus responsible for the bacterium's evasion of the host immune system. SpA includes five small three-helix-bundle domains that can each bind with high affinity to many host proteins such as antibodies. The interaction between a SpA domain and the Fc fragment of IgG was partially elucidated previously in the crystal structure 1FC2. Although informative, the previous structure was not properly folded and left many substantial questions unanswered, such as a detailed description of the tertiary structure of SpA domains in complex with Fc and the structural changes that take place upon binding. Here we report the 2.3-Å structure of a fully folded SpA domain in complex with Fc. Our structure indicates that there are extensive structural rearrangements necessary for binding Fc, including a general reduction in SpA conformational heterogeneity, freezing out of polyrotameric interfacial residues, and displacement of a SpA side chain by an Fc side chain in a molecular-recognition pocket. Such a loss of conformational heterogeneity upon formation of the protein-protein interface may occur when SpA binds its multiple binding partners. Suppression of conformational heterogeneity may be an important structural paradigm in functionally plastic proteins.

  4. Heterogeneity in Retroviral Nucleocapsid Protein Function

    NASA Astrophysics Data System (ADS)

    Landes, Christy

    2009-03-01

    Time-resolved single-molecule fluorescence spectroscopy was used to study the human T-cell lymphotropic virus type 1 (HTLV-1) nucleocapsid protein (NC) chaperone activity as compared to that of the HIV-1 NC protein. HTLV-1 NC contains two zinc fingers with each having a CCHC binding motif similar to HIV-1 NC. HIV-1 NC is required for recognition and packaging of the viral RNA and is also a nucleic acid chaperone protein that facilitates nucleic acid restructuring during reverse transcription. Because of similarities in structures between the two retroviruses, we have used single-molecule fluorescence energy transfer to investigate the chaperoning activity of HTLV-1 NC protein. The results indicate that HTLV-1 NC protein induces structural changes by opening the transactivation response (TAR)-DNA hairpin to an even greater extent than HIV-1 NC. However, unlike HIV-1 NC, HTLV-1 NC does not chaperone the strand-transfer reaction involving TAR-DNA. These results suggest that despite its effective destabilization capability, HTLV-1 NC is not as effective at overall chaperone function as is its HIV-1 counterpart.

  5. Sequence heterogeneity accelerates protein search for targets on DNA

    NASA Astrophysics Data System (ADS)

    Shvets, Alexey A.; Kolomeisky, Anatoly B.

    2015-12-01

    The process of protein search for specific binding sites on DNA is fundamentally important since it marks the beginning of all major biological processes. We present a theoretical investigation that probes the role of DNA sequence symmetry, heterogeneity, and chemical composition in the protein search dynamics. Using a discrete-state stochastic approach with a first-passage events analysis, which takes into account the most relevant physical-chemical processes, a full analytical description of the search dynamics is obtained. It is found that, contrary to existing views, the protein search is generally faster on DNA with more heterogeneous sequences. In addition, the search dynamics might be affected by the chemical composition near the target site. The physical origins of these phenomena are discussed. Our results suggest that biological processes might be effectively regulated by modifying chemical composition, symmetry, and heterogeneity of a genome.

  6. Sequence heterogeneity accelerates protein search for targets on DNA

    SciTech Connect

    Shvets, Alexey A.; Kolomeisky, Anatoly B.

    2015-12-28

    The process of protein search for specific binding sites on DNA is fundamentally important since it marks the beginning of all major biological processes. We present a theoretical investigation that probes the role of DNA sequence symmetry, heterogeneity, and chemical composition in the protein search dynamics. Using a discrete-state stochastic approach with a first-passage events analysis, which takes into account the most relevant physical-chemical processes, a full analytical description of the search dynamics is obtained. It is found that, contrary to existing views, the protein search is generally faster on DNA with more heterogeneous sequences. In addition, the search dynamics might be affected by the chemical composition near the target site. The physical origins of these phenomena are discussed. Our results suggest that biological processes might be effectively regulated by modifying chemical composition, symmetry, and heterogeneity of a genome.

  7. Immunochemical studies on heterogeneity of IgD myeloma proteins.

    PubMed Central

    Ohtani, H; Sakaguchi, K; Saito, M

    1981-01-01

    An antigenic heterogeneity among IgD myeloma proteins was tested by immunoelectrophoresis and double immunodiffusion in agar with four kinds of anti-delta(Fc) antisera produced by immunization with isolated Fc fragments of IgD myeloma proteins. According to antigenicity of the Fc fragment, IgD myeloma proteins were divided into two different groups. Anti-delta(Fc)-T1 (S.T.) antiserum, absorbed with te Y.S. myeloma protein or serum, either gave a faint precipitin line or failed to react against the isolated IgD myeloma proteins or sera. With the papain-digested IgD myeloma proteins and sera, anti-delta(Fc)-T1 antiserum either gave heavy precipitin lines or failed to react. Of twelve papain-digested sera containing IgD myeloma proteins tested, nine (75%) showed positive precipitin lines using anti-delta(Fc)-T1 antiserum. No relationship was found between the two groups of myeloma proteins with respect to IgD levels. SDS polyacrylamide gel electrophoresis of the IgD myeloma proteins (S.T. and Y.S.) showed no difference in the molecular weights of the whole myeloma proteins, and their light and heavy chains. Polyacrylamide gel electrophoresis of the IgD myeloma proteins (S.T. and Y.S.), after treatment with papain, revealed almost the same patterns. Images Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:6168563

  8. Sequence Heterogeneity Accelerates Protein Search for Targets on DNA

    NASA Astrophysics Data System (ADS)

    Shvets, Alexey; Kolomeisky, Anatoly

    The process of protein search for specific binding sites on DNA is fundamentally important since it marks the beginning of all major biological processes. We present a theoretical investigation that probes the role of DNA sequence symmetry, heterogeneity and chemical composition in the protein search dynamics. Using a discrete-state stochastic approach with a first-passage events analysis, which takes into account the most relevant physical-chemical processes, a full analytical description of the search dynamics is obtained. It is found that, contrary to existing views, the protein search is generally faster on DNA with more heterogeneous sequences. In addition, the search dynamics might be affected by the chemical composition near the target site. The physical origins of these phenomena are discussed. Our results suggest that biological processes might be effectively regulated by modifying chemical composition, symmetry and heterogeneity of a genome. The work was supported by the Welch Foundation (Grant C-1559), by the NSF (Grant CHE-1360979), and by the Center for Theoretical Biological Physics sponsored by the NSF (Grant PHY-1427654).

  9. Heterogeneous Nucleation of Protein Crystals on Fluorinated Layered Silicate

    PubMed Central

    Ino, Keita; Udagawa, Itsumi; Iwabata, Kazuki; Takakusagi, Yoichi; Kubota, Munehiro; Kurosaka, Keiichi; Arai, Kazuhito; Seki, Yasutaka; Nogawa, Masaya; Tsunoda, Tatsuo; Mizukami, Fujio; Taguchi, Hayao; Sakaguchi, Kengo

    2011-01-01

    Here, we describe an improved system for protein crystallization based on heterogeneous nucleation using fluorinated layered silicate. In addition, we also investigated the mechanism of nucleation on the silicate surface. Crystallization of lysozyme using silicates with different chemical compositions indicated that fluorosilicates promoted nucleation whereas the silicates without fluorine did not. The use of synthesized saponites for lysozyme crystallization confirmed that the substitution of hydroxyl groups contained in the lamellae structure for fluorine atoms is responsible for the nucleation-inducing property of the nucleant. Crystallization of twelve proteins with a wide range of pI values revealed that the nucleation promoting effect of the saponites tended to increase with increased substitution rate. Furthermore, the saponite with the highest fluorine content promoted nucleation in all the test proteins regardless of their overall net charge. Adsorption experiments of proteins on the saponites confirmed that the density of adsorbed molecules increased according to the substitution rate, thereby explaining the heterogeneous nucleation on the silicate surface. PMID:21818343

  10. Heterogeneous interactome between Litopenaeus vannamei plasma proteins and Vibrio parahaemolyticus outer membrane proteins.

    PubMed

    Liu, Xiang; She, Xin-Tao; Zhu, Qing-Feng; Li, Hui; Peng, Xuan-Xian

    2013-01-01

    A great loss has been suffered by microbial infectious diseases under intensive shrimp farming in recent years. In this background, the understanding of shrimp innate immunity becomes an importantly scientific issue, but little is known about the heterogeneous protein-protein interaction between pathogenic cells and hosts, which is a key step for the invading microbes to infect internet organs through bloodstream. In the present study, bacterial outer membrane (OM) protein array and pull-down approaches are used to isolate both Vibrio parahaemolyticus OM proteins that bind to shrimp serum proteins and the shrimp serum proteins that interact with bacterial cells, respectively. Three interacting shrimp serum proteins, hemocyanin, β-1,3-glucan binding protein and LV_HP_RA36F08r and thirty interacting OM proteins were determined. They form 63 heterogeneous protein-protein interactions. Nine out of the 30 OM proteins were randomly demonstrated to be up-regulated or down-regulated when bacterial cells were cultured with shrimp sera, indicating the biological significance of the network. The interesting findings uncover the complexity of struggle between host immunity and bacterial infection. Compared with our previous report on heterogeneous interactome between fish grill and bacterial OM proteins, the present study further extends the investigation from lower vertebrates to invertebrates and develops a bacterial OM protein array to identify the OM proteins bound with shrimp serum proteins, which elevates the frequencies of the bound OM proteins. Our results highlight the way to determine and understand the heterogeneous interaction between hosts and microbes.

  11. Rube Goldberg goes (ribo)nuclear? Molecular switches and sensors made from RNA

    PubMed Central

    SILVERMAN, SCOTT K.

    2003-01-01

    Switches and sensors play important roles in our everyday lives. The chemical properties of RNA make it amenable for use as a switch or sensor, both artificially and in nature. This review focuses on recent advances in artificial RNA switches and sensors. Researchers have been applying classical biochemical principles such as allostery in elegant ways that are influencing the development of biosensors and other applications. Particular attention is given here to allosteric ribozymes (aptazymes) that are regulated by small organic molecules, by proteins, or by oligonucleotides. Also discussed are ribozymes whose activities are controlled by various nonallosteric strategies. PMID:12649489

  12. Rube Goldberg goes (ribo)nuclear? Molecular switches and sensors made from RNA.

    PubMed

    Silverman, Scott K

    2003-04-01

    Switches and sensors play important roles in our everyday lives. The chemical properties of RNA make it amenable for use as a switch or sensor, both artificially and in nature. This review focuses on recent advances in artificial RNA switches and sensors. Researchers have been applying classical biochemical principles such as allostery in elegant ways that are influencing the development of biosensors and other applications. Particular attention is given here to allosteric ribozymes (aptazymes) that are regulated by small organic molecules, by proteins, or by oligonucleotides. Also discussed are ribozymes whose activities are controlled by various nonallosteric strategies.

  13. Demonstration of heterogeneity among the antigenic proteins of Mobiluncus species.

    PubMed Central

    Schwebke, J R; Hillier, S L; Fohn, M J; Lukehart, S A

    1990-01-01

    The protein and antigenic profiles of the American Type Culture Collection type strains of Mobiluncus species and those of 114 clinical isolates were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and immunoblotting with homologous polyvalent antisera. The majority of isolates (82%) possessed characteristic protein profiles and could be identified to the species level by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The major protein bands were also antigenic, and some antigenic cross-reactivity was noted between the two Mobiluncus species. All of the isolates were examined for reactivity with a panel of 12 monoclonal antibodies previously prepared against the type strains. While 56 of 60 clinical isolates of Mobiluncus curtisii (93%) reacted with one or more of the monoclonal antibodies, only 23 of 54 clinical isolates which were identified as Mobiluncus mulieris by biochemical methods (48%) reacted with one or more of the monoclonal antibodies. One of the 4 M. curtisii isolates (25%) and 11 of the 31 M. mulieris isolates (35%) which did not react with the monoclonal antibodies also had atypical protein profiles. These results demonstrate a high degree of heterogeneity in the protein and antigenic profiles of Mobiluncus isolates and suggest that further taxonomic division may be appropriate. Images PMID:1691207

  14. Combining heterogeneous data sources for accurate functional annotation of proteins

    PubMed Central

    2013-01-01

    Combining heterogeneous sources of data is essential for accurate prediction of protein function. The task is complicated by the fact that while sequence-based features can be readily compared across species, most other data are species-specific. In this paper, we present a multi-view extension to GOstruct, a structured-output framework for function annotation of proteins. The extended framework can learn from disparate data sources, with each data source provided to the framework in the form of a kernel. Our empirical results demonstrate that the multi-view framework is able to utilize all available information, yielding better performance than sequence-based models trained across species and models trained from collections of data within a given species. This version of GOstruct participated in the recent Critical Assessment of Functional Annotations (CAFA) challenge; since then we have significantly improved the natural language processing component of the method, which now provides performance that is on par with that provided by sequence information. The GOstruct framework is available for download at http://strut.sourceforge.net. PMID:23514123

  15. CombFunc: predicting protein function using heterogeneous data sources.

    PubMed

    Wass, Mark N; Barton, Geraint; Sternberg, Michael J E

    2012-07-01

    Only a small fraction of known proteins have been functionally characterized, making protein function prediction essential to propose annotations for uncharacterized proteins. In recent years many function prediction methods have been developed using various sources of biological data from protein sequence and structure to gene expression data. Here we present the CombFunc web server, which makes Gene Ontology (GO)-based protein function predictions. CombFunc incorporates ConFunc, our existing function prediction method, with other approaches for function prediction that use protein sequence, gene expression and protein-protein interaction data. In benchmarking on a set of 1686 proteins CombFunc obtains precision and recall of 0.71 and 0.64 respectively for gene ontology molecular function terms. For biological process GO terms precision of 0.74 and recall of 0.41 is obtained. CombFunc is available at http://www.sbg.bio.ic.ac.uk/combfunc.

  16. Proteomic and genomic analysis reveals novel Campylobacter jejuni outer membrane proteins and potential heterogeneity.

    PubMed

    Watson, Eleanor; Sherry, Aileen; Inglis, Neil F; Lainson, Alex; Jyothi, Dushyanth; Yaga, Raja; Manson, Erin; Imrie, Lisa; Everest, Paul; Smith, David G E

    2014-09-01

    Gram-negative bacterial outer membrane proteins play important roles in the interaction of bacteria with their environment including nutrient acquisition, adhesion and invasion, and antibiotic resistance. In this study we identified 47 proteins within the Sarkosyl-insoluble fraction of Campylobacter jejuni 81-176, using LC-ESI-MS/MS. Comparative analysis of outer membrane protein sequences was visualised to reveal protein distribution within a panel of Campylobacter spp., identifying several C. jejuni-specific proteins. Smith-Waterman analyses of C. jejuni homologues revealed high sequence conservation amongst a number of hypothetical proteins, sequence heterogeneity of other proteins and several proteins which are absent in a proportion of strains.

  17. Theory of polyelectrolyte adsorption on heterogeneously charged surfaces applied to soluble protein-polyelectrolyte complexes

    NASA Astrophysics Data System (ADS)

    de Vries, R.; Weinbreck, F.; de Kruif, C. G.

    2003-03-01

    Existing theoretical approaches to polymer adsorption on heterogeneous surfaces are applied to the problems of polyelectrolyte and polyampholyte adsorption on randomly charged surfaces. Also, analytical estimates are developed for the critical pH at which weakly charged polyelectrolytes and globular proteins start forming soluble complexes. Below a critical salt concentration, soluble complexes form "on the wrong side" of the protein isoelectric point due to the heterogeneity of the protein surface charge distribution. The analytical estimates are consistent with experimental data on soluble complexes in mixtures of gum arabic and whey protein isolate.

  18. CombFunc: predicting protein function using heterogeneous data sources

    PubMed Central

    Wass, Mark N.; Barton, Geraint; Sternberg, Michael J. E.

    2012-01-01

    Only a small fraction of known proteins have been functionally characterized, making protein function prediction essential to propose annotations for uncharacterized proteins. In recent years many function prediction methods have been developed using various sources of biological data from protein sequence and structure to gene expression data. Here we present the CombFunc web server, which makes Gene Ontology (GO)-based protein function predictions. CombFunc incorporates ConFunc, our existing function prediction method, with other approaches for function prediction that use protein sequence, gene expression and protein–protein interaction data. In benchmarking on a set of 1686 proteins CombFunc obtains precision and recall of 0.71 and 0.64 respectively for gene ontology molecular function terms. For biological process GO terms precision of 0.74 and recall of 0.41 is obtained. CombFunc is available at http://www.sbg.bio.ic.ac.uk/combfunc. PMID:22641853

  19. Charge heterogeneity study of a Fc-fusion protein, abatacept, using two-dimensional gel electrophoresis.

    PubMed

    Nebija, D; Noe, C R; Lachmann, B

    2015-08-01

    Medicinal products obtained by recombinant DNA technology are complex molecules and demonstrate a high degree of molecular heterogeneity. Charge heterogeneity and isoform pattern of this class of medicines, are parameters important for their quality, safety, and efficacy. In this study we report the application of two-dimensional gel electrophoresis (2-D electrophoresis) for the quality assessment, identification, charge heterogeneity and isoform pattern study of recombinant protein, CTLA4-Ig (abatacept), which has been selected as an example of the drug class, known as Fc-fusion proteins. In order to achieve an efficient separation of this complex analyte,2-D electrophoresis was optimized employing different experimental conditions regarding the selection of an immobilized pH gradient (IPG), sample pretreatment, presentation and detection procedure. Experimental datadocumented that 2-D electrophoresis is a suitable method for the assessment of identity, purity, structural integrity, isoform pattern and to monitor charge heterogeneity and post-translational glycosylation of the Fc-fusion protein, abatacept.

  20. Polar Fixation of Plasmids during Recombinant Protein Production in Bacillus megaterium Results in Population Heterogeneity.

    PubMed

    Münch, Karin M; Müller, Johannes; Wienecke, Sarah; Bergmann, Simone; Heyber, Steffi; Biedendieck, Rebekka; Münch, Richard; Jahn, Dieter

    2015-09-01

    During the past 2 decades, Bacillus megaterium has been systematically developed for the gram-per-liter scale production of recombinant proteins. The plasmid-based expression systems employed use a xylose-controlled promoter. Protein production analyses at the single-cell level using green fluorescent protein as a model product revealed cell culture heterogeneity characterized by a significant proportion of less productive bacteria. Due to the enormous size of B. megaterium, such bistable behavior seen in subpopulations was readily analyzed by time lapse microscopy and flow cytometry. Cell culture heterogeneity was not caused simply by plasmid loss: instead, an asymmetric distribution of plasmids during cell division was detected during the exponential-growth phase. Multicopy plasmids are generally randomly distributed between daughter cells. However, in vivo and in vitro experiments demonstrated that under conditions of strong protein production, plasmids are retained at one of the cell poles. Furthermore, it was found that cells with accumulated plasmids and high protein production ceased cell division. As a consequence, the overall protein production of the culture was achieved mainly by the subpopulation with a sufficient plasmid copy number. Based on our experimental data, we propose a model whereby the distribution of multicopy plasmids is controlled by polar fixation under protein production conditions. Thereby, cell lines with fluctuating plasmid abundance arise, which results in population heterogeneity. Our results provide initial insights into the mechanism of cellular heterogeneity during plasmid-based recombinant protein production in a Bacillus species.

  1. Terbium luminescence-lifetime heterogeneity and protein equilibrium conformational dynamics.

    PubMed Central

    Austin, R H; Stein, D L; Wang, J

    1987-01-01

    The fluorescence decay of the rare earth terbium when bound to the protein calmodulin changes from a simple exponential decay to a complex nonexponential decay as the temperature is lowered below 200 K. We have fit the observed decay curves by assuming that the terbium emission is a forced electric dipole transition and proteins have a distribution of continuous conformational states. Quantitative fits to the data indicate that the root-mean-square configurational deviation of the atoms surrounding the terbium ion is 0.2 A, in good agreement with other measurements. We further point out that because the protein seems to undergo a glass transition yet retains configurational order at room temperature, the proper name for the physical state of a protein at room temperature is the rubber-like state. PMID:3470740

  2. Intraclonal Protein Expression Heterogeneity in Recombinant CHO Cells

    PubMed Central

    Pilbrough, Warren; Munro, Trent P.; Gray, Peter

    2009-01-01

    Therapeutic glycoproteins have played a major role in the commercial success of biotechnology in the post-genomic era. But isolating recombinant mammalian cell lines for large-scale production remains costly and time-consuming, due to substantial variation and unpredictable stability of expression amongst transfected cells, requiring extensive clone screening to identify suitable high producers. Streamlining this process is of considerable interest to industry yet the underlying phenomena are still not well understood. Here we examine an antibody-expressing Chinese hamster ovary (CHO) clone at single-cell resolution using flow cytometry and vectors, which couple light and heavy chain transcription to fluorescent markers. Expression variation has traditionally been attributed to genetic heterogeneity arising from random genomic integration of vector DNA. It follows that single cell cloning should yield a homogeneous cell population. We show, in fact, that expression in a clone can be surprisingly heterogeneous (standard deviation 50 to 70% of the mean), approaching the level of variation in mixed transfectant pools, and each antibody chain varies in tandem. Phenotypic variation is fully developed within just 18 days of cloning, yet is not entirely explained by measurement noise, cell size, or the cell cycle. By monitoring the dynamic response of subpopulations and subclones, we show that cells also undergo slow stochastic fluctuations in expression (half-life 2 to 11 generations). Non-genetic diversity may therefore play a greater role in clonal variation than previously thought. This also has unexpected implications for expression stability. Stochastic gene expression noise and selection bias lead to perturbations from steady state at the time of cloning. The resulting transient response as clones reestablish their expression distribution is not ordinarily accounted for but can contribute to declines in median expression over timescales of up to 50 days. Noise

  3. Heterogeneous distribution of dye-labelled biomineralizaiton proteins in calcite crystals.

    PubMed

    Liu, Chuang; Xie, Liping; Zhang, Rongqing

    2015-12-17

    Biominerals are highly ordered crystals mediated by organic matters especially proteins in organisms. However, how specific proteins are distributed inside biominerals are not well understood. In the present study, we use fluorescein isothiocyanate (FITC) to label extracted proteins from the shells of bivalve Pinctada fucata. By confocal laser scanning microscopy (CLSM), we observe a heterogeneous distribution of dye-labelled proteins inside synthetic calcite at the microscale. Proteins from the prismatic calcite layers accumulate at the edge of crystals while proteins from the nacreous aragonite layers accumulate at the center of crystals. Raman and X-ray powder diffraction show that both the proteins cannot alter the crystal phase. Scanning electron microscope demonstrates both proteins are able to affect the crystal morphology. This study may provide a direct approach for the visualization of protein distributions in crystals by small-molecule dye-labelled proteins as the additives in the crystallization process and improve our understanding of intracrystalline proteins distribution in biogenic calcites.

  4. Structural heterogeneity of 6 M GdmCl-denatured proteins: implications for the mechanism of protein folding.

    PubMed

    Chang, Jui-Yoa

    2009-10-13

    An in vitro experiment with protein folding is typically initiated with 6 M GdmCl-denatured proteins, which are generally considered fully unfolded. However, studies conducted by various laboratories have shown that many 6 M GdmCl-denatured proteins are structurally heterogeneous and still retain nativelike residual structures. The extent of conformational heterogeneity of the 6 M GdmCl-denatured protein has significant implications for the folding landscape as well as the interpretation of the observed early stage folding mechanism. Using the method of disulfide scrambling, we are able to gain rough insight into the diverse structural properties of 6 M GdmCl-denatured proteins. It demonstrates that most 6 M GdmCl-denatured proteins are approximately fully denatured, but partially unfolded. Most of them comprise diverse conformational isomers. We review here the cumulative evidence obtained from various laboratories and also provide experimental data obtained in our laboratory.

  5. Protein-nanoparticle interactions: the effects of surface compositional and structural heterogeneity are scale dependent

    NASA Astrophysics Data System (ADS)

    Huang, Rixiang; Carney, Randy P.; Stellacci, Francesco; Lau, Boris L. T.

    2013-07-01

    Nanoparticles (NPs) in the biological environment are exposed to a large variety and concentration of proteins. Proteins are known to adsorb in a `corona' like structure on the surface of NPs. In this study, we focus on the effects of surface compositional and structural heterogeneity on protein adsorption by examining the interaction of self-assembled monolayer coated gold NPs (AuNPs) with two types of proteins: ubiquitin and fibrinogen. This work was designed to systematically investigate the role of surface heterogeneity in nanoparticle-protein interaction. We have chosen the particles as well as the proteins to provide different types (in distribution and length-scale) of heterogeneity. The goal was to unveil the role of heterogeneity and of its length-scale in the particle-protein interaction. Dynamic light scattering and circular dichroism spectroscopy were used to reveal different interactions at pH above and below the isoelectric points of the proteins, which is related to the charge heterogeneity on the protein surface. At pH 7.4, there was only a monolayer of proteins adsorbed onto the NPs and the secondary structure of proteins remained intact. At pH 4.0, large aggregates of nanoparticle-protein complexes were formed and the secondary structures of the proteins were significantly disrupted. In terms of interaction thermodynamics, results from isothermal titration calorimetry showed that ubiquitin adsorbed differently onto (1) AuNPs with charged and nonpolar terminals organized into nano-scale structure (66-34 OT), (2) AuNPs with randomly distributed terminals (66-34 brOT), and (3) AuNPs with homogeneously charged terminals (MUS). This difference in adsorption behavior was not observed when AuNPs interacted with fibrinogen. The results suggested that the interaction between the proteins and AuNPs was influenced by the surface heterogeneity on the AuNPs, and this influence depends on the scale of surface heterogeneity and the size of the proteins

  6. Heterogeneities in confined water and protein hydration water

    NASA Astrophysics Data System (ADS)

    Stanley, H. E.; Kumar, P.; Han, S.; Mazza, M. G.; Stokely, K.; Buldyrev, S. V.; Franzese, G.; Mallamace, F.; Xu, L.

    2009-12-01

    We report recent efforts to understand a broad range of experiments on confined water and protein hydration water, many initiated by a collaboration between workers at the University of Messina and MIT—the editors of this special issue. Preliminary calculations are not inconsistent with one tentative interpretation of these experiments as resulting from the system passing from the high-temperature high-pressure 'HDL' side of the Widom line (where the liquid might display non-Arrhenius behavior) to the low-temperature low-pressure 'LDL' side of the Widom line (where the liquid might display Arrhenius behavior). The Widom line—defined to be the line in the pressure-temperature plane where the correlation length has its maximum—arises if there is a critical point. Hence, interpreting the Messina-MIT experiments in terms of a Widom line is of potential relevance to testing, experimentally, the hypothesis that water displays a liquid-liquid critical point.

  7. Heterogeneous patterns on block copolymer thin film via solvent annealing: Effect on protein adsorption

    NASA Astrophysics Data System (ADS)

    Shen, Lei; Zhu, Jintao; Liang, Haojun

    2015-03-01

    Heterogeneous patterns consisting of nanometer-scaled hydrophobic/hydrophilic domains were generated by self-assembly of poly(styrene)-block-poly(2-hydroxyethyl methacrylate) (PS-b-PHEMA) block copolymer thin film. The effect of the heterogeneity of the polymer film surface on the nonspecific adsorption of the protein human plasma fibrinogen (FBN, 5.0 × 5.0 × 47.5 nm3) was investigated. The kinetics of the FBN adsorption varies from a single-component Langmuir model on homogeneous hydrophilic PHEMA to a two-stage spreading relaxation model on homogeneous hydrophobic PS surface. On a heterogeneous PS-b-PHEMA surface with majority PS part, the initial FBN adsorption rate remains the same as that on the homogeneous PS surface. However, hydrophilic PHEMA microdomains on the heterogeneous surface slow down the second spreading stage of the FBN adsorption process, leading to a surface excess of adsorbed FBN molecules less than the presumed one simply calculated as adsorption onto multiple domains. Importantly, when the PS-b-PHEMA surface is annealed to form minority domelike PS domains (diameter: ˜50-100 nm) surrounded by a majority PHEMA matrix, such surface morphology proves to be strongly protein-repulsive. These interesting findings can be attributed to the enhancement of the spread FBN molecule in a mobile state by the heterogeneity of polymer film surface before irreversible adsorption occurs.

  8. Heterogeneous distribution of dye-labelled biomineralizaiton proteins in calcite crystals

    PubMed Central

    Liu, Chuang; Xie, Liping; Zhang, Rongqing

    2015-01-01

    Biominerals are highly ordered crystals mediated by organic matters especially proteins in organisms. However, how specific proteins are distributed inside biominerals are not well understood. In the present study, we use fluorescein isothiocyanate (FITC) to label extracted proteins from the shells of bivalve Pinctada fucata. By confocal laser scanning microscopy (CLSM), we observe a heterogeneous distribution of dye-labelled proteins inside synthetic calcite at the microscale. Proteins from the prismatic calcite layers accumulate at the edge of crystals while proteins from the nacreous aragonite layers accumulate at the center of crystals. Raman and X-ray powder diffraction show that both the proteins cannot alter the crystal phase. Scanning electron microscope demonstrates both proteins are able to affect the crystal morphology. This study may provide a direct approach for the visualization of protein distributions in crystals by small-molecule dye-labelled proteins as the additives in the crystallization process and improve our understanding of intracrystalline proteins distribution in biogenic calcites. PMID:26675363

  9. Dynamics and heterogeneity of bovine hippocampal membranes: role of cholesterol and proteins.

    PubMed

    Mukherjee, Soumi; Kombrabail, Mamata; Krishnamoorthy, G; Chattopadhyay, Amitabha

    2007-09-01

    The structural and dynamic consequence of alterations in membrane lipid composition (specifically cholesterol) in neuronal membranes is poorly understood. Previous work from our laboratory has established bovine hippocampal membranes as a convenient natural source for studying neuronal receptors. In this paper, we have explored the role of cholesterol and proteins in the dynamics and heterogeneity of bovine hippocampal membranes using fluorescence lifetime distribution analysis of the environment-sensitive fluorescent probe Nile Red incorporated into such membranes by the maximum entropy method (MEM), and time-resolved fluorescence anisotropy measurements. The peak position and the width of the lifetime distribution of Nile Red show a progressive reduction with increasing cholesterol depletion from native hippocampal membranes indicating that the extent of heterogeneity decreases with decrease in membrane cholesterol content. This is accompanied by a concomitant decrease of the fluorescence anisotropy and rotational correlation time. Our results point out that the microenvironment experienced by Nile Red is relatively insensitive to the presence of proteins in hippocampal membranes. Interestingly, Nile Red lifetime distribution in liposomes of lipid extracts is similar to that of native membranes indicating that proteins do not contribute significantly to the high level of heterogeneity observed in native membranes. These results could be relevant in understanding the neuronal diseases characterized by defective membrane lipid metabolism.

  10. Heterogeneity of Zein mRNA and Protein in Maize 1

    PubMed Central

    Park, William D.; Lewis, Elizabeth D.; Rubenstein, Irwin

    1980-01-01

    Zein, the prolamine fraction of maize, is localized in the endosperm in membrane-bound structures called protein bodies, which have polyribosomes on their surfaces. These polysomes or the mRNA fraction isolated from them will direct the synthesis of zein-like proteins in vitro. The in vitro products consist primarily of two molecular weight classes but show considerable charge heterogeneity when analyzed by isoelectric focusing. Although the molecular weight classes are very similar for different inbred lines, the isoelectric focusing patterns differ. Results given here suggest that the extensive charge heterogeneity of zein proteins does not result from the presence of a large number of totally distinct mRNAs. Zein proteins synthesized in vitro fall into several families related by sequence homologies in their mRNAs. In Illinois High Protein (IHP) the major zein mRNAs can be classified into three families based on their binding to cloned complimentary DNA copies of IHP zein mRNA. Each of three other lines we have studied (W22, Oh43, and W64A) has zein mRNAs that are related to those of IHP. Among these four lines the molecular weights of the members of a given family are generally similar, but the number of members in a family and their isoelectric points differ. Images PMID:16661153

  11. Physical and Functional Interaction between Heterochromatin Protein 1α and the RNA-binding Protein Heterogeneous Nuclear Ribonucleoprotein U*

    PubMed Central

    Ameyar-Zazoua, Maya; Souidi, Mouloud; Fritsch, Lauriane; Robin, Philippe; Thomas, Audrey; Hamiche, Ali; Percipalle, Piergiorgio; Ait-Si-Ali, Slimane; Harel-Bellan, Annick

    2009-01-01

    By combining biochemical purification and mass spectrometry, we identified proteins associated with human heterochromatin protein 1α (HP1α) both in the nucleoplasm and in chromatin. Some of these are RNA-binding proteins, and among them is the protein heterogeneous nuclear ribonucleoprotein U (hnRNP U)/SAF-A, which is linked to chromatin organization and transcriptional regulation. Here, we demonstrate that hnRNP U is a bona fide HP1α-interacting molecule. More importantly, hnRNP U depletion reduces HP1α-dependent gene silencing and disturbs HP1α subcellular localization. Thus, our data demonstrate that hnRNP U is involved in HP1α function, shedding new light on the mode of action of HP1α and on the function of hnRNP U. PMID:19617346

  12. Molecular heterogeneity of arabinogalactan-protein from Coffea arabica instant coffee.

    PubMed

    Capek, P; Matulová, M; Navarini, L; Suggi-Liverani, F

    2013-08-01

    Arabinogalactan-protein complex (AGP), isolated from freeze-dried instant coffee powder of Coffea arabica beans, was subjected to ion-exchange chromatography. Stepwise elution with water and solutions of sodium chloride with increasing ionic strength afforded eight fractions (F1-F8). Chemical analyses have shown that compositions of individual conjugates varied in carbohydrate and protein contents, molecular mass and slightly in monosaccharide composition. Protein content was increasing by increasing ionic strength of the eluent and it was confirmed also by FT-IR spectra. NMR study has shown that carbohydrate moieties in individual ion exchange fractions differed in the degree of backbone and side chains branching. Performed study has confirmed a molecular heterogeneity of arabinogalactan-protein complex present in a commercial instant coffee.

  13. How Surface Heterogeneity Affects Protein Adsorption: Annealing of OTS Patterns and Albumin Adsorption Kinetics*

    PubMed Central

    Hodgkinson, Gerald N.; Hlady, Vladimir

    2009-01-01

    Fluorescence microscopy and intensity histogram analysis techniques were used to monitor spatially-resolved albumin adsorption kinetics to model heterogeneous surfaces on sub-μm scales. Several distinct protein subpopulations were resolved, each represented by a normal distribution of adsorption densities on the adsorbent surface. Histogram analyses provided dynamic information of mean adsorption density, spread in adsorption density, and surface area coverage for each distinct protein subpopulation. A simple adsorption model is proposed in which individual protein binding events are predicted by the summation of multiple protein's surface sub-site interactions with different binding energy sub-sites on adsorbent surfaces. This model is predictive of the albumin adsorption on the patterns produced by one step μ-contact printing (μCP) of octadecyltrichlorosilane (OTS) on glass but fails to describe adsorption once the same patterns are altered by a thermal annealing step. PMID:19746205

  14. Heterogeneous nucleotide occupancy stimulates functionality of phage shock protein F, an AAA+ transcriptional activator.

    PubMed

    Joly, Nicolas; Schumacher, Jörg; Buck, Martin

    2006-11-17

    The catalytic AAA+ domain (PspF1-275) of an enhancer-binding protein is necessary and sufficient to contact sigma54-RNA polymerase holoenzyme (Esigma54), remodel it, and in so doing catalyze open promoter complex formation. Whether ATP binding and hydrolysis is coordinated between subunits of PspF and the precise nature of the nucleotide(s) bound to the oligomeric forms responsible for substrate remodeling are unknown. We demonstrate that ADP stimulates the intrinsic ATPase activity of PspF1-275 and propose that this heterogeneous nucleotide occupancy in a PspF1-275 hexamer is functionally important for specific activity. Binding of ADP and ATP triggers the formation of functional PspF1-275 hexamers as shown by a gain of specific activity. Furthermore, ATP concentrations congruent with stoichiometric ATP binding to PspF1-275 inhibit ATP hydrolysis and Esigma54-promoter open complex formation. Demonstration of a heterogeneous nucleotide-bound state of a functional PspF1-275.Esigma54 complex provides clear biochemical evidence for heterogeneous nucleotide occupancy in this AAA+ protein. Based on our data, we propose a stochastic nucleotide binding and a coordinated hydrolysis mechanism in PspF1-275 hexamers.

  15. Heterogeneous binding of the SH3 client protein to the DnaK molecular chaperone

    PubMed Central

    Lee, Jung Ho; Zhang, Dongyu; Hughes, Christopher; Okuno, Yusuke; Sekhar, Ashok; Cavagnero, Silvia

    2015-01-01

    The molecular chaperone heat shock protein 70 (Hsp70) plays a vital role in cellular processes, including protein folding and assembly, and helps prevent aggregation under physiological and stress-related conditions. Although the structural changes undergone by full-length client proteins upon interaction with DnaK (i.e., Escherichia coli Hsp70) are fundamental to understand chaperone-mediated protein folding, these changes are still largely unexplored. Here, we show that multiple conformations of the SRC homology 3 domain (SH3) client protein interact with the ADP-bound form of the DnaK chaperone. Chaperone-bound SH3 is largely unstructured yet distinct from the unfolded state in the absence of DnaK. The bound client protein shares a highly flexible N terminus and multiple slowly interconverting conformations in different parts of the sequence. In all, there is significant structural and dynamical heterogeneity in the DnaK-bound client protein, revealing that proteins may undergo some conformational sampling while chaperone-bound. This result is important because it shows that the surface of the Hsp70 chaperone provides an aggregation-free environment able to support part of the search for the native state. PMID:26195753

  16. Resolution of Disulfide Heterogeneity in Nogo Receptor 1 Fusion Proteins by Molecular Engineering

    SciTech Connect

    P Weinreb; D Wen; F Qian; C Wildes; E Garber; L Walus; M Jung; J Wang; J Relton; et al.

    2011-12-31

    NgRI (Nogo-66 receptor) is part of a signalling complex that inhibits axon regeneration in the central nervous system. Truncated soluble versions of NgRI have been used successfully to promote axon regeneration in animal models of spinal-cord injury, raising interest in this protein as a potential therapeutic target. The LRR (leucine-rich repeat) regions in NgRI are flanked by N- and C-terminal disulfide-containing 'cap' domains (LRRNT and LRRCT respectively). In the present work we show that, although functionally active, the NgRI(310)-Fc fusion protein contains mislinked and heterogeneous disulfide patterns in the LRRCT domain, and we report the generation of a series of variant molecules specifically designed to prevent this heterogeneity. Using these variants we explored the effects of modifying the NgRI truncation site or the spacing between the NgRI and Fc domains, or replacing cysteines within the NgRI or IgG hinge regions. One variant, which incorporates replacements of Cys{sup 266} and Cys{sup 309} with alanine residues, completely eliminated disulfide scrambling while maintaining functional in vitro and in vivo efficacy. This modified NgRI-Fc molecule represents a significantly improved candidate for further pharmaceutical development, and may serve as a useful model for the optimization of other IgG fusion proteins made from LRR proteins.

  17. Proteins as templates for complex synthetic metalloclusters: towards biologically programmed heterogeneous catalysis.

    PubMed

    Fehl, Charlie; Davis, Benjamin G

    2016-05-01

    Despite nature's prevalent use of metals as prosthetics to adapt or enhance the behaviour of proteins, our ability to programme such architectural organization remains underdeveloped. Multi-metal clusters buried in proteins underpin the most remarkable chemical transformations in nature, but we are not yet in a position to fully mimic or exploit such systems. With the advent of copious, relevant structural information, judicious mechanistic studies and the use of accessible computational methods in protein design coupled with new synthetic methods for building biomacromolecules, we can envisage a 'new dawn' that will allow us to build de novo metalloenzymes that move beyond mono-metal centres. In particular, we highlight the need for systems that approach the multi-centred clusters that have evolved to couple electron shuttling with catalysis. Such hybrids may be viewed as exciting mid-points between homogeneous and heterogeneous catalysts which also exploit the primary benefits of biocatalysis.

  18. Proteins as templates for complex synthetic metalloclusters: towards biologically programmed heterogeneous catalysis

    PubMed Central

    Fehl, Charlie

    2016-01-01

    Despite nature’s prevalent use of metals as prosthetics to adapt or enhance the behaviour of proteins, our ability to programme such architectural organization remains underdeveloped. Multi-metal clusters buried in proteins underpin the most remarkable chemical transformations in nature, but we are not yet in a position to fully mimic or exploit such systems. With the advent of copious, relevant structural information, judicious mechanistic studies and the use of accessible computational methods in protein design coupled with new synthetic methods for building biomacromolecules, we can envisage a ‘new dawn’ that will allow us to build de novo metalloenzymes that move beyond mono-metal centres. In particular, we highlight the need for systems that approach the multi-centred clusters that have evolved to couple electron shuttling with catalysis. Such hybrids may be viewed as exciting mid-points between homogeneous and heterogeneous catalysts which also exploit the primary benefits of biocatalysis. PMID:27279776

  19. The heterogeneity of human antibody responses to vaccinia virus revealed through use of focused protein arrays

    PubMed Central

    Duke-Cohan, Jonathan S.; Wollenick, Kristin; Witten, Elizabeth A.; Seaman, Michael S.; Baden, Lindsey R.; Dolin, Raphael; Reinherz, Ellis L.

    2009-01-01

    The renewed interest in strategies to combat infectious agents with epidemic potential has led to a re-examination of vaccination protocols against smallpox. To help define which antigens elucidate a human antibody response, we have targeted proteins known or predicted to be presented on the surface of the intracellular mature virion (IMV) or the extracellular enveloped virion (EEV). The predicted ectodomains were expressed in a mammalian in vitro coupled transcription/translation reaction using tRNAlys precharged with lysine-ε-biotin followed by solid phase immobilization on 384 well neutravidin-coated plates. The generated array is highly specific and sensitive in a microELISA format. By comparison of binding of vaccinia-immune sera to the reticulocyte lysate-produced proteins and to secreted post-translationally-modified proteins, we demonstrate that for several proteins including the EEV proteins B5 and A33, proper recognition is dependent upon appropriate folding, with little dependence upon glycosylation per se. We further demonstrate that the humoral immune response to vaccinia among different individuals is not uniform in specificity or strength, as different IMV and EEV targets predominate within the group of immunogenic proteins. This heterogeneity likely results from the diversity of HLA Class II alleles and CD4 T helper cell epitopes stimulating B cell antibody production. Our findings have important implications both for design of new recombinant subunit vaccines as well as for methods of assaying the human antibody response utilizing recombinant proteins produced in vitro. PMID:19146908

  20. Multiscale conformational heterogeneity in staphylococcal protein a: possible determinant of functional plasticity.

    PubMed

    Deis, Lindsay N; Pemble, Charles W; Qi, Yang; Hagarman, Andrew; Richardson, David C; Richardson, Jane S; Oas, Terrence G

    2014-10-07

    The Staphylococcus aureus virulence factor staphylococcal protein A (SpA) is a major contributor to bacterial evasion of the host immune system, through high-affinity binding to host proteins such as antibodies. SpA includes five small three-helix-bundle domains (E-D-A-B-C) separated by conserved flexible linkers. Prior attempts to crystallize individual domains in the absence of a binding partner have apparently been unsuccessful. There have also been no previous structures of tandem domains. Here we report the high-resolution crystal structures of a single C domain, and of two B domains connected by the conserved linker. Both structures exhibit extensive multiscale conformational heterogeneity, which required novel modeling protocols. Comparison of domain structures shows that helix1 orientation is especially heterogeneous, coordinated with changes in side chain conformational networks and contacting protein interfaces. This represents the kind of structural plasticity that could enable SpA to bind multiple partners.

  1. Heterogeneity of the Abnormal Prion Protein (PrPSc) of the Chandler Scrapie Strain

    PubMed Central

    Kasai, Kazuo; Iwamaru, Yoshifumi; Masujin, Kentaro; Imamura, Morikazu; Mohri, Shirou; Yokoyama, Takashi

    2013-01-01

    The pathological prion protein, PrPSc, displays various sizes of aggregates. In this study, we investigated the conformation, aggregation stability and proteinase K (PK)-sensitivity of small and large PrPSc aggregates of mouse-adapted prion strains. We showed that small PrPSc aggregates, previously thought to be PK-sensitive, are resistant to PK digestion. Furthermore, we showed that small PrPSc aggregates of the Chandler scrapie strain have greater resistance to PK digestion and aggregation-denaturation than large PrPSc aggregates of this strain. We conclude that this strain consists of heterogeneous PrPSc. PMID:25436883

  2. Matricellular protein SPARCL1 regulates tumor microenvironment–dependent endothelial cell heterogeneity in colorectal carcinoma

    PubMed Central

    Liebl, Andrea; Schellerer, Vera S.; Schütz, Manuela; Kölbel, Patrick; Schaal, Ute; Haep, Lisa; Regensburger, Daniela; Wittmann, Thomas; Klein-Hitpass, Ludger; Rau, Tilman T.; Dietel, Barbara; Méniel, Valérie S.; Clarke, Alan R.; Croner, Roland S.; Hohenberger, Werner

    2016-01-01

    Different tumor microenvironments (TMEs) induce stromal cell plasticity that affects tumorigenesis. The impact of TME-dependent heterogeneity of tumor endothelial cells (TECs) on tumorigenesis is unclear. Here, we isolated pure TECs from human colorectal carcinomas (CRCs) that exhibited TMEs with either improved (Th1-TME CRCs) or worse clinical prognosis (control-TME CRCs). Transcriptome analyses identified markedly different gene clusters that reflected the tumorigenic and angiogenic activities of the respective TMEs. The gene encoding the matricellular protein SPARCL1 was most strongly upregulated in Th1-TME TECs. It was also highly expressed in ECs in healthy colon tissues and Th1-TME CRCs but low in control-TME CRCs. In vitro, SPARCL1 expression was induced in confluent, quiescent ECs and functionally contributed to EC quiescence by inhibiting proliferation, migration, and sprouting, whereas siRNA-mediated knockdown increased sprouting. In human CRC tissues and mouse models, vessels with SPARCL1 expression were larger and more densely covered by mural cells. SPARCL1 secretion from quiescent ECs inhibited mural cell migration, which likely led to stabilized mural cell coverage of mature vessels. Together, these findings demonstrate TME-dependent intertumoral TEC heterogeneity in CRC. They further indicate that TEC heterogeneity is regulated by SPARCL1, which promotes the cell quiescence and vessel homeostasis contributing to the favorable prognoses associated with Th1-TME CRCs. PMID:27721236

  3. Heterogeneous expression of protein and mRNA in pyruvate dehydrogenase deficiency.

    PubMed Central

    Wexler, I D; Kerr, D S; Ho, L; Lusk, M M; Pepin, R A; Javed, A A; Mole, J E; Jesse, B W; Thekkumkara, T J; Pons, G

    1988-01-01

    Deficiency of pyruvate dehydrogenase [pyruvate:lipoamide 2-oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1], the first component of the pyruvate dehydrogenase complex, is associated with lactic acidosis and central nervous system dysfunction. Using both specific antibodies to pyruvate dehydrogenase and cDNAs coding for its two alpha and beta subunits, we characterized pyruvate dehydrogenase deficiency in 11 patients. Three different patterns were found on immunologic and RNA blot analyses. (i) Seven patients had immunologically detectable crossreactive material for the alpha and beta proteins of pyruvate dehydrogenase. (ii) Two patients had no detectable crossreactive protein for either the alpha or beta subunit but had normal amounts of mRNA for both alpha and beta subunits. (iii) The remaining two patients also had no detectable crossreactive protein but had diminished amounts of mRNA for the alpha subunit of pyruvate dehydrogenase only. These results indicate that loss of pyruvate dehydrogenase activity may be associated with either absent or catalytically inactive proteins, and in those cases in which this enzyme is absent, mRNA for one of the subunits may also be missing. When mRNA for one of the subunits is lacking, both protein subunits are absent, suggesting that a mutation affecting the expression of one of the subunit proteins causes the remaining uncomplexed subunit to be unstable. The results show that several different mutations account for the molecular heterogeneity of pyruvate dehydrogenase deficiency. Images PMID:3140238

  4. Cytoplasmic sequestration of FUS/TLS associated with ALS alters histone marks through loss of nuclear protein arginine methyltransferase 1.

    PubMed

    Tibshirani, Michael; Tradewell, Miranda L; Mattina, Katie R; Minotti, Sandra; Yang, Wencheng; Zhou, Hongru; Strong, Michael J; Hayward, Lawrence J; Durham, Heather D

    2015-02-01

    Mutations in the RNA-binding protein FUS/TLS (FUS) have been linked to the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Although predominantly nuclear, this heterogenous nuclear ribonuclear protein (hnRNP) has multiple functions in RNA processing including intracellular trafficking. In ALS, mutant or wild-type (WT) FUS can form neuronal cytoplasmic inclusions. Asymmetric arginine methylation of FUS by the class 1 arginine methyltransferase, protein arginine methyltransferase 1 (PRMT1), regulates nucleocytoplasmic shuttling of FUS. In motor neurons of primary spinal cord cultures, redistribution of endogenous mouse and that of ectopically expressed WT or mutant human FUS to the cytoplasm led to nuclear depletion of PRMT1, abrogating methylation of its nuclear substrates. Specifically, hypomethylation of arginine 3 of histone 4 resulted in decreased acetylation of lysine 9/14 of histone 3 and transcriptional repression. Distribution of neuronal PRMT1 coincident with FUS also was detected in vivo in the spinal cord of FUS(R495X) transgenic mice. However, nuclear PRMT1 was not stable postmortem obviating meaningful evaluation of ALS autopsy cases. This study provides evidence for loss of PRMT1 function as a consequence of cytoplasmic accumulation of FUS in the pathogenesis of ALS, including changes in the histone code regulating gene transcription.

  5. Heterogeneity of normal prion protein in two- dimensional immunoblot: presence of various glycosylated and truncated forms.

    PubMed

    Pan, Tao; Li, Ruliang; Wong, Boon-Seng; Liu, Tong; Gambetti, Pierluigi; Sy, Man-Sun

    2002-06-01

    The common use of one-dimensional (1-D) immunoblot with a single monoclonal antibody (Mab) engenders the notion that the normal or cellular prion protein (PrP(C) ) comprises few and simple forms. In this study we used two-dimensional (2-D) immunoblot with a panel Mabs to various regions of the prion protein to demonstrate the complexity of the PrP(C) present in human brain. We distinguished over 50 immunoblot spots, each representing a distinct PrP(C) species based on combinations of different molecular weights and isoelectric points (pIs). The PrP(C) heterogeneity is due to the presence of a full-length and two major truncated forms as well as to the diversity of the glycans linked to most of these forms. The two major truncated forms result from distinct cleavage sites located at the N-terminus. In addition, enzymatic removal of sialic acid and lectin binding studies indicate that the glycans linked to the full-length and truncated PrP(C) forms differ in their structure and ratios of the glycoforms. The truncation of PrP(C) and the heterogeneity of the linked glycans may play a role in regulating PrP(C) function. Furthermore, the presence of relatively large quantities of different PrP(C) species may provide additional mechanisms by which the diversity of prion strains could be generated.

  6. Ligand heterogeneity of the cysteine protease binding protein family in the parasitic protist Entamoeba histolytica.

    PubMed

    Marumo, Konomi; Nakada-Tsukui, Kumiko; Tomii, Kentaro; Nozaki, Tomoyoshi

    2014-08-01

    Lysosomal soluble proteins are targeted to endosomes and lysosomes by specific receptors resident in the endoplasmic reticulum and/or the Golgi apparatus. The enteric protozoan parasite Entamoeba histolytica has a novel class of lysosomal targeting receptors, named the cysteine protease binding protein family (CPBF). Among 11 CPBFs (CPBF1-11), ligands for three members, CPBF1, CPBF6 and CPBF8, were previously shown to be cysteine proteases, α- and γ- amylases, and β-hexosaminidase and lysozymes, respectively. To further understand the heterogeneity of the ligands of CPBFs, we attempted to isolate and identify the ligands for other members of CPBFs, namely CPBF2, 3, 4, 5, 7, 9, 10 and 11, by immunoprecipitation and mass spectrometric analysis. We found that CPBF2 and CPBF10 bound to α-amylases while CPBF7 bound to β-hexosaminidases. It is intriguing that cysteine protease are exclusively recognised by CPBF1, whereas three α-amylases and β-hexosaminidases are redundantly recognised by three and two CPBFs, respectively. It was shown by bioinformatics analysis and phylogenetic reconstruction that each CPBF contains six prepeptidase carboxyl-terminal domains, and the domain configuration is evolutionarily conserved among CPBFs. Taken together, CPBFs with unique and conserved domain organisation have a remarkable ligand heterogeneity toward cysteine protease and carbohydrate degradation enzymes. Further structural studies are needed to elucidate the structural basis of the ligand specificity.

  7. Surface heterogeneity: a friend or foe of protein adsorption - insights from theoretical simulations.

    PubMed

    Penna, Matthew; Ley, Kamron; Maclaughlin, Shane; Yarovsky, Irene

    2016-10-06

    A lack in the detailed understanding of mechanisms through which proteins adsorb or are repelled at various solid/liquid interfaces limits the capacity to rationally design and produce more sophisticated surfaces with controlled protein adsorption in both biomedical and industrial settings. To date there are three main approaches to achieve anti biofouling efficacy, namely chemically adjusting the surface hydrophobicity and introducing various degrees of surface roughness, or a combination of both. More recently, surface nanostructuring has been shown to have an effect on protein adsorption. However, the current resolution of experimental techniques makes it difficult to investigate these three phase systems at the molecular level. In this molecular dynamics study we explore in all-atom detail the adsorption process of one of the most surface active proteins, EAS hydrophobin, known for its versatile ability to self-assemble on both hydrophobic and hydrophilic surfaces forming stable monolayers that facilitate further biofilm growth. We model the adsorption of this protein on organic ligand protected silica surfaces with varying degrees of chemical heterogeneity and roughness, including fully homogenous hydrophobic and hydrophilic surfaces for comparison. We present a detailed characterisation of the functionalised surface structure and dynamics for each of these systems, and the effect the ligands have on interfacial water, the adsorption process and conformational rearrangements of the protein. Results suggest that the ligand arrangement that produces the highest hydrophilic chain mobility and the lack of significant hydrophobic patches shows the most promising anti-fouling efficacy toward hydrophobin. However, the presence on the protein surface of a flexible loop with amphipathic character (the Cys3-Cys4 loop) is seen to facilitate EAS adsorption on all surfaces by enabling the protein to match the surface pattern.

  8. Protein Kinase C-{delta} mediates down-regulation of heterogeneous nuclear ribonucleoprotein K protein: involvement in apoptosis induction

    SciTech Connect

    Gao, Feng-Hou; Wu, Ying-Li; Zhao, Meng; Chen, Guo-Qiang

    2009-11-15

    We reported previously that NSC606985, a camptothecin analogue, induces apoptosis of acute myeloid leukemia (AML) cells through proteolytic activation of protein kinase C delta ({Delta}PKC-{delta}). By subcellular proteome analysis, heterogeneous nuclear ribonucleoprotein K (hnRNP K) was identified as being significantly down-regulated in NSC606985-treated leukemic NB4 cells. HnRNP K, a docking protein for DNA, RNA, and transcriptional or translational molecules, is implicated in a host of processes involving the regulation of gene expression. However, the molecular mechanisms of hnRNP K reduction and its roles during apoptosis are still not understood. In the present study, we found that, following the appearance of the {Delta}PKC-{delta}, hnRNP K protein was significantly down-regulated in NSC606985, doxorubicin, arsenic trioxide and ultraviolet-induced apoptosis. We further provided evidence that {Delta}PKC-{delta} mediated the down-regulation of hnRNP K protein during apoptosis: PKC-{delta} inhibitor could rescue the reduction of hnRNP K; hnRNP K failed to be decreased in PKC-{delta}-deficient apoptotic KG1a cells; conditional induction of {Delta}PKC-{delta} in U937T cells directly down-regulated hnRNP K protein. Moreover, the proteasome inhibitor also inhibited the down-regulation of hnRNP K protein by apoptosis inducer and the conditional expression of {Delta}PKC-{delta}. More intriguingly, the suppression of hnRNP K with siRNA transfection significantly induced apoptosis. To our knowledge, this is the first demonstration that proteolytically activated PKC-{delta} down-regulates hnRNP K protein in a proteasome-dependent manner, which plays an important role in apoptosis induction.

  9. Functional Heterogeneity of the UpaH Autotransporter Protein from Uropathogenic Escherichia coli

    PubMed Central

    Allsopp, Luke P.; Beloin, Christophe; Moriel, Danilo Gomes; Totsika, Makrina; Ghigo, Jean-Marc

    2012-01-01

    Uropathogenic Escherichia coli (UPEC) is responsible for the majority of urinary tract infections (UTI). To cause a UTI, UPEC must adhere to the epithelial cells of the urinary tract and overcome the shear flow forces of urine. This function is mediated primarily by fimbrial adhesins, which mediate specific attachment to host cell receptors. Another group of adhesins that contributes to UPEC-mediated UTI is autotransporter (AT) proteins. AT proteins possess a range of virulence properties, such as adherence, aggregation, invasion, and biofilm formation. One recently characterized AT protein of UPEC is UpaH, a large adhesin-involved-in-diffuse-adherence (AIDA-I)-type AT protein that contributes to biofilm formation and bladder colonization. In this study we characterized a series of naturally occurring variants of UpaH. We demonstrate that extensive sequence variation exists within the passenger-encoding domain of UpaH variants from different UPEC strains. This sequence variation is associated with functional heterogeneity with respect to the ability of UpaH to mediate biofilm formation. In contrast, all of the UpaH variants examined retained a conserved ability to mediate binding to extracellular matrix (ECM) proteins. Bioinformatic analysis of the UpaH passenger domain identified a conserved region (UpaHCR) and a hydrophobic region (UpaHHR). Deletion of these domains reduced biofilm formation but not the binding to ECM proteins. Despite variation in the upaH sequence, the transcription of upaH was repressed by a conserved mechanism involving the global regulator H-NS, and mutation of the hns gene relieved this repression. Overall, our findings shed new light on the regulation and functions of the UpaH AT protein. PMID:22904291

  10. Protein and gene expression characteristics of heterogeneous nuclear ribonucleoprotein H1 in esophageal squamous cell carcinoma

    PubMed Central

    Sun, Yu-Lin; Liu, Fei; Liu, Fang; Zhao, Xiao-Hang

    2016-01-01

    AIM To investigate the expression characteristics of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) mRNA and protein in cell lines and tissues of esophageal squamous cell carcinoma (ESCC). METHODS Western blotting was used to assess the expression of HNRNPH1 protein in seven ESCC cell lines and 30 paired fresh tissue specimens. The subcellular localization of HNRNPH1 was determined by immunofluorescence in ESCC cells. The RNA sequencing data from 87 patients with ESCC were obtained from the cancer genome atlas (TCGA), and the expression and clinical characteristics analysis of different transcript variants of HNRNPH1 were evaluated in this dataset. In addition, immunohistochemistry was carried out to detect the expression of HNRNPH1 protein in 125 patients. RESULTS The expression of HNRNPH1 protein varied across different ESCC cell lines. It was exclusively restricted to the nucleus of the ESCC cells. There are two transcript variants of the HNRNPH1 gene. Variant 1 was constitutively expressed, and its expression did not change during tumorigenesis. In contrast, levels of variant 2 were low in non-tumorous tissues and were dramatically increased in ESCC (P = 0.0026). The high levels of variant 2 were associated with poorer differentiated tumors (P = 0.0287). Furthermore, in paired fresh tissue specimens, HNRNPH1 protein was overexpressed in 73.3% (22/30) of neoplastic tissues. HNRNPH1 was significantly upregulated in ESCC, with strong staining in 43.2% (54/125) of tumor tissues and 22.4% (28/125) of matched non-cancerous tissues (P = 0.0005). Positive HNRNPH1 expression was significantly associated with poor tumor differentiation degree (P = 0.0337). CONCLUSION The different alternative transcript variants of HNRNPH1 exhibited different expression changes during tumorigenesis. Its mRNA and protein were overexpressed in ESCC and associated with poorer differentiation of tumor cells. These findings highlight the potential of HNRNPH1 in the therapy and diagnosis

  11. Molecular heterogeneity in deficiency of complement protein C2 type I.

    PubMed Central

    Wang, X; Circolo, A; Lokki, M L; Shackelford, P G; Wetsel, R A; Colten, H R

    1998-01-01

    Deficiency of the complement protein C2 (C2D), one of the most common genetic deficiencies of the complement system, is associated with rheumatological disorders and increased susceptibility to infection. Two types of C2D have been recognized, each in the context of specific major histocompatibility complex (MHC) haplotypes; type I, a deletion, frameshift and premature stop codon resulting in absence of detectable C2 protein synthesis, and type II, missense mutations resulting in a block in secretion of C2 proteins. Analysis of C2 expression in a child with C2 deficiency, a MHC haplotype different from those associated with type I or II C2D, and recurrent infections revealed additional molecular heterogeneity among C2 deficient patients. No detectable C2 protein was synthesized in the child's fibroblasts under conditions supporting C2 synthesis and secretion in normals and the child's C2 mRNA was reduced to 42% of normal. Nucleotide sequencing of RT-PCR fibroblast mRNA and genomic DNA revealed a type I C2 deficiency (28 base-pair deletion) on one allele and a previously unrecognized two base-pair deletion in exon 2 on the other. Expression of the closely linked factor B gene was markedly decreased (Bf mRNA 25% of normal), though Bf was up-regulated appropriately by interferon-gamma and the flanking sequence containing the Bf promoter was normal in this C2-deficient patient. Moreover, the concentration of Bf protein was normal in the patient's plasma. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:9616367

  12. Heterogeneous Expression of the Core Circadian Clock Proteins among Neuronal Cell Types in Mouse Retina

    PubMed Central

    Liu, Xiaoqin; Zhang, Zhijing; Ribelayga, Christophe P.

    2012-01-01

    Circadian rhythms in metabolism, physiology, and behavior originate from cell-autonomous circadian clocks located in many organs and structures throughout the body and that share a common molecular mechanism based on the clock genes and their protein products. In the mammalian neural retina, despite evidence supporting the presence of several circadian clocks regulating many facets of retinal physiology and function, the exact cellular location and genetic signature of the retinal clock cells remain largely unknown. Here we examined the expression of the core circadian clock proteins CLOCK, BMAL1, NPAS2, PERIOD 1(PER1), PERIOD 2 (PER2), and CRYPTOCHROME2 (CRY2) in identified neurons of the mouse retina during daily and circadian cycles. We found concurrent clock protein expression in most retinal neurons, including cone photoreceptors, dopaminergic amacrine cells, and melanopsin-expressing intrinsically photosensitive ganglion cells. Remarkably, diurnal and circadian rhythms of expression of all clock proteins were observed in the cones whereas only CRY2 expression was found to be rhythmic in the dopaminergic amacrine cells. Only a low level of expression of the clock proteins was detected in the rods at any time of the daily or circadian cycle. Our observations provide evidence that cones and not rods are cell-autonomous circadian clocks and reveal an important disparity in the expression of the core clock components among neuronal cell types. We propose that the overall temporal architecture of the mammalian retina does not result from the synchronous activity of pervasive identical clocks but rather reflects the cellular and regional heterogeneity in clock function within retinal tissue. PMID:23189207

  13. Regional heterogeneity of cellular prion protein isoforms in the mouse brain.

    PubMed

    Beringue, Vincent; Mallinson, Gary; Kaisar, Maria; Tayebi, Mourad; Sattar, Zahid; Jackson, Graham; Anstee, David; Collinge, John; Hawke, Simon

    2003-09-01

    Prion diseases are a group of invariably fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease in humans, scrapie in sheep and goats, and bovine spongiform encephalopathy in cattle. The infectious agent or prion is largely composed of an abnormal isoform (PrPSc) of a host encoded normal cellular protein (PrPc). The conversion of PrPc to PrPSc is a dynamic process and, for reasons that are not clear, the distribution of spongiform change and PrPSc deposition varies among prion strains. An obvious explanation for this would be that the transformation efficiency in any given brain region depends on favourable interactions between conformations of PrPc and the prion strain being propagated within it. However, identification of specific PrPc conformations has until now been hampered by a lack of suitable panels of antibodies that discriminate PrPc subspecies under native conditions. In this study, we show that monoclonal antibodies raised against recombinant human prion protein folded into alpha or beta conformations exhibit striking heterogeneity in their specificity for truncations and glycoforms of mouse brain PrPc. We then show that some of these PrPc isoforms are expressed differentially in certain mouse brain regions. This suggests that variation in the expression of PrPc conformations in different brain regions may dictate the pattern of PrPSc deposition and vacuolation, characteristic for different prion strains.

  14. Probing the Heterogeneity of Protein Kinase Activation in Cells by Super-resolution Microscopy

    PubMed Central

    2016-01-01

    Heterogeneity of mitogen-activated protein kinase (MAPK) activation in genetically identical cells, which occurs in response to epidermal growth factor receptor (EGFR) signaling, remains poorly understood. MAPK cascades integrate signals emanating from different EGFR spatial locations, including the plasma membrane and endocytic compartment. We previously hypothesized that in EGF-stimulated cells the MAPK phosphorylation (pMAPK) level and activity are largely determined by the spatial organization of the EGFR clusters within the cell. For experimental testing of this hypothesis, we used super-resolution microscopy to define EGFR clusters by receptor numbers (N) and average intracluster distances (d). From these data, we predicted the extent of pMAPK with 85% accuracy on a cell-to-cell basis with control data returning 54% accuracy (P < 0.001). For comparison, the prediction accuracy was only 61% (P = 0.382) when the diffraction-limited averaged fluorescence intensity/cluster was used. Large clusters (N ≥ 3) with d > 50 nm were most predictive for pMAPK level in cells. Electron microscopy revealed that these large clusters were primarily localized to the limiting membrane of multivesicular bodies (MVB). Many tighter packed dimers/multimers (d < 50 nm) were found on intraluminal vesicles within MVBs, where they were unlikely to activate MAPK because of the physical separation. Our results suggest that cell-to-cell differences in N and d contain crucial information to predict EGFR-activated cellular pMAPK levels and explain pMAPK heterogeneity in isogenic cells. PMID:27768850

  15. Resolving breast cancer heterogeneity by searching reliable protein cancer biomarkers in the breast fluid secretome

    PubMed Central

    2013-01-01

    Background One of the major goals in cancer research is to find and evaluate the early presence of biomarkers in human fluids and tissues. To resolve the complex cell heterogeneity of a tumor mass, it will be useful to characterize the intricate biomolecular composition of tumor microenvironment (the so called cancer secretome), validating secreted proteins as early biomarkers of cancer initiation and progression. This approach is not broadly applicable because of the paucity of well validated and FDA-approved biomarkers and because most of the candidate biomarkers are mainly organ-specific rather than tumor-specific. For these reasons, there is an urgent need to identify and validate a panel of biomarker combinations for early detection of human tumors. This is especially important for breast cancer, the cancer spread most worldwide among women. It is well known that patients with early diagnosed breast cancer live longer, require less extensive treatment and fare better than patients with more aggressive and/or advanced disease. Results In the frame of searching breast cancer biomarkers (especially using nipple aspirate fluid mirroring breast microenvironment), studies have highlighted an optimal combination of well-known biomarkers: uPA + PAI-1 + TF. When individually investigated they did not show perfect accuracy in predicting the presence of breast cancer, whereas the triple combination has been demonstrated to be highly predictive of pre-cancer and/or cancerous conditions, approaching 97-100% accuracy. Conclusion Despite the heterogeneous composition of breast cancer and the difficulties to find specific breast cancer biomolecules, the noninvasive analysis of the nipple aspirate fluid secretome may significantly improve the discovery of promising biomarkers, helping also the differentiation among benign and invasive breast diseases, opening new frontiers in early oncoproteomics. PMID:23849048

  16. Heterogenic expression of genes encoding secreted proteins at the periphery of Aspergillus niger colonies.

    PubMed

    Vinck, Arman; de Bekker, Charissa; Ossin, Adam; Ohm, Robin A; de Vries, Ronald P; Wösten, Han A B

    2011-01-01

    Colonization of a substrate by fungi starts with the invasion of exploring hyphae. These hyphae secrete enzymes that degrade the organic material into small molecules that can be taken up by the fungus to serve as nutrients. We previously showed that only part of the exploring hyphae of Aspergillus niger highly express the glucoamylase gene glaA. This was an unexpected finding since all exploring hyphae are exposed to the same environmental conditions. Using GFP as a reporter, we here demonstrate that the acid amylase gene aamA, the α-glucuronidase gene aguA, and the feruloyl esterase gene faeA of A. niger are also subject to heterogenic expression within the exploring mycelium. Coexpression studies using GFP and dTomato as reporters showed that hyphae that highly express one of these genes also highly express the other genes encoding secreted proteins. Moreover, these hyphae also highly express the amylolytic regulatory gene amyR, and the glyceraldehyde-3-phosphate dehydrogenase gene gpdA. In situ hybridization demonstrated that the high expressers are characterized by a high 18S rRNA content. Taken together, it is concluded that two subpopulations of hyphae can be distinguished within the exploring mycelium of A. niger. The experimental data indicate that these subpopulations differ in their transcriptional and translational activity.

  17. Heterogeneity of elderly depression: increased risk of Alzheimer's disease and Aβ protein metabolism.

    PubMed

    Namekawa, Yuki; Baba, Hajime; Maeshima, Hitoshi; Nakano, Yoshiyuki; Satomura, Emi; Takebayashi, Naoko; Nomoto, Hiroshi; Suzuki, Toshihito; Arai, Heii

    2013-06-03

    Epidemiological studies have proposed that depression may increase the risk for Alzheimer's disease (AD), even in patients with early-onset depression. Although metabolism of amyloid β protein (Aβ) in elderly depression received attention in terms of their correlation, there is a serious heterogeneity in elderly depression in terms of age at onset of depression. Moreover, it is unknown whether early-onset major depressive disorder (MDD) has a long-term effect on the involvement of Aβ metabolism and later development of AD. Thus, we evaluated serum Aβ40 and Aβ42 levels, the Aβ40/Aβ42 ratio in 89 elderly (≥60 years of age) inpatients with MDD and 81 age-matched healthy controls, and compared them among patients with early-onset (<60 years) and late-onset (≥60years) MDD and controls. The results showed that the serum Aβ40/Aβ42 ratio was significantly higher in patients with both early- and late-onset MDD than in controls (early-onset, p=0.010; late-onset, p=0.043), and it is of great interest that the serum Aβ40/Aβ42 ratio was negatively correlated with the age at MDD onset (R=-0.201, p=0.032). These results suggest that an earlier onset of MDD may have a more serious abnormality in Aβ metabolism, possibly explaining a biological mechanism underlying the link between depression and AD.

  18. Heterogeneity in spike protein genes of porcine epidemic diarrhea viruses isolated in Korea.

    PubMed

    Lee, Dong-Kyu; Park, Choi-Kyu; Kim, Seong-Hee; Lee, Changhee

    2010-05-01

    Porcine epidemic diarrhea virus (PEDV) has plagued the domestic swine industry in Korea causing significant economic impacts on pig production nationwide. In the present study, we determined the complete nucleotide sequences of the spike (S) glycoprotein genes of seven Korean PEDV isolates. The entire S genes of all isolates were found to be nine nucleotides longer in length than other PEDV reference strains. This size difference was due to the combined presence of notable 15 bp insertion and 6 bp deletion within the N-terminal region of the S1 domain of the Korean isolates. In addition, the largest number of amino acid variations was accumulated in the S1 N-terminal region, leading to the presence of hypervariability in the isolates. Sequence comparisons at the peptide level of the S proteins revealed that all seven Korean isolates shared diverse similarities ranging from a 93.6% to 99.6% identity with each other but exhibited a 92.2% to 93.7% identity with other reference strains. Collectively, the sequence analysis data indicate the diversity of the PEDV isolates currently prevalent in Korea that represents a heterogeneous group. Phylogenetic analyses showed two separate clusters, in which all Korean field isolates were grouped together in the second cluster (group 2). The results indicate that prevailing isolates in Korea are phylogenetically more closely related to each other rather than other reference strains. Interestingly, the tree topology based on the nucleotide sequences representing the S1 domain or the S1 N-terminal region most nearly resembled the full S gene-based phylogenetic tree. Therefore, our data implicates a potential usefulness of the partial S protein gene including the N-terminal region in unveiling genetic relatedness of PEDV isolates.

  19. Heterogeneity of high-mobility-group protein 2. Enrichment of a rapidly migrating form in testis.

    PubMed Central

    Bucci, L R; Brock, W A; Meistrich, M L

    1985-01-01

    A determination of the absolute amounts of high-mobility-group proteins 1 and 2 (HMG1 and HMG2) in rat tissues demonstrated that amounts of HMG2 were low in non-proliferating tissues, somewhat higher in proliferating and lymphoid tissues, but were extremely elevated in the testis. This increase was due to a germ-cell-specific form of HMG2 with increased mobility relative to somatic HMG2 on acid/urea/polyacrylamide-gel electrophoresis. To determine if the findings in the rat were a general feature of spermatogenesis, testis (germinal), spleen (lymphoid), and liver (non-proliferating) tissues from various vertebrate species were examined for their relative amounts of HMG1 and HMG2, and for HMG2 heterogeneity. Bull, chimpanzee, cynomologus monkey, dog, gopher, guinea pig, hamster, mouse, opossum, rabbit, rat, rhesus monkey, squirrel and toad (Xenopus) tissues were analysed. Nearly all species showed relatively high contents of HMG2 in testis tissue, whereas HMG1 contents were similar in all species and tissues. Ten of thirteen species showed a rapidly migrating HMG2 subtype in testis tissue, separable by acid/urea/polyacrylamide-gel electrophoresis. Xenopus, which lacks HMG2 in somatic tissues, showed an HMG2-like protein in testis tissue. Although the rapidly migrating HMG2 subtype in species other than rat was not testis-specific, it was always enriched in the testis. This study indicates that increased amounts of HMG2 and the enrichment of a rapidly migrating HMG2 subtype are general features of spermatogenic cells. Images Fig. 1. Fig. 2. Fig. 3. PMID:4038257

  20. Influences of heterogeneous native contact energy and many-body interactions on the prediction of protein folding mechanisms.

    PubMed

    Zhang, Zhuqing; Ouyang, Yanhua; Chen, Tao

    2016-11-16

    Since single-point mutant perturbation has been used to probe protein folding mechanisms in experiments, the ϕ-value has become a critical parameter to infer the transition state (TS) for two-state proteins. Experimentally, large scale analysis has shown a nearly single uniform ϕ-value with normally distributed error from 24 different proteins; moreover, in zero stability conditions, the intrinsic variable ϕ(0) is around 0.36. To explore how and to what extent theoretical models can capture experimental phenomena, we here use structure-based explicit chain coarse-grained models to investigate the influence of single-point mutant perturbation on protein folding for single domain two-state proteins. Our results indicate that uniform, additive contact energetic interactions cannot predict experimental Brønsted plots well. Those points deviate largely from the main data sets in Brønsted plots, are mostly hydrophobic, and are located in N- and C-terminal contacting regions. Heterogenous contact energy, which is dependent on sequence separation, can narrow the point dispersion in a Brønsted plot. Moreover, we demonstrate that combining many-body interactions with heterogeneous native contact energy can present mean ϕ-values consistent with experimental findings, with a comparable distributed error. This indicates that for more accurate elucidation of protein folding mechanisms by residue-level structure-based models, these elements should be considered.

  1. Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential.

    PubMed

    Mitchell, Rod T; E Camacho-Moll, Maria; Macdonald, Joni; Anderson, Richard A; Kelnar, Christopher J H; O'Donnell, Marie; Sharpe, Richard M; Smith, Lee B; Grigor, Ken M; Wallace, W Hamish B; Stoop, Hans; Wolffenbuttel, Katja P; Donat, Roland; Saunders, Philippa Tk; Looijenga, Leendert Hj

    2014-09-01

    Testicular germ cell cancer develops from premalignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4(+)/MAGEA4(-)) into pre-spermatogonia (OCT4(-)/MAGEA4(+)). Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described, however the importance of these subpopulations in terms of invasive potential has not been reported. We hypothesized that cells expressing an immature (OCT4(+)/MAGEA4(-)) germ cell profile would exhibit an increased proliferation rate compared with those with a mature profile (OCT4(+)/MAGEA4(+)). Therefore, we performed triple immunofluorescence and stereology to quantify the different intratubular germ cell neoplasia cell subpopulations, based on expression of germ cell (OCT4, PLAP, AP2γ, MAGEA4, VASA) and proliferation (Ki67) markers, in testis sections from patients with preinvasive disease, seminoma, and non-seminoma. We compared these subpopulations with normal human fetal testis and with seminoma cells. Heterogeneity of protein expression was demonstrated in intratubular germ cell neoplasia cells with respect to gonocyte and spermatogonial markers. It included an embryonic/fetal germ cell subpopulation lacking expression of the definitive intratubular germ cell neoplasia marker OCT4, that did not correspond to a physiological (fetal) germ cell subpopulation. OCT4(+)/MAGEA4(-) cells showed a significantly increased rate of proliferation compared with the OCT4(+)/MAGEA4(+) population (12.8 versus 3.4%, P<0.0001) irrespective of histological tumor type, reflected in the predominance of OCT4(+)/MAGEA4(-) cells in the invasive tumor component. Surprisingly, OCT4(+)/MAGEA4(-) cells in patients with preinvasive disease showed significantly higher proliferation compared to those with seminoma or non-seminoma (18.1 versus 10.2 versus 7.2%, P<0.05, respectively). In conclusion, this study

  2. Monoclonal antibodies specific for adenovirus early region 1A proteins: extensive heterogeneity in early region 1A products.

    PubMed Central

    Harlow, E; Franza, B R; Schley, C

    1985-01-01

    Hybridomas secreting monoclonal antibodies specific for the adenovirus early region 1A (E1A) proteins were prepared from BALB/c mice immunized with a bacterial trpE-E1A fusion protein. This protein is encoded by a hybrid gene that joins a portion of the Escherichia coli trpE gene and a cDNA copy of the E1A 13S mRNA (Spindler et al., J. Virol. 49:132-141, 1984). Eighty-three hybridomas that secrete antibodies which recognize the immunogen were isolated and single cell cloned. Twenty-nine of these antibodies are specific for the E1A portion of the fusion protein. Only 12 of the monoclonal antibodies can efficiently immunoprecipitate E1A polypeptides from detergent lysates of infected cells. E1A polypeptides were analyzed on one-dimensional, sodium dodecyl sulfate-polyacrylamide gels and two-dimensional, isoelectric focusing polyacrylamide gels. The E1A proteins that are specifically immunoprecipitated by the monoclonal antibodies are heterogeneous in size and charge and can be resolved into approximately 60 polypeptide species. This heterogeneity is due not only to synthesis from multiple E1A mRNAs, but also at least in part to post-translational modification. Several of the monoclonal antibodies divide the E1A polypeptides into immunological subclasses based on the ability of the antibodies to bind to the antigen. In particular, two of the monoclonal antibodies bind to the polypeptides synthesized from the 13S E1A mRNA, but not to other E1A proteins. Images PMID:3894685

  3. The Impact of Heterogeneity and Dark Acceptor States on FRET: Implications for Using Fluorescent Protein Donors and Acceptors

    PubMed Central

    Vogel, Steven S.; Nguyen, Tuan A.; van der Meer, B. Wieb; Blank, Paul S.

    2012-01-01

    Förster resonance energy transfer (FRET) microscopy is widely used to study protein interactions in living cells. Typically, spectral variants of the Green Fluorescent Protein (FPs) are incorporated into proteins expressed in cells, and FRET between donor and acceptor FPs is assayed. As appreciable FRET occurs only when donors and acceptors are within 10 nm of each other, the presence of FRET can be indicative of aggregation that may denote association of interacting species. By monitoring the excited-state (fluorescence) decay of the donor in the presence and absence of acceptors, dual-component decay analysis has been used to reveal the fraction of donors that are FRET positive (i.e., in aggregates)._However, control experiments using constructs containing both a donor and an acceptor FP on the same protein repeatedly indicate that a large fraction of these donors are FRET negative, thus rendering the interpretation of dual-component analysis for aggregates between separately donor-containing and acceptor-containing proteins problematic. Using Monte-Carlo simulations and analytical expressions, two possible sources for such anomalous behavior are explored: 1) conformational heterogeneity of the proteins, such that variations in the distance separating donor and acceptor FPs and/or their relative orientations persist on time-scales long in comparison with the excited-state lifetime, and 2) FP dark states. PMID:23152925

  4. Surfactant protein-C chromatin-bound green fluorescence protein reporter mice reveal heterogeneity of surfactant protein C-expressing lung cells.

    PubMed

    Lee, Joo-Hyeon; Kim, Jonghwan; Gludish, David; Roach, Rebecca R; Saunders, Arven H; Barrios, Juliana; Woo, Andrew Jonghan; Chen, Huaiyong; Conner, David A; Fujiwara, Yuko; Stripp, Barry R; Kim, Carla F

    2013-03-01

    The regeneration of alveolar epithelial cells is a critical aspect of alveolar reorganization after lung injury. Although alveolar Type II (AT2) cells have been described as progenitor cells for alveolar epithelia, more remains to be understood about how their progenitor cell properties are regulated. A nuclear, chromatin-bound green fluorescence protein reporter (H2B-GFP) was driven from the murine surfactant protein-C (SPC) promoter to generate SPC H2B-GFP transgenic mice. The SPC H2B-GFP allele allowed the FACS-based enrichment and gene expression profiling of AT2 cells. Approximately 97% of AT2 cells were GFP-labeled on Postnatal Day 1, and the percentage of GFP-labeled AT2 cells decreased to approximately 63% at Postnatal Week 8. Isolated young adult SPC H2B-GFP(+) cells displayed proliferation, differentiation, and self-renewal capacity in the presence of lung fibroblasts in a Matrigel-based three-dimensional culture system. Heterogeneity within the GFP(+) population was revealed, because cells with distinct alveolar and bronchiolar gene expression arose in three-dimensional cultures. CD74, a surface marker highly enriched on GFP(+) cells, was identified as a positive selection marker, providing 3-fold enrichment for AT2 cells. In vivo, GFP expression was induced within other epithelial cell types during maturation of the distal lung. The utility of the SPC H2B-GFP murine model for the identification of AT2 cells was greatest in early postnatal lungs and more limited with age, when some discordance between SPC and GFP expression was observed. In adult mice, this allele may allow for the enrichment and future characterization of other SPC-expressing alveolar and bronchiolar cells, including putative stem/progenitor cell populations.

  5. Heterogenous turnover of sperm and seminal vesicle proteins in the mouse revealed by dynamic metabolic labeling.

    PubMed

    Claydon, Amy J; Ramm, Steven A; Pennington, Andrea; Hurst, Jane L; Stockley, Paula; Beynon, Robert

    2012-06-01

    Plasticity in ejaculate composition is predicted as an adaptive response to the evolutionary selective pressure of sperm competition. However, to respond rapidly to local competitive conditions requires dynamic modulation in the production of functionally relevant ejaculate proteins. Here we combine metabolic labeling of proteins with proteomics to explore the opportunity for such modulation within mammalian ejaculates. We assessed the rate at which proteins are synthesized and incorporated in the seminal vesicles of male house mice (Mus musculus domesticus), where major seminal fluid proteins with potential roles in sperm competition are produced. We compared rates of protein turnover in the seminal vesicle with those during spermatogenesis, the timing of which is well known in mice. The subjects were fed a diet containing deuterated valine ([(2)H(8)]valine) for up to 35 days, and the incorporation of dietary-labeled amino acid into seminal vesicle- or sperm-specific proteins was assessed by liquid chromatography-mass spectrometry of samples recovered from the seminal vesicle lumen and cauda epididymis, respectively. Analyses of epididymal contents were consistent with the known duration of spermatogenesis and sperm maturation in this species and in addition revealed evidence for a subset of epididymal proteins subject to rapid turnover. For seminal vesicle proteins, incorporation of the stable isotope was evident from day 2 of labeling, reaching a plateau of labeling by day 24. Hence, even in the absence of copulation, the seminal vesicle proteins and certain epididymal proteins demonstrate considerable turnover, a response that is consonant with the capacity to rapidly modulate protein production. These techniques can now be used to assess the extent of phenotypic plasticity in mammalian ejaculate production and allocation according to social and environmental cues of sperm competition.

  6. Characterization and molecular basis of heterogeneity of the African swine fever virus envelope protein p54.

    PubMed Central

    Rodriguez, F; Alcaraz, C; Eiras, A; Yáñez, R J; Rodriguez, J M; Alonso, C; Rodriguez, J F; Escribano, J M

    1994-01-01

    It has been reported that the propagation of African swine fever virus (ASFV) in cell culture generates viral subpopulations differing in protein p54 (C. Alcaraz, A. Brun, F. Ruiz-Gonzalvo, and J. M. Escribano, Virus Res. 23:173-182, 1992). A recombinant bacteriophage expressing a 328-bp fragment of the p54 gene was selected in a lambda phage expression library of ASFV genomic fragments by immunoscreening with antibodies against p54 protein. The sequence of this recombinant phage allowed the location of the p54 gene in the EcoRI E fragment of the ASFV genome. Nucleotide sequence obtained from this fragment revealed an open reading frame encoding a protein of 183 amino acids with a calculated molecular weight of 19,861. This protein contains a transmembrane domain and a Gly-Gly-X motif, a recognition sequence for protein processing of several ASFV structural proteins. In addition, two direct tandem repetitions were also found within this open reading frame. Further characterization of the transcription and gene product revealed that the p54 gene is translated from a late mRNA and the protein is incorporated to the external membrane of the virus particle. A comparison of the nucleotide sequence of the p54 gene carried by two virulent ASFV strains (E70 and E75) with that obtained from virus Ba71V showed 100% similarity. However, when p54 genes from viral clones generated by cell culture passage and coding for p54 proteins with different electrophoretic mobility were sequenced, they showed changes in the number of copies of a 12-nucleotide sequence repeat. These changes produce alterations in the number of copies of the amino acid sequence Pro-Ala-Ala-Ala present in p54, resulting in stepwise modifications in the molecular weight of the protein. These duplications and deletions of a tandem repeat sequence array within a protein coding region constitute a novel mechanism of genetic diversification in ASFV. Images PMID:7933107

  7. A Novel Heterogeneous Nuclear Ribonucleoprotein-Like Protein Interacts with NS1 of the Minute Virus of Mice

    PubMed Central

    Harris, Colin E.; Boden, Richard A.; Astell, Caroline R.

    1999-01-01

    NS1, the major nonstructural parvovirus protein of the minute virus of mice, is a multifunctional protein responsible for several aspects of viral replication. NS1 transactivates the P38 promoter (used to express the structural proteins), as well as its own strong promoter, P4. To study the mechanism of activation and to map regions of NS1 responsible for transactivation, NS1 and various deletions of NS1 were cloned in frame with the GAL4DB and cotransfected into COS-7 and LA9 cells with a synthetic GAL4-responsive reporter plasmid. These studies showed NS1 can directly activate transcription through its 129 carboxyl-terminal amino acid residues. Any deletion from this region of the C terminus, even as few as 8 amino acids, completely abolishes transactivation. A yeast two-hybrid system used to identify protein-protein interactions demonstrated that NS1 is able to dimerize when expressed in yeast cells. However, only an almost complete NS11–638 bait was able to interact with the full-length NS1. A two-hybrid screen identified a HeLa cell cDNA clone (NS1-associated protein 1 [NSAP1]) that interacts with NS11–276 and NS11–638. An additional sequence was predicted from human EST (expressed sequence tag) data, and the cDNA was estimated to be at least 2,221 bp long, potentially encoding a 562-amino-acid protein product. A polyclonal antibody raised to a synthetic peptide within NSAP1 recognizes an ∼65-kDa cellular protein. This NSAP1 cDNA has not previously been characterized, but the predicted protein sequence is 80% identical to the recently identified heterogeneous nuclear ribonucleoprotein (hnRNP) R (W. Hassfeld et al., Nucleic Acids Res. 26:439–445, 1998). NSAP1 contains four ribonucleoprotein domains, as well as a highly repetitive C-terminal region. A closely related mouse cDNA (deduced from murine EST data) encodes a protein with only a single amino acid residue change from the human protein. NSAP1 is predicted to be a 65-kDa polynucleotide binding

  8. Heterogeneous nuclear ribonucleoprotein A1 regulates rhythmic synthesis of mouse Nfil3 protein via IRES-mediated translation.

    PubMed

    Kim, Hyo-Jin; Lee, Hwa-Rim; Seo, Ji-Young; Ryu, Hye Guk; Lee, Kyung-Ha; Kim, Do-Yeon; Kim, Kyong-Tai

    2017-02-21

    Nuclear factor, interleukin 3, regulated (Nfil3, also known as E4 Promoter-Binding Protein 4 (E4BP4)) protein is a transcription factor that binds to DNA and generally represses target gene expression. In the circadian clock system, Nfil3 binds to a D-box element residing in the promoter of clock genes and contributes to their robust oscillation. Here, we show that the 5'-untranslated region (5'-UTR) of Nfil3 mRNA contains an internal ribosome entry site (IRES) and that IRES-mediated translation occurs in a phase-dependent manner. We demonstrate that heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) binds to a specific region of Nfil3 mRNA and regulates IRES-mediated translation. Knockdown of hnRNP A1 almost completely abolishes protein oscillation without affecting mRNA oscillation. Moreover, we observe that intracellular calcium levels, which are closely related to bone formation, depend on Nfil3 levels in osteoblast cell lines. We suggest that the 5'-UTR mediated cap-independent translation of Nfil3 mRNA contributes to the rhythmic expression of Nfil3 by interacting with the RNA binding protein hnRNP A1. These data provide new evidence that the posttranscriptional regulation of clock gene expression is important during bone metabolism.

  9. Respiratory chain protein turnover rates in mice are highly heterogeneous but strikingly conserved across tissues, ages, and treatments.

    PubMed

    Karunadharma, Pabalu P; Basisty, Nathan; Chiao, Ying Ann; Dai, Dao-Fu; Drake, Rachel; Levy, Nick; Koh, William J; Emond, Mary J; Kruse, Shane; Marcinek, David; Maccoss, Michael J; Rabinovitch, Peter S

    2015-08-01

    The mitochondrial respiratory chain (RC) produces most of the cellular ATP and requires strict quality-control mechanisms. To examine RC subunit proteostasis in vivo, we measured RC protein half-lives (HLs) in mice by liquid chromatography-tandem mass spectrometry with metabolic [(2)H3]-leucine heavy isotope labeling under divergent conditions. We studied 7 tissues/fractions of young and old mice on control diet or one of 2 diet regimens (caloric restriction or rapamycin) that altered protein turnover (42 conditions in total). We observed a 6.5-fold difference in mean HL across tissues and an 11.5-fold difference across all conditions. Normalization to the mean HL of each condition showed that relative HLs were conserved across conditions (Spearman's ρ = 0.57; P < 10(-4)), but were highly heterogeneous between subunits, with a 7.3-fold mean range overall, and a 2.2- to 4.6-fold range within each complex. To identify factors regulating this conserved distribution, we performed statistical analyses to study the correlation of HLs to the properties of the subunits. HLs significantly correlated with localization within the mitochondria, evolutionary origin, location of protein-encoding, and ubiquitination levels. These findings challenge the notion that all subunits in a complex turnover at comparable rates and suggest that there are common rules governing the differential proteolysis of RC protein subunits under divergent cellular conditions.

  10. Heterogeneous nuclear ribonucleoprotein A1 regulates rhythmic synthesis of mouse Nfil3 protein via IRES-mediated translation

    PubMed Central

    Kim, Hyo-Jin; Lee, Hwa-Rim; Seo, Ji-Young; Ryu, Hye Guk; Lee, Kyung-Ha; Kim, Do-Yeon; Kim, Kyong-Tai

    2017-01-01

    Nuclear factor, interleukin 3, regulated (Nfil3, also known as E4 Promoter-Binding Protein 4 (E4BP4)) protein is a transcription factor that binds to DNA and generally represses target gene expression. In the circadian clock system, Nfil3 binds to a D-box element residing in the promoter of clock genes and contributes to their robust oscillation. Here, we show that the 5′-untranslated region (5′-UTR) of Nfil3 mRNA contains an internal ribosome entry site (IRES) and that IRES-mediated translation occurs in a phase-dependent manner. We demonstrate that heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) binds to a specific region of Nfil3 mRNA and regulates IRES-mediated translation. Knockdown of hnRNP A1 almost completely abolishes protein oscillation without affecting mRNA oscillation. Moreover, we observe that intracellular calcium levels, which are closely related to bone formation, depend on Nfil3 levels in osteoblast cell lines. We suggest that the 5′-UTR mediated cap-independent translation of Nfil3 mRNA contributes to the rhythmic expression of Nfil3 by interacting with the RNA binding protein hnRNP A1. These data provide new evidence that the posttranscriptional regulation of clock gene expression is important during bone metabolism. PMID:28220845

  11. The A1 and A1B proteins of heterogeneous nuclear ribonucleoparticles modulate 5' splice site selection in vivo.

    PubMed Central

    Yang, X; Bani, M R; Lu, S J; Rowan, S; Ben-David, Y; Chabot, B

    1994-01-01

    Recent in vitro results suggest that the heterogeneous nuclear ribonucleoparticle (hnRNP) A1 protein modulates alternative splicing by favoring distal 5' splice site (5'SS) selection and exon skipping. We used a mouse erythroleukemia (MEL) cell line (CB3C7) deficient in the expression of hnRNP A1 to test whether variations in hnRNP A1 and AlB protein levels affected alternative splicing in vivo. In contrast to A1-expressing MEL cell lines, CB3C7 cells preferentially selected the proximal 13S and 12S 5'SS on the adenovirus E1A pre-mRNA. Transiently expressing the A1 or A1B cDNA in CB3C7 cells shifted 5'SS selection toward the more distal 9S donor site. A1 protein synthesis was required for this effect since the expression of a mutated A1 cDNA did not affect 5'SS selection. These results demonstrate that in vivo variations in hnRNP A1 protein levels can influence 5'SS selection. Images PMID:8041722

  12. Experiment and theory for heterogeneous nucleation of protein crystals in a porous medium.

    PubMed

    Chayen, Naomi E; Saridakis, Emmanuel; Sear, Richard P

    2006-01-17

    The determination of high-resolution structures of proteins requires crystals of suitable quality. Because of the new impetus given to structural biology by structural genomics/proteomics, the problem of crystallizing proteins is becoming increasingly acute. There is therefore an urgent requirement for the development of new efficient methods to aid crystal growth. Nucleation is the crucial step that determines the entire crystallization process. Hence, the holy grail is to design a "universal nucleant," a substrate that induces the nucleation of crystals of any protein. We report a theory for nucleation on disordered porous media and its experimental testing and validation using a mesoporous bioactive gel-glass. This material induced the crystallization of the largest number of proteins ever crystallized using a single nucleant. The combination of the model and the experimental results opens up the scope for the rational design of nucleants, leading to alternative means of controlling crystallization.

  13. Characterization of a heterogeneous chicken plasma protein, HEF, by analytical isotachophoresis in agarose gel.

    PubMed

    Nicolaisen, E M

    1985-02-22

    Chicken plasma contains proteins that associate with immunoglobulin. One of these proteins enhances the titre of haemagglutinating alloantibodies, and it was therefore named HEF, haemagglutination enhancing factor. A purified HEF preparation mixed with ampholytes splits into four bands in analytical agarose isotachophoresis. One of the HEF bands can be separated from two others with beta-alanine as discrete spacer. The separated HEF populations differ in molecular size and in their ability to enhance agglutination.

  14. Dynamics of backbone conformational heterogeneity in Bacillus subtilis ribonuclease P protein.

    PubMed

    Henkels, Christopher H; Chang, Yu-Chu; Chamberlin, Stacy I; Oas, Terrence G

    2007-12-25

    Interconversion of protein conformations is imperative to function, as evidenced by conformational changes associated with enzyme catalytic cycles, ligand binding and post-translational modifications. In this study, we used 15N NMR relaxation experiments to probe the fast (i.e., ps-ns) and slow (i.e., micros-ms) conformational dynamics of Bacillus subtilis ribonuclease P protein (P protein) in its folded state, bound to two sulfate anions. Using the Lipari-Szabo mapping method [Andrec, M., Montelione, G. T., and Levy, R. M. (2000) J. Biomol. NMR 18, 83-100] to interpret the data, we find evidence for P protein dynamics on the mus-ms time scale in the ensemble. The residues that exhibit these slow internal motions are found in regions that have been previously identified as part of the P protein-P RNA interface. These results suggest that structural flexibility within the P protein ensemble may be important for proper RNase P holoenzyme assembly and/or catalysis.

  15. Subpopulations of cholinergic, GABAergic and glutamatergic neurons in the pedunculopontine nucleus contain calcium-binding proteins and are heterogeneously distributed.

    PubMed

    Martinez-Gonzalez, Cristina; Wang, Hui-Ling; Micklem, Benjamin R; Bolam, J Paul; Mena-Segovia, Juan

    2012-03-01

    Neurons in the pedunculopontine nucleus (PPN) are highly heterogeneous in their discharge properties, their neurochemical markers, their pattern of connectivity and the behavioural processes in which they participate. Three main transmitter phenotypes have been described, cholinergic, GABAergic and glutamatergic, and yet electrophysiological evidence suggests heterogeneity within these subtypes. To gain further insight into the molecular composition of these three populations in the rat, we investigated the pattern of expression of calcium binding proteins (CBPs) across distinct regions of the PPN and in relation to the presence of other neurochemical markers. Calbindin- and calretinin-positive neurons are as abundant as cholinergic neurons, and their expression follows a rostro-caudal gradient, whereas parvalbumin is expressed by a low number of neurons. We observed a high degree of expression of CBPs by GABAergic and glutamatergic neurons, with a large majority of calbindin- and calretinin-positive neurons expressing GAD or VGluT2 mRNA. Notably, CBP-positive neurons expressing GAD mRNA were more concentrated in the rostral PPN, whereas the caudal PPN was characterized by a higher density of CBP-positive neurons expressing VGluT2 mRNA. In contrast to these two large populations, in cholinergic neurons expression of calretinin is observed only in low numbers and expression of calbindin is virtually non-existent. These findings thus identify novel subtypes of cholinergic, GABAergic and glutamatergic neurons based on their expression of CBPs, and further contribute to the notion of the PPN as a highly heterogeneous structure, an attribute that is likely to underlie its functional complexity.

  16. Promiscuous stimulation of ParF protein polymerization by heterogeneous centromere binding factors.

    PubMed

    Machón, Cristina; Fothergill, Timothy J G; Barillà, Daniela; Hayes, Finbarr

    2007-11-16

    The segrosome is the nucleoprotein complex that mediates accurate segregation of bacterial plasmids. The segrosome of plasmid TP228 comprises ParF and ParG proteins that assemble on the parH centromere. ParF, which exemplifies one clade of the ubiquitous ParA superfamily of segregation proteins, polymerizes extensively in response to ATP binding. Polymerization is modulated by the ParG centromere binding factor (CBF). The segrosomes of plasmids pTAR, pVT745 and pB171 include ParA homologues of the ParF subgroup, as well as diverse homodimeric CBFs with no primary sequence similarity to ParG, or each other. Centromere binding by these analogues is largely specific. Here, we establish that the ParF homologues of pTAR and pB171 filament modestly with ATP, and that nucleotide hydrolysis is not required for this polymerization, which is more prodigious when the cognate CBF is also present. By contrast, the ParF homologue of plasmid pVT745 did not respond appreciably to ATP alone, but polymerized extensively in the presence of both its cognate CBF and ATP. The co-factors also stimulated nucleotide-independent polymerization of cognate ParF proteins. Moreover, apart from the CBF of pTAR, the disparate ParG analogues promoted polymerization of non-cognate ParF proteins suggesting that filamentation of the ParF proteins is enhanced by a common mechanism. Like ParG, the co-factors may be modular, possessing a centromere-specific interaction domain linked to a flexible region containing determinants that promiscuously stimulate ParF polymerization. The CBFs appear to function as bacterial analogues of formins, microtubule-associated proteins or related ancillary factors that regulate eucaryotic cytoskeletal dynamics.

  17. A simple two-state protein unfolds mechanically via multiple heterogeneous pathways at single-molecule resolution

    PubMed Central

    Schönfelder, Jörg; Perez-Jimenez, Raul; Muñoz, Victor

    2016-01-01

    A major drive in protein folding has been to develop experimental technologies to resolve the myriads of microscopic pathways and complex mechanisms that purportedly underlie simple two-state folding behaviour. This is key for cross-validating predictions from theory and modern computer simulations. Detecting such complexity experimentally has remained elusive even using methods with improved time, structural or single-molecule resolution. Here, we investigate the mechanical unfolding of cold shock protein B (Csp), a showcase two-state folder, using single-molecule force-spectroscopy. Under controlled-moderate pulling forces, the unfolding of Csp emerges as highly heterogeneous with trajectories ranging from single sweeps to different combinations of multiple long-lived mechanical intermediates that also vary in order of appearance. Steered molecular dynamics simulations closely reproduce the experimental observations, thus matching unfolding patterns with structural events. Our results provide a direct glimpse at the nanoscale complexity underlying two-state folding, and postulate these combined methods as unique tools for dissecting the mechanical unfolding mechanisms of such proteins. PMID:27248054

  18. A simple two-state protein unfolds mechanically via multiple heterogeneous pathways at single-molecule resolution

    NASA Astrophysics Data System (ADS)

    Schönfelder, Jörg; Perez-Jimenez, Raul; Muñoz, Victor

    2016-06-01

    A major drive in protein folding has been to develop experimental technologies to resolve the myriads of microscopic pathways and complex mechanisms that purportedly underlie simple two-state folding behaviour. This is key for cross-validating predictions from theory and modern computer simulations. Detecting such complexity experimentally has remained elusive even using methods with improved time, structural or single-molecule resolution. Here, we investigate the mechanical unfolding of cold shock protein B (Csp), a showcase two-state folder, using single-molecule force-spectroscopy. Under controlled-moderate pulling forces, the unfolding of Csp emerges as highly heterogeneous with trajectories ranging from single sweeps to different combinations of multiple long-lived mechanical intermediates that also vary in order of appearance. Steered molecular dynamics simulations closely reproduce the experimental observations, thus matching unfolding patterns with structural events. Our results provide a direct glimpse at the nanoscale complexity underlying two-state folding, and postulate these combined methods as unique tools for dissecting the mechanical unfolding mechanisms of such proteins.

  19. The unconventional secretion of stress-inducible protein 1 by a heterogeneous population of extracellular vesicles.

    PubMed

    Hajj, Glaucia N M; Arantes, Camila P; Dias, Marcos Vinicios Salles; Roffé, Martín; Costa-Silva, Bruno; Lopes, Marilene H; Porto-Carreiro, Isabel; Rabachini, Tatiana; Lima, Flávia R; Beraldo, Flávio H; Prado, Marco A M; Prado, Marco M A; Linden, Rafael; Martins, Vilma R

    2013-09-01

    The co-chaperone stress-inducible protein 1 (STI1) is released by astrocytes, and has important neurotrophic properties upon binding to prion protein (PrP(C)). However, STI1 lacks a signal peptide and pharmacological approaches pointed that it does not follow a classical secretion mechanism. Ultracentrifugation, size exclusion chromatography, electron microscopy, vesicle labeling, and particle tracking analysis were used to identify three major types of extracellular vesicles (EVs) released from astrocytes with sizes ranging from 20-50, 100-200, and 300-400 nm. These EVs carry STI1 and present many exosomal markers, even though only a subpopulation had the typical exosomal morphology. The only protein, from those evaluated here, present exclusively in vesicles that have exosomal morphology was PrP(C). STI1 partially co-localized with Rab5 and Rab7 in endosomal compartments, and a dominant-negative for vacuolar protein sorting 4A (VPS4A), required for formation of multivesicular bodies (MVBs), impaired EV and STI1 release. Flow cytometry and PK digestion demonstrated that STI1 localized to the outer leaflet of EVs, and its association with EVs greatly increased STI1 activity upon PrP(C)-dependent neuronal signaling. These results indicate that astrocytes secrete a diverse population of EVs derived from MVBs that contain STI1 and suggest that the interaction between EVs and neuronal surface components enhances STI1-PrP(C) signaling.

  20. Protein Stable Isotope Fingerprinting (P-SIF): A New Tool to Understand Natural Isotopic Heterogeneity of Mixed Microbial Ecosystems

    NASA Astrophysics Data System (ADS)

    Pearson, A.; Mohr, W.; Tang, T.; Sattin, S.; Bovee, R.

    2014-12-01

    Protein stable isotope fingerprinting (P-SIF) is a method to measure the carbon isotope ratios of whole proteins separated from complex mixtures, including cultures and environmental samples. The goal of P-SIF is to expose the links between identity and function in microbial ecosystems by (i) determining the ratios of 13C/12C (values of δ13C) for different taxonomic divisions, and (ii) using those values as clues to the metabolic pathways employed by the respective organisms, while (iii) not perturbing the system, i.e., not adding exogenous substrates or isotope labels. To accomplish this, we employ two-dimensional HPLC to resolve a sample containing ca. 5-10 mg of mixed proteins into 960-1440 fractions. Each fraction then is split in two aliquots: The first is digested with trypsin for peptide sequencing, while the second is measured in triplicate using an isotope-ratio mass spectrometer interfaced with a spooling wire microcombustion device. Data from pure cultures show that bacteria have a narrow distribution of protein δ13C values within individual taxa (±0.7-1.2‰, 1σ). This is moderately larger than the mean precision of the triplicate isotope measurements (±0.5‰, 1σ) and may reflect heterogeneous distribution of 13C among the amino acids. When cells from different species are mixed together prior to protein extraction and separation, the results can predict accurately (to within ±1σ) the δ13C values of the original taxa. The number of data points required for this endmember prediction is ≥20/taxon, yielding a theoretical resolution of ca. 10 taxonomic units/sample. Initial tests on environmental samples suggest the approach will be useful to determine the overall trophic breadth of mixed microbial ecosystems.

  1. A method to resolve the composition of heterogeneous affinity-purified protein complexes assembled around a common protein by chemical cross-linking, gel electrophoresis and mass spectrometry.

    PubMed

    Rudashevskaya, Elena L; Sacco, Roberto; Kratochwill, Klaus; Huber, Marie L; Gstaiger, Matthias; Superti-Furga, Giulio; Bennett, Keiryn L

    2013-01-01

    Protein complexes form, dissociate and re-form in order to perform specific cellular functions. In this two-pronged protocol, noncovalent protein complexes are initially isolated by affinity purification for subsequent identification of the components by liquid chromatography high-resolution mass spectrometry (LC-MS) on a hybrid LTQ Orbitrap Velos. In the second prong of the approach, the affinity-purification strategy includes a chemical cross-linking step to 'freeze' a series of concurrently formed, heterogeneous protein subcomplex species that are visualized by gel electrophoresis. This branch of the methodology amalgamates standard and well-practiced laboratory methods to reveal compositional changes that occur in protein complex architecture. By using mouse N-terminally tagged streptavidin-binding peptide-hemagglutinin-TANK-binding kinase 1 (SH-TBK1), we chemically cross-linked the affinity-purified complex of SH-TBK1 with the homobifunctional lysine-specific reagent bis(sulfosuccinimidyl) suberate (BS(3)), and we separated the resultant protein complexes by denaturation and by silver-stained one- and two-dimensional SDS-PAGE. We observed a range of cross-linked TBK1 complexes of variable pI and M(r) and confirmed them by immunoblotting. LC-MS analysis of in situ-digested cross-linked proteins shows differences in the composition of the TBK1 subcomplexes. The protocol is inherently simple and can be readily extended to the investigation of a range of protein complexes. From cell lysis to data generation by LC-MS, the protocol takes approximately 2.5 to 5.5 d to perform.

  2. Primary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: a diversity of RNA binding proteins is generated by small peptide inserts.

    PubMed Central

    Burd, C G; Swanson, M S; Görlach, M; Dreyfuss, G

    1989-01-01

    We have isolated cDNAs for the major heterogeneous nuclear ribonucleoprotein (hnRNP) A2, B1, and C2 proteins and determined their nucleotide and deduced amino acid sequences. The A2 and B1 cDNAs are identical except for a 36-nucleotide in-frame insert in B1. Similarly, the sequence of the C2 protein cDNA is related to that of C1 in that C2 contains an extra 39 in-frame nucleotides. Therefore, the B1 amino acid sequence is identical to A2 except for the insertion of 12 amino acids near its amino terminus, and C1 and C2 are also identical to each other except for an extra 13 amino acids near the middle of C2. All three proteins are members of a large family of RNA binding proteins that contain the consensus sequence-type RNA binding domain (CS-RBD). The A2 and B1 proteins have a modular structure similar to that of the hnRNP protein A1: they contain two CS-RBDs and a glycine-rich auxiliary domain at the carboxyl terminus. The CS-RBDs of A2 and B1 have approximately 80% amino acid identity with those of A1, whereas the glycine-rich auxiliary domain is considerably more divergent with less than 30% of the amino acids being identical. These findings indicate that the addition of small peptides, probably by alternative pre-mRNA splicing, generates some of the diversity apparent among hnRNP proteins. Images PMID:2557628

  3. Energy transfer at heterogeneous protein-protein interfaces to investigate the molecular behaviour in the crowding environment

    NASA Astrophysics Data System (ADS)

    Ota, Chikashi

    2017-03-01

    Investigation of the behaviour of proteins in crowded environments is crucial for understanding the role of proteins in biological environments. In this study, the behaviour of bovine serum albumin (BSA) in crowded (highly concentrated) environments was investigated using time-resolved fluorescence spectroscopy as a model system. By using energy transfer as a molecular ruler, the crowding effect was clearly observed in the time resolved spectra. In addition, by using both time resolved anisotropy measurement and Raman spectroscopy, more detail insights from conformational and dynamic points of view were described. Consequently, it was revealed that in the highly concentrated solution, most of the BSA molecules are in the fast-reversible oligomeric state and the association at the "hard" and "soft" interfaces between protein surfaces occurred in a highly crowded environment with the aid of a charge-charge and short-range attractive interface. From both the conformational and dynamic aspects, the detail spectroscopic understanding of the behaviour of BSA in the crowding environment was obtained.

  4. Heterogeneity of Arabinogalactan-Proteins on the Plasma Membrane of Rose Cells.

    PubMed Central

    Serpe, M. D.; Nothnagel, E. A.

    1996-01-01

    Arabinogalactan-proteins (AGPs) have been purified from the plasma membrane of suspension-cultured Paul's Scarlet rose (Rosa sp.) cells. The two most abundant and homogeneous plasma membrane AGP fractions were named plasma membrane AGP1 (PM-AGP1) and plasma membrane AGP2 (PM-AGP2) and had apparent molecular masses of 140 and 217 kD, respectively. Both PM-AGP1 and PM-AGP2 had [beta]-(1-3)-, [beta]-(1,6)-, and [beta]-(1,3,6)-galactopyranosyl residues, predominantly terminal [alpha]-arabinofuranosyl residues, and (1,4)- and terminal glucuronopyranosyl residues. The protein moieties of PM-AGP1 and PM-AGP2 were both rich in hydroxyproline, alanine, and serine, but differed in the abundance of hydroxyproline, which was 1.6 times higher in PM-AGP2 than in PM-AGP1. Another difference was the overall protein content, which was 3.7% (w/w) in PM-AGP1 and 15% in PM-AGP2. As judged by their behavior on reverse-phase chromatography, PM-AGP1 and PM-AGP2 were not more hydrophobic than AGPs from the cell wall or culture medium. In contrast, a minor plasma membrane AGP fraction eluted later on reverse-phase chromatography and was more negatively charged at pH 5 than either PM-AGP1 or PM-AGP2. The more negatively charged fraction contained molecules with a glycosyl composition characteristic of AGPs and included at least two different macromolecules. The results of this investigation indicate that Rosa plasma membrane contains at least four distinct AGPs or AGP-like molecules. These molecules differed from each other in size, charge, hydrophobicity, amino-acyl composition, and/or protein content. PMID:12226444

  5. Structure of a heterogeneous, glycosylated, lipid-bound, in vivo-grown protein crystal at atomic resolution from the viviparous cockroach Diploptera punctata

    PubMed Central

    Banerjee, Sanchari; Coussens, Nathan P.; Gallat, François-Xavier; Sathyanarayanan, Nitish; Srikanth, Jandhyam; Yagi, Koichiro J.; Gray, James S. S.; Tobe, Stephen S.; Stay, Barbara; Chavas, Leonard M. G.; Ramaswamy, Subramanian

    2016-01-01

    Macromolecular crystals for X-ray diffraction studies are typically grown in vitro from pure and homogeneous samples; however, there are examples of protein crystals that have been identified in vivo. Recent developments in micro-crystallography techniques and the advent of X-ray free-electron lasers have allowed the determination of several protein structures from crystals grown in cellulo. Here, an atomic resolution (1.2 Å) crystal structure is reported of heterogeneous milk proteins grown inside a living organism in their functional niche. These in vivo-grown crystals were isolated from the midgut of an embryo within the only known viviparous cockroach, Diploptera punctata. The milk proteins crystallized in space group P1, and a structure was determined by anomalous dispersion from the native S atoms. The data revealed glycosylated proteins that adopt a lipocalin fold, bind lipids and organize to form a tightly packed crystalline lattice. A single crystal is estimated to contain more than three times the energy of an equivalent mass of dairy milk. This unique storage form of nourishment for developing embryos allows access to a constant supply of complete nutrients. Notably, the crystalline cockroach-milk proteins are highly heterogeneous with respect to amino-acid sequence, glycosylation and bound fatty-acid composition. These data present a unique example of protein heterogeneity within a single in vivo-grown crystal of a natural protein in its native environment at atomic resolution. PMID:27437115

  6. Structure of a heterogeneous, glycosylated, lipid-bound, in vivo-grown protein crystal at atomic resolution from the viviparous cockroach Diploptera punctata.

    PubMed

    Banerjee, Sanchari; Coussens, Nathan P; Gallat, François-Xavier; Sathyanarayanan, Nitish; Srikanth, Jandhyam; Yagi, Koichiro J; Gray, James S S; Tobe, Stephen S; Stay, Barbara; Chavas, Leonard M G; Ramaswamy, Subramanian

    2016-07-01

    Macromolecular crystals for X-ray diffraction studies are typically grown in vitro from pure and homogeneous samples; however, there are examples of protein crystals that have been identified in vivo. Recent developments in micro-crystallography techniques and the advent of X-ray free-electron lasers have allowed the determination of several protein structures from crystals grown in cellulo. Here, an atomic resolution (1.2 Å) crystal structure is reported of heterogeneous milk proteins grown inside a living organism in their functional niche. These in vivo-grown crystals were isolated from the midgut of an embryo within the only known viviparous cockroach, Diploptera punctata. The milk proteins crystallized in space group P1, and a structure was determined by anomalous dispersion from the native S atoms. The data revealed glycosylated proteins that adopt a lipocalin fold, bind lipids and organize to form a tightly packed crystalline lattice. A single crystal is estimated to contain more than three times the energy of an equivalent mass of dairy milk. This unique storage form of nourishment for developing embryos allows access to a constant supply of complete nutrients. Notably, the crystalline cockroach-milk proteins are highly heterogeneous with respect to amino-acid sequence, glycosylation and bound fatty-acid composition. These data present a unique example of protein heterogeneity within a single in vivo-grown crystal of a natural protein in its native environment at atomic resolution.

  7. An eriophyid mite-transmitted plant virus contains eight genomic RNA segments with unusual heterogeneity in the nucleocapsid protein.

    PubMed

    Tatineni, Satyanarayana; McMechan, Anthony J; Wosula, Everlyne N; Wegulo, Stephen N; Graybosch, Robert A; French, Roy; Hein, Gary L

    2014-10-01

    Eriophyid mite-transmitted, multipartite, negative-sense RNA plant viruses with membrane-bound spherical virions are classified in the genus Emaravirus. We report here that the eriophyid mite-transmitted Wheat mosaic virus (WMoV), an Emaravirus, contains eight genomic RNA segments, the most in a known negative-sense RNA plant virus. Remarkably, two RNA 3 consensus sequences, encoding the nucleocapsid protein, were found with 12.5% sequence divergence, while no heterogeneity was observed in the consensus sequences of additional genomic RNA segments. The RNA-dependent RNA polymerase, glycoprotein precursor, nucleocapsid, and P4 proteins of WMoV exhibited limited sequence homology with the orthologous proteins of other emaraviruses, while proteins encoded by additional genomic RNA segments displayed no significant homology with proteins reported in GenBank, suggesting that the genus Emaravirus evolved further with a divergent octapartite genome. Phylogenetic analyses revealed that WMoV formed an evolutionary link between members of the Emaravirus genus and the family Bunyaviridae. Furthermore, genomic-length virus- and virus-complementary (vc)-sense strands of all WMoV genomic RNAs accumulated asymmetrically in infected wheat, with 10- to 20-fold more virus-sense genomic RNAs than vc-sense RNAs. These data further confirm the octapartite negative-sense polarity of the WMoV genome. In WMoV-infected wheat, subgenomic-length mRNAs of vc sense were detected for genomic RNAs 3, 4, 7, and 8 but not for other RNA species, suggesting that the open reading frames present in the complementary sense of genomic RNAs are expressed through subgenomic- or near-genomic-length vc-sense mRNAs. Importance: Wheat mosaic virus (WMoV), an Emaravirus, is the causal agent of High Plains disease of wheat and maize. In this study, we demonstrated that the genome of WMoV comprises eight negative-sense RNA segments with an unusual sequence polymorphism in an RNA encoding the nucleocapsid protein

  8. Regional and phenotype heterogeneity of cellular prion proteins in the human brain.

    PubMed

    Kuczius, Thorsten; Koch, Richard; Keyvani, Kathy; Karch, Helge; Grassi, Jacques; Groschup, Martin H

    2007-05-01

    Transmissible spongiform encephalopathies (TSEs) are neurological disorders that include genetic, infectious and sporadic forms of human Creutzfeldt-Jakob disease (CJD). The pathogenic agent is the prion protein that is composed of an abnormal isoform (PrP(Sc)) of a host-encoded protein (PrP(C)). Analysis of the relative amounts of PrP(Sc) glycoforms has been used to discriminate between various agents involved in TSE. The distribution and efficiency of conversion to PrP(Sc) can be influenced by differences in the expression of PrP(C). However, little attention has been given so far to the banding patterns of PrP(C). Using four different antibodies recognizing amino- and carboxyl-terminal PrP sequences we analysed the glycoforms of PrP(C) in seven regions of the human brain using brains obtained from six subjects. For determination of the staining intensities, signals were quantified by densitometry and reproducible patterns were accomplished by many repeated immunoblot analyses. When amino-terminal binding antibodies were used for detection, PrP(C) in the frontal neocortex, nucleus lentiformis, thalamus, hippocampus and cerebellum displayed a glycotype with high staining of the diglycosylated isoforms. This was different from patterns in the pons and medulla oblongata, which showed a high intensity of the nonglycosylated isoform, and PrP(C) proteins, approximately 27 kDa in size, exhibited high staining using the carboxyl-terminal binding antibodies. This intense staining followed from an overlay of full-length and truncated PrP(C) isoforms. Furthermore, we found marked differences in the expression of PrP(C). Variations in the processing of PrP(C) may lead to interregional differences in the glycoform composition of PrP(Sc) in human brains.

  9. Quantitative model for the heterogeneity of atomic position fluctuations in proteins: A simulation study

    SciTech Connect

    Kneller, Gerald R.; Hinsen, Konrad

    2009-07-28

    We propose a simple analytical model for the elastic incoherent structure factor of proteins measured by neutron scattering, which allows extracting the distribution of atomic position fluctuations from a fit of the model to the experimental data. The method is validated by applying it to elastic incoherent structure factors of lysozyme which have been obtained by molecular dynamics simulation and by normal mode analysis, respectively, and for which distributions of the atomic position fluctuations can be generated numerically for direct comparison with the predictions of the model. The comparison shows a remarkable agreement, in particular, concerning the lower limit for the position fluctuations, which is pronounced in the numerical data.

  10. Molecular heterogeneity in major urinary proteins of Mus musculus subspecies: potential candidates involved in speciation

    PubMed Central

    Hurst, Jane L.; Beynon, Robert J.; Armstrong, Stuart D.; Davidson, Amanda J.; Roberts, Sarah A.; Gómez-Baena, Guadalupe; Smadja, Carole M.; Ganem, Guila

    2017-01-01

    When hybridisation carries a cost, natural selection is predicted to favour evolution of traits that allow assortative mating (reinforcement). Incipient speciation between the two European house mouse subspecies, Mus musculus domesticus and M.m.musculus, sharing a hybrid zone, provides an opportunity to understand evolution of assortative mating at a molecular level. Mouse urine odours allow subspecific mate discrimination, with assortative preferences evident in the hybrid zone but not in allopatry. Here we assess the potential of MUPs (major urinary proteins) as candidates for signal divergence by comparing MUP expression in urine samples from the Danish hybrid zone border (contact) and from allopatric populations. Mass spectrometric characterisation identified novel MUPs in both subspecies involving mostly new combinations of amino acid changes previously observed in M.m.domesticus. The subspecies expressed distinct MUP signatures, with most MUPs expressed by only one subspecies. Expression of at least eight MUPs showed significant subspecies divergence both in allopatry and contact zone. Another seven MUPs showed divergence in expression between the subspecies only in the contact zone, consistent with divergence by reinforcement. These proteins are candidates for the semiochemical barrier to hybridisation, providing an opportunity to characterise the nature and evolution of a putative species recognition signal. PMID:28337988

  11. Heterogeneous nuclear expression of the promyelocytic leukemia (PML) protein in normal and neoplastic human tissues.

    PubMed Central

    Gambacorta, M.; Flenghi, L.; Fagioli, M.; Pileri, S.; Leoncini, L.; Bigerna, B.; Pacini, R.; Tanci, L. N.; Pasqualucci, L.; Ascani, S.; Mencarelli, A.; Liso, A.; Pelicci, P. G.; Falini, B.

    1996-01-01

    The RING-finger promyelocytic leukemia (PML) protein is the product of the PML gene that fuses with the retinoic acid receptor-alpha gene in the t(15; 17) translocation of acute promyelocytic leukemia. Wild-type PML localizes in the nucleus with a typical speckled pattern that is a consequence of the concentration of the protein within discrete subnuclear domains known as nuclear bodies. Delocalization of PML from nuclear bodies has been documented in acute promyelocytic leukemia cells and suggested to contribute to leukemogenesis. In an attempt to get new insights into the function of the wild-type PML protein and to investigate whether it displays an altered expression pattern in neoplasms other than acute promyelocytic leukemia, we stained a large number of normal and neoplastic human tissues with a new murine monoclonal antibody (PG-M3) directed against the amino-terminal region of PML. As the PG-M3 epitope is partially resistant to fixatives, only cells that overexpress PML are detected by the antibody in microwave-heated paraffin sections. Among normal tissues, PML was characteristically up-regulated in activated epithelioid histiocytes and fibroblasts in a variety of pathological conditions, columnar epithelium in small active thyroid follicles, well differentiated foamy cells in the center of sebaceous glands, and hypersecretory endometria (Arias-Stella). Interferons, the PML of which is a primary target gene, and estrogens are likely to represent some of the cytokines and/or hormones that may be involved in the up-regulation of PML under these circumstances. In keeping with this concept, we found that PML is frequently overexpressed in Hodgkin and Reed-Sternberg cells of Hodgkin's disease, a tumor of cytokine-producing cells. Among solid tumors, overexpression of PML was frequently found in carcinomas of larynx and thyroid (papillary), epithelial thymomas, and Kaposi's sarcoma, whereas carcinomas of the lung, thyroid (follicular), breast, and colon were

  12. Genomic and transcriptional analysis of protein heterogeneity of the honeybee venom allergen Api m 6.

    PubMed

    Peiren, N; de Graaf, D C; Evans, J D; Jacobs, F J

    2006-10-01

    Several components of honeybee venom are known to cause allergenic responses in humans and other vertebrates. One such component, the minor allergen Api m 6, has been known to show amino acid variation but the genetic mechanism for this variation is unknown. Here we show that Api m 6 is derived from a single locus, and that substantial protein-level variation has a simple genome-level cause, without the need to invoke multiple loci or alternatively spliced exons. Api m 6 sits near a misassembled section of the honeybee genome sequence, and we propose that a substantial number of indels at and near Api m 6 might be the root cause of this misassembly. We suggest that genes such as Api m 6 with coding-region or untranslated region indels might have had a strong effect on the assembly of this draft of the honeybee genome.

  13. Restriction of immunoglobulin heterogeneity, autoimmunity and serum protein levels in aged people.

    PubMed Central

    Riesen, W; Keller, H; Skvaril, F; Morell, A; Barandun, S

    1976-01-01

    Ninety-one sera of persons above 80 years of age were screened for autoantibody activity against lipoproteins (anti-LDL 7, anti-HDL 6 positive), for rheumatoid factor activity (Latex 14, Waaler-Rose 7 positive) and for antinuclear factors (11 positive). Among the sera with autoantibody activity 29 percent showed deviations of the normal kappa/lambda ratio of immunoglobulins, as opposed to 22 percent of the sera without detected autoantibody activity. In 3 percent of the sera an M component was detected. Determination of the alpha1-acid glycoprotein, alpha1-antitrypsin, haptoglobin, haemopexin, complement component C3c and C4, IgG, IgA and IgM levels showed significant increases in alpha-, and beta-globulins as well as in IgG and IgA in sera of the aged persons as compared to a normal population between 20 and 60 years old. No significant difference was noted between the gamma-globulin concentration in sera of aged persons with or without autoantibody activity. The evaluation of the relationship between serum protein levels and alterations of the kappa/lambda ratio indicated that the alpha- and the beta-globulins were significantly raised in sera with altered kappa/lambda ratios, whereas, with the exception of M component containing sera the gamma-globulin levels seemed not significantly affected by changes in this ratio. PMID:62632

  14. Molecular characterization of two small heat shock protein genes in rice: their expression patterns, localizations, networks, and heterogeneous overexpressions.

    PubMed

    Ham, Deok-Jae; Moon, Jun-Chul; Hwang, Sun-Goo; Jang, Cheol Seong

    2013-09-28

    Heat stress is an example of a severe abiotic stress that plants can suffer in the field, causing a significant detrimental effect on their growth and productivity. Understanding the mechanism of plant response to heat stress is important for improving the productivity of crop plants under global warming. We used a microarray dataset that is deposited in the public database to evaluate plant responses to heat stress, and we selected the top 10 genes that are highly expressed under heat stress in rice. Two genes, OsSHSP1 (Os03g16030) and OsSHSP2 (Os01g04380), were selected for further study. These genes were highly induced in response to salt and drought but not in response to cold. In addition, OsSHSP1 and OsSHSP2 gene transcripts were induced under abscisic acid and salicylic acid but not under jasmonic acid and ethylene. Subcellular localization of proteins of 35S::OsSHSP1 were associated with the cytosol, whereas those of and 35S::OsSHSP2 were associated with the cytosol and nucleus. Heterogeneous overexpression of both genes exhibited higher germination rates than those of wild-type plants under the salt treatment, but not under heat or drought stress, supporting a hypothesis regarding functional specialization of members of small heat-shock protein family over evolutionary time. The network of both genes harboring nine sHSPs as well as at least 13 other chaperone genes might support the idea of a role for sHSPs in the chaperone network. Our findings might provide clues to shed light on the molecular functions of OsSHSP1 and OsSHSP2 in response to abiotic stresses, especially heat stress.

  15. SUMO meets meiosis: an encounter at the synaptonemal complex: SUMO chains and sumoylated proteins suggest that heterogeneous and complex interactions lie at the centre of the synaptonemal complex.

    PubMed

    Watts, Felicity Z; Hoffmann, Eva

    2011-07-01

    Recent discoveries have identified the small ubiquitin-like modifier (SUMO) as the potential 'missing link' that could explain how the synaptonemal complex (SC) is formed during meiosis. The SC is important for a variety of chromosome interactions during meiosis and appears ladder-like. It is formed when 'axes' of the two homologous chromosomes become connected by the deposition of transverse filaments, forming the steps of the ladder. Although several components of axial and transverse elements have been identified, how the two are connected to form the SC has remained an enigma. Recent discoveries suggest that SUMO modification underlies protein-protein interactions within the SC of budding yeast. The versatility of SUMO in regulating protein-protein interactions adds an exciting new dimension to our understanding of the SC and suggests that SCs are not homogenous structures throughout the nucleus. We propose that this heterogeneity may allow differential regulation of chromosome structure and function.

  16. Lipid lateral heterogeneity in phosphatidylcholine/phosphatidylserine/diacylglycerol vesicles and its influence on protein kinase C activation.

    PubMed Central

    Dibble, A R; Hinderliter, A K; Sando, J J; Biltonen, R L

    1996-01-01

    To test the hypothesis that the activation of protein kinase C (PKC) is influenced by lateral heterogeneities of the components of the lipid bilayer, the thermotropic phase behavior of dimyristoylphosphatidylcholine (DMPC)/dimyristoylphosphatidylserine (DMPS)/dioleoylglycerol (DO) vesicles was compared with the activation of PKC by this system. Differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy were used to monitor the main transition (i.e., the gel-to-fluid phase transition) as a function of mole fraction DO (chi(DO)) in DMPC/DO, DMPS/DO, and [DMPC/DMPS (1:1, mol/mol)]/DO multilamellar vesicles (MLVs). In each case, when chi(DO) < or approximately 0.3, DO significantly broadened the main transition and shifted it to lower temperatures; but when chi(DO) > approximately 0.3, the main transition became highly cooperative, i.e., narrow, again. The coexistence of overlapping narrow and broad transitions was clearly evident in DSC thermograms from chi(DO) approximately 0.1 to chi(DO) approximately 0.3, with the more cooperative transition growing at the expense of the broader one as chi(DO) increased. FTIR spectroscopy, using analogs of DMPC and DMPS with perdeuterated acyl chains, showed that the melting profiles of all three lipid components in [DMPC/DMPS (1:1, mol/mol)]/DO MLVs virtually overlay when chi(DO) = 0.33, suggesting that a new type of phase, with a phospholipid/DO mole ratio near 2:1, is formed in this system. Collectively, the results are consistent with the coexistence of DO-poor and DO-rich domains throughout the compositions chi(DO) approximately 0.1 to chi(DO) approximately 0.3, even at temperatures above the main transition. Comparison of the phase behavior of the binary mixtures with that of the ternary mixtures suggests that DMPS/DO interactions may be more favorable than DMPC/DO interactions in the ternary system, especially in the gel state. PKC activity was measured using [DMPC/DMPS (1:1, mol/mol)]/DO MLVs

  17. Copper and Zinc Interactions with Cellular Prion Proteins Change Solubility of Full-Length Glycosylated Isoforms and Induce the Occurrence of Heterogeneous Phenotypes

    PubMed Central

    Brim, Svetlana; Groschup, Martin H.; Kuczius, Thorsten

    2016-01-01

    Prion diseases are characterized biochemically by protein aggregation of infectious prion isoforms (PrPSc), which result from the conformational conversion of physiological prion proteins (PrPC). PrPC are variable post-translationally modified glycoproteins, which exist as full length and as aminoterminally truncated glycosylated proteins and which exhibit differential detergent solubility. This implicates the presence of heterogeneous phenotypes, which overlap as protein complexes at the same molecular masses. Although the biological function of PrPC is still enigmatic, evidence reveals that PrPC exhibits metal-binding properties, which result in structural changes and decreased solubility. In this study, we analyzed the yield of PrPC metal binding affiliated with low solubility and changes in protein banding patterns. By implementing a high-speed centrifugation step, the interaction of zinc ions with PrPC was shown to generate large quantities of proteins with low solubility, consisting mainly of full-length glycosylated PrPC; whereas unglycosylated PrPC remained in the supernatants as well as truncated glycosylated proteins which lack of octarepeat sequence necessary for metal binding. This effect was considerably lower when PrPC interacted with copper ions; the presence of other metals tested exhibited no effect under these conditions. The binding of zinc and copper to PrPC demonstrated differentially soluble protein yields within distinct PrPC subtypes. PrPC–Zn2+-interaction may provide a means to differentiate glycosylated and unglycosylated subtypes and offers detailed analysis of metal-bound and metal-free protein conversion assays. PMID:27093554

  18. Purification and partial sequencing of the nuclear autoantigen RA33 shows that it is indistinguishable from the A2 protein of the heterogeneous nuclear ribonucleoprotein complex.

    PubMed Central

    Steiner, G; Hartmuth, K; Skriner, K; Maurer-Fogy, I; Sinski, A; Thalmann, E; Hassfeld, W; Barta, A; Smolen, J S

    1992-01-01

    RA33 is a nuclear autoantigen with an apparent molecular mass of 33 kD. Autoantibodies against RA33 are found in about 30% of sera from RA patients, but only occasionally in sera from patients with other connective tissue diseases. To characterize RA33, the antigen was purified from HeLa cell nuclear extracts to more than 90% homogeneity by affinity chromatography on heparin-Sepharose and by chromatofocusing. Sequence analysis of five tryptic peptides revealed that their sequences matched corresponding sequences of the A2 protein of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex. Furthermore, RA33 was shown to be present in the 40S hnRNP complex and to behave indistinguishably from A2 in binding to single stranded DNA. In summary, these data strongly indicate that RA33 and A2 are the same protein, and thus identify on a molecular level a new autoantigen. Images PMID:1522214

  19. Immunohistochemical localization of adenosine deaminase complexing protein in intestinal mucosa and in colorectal adenocarcinoma as a marker for tumour cell heterogeneity.

    PubMed

    Ten Kate, J; Wijnen, J T; Boldewijn, J; Khan, P M; Bosman, F T

    1985-01-01

    Adenosine deaminase complexing protein (ADCP), a dimeric glycoprotein, has been reported to be decreased or deficient in transformed or cancer-derived cell lines, indicating its potential significance as an indicator of malignant transformation. A similar deficiency was reported in total homogenates of tumours of colon, kidney, lung and liver. In previous biochemical studies we failed to confirm the consistent reduction in ADCP concentration in cancer tissues. A possible explanation for our findings was thought to be intercellular heterogeneity in ADCP expression in individual tumour cells. To study ADCP expression in individual cells, we developed an immunohistochemical method which was applied to tissue sections. Paraformaldehyde--lysine--periodate (PLP) solution was found to be a suitable fixative. Fixed tissue samples were paraffin-embedded, sectioned and stained for ADCP, using an indirect peroxidase-labelled antibody procedure. The protein was localized in normal colonic mucosa, mainly in the brush border region of the luminal epithelium and in cytoplasmic granules. Intense ADCP immunoreactivity was found also in the basal part of some cells. In cancer cells, three staining patterns were observed: membranous, diffuse cytoplasmic and granular cytoplasmic. The adenocarcinomas exhibited significant intratumour and intertumour heterogeneity in their staining types. Further studies on ADCP expression in colorectal cancer in relation to clinical and histopathological characteristics are warranted in order to fully evaluate the potential significance of ADCP as a cancer associated antigen.

  20. The human telomerase RNA component, hTR, activates the DNA-dependent protein kinase to phosphorylate heterogeneous nuclear ribonucleoprotein A1.

    PubMed

    Ting, Nicholas S Y; Pohorelic, Brant; Yu, Yaping; Lees-Miller, Susan P; Beattie, Tara L

    2009-10-01

    Telomere integrity in human cells is maintained by the dynamic interplay between telomerase, telomere associated proteins, and DNA repair proteins. These interactions are vital to suppress DNA damage responses and unfavorable changes in chromosome dynamics. The DNA-dependent protein kinase (DNA-PK) is critical for this process. Cells deficient for functional DNA-PKcs show increased rates of telomere loss, accompanied by chromosomal fusions and translocations. Treatment of cells with specific DNA-PK kinase inhibitors leads to similar phenotypes. These observations indicate that the kinase activity of DNA-PK is required for its function at telomeres possibly through phosphorylation of essential proteins needed for telomere length maintenance. Here we show that the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a direct substrate for DNA-PK in vitro. Phosphorylation of hnRNP A1 is stimulated not only by the presence of DNA but also by the telomerase RNA component, hTR. Furthermore, we show that hnRNP A1 is phosphorylated in vivo in a DNA-PK-dependent manner and that this phosphorylation is greatly reduced in cell lines which lack hTR. These data are the first to report that hTR stimulates the kinase activity of DNA-PK toward a known telomere-associated protein, and may provide further insights into the function of DNA-PK at telomeres.

  1. Bio-mimetic nanostructure self-assembled from Au@Ag heterogeneous nanorods and phage fusion proteins for targeted tumor optical detection and photothermal therapy.

    PubMed

    Wang, Fei; Liu, Pei; Sun, Lin; Li, Cuncheng; Petrenko, Valery A; Liu, Aihua

    2014-10-28

    Nanomaterials with near-infrared (NIR) absorption have been widely studied in cancer detection and photothermal therapy (PTT), while it remains a great challenge in targeting tumor efficiently with minimal side effects. Herein we report a novel multifunctional phage-mimetic nanostructure, which was prepared by layer-by-layer self-assembly of Au@Ag heterogenous nanorods (NRs) with rhodamine 6G, and specific pVIII fusion proteins. Au@Ag NRs, first being applied for PTT, exhibited excellent stability, cost-effectivity, biocompatibility and tunable NIR absorption. The fusion proteins were isolated from phage DDAGNRQP specifically selected from f8/8 landscape phage library against colorectal cancer cells in a high-throughput way. Considering the definite charge distribution and low molecular weight, phage fusion proteins were assembled on the negatively charged NR core by electrostatic interactions, exposing the N-terminus fused with DDAGNRQP peptide on the surface. The fluorescent images showed that assembled phage fusion proteins can direct the nanostructure into cancer cells. The nanostructure was more efficient than gold nanorods and silver nanotriangle-based photothermal agents and was capable of specifically ablating SW620 cells after 10 min illumination with an 808 nm laser in the light intensity of 4 W/cm(2). The prepared nanostructure would become an ideal reagent for simutaneously targeted optical imaging and PTT of tumor.

  2. Bio-mimetic Nanostructure Self-assembled from Au@Ag Heterogeneous Nanorods and Phage Fusion Proteins for Targeted Tumor Optical Detection and Photothermal Therapy

    NASA Astrophysics Data System (ADS)

    Wang, Fei; Liu, Pei; Sun, Lin; Li, Cuncheng; Petrenko, Valery A.; Liu, Aihua

    2014-10-01

    Nanomaterials with near-infrared (NIR) absorption have been widely studied in cancer detection and photothermal therapy (PTT), while it remains a great challenge in targeting tumor efficiently with minimal side effects. Herein we report a novel multifunctional phage-mimetic nanostructure, which was prepared by layer-by-layer self-assembly of Au@Ag heterogenous nanorods (NRs) with rhodamine 6G, and specific pVIII fusion proteins. Au@Ag NRs, first being applied for PTT, exhibited excellent stability, cost-effectivity, biocompatibility and tunable NIR absorption. The fusion proteins were isolated from phage DDAGNRQP specifically selected from f8/8 landscape phage library against colorectal cancer cells in a high-throughput way. Considering the definite charge distribution and low molecular weight, phage fusion proteins were assembled on the negatively charged NR core by electrostatic interactions, exposing the N-terminus fused with DDAGNRQP peptide on the surface. The fluorescent images showed that assembled phage fusion proteins can direct the nanostructure into cancer cells. The nanostructure was more efficient than gold nanorods and silver nanotriangle-based photothermal agents and was capable of specifically ablating SW620 cells after 10 min illumination with an 808 nm laser in the light intensity of 4 W/cm2. The prepared nanostructure would become an ideal reagent for simutaneously targeted optical imaging and PTT of tumor.

  3. A single molecule approach for measuring the transport properties and energetics of membrane proteins in heterogeneous planar bio-mimetic assemblies

    NASA Astrophysics Data System (ADS)

    Poudel, Kumud Raj

    The significance of transmembrane protein research is well documented. Numerous studies have clearly established the biological, biophysical and pharmaceutical importance that these membrane components serve. Communications through receptors regulate countless body functions and they also provide structural support to the cell. However, a lack of high-resolution structure data has limited our understanding of these proteins that make it necessary to study them in in-vitro platforms or 'bio-mimetic' assemblies. Albeit that an assortment of platforms have been suggested for in-vitro studies, the issues, however, remain the same. The lack of mobility of the proteins in artificial environments, the question of functionality that arises with mobility and the search in general for the best assembly, is still a work in progress. In this work, we have taken some of the most accepted platforms in the field and characterized them through the lens of single molecule spectroscopy. We have addressed the question of mobility by reducing it down to a single molecule and comparing it with the bulk. By utilizing the Serotonin Receptor 5HT3A we have shown that techniques such as passivation of the substrates in the assemblies by Bovine Serum Albumin has a significant effect at the molecular level. The larger size of the intracellular domain for the 5HT3A served as a great probe to understand and evaluate the interaction of a surface passivator with the integrated membrane protein. We have also taken this a step further by developing a novel, single cushion 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) assembly and added another degree of complexity- through a phase transition. We have utilized phase transition to get an insight into the local protein environment, activation energies, heterogeneity and diffusion characteristics by using Annexin V as our probe. The work presented here studies two completely different biological platforms using two entirely different transmembrane

  4. Heterogeneous Catalysis.

    ERIC Educational Resources Information Center

    Miranda, R.

    1989-01-01

    Described is a heterogeneous catalysis course which has elements of materials processing embedded in the classical format of catalytic mechanisms and surface chemistry. A course outline and list of examples of recent review papers written by students are provided. (MVL)

  5. Heterogeneous catalysis.

    PubMed

    Schlögl, Robert

    2015-03-09

    A heterogeneous catalyst is a functional material that continually creates active sites with its reactants under reaction conditions. These sites change the rates of chemical reactions of the reactants localized on them without changing the thermodynamic equilibrium between the materials.

  6. Phosphorylation of serine residues in histidine-tag sequences attached to recombinant protein kinases: a cause of heterogeneity in mass and complications in function.

    PubMed

    Du, Ping; Loulakis, Pat; Luo, Chun; Mistry, Anil; Simons, Samuel P; LeMotte, Peter K; Rajamohan, Francis; Rafidi, Kristina; Coleman, Kevin G; Geoghegan, Kieran F; Xie, Zhi

    2005-12-01

    High-level recombinant expression of protein kinases in eukaryotic cells or Escherichia coli commonly gives products that are phosphorylated by autocatalysis or by the action of endogenous kinases. Here, we report that phosphorylation occurred on serine residues adjacent to hexahistidine affinity tags (His-tags) derived from several commercial expression vectors and fused to overexpressed kinases. The result was observed with a variety of recombinant kinases expressed in either insect cells or E. coli. Multiple phosphorylations of His-tagged full-length Aurora A, a protein serine/threonine kinase, were detected by mass spectrometry when it was expressed in insect cells in the presence of okadaic acid, a protein phosphatase inhibitor. Peptide mapping by liquid chromatography-mass spectrometry detected phosphorylations on all three serine residues in an N-terminal tag, alpha-N-acetyl-MHHHHHHSSGLPRGS. The same sequence was also phosphorylated, but only at a low level, when a His-tagged protein tyrosine kinase, Pyk2 was expressed in insect cells and activated in vitro. When catalytic domains of Aurora A and several other protein serine/threonine kinases were expressed in E. coli, serines in the affinity tag sequence GSSHHHHHHSSGLVPRGS were also variably phosphorylated. His-Aurora A with hyperphosphorylation of the serine residues in the tag aggregated and resisted thrombin-catalyzed removal of the tag. Treatment with alkaline phosphatase partly restored sensitivity to thrombin. The same His-tag sequence was also detected bearing alpha-N-d-gluconoylation in addition to multiple phosphorylations. The results show that histidine-tag sequences can receive complicated posttranslational modification, and that the hyperphosphorylation and resulting heterogeneity of the recombinant fusion proteins can interfere with downstream applications.

  7. Surface-labelling studies on skeletal-muscle cells in vitro. Heterogeneity of iodinated cell-surface proteins.

    PubMed Central

    Cates, G A; Holland, P C

    1980-01-01

    1. Two distinct classes of protein were detected at the surface of chick-embryo skeletal-muscle cells after iodination of the cells in monolayer culture. 2. The two classes of iodinated proteins differed in their ability to co-purify with a vesicular plasma-membrane fraction prepared from surface-labelled cells. 3. One class consisted of predominantly high-molecular-weight glycoproteins that co-purified with the plasma-membrane fraction, but showed no significant qualitative or quantitative alterations in labelling with 125I and lactoperoxidase during myogenesis. 4. A second class of predominantly lower-molecular-weight proteins showed reproducible quantitative alterations in 125I-labelling during myogenesis but failed to co-purify with the plasma-membrane fraction. 5. This second class of proteins may represent matrix proteins involved in intercellular adhesion or adhesion of cells to the substratum. They are unlikely to be directly required for the process of plasma-membrane fusion during myogenesis, since they do not copurify with a vesicular plasma-membrane fraction known to be capable of Ca2+-dependent fusion in vitro. PMID:7370009

  8. The C-protein tetramer binds 230 to 240 nucleotides of pre-mRNA and nucleates the assembly of 40S heterogeneous nuclear ribonucleoprotein particles.

    PubMed Central

    Huang, M; Rech, J E; Northington, S J; Flicker, P F; Mayeda, A; Krainer, A R; LeStourgeon, W M

    1994-01-01

    A series of in vitro protein-RNA binding studies using purified native (C1)3C2 and (A2)3B1 tetramers, total soluble heterogeneous nuclear ribonucleoprotein (hnRNP), and pre-mRNA molecules differing in length and sequence have revealed that a single C-protein tetramer has an RNA site size of 230 to 240 nucleotides (nt). Two tetramers bind twice this RNA length, and three tetramers fold monoparticle lengths of RNA (700 nt) into a unique 19S triangular complex. In the absence of this unique structure, the basic A- and B-group proteins bind RNA to form several different artifactual structures which are not present in preparations of native hnRNP and which do not function in hnRNP assembly. Three (A2)3B1 tetramers bind the 19S complex to form a 35S assembly intermediate. Following UV irradiation to immobilize the C proteins on the packaged RNA, the 19S triangular complex is recovered as a remnant structure from both native and reconstituted hnRNP particles. C protein-RNA complexes composed of three, six, or nine tetramers (one, two, or three triangular complexes) nucleate the stoichiometric assembly of monomer, dimer, and trimer hnRNP particles. The binding of C-protein tetramers to RNAs longer than 230 nt is through a self-cooperative combinatorial mode. RNA packaged in the 19S complex and in 40S hnRNP particles is efficiently spliced in vitro. These findings demonstrate that formation of the triangular C protein-RNA complex is an obligate first event in the in vitro and probably the in vivo assembly the 40S hnRNP core particle, and they provide insight into the mechanism through which the core proteins package 700-nt increments of RNA. These findings also demonstrate that unless excluded by other factors, the C proteins are likely to be located along the length of nascent transcripts. Images PMID:8264621

  9. Heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by increasing protein translation of selected transcripts in cancer cells.

    PubMed

    Chang, Elizabeth T; Parekh, Palak R; Yang, Qingyuan; Nguyen, Duc M; Carrier, France

    2016-03-01

    The heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by coordinating the translation of selected transcripts associated with proliferation and survival. hnRNP A18 binds to and stabilizes the transcripts of pro-survival genes harboring its RNA signature motif in their 3'UTRs. hnRNP A18 binds to ATR, RPA, TRX, HIF-1α and several protein translation factor mRNAs on polysomes and increases de novo protein translation under cellular stress. Most importantly, down regulation of hnRNP A18 decreases proliferation, invasion and migration in addition to significantly reducing tumor growth in two mouse xenograft models, melanoma and breast cancer. Moreover, tissue microarrays performed on human melanoma, prostate, breast and colon cancer indicate that hnRNP A18 is over expressed in 40 to 60% of these malignant tissue as compared to normal adjacent tissue. Immunohistochemistry data indicate that hnRNP A18 is over expressed in the stroma and hypoxic areas of human tumors. These data thus indicate that hnRNP A18 can promote tumor growth in in vivo models by coordinating the translation of pro-survival transcripts to support the demands of proliferating cells and increase survival under cellular stress. hnRNP A18 therefore represents a new target to selectively inhibit protein translation in tumor cells.

  10. Heterogeneous reaction kinetics and mechanism of the nitration of aerosolized protein by O3 and NO2

    NASA Astrophysics Data System (ADS)

    Shiraiwa, Manabu; Sosedova, Yulia; Rouvière, Aurélie; Ammann, Markus; Pöschl, Ulrich

    2010-05-01

    The effects of air pollution on allergic diseases are not yet well-understood. Proteins contained in biogenic aerosol particles (pollen, spores, bacteria, etc.), which accounts for up to 5% of urban air particulate matter, are efficiently nitrated in polluted environments before inhalation and deposition in the human respiratory tract [1], which is likely to trigger immune reactions for allergies. Proteins undergo a nitration reaction that leads to the formation of 3-nitrotyrosine residues. The kinetics and reaction mechanism of protein nitration are still largely unknown. The kinetics of nitration of protein particles by O3 and NO2 was measured using the short-lived radioactive tracer 13N. The routine for the online production of 13N-labeled nitrogen dioxide and the main experimental setup were reported previously [2]. Bovine serum albumin (BSA) was used as a model protein compound. Deliquesced NaCl particles were also used as a reference. Particles generated by an ultrasonic nebulizer were mixed with O3 (0 - 150 ppb) and NO2 (5 - 100 ppb) in a flow tube reactor under humid conditions (30 - 75 % RH), which lead to gel-like swelling of the protein [3, 4]. The reaction time was varied in the range of 4 -10 min by changing the position of the inlet of the reactor. The surface concentration of particles was monitored by a scanning mobility particle sizer (SMPS). After passing through the flow tube reactor, the gas and aerosol flow entered a narrow parallel-plate diffusion denuder coated to selectively absorb gas phase NO2, followed by a particle filter collecting the particles. The γ detectors were attached to each denuders and the filter to count the amount of gamma quanta, which are emitted in the decay of 13N. From the count-rate, the concentration of the corresponding species was derived, which was used for the calculation of uptake coefficients of NO2 (γNO2). In absence of O3 in the flow tube reactor, NO2 uptake by both BSA and deliquesced NaCl were below the

  11. Conformational Heterogeneity Determined by Folding and Oligomer Assembly Routes of the Interferon Response Inhibitor NS1 Protein, Unique to Human Respiratory Syncytial Virus.

    PubMed

    Pretel, Esteban; Sánchez, Ignacio E; Fassolari, Marisol; Chemes, Lucía B; de Prat-Gay, Gonzalo

    2015-08-25

    The nonstructural NS1 protein is an essential virulence factor of the human respiratory syncytial virus, with a predominant role in the inhibition of the host antiviral innate immune response. This inhibition is mediated by multiple protein-protein interactions and involves the formation of large oligomeric complexes. There is neither a structure nor sequence or functional homologues of this protein, which points to a distinctive mechanism for blocking the interferon response among viruses. The NS1 native monomer follows a simple unfolding kinetics via a nativelike transition state ensemble, with a half-life of 45 min, in agreement with a highly stable core structure at equilibrium. Refolding is a complex process that involves several slowly interconverting species compatible with proline isomerization. However, an ultrafast folding event with a half-life of 0.2 ms is indicative of a highly folding compatible species within the unfolded state ensemble. On the other hand, the oligomeric assembly route from the native monomer, which does not involve unfolding, shows a monodisperse and irreversible end-point species triggered by a mild temperature change, with half-lives of 160 and 26 min at 37 and 47 °C, respectively, and at a low protein concentration (10 μM). A large secondary structure change into β-sheet structure and the formation of a dimeric nucleus precede polymerization by the sequential addition of monomers at the surprisingly low rate of one monomer every 34 s. The polymerization phase is followed by the binding to thioflavin-T indicative of amyloid-like, albeit soluble, repetitive β-sheet quaternary structure. The overall process is reversible only up until ~8 min, a time window in which most of the secondary structure change takes place. NS1's multiple binding activities must be accommodated in a few binding interfaces at most, something to be considered remarkable given its small size (15 kDa). Thus, conformational heterogeneity, and in particular

  12. Patient-derived glioblastoma cells show significant heterogeneity in treatment responses to the inhibitor-of-apoptosis-protein antagonist birinapant

    PubMed Central

    Zakaria, Z; Tivnan, A; Flanagan, L; Murray, D W; Salvucci, M; Stringer, B W; Day, B W; Boyd, A W; Kögel, D; Rehm, M; O'Brien, D F; Byrne, A T; Prehn, J H M

    2016-01-01

    Background: Resistance to temozolomide (TMZ) greatly limits chemotherapeutic effectiveness in glioblastoma (GBM). Here we analysed the ability of the Inhibitor-of-apoptosis-protein (IAP) antagonist birinapant to enhance treatment responses to TMZ in both commercially available and patient-derived GBM cells. Methods: Responses to TMZ and birinapant were analysed in a panel of commercial and patient-derived GBM cell lines using colorimetric viability assays, flow cytometry, morphological analysis and protein expression profiling of pro- and antiapoptotic proteins. Responses in vivo were analysed in an orthotopic xenograft GBM model. Results: Single-agent treatment experiments categorised GBM cells into TMZ-sensitive cells, birinapant-sensitive cells, and cells that were insensitive to either treatment. Combination treatment allowed sensitisation to therapy in only a subset of resistant GBM cells. Cell death analysis identified three principal response patterns: Type A cells that readily activated caspase-8 and cell death in response to TMZ while addition of birinapant further sensitised the cells to TMZ-induced cell death; Type B cells that readily activated caspase-8 and cell death in response to birinapant but did not show further sensitisation with TMZ; and Type C cells that showed no significant cell death or moderately enhanced cell death in the combined treatment paradigm. Furthermore, in vivo, a Type C patient-derived cell line that was TMZ-insensitive in vitro and showed a strong sensitivity to TMZ and TMZ plus birinapant treatments. Conclusions: Our results demonstrate remarkable differences in responses of patient-derived GBM cells to birinapant single and combination treatments, and suggest that therapeutic responses in vivo may be greatly affected by the tumour microenvironment. PMID:26657652

  13. Rate heterogeneity in six protein-coding genes from the holoparasite Balanophora (Balanophoraceae) and other taxa of Santalales

    PubMed Central

    Su, Huei-Jiun; Hu, Jer-Ming

    2012-01-01

    Background and Aims The holoparasitic flowering plant Balanophora displays extreme floral reduction and was previously found to have enormous rate acceleration in the nuclear 18S rDNA region. So far, it remains unclear whether non-ribosomal, protein-coding genes of Balanophora also evolve in an accelerated fashion and whether the genes with high substitution rates retain their functionality. To tackle these issues, six different genes were sequenced from two Balanophora species and their rate variation and expression patterns were examined. Methods Sequences including nuclear PI, euAP3, TM6, LFY and RPB2 and mitochondrial matR were determined from two Balanophora spp. and compared with selected hemiparasitic species of Santalales and autotrophic core eudicots. Gene expression was detected for the six protein-coding genes and the expression patterns of the three B-class genes (PI, AP3 and TM6) were further examined across different organs of B. laxiflora using RT-PCR. Key Results Balanophora mitochondrial matR is highly accelerated in both nonsynonymous (dN) and synonymous (dS) substitution rates, whereas the rate variation of nuclear genes LFY, PI, euAP3, TM6 and RPB2 are less dramatic. Significant dS increases were detected in Balanophora PI, TM6, RPB2 and dN accelerations in euAP3. All of the protein-coding genes are expressed in inflorescences, indicative of their functionality. PI is restrictively expressed in tepals, synandria and floral bracts, whereas AP3 and TM6 are widely expressed in both male and female inflorescences. Conclusions Despite the observation that rates of sequence evolution are generally higher in Balanophora than in hemiparasitic species of Santalales and autotrophic core eudicots, the five nuclear protein-coding genes are functional and are evolving at a much slower rate than 18S rDNA. The mechanism or mechanisms responsible for rapid sequence evolution and concomitant rate acceleration for 18S rDNA and matR are currently not well

  14. Heterogeneous side chain conformation highlights a network of interactions implicated in hysteresis of the knotted protein, minimal tied trefoil

    NASA Astrophysics Data System (ADS)

    Burban, David J.; Haglund, Ellinor; Capraro, Dominique T.; Jennings, Patricia A.

    2015-09-01

    Hysteresis is a signature for a bistability in the native landscape of a protein with significant transition state barriers for the interconversion of stable species. Large global stability, as in GFP, contributes to the observation of this rare hysteretic phenomenon in folding. The signature for such behavior is non-coincidence in the unfolding and refolding transitions, despite waiting significantly longer than the time necessary for complete denaturation. Our work indicates that hysteresis in the knotted protein, the minimal tied trefoil from Thermotoga maritma (MTTTm), is mediated by a network of side chain interactions within a tightly packed core. These initially identified interactions include proline 62 from a tight β-like turn, phenylalanine 65 at the beginning of the knotting loop, and histidine 114 that initiates the threading element. It is this tightly packed region and the knotting element that we propose is disrupted with prolonged incubation in the denatured state, and is involved in the observed hysteresis. Interestingly, the disruption is not linked to backbone interactions, but rather to the packing of side chains in this critical region.

  15. Re-emergence of circulatory foot-and-mouth disease virus serotypes Asia1 in Bangladesh and VP1 protein heterogeneity with vaccine strain IND 63/72.

    PubMed

    Ullah, H; Siddique, M A; Al Amin, Md; Das, B C; Sultana, M; Hossain, M A

    2015-02-01

    Foot-and-mouth disease virus (FMDV) serotypes O, A and Asia1 are responsible for significant number of disease outbreaks in Bangladesh; however serotype Asia1 has not been reported in circulation since 1996. The present investigation reports the detection of serotype FMDV Asia1 from local farms in 2012 and 2013 outbreaks. The farms were located in Jessore and Gazipur districts, and one of these farms was under vaccine control programme. Phylogenetic analysis of the complete VP1 gene revealed that FMDV Asia1 is under genetic lineage C having close similarity to the Asia1 sequences of Indian origin. The circulatory genotype Asia1 showed VP1 protein sequence heterogeneity of eight amino acid substitutions within the G-H loop with the vaccine strain [IND 63/72 (AY304994)] used in vaccination programme. ELISA assay revealed that, of seven, only one local field serum sample (cattle vaccinated 38 days earlier) was positive at a titre level of >2.4 (log10) but failed to protect the cattle from infection occurred by the virus. This investigation focused that the eight amino acid substitution in VP1 protein at G-H loop of the locally circulated FMDV serotype Asia1 strain may be a reason for current vaccination failure.

  16. NonO, a non-POU-domain-containing, octamer-binding protein, is the mammalian homolog of Drosophila nonAdiss.

    PubMed

    Yang, Y S; Hanke, J H; Carayannopoulos, L; Craft, C M; Capra, J D; Tucker, P W

    1993-09-01

    We have cloned the ubiquitous form of an octamer-binding, 60-kDa protein (NonO) that appears to be the mammalian equivalent of the Drosophila visual and courtship song behavior protein, no-on-transient A/dissonance (nonAdiss). A region unprecedently rich in aromatic amino acids containing two ribonuclear protein binding motifs is highly conserved between the two proteins. A ubiquitous form of NonO is present in all adult tissues, whereas lymphocytes and retina express unique forms of NonO mRNA. The ubiquitous form contains a potential helix-turn-helix motif followed by a highly charged region but differs from prototypic octamer-binding factors by lacking the POU DNA-binding domain. In addition to its conventional octamer duplex-binding, NonO binds single-stranded DNA and RNA at a site independent of the duplex site.

  17. Targeting eNOS and beyond: Emerging heterogeneity of the role of endothelial Rho proteins in stroke protection

    PubMed Central

    Sawada, Naoki; Liao, James K.

    2010-01-01

    Summary Currently available modalities for the treatment of acute ischemic stroke are aimed to preserve or augment cerebral blood flow (CBF). Experimental evidence suggests that statins, which show 25–30% reduction of stroke incidence in clinical trials, confer stroke protection by upregulation of eNOS and increasing CBF. The upregulation of eNOS by statins is mediated by inhibition of small GTP-binding protein RhoA. Our recent study uncovered a unique role for a Rho-family member Rac1 in stroke protection. Rac1 in endothelium does not affect CBF. Instead, inhibition of endothelial Rac1 leads to broad upregulation of genes relevant to neurovascular protection. Intriguingly, inhibition of endothelial Rac1 enhances neuronal cell survival through endothelium-derived neurotrophic factors including artemin. This review discusses the emerging therapeutic opportunities to target the neurovascular signaling beyond the blood-brain barrier, with special emphasis on the novel role of endothelial Rac1 in stroke protection. PMID:19673606

  18. Heterogeneity of myofibrillar proteins in lobster fast and slow muscles: variants of troponin, paramyosin, and myosin light chains comprise four distinct protein assemblages

    SciTech Connect

    Mykles, D.L.

    1985-01-01

    Fast and slow muscles from the claws and abdomen of the American lobster Homarus americanus were examined for adenosine triphosphatase (ATPase) activity and for differences in myofibrillar proteins. Both myosin and actomyosin ATPase were correlated with fiber composition and contractile speed. Four distinct patterns of myofibrilla proteins observed in sodium dodecyl sulfate-polyacrylamide gels were distinguished by different assemblages of regulatory and contractile protein variants. A total of three species of troponin-T, five species of troponin-I, and three species of troponin-C were observed. Lobster myosins contained two groups of light chains (LC), termed alpha and beta. There were three ..cap alpha..-LC variants and two ..beta..-LC variants. There were no apparent differences in myosin heavy chain, actin, and tropomyosin. Only paramyosin showed a pattern completely consistent with muscle fiber type: slow fibers contained a species (105 kD) slightly smaller than the principle variant (110 kD) in fast fibers. It is proposed that the type of paramyosin present could provide a biochemical marker to identify the fiber composition of muscles that have not been fully characterized. The diversity of troponin and myosin LC variants suggests that subtle differences in physiological performance exist within the broader categories of fast- and slow-twitch muscles. 31 references, 6 figures, 2 tables.

  19. [Heterogeneity and polymorphism of functionally specialized blood proteins in migratory fish: case study of the North Caspian population of the Russian sturgeon during sea and river periods of life. 1. Albumins].

    PubMed

    Luk'ianenko, V I; Khabarov, M V; Luk'ianenko, V V

    2002-01-01

    A comparative study of the levels of heterogeneity and polymorphism of albumins, the most important functionally specialized blood proteins, has been carried out. The albumin system of Russian sturgeon undergoes distinct changes while the fish change habitat during the spawning migration from sea to river. They are expressed as an increased level of heterogeneity, an increased content of serum albumins in fish during the river period of life as compared to the sea period, and an increased share of a slow component of albuminograms. These changes suggest a significant role of the blood albumin system in adaptation of the Caspian sturgeon migratory species to fresh water life conditions.

  20. Differential protein structural disturbances and suppression of assembly partners produced by nonsense GABRG2 epilepsy mutations: implications for disease phenotypic heterogeneity.

    PubMed

    Wang, Juexin; Shen, Dingding; Xia, Geqing; Shen, Wangzhen; Macdonald, Robert L; Xu, Dong; Kang, Jing-Qiong

    2016-10-20

    Mutations in GABAA receptor subunit genes are frequently associated with epilepsy, and nonsense mutations in GABRG2 are associated with several epilepsy syndromes including childhood absence epilepsy, generalized tonic clonic seizures and the epileptic encephalopathy, Dravet syndrome. The molecular basis for the phenotypic heterogeneity of mutations is unclear. Here we focused on three nonsense mutations in GABRG2 (GABRG2(R136*), GABRG2(Q390*) and GABRG2(W429*)) associated with epilepsies of different severities. Structural modeling and structure-based analysis indicated that the surface of the wild-type γ2 subunit was naturally hydrophobic, which is suitable to be buried in the cell membrane. Different mutant γ2 subunits had different stabilities and different interactions with their wild-type subunit binding partners because they adopted different conformations and had different surface hydrophobicities and different tendency to dimerize. We utilized flow cytometry and biochemical approaches in combination with lifted whole cell patch-clamp recordings. We demonstrated that the truncated subunits had no to minimal surface expression and unchanged or reduced surface expression of wild-type partnering subunits. The amplitudes of GABA-evoked currents from the mutant α1β2γ2(R136*), α1β2γ2(Q390*) and α1β2γ2(W429*) receptors were reduced compared to the currents from α1β2γ2 receptors but with differentially reduced levels. This thus suggests differential protein structure disturbances are correlated with disease severity.

  1. Molecular Basis for Structural Heterogeneity of an Intrinsically Disordered Protein Bound to a Partner by Combined ESI-IM-MS and Modeling

    NASA Astrophysics Data System (ADS)

    D'Urzo, Annalisa; Konijnenberg, Albert; Rossetti, Giulia; Habchi, Johnny; Li, Jinyu; Carloni, Paolo; Sobott, Frank; Longhi, Sonia; Grandori, Rita

    2015-03-01

    Intrinsically disordered proteins (IDPs) form biologically active complexes that can retain a high degree of conformational disorder, escaping structural characterization by conventional approaches. An example is offered by the complex between the intrinsically disordered NTAIL domain and the phosphoprotein X domain (PXD) from measles virus (MeV). Here, distinct conformers of the complex are detected by electrospray ionization-mass spectrometry (ESI-MS) and ion mobility (IM) techniques yielding estimates for the solvent-accessible surface area (SASA) in solution and the average collision cross-section (CCS) in the gas phase. Computational modeling of the complex in solution, based on experimental constraints, provides atomic-resolution structural models featuring different levels of compactness. The resulting models indicate high structural heterogeneity. The intermolecular interactions are predominantly hydrophobic, not only in the ordered core of the complex, but also in the dynamic, disordered regions. Electrostatic interactions become involved in the more compact states. This system represents an illustrative example of a hydrophobic complex that could be directly detected in the gas phase by native mass spectrometry. This work represents the first attempt to modeling the entire NTAIL domain bound to PXD at atomic resolution.

  2. Differential protein structural disturbances and suppression of assembly partners produced by nonsense GABRG2 epilepsy mutations: implications for disease phenotypic heterogeneity

    PubMed Central

    Wang, Juexin; Shen, Dingding; Xia, Geqing; Shen, Wangzhen; Macdonald, Robert L.; Xu, Dong; Kang, Jing-Qiong

    2016-01-01

    Mutations in GABAA receptor subunit genes are frequently associated with epilepsy, and nonsense mutations in GABRG2 are associated with several epilepsy syndromes including childhood absence epilepsy, generalized tonic clonic seizures and the epileptic encephalopathy, Dravet syndrome. The molecular basis for the phenotypic heterogeneity of mutations is unclear. Here we focused on three nonsense mutations in GABRG2 (GABRG2(R136*), GABRG2(Q390*) and GABRG2(W429*)) associated with epilepsies of different severities. Structural modeling and structure-based analysis indicated that the surface of the wild-type γ2 subunit was naturally hydrophobic, which is suitable to be buried in the cell membrane. Different mutant γ2 subunits had different stabilities and different interactions with their wild-type subunit binding partners because they adopted different conformations and had different surface hydrophobicities and different tendency to dimerize. We utilized flow cytometry and biochemical approaches in combination with lifted whole cell patch-clamp recordings. We demonstrated that the truncated subunits had no to minimal surface expression and unchanged or reduced surface expression of wild-type partnering subunits. The amplitudes of GABA-evoked currents from the mutant α1β2γ2(R136*), α1β2γ2(Q390*) and α1β2γ2(W429*) receptors were reduced compared to the currents from α1β2γ2 receptors but with differentially reduced levels. This thus suggests differential protein structure disturbances are correlated with disease severity. PMID:27762395

  3. The heterogeneity of spermatogonia is revealed by their topology and expression of marker proteins including the germ cell-specific proteins Nanos2 and Nanos3.

    PubMed

    Suzuki, Hitomi; Sada, Aiko; Yoshida, Shosei; Saga, Yumiko

    2009-12-15

    Spermatogonial stem cells (SSCs) reside in undifferentiated type-A spermatogonia and contribute to continuous spermatogenesis by maintaining the balance between self-renewal and differentiation, thereby meeting the biological demand in the testis. Spermatogonia have to date been characterized principally through their morphology, but we herein report the detailed characterization of undifferentiated spermatogonia in mouse testes based on their gene expression profiles in combination with topological features. The detection of the germ cell-specific proteins Nanos2 and Nanos3 as markers of spermatogonia has enabled the clear dissection of complex populations of these cells as Nanos2 was recently shown to be involved in the maintenance of stem cells. Nanos2 is found to be almost exclusively expressed in A(s) to A(pr) cells, whereas Nanos3 is detectable in most undifferentiated spermatogonia (A(s) to A(al)) and differentiating A(1) spermatogonia. In our present study, we find that A(s) and A(pr) can be basically classified into three categories: (1) GFRalpha1(+)Nanos2(+)Nanos3(-)Ngn3(-), (2) GFRalpha1(+)Nanos2(+)Nanos3(+)Ngn3(-), and (3) GFRalpha1(-)Nanos2(+/-)Nanos3(+)Ngn3(+). We propose that the first of these groups is most likely to include the stem cell population and that Nanos3 may function in transit amplifying cells.

  4. Tracer-based estimates of protein flux in cases of incomplete product renewal: evidence and implications of heterogeneity in collagen turnover

    PubMed Central

    Zhou, Haihong; Wang, Sheng-Ping; Herath, Kithsiri; Kasumov, Takhar; Sadygov, Rovshan G.; Kelley, David E.

    2015-01-01

    The synthesis of various molecules can be estimated by measuring the incorporation of a labeled precursor into a product of interest. Unfortunately, a central problem in many studies has been an inability to estimate the intracellular dilution of the precursor and therein correctly calculate the synthesis of the product; it is generally assumed that measuring the true product labeling is straightforward. We initiated a study to examine liver collagen synthesis and identified an apparent problem with assumptions regarding measurements of the product labeling. Since it is well known that collagen production is relatively slow, we relied on the use of [2H]H2O labeling (analogous to a primed infusion) and sampled animals over the course of 16 days. Although the water labeling (the precursor) remained stable and we observed the incorporation of labeled amino acids into collagen, the asymptotic protein labeling was considerably lower than what would be expected based on the precursor labeling. Although this observation is not necessarily surprising (i.e., one might expect that a substantial fraction of the collagen pool would appear “inert” or turn over at a very slow rate), its implications are of interest in certain areas. Herein, we discuss a novel situation in which tracers are used to quantify rates of flux under conditions where a product may not undergo complete replacement. We demonstrate how heterogeneity in the product pool can lead one to the wrong conclusions regarding estimates of flux, and we outline an approach that may help to minimize errors surrounding data interpretation. PMID:26015435

  5. Heterogeneity of Raft-Type Membrane Microdomains Associated with VP4, the Rotavirus Spike Protein, in Caco-2 and MA 104 Cells▿

    PubMed Central

    Delmas, Olivier; Breton, Michelyne; Sapin, Catherine; Le Bivic, André; Colard, Odile; Trugnan, Germain

    2007-01-01

    Previous studies have shown that rotavirus virions, a major cause of infantile diarrhea, assemble within small intestinal enterocytes and are released at the apical pole without significant cell lysis. In contrast, for the poorly differentiated kidney epithelial MA 104 cells, which have been used extensively to study rotavirus assembly, it has been shown that rotavirus is released by cell lysis. The subsequent discovery that rotavirus particles associate with raft-type membrane microdomains (RTM) in Caco-2 cells provided a simple explanation for rotavirus polarized targeting. However, the results presented here, together with those recently published by another group, demonstrate that rotavirus also associates with RTM in MA 104 cells, thus indicating that a simple interaction of rotavirus with rafts is not sufficient to explain its apical targeting in intestinal cells. In the present study, we explore the possibility that RTM may have distinct physicochemical properties that may account for the differences observed in the rotavirus cell cycle between MA 104 and Caco-2 cells. We show here that VP4 association with rafts is sensitive to cholesterol extraction by methyl-β-cyclodextrin treatment in MA 104 cells and insensitive in Caco-2 cells. Using the VP4 spike protein as bait, VP4-enriched raft subsets were immunopurified. They contained 10 to 15% of the lipids present in total raft membranes. We found that the nature and proportion of phospholipids and glycosphingolipids were different between the two cell lines. We propose that this raft heterogeneity may support the cell type dependency of virus assembly and release. PMID:17135322

  6. Human milk fat globules: polar lipid composition and in situ structural investigations revealing the heterogeneous distribution of proteins and the lateral segregation of sphingomyelin in the biological membrane.

    PubMed

    Lopez, Christelle; Ménard, Olivia

    2011-03-01

    Although human milk fat globules (MFG) are of primary importance since they are the exclusive lipid delivery carriers in the gastrointestinal tract of breast-fed infants, they remain the poorly understood aspect of milk. The objectives of this study were to investigate these unique colloidal assemblies and their interfacial properties, i.e. composition and structure of their biological membrane. In mature breast milk, MFG have a mean diameter of 4-5 microm, a surface area of about 2m(2)/g fat and an apparent zeta potential ζ=-6.7 ± 0.5 mV at 37°C. Human MFG contain 3-4mg polar lipids/g fat as quantified by HPLC/ELSD. The main polar lipids are sphingomyelin (SM; 36-45%, w/w), phosphatidylcholine (19-23%, w/w) and phosphatidylethanolamine (10-15%, w/w). In situ structural investigations of human MFG have been performed using light and confocal microscopy with adapted fluorescent probes, i.e. Nile Red, the extrinsic phospholipid Rh-DOPE, Fast Green and the lectin WGA-488. This study revealed a spatial heterogeneity in the human milk fat globule membrane (MFGM), with the lateral segregation of SM in liquid-ordered phase domains of various shapes and sizes surrounded by a liquid-disordered phase composed of the glycerophospholipids in which the proteins are dispersed. The glycocalyx formed by glycoproteins and cytoplasmic remnents have also been characterised around human MFG. A new model for the structure of the human MFGM is proposed and discussed. The unique composition and lateral organisation of the human MFGM components could be of metabolic significance and have health impact for the infants that need to be further explored.

  7. Interacting protein partners of Arabidopsis RNA-binding protein AtRBP45b.

    PubMed

    Muthuramalingam, M; Wang, Y; Li, Y; Mahalingam, R

    2017-05-01

    RNA binding proteins, important players in post-transcriptional gene regulation, usually exist in ribonuclear complexes. However, even in model systems like Arabidopsis characterisation of RBP associated proteins is limited. In this study, we investigated the interacting proteins of the Arabidopsis AtRBP45b, which is involved in stress signalling. In vivo localisation of AtRBP45b was conducted using 35S-GFP. FLAG-tagged AtRBP45b under control of the 35S promoter in the Atrbp45b-1 mutant background was used to pull down AtRBP45b interacting proteins. Yeast two-hybrid analysis, fluorescence energy resonance transfer assays were used to confirm the veracity of the AtRBP45b interacting proteins. In planta GFP-tagging indicated AtRBP45b is localised to the nucleus and the cytosol. AtRBP45b protein has a N-terminal proline-rich region and a C-terminal glutamine-rich domain that are usually involved in protein-protein interactions. Co-immunoprecipitation followed by mass spectrometry-based protein sequencing led to identification of 30 proteins that interacted with AtRBP45b. Using information from interactome databases (BIOGRID, INTACT and STRING), pull-down assays and localisation data, 12 putative interacting proteins were selected for yeast two-hybrid analysis. Cap-binding protein (CBP20, At5g44200) and polyA-binding protein (PAB8, At1g49760) were shown to interact with AtRBP45b. Based on its interacting partners we speculate that AtRBP45b may play an important role in RNA metabolism, especially in aspects related to mRNA stability and translation initiation during stress conditions in plants.

  8. Purification, cloning, and expression of a murine phosphoprotein that binds the kappa B motif in vitro identifies it as the homolog of the human heterogeneous nuclear ribonucleoprotein K protein. Description of a novel DNA-dependent phosphorylation process.

    PubMed

    Ostrowski, J; Van Seuningen, I; Seger, R; Rauch, C T; Sleath, P R; McMullen, B A; Bomsztyk, K

    1994-07-01

    The kappa B enhancer element regulates expression of many genes involved in immune responses and other processes. kappa B motif binds a number of proteins, some but not all, are related to the NF-kappa B family of transcription factors. We have previously identified a 65-kDa phosphoprotein that is specifically recognized by the kappa B motif (Ostrowski, J., Sims, J. E., Sibley, C. H., Valentine, M. A., Dower, S. K., Meier, K. E., and Bomsztyk, K. (1991) J. Biol. Chem. 266, 12722-12733). This protein is closely associated with a serine/threonine kinase that is responsive to treatment of cells with interleukin-1 and other agents. We report here purification, cloning, and expression of this kappa B motif-binding phosphoprotein. The primary structure deduced from the isolated murine cDNA, identifies the protein as the homolog of the human heterogeneous nuclear ribonucleoprotein K protein. Antipeptide antibodies and expression of the cloned cDNA in Escherichia coli, demonstrated that the K protein is the authentic phosphoprotein that binds the kappa B motif in vitro. We also demonstrate that the in vitro phosphorylation of the natural and the recombinant K proteins by the associated kinase is stimulated by the kappa B motif.

  9. Heterogeneity of vertebrate brain tubulins.

    PubMed Central

    Field, D J; Collins, R A; Lee, J C

    1984-01-01

    We have examined the extent of brain tubulin heterogeneity in six vertebrate species commonly used in tubulin research (rat, calf, pig, chicken, human, and lamb) using isoelectric focusing, two-dimensional electrophoresis, and peptide mapping procedures that provide higher resolution than previously available. The extent of heterogeneity is extremely similar in all of these organisms, as judged by number, range of isoelectric points, and distribution of the isotubulins. A minimum of 6 alpha and 12 beta tubulins was resolved from all sources. Even the pattern of spots on two-dimensional peptide maps is remarkably similar. These similarities suggest that the populations of tubulin in all of these brains should have similar overall physical properties. It is particularly interesting that chicken, which has only four or five beta-tubulin genes, contains approximately 12 beta tubulins. Thus, post-translational modification must generate at least some of the tubulin heterogeneity. Mammalian species, which contain 15-20 tubulin DNA sequences, do not show any more tubulin protein heterogeneity than does chicken. This suggests that expression of only a small number of the mammalian genes may be required to generate the observed tubulin heterogeneity. Images PMID:6588378

  10. A physical mechanism of cancer heterogeneity

    NASA Astrophysics Data System (ADS)

    Chen, Cong; Wang, Jin

    2016-02-01

    We studied a core cancer gene regulatory network motif to uncover possible source of cancer heterogeneity from epigenetic sources. When the time scale of the protein regulation to the gene is faster compared to the protein synthesis and degradation (adiabatic regime), normal state, cancer state and an intermediate premalignant state emerge. Due to the epigenetics such as DNA methylation and histone remodification, the time scale of the protein regulation to the gene can be slower or comparable to the protein synthesis and degradation (non-adiabatic regime). In this case, many more states emerge as possible phenotype alternations. This gives the origin of the heterogeneity. The cancer heterogeneity is reflected from the emergence of more phenotypic states, larger protein concentration fluctuations, wider kinetic distributions and multiplicity of kinetic paths from normal to cancer state, higher energy cost per gene switching, and weaker stability.

  11. Lipid rafts: heterogeneity on the high seas.

    PubMed Central

    Pike, Linda J

    2004-01-01

    Lipid rafts are membrane microdomains that are enriched in cholesterol and glycosphingolipids. They have been implicated in processes as diverse as signal transduction, endocytosis and cholesterol trafficking. Recent evidence suggests that this diversity of function is accompanied by a diversity in the composition of lipid rafts. The rafts in cells appear to be heterogeneous both in terms of their protein and their lipid content, and can be localized to different regions of the cell. This review summarizes the data supporting the concept of heterogeneity among lipid rafts and outlines the evidence for cross-talk between raft components. Based on differences in the ways in which proteins interact with rafts, the Induced-Fit Model of Raft Heterogeneity is proposed to explain the establishment and maintenance of heterogeneity within raft populations. PMID:14662007

  12. Treponema pallidum subsp. pallidum TP0136 Protein Is Heterogeneous among Isolates and Binds Cellular and Plasma Fibronectin via its NH2-Terminal End

    PubMed Central

    Ke, Wujian; Molini, Barbara J.; Lukehart, Sheila A.; Giacani, Lorenzo

    2015-01-01

    Adherence-mediated colonization plays an important role in pathogenesis of microbial infections, particularly those caused by extracellular pathogens responsible for systemic diseases, such as Treponema pallidum subsp. pallidum (T. pallidum), the agent of syphilis. Among T. pallidum adhesins, TP0136 is known to bind fibronectin (Fn), an important constituent of the host extracellular matrix. To deepen our understanding of the TP0136-Fn interaction dynamics, we used two naturally-occurring sequence variants of the TP0136 protein to investigate which region of the protein is responsible for Fn binding, and whether TP0136 would adhere to human cellular Fn in addition to plasma Fn and super Fn as previously reported. Fn binding assays were performed with recombinant proteins representing the two full-length TP0136 variants and their discrete regions. As a complementary approach, we tested inhibition of T. pallidum binding to Fn by recombinant full-length TP0136 proteins and fragments, as well as by anti-TP0136 immune sera. Our results show that TP0136 adheres more efficiently to cellular Fn than to plasma Fn, that the TP0136 NH2-terminal conserved region of the protein is primarily responsible for binding to plasma Fn but that binding sites for cellular Fn are also present in the protein’s central and COOH-terminal regions. Additionally, message quantification studies show that tp0136 is highly transcribed during experimental infection, and that its message level increases in parallel to the host immune pressure on the pathogen, which suggests a possible role for this protein in T. pallidum persistence. In a time where syphilis incidence is high, our data will help in the quest to identify suitable targets for development of a much needed vaccine against this important disease. PMID:25793702

  13. Heterogeneity in ess transcriptional organization and variable contribution of the Ess/Type VII protein secretion system to virulence across closely related Staphylocccus aureus strains

    PubMed Central

    Kneuper, Holger; Cao, Zhen Ping; Twomey, Kate B; Zoltner, Martin; Jäger, Franziska; Cargill, James S; Chalmers, James; van der Kooi-Pol, Magdalena M; van Dijl, Jan Maarten; Ryan, Robert P; Hunter, William N; Palmer, Tracy

    2014-01-01

    The Type VII protein secretion system, found in Gram-positive bacteria, secretes small proteins, containing a conserved W-x-G amino acid sequence motif, to the growth medium. Staphylococcus aureus has a conserved Type VII secretion system, termed Ess, which is dispensable for laboratory growth but required for virulence. In this study we show that there are unexpected differences in the organization of the ess gene cluster between closely related strains of S. aureus. We further show that in laboratory growth medium different strains of S. aureus secrete the EsxA and EsxC substrate proteins at different growth points, and that the Ess system in strain Newman is inactive under these conditions. Systematic deletion analysis in S. aureus RN6390 is consistent with the EsaA, EsaB, EssA, EssB, EssC and EsxA proteins comprising core components of the secretion machinery in this strain. Finally we demonstrate that the Ess secretion machinery of two S. aureus strains, RN6390 and COL, is important for nasal colonization and virulence in the murine lung pneumonia model. Surprisingly, however, the secretion system plays no role in the virulence of strain SA113 under the same conditions. PMID:25040609

  14. Heterogeneity in ess transcriptional organization and variable contribution of the Ess/Type VII protein secretion system to virulence across closely related Staphylocccus aureus strains.

    PubMed

    Kneuper, Holger; Cao, Zhen Ping; Twomey, Kate B; Zoltner, Martin; Jäger, Franziska; Cargill, James S; Chalmers, James; van der Kooi-Pol, Magdalena M; van Dijl, Jan Maarten; Ryan, Robert P; Hunter, William N; Palmer, Tracy

    2014-09-01

    The Type VII protein secretion system, found in Gram-positive bacteria, secretes small proteins, containing a conserved W-x-G amino acid sequence motif, to the growth medium. Staphylococcus aureus has a conserved Type VII secretion system, termed Ess, which is dispensable for laboratory growth but required for virulence. In this study we show that there are unexpected differences in the organization of the ess gene cluster between closely related strains of S. aureus. We further show that in laboratory growth medium different strains of S. aureus secrete the EsxA and EsxC substrate proteins at different growth points, and that the Ess system in strain Newman is inactive under these conditions. Systematic deletion analysis in S. aureus RN6390 is consistent with the EsaA, EsaB, EssA, EssB, EssC and EsxA proteins comprising core components of the secretion machinery in this strain. Finally we demonstrate that the Ess secretion machinery of two S. aureus strains, RN6390 and COL, is important for nasal colonization and virulence in the murine lung pneumonia model. Surprisingly, however, the secretion system plays no role in the virulence of strain SA113 under the same conditions.

  15. Inferring biological dynamics in heterogeneous cellular environments

    NASA Astrophysics Data System (ADS)

    Pressé, Steve

    In complex environments, it often appears that biomolecules such as proteins do not diffuse normally. That is, their mean square displacement does not scale linearly with time. This anomalous diffusion happens for multiple reasons: proteins can bind to structures and other proteins; fluorophores used to label proteins may flicker or blink making it appear that the labeled protein is diffusing anomalously; and proteins can diffuse in differently crowded environments. Here we describe methods for learning about such processes from imaging data collected inside the heterogeneous environment of the living cell. Refs.: ''Inferring Diffusional Dynamics from FCS in Heterogeneous Nuclear Environments'' Konstantinos Tsekouras, Amanda Siegel, Richard N. Day, Steve Pressé*, Biophys. J. , 109, 7 (2015). ''A data-driven alternative to the fractional Fokker-Planck equation'' Steve Pressé*, J. Stat. Phys.: Th. and Expmt. , P07009 (2015).

  16. Phenotypically heterogeneous populations in spatially heterogeneous environments

    NASA Astrophysics Data System (ADS)

    Patra, Pintu; Klumpp, Stefan

    2014-03-01

    The spatial expansion of a population in a nonuniform environment may benefit from phenotypic heterogeneity with interconverting subpopulations using different survival strategies. We analyze the crossing of an antibiotic-containing environment by a bacterial population consisting of rapidly growing normal cells and slow-growing, but antibiotic-tolerant persister cells. The dynamics of crossing is characterized by mean first arrival times and is found to be surprisingly complex. It displays three distinct regimes with different scaling behavior that can be understood based on an analytical approximation. Our results suggest that a phenotypically heterogeneous population has a fitness advantage in nonuniform environments and can spread more rapidly than a homogeneous population.

  17. Patterns of Emphysema Heterogeneity

    PubMed Central

    Valipour, Arschang; Shah, Pallav L.; Gesierich, Wolfgang; Eberhardt, Ralf; Snell, Greg; Strange, Charlie; Barry, Robert; Gupta, Avina; Henne, Erik; Bandyopadhyay, Sourish; Raffy, Philippe; Yin, Youbing; Tschirren, Juerg; Herth, Felix J.F.

    2016-01-01

    Background Although lobar patterns of emphysema heterogeneity are indicative of optimal target sites for lung volume reduction (LVR) strategies, the presence of segmental, or sublobar, heterogeneity is often underappreciated. Objective The aim of this study was to understand lobar and segmental patterns of emphysema heterogeneity, which may more precisely indicate optimal target sites for LVR procedures. Methods Patterns of emphysema heterogeneity were evaluated in a representative cohort of 150 severe (GOLD stage III/IV) chronic obstructive pulmonary disease (COPD) patients from the COPDGene study. High-resolution computerized tomography analysis software was used to measure tissue destruction throughout the lungs to compute heterogeneity (≥ 15% difference in tissue destruction) between (inter-) and within (intra-) lobes for each patient. Emphysema tissue destruction was characterized segmentally to define patterns of heterogeneity. Results Segmental tissue destruction revealed interlobar heterogeneity in the left lung (57%) and right lung (52%). Intralobar heterogeneity was observed in at least one lobe of all patients. No patient presented true homogeneity at a segmental level. There was true homogeneity across both lungs in 3% of the cohort when defining heterogeneity as ≥ 30% difference in tissue destruction. Conclusion Many LVR technologies for treatment of emphysema have focused on interlobar heterogeneity and target an entire lobe per procedure. Our observations suggest that a high proportion of patients with emphysema are affected by interlobar as well as intralobar heterogeneity. These findings prompt the need for a segmental approach to LVR in the majority of patients to treat only the most diseased segments and preserve healthier ones. PMID:26430783

  18. Sequence heterogeneity in the gene encoding the rhoptry-associated protein-1 (RAP-1) of Babesia caballi isolates from South Africa.

    PubMed

    Bhoora, Raksha; Quan, Melvyn; Zweygarth, Erich; Guthrie, Alan J; Prinsloo, Sandra A; Collins, Nicola E

    2010-05-11

    A competitive-inhibition enzyme-linked immunosorbent assay (cELISA) developed for the detection of antibody specific for Babesia caballi was used to test sera collected from 1237 South African horses. None of these samples tested positive using the cELISA, although 63 samples tested positive for B. caballi antibody using the indirect fluorescent antibody test (IFAT). We therefore characterized the rap-1 gene that codes for the antigen (rhoptry-associated protein, RAP-1) used in the cELISA, from South African B. caballi isolates. Three sets of primers were designed to amplify the complete gene and flanking regions (approximately 1800 bp), but only one set of primers yielded PCR products, and we were only able to amplify a region at the 5' end of the gene (615 bp) from ten South African B. caballiin vitro-cultured isolates. Sequence data from seven of these were obtained. The sequences showed between 79% and 81% identity to B. caballirap-1 gene sequences that have been reported in the literature (accession numbers: AF092736 and AB017700). The GenomeWalker Universal kit (Clonetech) was used to amplify the regions flanking the 615bp B. caballirap-1 fragment from two South African isolates. Amplified products were cloned into the pGEM-T Easy vector and sequenced. The complete rap-1 gene sequence, comprising a single open reading frame of 1479 bp that encodes a protein consisting of 493 amino acids, was obtained from the two South African isolates. This sequence data was used to redesign the amplification primers and rap-1 homologues were obtained from a further eight isolates. BLASTP analysis indicated an amino acid identity of between 57.9% and 65.1% to the two RAP-1 protein sequences, AF092736 and AB017700, with most differences occurring at the carboxy-terminus. The amino acid sequence differences probably explain why it was not possible to detect B. caballi antibody in IFAT positive sera from South Africa using the cELISA. Redesigning the current cELISA using a

  19. The proximal region of the 3'-untranslated region of cyclooxygenase-2 is recognized by a multimeric protein complex containing HuR, TIA-1, TIAR, and the heterogeneous nuclear ribonucleoprotein U.

    PubMed

    Cok, Steven J; Acton, Stephen J; Morrison, Aubrey R

    2003-09-19

    Cyclooxygenase-2 (COX-2) is an early response gene induced in renal mesangial cells by interleukin-1beta (IL-1beta). The 3'-untranslated region (3'-UTR) of COX-2 mRNA plays an important role in IL-1beta induction by regulating message stability and translational efficiency. The first 60 nucleotides of the 3'-UTR of COX-2 are highly conserved and contain multiple copies of the regulatory sequence AUUUA. Introduction of the 60-nucleotide sequence into the 3'-UTR of a heterologous reporter gene resulted in a 70% decrease in reporter gene expression. Electrophoretic mobility shift assays (EMSAs) demonstrated that mesangial cell nuclear fractions contain a multimeric protein complex that bound this region of COX-2 mRNA in a sequence-specific manner. We identified four members of the protein-RNA complex as HuR, TIA-1, TIAR, and the heterogeneous nuclear ribonucleoprotein U (hnRNP U). Treatment of mesangial cells with IL-1beta caused an increase in cytosolic HuR, which was accompanied by an increase in COX-2 mRNA that co-immunoprecipitated with cytosolic HuR. Therefore, we propose that HuR binds to the proximal region of the 3'-UTR of COX-2 following stimulation by IL-1beta and increases the expression of COX-2 mRNA by facilitating its transport out of the nucleus.

  20. Tumour Cell Heterogeneity

    PubMed Central

    Gay, Laura; Baker, Ann-Marie; Graham, Trevor A.

    2016-01-01

    The population of cells that make up a cancer are manifestly heterogeneous at the genetic, epigenetic, and phenotypic levels. In this mini-review, we summarise the extent of intra-tumour heterogeneity (ITH) across human malignancies, review the mechanisms that are responsible for generating and maintaining ITH, and discuss the ramifications and opportunities that ITH presents for cancer prognostication and treatment. PMID:26973786

  1. Heterogeneity of mast cells and expression of Annexin A1 protein in a second degree burn model with silver sulfadiazine treatment

    PubMed Central

    Souza, Helena Ribeiro; de Azevedo, Lucas Ribeiro; Possebon, Lucas; Costa, Sara de Souza; Iyomasa-Pilon, Melina Mizusaki; Oliani, Sonia Maria; Girol, Ana Paula

    2017-01-01

    Mast cells (MCs) participate in all stages of skin healing and one of their mediators is the Annexin A1 protein (AnxA1), linked to inflammation, proliferation, migration and apoptosis processes, but not studied in thermal burns yet. Therefore, our objectives were to evaluate the behavior of MCs and AnxA1 in a second degree burn model, treated or not with silver sulfadiazine 1% (SDP 1%) and associated to macrophages quantification and cytokines dosages. MCs counts showed few cells in the early stages of repair but increased MCs in the final phases in the untreated group. The normal skin presented numerous tryptase-positive MCs that were reduced after burning in all analyzed periods. Differently, few chymase-positive MCs were observed in the early stages of healing, however, increased chymase-positive MCs were found at the final phase in the untreated group. MCs also showed high immunoreactivity for AnxA1 on day 3 in both groups. In the tissue there was a strong protein expression in the early stages of healing, but in the final phases only in the SDP treated animals. TNF-α, IL-1β, IL-6, IL-10 and MCP-1 levels and macrophages quantification were increased in inflammation and reepithelialization phases. Reduced IL-1β, IL-6 and IL-10 levels and numerous macrophages occurred in the treated animals during tissue repair. Our results indicate modulation in the profile of MCs and AnxA1expression during healing by the treatment with SDP 1%, pointing them as targets for therapeutic interventions on skin burns. PMID:28278234

  2. Epitope mapping with synthetic peptides of 52-kD SSA/Ro protein reveals heterogeneous antibody profiles in human autoimmune sera.

    PubMed Central

    Ricchiuti, V; Briand, J P; Meyer, O; Isenberg, D A; Pruijn, G; Muller, S

    1994-01-01

    The reactivity of autoantibodies present in the sera of 489 patients with Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and other autoimmune diseases was investigated by ELISA using recombinant 52-kD SSA/Ro protein (rRo52) and 39 overlapping synthetic peptides representing the entire sequence of Ro52. We report that IgG antibodies reacting with rRo52 were present in the sera of a large number of patients with SS (67% of patients with primary SS and 46% of patients with SS associated with SLE), whereas they were less frequent (10-25%) in SLE, rheumatoid arthritis (RA), juvenile chronic arthritis (JCA) and mixed connective tissue disease (MCTD), and absent in scleroderma. Among the 39 peptides tested, five were recognized by sera from 30-65% of patients with SS, namely peptides representing residues 2-11, 107-122, 107-126, 277-292 and 365-382. Patients with JCA had raised levels of IgG antibodies reacting with peptides 2-11 and 365-382, and 51% of patients with MCTD had raised levels of IgG antibodies reacting with peptide 365-382. None of the five peptides was recognized by more than 20% of sera from patients with SLE and RA. Interestingly, and of importance in the field of diagnostic tests based on peptides, the reactivity of antibodies to the Ro52 synthetic peptides varied greatly according to the origin of sera. Inhibition experiments using either patients' sera or antibodies induced in rabbits against Ro52 peptides showed that the four domains 2-11, 107-122, 277-292 and 365-382 are accessible on the surface of the Ro52 protein. These regions may thus be involved in the induction of specific antibodies in autoimmune patients. Images Fig. 5 PMID:7511075

  3. A heterogeneous tag-attachment to the homodimeric type 1 photosynthetic reaction center core protein in the green sulfur bacterium Chlorobaculum tepidum.

    PubMed

    Azai, Chihiro; Kim, Kwang; Kondo, Toru; Harada, Jiro; Itoh, Shigeru; Oh-oka, Hirozo

    2011-07-01

    The 6xHis-tag-pscA gene, which was genetically engineered to express N-terminally histidine (His)-tagged PscA, was inserted into a coding region of the recA gene in the green sulfur bacterium Chlorobaculum tepidum (C. tepidum). Although the inactivation of the recA gene strongly suppressed a homologous recombination in C. tepidum genomic DNA, the mutant grew well under normal photosynthetic conditions. The His-tagged reaction center (RC) complex could be obtained simply by Ni(2+)-affinity chromatography after detergent solubilization of chlorosome-containing membranes. The complex consisted of three subunits, PscA, PscB, and PscC, in addition to the Fenna-Matthews-Olson protein, but there was no PscD. Low-temperature EPR spectroscopic studies in combination with transient absorption measurements indicated that the complex contained all intrinsic electron transfer cofactors as detected in the wild-type strain. Furthermore, the LC/MS/MS analysis revealed that the core protein consisted of a mixture of a His-/His-tagged PscA homodimer and a non-/His-tagged PscA heterodimer. The development of the pscA gene duplication method presented here, thus, enables not only a quick and large-scale preparation of the RC complex from C. tepidum but also site-directed mutagenesis experiments on the artificially incorporated 6xHis-tag-pscA gene itself, since the expression of the authentic PscA/PscA homodimeric RC complex could complement any defect in mutated His-tagged PscA. This method would provide an invaluable tool for structural and functional analyses of the homodimeric type 1 RC complex.

  4. Heterogeneous Atmospheric Chemistry

    NASA Astrophysics Data System (ADS)

    Schryer, David R.

    In the past few years it has become increasingly clear that heterogeneous, or multiphase, processes play an important role in the atmosphere. Unfortunately the literature on the subject, although now fairly extensive, is still rather dispersed. Furthermore, much of the expertise regarding heterogeneous processes lies in fields not directly related to atmospheric science. Therefore, it seemed desirable to bring together for an exchange of ideas, information, and methodologies the various atmospheric scientists who are actively studying heterogeneous processes as well as other researchers studying similar processes in the context of other fields.

  5. Towards heterogeneous distributed debugging

    SciTech Connect

    Damodaran-Kamal, S.K.

    1995-04-01

    Several years of research and development in parallel debugger design have given up several techniques, though implemented in a wide range of tools for an equally wide range of systems. This paper is an evaluation of these myriad techniques as applied to the design of a heterogeneous distributed debugger. The evaluation is based on what features users perceive as useful, as well as the ease of implementation of the features using the available technology. A preliminary architecture for such a heterogeneous tool is proposed. Our effort in this paper is significantly different from the other efforts at creating portable and heterogeneous distributed debuggers in that we concentrate on support for all the important issues in parallel debugging, instead of simply concentrating on portability and heterogeneity.

  6. Heterogeneous atmospheric chemistry

    NASA Technical Reports Server (NTRS)

    Schryer, D. R.

    1982-01-01

    The present conference on heterogeneous atmospheric chemistry considers such topics concerning clusters, particles and microparticles as common problems in nucleation and growth, chemical kinetics, and catalysis, chemical reactions with aerosols, electron beam studies of natural and anthropogenic microparticles, and structural studies employing molecular beam techniques, as well as such gas-solid interaction topics as photoassisted reactions, catalyzed photolysis, and heterogeneous catalysis. Also discussed are sulfur dioxide absorption, oxidation, and oxidation inhibition in falling drops, sulfur dioxide/water equilibria, the evidence for heterogeneous catalysis in the atmosphere, the importance of heterogeneous processes to tropospheric chemistry, soot-catalyzed atmospheric reactions, and the concentrations and mechanisms of formation of sulfate in the atmospheric boundary layer.

  7. Heterogeneous basic catalysis

    SciTech Connect

    Hattori, Hideshi

    1995-05-01

    Heterogeneous acid catalysis attracted much attention primarily because heterogeneous acidic catalysts act as catalysts in petroleum refinery and are known as a main catalyst in the cracking process which is the largest process among the industrial chemical processes. In contrast to these extensive studies of heterogeneous acidic catalysts, fewer efforts have been given to the study of heterogeneous basic catalysts. The types of heterogeneous basic catalysts are listed in Table 1. Except for non-oxide catalysts, the basic sites are believed to be surface O atoms. The studies of heterogeneous catalysis have been continuous and progressed steadily. They have never been reviewed in the chemical Reviews before. It is more useful and informative to describe the studies of heterogeneous basic catalysis performed for a long period. In the present article, therefore, the cited papers are not restricted to those published recently, but include those published for the last 25 years. The paper first describes the generation of basic sites before describing methods used in the characterization of basic surfaces. These are indicator methods, temperature programmed desorption (TPD) of CO{sub 2}, UV absorption and luminescence spectroscopies, TPD of H{sub 2}, XPS, IR of CO{sub 2}, IR of pyrrole, and oxygen exchange between CO{sub 2} and the surface. The paper then discusses studies on the catalysis by heterogeneous basic catalysts. Some of these reactions are dehydration, dehydrogenation, hydrogenation, amination, alkylation, ring transformation, and reactions of organosilanes. Catalysts discussed are single component metal oxides, zeolites, non-oxide types, and superbasic catalysts. 141 refs.

  8. Heterogeneity in hand veins responses to acetylcholine is not associated with polymorphisms in the G-protein beta3-subunit (C825T) and endothelial nitric oxide synthase (G894T) genes but with serum low density lipoprotein cholesterol.

    PubMed

    Grossmann, M; Dobrev, D; Siffert, W; Kirch, W

    2001-06-01

    Vascular responses to acetylcholine (ACh) are notoriously variable, the reason for this phenomenon is unknown. We tested the hypothesis that the variability in venous response to acetylcholine may be associated with two recently identified genetic polymorphisms for proteins involved in the signal transduction pathway, i.e. the G-protein beta3-subunit (GNB3) and endothelial nitric oxide synthase (eNOS). The dorsal hand vein technique was used in 37 healthy subjects. Hand veins were preconstricted with the alpha1-adrenoceptor agonist phenylephrine and the venodilator response to local ACh infusion was measured with and without comedication of acetylsalicylic acid or co-infusion of N(G)-monomethyl-L-arginine (L-NMMA). In addition, all subjects received routine laboratory tests and 26 of them were genotyped for the C825T polymorphism of the GNB3 gene and for the G894T polymorphism of the eNOS gene. A striking variability in venous response to ACh was found with dilation observed in the low ACh concentration range and reduced dilation or even constriction at high concentrations. ACh-induced venodilation was mediated by muscarinic receptors and abolished in the presence of both acetylsalicylic acid and L-NMMA suggesting dependence on endothelium. We did not find any association of the variability in ACh response with GNB3 or eNOS allele status. On the other hand, a significant positive correlation between ACh responsiveness and low density lipoprotein-cholesterol status was detected. Two recently discovered gene polymorphisms are not responsible for the profound heterogeneity in venodilator response to ACh. Surprisingly, this variability appears to relate to the lipid status of the subjects. The exact nature of this new finding requires further study.

  9. Proteins.

    ERIC Educational Resources Information Center

    Doolittle, Russell F.

    1985-01-01

    Examines proteins which give rise to structure and, by virtue of selective binding to other molecules, make genes. Binding sites, amino acids, protein evolution, and molecular paleontology are discussed. Work with encoding segments of deoxyribonucleic acid (exons) and noncoding stretches (introns) provides new information for hypotheses. (DH)

  10. Characterization of Paper Heterogeneity

    NASA Astrophysics Data System (ADS)

    Considine, John M.

    Paper and paperboard are the most widely-used green materials in the world because they are renewable, recyclable, reusable, and compostable. Continued and expanded use of these materials and their potential use in new products requires a comprehensive understanding of the variability of their mechanical properties. This work develops new methods to characterize the mechanical properties of heterogeneous materials through a combination of techniques in experimental mechanics, materials science and numerical analysis. Current methods to analyze heterogeneous materials focus on crystalline materials or polymer-crystalline composites, where material boundaries are usually distinct. This work creates a methodology to analyze small, continuously-varying stiffness gradients in 100% polymer systems and is especially relevant to paper materials where factors influencing heterogeneity include local mass, fiber orientation, individual pulp fiber properties, local density, and drying restraint. A unique approach was used to understand the effect of heterogeneity on paper tensile strength. Additional variation was intentionally introduced, in the form of different size holes, and their effect on strength was measured. By modifying two strength criteria, an estimate of strength in the absence of heterogeneity was determined. In order to characterize stiffness heterogeneity, a novel load fixture was developed to excite full-field normal and shear strains for anisotropic stiffness determination. Surface strains were measured with digital image correlation and were analyzed with the VFM (Virtual Fields Method). This approach led to VFM-identified stiffnesses that were similar to values determined by conventional tests. The load fixture and VFM analyses were used to measure local stiffness and local stiffness variation on heterogeneous anisotropic materials. The approach was validated on simulated heterogeneous materials and was applied experimentally to three different paperboards

  11. Protein

    MedlinePlus

    ... Search for: Harvard T.H. Chan School of Public Health Email People Departments Calendar Careers Give my.harvard ... Nutrition Source Harvard T.H. Chan School of Public Health > The Nutrition Source > What Should I Eat? > Protein ...

  12. Protein

    MedlinePlus

    ... Go lean with protein. • Choose lean meats and poultry. Lean beef cuts include round steaks (top loin, ... main dishes. • Use nuts to replace meat or poultry, not in addition to meat or poultry (i. ...

  13. Spatial heterogeneity in medulloblastoma.

    PubMed

    Morrissy, A Sorana; Cavalli, Florence M G; Remke, Marc; Ramaswamy, Vijay; Shih, David J H; Holgado, Borja L; Farooq, Hamza; Donovan, Laura K; Garzia, Livia; Agnihotri, Sameer; Kiehna, Erin N; Mercier, Eloi; Mayoh, Chelsea; Papillon-Cavanagh, Simon; Nikbakht, Hamid; Gayden, Tenzin; Torchia, Jonathon; Picard, Daniel; Merino, Diana M; Vladoiu, Maria; Luu, Betty; Wu, Xiaochong; Daniels, Craig; Horswell, Stuart; Thompson, Yuan Yao; Hovestadt, Volker; Northcott, Paul A; Jones, David T W; Peacock, John; Wang, Xin; Mack, Stephen C; Reimand, Jüri; Albrecht, Steffen; Fontebasso, Adam M; Thiessen, Nina; Li, Yisu; Schein, Jacqueline E; Lee, Darlene; Carlsen, Rebecca; Mayo, Michael; Tse, Kane; Tam, Angela; Dhalla, Noreen; Ally, Adrian; Chuah, Eric; Cheng, Young; Plettner, Patrick; Li, Haiyan I; Corbett, Richard D; Wong, Tina; Long, William; Loukides, James; Buczkowicz, Pawel; Hawkins, Cynthia E; Tabori, Uri; Rood, Brian R; Myseros, John S; Packer, Roger J; Korshunov, Andrey; Lichter, Peter; Kool, Marcel; Pfister, Stefan M; Schüller, Ulrich; Dirks, Peter; Huang, Annie; Bouffet, Eric; Rutka, James T; Bader, Gary D; Swanton, Charles; Ma, Yusanne; Moore, Richard A; Mungall, Andrew J; Majewski, Jacek; Jones, Steven J M; Das, Sunit; Malkin, David; Jabado, Nada; Marra, Marco A; Taylor, Michael D

    2017-04-10

    Spatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy. Conversely, somatic mutations that affect genes suitable for targeted therapeutics demonstrated high levels of spatial heterogeneity in MB, malignant glioma, and renal cell carcinoma (RCC). Actionable targets found in a single MB biopsy were seldom clonal across the entire tumor, which brings the efficacy of monotherapies against a single target into question. Clinical trials of targeted therapies for MB should first ensure the spatially ubiquitous nature of the target mutation.

  14. Cancer heterogeneity and imaging.

    PubMed

    O'Connor, James P B

    2016-10-04

    There is interest in identifying and quantifying tumor heterogeneity at the genomic, tissue pathology and clinical imaging scales, as this may help better understand tumor biology and may yield useful biomarkers for guiding therapy-based decision making. This review focuses on the role and value of using x-ray, CT, MRI and PET based imaging methods that identify, measure and map tumor heterogeneity. In particular we highlight the potential value of these techniques and the key challenges required to validate and qualify these biomarkers for clinical use.

  15. Phosphorylation of the C proteins in heterogeneous ribonucleoprotein (hnRNP) particles in HeLa cells: Characterization of in vivo phosphorylation, comparison with in vitro phosphorylation using casein kinase II, and preliminary studies on the effects of phosphorylation on particle structure

    SciTech Connect

    Kleiman, N.J.

    1989-01-01

    Newly formed pre-messenger RNA associates with protein to form heterogeneous ribonucleoprotein (hnRNP) particles. In HeLa cells, hnRNP particles contain six core proteins. Two proteins, termed C{sub 1} and C{sub 2}, are phosphorylated in vitro by casein kinase 11 (CKII). C{sub 1} protein became {sup 32}P-labeled after HeLa cells were incubated with ({sup 32}P)-orthophosphate in vivo (ibid). Because phosphorylation is a ubiquitous regulatory mechanism, C protein phosphorylation was studied in greater detail. C protein phosphorylation in hnRNP particles was investigated in HeLa cells incubated with ({sup 32}P)-orthophosphate in vivo. Immunoblotting in pH 3.5-10 isoelectric focusing (IEF) gels indicated that C proteins focus only at pH 5.0. In pH 4.5-5.5 IEF gels, individually purified C, and 2 proteins resolve into the same four closely spaced, {sup 32}P-labeled bands. A fifth, unlabeled, more basic species was detached when hnRNP particles were purified without NaF. All {sup 32}P-labeled species contained identical amounts of {sup 32}P per unit protein suggesting that charge heterogeneity is not due to differential phosphorylation. Attempts to detect bound carbohydrate were unsuccessful. {sup 32}P-labeled phosphate was readily removed by potato acid phosphatase. E. coli alkaline phosphatase and snake venom phosphodiesterase were ineffective. {sup 32}P-label was found exclusively in phosphoserine. One-dimensional peptide mapping with chymotrypsin and S. aureus protease detected two phosphorylated peptides. C protein phosphorylation was also investigated in vitro. Incubation of hnRNP particles with rabbit liver CKII and {sup 32}P-ATP followed by IEF in pH 4.5-5.5 gels indicated that all four C protein species were {sup 32}P-labeled. {sup 32}P-label was found exclusively in phosphoserine.

  16. Heterogeneous Uncertainty Management

    DTIC Science & Technology

    2008-03-08

    probabilistic ( HTP ) agents, the concept of probabilistic version of XML and RDF, and probabilistic methods to reason about collections of moving objects. S...heterogeneous temporal probabilistic ( HTP ) agents, the concept of probabilistic version of XML and RDF, and probabilistic methods to reason about...temporal probabilistic ( HTP ) agent. HTP agents can build temporal probabilistic reasoning capabilities on top of multiple databases and software

  17. Heterogeneous waste processing

    DOEpatents

    Vanderberg, Laura A.; Sauer, Nancy N.; Brainard, James R.; Foreman, Trudi M.; Hanners, John L.

    2000-01-01

    A combination of treatment methods are provided for treatment of heterogeneous waste including: (1) treatment for any organic compounds present; (2) removal of metals from the waste; and, (3) bulk volume reduction, with at least two of the three treatment methods employed and all three treatment methods emplyed where suitable.

  18. Scales of mantle heterogeneity

    NASA Astrophysics Data System (ADS)

    Moore, J. C.; Akber-Knutson, S.; Konter, J.; Kellogg, J.; Hart, S.; Kellogg, L. H.; Romanowicz, B.

    2004-12-01

    A long-standing question in mantle dynamics concerns the scale of heterogeneity in the mantle. Mantle convection tends to both destroy (through stirring) and create (through melt extraction and subduction) heterogeneity in bulk and trace element composition. Over time, these competing processes create variations in geochemical composition along mid-oceanic ridges and among oceanic islands, spanning a range of scales from extremely long wavelength (for example, the DUPAL anomaly) to very small scale (for example, variations amongst melt inclusions). While geochemical data and seismic observations can be used to constrain the length scales of mantle heterogeneity, dynamical mixing calculations can illustrate the processes and timescales involved in stirring and mixing. At the Summer 2004 CIDER workshop on Relating Geochemical and Seismological Heterogeneity in the Earth's Mantle, an interdisciplinary group evaluated scales of heterogeneity in the Earth's mantle using a combined analysis of geochemical data, seismological data and results of numerical models of mixing. We mined the PetDB database for isotopic data from glass and whole rock analyses for the Mid-Atlantic Ridge (MAR) and the East Pacific Rise (EPR), projecting them along the ridge length. We examined Sr isotope variability along the East Pacific rise by looking at the difference in Sr ratio between adjacent samples as a function of distance between the samples. The East Pacific Rise exhibits an overall bowl shape of normal MORB characteristics, with higher values in the higher latitudes (there is, however, an unfortunate gap in sampling, roughly 2000 km long). These background characteristics are punctuated with spikes in values at various locations, some, but not all of which are associated with off-axis volcanism. A Lomb-Scargle periodogram for unevenly spaced data was utilized to construct a power spectrum of the scale lengths of heterogeneity along both ridges. Using the same isotopic systems (Sr, Nd

  19. The membrane: transertion as an organizing principle in membrane heterogeneity

    PubMed Central

    Matsumoto, Kouji; Hara, Hiroshi; Fishov, Itzhak; Mileykovskaya, Eugenia; Norris, Vic

    2015-01-01

    The bacterial membrane exhibits a significantly heterogeneous distribution of lipids and proteins. This heterogeneity results mainly from lipid–lipid, protein–protein, and lipid–protein associations which are orchestrated by the coupled transcription, translation and insertion of nascent proteins into and through membrane (transertion). Transertion is central not only to the individual assembly and disassembly of large physically linked groups of macromolecules (alias hyperstructures) but also to the interactions between these hyperstructures. We review here these interactions in the context of the processes in Bacillus subtilis and Escherichia coli of nutrient sensing, membrane synthesis, cytoskeletal dynamics, DNA replication, chromosome segregation, and cell division. PMID:26124753

  20. Heterogeneity in Desiccated Solutions: Implications for Biostabilization

    PubMed Central

    Ragoonanan, Vishard; Aksan, Alptekin

    2008-01-01

    Biopreservation processes such as freezing and drying inherently introduce heterogeneity. We focused on exploring the mechanisms responsible for heterogeneity in isothermal, diffusively dried biopreservation solutions that contain a model protein. The biopreservation solutions used contained trehalose (a sugar known for its stabilization effect) and salts (LiCl, NaCl, MgCl2, and CaCl2). Performing Fourier transform infrared spectroscopy analysis on the desiccated droplets, spatial distributions of the components within the dried droplet, as well as their specific interactions, were investigated. It was established that the formation of multiple thermodynamic states was induced by the spatial variations in the cosolute concentration gradients, directly affecting the final structure of the preserved protein. The spatial distribution gradients were formed by two competing flows that formed within the drying droplet: a dominant peripheral flow, induced by contact line pinning, and the Marangoni flow, induced by surface tension gradients. It was found that the changes in cosolute concentrations and drying conditions affected the spatial heterogeneity and stability of the product. It was also found that trehalose and salts had a synergistic stabilizing effect on the protein structure, which originated from destructuring of the vicinal water, which in turn mediated the interactions of trehalose with the protein. This interaction was observed by the change in the glycosidic CO, and the CH stretch vibrations of the trehalose molecule. PMID:18055531

  1. Concepts in Heterogeneous Catalysis

    DTIC Science & Technology

    1974-06-01

    OxIdlaing Species In Heterogeneous Catalytic Oxidation. In the history of the study of heterogeneioum oxidation catalysis, reaction mechanisms have’ been...for sonti timie but recent workŔ’ onl the lplatitnum-rtothe~idina alloy systemn semi- s quite promising 10) lvad ito at bettr understanding. 1t wait...chemical nature of the catalyst, its previous history , and on the courac of the catalytic reaction itself. The energy spectrum of the active surface

  2. Heterogeneities in granular dynamics

    PubMed Central

    Mehta, A.; Barker, G. C.; Luck, J. M.

    2008-01-01

    The absence of Brownian motion in granular media is a source of much complexity, including the prevalence of heterogeneity, whether static or dynamic, within a given system. Such strong heterogeneities can exist as a function of depth in a box of grains; this is the system we study here. First, we present results from three-dimensional, cooperative and stochastic Monte Carlo shaking simulations of spheres on heterogeneous density fluctuations. Next, we juxtapose these with results obtained from a theoretical model of a column of grains under gravity; frustration via competing local fields is included in our model, whereas the effect of gravity is to slow down the dynamics of successively deeper layers. The combined conclusions suggest that the dynamics of a real granular column can be divided into different phases—ballistic, logarithmic, activated, and glassy—as a function of depth. The nature of the ground states and their retrieval (under zero-temperature dynamics) is analyzed; the glassy phase shows clear evidence of its intrinsic (“crystalline”) states, which lie below a band of approximately degenerate ground states. In the other three phases, by contrast, the system jams into a state chosen randomly from this upper band of metastable states. PMID:18541918

  3. Tumour Heterogeneity: The Key Advantages of Single-Cell Analysis

    PubMed Central

    Tellez-Gabriel, Marta; Ory, Benjamin; Lamoureux, Francois; Heymann, Marie-Francoise; Heymann, Dominique

    2016-01-01

    Tumour heterogeneity refers to the fact that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation and metastatic potential. This phenomenon occurs both between tumours (inter-tumour heterogeneity) and within tumours (intra-tumour heterogeneity), and it is caused by genetic and non-genetic factors. The heterogeneity of cancer cells introduces significant challenges in using molecular prognostic markers as well as for classifying patients that might benefit from specific therapies. Thus, research efforts for characterizing heterogeneity would be useful for a better understanding of the causes and progression of disease. It has been suggested that the study of heterogeneity within Circulating Tumour Cells (CTCs) could also reflect the full spectrum of mutations of the disease more accurately than a single biopsy of a primary or metastatic tumour. In previous years, many high throughput methodologies have raised for the study of heterogeneity at different levels (i.e., RNA, DNA, protein and epigenetic events). The aim of the current review is to stress clinical implications of tumour heterogeneity, as well as current available methodologies for their study, paying specific attention to those able to assess heterogeneity at the single cell level. PMID:27999407

  4. Unravelling mononuclear phagocyte heterogeneity

    PubMed Central

    Geissmann, Frédéric; Gordon, Siamon; Hume, David A.; Mowat, Allan M.; Randolph, Gwendalyn J.

    2011-01-01

    When Ralph Steinman and Zanvil Cohn first described dendritic cells (DCs) in 1973 it took many years to convince the immunology community that these cells were truly distinct from macrophages. Almost four decades later, the DC is regarded as the key initiator of adaptive immune responses; however, distinguishing DCs from macrophages still leads to confusion and debate in the field. Here, Nature Reviews Immunology asks five experts to discuss the issue of heterogeneity in the mononuclear phagocyte system and to give their opinion on the importance of defining these cells for future research. PMID:20467425

  5. Membrane adhesion and the formation of heterogeneities: biology, biophysics, and biotechnology

    PubMed Central

    Gordon, V. D.; O’Halloran, T.J.; Shindell, O.

    2015-01-01

    Membrane adhesion is essential to many vital biological processes. Sites of membrane adhesion are often associated with heterogeneities in the lipid and protein composition of the membrane. These heterogeneities are thought to play functional roles by facilitating interactions between proteins. However, the causal links between membrane adhesion and membrane heterogeneities are not known. Here we survey the state of the field and indicate what we think are understudied areas ripe for development. PMID:25866854

  6. Astrocyte heterogeneity in the brain: from development to disease

    PubMed Central

    Schitine, Clarissa; Nogaroli, Luciana; Costa, Marcos R.; Hedin-Pereira, Cecilia

    2015-01-01

    In the last decades, astrocytes have risen from passive supporters of neuronal activity to central players in brain function and cognition. Likewise, the heterogeneity of astrocytes starts to become recognized in contrast to the homogeneous population previously predicted. In this review, we focused on astrocyte heterogeneity in terms of their morphological, protein expression and functional aspects, and debate in a historical perspective the diversity encountered in glial progenitors and how they may reflect mature astrocyte heterogeneity. We discussed data that show that different progenitors may have unsuspected roles in developmental processes. We have approached the functions of astrocyte subpopulations on the onset of psychiatric and neurological diseases. PMID:25852472

  7. Disordered hyperuniform heterogeneous materials

    NASA Astrophysics Data System (ADS)

    Torquato, Salvatore

    2016-10-01

    Disordered hyperuniform many-body systems are distinguishable states of matter that lie between a crystal and liquid: they are like perfect crystals in the way they suppress large-scale density fluctuations and yet are like liquids or glasses in that they are statistically isotropic with no Bragg peaks. These systems play a vital role in a number of fundamental and applied problems: glass formation, jamming, rigidity, photonic and electronic band structure, localization of waves and excitations, self-organization, fluid dynamics, quantum systems, and pure mathematics. Much of what we know theoretically about disordered hyperuniform states of matter involves many-particle systems. In this paper, we derive new rigorous criteria that disordered hyperuniform two-phase heterogeneous materials must obey and explore their consequences. Two-phase heterogeneous media are ubiquitous; examples include composites and porous media, biological media, foams, polymer blends, granular media, cellular solids, and colloids. We begin by obtaining some results that apply to hyperuniform two-phase media in which one phase is a sphere packing in d-dimensional Euclidean space {{{R}}d} . Among other results, we rigorously establish the requirements for packings of spheres of different sizes to be ‘multihyperuniform’. We then consider hyperuniformity for general two-phase media in {{{R}}d} . Here we apply realizability conditions for an autocovariance function and its associated spectral density of a two-phase medium, and then incorporate hyperuniformity as a constraint in order to derive new conditions. We show that some functional forms can immediately be eliminated from consideration and identify other forms that are allowable. Specific examples and counterexamples are described. Contact is made with well-known microstructural models (e.g. overlapping spheres and checkerboards) as well as irregular phase-separation and Turing-type patterns. We also ascertain a family of

  8. Disordered hyperuniform heterogeneous materials.

    PubMed

    Torquato, Salvatore

    2016-10-19

    Disordered hyperuniform many-body systems are distinguishable states of matter that lie between a crystal and liquid: they are like perfect crystals in the way they suppress large-scale density fluctuations and yet are like liquids or glasses in that they are statistically isotropic with no Bragg peaks. These systems play a vital role in a number of fundamental and applied problems: glass formation, jamming, rigidity, photonic and electronic band structure, localization of waves and excitations, self-organization, fluid dynamics, quantum systems, and pure mathematics. Much of what we know theoretically about disordered hyperuniform states of matter involves many-particle systems. In this paper, we derive new rigorous criteria that disordered hyperuniform two-phase heterogeneous materials must obey and explore their consequences. Two-phase heterogeneous media are ubiquitous; examples include composites and porous media, biological media, foams, polymer blends, granular media, cellular solids, and colloids. We begin by obtaining some results that apply to hyperuniform two-phase media in which one phase is a sphere packing in d-dimensional Euclidean space [Formula: see text]. Among other results, we rigorously establish the requirements for packings of spheres of different sizes to be 'multihyperuniform'. We then consider hyperuniformity for general two-phase media in [Formula: see text]. Here we apply realizability conditions for an autocovariance function and its associated spectral density of a two-phase medium, and then incorporate hyperuniformity as a constraint in order to derive new conditions. We show that some functional forms can immediately be eliminated from consideration and identify other forms that are allowable. Specific examples and counterexamples are described. Contact is made with well-known microstructural models (e.g. overlapping spheres and checkerboards) as well as irregular phase-separation and Turing-type patterns. We also ascertain a family

  9. Phenotypic Heterogeneity of Monogenic Frontotemporal Dementia

    PubMed Central

    Benussi, Alberto; Padovani, Alessandro; Borroni, Barbara

    2015-01-01

    Frontotemporal dementia (FTD) is a genetically and pathologically heterogeneous disorder characterized by personality changes, language impairment, and deficits of executive functions associated with frontal and temporal lobe degeneration. Different phenotypes have been defined on the basis of presenting clinical symptoms, i.e., the behavioral variant of FTD, the agrammatic variant of primary progressive aphasia, and the semantic variant of PPA. Some patients have an associated movement disorder, either parkinsonism, as in progressive supranuclear palsy and corticobasal syndrome, or motor neuron disease (FTD–MND). A family history of dementia is found in 40% of cases of FTD and about 10% have a clear autosomal-dominant inheritance. Genetic studies have identified several genes associated with monogenic FTD: microtubule-associated protein tau, progranulin, TAR DNA-binding protein 43, valosin-containing protein, charged multivesicular body protein 2B, fused in sarcoma, and the hexanucleotide repeat expansion in intron 1 of the chromosome 9 open reading frame 72. Patients often present with an extensive phenotypic variability, even among different members of the same kindred carrying an identical disease mutation. The objective of the present work is to review and evaluate available literature data in order to highlight recent advances in clinical, biological, and neuroimaging features of monogenic frontotemporal lobar degeneration and try to identify different mechanisms underlying the extreme phenotypic heterogeneity that characterizes this disease. PMID:26388768

  10. Heterogeneity in Waardenburg syndrome.

    PubMed Central

    Hageman, M J; Delleman, J W

    1977-01-01

    Heterogeneity of Waardenburg syndrome is demonstrated in a review of 1,285 patients from the literature and 34 previously unreported patients in five families in the Netherlands. The syndrome seems to consist of two genetically distinct entities that can be differentiated clinically: type I, Waardenburg syndrome with dystopia canthorum; and type II, Waardenburg syndrome without dystopia canthorum. Both types have an autosomal dominant mode of inheritance. The incidence of bilateral deafness in the two types of the syndrome was found in one-fourth with type I and about half of the patients with type II. This difference has important consequences for genetic counseling. Images Fig. 7 Fig. 8 Fig. 9 PMID:331943

  11. Aggregation of Heterogeneously Charged Colloids.

    PubMed

    Dempster, Joshua M; Olvera de la Cruz, Monica

    2016-06-28

    Patchy colloids are attractive as programmable building blocks for metamaterials. Inverse patchy colloids, in which a charged surface is decorated with patches of the opposite charge, are additionally noteworthy as models for heterogeneously charged biological materials such as proteins. We study the phases and aggregation behavior of a single charged patch in an oppositely charged colloid with a single-site model. This single-patch inverse patchy colloid model shows a large number of phases when varying patch size. For large patch sizes we find ferroelectric crystals, while small patch sizes produce cross-linked gels. Intermediate values produce monodisperse clusters and unusual worm structures that preserve finite ratios of area to volume. The polarization observed at large patch sizes is robust under extreme disorder in patch size and shape. We examine phase-temperature dependence and coexistence curves and find that large patch sizes produce polarized liquids, in contrast to mean-field predictions. Finally, we introduce small numbers of unpatched charged colloids. These can either suppress or encourage aggregation depending on their concentration and the size of the patches on the patched colloids. These effects can be exploited to control aggregation and to measure effective patch size.

  12. Interconnecting heterogeneous database management systems

    NASA Technical Reports Server (NTRS)

    Gligor, V. D.; Luckenbaugh, G. L.

    1984-01-01

    It is pointed out that there is still a great need for the development of improved communication between remote, heterogeneous database management systems (DBMS). Problems regarding the effective communication between distributed DBMSs are primarily related to significant differences between local data managers, local data models and representations, and local transaction managers. A system of interconnected DBMSs which exhibit such differences is called a network of distributed, heterogeneous DBMSs. In order to achieve effective interconnection of remote, heterogeneous DBMSs, the users must have uniform, integrated access to the different DBMs. The present investigation is mainly concerned with an analysis of the existing approaches to interconnecting heterogeneous DBMSs, taking into account four experimental DBMS projects.

  13. p53 mutation heterogeneity in cancer

    SciTech Connect

    Soussi, T. . E-mail: thierry.soussi@free.fr; Lozano, G.

    2005-06-10

    The p53 gene is inactivated in about 50% of human cancers and the p53 protein is an essential component of the cell response induced by genotoxic stresses such as those generated by radiotherapy or chemotherapy. It is therefore highly likely that these alterations are an important component in tumor resistance to therapy. The particular characteristics of these alterations, 80% of which are missense mutations leading to functionally heterogeneous proteins, make p53 a unique gene in the class of tumor suppressor genes. A considerable number of mutant p53 proteins probably have an oncogenic activity per se and therefore actively participate in cell transformation. The fact that the apoptotic and antiproliferative functions of p53 can be dissociated in certain mutants also suggests another level of complexity in the relationships between p53 inactivation and neoplasia.

  14. Etiologic heterogeneity in alcoholism.

    PubMed

    Gilligan, S B; Reich, T; Cloninger, C R

    1987-01-01

    Etiologic heterogeneity in alcohol abuse was evaluated in 195 extended pedigrees, comprising 288 nuclear families of 140 male and 55 female Caucasian American hospitalized alcoholics. Previous adoption studies in Sweden demonstrated differential heritability of two patterns of alcohol abuse in men: type-2 alcoholism exhibited early onset of abuse associated with criminal behavior, while type-1 abuse began at a later age, uncomplicated by antisocial traits. Alcohol abuse in female Swedish adoptees was relatively homogeneous and similar to the late-onset, type-1 abuse. The notion of etiologic heterogeneity, as suggested by the Stockholm Adoption Studies, was examined in the American pedigrees by contrasting the models of familial transmission of susceptibility to alcoholism obtained via segregation analyses of families of male versus female probands. Families of male probands demonstrated significant familial resemblance, accounted for by a multifactorial-polygenic background in addition to a major (gene) effect. In contrast, familial resemblance in the pedigrees of female probands was attributed solely to a multifactorial-polygenic effect. We considered whether some families of male alcoholics were similar to families of female probands, who expressed type-1 abuse predominantly. Pedigrees of male probands were separated in two groups: (1) "female-like" families had a better likelihood for the model obtained for families of female probands than the one for families of all male probands, (2) "male-like" families had a better likelihood for the model of familial transmission describing families of all male probands. A statistically significant difference in the pattern of familial transmission was observed between the "male-like" and "female-like" groups. Discriminant function analysis of alcohol-related symptoms showed that the familial subtypes differed in clinical features as well. Alcohol abuse by male relatives in "male-like" families was characterized by the

  15. Data manipulation in heterogeneous databases

    SciTech Connect

    Chatterjee, A.; Segev, A.

    1991-10-01

    Many important information systems applications require access to data stored in multiple heterogeneous databases. This paper examines a problem in inter-database data manipulation within a heterogeneous environment, where conventional techniques are no longer useful. To solve the problem, a broader definition for join operator is proposed. Also, a method to probabilistically estimate the accuracy of the join is discussed.

  16. Interference Management in Heterogeneous Networks

    DTIC Science & Technology

    2013-06-01

    INTERFERENCE MANAGEMENT IN HETEROGENEOUS NETWORKS UNIVERSITY OF MARYLAND JUNE 2013 FINAL TECHNICAL REPORT APPROVED...3. DATES COVERED (From - To) AUG 2011 – FEB 2013 4. TITLE AND SUBTITLE INTERFERENCE MANAGEMENT IN HETEROGENEOUS NETWORKS 5a. CONTRACT NUMBER...However, such deployments require efficient frequency allocation schemes for managing interference from the pico- and macro base stations that are

  17. Theory of heterogeneous viscoelasticity

    NASA Astrophysics Data System (ADS)

    Schirmacher, Walter; Ruocco, Giancarlo; Mazzone, Valerio

    2016-03-01

    We review a new theory of viscoelasticity of a glass-forming viscous liquid near and below the glass transition. In our model, we assume that each point in the material has a specific viscosity, which varies randomly in space according to a fluctuating activation free energy. We include a Maxwellian elastic term, and assume that the corresponding shear modulus fluctuates as well with the same distribution as that of the activation barriers. The model is solved in coherent potential approximation, for which a derivation is given. The theory predicts an Arrhenius-type temperature dependence of the viscosity in the vanishing frequency limit, independent of the distribution of the activation barriers. The theory implies that this activation energy is generally different from that of a diffusing particle with the same barrier height distribution. If the distribution of activation barriers is assumed to have the Gaussian form, the finite-frequency version of the theory describes well the typical low-temperature alpha relaxation peak of glasses. Beta relaxation can be included by adding another Gaussian with centre at much lower energies than that is responsible for the alpha relaxation. At high frequencies, our theory reduces to the description of an elastic medium with spatially fluctuating elastic moduli (heterogeneous elasticity theory), which explains the occurrence of the boson peak-related vibrational anomalies of glasses.

  18. Angiotensin II receptor heterogeneity

    SciTech Connect

    Herblin, W.F.; Chiu, A.T.; McCall, D.E.; Ardecky, R.J.; Carini, D.J.; Duncia, J.V.; Pease, L.J.; Wong, P.C.; Wexler, R.R.; Johnson, A.L. )

    1991-04-01

    The possibility of receptor heterogeneity in the angiotensin II (AII) system has been suggested previously, based on differences in Kd values or sensitivity to thiol reagents. One of the authors earliest indications was the frequent observation of incomplete inhibition of the binding of AII to adrenal cortical membranes. Autoradiographic studies demonstrated that all of the labeling of the rat adrenal was blocked by unlabeled AII or saralasin, but not by DuP 753. The predominant receptor in the rat adrenal cortex (80%) is sensitive to dithiothreitol (DTT) and DuP 753, and is designated AII-1. The residual sites in the adrenal cortex and almost all of the sites in the rat adrenal medulla are insensitive to both DTT and DuP 753, but were blocked by EXP655. These sites have been confirmed by ligand binding studies and are designated AII-2. The rabbit adrenal cortex is unique in yielding a nonuniform distribution of AII-2 sites around the outer layer of glomerulosa cells. In the rabbit kidney, the sites on the glomeruli are AII-1, but the sites on the kidney capsule are AII-2. Angiotensin III appears to have a higher affinity for AII-2 sites since it inhibits the binding to the rabbit kidney capsule but not the glomeruli. Elucidation of the distribution and function of these diverse sites should permit the development of more selective and specific therapeutic strategies.

  19. Heterogeneous recording media

    NASA Astrophysics Data System (ADS)

    Sukhanov, Vitaly I.

    1991-02-01

    The paper summarizes the results of investigations performed to obtain deep 3-D holograms with 102 i0 mkm physical thickness allowing the postexposure amplification and the a posteriori changing of the grating parameters. This aim has been achieved by developing heterogeneous systems on the basis of porous glass with light-sensitive compositions introduced into it. 1. INTRODUCTION. LIGHT-SENSITIVE MEDIA FOR 3-D HOLOGRAMS RECORDING. The 3-D holograms have many useful properties: very high diffraction efficiency angular and spectral selectivity but low level of noise. It shoud be noted that in this case deep 3-D holograms are dealt with whose physical thickness is as high as 102 -i mkm. Such hologram recording is usually done using homogeneous light-sensitive media for example dyed acid-halide and electrooptical crystals photochrome glass photostructurized polimer compositions and so on. The nature of photophisical and photochemical processes responsible for the light sensitivity of these materials exclude the possibility of post-exposure treatment. This does not allow to enhance the recorded holograms and considerably hampers their fixing or makes it practically impossible. The object of our work is to create the media which are quite suitable for two-stage processes of the deep hologram formation with post-exposure processing. Such material must satisfy the following requirements: a)they must have high permeability for the developing substances in order to make the development duration suitable for practical applications b)they must be shrinkproof to prevent deformation of the

  20. Reference Point Heterogeneity

    PubMed Central

    Terzi, Ayse; Koedijk, Kees; Noussair, Charles N.; Pownall, Rachel

    2016-01-01

    It is well-established that, when confronted with a decision to be taken under risk, individuals use reference payoff levels as important inputs. The purpose of this paper is to study which reference points characterize decisions in a setting in which there are several plausible reference levels of payoff. We report an experiment, in which we investigate which of four potential reference points: (1) a population average payoff level, (2) the announced expected payoff of peers in a similar decision situation, (3) a historical average level of earnings that others have received in the same task, and (4) an announced anticipated individual payoff level, best describes decisions in a decontextualized risky decision making task. We find heterogeneity among individuals in the reference points they employ. The population average payoff level is the modal reference point, followed by experimenter's stated expectation of a participant's individual earnings, followed in turn by the average earnings of other participants in previous sessions of the same experiment. A sizeable share of individuals show multiple reference points simultaneously. The reference point that best fits the choices of the individual is not affected by a shock to her income. PMID:27672374

  1. Reference Point Heterogeneity.

    PubMed

    Terzi, Ayse; Koedijk, Kees; Noussair, Charles N; Pownall, Rachel

    2016-01-01

    It is well-established that, when confronted with a decision to be taken under risk, individuals use reference payoff levels as important inputs. The purpose of this paper is to study which reference points characterize decisions in a setting in which there are several plausible reference levels of payoff. We report an experiment, in which we investigate which of four potential reference points: (1) a population average payoff level, (2) the announced expected payoff of peers in a similar decision situation, (3) a historical average level of earnings that others have received in the same task, and (4) an announced anticipated individual payoff level, best describes decisions in a decontextualized risky decision making task. We find heterogeneity among individuals in the reference points they employ. The population average payoff level is the modal reference point, followed by experimenter's stated expectation of a participant's individual earnings, followed in turn by the average earnings of other participants in previous sessions of the same experiment. A sizeable share of individuals show multiple reference points simultaneously. The reference point that best fits the choices of the individual is not affected by a shock to her income.

  2. Emerging Understanding of Multiscale Tumor Heterogeneity

    PubMed Central

    Gerdes, Michael J.; Sood, Anup; Sevinsky, Christopher; Pris, Andrew D.; Zavodszky, Maria I.; Ginty, Fiona

    2014-01-01

    Cancer is a multifaceted disease characterized by heterogeneous genetic alterations and cellular metabolism, at the organ, tissue, and cellular level. Key features of cancer heterogeneity are summarized by 10 acquired capabilities, which govern malignant transformation and progression of invasive tumors. The relative contribution of these hallmark features to the disease process varies between cancers. At the DNA and cellular level, germ-line and somatic gene mutations are found across all cancer types, causing abnormal protein production, cell behavior, and growth. The tumor microenvironment and its individual components (immune cells, fibroblasts, collagen, and blood vessels) can also facilitate or restrict tumor growth and metastasis. Oncology research is currently in the midst of a tremendous surge of comprehension of these disease mechanisms. This will lead not only to novel drug targets but also to new challenges in drug discovery. Integrated, multi-omic, multiplexed technologies are essential tools in the quest to understand all of the various cellular changes involved in tumorigenesis. This review examines features of cancer heterogeneity and discusses how multiplexed technologies can facilitate a more comprehensive understanding of these features. PMID:25566504

  3. Processing heterogeneous biomass

    PubMed Central

    Buyel, Johannes F.; Fischer, Rainer

    2013-01-01

    Plants have been developed as an alternative platform for the production of biopharmaceutical proteins, culminating recently with the FDA approval of the first plant-derived recombinant pharmaceutical enzyme for human use (ELELYSOÔ by Protalix Biotherapeutics). Among the many different plant-based technologies that have been proposed, transient expression mediated by Agrobacterium tumefaciens has proven to be particularly suitable for the rapid production of vaccines in response to emerging pandemics. However, one potential drawback of transient expression in whole plants is the large variation in recombinant protein expression levels among different leaves, which introduces a level of uncertainty in process design that can increase the regulatory burden and production costs. Transient expression is also used to test expression constructs prior to the longer and more expensive process of generating transgenic plants, and here the variation can produce misleading results leading to erroneous conclusions about the relative activity of different promoters and other regulatory elements. Such variation can be caused by loosely controlled environmental and process factors such incubation temperature, plant characteristics and the method and timing of harvesting. Here we discuss differences between transgenic plants and transient expression in intact plants, and their specific pitfalls for model building. We also highlight which aspects researchers should consider when using a DoE approach to investigate protein expression in plants, both for fundamental research and process development. PMID:22895059

  4. Homogeneous, Heterogeneous, and Enzymatic Catalysis.

    ERIC Educational Resources Information Center

    Oyama, S. Ted; Somorjai, Gabor A.

    1988-01-01

    Discusses three areas of catalysis: homegeneous, heterogeneous, and enzymatic. Explains fundamentals and economic impact of catalysis. Lists and discusses common industrial catalysts. Provides a list of 107 references. (MVL)

  5. Heterogeneity in motor driven transport

    NASA Astrophysics Data System (ADS)

    Tabei, Ali

    2015-03-01

    I will discuss quantitative analysis of particle tracking data for motor driven vesicles inside an insulin secreting cell. We use this method to study the dynamical and structural heterogeneity inside the cell. I will discuss our effort to explain the origin of observed heterogeneity in intracellular transport. Finally, I will explain how analyzing directional correlations in transport trajectories reveals self-similarity in the diffusion media.

  6. Compositional heterogeneity and phylogenomic inference of metazoan relationships.

    PubMed

    Nesnidal, Maximilian P; Helmkampf, Martin; Bruchhaus, Iris; Hausdorf, Bernhard

    2010-09-01

    Compositional heterogeneity of sequences between taxa may cause systematic error in phylogenetic inference. The potential influence of such bias might be mitigated by strategies to reduce compositional heterogeneity in the data set or by phylogeny reconstruction methods that account for compositional heterogeneity. We adopted several of these strategies to analyze a large ribosomal protein data set representing all major metazoan taxa. Posterior predictive tests revealed that there is compositional bias in this data set. Only a few taxa with strongly deviating amino acid composition had to be excluded to reduce this bias. Thus, this is a good solution, if these taxa are not central to the phylogenetic question at hand. Deleting individual proteins from the data matrix may be an appropriate method, if compositional heterogeneity among taxa is concentrated in a few proteins. However, half of the ribosomal proteins had to be excluded to reduce the compositional heterogeneity to a degree that the CAT model was no longer significantly violated. Recoding of amino acids into groups is another alternative but causes a loss of information and may result in badly resolved trees as demonstrated by the present data set. Bayesian inference with the CAT-BP model directly accounts for compositional heterogeneity between lineages by introducing breakpoints along the branches of the phylogeny at which the amino acid composition is allowed to change but is computationally expensive. Finally, a neighbor joining tree based on equal input distances that consider pattern and rate heterogeneity showed several unusual groupings, which are most likely artifacts, probably caused by the loss of information resulting from the transformation of the sequence data into distances. As long as no more efficient phylogenetic inference methods are available that can directly account for compositional heterogeneity in large data sets, using methods for reducing compositional heterogeneity in the data

  7. Using Inorganic Crystals To Grow Protein Crystals

    NASA Technical Reports Server (NTRS)

    Shlichta, Paul J.; Mcpherson, Alexander A.

    1989-01-01

    Solid materials serve as nucleating agents. Protein crystals induced by heterogeneous nucleation and in some cases by epitaxy to grow at lower supersaturations than needed for spontaneous nucleation. Heterogeneous nucleation makes possible to grow large, defect-free single crystals of protein more readily. Such protein crystals benefits research in biochemistry and pharmacology.

  8. Directly measuring single-molecule heterogeneity using force spectroscopy

    PubMed Central

    Hinczewski, Michael; Thirumalai, D.

    2016-01-01

    One of the most intriguing results of single-molecule experiments on proteins and nucleic acids is the discovery of functional heterogeneity: the observation that complex cellular machines exhibit multiple, biologically active conformations. The structural differences between these conformations may be subtle, but each distinct state can be remarkably long-lived, with interconversions between states occurring only at macroscopic timescales, fractions of a second or longer. Although we now have proof of functional heterogeneity in a handful of systems—enzymes, motors, adhesion complexes—identifying and measuring it remains a formidable challenge. Here, we show that evidence of this phenomenon is more widespread than previously known, encoded in data collected from some of the most well-established single-molecule techniques: atomic force microscopy or optical tweezer pulling experiments. We present a theoretical procedure for analyzing distributions of rupture/unfolding forces recorded at different pulling speeds. This results in a single parameter, quantifying the degree of heterogeneity, and also leads to bounds on the equilibration and conformational interconversion timescales. Surveying 10 published datasets, we find heterogeneity in 5 of them, all with interconversion rates slower than 10 s−1. Moreover, we identify two systems where additional data at realizable pulling velocities is likely to find a theoretically predicted, but so far unobserved crossover regime between heterogeneous and nonheterogeneous behavior. The significance of this regime is that it will allow far more precise estimates of the slow conformational switching times, one of the least understood aspects of functional heterogeneity. PMID:27317744

  9. Dealing with spatial heterogeneity

    NASA Astrophysics Data System (ADS)

    Marsily, Gh.; Delay, F.; Gonçalvès, J.; Renard, Ph.; Teles, V.; Violette, S.

    2005-03-01

    Heterogeneity can be dealt with by defining homogeneous equivalent properties, known as averaging, or by trying to describe the spatial variability of the rock properties from geologic observations and local measurements. The techniques available for these descriptions are mostly continuous Geostatistical models, or discontinuous facies models such as the Boolean, Indicator or Gaussian-Threshold models and the Markov chain model. These facies models are better suited to treating issues of rock strata connectivity, e.g. buried high permeability channels or low permeability barriers, which greatly affect flow and, above all, transport in aquifers. Genetic models provide new ways to incorporate more geology into the facies description, an approach that has been well developed in the oil industry, but not enough in hydrogeology. The conclusion is that future work should be focused on improving the facies models, comparing them, and designing new in situ testing procedures (including geophysics) that would help identify the facies geometry and properties. A world-wide catalog of aquifer facies geometry and properties, which could combine site genesis and description with methods used to assess the system, would be of great value for practical applications. On peut aborder le problème de l'hétérogénéité en s'efforçant de définir une perméabilité équivalente homogène, par prise de moyenne, ou au contraire en décrivant la variation dans l'espace des propriétés des roches à partir des observations géologiques et des mesures locales. Les techniques disponibles pour une telle description sont soit continues, comme l'approche Géostatistique, soit discontinues, comme les modèles de faciès, Booléens, ou bien par Indicatrices ou Gaussiennes Seuillées, ou enfin Markoviens. Ces modèles de faciès sont mieux capables de prendre en compte la connectivité des strates géologiques, telles que les chenaux enfouis à forte perméabilité, ou au contraire les faci

  10. Reaction Selectivity in Heterogeneous Catalysis

    SciTech Connect

    Somorjai, Gabor A.; Kliewer, Christopher J.

    2009-02-02

    The understanding of selectivity in heterogeneous catalysis is of paramount importance to our society today. In this review we outline the current state of the art in research on selectivity in heterogeneous catalysis. Current in-situ surface science techniques have revealed several important features of catalytic selectivity. Sum frequency generation vibrational spectroscopy has shown us the importance of understanding the reaction intermediates and mechanism of a heterogeneous reaction, and can readily yield information as to the effect of temperature, pressure, catalyst geometry, surface promoters, and catalyst composition on the reaction mechanism. DFT calculations are quickly approaching the ability to assist in the interpretation of observed surface spectra, thereby making surface spectroscopy an even more powerful tool. HP-STM has revealed three vitally important parameters in heterogeneous selectivity: adsorbate mobility, catalyst mobility, and selective site-blocking. The development of size controlled nanoparticles from 0.8 to 10 nm, of controlled shape, and of controlled bimetallic composition has revealed several important variables for catalytic selectivity. Lastly, DFT calculations may be paving the way to guiding the composition choice for multi-metallic heterogeneous catalysis for the intelligent design of catalysts incorporating the many factors of selectivity we have learned.

  11. Cancer heterogeneity determined by functional proteomics.

    PubMed

    Szász, A Marcell; Győrffy, Balázs; Marko-Varga, György

    2016-08-26

    Current manuscript gives a synopsis of tumor heterogeneity related to patient samples analyzed by proteomics, protein expression analysis and imaging mass spectrometry. First, we discuss the pathophysiologocal background of cancer biology as a multifactorial and challenging diseases. Disease pathology forms the basis for protein target selection. Therefore, histopathological diagnostics and grading of tumors is highlighted. Pathology is the cornerstone of state-of-the-art diagnostics of tumors today both by establishing dignity and - when needed - describing molecular properties of the cancers. Drug development by the pharmaceutical industry utilizes proteomics studies to pinpoint the most relevant targets. Molecular studies profiling affinity-interactions of the protein(s) with targeted small drug molecules to reach efficacy and optimal patient safety are today requested by the FDA and other agencies for new drug development. An understading of basic mechanisms, controlling drug action and drug binding is central, as a new era of personalized medicine becomes an important milestone solution for the healthcare sector as well as the Pharma and Biotech industry. Development of further diagnostic, prognostic and predictive tests will aid current and future treatment of cancer patients. In the paper we present current status of Proteomics that we believe requires attention in order to collectively advance forward in the fight against cancer, addressing the burning opportunities and challenges.

  12. Tubulin heterogeneity in the trypanosome Crithidia fasciculata.

    PubMed Central

    Russell, D G; Miller, D; Gull, K

    1984-01-01

    The interphase cell of Crithidia fasciculata has three discrete tubulin populations: the subpellicular microtubules, the axonemal microtubules, and the nonpolymerized cytoplasmic pool protein. These three tubulin populations were independently and selectively purified, yielding, in each case, microtubule protein capable of self-assembly. All three preparations polymerized to form ribbons and sheets rather than the more usual microtubular structures. Analyses of the tubulin by two-dimensional polyacrylamide gel electrophoresis, isoelectric focusing, and peptide mapping indicated that the beta-tubulin complex remained constant regardless of source but that some heterogeneity was present in the alpha subunit. Cytoplasmic pool alpha tubulins (alpha 1/alpha 2) were the only alpha isotypes in the cytoplasm and also formed most of the alpha tubulin species in the pellicular fraction. Flagellar alpha tubulin (alpha 3) was the sole alpha isotype in the flagella; it appeared in small amounts in the pellicular fraction but was completely absent from the cytoplasm. In vitro translation products from polyadenylated RNA from C. fasciculata were also examined by two-dimensional polyacrylamide gel electrophoresis and possessed a protein corresponding to alpha 1/alpha 2 tubulin but lacked any alpha 3 tubulin. The alpha 3 polypeptide arose from a post-translational modification of a precursor polypeptide not identifiable by two-dimensional polyacrylamide gel electrophoresis as alpha 3. Peptide mapping data indicated that cytoplasmic alpha tubulin is the most likely precursor. These results demonstrate alpha-tubulin heterogeneity in this organism and also how close the relationship between flagellar and cytoskeletal tubulins can be among lower eucaryotes. Images PMID:6717441

  13. Simulator for heterogeneous dataflow architectures

    NASA Technical Reports Server (NTRS)

    Malekpour, Mahyar R.

    1993-01-01

    A new simulator is developed to simulate the execution of an algorithm graph in accordance with the Algorithm to Architecture Mapping Model (ATAMM) rules. ATAMM is a Petri Net model which describes the periodic execution of large-grained, data-independent dataflow graphs and which provides predictable steady state time-optimized performance. This simulator extends the ATAMM simulation capability from a heterogenous set of resources, or functional units, to a more general heterogenous architecture. Simulation test cases show that the simulator accurately executes the ATAMM rules for both a heterogenous architecture and a homogenous architecture, which is the special case for only one processor type. The simulator forms one tool in an ATAMM Integrated Environment which contains other tools for graph entry, graph modification for performance optimization, and playback of simulations for analysis.

  14. Simulator for heterogeneous dataflow architectures

    NASA Astrophysics Data System (ADS)

    Malekpour, Mahyar R.

    1993-09-01

    A new simulator is developed to simulate the execution of an algorithm graph in accordance with the Algorithm to Architecture Mapping Model (ATAMM) rules. ATAMM is a Petri Net model which describes the periodic execution of large-grained, data-independent dataflow graphs and which provides predictable steady state time-optimized performance. This simulator extends the ATAMM simulation capability from a heterogenous set of resources, or functional units, to a more general heterogenous architecture. Simulation test cases show that the simulator accurately executes the ATAMM rules for both a heterogenous architecture and a homogenous architecture, which is the special case for only one processor type. The simulator forms one tool in an ATAMM Integrated Environment which contains other tools for graph entry, graph modification for performance optimization, and playback of simulations for analysis.

  15. Static heterogeneities in liquid water

    NASA Astrophysics Data System (ADS)

    Stanley, H. Eugene; Buldyrev, Sergey V.; Giovambattista, Nicolas

    2004-10-01

    The thermodynamic behavior of water seems to be closely related to static heterogeneities. These static heterogeneities are related to the local structure of water molecules, and when properly characterized, may offer an economical explanation of thermodynamic data. The key feature of liquid water is not so much that the existence of hydrogen bonds, first pointed out by Linus Pauling, but rather the local geometry of the liquid molecules is not spherical or oblong but tetrahedral. In the consideration of static heterogeneities, this local geometry is critical. Recent experiments suggested more than one phase of amorphous solid water, while simulations suggest that one of these phases is metastable with respect to another, so that in fact there are only two stable phases.

  16. Dynamic fracture of heterogeneous materials

    SciTech Connect

    Stout, M.G.; Liu, C.; Addessio, F.L.; Williams, T.O.; Bennett, J.G.; Haberman, K.S.; Asay, B.W.

    1998-12-31

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The objective of this project was to investigate the fundamental aspects of the process of dynamic fracture propagation in heterogeneous materials. The work focused on three important, but poorly understood, aspects of dynamic fracture for materials with a heterogeneous microstructure. These were: the appropriateness of using a single-parameter asymptotic analysis to describe dynamic crack-tip deformation fields, the temperature rises at the tip and on the flanks of a running crack, and the constitutive modeling of damage initiation and accumulation.

  17. Molecular ingredients of heterogeneous catalysis

    SciTech Connect

    Somorjai, G.A.

    1982-06-01

    The purpose of this paper is to present a review and status report to those in theoretical chemistry of the rapidly developing surface science of heterogeneous catalysis. The art of catalysis is developing into science. This profound change provides one with opportunities not only to understand the molecular ingredients of important catalytic systems but also to develop new and improved catalyst. The participation of theorists to find answers to important questions is sorely needed for the sound development of the field. It is the authors hope that some of the outstanding problems of heterogeneous catalysis that are identified in this paper will be investigated. For this purpose the paper is divided into several sections. The brief Introduction to the methodology and recent results of the surface science of heterogeneous catalysis is followed by a review of the concepts of heterogeneous catalysis. Then, the experimental results that identified the three molecular ingredients of catalysis, structure, carbonaceous deposit and the oxidation state of surface atoms are described. Each section is closed with a summary and a list of problems that require theoretical and experimental scrutiny. Finally attempts to build new catalyst systems and the theoretical and experimental problems that appeared in the course of this research are described.

  18. Teaching about Heterogeneous Response Models

    ERIC Educational Resources Information Center

    Murray, Michael P.

    2014-01-01

    Individuals vary in their responses to incentives and opportunities. For example, additional education will affect one person differently than another. In recent years, econometricians have given increased attention to such heterogeneous responses and to the consequences of such responses for interpreting regression estimates, especially…

  19. Floodplain heterogeneity and meander migration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The impact of horizontal heterogeneity of floodplain soils on rates and patterns of meander migration is analyzed with a Ikeda et al. (1981)-type model for hydrodynamics and bed morphodynamics, coupled with a physically-based bank erosion model according to the approach developed by Motta et al. (20...

  20. Heterogeneous porous media in hydrology

    NASA Astrophysics Data System (ADS)

    Ababou, Rachid

    In natural geologic formations, flow and transport-related processes are perturbed by multidimensional and anisotropic material heterogeneities of diverse sizes, shapes, and origins (bedding, layering, inclusions, fractures, grains, for example). Heterogeneity tends to disperse and mix transported quantities and may initiate new transfer mechanisms not seen in ideally homogeneous porous media. Effective properties such as conductivity and dispersivity may not be simple averages of locally measured quantities.The special session, “Effective Constitutive Laws for Heterogeneous Porous Media,” convened at AGU's 1992 Fall Meeting in San Francisco, addressed these issue. Over forty-five contributions, both oral and poster, covering a broad range of physical phenomena were presented. The common theme was the macroscale characterization and modeling of flow and flow-related processes in geologic media that are heterogeneous at various scales (from grain size or fracture aperture, up to regional scales). The processes analyzed in the session included coupled hydro-mechanical processes; Darcy-type flow in the saturated, unsaturated, or two-phase regimes; tracer transport, dilution, and dispersion. These processes were studied for either continuous (porous) or discontinuous (fractured) media.

  1. Social Capital and Community Heterogeneity

    ERIC Educational Resources Information Center

    Coffe, Hilde

    2009-01-01

    Recent findings indicate that more pronounced community heterogeneity is associated with lower levels of social capital. These studies, however, concentrate on specific aspects in which people differ (such as income inequality or ethnic diversity). In the present paper, we introduce the number of parties in the local party system as a more…

  2. Surface science of heterogeneous reactions.

    PubMed

    White, J M

    1982-10-29

    Some of the present and future directions for surface science as a growing and naturally interdisciplinary subject are reviewed. Particular attention is given to surface reaction chemistry as it is related to heterogenous catalysis, a subject area where there are abundant opportunities for detailed measurements of structure and dynamics at the molecular level.

  3. Flammability of Heterogeneously Combusting Metals

    NASA Technical Reports Server (NTRS)

    Jones, Peter D.

    1998-01-01

    Most engineering materials, including some metals, most notably aluminum, burn in homogeneous combustion. 'Homogeneous' refers to both the fuel and the oxidizer being in the same phase, which is usually gaseous. The fuel and oxidizer are well mixed in the combustion reaction zone, and heat is released according to some relation like q(sub c) = delta H(sub c)c[((rho/rho(sub 0))]exp a)(exp -E(sub c)/RT), Eq. (1) where the pressure exponent a is usually close to unity. As long as there is enough heat released, combustion is sustained. It is useful to conceive of a threshold pressure beyond which there is sufficient heat to keep the temperature high enough to sustain combustion, and beneath which the heat is so low that temperature drains away and the combustion is extinguished. Some materials burn in heterogeneous combustion, in which the fuel and oxidizer are in different phases. These include iron and nickel based alloys, which burn in the liquid phase with gaseous oxygen. Heterogeneous combustion takes place on the surface of the material (fuel). Products of combustion may appear as a solid slag (oxide) which progressively covers the fuel. Propagation of the combustion melts and exposes fresh fuel. Heterogeneous combustion heat release also follows the general form of Eq.(1), except that the pressure exponent a tends to be much less than 1. Therefore, the increase in heat release with increasing pressure is not as dramatic as it is in homogeneous combustion. Although the concept of a threshold pressure still holds in heterogeneous combustion, the threshold is more difficult to identify experimentally, and pressure itself becomes less important relative to the heat transfer paths extant in any specific application. However, the constants C, a, and E(sub c) may still be identified by suitable data reduction from heterogeneous combustion experiments, and may be applied in a heat transfer model to judge the flammability of a material in any particular actual

  4. Resolution of structural heterogeneity in dynamic crystallography

    PubMed Central

    Ren, Zhong; Chan, Peter W. Y.; Moffat, Keith; Pai, Emil F.; Royer, William E.; Šrajer, Vukica; Yang, Xiaojing

    2013-01-01

    Dynamic behavior of proteins is critical to their function. X-­ray crystallography, a powerful yet mostly static technique, faces inherent challenges in acquiring dynamic information despite decades of effort. Dynamic ‘structural changes’ are often indirectly inferred from ‘structural differences’ by comparing related static structures. In contrast, the direct observation of dynamic structural changes requires the initiation of a biochemical reaction or process in a crystal. Both the direct and the indirect approaches share a common challenge in analysis: how to interpret the structural heterogeneity intrinsic to all dynamic processes. This paper presents a real-space approach to this challenge, in which a suite of analytical methods and tools to identify and refine the mixed structural species present in multiple crystallographic data sets have been developed. These methods have been applied to representative scenarios in dynamic crystallography, and reveal structural information that is otherwise difficult to interpret or inaccessible using conventional methods. PMID:23695239

  5. Resolution of structural heterogeneity in dynamic crystallography.

    PubMed

    Ren, Zhong; Chan, Peter W Y; Moffat, Keith; Pai, Emil F; Royer, William E; Šrajer, Vukica; Yang, Xiaojing

    2013-06-01

    Dynamic behavior of proteins is critical to their function. X-ray crystallography, a powerful yet mostly static technique, faces inherent challenges in acquiring dynamic information despite decades of effort. Dynamic `structural changes' are often indirectly inferred from `structural differences' by comparing related static structures. In contrast, the direct observation of dynamic structural changes requires the initiation of a biochemical reaction or process in a crystal. Both the direct and the indirect approaches share a common challenge in analysis: how to interpret the structural heterogeneity intrinsic to all dynamic processes. This paper presents a real-space approach to this challenge, in which a suite of analytical methods and tools to identify and refine the mixed structural species present in multiple crystallographic data sets have been developed. These methods have been applied to representative scenarios in dynamic crystallography, and reveal structural information that is otherwise difficult to interpret or inaccessible using conventional methods.

  6. Surface heterogeneity of small asteroids

    NASA Astrophysics Data System (ADS)

    Sasaki, Sho

    A rubble pile model of asteroid origin would predict averaged rather homogeneous surface of an asteroid. Previous spacecraft observations (mostly S-type asteroids) did not show large color/albedo variation on the surface. Vesta would be exceptional since HST observation suggested that its surface should be heterogeneous due to the impact excavation of the interior. As for a young asteroid (832) Karin (age being 5Ma), Sasaki et al. (2004) detected variation of infrared spectra which could be explained by the difference of the space weathering degree. They discussed the possibility of the survival of the old surface. However, the variation was not confirmed by later observation (Chapman et al., 2007; Vernazza et al., 2007). Recent observation of a small (550m) asteroid Itokawa by Hayabusa spacecraft revealed that Itokawa is heterogeneous in color and albedo although the overall rocky structure is considered as a rubble pile (Saito et al., 2006). The color difference can be explained by the difference of weathering degree (Ishiguro et al., 2008). The heterogeneity could be explained by mass movement caused by rapid rotation from YORP effect (Scheeres et al., 2007) or seismic shaking (Sasaki, 2006). Probably small silicate asteroids without significant regolith could have heterogeneous in color and albedo. On large asteroids (˜ a few 10km), regolith reaccumulation should have covered the underlying heterogeneity. References: Chapman, C. R. et al (2007) Icarus, 191, 323-329 Ishiguro, M. et al. (2008) MAPS, in press. Saito, J. et al. (2006) Science, 312, 1341-1344 Sasaki, S. (2006) in Spacecraft Reconnaissance of Asteroid and Comet Interiors Sasaki, T. et al (2004) Astrophys. J. 615, L161-L164 Scheeres, D. J. (2007) Icarus 188, 425-429 Vernazza, P. et al. (2007) Icarus 191, 330-336.

  7. Heterogeneous ribonucleoprotein C displays a repressor activity mediated by T-cell intracellular antigen-1-related/like protein to modulate Fas exon 6 splicing through a mechanism involving Hu antigen R.

    PubMed

    Izquierdo, José M

    2010-12-01

    T-cell intracellular antigen (TIA)-proteins are known regulators of alternative pre-mRNA splicing. In this study, pull-down experiments and mass spectrometry indicate that TIAR/TIAL1 and hnRNP C1/C2 are associated in HeLa nuclear extracts. Co-immunoprecipitation and GST-pull-down assays confirmed this interaction. Interestingly, binding requires the glutamine-rich (Q-rich) C-terminal domain of TIAR and the leucine-rich plus acidic residues-rich C-terminal domains of hnRNP C1/C2. This interaction also occurs in an RNA-dependent manner. Recombinant GFP-TIAR and RFP-hnRNP C1 proteins display partial nuclear co-localization when overexpressed in HeLa cells, and this requires the Q-rich domain of TIAR. hnRNP C1 overexpression in the presence of rate-limiting amounts of TIAR in HeLa and HEK293 cells affects alternative splicing of Fas and FGFR2 minigenes, promoting Fas exon 6 and FGFR2 exon K-SAM skipping, respectively. The repressor activity of hnRNP C1 on Fas exon 6 splicing is mediated by Hu antigen R (HuR). Experiments involving tethering approaches showed that the repressor capacity of hnRNP C1 is associated with an exonic splicing silencer in Fas exon 6. This effect was reversed by splice-site strengthening and is linked to its basic leucine zipper-like motif. These results suggest that hnRNP C1/C2 acts as a bridge between HuR and TIAR to modulate alternative Fas splicing.

  8. Biodiesel production using heterogeneous catalysts.

    PubMed

    Semwal, Surbhi; Arora, Ajay K; Badoni, Rajendra P; Tuli, Deepak K

    2011-02-01

    The production and use of biodiesel has seen a quantum jump in the recent past due to benefits associated with its ability to mitigate greenhouse gas (GHG). There are large number of commercial plants producing biodiesel by transesterification of vegetable oils and fats based on base catalyzed (caustic) homogeneous transesterification of oils. However, homogeneous process needs steps of glycerol separation, washings, very stringent and extremely low limits of Na, K, glycerides and moisture limits in biodiesel. Heterogeneous catalyzed production of biodiesel has emerged as a preferred route as it is environmentally benign needs no water washing and product separation is much easier. The present report is review of the progress made in development of heterogeneous catalysts suitable for biodiesel production. This review shall help in selection of suitable catalysts and the optimum conditions for biodiesel production.

  9. NASA GSFC Perspective on Heterogeneous Processing

    NASA Technical Reports Server (NTRS)

    Powell, Wesley A.

    2016-01-01

    This presentation provides an overview of NASA GSFC, our onboard processing applications, the applicability heterogeneous processing to these applications, and necessary developments to enable heterogeneous processing to be infused into our missions.

  10. Temperature chaos and quenched heterogeneities

    NASA Astrophysics Data System (ADS)

    Barucca, Paolo; Parisi, Giorgio; Rizzo, Tommaso

    2014-03-01

    We present a treatable generalization of the Sherrington-Kirkpatrick (SK) model which introduces correlations in the elements of the coupling matrix through multiplicative disorder on the single variables and investigate the consequences on the phase diagram. We define a generalized qEA parameter and test the structural stability of the SK results in this correlated case evaluating the de Almeida-Thouless line of the model. As a main result we demonstrate the increase of temperature chaos effects due to heterogeneities.

  11. On comparing heterogeneity across biomarkers.

    PubMed

    Steininger, Robert J; Rajaram, Satwik; Girard, Luc; Minna, John D; Wu, Lani F; Altschuler, Steven J

    2015-06-01

    Microscopy reveals complex patterns of cellular heterogeneity that can be biologically informative. However, a limitation of microscopy is that only a small number of biomarkers can typically be monitored simultaneously. Thus, a natural question is whether additional biomarkers provide a deeper characterization of the distribution of cellular states in a population. How much information about a cell's phenotypic state in one biomarker is gained by knowing its state in another biomarker? Here, we describe a framework for comparing phenotypic states across biomarkers. Our approach overcomes the current limitation of microscopy by not requiring costaining biomarkers on the same cells; instead, we require staining of biomarkers (possibly separately) on a common collection of phenotypically diverse cell lines. We evaluate our approach on two image datasets: 33 oncogenically diverse lung cancer cell lines stained with 7 biomarkers, and 49 less diverse subclones of one lung cancer cell line stained with 12 biomarkers. We first validate our method by comparing it to the "gold standard" of costaining. We then apply our approach to all pairs of biomarkers and use it to identify biomarkers that yield similar patterns of heterogeneity. The results presented in this work suggest that many biomarkers provide redundant information about heterogeneity. Thus, our approach provides a practical guide for selecting independently informative biomarkers and, more generally, will yield insights into both the connectivity of biological networks and the complexity of the state space of biological systems.

  12. Soft Dielectrics: Heterogeneity and Instabilities

    NASA Astrophysics Data System (ADS)

    Rudykh, Stephan; Debotton, Gal; Bhattacharya, Kaushik

    2012-02-01

    Dielectric Elastomers are capable of large deformations in response to electrical stimuli. Heterogeneous soft dielectrics with proper microstructures demonstrate much stronger electromechanical coupling than their homogeneous constituents. In turn, the heterogeneity is an origin for instability developments leading to drastic change in the composite microstructure. In this talk, the electromechanical instabilities are considered. Stability of anisotropic soft dielectrics is analyzed. Ways to achieve giant deformations and manipulating extreme material properties are discussed. 1. S. Rudykh and G. deBotton, ``Instabilities of Hyperelastic Fiber Composites: Micromechanical Versus Numerical Analyses.'' Journal of Elasticity, 2011. http://dx.doi.org/2010.1007/s10659-011-9313-x 2. S. Rudykh, K. Bhattacharya and G. deBotton, ``Snap-through actuation of thick-wall electroactive balloons.'' International Journal of Non-Linear Mechanics, 2011. http://dx.doi.org/10.1016/j.ijnonlinmec.2011.05.006 3. S. Rudykh and G. deBotton, ``Stability of Anisotropic Electroactive Polymers with Application to Layered Media.'' Zeitschrift f"ur angewandte Mathematik und Physik, 2011. http://dx.doi.org/10.1007/s00033-011-0136-1 4. S. Rudykh, A. Lewinstein, G. Uner and G. deBotton, ``Giant Enhancement of the Electromechanical Coupling in Soft Heterogeneous Dielectrics.'' 2011 http://arxiv.org/abs/1105.4217v1

  13. Measuring heterogeneous remanence in paleomagnetism

    NASA Astrophysics Data System (ADS)

    Borradaile, Graham J.; Geneviciene, Ieva

    2007-06-01

    Remanence directions of from the same block-sample may be inconsistent or unrepresentative due to orientation and location heterogeneity of their remanence-bearing minerals (RBM). Magnetization-heterogeneity is usually undetectable at the specimen-level but we replicated its effects by measuring 8 small specimens with stable magnetizations (8 or 5.2 cm3). These were assembled into a single large multi-specimen inside 125 cm3 containers that were measured in a Molspin ``BigSpin'' magnetometer. Large-specimen remanence directions deflect towards the direction of any strongly magnetized sub-specimen. Differences between the large-specimen remanence and that for the group of individually measured sub-specimens worsened when one sub-specimen was mis-oriented. These discrepancies were cancelled or reduced using larger numbers of specimen orientations in the magnetometer. Conventional schemes with 4 or 6 different measurement-orientations may fail to suppress heterogeneity-effects whereas our 12-orientation protocol may succeed. For most specimens, acceptable remanence-homogeneity is present where similar remanence-directions are recorded from 4, 6, and 12 different spin-orientations.

  14. Analyzing and modeling heterogeneous behavior

    NASA Astrophysics Data System (ADS)

    Lin, Zhiting; Wu, Xiaoqing; He, Dongyue; Zhu, Qiang; Ni, Jixiang

    2016-05-01

    Recently, it was pointed out that the non-Poisson statistics with heavy tail existed in many scenarios of human behaviors. But most of these studies claimed that power-law characterized diverse aspects of human mobility patterns. In this paper, we suggest that human behavior may not be driven by identical mechanisms and can be modeled as a Semi-Markov Modulated Process. To verify our suggestion and model, we analyzed a total of 1,619,934 records of library visitations (including undergraduate and graduate students). It is found that the distribution of visitation intervals is well fitted with three sections of lines instead of the traditional power law distribution in log-log scale. The results confirm that some human behaviors cannot be simply expressed as power law or any other simple functions. At the same time, we divided the data into groups and extracted period bursty events. Through careful analysis in different groups, we drew a conclusion that aggregate behavior might be composed of heterogeneous behaviors, and even the behaviors of the same type tended to be different in different period. The aggregate behavior is supposed to be formed by "heterogeneous groups". We performed a series of experiments. Simulation results showed that we just needed to set up two states Semi-Markov Modulated Process to construct proper representation of heterogeneous behavior.

  15. Interference, heterogeneity and disease gene mapping

    SciTech Connect

    Keats, B.

    1996-12-31

    The Human Genome Project has had a major impact on genetic research over the past five years. The number of mapped genes is now over 3,000 compared with approximately 1,600 in 1989 and only about 260 ten years before that. The realization that extensive variation could be detected in anonymous DNA segments greatly enhanced the potential for mapping by linkage analysis. Previously, linkage studies had depended on polymorphisms that could be detected in red blood cell antigens, proteins (revealed by electrophoresis and isoelectric focusing), and cytogenetic heteromorphisms. The identification of thousands of polymorphic DNA markers throughout the human genome has led to the construction of high density genetic linkage maps. These maps provide the data necessary to test hypotheses concerning differences in recombination rates and levels of interference. They are also important for disease gene mapping because the existence of these genes must be inferred from the phenotype. Showing linkage of a disease gene to a DNA marker is the first step towards isolating the disease gene, determining its protein product, and developing effective therapies. However, interpretation of results is not always straightforward. Factors such as etiological heterogeneity and undetected irregular segregation can lead to confusing linkage results and incorrect conclusions about the locations of disease genes. This paper will discuss these phenomena and present examples that illustrate the problems, as well as approaches to dealing with them. 23 refs., 3 figs., 3 tabs.

  16. Modeling Cellular Noise Underlying Heterogeneous Cell Responses in the Epidermal Growth Factor Signaling Pathway

    PubMed Central

    Iwamoto, Kazunari; Shindo, Yuki; Takahashi, Koichi

    2016-01-01

    Cellular heterogeneity, which plays an essential role in biological phenomena, such as drug resistance and migration, is considered to arise from intrinsic (i.e., reaction kinetics) and extrinsic (i.e., protein variability) noise in the cell. However, the mechanistic effects of these types of noise to determine the heterogeneity of signal responses have not been elucidated. Here, we report that the output of epidermal growth factor (EGF) signaling activity is modulated by cellular noise, particularly by extrinsic noise of particular signaling components in the pathway. We developed a mathematical model of the EGF signaling pathway incorporating regulation between extracellular signal-regulated kinase (ERK) and nuclear pore complex (NPC), which is necessary for switch-like activation of the nuclear ERK response. As the threshold of switch-like behavior is more sensitive to perturbations than the graded response, the effect of biological noise is potentially critical for cell fate decision. Our simulation analysis indicated that extrinsic noise, but not intrinsic noise, contributes to cell-to-cell heterogeneity of nuclear ERK. In addition, we accurately estimated variations in abundance of the signal proteins between individual cells by direct comparison of experimental data with simulation results using Apparent Measurement Error (AME). AME was constant regardless of whether the protein levels varied in a correlated manner, while covariation among proteins influenced cell-to-cell heterogeneity of nuclear ERK, suppressing the variation. Simulations using the estimated protein abundances showed that each protein species has different effects on cell-to-cell variation in the nuclear ERK response. In particular, variability of EGF receptor, Ras, Raf, and MEK strongly influenced cellular heterogeneity, while others did not. Overall, our results indicated that cellular heterogeneity in response to EGF is strongly driven by extrinsic noise, and that such heterogeneity

  17. Hypomorphic mutation in hnRNP U results in post-implantation lethality.

    PubMed

    Roshon, Michael J; Ruley, H Earl

    2005-04-01

    The present study characterized an embryonic lethal mutation induced by insertion of the U3Neo gene trap retrovirus into an intron of the gene encoding heterogeneous ribonuclear protein U (Hnrnpu), which maps to the distal arm of mouse chromosome 1. Murine hnRNP U was found to be identical to the human protein at all but one of 341 amino acid residues. Embryos homozygous for the provirus showed obvious abnormalities after 6.5 days of development (E6.5) and were resorbed by E10.5. Expression of the inserted neomycin-resistance gene involved alternative splicing to a cryptic 3' splice site located in the neomycin resistance gene resulting in a hypomorphic mutation. Homozygous mutant cell lines isolated from preimplantation blastocysts expressed hnRNP U transcripts at levels 2 to 5 times lower than wild-type cells, suggesting that nearly wild-type levels of hnRNP U are required for embryonic development.

  18. Stress relaxation in heterogeneous polymers

    NASA Astrophysics Data System (ADS)

    Witten, T. A.

    1992-05-01

    When heterogeneous polymers such as diblock copolymers form a microdomain phase, an imposed strain gives rise to stress from two sources, and several mechanisms of stress relaxation. The release of stress by disentanglement is strongly influenced by the effective confinement of the junction points to the domain boundaries and by the stretching of the chains. Using accepted notions of entangled chain kinetics, it is argued that the relaxation time for sliding stress is exponential in the chainlength to the 7/9 power. A method for calculating the frequency-dependent dynamic modulus is sketched. Despite the slow relaxation implied by these mechanisms, it appears possible to create domains of high energy.

  19. A Heterogeneous Medium Analytical Benchmark

    SciTech Connect

    Ganapol, B.D.

    1999-09-27

    A benchmark, called benchmark BLUE, has been developed for one-group neutral particle (neutron or photon) transport in a one-dimensional sub-critical heterogeneous plane parallel medium with surface illumination. General anisotropic scattering is accommodated through the Green's Function Method (GFM). Numerical Fourier transform inversion is used to generate the required Green's functions which are kernels to coupled integral equations that give the exiting angular fluxes. The interior scalar flux is then obtained through quadrature. A compound iterative procedure for quadrature order and slab surface source convergence provides highly accurate benchmark qualities (4- to 5- places of accuracy) results.

  20. Interregional equilibrium with heterogeneous labor.

    PubMed

    Michel, P; Perrot, A; Thisse J-f

    1996-02-01

    "The impact of labor migration on interregional equilibrium is studied when workers are heterogeneous in productivity and regional mobility. The skilled respond to market disequilibrium by moving into the most attractive region. The unskilled are immobile in the short-run and move with the skilled in the long-run. Both regions have a neoclassical production function affected by an externality depending on the number of skilled. Workers move according to the utility differential when regional amenities vary with population or according to the wage differential. The equilibrium pattern depends on the unskilled's mobility and on migration incentives. Typically, regional imbalance characterizes the equilibrium which is often suboptimal."

  1. Heterogeneous photocatalysts in organic synthesis

    NASA Astrophysics Data System (ADS)

    Cherevatskaya, M.; König, B.

    2014-03-01

    The review deals with the application of inorganic semiconductors in organic synthesis. Although the majority of reported reactions still aim at the photocatalytic decomposition of organic compounds, the number of examples in synthetic applications is growing. The principal mechanisms of heterogeneous semiconductor photocatalysis are considered and examples illustrating the use of inorganic semiconductors in organic synthesis are given. The discussion is arranged according to the required excitation wavelength (UV or visible light) and to the new bond that is formed (carbon-carbon or carbon-heteroatom bond). The bibliography includes 47 references.

  2. Proteomics analysis of heterogeneous flagella in brown algae (stramenopiles).

    PubMed

    Fu, Gang; Nagasato, Chikako; Oka, Seiko; Cock, J Mark; Motomura, Taizo

    2014-09-01

    Flagella are conserved organelles among eukaryotes and they are composed of many proteins, which are necessary for flagellar assembly, maintenance and function. Stramenopiles, which include brown algae, diatoms and oomycetes, possess two laterally inserted flagella. The anterior flagellum (AF) extends forward and bears tripartite mastigonemes, whilst the smooth posterior flagellum (PF) often has a paraflagellar body structure. These heterogeneous flagella have served as crucial structures in algal studies especially from a viewpoint of phylogeny. However, the protein compositions of the flagella are still largely unknown. Here we report a LC-MS/MS based proteomics analysis of brown algal flagella. In total, 495 flagellar proteins were identified. Functional annotation of the proteome data revealed that brown algal flagellar proteins were associated with cell motility, signal transduction and various metabolic activities. We separately isolated AF and PF and analyzed their protein compositions. This analysis led to the identification of several AF- and PF-specific proteins. Among the PF-specific proteins, we found a candidate novel blue light receptor protein involved in phototaxis, and named it HELMCHROME because of the steering function of PF. Immunological analysis revealed that this protein was localized along the whole length of the PF and concentrated in the paraflagellar body.

  3. Simulating Heterogeneous Tumor Cell Populations

    PubMed Central

    Bar-Sagi, Dafna; Mishra, Bud

    2016-01-01

    Certain tumor phenomena, like metabolic heterogeneity and local stable regions of chronic hypoxia, signify a tumor’s resistance to therapy. Although recent research has shed light on the intracellular mechanisms of cancer metabolic reprogramming, little is known about how tumors become metabolically heterogeneous or chronically hypoxic, namely the initial conditions and spatiotemporal dynamics that drive these cell population conditions. To study these aspects, we developed a minimal, spatially-resolved simulation framework for modeling tissue-scale mixed populations of cells based on diffusible particles the cells consume and release, the concentrations of which determine their behavior in arbitrarily complex ways, and on stochastic reproduction. We simulate cell populations that self-sort to facilitate metabolic symbiosis, that grow according to tumor-stroma signaling patterns, and that give rise to stable local regions of chronic hypoxia near blood vessels. We raise two novel questions in the context of these results: (1) How will two metabolically symbiotic cell subpopulations self-sort in the presence of glucose, oxygen, and lactate gradients? We observe a robust pattern of alternating striations. (2) What is the proper time scale to observe stable local regions of chronic hypoxia? We observe the stability is a function of the balance of three factors related to O2—diffusion rate, local vessel release rate, and viable and hypoxic tumor cell consumption rate. We anticipate our simulation framework will help researchers design better experiments and generate novel hypotheses to better understand dynamic, emergent whole-tumor behavior. PMID:28030620

  4. Shock Initiation of Heterogeneous Explosives

    SciTech Connect

    Reaugh, J E

    2004-05-10

    The fundamental picture that shock initiation in heterogeneous explosives is caused by the linking of hot spots formed at inhomogeneities was put forward by several researchers in the 1950's and 1960's, and more recently. Our work uses the computer hardware and software developed in the Advanced Simulation and Computing (ASC) program of the U.S. Department of Energy to explicitly include heterogeneities at the scale of the explosive grains and to calculate the consequences of realistic although approximate models of explosive behavior. Our simulations are performed with ALE-3D, a three-dimensional, elastic-plastic-hydrodynamic Arbitrary Lagrange-Euler finite-difference program, which includes chemical kinetics and heat transfer, and which is under development at this laboratory. We developed the parameter values for a reactive-flow model to describe the non-ideal detonation behavior of an HMX-based explosive from the results of grain-scale simulations. In doing so, we reduced the number of free parameters that are inferred from comparison with experiment to a single one - the characteristic defect dimension. We also performed simulations of the run to detonation in small volumes of explosive. These simulations illustrate the development of the reaction zone and the acceleration of the shock front as the flame fronts start from hot spots, grow, and interact behind the shock front. In this way, our grain-scale simulations can also connect to continuum experiments directly.

  5. Heterogeneous Transmutation Sodium Fast Reactor

    SciTech Connect

    S. E. Bays

    2007-09-01

    The threshold-fission (fertile) nature of Am-241 is used to destroy this minor actinide by capitalizing upon neutron capture instead of fission within a sodium fast reactor. This neutron-capture and its subsequent decay chain leads to the breeding of even neutron number plutonium isotopes. A slightly moderated target design is proposed for breeding plutonium in an axial blanket located above the active “fast reactor” driver fuel region. A parametric study on the core height and fuel pin diameter-to-pitch ratio is used to explore the reactor and fuel cycle aspects of this design. This study resulted in both non-flattened and flattened core geometries. Both of these designs demonstrated a high capacity for removing americium from the fuel cycle. A reactivity coefficient analysis revealed that this heterogeneous design will have comparable safety aspects to a homogeneous reactor of comparable size. A mass balance analysis revealed that the heterogeneous design may reduce the number of fast reactors needed to close the current once-through light water reactor fuel cycle.

  6. Heterogeneous Integration of Compound Semiconductors

    NASA Astrophysics Data System (ADS)

    Moutanabbir, Oussama; Gösele, Ulrich

    2010-08-01

    The ability to tailor compound semiconductors and to integrate them onto foreign substrates can lead to superior or novel functionalities with a potential impact on various areas in electronics, optoelectronics, spintronics, biosensing, and photovoltaics. This review provides a brief description of different approaches to achieve this heterogeneous integration, with an emphasis on the ion-cut process, also known commercially as the Smart-Cut™ process. This process combines semiconductor wafer bonding and undercutting using defect engineering by light ion implantation. Bulk-quality heterostructures frequently unattainable by direct epitaxial growth can be produced, provided that a list of technical criteria is fulfilled, thus offering an additional degree of freedom in the design and fabrication of heterogeneous and flexible devices. Ion cutting is a generic process that can be employed to split and transfer fine monocrystalline layers from various crystals. Materials and engineering issues as well as our current understanding of the underlying physics involved in its application to cleaving thin layers from freestanding GaN, InP, and GaAs wafers are presented.

  7. Dispersivity in heterogeneous permeable media

    SciTech Connect

    Chesnut, D.A.

    1994-01-01

    When one fluid displaces another through a one-dimensional porous medium, the composition changes from pure displacing fluid at the inlet to pure displaced fluid some distance downstream. The distance over which an arbitrary percentage of this change occurs is defined as the mixing zone length, which increases with increasing average distance traveled by the displacement front. For continuous injection, the mixing zone size can be determined from a breakthrough curve as the time required for the effluent displacing fluid concentration to change from, say, 10% to 90%. In classical dispersion theory, the mixing zone grows in proportion to the square root of the mean distance traveled, or, equivalently, to the square root of the mean breakthrough time. In a multi-dimensional heterogeneous medium, especially at field scales, the size of the mixing zone grows almost linearly with mean distance or travel time. If an observed breakthrough curve is forced to fit the, clinical theory, the resulting effective dispersivity, instead of being constant, also increases almost linearly with the spatial or temporal scale of the problem. This occurs because the heterogeneity in flow properties creates a corresponding velocity distribution along the different flow pathways from the inlet to the outlet of the system. Mixing occurs mostly at the outlet, or wherever the fluid is sampled, rather than within the medium. In this paper, we consider the effects. of this behavior on radionuclide or other contaminant migration.

  8. Marked heterogeneity of HER2/NEU gene amplification in endometrial serous carcinoma.

    PubMed

    Buza, Natalia; Hui, Pei

    2013-12-01

    Significant heterogeneity of HER2 protein expression has been recently observed in HER2 positive endometrial serous carcinomas. Tumor cells with HER2 overexpression and/or gene amplification in a heterogeneous tumor may represent a biologically more aggressive subclone that is clinically relevant to prognosis and potential targeted therapy. To correlate with HER2 protein heterogeneity, we investigated the heterogeneity of HER2/NEU gene amplification in endometrial serous carcinoma. A total of 17 endometrial serous carcinomas with heterogeneous HER2 protein expression were selected for the study, including nine cases with a 3+ and eight cases with a 2+ immunohistochemical score. Initial reflex HER2 FISH was available for seven of the eight 2+ cases, five of which showed HER2/NEU gene amplification. All 17 cases underwent repeat FISH targeting larger tumor tissue areas. Ten cases (72%) displayed striking heterogeneity of HER2/NEU gene copy number in the form of cluster amplification. Diffuse HER2 amplification was observed in four cases, no amplification was seen in three tumors. In cases with cluster amplification, HER2 protein overexpression by immunohistochemistry closely correlated at the cellular level with HER2/NEU gene amplification. In conclusion, the significant percentage of cases with heterogeneous HER2/NEU gene amplification indicates that the existing HER2 testing guidelines designed for breast cancer may not be applicable to endometrial serous carcinoma. Clinical testing on multiple different tumor samples or large tumor tissue sections is recommended for both immunohistochemistry and FISH assessment of HER2 status. Direct comparison with the HER2 immunostaining pattern may be helpful in detecting HER2 amplified areas in a heterogeneous tumor.

  9. Unlocking Proteomic Heterogeneity in Complex Diseases through Visual Analytics

    PubMed Central

    Bhavnani, Suresh K.; Dang, Bryant; Bellala, Gowtham; Divekar, Rohit; Visweswaran, Shyam; Brasier, Allan; Kurosky, Alex

    2015-01-01

    Despite years of preclinical development, biological interventions designed to treat complex diseases like asthma often fail in phase III clinical trials. These failures suggest that current methods to analyze biomedical data might be missing critical aspects of biological complexity such as the assumption that cases and controls come from homogeneous distributions. Here we discuss why and how methods from the rapidly evolving field of visual analytics can help translational teams (consisting of biologists, clinicians, and bioinformaticians) to address the challenge of modeling and inferring heterogeneity in the proteomic and phenotypic profiles of patients with complex diseases. Because a primary goal of visual analytics is to amplify the cognitive capacities of humans for detecting patterns in complex data, we begin with an overview of the cognitive foundations for the field of visual analytics. Next, we organize the primary ways in which a specific form of visual analytics called networks have been used to model and infer biological mechanisms, which help to identify the properties of networks that are particularly useful for the discovery and analysis of proteomic heterogeneity in complex diseases. We describe one such approach called subject-protein networks, and demonstrate its application on two proteomic datasets. This demonstration provides insights to help translational teams overcome theoretical, practical, and pedagogical hurdles for the widespread use of subject-protein networks for analyzing molecular heterogeneities, with the translational goal of designing biomarker-based clinical trials, and accelerating the development of personalized approaches to medicine. PMID:25684269

  10. Heterogeneity of monoclonal antibodies revealed by charge-sensitive methods.

    PubMed

    Vlasak, J; Ionescu, R

    2008-12-01

    The expanding field of monoclonal antibody-based pharmaceuticals has triggered increased interest in analytical characterization of these large proteins and in understanding of their heterogeneity and degradation pathways. As a result, a large number of enzymatic modifications as well as chemical and physical degradations have been reported in monoclonal antibodies in recent years. Most heterogeneity is related to changes in the surface charge of the antibody, either directly, as a change in the number of charged residues, or indirectly as a chemical or physical alteration that changes surface-charge distribution. This review presents an overview of the sources of charge-related heterogeneity in monoclonal antibodies and the methods used for their detection. A detailed section is dedicated to deamidation of asparagine and isomerization of aspartic acid residues, two ubiquitous degradation pathways detected in antibodies and other proteins as well. Finally, kinetic modeling of the accumulation of antibody variants is presented as a tool to determine the expected fraction of molecules that have undergone one or more degradation reactions.

  11. Constructing module maps for integrated analysis of heterogeneous biological networks

    PubMed Central

    Amar, David; Shamir, Ron

    2014-01-01

    Improved methods for integrated analysis of heterogeneous large-scale omic data are direly needed. Here, we take a network-based approach to this challenge. Given two networks, representing different types of gene interactions, we construct a map of linked modules, where modules are genes strongly connected in the first network and links represent strong inter-module connections in the second. We develop novel algorithms that considerably outperform prior art on simulated and real data from three distinct domains. First, by analyzing protein–protein interactions and negative genetic interactions in yeast, we discover epistatic relations among protein complexes. Second, we analyze protein–protein interactions and DNA damage-specific positive genetic interactions in yeast and reveal functional rewiring among protein complexes, suggesting novel mechanisms of DNA damage response. Finally, using transcriptomes of non–small-cell lung cancer patients, we analyze networks of global co-expression and disease-dependent differential co-expression and identify a sharp drop in correlation between two modules of immune activation processes, with possible microRNA control. Our study demonstrates that module maps are a powerful tool for deeper analysis of heterogeneous high-throughput omic data. PMID:24497192

  12. HETEROGENEOUS REBURNING BY MIXED FUELS

    SciTech Connect

    Wei-Yin Chen; Benson B. Gathitu

    2005-01-14

    Recent studies of heterogeneous reburning, i.e., reburning involving a coal-derived char, have elucidated its variables, kinetics and mechanisms that are valuable to the development of a highly efficient reburning process. Young lignite chars contain catalysts that not only reduce NO, but they also reduce HCN that is an important intermediate that recycles to NO in the burnout zone. Gaseous CO scavenges the surface oxides that are formed during NO reduction, regenerating the active sites on the char surface. Based on this mechanistic information, cost-effective mixed fuels containing these multiple features has been designed and tested in a simulated reburning apparatus. Remarkably high reduction of NO and HCN has been observed and it is anticipated that mixed fuel will remove 85% of NO in a three-stage reburning process.

  13. Surface science and heterogeneous catalysis

    SciTech Connect

    Somorjai, G.A.

    1980-05-01

    The catalytic reactions studied include hydrocarbon conversion over platinum, the transition metal-catalyzed hydrogenation of carbon monoxide, and the photocatalyzed dissociation of water over oxide surfaces. The method of combined surface science and catalytic studies is similar to those used in synthetic organic chemistry. The single-crystal models for the working catalyst are compared with real catalysts by comparing the rates of cyclopropane ring opening on platinum and the hydrogenation of carbon monoxide on rhodium single crystal surface with those on practical commercial catalyst systems. Excellent agreement was obtained for these reactions. This document reviews what was learned about heterogeneous catalysis from these surface science approaches over the past 15 years and present models of the active catalyst surface.

  14. The heterogeneity of ovarian cancer.

    PubMed

    Meinhold-Heerlein, I; Hauptmann, S

    2014-02-01

    Ovarian cancer carries the worst prognosis of all gynecological malignancies. This is mainly due to its resistance against commonly used cytostatic drugs as well as the lack of a screening method for its detection at an early stage. Both basic and translational research have shown over the past decades that ovarian cancer as a medical term includes several types of tumors with different phenotypes, molecular biology, etiology, tumor progression, and even different prognosis. In this issue of Archives of Gynecology and Obstetrics, J. Dietel presents a review article about novel findings of the etiopathogenesis of ovarian cancer and the role that fallopian tubes may play. He also outlines the implied clinical consequences. Here, we give a brief overview of the heterogeneity of ovarian cancer to introduce the topic.

  15. Genetic heterogeneity of hepatocellular carcinoma

    SciTech Connect

    Unsal, H.; Isselbacher, K.J. ); Yakicier, C.; Marcais, C.; Ozturk, M. ); Kew, M. ); Volkmann, M. ); Zentgraf, H. )

    1994-01-18

    The authors studied 80 hepatocellular carcinomas from three continents for p53 gene (TP53) mutations and hepatitis B virus (HBV) sequences. p53 mutations were frequent in tumors from Mozambique but not in tumors from South Africa, China, and Germany. Independent of geographic origin, most tumors were positive for HBV sequences. X gene coding sequences of HBV were detected in 78% of tumors, whereas viral sequences in the surface antigen- and core antigen-encoding regions were present in less than 35% of tumors. These observations indicate that hepatocellular carcinomas are genetically heterogeneous. Mozambican-types of hepatocellular carcinomas are characterized by a high incidence of p53 mutations related to aflatoxins. In other tumors, the rarity of p53 mutations combined with the frequent presence of viral X gene coding sequences suggests a possible interference of HBV with the wild-type p53 function.

  16. Data Integration for Heterogenous Datasets

    PubMed Central

    2014-01-01

    Abstract More and more, the needs of data analysts are requiring the use of data outside the control of their own organizations. The increasing amount of data available on the Web, the new technologies for linking data across datasets, and the increasing need to integrate structured and unstructured data are all driving this trend. In this article, we provide a technical overview of the emerging “broad data” area, in which the variety of heterogeneous data being used, rather than the scale of the data being analyzed, is the limiting factor in data analysis efforts. The article explores some of the emerging themes in data discovery, data integration, linked data, and the combination of structured and unstructured data. PMID:25553272

  17. Heterogeneous Reburning By Mixed Fuels

    SciTech Connect

    Anderson Hall

    2009-03-31

    Recent studies of heterogeneous reburning, i.e., reburning involving a coal-derived char, have elucidated its variables, kinetics and mechanisms that are valuable to the development of a highly efficient reburning process. Young lignite chars contain catalysts that not only reduce NO, but they also reduce HCN that is an important intermediate that recycles to NO in the burnout zone. Gaseous CO scavenges the surface oxides that are formed during NO reduction, regenerating the active sites on the char surface. Based on this mechanistic information, cost-effective mixed fuels containing these multiple features has been designed and tested in a simulated reburning apparatus. Remarkably high reduction of NO and HCN has been observed and it is anticipated that mixed fuel will remove 85% of NO in a three-stage reburning process.

  18. (90377) Sedna: Heterogeneous Surface Composition

    NASA Astrophysics Data System (ADS)

    Dalle Ore, Cristina M.; Barucci, M.; Alvarez-Candal, A.; de Bergh, C.; Merlin, F.; Dumas, C.; Cruikshank, D. P.

    2010-10-01

    The peculiar TNO (90377) Sedna is one of the most remote solar system objects accessible to investigations (current heliocentric distance 88AU). This dwarf planet is one of the reddest objects following the taxonomic group RR. To better constrain its surface composition and to investigate the possible heterogeneity of the surface of Sedna, several observations have been carried out at ESO-VLT with the powerful spectrometer SINFONI, which observes the H and K bands simultaneously. Even if Sedna, given its faintness, was at the limit of observations, the new analyzed spectra (obtained in 2005, 2007, and 2008) show a different behavior, particularly in the K band. Spectral modeling using the Shkuratov radiative transfer method has been performed using the various sets of data, including visible and Spitzer data, for a large wavelength range 0.4-4.5 microns, and the albedo value (0.21) estimated by Stansberry et al. (2008). We find that the surface of Sedna is not completely homogeneous. The visible and near-IR spectra can be modeled with organic materials (triton and titan tholin), serpentine, and H2O ice in fairly significant amounts, and CH4, N2 and C2H6 in varying trace amounts. One of the spectra, showing a different signature in the K-band, observed as part of the October 2005 group of data, is best modeled with CH3OH in place of CH4, with reduced amounts of serpentine and with the addition of olivine. The compositional surface heterogeneity can give clues to the origin and past history of this peculiar distant object.

  19. Passive ventricular remodeling in cardiac disease: focus on heterogeneity

    PubMed Central

    Kessler, Elise L.; Boulaksil, Mohamed; van Rijen, Harold V. M.; Vos, Marc A.; van Veen, Toon A. B.

    2014-01-01

    Passive ventricular remodeling is defined by the process of molecular ventricular adaptation to different forms of cardiac pathophysiology. It includes changes in tissue architecture, such as hypertrophy, fiber disarray, alterations in cell size and fibrosis. Besides that, it also includes molecular remodeling of gap junctions, especially those composed by Connexin43 proteins (Cx43) in the ventricles that affect cell-to-cell propagation of the electrical impulse, and changes in the sodium channels that modify excitability. All those alterations appear mainly in a heterogeneous manner, creating irregular and inhomogeneous electrical and mechanical coupling throughout the heart. This can predispose to reentry arrhythmias and adds to a further deterioration into heart failure. In this review, passive ventricular remodeling is described in Hypertrophic Cardiomyopathy (HCM), Dilated Cardiomyopathy (DCM), Ischemic Cardiomyopathy (ICM), and Arrhythmogenic Cardiomyopathy (ACM), with a main focus on the heterogeneity of those alterations mentioned above. PMID:25566084

  20. Heterogeneity in pepper isolates of cucumber mosaic virus

    USGS Publications Warehouse

    Rodriguez-Alvarado, G.; Kurath, G.; Dodds, J.A.

    1995-01-01

    Twenty-four cucumber mosaic cucumovirus (CMV) field isolates from pepper crops in Cali-fornia were characterized and compared by nucleic acid hybridization subgrouping, virion electrophoresis, and biological effects in several hosts. Isolates, belonging to subgroup I or subgroup II, were found that induced severe symptoms in mechanically inoculated bell pep-pers. Only two isolates, both from subgroup II, were mild. A group of 19 isolates collected from a single field were all in subgroup II and appeared identical by virion electrophoresis, but they exhibited varying degrees of symptom severity in peppers. As a more detailed indicator of heterogeneity, these 19 isolates were examined by RNase protection assays to delect sequence variation in the coat protein gene region of their genomes. The patterns of bands observed were complex and a high degree of genomic heterogeneity was detected between isolates, with no apparent correlation to symptomatology in bell pepper.

  1. Nonlinear Poisson equation for heterogeneous media.

    PubMed

    Hu, Langhua; Wei, Guo-Wei

    2012-08-22

    The Poisson equation is a widely accepted model for electrostatic analysis. However, the Poisson equation is derived based on electric polarizations in a linear, isotropic, and homogeneous dielectric medium. This article introduces a nonlinear Poisson equation to take into consideration of hyperpolarization effects due to intensive charges and possible nonlinear, anisotropic, and heterogeneous media. Variational principle is utilized to derive the nonlinear Poisson model from an electrostatic energy functional. To apply the proposed nonlinear Poisson equation for the solvation analysis, we also construct a nonpolar solvation energy functional based on the nonlinear Poisson equation by using the geometric measure theory. At a fixed temperature, the proposed nonlinear Poisson theory is extensively validated by the electrostatic analysis of the Kirkwood model and a set of 20 proteins, and the solvation analysis of a set of 17 small molecules whose experimental measurements are also available for a comparison. Moreover, the nonlinear Poisson equation is further applied to the solvation analysis of 21 compounds at different temperatures. Numerical results are compared to theoretical prediction, experimental measurements, and those obtained from other theoretical methods in the literature. A good agreement between our results and experimental data as well as theoretical results suggests that the proposed nonlinear Poisson model is a potentially useful model for electrostatic analysis involving hyperpolarization effects.

  2. Nonlinear Poisson Equation for Heterogeneous Media

    PubMed Central

    Hu, Langhua; Wei, Guo-Wei

    2012-01-01

    The Poisson equation is a widely accepted model for electrostatic analysis. However, the Poisson equation is derived based on electric polarizations in a linear, isotropic, and homogeneous dielectric medium. This article introduces a nonlinear Poisson equation to take into consideration of hyperpolarization effects due to intensive charges and possible nonlinear, anisotropic, and heterogeneous media. Variational principle is utilized to derive the nonlinear Poisson model from an electrostatic energy functional. To apply the proposed nonlinear Poisson equation for the solvation analysis, we also construct a nonpolar solvation energy functional based on the nonlinear Poisson equation by using the geometric measure theory. At a fixed temperature, the proposed nonlinear Poisson theory is extensively validated by the electrostatic analysis of the Kirkwood model and a set of 20 proteins, and the solvation analysis of a set of 17 small molecules whose experimental measurements are also available for a comparison. Moreover, the nonlinear Poisson equation is further applied to the solvation analysis of 21 compounds at different temperatures. Numerical results are compared to theoretical prediction, experimental measurements, and those obtained from other theoretical methods in the literature. A good agreement between our results and experimental data as well as theoretical results suggests that the proposed nonlinear Poisson model is a potentially useful model for electrostatic analysis involving hyperpolarization effects. PMID:22947937

  3. Chemical and seismological constraints on mantle heterogeneity.

    PubMed

    Helffrich, George

    2002-11-15

    Recent seismological studies that use scattered waves to detect heterogeneities in the mantle reveal the presence of a small, distributed elastic heterogeneity in the lower mantle which does not appear to be thermal in nature. The characteristic size of these heterogeneities appears to be ca. 8 km, suggesting that they represent subducted recycled oceanic crust. With this stimulus, old ideas that the mantle is heterogeneous in structure, rather than stratified, are reinterpreted and a simple, end-member model for the heterogeneity structure is proposed. The volumetrically largest components in the model are recycled oceanic crust, which contains the heat-producing elements, and mantle depleted of these and other incompatible trace elements. About 10% of the mantle's mass is made up of recycled oceanic crust, which is associated with the observed small-scale seismic heterogeneity. The way this heterogeneity is distributed is in convectively stretched and thinned bodies ranging downwards in size from 8 km. With the present techniques to detect small bodies through scattering, only ca. 55% of the mantle's small-scale heterogeneities are detectable seismically.

  4. Functional Heterogeneity and Senior Management Team Effectiveness

    ERIC Educational Resources Information Center

    Benoliel, Pascale; Somech, Anit

    2016-01-01

    Purpose: There has been an increasing trend toward the creation of senior management teams (SMTs) which are characterized by a high degree of functional heterogeneity. Although such teams may create better linkages to information, along with the benefits of functional heterogeneity comes the potential for conflicts that stem from the value…

  5. The composition of heterogeneous control laws

    NASA Technical Reports Server (NTRS)

    Kuipers, Benjamin; Astrom, Karl

    1991-01-01

    The fuzzy control literature and industrial practice provide certain nonlinear methods for combining heterogeneous control laws, but these methods have been very difficult to analyze theoretically. An alternate formulation and extension of this approach is presented that has several practical and theoretical benefits. An example of heterogeneous control is given and two alternate analysis methods are presented.

  6. Understanding the Executive Functioning Heterogeneity in Schizophrenia

    ERIC Educational Resources Information Center

    Raffard, Stephane; Bayard, Sophie

    2012-01-01

    Schizophrenia is characterized by heterogeneous brain abnormalities involving cerebral regions implied in the executive functioning. The dysexecutive syndrome is one of the most prominent and functionally cognitive features of schizophrenia. Nevertheless, it is not clear to what extend executive deficits are heterogeneous in schizophrenia…

  7. Heterogeneity assessment of functional T cell avidity

    PubMed Central

    Ioannidou, Kalliopi; Baumgaertner, Petra; Gannon, Philippe O.; Speiser, Michel F.; Allard, Mathilde; Hebeisen, Michael; Rufer, Nathalie; Speiser, Daniel E.

    2017-01-01

    The potency of cellular immune responses strongly depends on T cell avidity to antigen. Yet, functional avidity measurements are rarely performed in patients, mainly due to the technical challenges of characterizing heterogeneous T cells. The mean functional T cell avidity can be determined by the IFN-γ Elispot assay, with titrated amounts of peptide. Using this assay, we developed a method revealing the heterogeneity of functional avidity, represented by the steepness/hillslope of the peptide titration curve, documented by proof of principle experiments and mathematical modeling. Our data show that not only natural polyclonal CD8 T cell populations from cancer patients, but also monoclonal T cells differ strongly in their heterogeneity of functional avidity. Interestingly, clones and polyclonal cells displayed comparable ranges of heterogeneity. We conclude that besides the mean functional avidity, it is feasible and useful to determine its heterogeneity (hillslope) for characterizing T cell responses in basic research and patient investigation. PMID:28287160

  8. Operating a heterogeneous telescope network

    NASA Astrophysics Data System (ADS)

    Allan, Alasdair; Bischoff, Karsten; Burgdorf, Martin; Cavanagh, Brad; Christian, Damien; Clay, Neil; Dickens, Rob; Economou, Frossie; Fadavi, Mehri; Frazer, Stephen; Granzer, Thomas; Grosvenor, Sandy; Hessman, Frederic V.; Jenness, Tim; Koratkar, Anuradha; Lehner, Matthew; Mottram, Chris; Naylor, Tim; Saunders, Eric S.; Solomos, Nikolaos; Steele, Iain A.; Tuparev, Georg; Vestrand, W. Thomas; White, Robert R.; Yost, Sarah

    2006-06-01

    In the last few years the ubiquitous availability of high bandwidth networks has changed the way both robotic and non-robotic telescopes operate, with single isolated telescopes being integrated into expanding "smart" telescope networks that can span continents and respond to transient events in seconds. The Heterogeneous Telescope Networks (HTN)* Consortium represents a number of major research groups in the field of robotic telescopes, and together we are proposing a standards based approach to providing interoperability between the existing proprietary telescope networks. We further propose standards for interoperability, and integration with, the emerging Virtual Observatory. We present the results of the first interoperability meeting held last year and discuss the protocol and transport standards agreed at the meeting, which deals with the complex issue of how to optimally schedule observations on geographically distributed resources. We discuss a free market approach to this scheduling problem, which must initially be based on ad-hoc agreements between the participants in the network, but which may eventually expand into a electronic market for the exchange of telescope time.

  9. Distributional Scaling in Heterogeneous Aquifers

    NASA Astrophysics Data System (ADS)

    Polsinelli, J. F.

    2015-12-01

    An investigation is undertaken into the fractal scaling properties of the piezometric head in a heterogeneous unconfined aquifer. The governing equations for the unconfined flow are derived from conservation of mass and the Darcy law. The Dupuit approximation will be used to model the dynamics. The spatially varying nature of the tendency to conduct flow (e.g. the hydraulic conductivity) is represented as a stochastic process. Experimental studies in the literature have indicated that the conductivity belongs to a class of non-stationary stochastic fields, called H-ss fields. The uncertainty in the soil parameters is imparted onto the flow variables; in groundwater investigations the potentiometric head will be a random function. The structure of the head field will be analyzed with an emphasis on the scaling properties. The scaling scheme for the modeling equations and the simulation procedure for the saturated hydraulic conductivity process will be explained, then the method will be validated through numerical experimentation using the USGS Modflow-2005 software. The results of the numerical simulations demonstrate that the head will exhibit multi-fractal scaling if the hydraulic conductivity exhibits multi-fractal scaling and the differential equations for the groundwater equation satisfy a particular set of scale invariance conditions.

  10. Genetic heterogeneity in juvenile NCL

    SciTech Connect

    Hart, Y.M.; Andermann, E.; Mitchison, H.M.

    1994-09-01

    The neuronal ceroid lipofuscinoses (NCL) are a group of related lysosomal storage diseases classified according to the age of onset, clinical syndrome, and pathology. The clinical syndromes include myoclonus, visual failure, progressive dementia, ataxia and generalized tonic clonic seizures in varying combinations depending on the age of onset and pathology. The mode of inheritance is autosomal recessive in most cases, except for several families with the adult form (Kufs` disease) which have autosomal dominant inheritance. Linkage for the infantile (Halatia-Santavuori) form (CLN1), characterized ultrastructurally by lysosomal granular osmiophilic deposits (GROD), has been demonstrated with markers on chromosome lp, while the gene for the typical juvenile (Spielmeyer-Vogt) form (CLN3), characterized by fingerprint-profile inclusions, has been linked to chromosome 16p. The gene locations of the late infantile (Jansky-Bielschowsky) and adult (Kufs` disease) forms are unknown, although it has recently been shown that the late infantile form does not link to chromosome 16p. We describe three siblings, including a pair of monozygotic twins, with juvenile onset NCL with GROD in whom linkage to the CLN3 region of chromsome 16p has been excluded. This would suggest that there is genetic heterogeneity not only among the different clinical syndromes, but also among identical clinical syndromes with different ultrastructural characteristics. Preliminary studies of linkage to chromosome 1p employing the microsatellite marker HY-TM1 have been uninformative. Further studies with other chromosome 1 markers are underway.

  11. Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design

    PubMed Central

    Diaz-Cano, Salvador J.

    2012-01-01

    Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma), mechanisms of intercellular transference of genetic information (exosomes), and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning. PMID:22408433

  12. Heterochronic phosphorelay gene expression as a source of heterogeneity in Bacillus subtilis spore formation.

    PubMed

    de Jong, Imke G; Veening, Jan-Willem; Kuipers, Oscar P

    2010-04-01

    In response to limiting nutrient sources and cell density signals, Bacillus subtilis can differentiate and form highly resistant endospores. Initiation of spore development is governed by the master regulator Spo0A, which is activated by phosphorylation via a multicomponent phosphorelay. Interestingly, only part of a clonal population will enter this developmental pathway, a phenomenon known as sporulation bistability or sporulation heterogeneity. How sporulation heterogeneity is established is largely unknown. To investigate the origins of sporulation heterogeneity, we constructed promoter-green fluorescent protein (GFP) fusions to the main phosphorelay genes and perturbed their expression levels. Using time-lapse fluorescence microscopy and flow cytometry, we showed that expression of the phosphorelay genes is distributed in a unimodal manner. However, single-cell trajectories revealed that phosphorelay gene expression is highly dynamic or "heterochronic" between individual cells and that stochasticity of phosphorelay gene transcription might be an important regulatory mechanism for sporulation heterogeneity. Furthermore, we showed that artificial induction or depletion of the phosphorelay phosphate flow results in loss of sporulation heterogeneity. Our data suggest that sporulation heterogeneity originates from highly dynamic and variable gene activity of the phosphorelay components, resulting in large cell-to-cell variability with regard to phosphate input into the system. These transcriptional and posttranslational differences in phosphorelay activity appear to be sufficient to generate a heterogeneous sporulation signal without the need of the positive-feedback loop established by the sigma factor SigH.

  13. A model of electrophysiological heterogeneity in periglomerular cells

    PubMed Central

    Sethupathy, Praveen; Rubin, Daniel B.; Li, Guoshi; Cleland, Thomas A.

    2013-01-01

    Olfactory bulb (OB) periglomerular (PG) cells are heterogeneous with respect to several features, including morphology, connectivity, patterns of protein expression, and electrophysiological properties. However, these features rarely correlate with one another, suggesting that the differentiating properties of PG cells may arise from multiple independent adaptive variables rather than representing discrete cell classes. We use computational modeling to assess this hypothesis with respect to electrophysiological properties. Specifically, we show that the heterogeneous electrophysiological properties demonstrated in PG cell recordings can be explained solely by differences in the relative expression levels of ion channel species in the cell, without recourse to modifying channel kinetic properties themselves. This PG cell model can therefore be used as the basis for diverse cellular and network-level analyses of OB computations. Moreover, this simple basis for heterogeneity contributes to an emerging hypothesis that glomerular-layer interneurons may be better described as a single population expressing distributions of partially independent, potentially plastic properties, rather than as a set of discrete cell classes. PMID:23637658

  14. Transcriptional and phenotypical heterogeneity of Trypanosoma cruzi cell populations

    PubMed Central

    Seco-Hidalgo, Víctor; De Pablos, Luis Miguel; Osuna, Antonio

    2015-01-01

    Trypanosoma cruzi has a complex life cycle comprising pools of cell populations which circulate among humans, vectors, sylvatic reservoirs and domestic animals. Recent experimental evidence has demonstrated the importance of clonal variations for parasite population dynamics, survival and evolution. By limiting dilution assays, we have isolated seven isogenic clonal cell lines derived from the Pan4 strain of T. cruzi. Applying different molecular techniques, we have been able to provide a comprehensive characterization of the expression heterogeneity in the mucin-associated surface protein (MASP) gene family, where all the clonal isogenic populations were transcriptionally different. Hierarchical cluster analysis and sequence comparison among different MASP cDNA libraries showed that, despite the great variability in MASP expression, some members of the transcriptome (including MASP pseudogenes) are conserved, not only in the life-cycle stages but also among different strains of T. cruzi. Finally, other important aspects for the parasite, such as growth, spontaneous metacyclogenesis or excretion of different catabolites, were also compared among the clones, demonstrating that T. cruzi populations of cells are also phenotypically heterogeneous. Although the evolutionary strategy that sustains the MASP expression polymorphism remains unknown, we suggest that MASP clonal variability and phenotypic heterogeneities found in this study might provide an advantage, allowing a rapid response to environmental pressure or changes during the life cycle of T. cruzi. PMID:26674416

  15. Genetic heterogeneity and HOMOG analysis in British malignant hyperthermia families.

    PubMed Central

    Robinson, R; Curran, J L; Hall, W J; Halsall, P J; Hopkins, P M; Markham, A F; Stewart, A D; West, S P; Ellis, F R

    1998-01-01

    Malignant hyperthermia (MH) is an autosomal dominant genetic condition that presents in susceptible people undergoing general anaesthesia. The clinical disorder is a major cause of anaesthetic morbidity and mortality. The UK Malignant Hyperthermia Group has performed genetic linkage analysis on 20 large, well defined malignant hyperthermia families, using hypervariable markers on chromosome 19q13.1, including the candidate MH gene RYR1, the gene coding for the skeletal muscle ryanodine receptor protein. The results were analysed using LINKAGE to perform two point and multipoint lod scores, then HOMOG to calculate levels of heterogeneity. The results clearly showed genetic heterogeneity between MH families; nine of the families gave results entirely consistent with linkage to the region around RYR1 while the same region was clearly excluded in three families. In the remaining eight MHS families there were single recombinant events between RYR1 and MH susceptibility. HOMOG analysis was of little added benefit in determining the likelihood of linkage to RYR1 in these families. This confirmation of the presence of heterogeneity in the UK MH population, along with the possibility of the presence of two MH genes in some pedigrees, indicates that it would be premature and potentially dangerous to offer diagnosis of MH by DNA based methods at this time. PMID:9541102

  16. Learning from Heterogeneous Data Sources: An Application in Spatial Proteomics.

    PubMed

    Breckels, Lisa M; Holden, Sean B; Wojnar, David; Mulvey, Claire M; Christoforou, Andy; Groen, Arnoud; Trotter, Matthew W B; Kohlbacher, Oliver; Lilley, Kathryn S; Gatto, Laurent

    2016-05-01

    Sub-cellular localisation of proteins is an essential post-translational regulatory mechanism that can be assayed using high-throughput mass spectrometry (MS). These MS-based spatial proteomics experiments enable us to pinpoint the sub-cellular distribution of thousands of proteins in a specific system under controlled conditions. Recent advances in high-throughput MS methods have yielded a plethora of experimental spatial proteomics data for the cell biology community. Yet, there are many third-party data sources, such as immunofluorescence microscopy or protein annotations and sequences, which represent a rich and vast source of complementary information. We present a unique transfer learning classification framework that utilises a nearest-neighbour or support vector machine system, to integrate heterogeneous data sources to considerably improve on the quantity and quality of sub-cellular protein assignment. We demonstrate the utility of our algorithms through evaluation of five experimental datasets, from four different species in conjunction with four different auxiliary data sources to classify proteins to tens of sub-cellular compartments with high generalisation accuracy. We further apply the method to an experiment on pluripotent mouse embryonic stem cells to classify a set of previously unknown proteins, and validate our findings against a recent high resolution map of the mouse stem cell proteome. The methodology is distributed as part of the open-source Bioconductor pRoloc suite for spatial proteomics data analysis.

  17. Learning from Heterogeneous Data Sources: An Application in Spatial Proteomics

    PubMed Central

    Breckels, Lisa M.; Holden, Sean B.; Wojnar, David; Mulvey, Claire M.; Christoforou, Andy; Groen, Arnoud; Trotter, Matthew W. B.; Kohlbacher, Oliver; Lilley, Kathryn S.; Gatto, Laurent

    2016-01-01

    Sub-cellular localisation of proteins is an essential post-translational regulatory mechanism that can be assayed using high-throughput mass spectrometry (MS). These MS-based spatial proteomics experiments enable us to pinpoint the sub-cellular distribution of thousands of proteins in a specific system under controlled conditions. Recent advances in high-throughput MS methods have yielded a plethora of experimental spatial proteomics data for the cell biology community. Yet, there are many third-party data sources, such as immunofluorescence microscopy or protein annotations and sequences, which represent a rich and vast source of complementary information. We present a unique transfer learning classification framework that utilises a nearest-neighbour or support vector machine system, to integrate heterogeneous data sources to considerably improve on the quantity and quality of sub-cellular protein assignment. We demonstrate the utility of our algorithms through evaluation of five experimental datasets, from four different species in conjunction with four different auxiliary data sources to classify proteins to tens of sub-cellular compartments with high generalisation accuracy. We further apply the method to an experiment on pluripotent mouse embryonic stem cells to classify a set of previously unknown proteins, and validate our findings against a recent high resolution map of the mouse stem cell proteome. The methodology is distributed as part of the open-source Bioconductor pRoloc suite for spatial proteomics data analysis. PMID:27175778

  18. Molecular modeling of heterogeneous catalysis

    NASA Astrophysics Data System (ADS)

    Gislason, Jason Joseph

    A novel method for modeling heterogeneous catalysis was developed to further facilitate the understanding of catalytic reactor mechanisms. The method employs molecular dynamics simulations, statistical mechanical, and Unity Bond Index - Quadratic Exponential Potential (UBI-QEP) calculations to calculate the rate constants for reactions on metal surfaces. The primary difficulty of molecular dynamics simulations on metal surfaces has been the lack of reliable reactive potential energy surfaces. We have overcome this through the development of the Normalized Bond Index - Reactive Potential Function (NBI-RPF), which can accurately describe the reaction of adsorbates on metal surfaces. The first calculations of rate constants for a reaction on a metal surface using molecular dynamics simulations are presented. This method is applied to the determination of the mechanism for selective hydrogenation of acetylene in an ethylene rich flow. It was determined that the selectivity for acetylene hydrogenation is attributable to the higher reactivity of acetylene versus ethylene with respect to hydrogenation by molecular hydrogen. It was shown that hydrogen transfer from the carbonaceous layer to acetylene or ethylene is insignificant in the hydrogenation process. Molecular dynamics simulations and molecular mechanics calculations were used to determine the diffusion rate constants for dimethylnaphthalene isomers is mordenite. 2,6-dimethylnaphthalene and 2,7-dimethylnaphthalene were found to have similar diffusion rate constants. Grand canonical Monte Carlo calculations were performed on the competitive adsorption of 2,6-dimethylnaphthalene and 2,7-dimethylnaphthalene in type X zeolites exchanged individually with barium, calcium, potassium, and rubidium ions, calcium exchanged MCM-22, and hydrogen form mordenite (MOR), X zeolite, Y zeolite, hypBEB, ZSM- 12, and MCM-22. These calculations showed that barium exchanged X zeolite was the most selective toward 2

  19. Isotopic heterogeneity in volcanic rocks

    NASA Astrophysics Data System (ADS)

    Wolff, J. A.; Ramos, F. C.; Tollstrup, D. L.

    2003-04-01

    The growing microsample database on volcanic rocks is showing that isotopic disequilibrium between and among phenocryst phases, their melt inclusions, and groundmass is the rule rather than the exception. This applies even in cases of little or no petrographic evidence for disequilibrium. Erupted magmas must therefore be regarded, to some extent, as mechanical mixtures of isotopically distinct components assembled from different sources. The preservation of isotopic disequilibrium requires that the assembly takes place before diffusion can eradicate evidence of disequilibrium. For a wide range of magmas (mafic, intermediate and felsic, silica under- and oversaturated) from different volcano types (flood basalts, monogenetic cones, stratocones, silicic calderas) this timescale ranges from thousands of years down to one year or less, with no consistent pattern of mixing-to-eruption time vs. volcano or magma type. Among many issues arising from these findings, we note that estimation of magmatic temperatures from application of equilibrium thermodynamics to phenocryst assemblages in volcanic rocks should be approached with extreme caution. The isotope ratio variations observed among the components of a single volcanic rock sample, in most cases, indicate interaction between magma and the local wall-rock. This is consistent with the view that the vast majority of magmas undergo modification during transport through and residence within the crust. Three physical origins of heterogeneity have been proposed: melting of wallrock, magmatic recharge, and mixing of components within a magma chamber initially segregated into melt-rich and crystal-rich portions. Time constraints on preservation of disequilibrium imply either a causal link with eruption, or that these processes occur through the lifetime of a chamber.

  20. Mechanical heterogeneities and lithospheric extension

    NASA Astrophysics Data System (ADS)

    Duretz, Thibault; Petri, Benoit; Mohn, Geoffroy; Schenker, Filippo L.; Schmalholz, Stefan

    2016-04-01

    Detailed geological and geophysical studies of passive margins have highlighted the multi-stage and depth-dependent aspect of lithospheric thinning. Lithospheric thinning involves a variety of structures (normal faults, low angle detachments, extensional shear zones, extraction faults) and leads to a complex architecture of passive margins (with e.g. necking zone, mantle exhumation, continental allochthons). The processes controlling the generation and evolution of these structures as well as the impact of pre-rift inheritance are so far incompletely understood. In this study, we investigate the impact of pre-rift inheritance on the development of rifted margins using two-dimensional thermo-mechanical models of lithospheric thinning. To first order, we represent the pre-rift mechanical heterogeneities with lithological layering. The rheologies are kept simple (visco-plastic) and do not involve any strain softening mechanism. Our models show that mechanical layering causes multi-stage and depth-dependent extension. In the initial rifting phase, lithospheric extension is decoupled: as the crust undergoes thinning by brittle (frictional-plastic) faults, the lithospheric mantle accommodates extension by symmetric ductile necking. In a second rifting phase, deformation in the crust and lithospheric mantle is coupled and marks the beginning of an asymmetric extension stage. Low angle extensional shear zones develop across the lithosphere and exhume subcontinental mantle. Furthemore, crustal allochthons and adjacent basins develop coevally. We describe as well the thermal evolution predicted by the numerical models and discuss the first-order implications of our results in the context of the Alpine geological history.

  1. Interoperability of heterogeneous distributed systems

    NASA Astrophysics Data System (ADS)

    Zaschke, C.; Essendorfer, B.; Kerth, C.

    2016-05-01

    To achieve knowledge superiority in today's operations interoperability is the key. Budget restrictions as well as the complexity and multiplicity of threats combined with the fact that not single nations but whole areas are subject to attacks force nations to collaborate and share information as appropriate. Multiple data and information sources produce different kinds of data, real time and non-real time, in different formats that are disseminated to the respective command and control level for further distribution. The data is most of the time highly sensitive and restricted in terms of sharing. The question is how to make this data available to the right people at the right time with the right granularity. The Coalition Shared Data concept aims to provide a solution to these questions. It has been developed within several multinational projects and evolved over time. A continuous improvement process was established and resulted in the adaptation of the architecture as well as the technical solution and the processes it supports. Coming from the idea of making use of existing standards and basing the concept on sharing of data through standardized interfaces and formats and enabling metadata based query the concept merged with a more sophisticated service based approach. The paper addresses concepts for information sharing to facilitate interoperability between heterogeneous distributed systems. It introduces the methods that were used and the challenges that had to be overcome. Furthermore, the paper gives a perspective how the concept could be used in the future and what measures have to be taken to successfully bring it into operations.

  2. Frictional Heterogeneities Along Carbonate Faults

    NASA Astrophysics Data System (ADS)

    Collettini, C.; Carpenter, B. M.; Scuderi, M.; Tesei, T.

    2014-12-01

    The understanding of fault-slip behaviour in carbonates has an important societal impact as a) a significant number of earthquakes nucleate within or propagate through these rocks, and b) half of the known petroleum reserves occur within carbonate reservoirs, which likely contain faults that experience fluid pressure fluctuations. Field studies on carbonate-bearing faults that are exhumed analogues of currently active structures of the seismogenic crust, show that fault rock types are systematically controlled by the lithology of the faulted protolith: localization associated with cataclasis, thermal decomposition and plastic deformation commonly affect fault rocks in massive limestone, whereas distributed deformation, pressure-solution and frictional sliding along phyllosilicates are observed in marly rocks. In addition, hydraulic fractures, indicating cyclic fluid pressure build-ups during the fault activity, are widespread. Standard double direct friction experiments on fault rocks from massive limestones show high friction, velocity neutral/weakening behaviour and significant re-strengthening during hold periods, on the contrary, phyllosilicate-rich shear zones are characterized by low friction, significant velocity strengthening behavior and no healing. We are currently running friction experiments on large rock samples (20x20 cm) in order to reproduce and characterize the interaction of fault rock frictional heterogeneities observed in the field. In addition we have been performing experiments at near lithostatic fluid pressure in the double direct shear configuration within a pressure vessel to test the Rate and State friction stability under these conditions. Our combination of structural observations and mechanical data have been revealing the processes and structures that are at the base of the broad spectrum of fault slip behaviors recently documented by high-resolution geodetic and seismological data.

  3. Molecular genetic heterogeneity in undifferentiated endometrial carcinomas.

    PubMed

    Rosa-Rosa, Juan M; Leskelä, Susanna; Cristóbal-Lana, Eva; Santón, Almudena; López-García, Ma Ángeles; Muñoz, Gloria; Pérez-Mies, Belen; Biscuola, Michele; Prat, Jaime; Esther, Oliva E; Soslow, Robert A; Matias-Guiu, Xavier; Palacios, Jose

    2016-11-01

    Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly aggressive subtypes of uterine cancer, not well characterized at a molecular level. To investigate whether dedifferentiated carcinomas carry molecular genetic alterations similar to those of pure undifferentiated carcinomas, and to gain insight into the pathogenesis of these tumors, we selected a cohort of 18 undifferentiated endometrial carcinomas, 8 of them with a well-differentiated endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and studied them by immunohistochemistry and massive parallel and Sanger sequencing. Whole-exome sequencing of the endometrioid and undifferentiated components, as well as normal myometrium, was also carried out in one case. According to The Cancer Genome Atlas classification, we distributed 95% of the undifferentiated carcinomas in this series as follows: (a) hypermutated tumors with loss of any mismatch repair protein expression and microsatellite instability (eight cases, 45%); (b) ultramutated carcinomas carrying mutations in the exonuclease domain of POLE (two cases, 11%); (c) high copy number alterations (copy-number high) tumors group exhibiting only TP53 mutations and high number of alterations detected by FISH (two cases, 11%); and (d) low copy number alterations (copy-number low) tumors with molecular alterations typical of endometrioid endometrial carcinomas (five cases, 28%). Two of the latter cases, however, also had TP53 mutations and higher number of alterations detected by FISH and could have progressed to a copy-number high phenotype. Most dedifferentiated carcinomas belonged to the hypermutated group, whereas pure undifferentiated carcinomas shared molecular genetic alterations with copy-number low or copy-number high tumors. These results indicate that undifferentiated and dedifferentiated endometrial carcinomas are molecularly heterogeneous tumors, which may have prognostic value.

  4. Heterogeneous Chemistry Involving Methanol in Tropospheric Clouds

    NASA Technical Reports Server (NTRS)

    Tabazadeh, A.; Yokelson, R. J.; Singh, H. B.; Hobbs, P. V.; Crawford, J. H.; Iraci, L. T.

    2004-01-01

    In this report we analyze airborne measurements to suggest that methanol in biomass burning smoke is lost heterogeneously in clouds. When a smoke plume intersected a cumulus cloud during the SAFARI 2000 field project, the observed methanol gas phase concentration rapidly declined. Current understanding of gas and aqueous phase chemistry cannot explain the loss of methanol documented by these measurements. Two plausible heterogeneous reactions are proposed to explain the observed simultaneous loss and production of methanol and formaldehyde, respectively. If the rapid heterogeneous processing of methanol, seen in a cloud impacted by smoke, occurs in more pristine clouds, it could affect the oxidizing capacity of the troposphere on a global scale.

  5. A heterogeneous graph-based recommendation simulator

    SciTech Connect

    Yeonchan, Ahn; Sungchan, Park; Lee, Matt Sangkeun; Sang-goo, Lee

    2013-01-01

    Heterogeneous graph-based recommendation frameworks have flexibility in that they can incorporate various recommendation algorithms and various kinds of information to produce better results. In this demonstration, we present a heterogeneous graph-based recommendation simulator which enables participants to experience the flexibility of a heterogeneous graph-based recommendation method. With our system, participants can simulate various recommendation semantics by expressing the semantics via meaningful paths like User Movie User Movie. The simulator then returns the recommendation results on the fly based on the user-customized semantics using a fast Monte Carlo algorithm.

  6. Increasing selection response by Bayesian modeling of heterogeneous environmental variances

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heterogeneity of environmental variance among genotypes reduces selection response because genotypes with higher variance are more likely to be selected than low-variance genotypes. Modeling heterogeneous variances to obtain weighted means corrected for heterogeneous variances is difficult in likel...

  7. Computational Mechanics for Heterogeneous Materials

    SciTech Connect

    Lechman, Jeremy B.; Baczewski, Andrew David; Stephen Bond; Erikson, William W.; Lehoucq, Richard B.; Mondy, Lisa Ann; Noble, David R.; Pierce, Flint; Roberts, Christine; van Swol, Frank B.; Yarrington, Cole

    2013-11-01

    The subject of this work is the development of models for the numerical simulation of matter, momentum, and energy balance in heterogeneous materials. These are materials that consist of multiple phases or species or that are structured on some (perhaps many) scale(s). By computational mechanics we mean to refer generally to the standard type of modeling that is done at the level of macroscopic balance laws (mass, momentum, energy). We will refer to the flow or flux of these quantities in a generalized sense as transport. At issue here are the forms of the governing equations in these complex materials which are potentially strongly inhomogeneous below some correlation length scale and are yet homogeneous on larger length scales. The question then becomes one of how to model this behavior and what are the proper multi-scale equations to capture the transport mechanisms across scales. To address this we look to the area of generalized stochastic process that underlie the transport processes in homogeneous materials. The archetypal example being the relationship between a random walk or Brownian motion stochastic processes and the associated Fokker-Planck or diffusion equation. Here we are interested in how this classical setting changes when inhomogeneities or correlations in structure are introduced into the problem. Aspects of non-classical behavior need to be addressed, such as non-Fickian behavior of the mean-squared-displacement (MSD) and non-Gaussian behavior of the underlying probability distribution of jumps. We present an experimental technique and apparatus built to investigate some of these issues. We also discuss diffusive processes in inhomogeneous systems, and the role of the chemical potential in diffusion of hard spheres is considered. Also, the relevance to liquid metal solutions is considered. Finally we present an example of how inhomogeneities in material microstructure introduce fluctuations at the meso-scale for a thermal conduction problem

  8. Eradication of infectious diseases in heterogeneous populations

    SciTech Connect

    Travis, C.C.; Lenhart, S.M.

    1987-04-01

    A model is presented of infectious disease in heterogeneous populations, which allows for variable intra- to intergroup contact ratios. The authors give necessary and sufficient conditions for disease eradication by means of vaccination. Smallpox is used as an illustrative example.

  9. Heterogeneous Clustering: Operational and User Impacts

    NASA Technical Reports Server (NTRS)

    Salm, Saita Wood

    1999-01-01

    Heterogeneous clustering can improve overall utilization of multiple hosts and can provide better turnaround to users by balancing workloads across hosts. Building a cluster requires both operational changes and revisions in user scripts.

  10. Exploring heterogeneous market hypothesis using realized volatility

    NASA Astrophysics Data System (ADS)

    Chin, Wen Cheong; Isa, Zaidi; Mohd Nor, Abu Hassan Shaari

    2013-04-01

    This study investigates the heterogeneous market hypothesis using high frequency data. The cascaded heterogeneous trading activities with different time durations are modelled by the heterogeneous autoregressive framework. The empirical study indicated the presence of long memory behaviour and predictability elements in the financial time series which supported heterogeneous market hypothesis. Besides the common sum-of-square intraday realized volatility, we also advocated two power variation realized volatilities in forecast evaluation and risk measurement in order to overcome the possible abrupt jumps during the credit crisis. Finally, the empirical results are used in determining the market risk using the value-at-risk approach. The findings of this study have implications for informationally market efficiency analysis, portfolio strategies and risk managements.

  11. Heterogeneous treatment in the variational nodal method

    SciTech Connect

    Fanning, T.H.; Palmiotti, G.

    1995-06-01

    The variational nodal transport method is reduced to its diffusion form and generalized for the treatment of heterogeneous nodes while maintaining nodal balances. Adapting variational methods to heterogeneous nodes requires the ability to integrate over a node with discontinuous cross sections. In this work, integrals are evaluated using composite gaussian quadrature rules, which permit accurate integration while minimizing computing time. Allowing structure within a nodal solution scheme avoids some of the necessity of cross section homogenization, and more accurately defines the intra-nodal flux shape. Ideally, any desired heterogeneity can be constructed within the node; but in reality, the finite set of basis functions limits the practical resolution to which fine detail can be defined within the node. Preliminary comparison tests show that the heterogeneous variational nodal method provides satisfactory results even if some improvements are needed for very difficult, configurations.

  12. Heterogeneity and Risk Sharing in Village Economies.

    PubMed

    Chiappori, Pierre-André; Samphantharak, Krislert; Schulhofer-Wohl, Sam; Townsend, Robert M

    2014-03-01

    We show how to use panel data on household consumption to directly estimate households' risk preferences. Specifically, we measure heterogeneity in risk aversion among households in Thai villages using a full risk-sharing model, which we then test allowing for this heterogeneity. There is substantial, statistically significant heterogeneity in estimated risk preferences. Full insurance cannot be rejected. As the risk sharing, as-if-complete-markets theory might predict, estimated risk preferences are unrelated to wealth or other characteristics. The heterogeneity matters for policy: Although the average household would benefit from eliminating village-level risk, less-risk-averse households who are paid to absorb that risk would be worse off by several percent of household consumption.

  13. Heterogeneity and Risk Sharing in Village Economies*

    PubMed Central

    Chiappori, Pierre-André; Samphantharak, Krislert; Schulhofer-Wohl, Sam; Townsend, Robert M.

    2013-01-01

    We show how to use panel data on household consumption to directly estimate households’ risk preferences. Specifically, we measure heterogeneity in risk aversion among households in Thai villages using a full risk-sharing model, which we then test allowing for this heterogeneity. There is substantial, statistically significant heterogeneity in estimated risk preferences. Full insurance cannot be rejected. As the risk sharing, as-if-complete-markets theory might predict, estimated risk preferences are unrelated to wealth or other characteristics. The heterogeneity matters for policy: Although the average household would benefit from eliminating village-level risk, less-risk-averse households who are paid to absorb that risk would be worse off by several percent of household consumption. PMID:24932226

  14. Heterogeneous photocatalytic oxidation of atmospheric trace contaminants

    NASA Technical Reports Server (NTRS)

    Ollis, David F.

    1993-01-01

    Work performed during the period 1 May - 31 Oct. 1992 on heterogeneous photocatalytic oxidation of atmospheric trace contaminants is presented. Topics discussed include photoreactor monolith fundamental studies and monolith reactor operation: batch recirculation system.

  15. Intelligent Classification in Huge Heterogeneous Data Sets

    DTIC Science & Technology

    2015-06-01

    signals and through data dimension reduction, and to develop and tailor algorithms for the extraction of intelligence from several huge heterogeneous...dimension reduction and feature extraction . These techniques are employed when no training set is available, and therefore also no target output...algorithms for application to huge, heterogeneous data sets enabling the extraction of intelligence from information. The approach uses two-scale supervised

  16. Genomic and epigenomic heterogeneity of hepatocellular carcinoma.

    PubMed

    Lin, De-Chen; Mayakonda, Anand; Dinh, Huy Q; Huang, Pinbo; Lin, Lehang; Liu, Xiaoping; Ding, Ling-Wen; Wang, Jie; Berman, Benjamin; Song, Erwei; Yin, Dong; Koeffler, H Phillip

    2017-02-20

    Understanding the intratumoral heterogeneity of hepatocellular carcinoma (HCC) is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diversity was found in all 11 HCC cases, with 29% of driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, and STAG2. Similar with other cancer types, TP53 mutations were always shared between all tumor regions i.e. located on the "trunk" of the evolutionary tree. In addition, we found that variants within several drug targets such as KIT, SYK and PIK3CA were mutated in a fully clonal manner, indicating their therapeutic potentials for HCC. Temporal dissection of mutational signatures suggested that mutagenic processes associated with exposure to aristolochic acid and aflatoxin might play a more important role in early, as opposed to late, stages of HCC development. Moreover, we observed extensive intratumoral epigenetic heterogeneity in HCC based on multiple independent analytical methods and showed that intratumoral methylation heterogeneity might play important roles in the biology of HCC cells. Our results also demonstrated prominent heterogeneity of intratumoral methylation even in a stable HCC genome. Together, these findings highlight widespread intratumoral heterogeneity at both the genomic and epigenomic levels in HCC and provide an important molecular foundation for better understanding the pathogenesis of this malignancy.

  17. Materials properties: heterogeneity and appropriate sampling modes.

    PubMed

    Esbensen, Kim H

    2015-01-01

    The target audience for this Special Section comprises parties related to the food and feed sectors, e.g., field samplers, academic and industrial scientists, laboratory personnel, companies, organizations, regulatory bodies, and agencies who are responsible for sampling, as well as project leaders, project managers, quality managers, supervisors, and directors. All these entities face heterogeneous materials, and the characteristics of heterogeneous materials needs to be competently understood by all of them. Before delivering analytical results for decision-making, one form or other of primary sampling is always necessary, which must counteract the effects of the sampling target heterogeneity. Up to five types of sampling error may arise as a specific sampling process interacts with a heterogeneous material; two sampling errors arise because of the heterogeneity of the sampling target, and three additional sampling errors are produced by the sampling process itself-if not properly understood, reduced, and/or eliminated, which is the role of Theory of Sampling. This paper discusses the phenomenon and concepts involved in understanding, describing, and managing the adverse effects of heterogeneity in sampling.

  18. Colloid straining within saturated heterogeneous porous media.

    PubMed

    Porubcan, Alexis A; Xu, Shangping

    2011-02-01

    The transport of 0.46 μm, 2.94 μm, 5.1 μm and 6.06 μm latex particles in heterogeneous porous media prepared from the mixing of 0.78 mm, 0.46 mm and 0.23 mm quartz sands was investigated through column transport experiments. It was observed that the 0.46 μm particles traveled conservatively within the heterogeneous porous media, suggesting that under the experimental conditions employed in this research the strong repulsive interactions between the negatively charged latex particles and the clean quartz sands led to minimal colloid immobilization due to physicochemical filtration. The immobilization of the 2.94 μm, 5.1 μm and 6.06 μm latex particles was thus attributed to colloid straining. Experimental results showed that the straining of colloidal particles within heterogeneous sand mixtures increased when the fraction of finer sands increased. The mathematical model that was developed and tested based on results obtained using uniform sands (Xu et al., 2006) was found to be able to describe colloid straining within heterogeneous porous media. Examination of the relationship between the best-fit values of the clean-bed straining rate coefficients (k(0)) and the ratio of colloid diameter (d(p)) and sand grain size (d(g)) indicated that when number-average sizes were used to represent the size of the heterogeneous porous media, there existed a consistent relationship for both uniform sands and heterogeneous sand mixtures. Similarly, the use of the number-averaged sizes for the heterogeneous porous media produced a uniform relationship between the colloid straining capacity term (λ) and the ratio of d(p)/d(g) for all the sand treatments.

  19. Genetic heterogeneity in Malattia Leventinese.

    PubMed

    Toto, L; Parodi, M B; Baralle, F; Casari, G; Ravalico, G; Romano, M

    2002-11-01

    Malattia Leventinese (ML) is a dominant macular dystrophy characterized by drusen at the posterior pole. ML has been associated with a single mutation (R345W) in the EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP-1) gene, but also the EFEMP-2 gene, known to share genetic homology with EFEMP-1, is considered a candidate gene for this genetic disorder. We have characterized clinically and genetically seven members of a three-generation family affected by ML. Results showed that five family members were clinically affected but the DNA sequencing failed to reveal the typical R345W mutation. Furthermore, the linkage analysis to EFEMP-1 (using polymorphic markers D2S337 and D2S2368) and to EFEMP-2 (using D11S987 and D11S1314 markers) gave negative results. Therefore, our results suggest EFEMP-1 or EFEMP-2 genes cannot be excluded as being responsible for ML but other genes have to be considered in the pathogenesis of the disease.

  20. Computational model of heterogeneous heating in melanin

    NASA Astrophysics Data System (ADS)

    Kellicker, Jason; DiMarzio, Charles A.; Kowalski, Gregory J.

    2015-03-01

    Melanin particles often present as an aggregate of smaller melanin pigment granules and have a heterogeneous surface morphology. When irradiated with light within the absorption spectrum of melanin, these heterogeneities produce measurable concentrations of the electric field that result in temperature gradients from thermal effects that are not seen with spherical or ellipsoidal modeling of melanin. Modeling melanin without taking into consideration the heterogeneous surface morphology yields results that underestimate the strongest signals or over{estimate their spatial extent. We present a new technique to image phase changes induced by heating using a computational model of melanin that exhibits these surface heterogeneities. From this analysis, we demonstrate the heterogeneous energy absorption and resulting heating that occurs at the surface of the melanin granule that is consistent with three{photon absorption. Using the three{photon dluorescence as a beacon, we propose a method for detecting the extents of the melanin granule using photothermal microscopy to measure the phase changes resulting from the heating of the melanin.

  1. Emergence of Persistent Infection due to Heterogeneity

    NASA Astrophysics Data System (ADS)

    Agrawal, Vidit; Moitra, Promit; Sinha, Sudeshna

    2017-02-01

    We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual. We investigate the persistence of contagion qualitatively and quantitatively, under increasing heterogeneity in the partitioning of the population into different disease compartments, as well as increasing heterogeneity in the phases of the disease among individuals within a compartment. We observe that when the initial population is uniform, consisting of individuals at the same stage of disease progression, infection arising from a contagious seed does not persist. However when the initial population consists of randomly distributed refractory and susceptible individuals, a single source of infection can lead to sustained infection in the population, as heterogeneity facilitates the de-synchronization of the phases in the disease cycle of the individuals. We also show how the average size of the window of persistence of infection depends on the degree of heterogeneity in the initial composition of the population. In particular, we show that the infection eventually dies out when the entire initial population is susceptible, while even a few susceptibles among an heterogeneous refractory population gives rise to a large persistent infected set.

  2. Heterogeneity of liver cancer and personalized therapy.

    PubMed

    Li, Liang; Wang, Hongyang

    2016-09-01

    Liver cancer is an extraordinarily heterogeneous malignant disease among the tumors that have so far been identified. Hepatocellular carcinoma (HCC) arises most frequently in the setting of chronic liver inflammation and fibrosis, and takes a variety of course in individual patients to process to tumor. The risk factors such as HBV and/or HCV infections, aflatoxin infection, abuse alcohol intake, metabolic syndrome, obesity and diabetes are closely related to the environmental and genetic susceptibilities to HCC. The consequent resulting genomic instability, molecular and signal transduction network disorders and microenvironmental discrepancies are characterized by the extraordinary heterogeneity of liver cancer. The histology-based definition of the morphological heterogeneity of liver cancer has been modified and refined to treat patients with targeted therapies, but this still cannot solve all the problems. Lack of consistent outcome for anticancer agents and conventional therapies in liver cancer treatment calls for assessing the benefits of new molecularly targeted drugs and combined therapy, under the heterogeneity condition of tumor. The present review article will provide the complex mechanism and phenotype of liver cancer heterogeneity, and help us to execute precision medicine in a really personalized manner.

  3. Emergence of Persistent Infection due to Heterogeneity

    PubMed Central

    Agrawal, Vidit; Moitra, Promit; Sinha, Sudeshna

    2017-01-01

    We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual. We investigate the persistence of contagion qualitatively and quantitatively, under increasing heterogeneity in the partitioning of the population into different disease compartments, as well as increasing heterogeneity in the phases of the disease among individuals within a compartment. We observe that when the initial population is uniform, consisting of individuals at the same stage of disease progression, infection arising from a contagious seed does not persist. However when the initial population consists of randomly distributed refractory and susceptible individuals, a single source of infection can lead to sustained infection in the population, as heterogeneity facilitates the de-synchronization of the phases in the disease cycle of the individuals. We also show how the average size of the window of persistence of infection depends on the degree of heterogeneity in the initial composition of the population. In particular, we show that the infection eventually dies out when the entire initial population is susceptible, while even a few susceptibles among an heterogeneous refractory population gives rise to a large persistent infected set. PMID:28145522

  4. Estimating flow heterogeneity in natural fracture systems

    NASA Astrophysics Data System (ADS)

    Leckenby, Robert J.; Sanderson, David J.; Lonergan, Lidia

    2005-10-01

    Examples of small to medium scale fault systems have been mapped in Jurassic sedimentary rocks in north Somerset, England. These examples include contractional and dilational strike-slip oversteps as well as normal faults. These maps form the basis of calculations performed to investigate heterogeneity in natural fracture systems with the aim of predicting fluid flow localisation in different fault styles. As there is no way to measure fracture aperture directly, we use vein thickness to represent an integrated flow path or 'palaeo-aperture' from which we derive a representation of the flow distribution. Three different methods are used to estimate flow heterogeneity based on: (1) fracture density (the ratio of fracture length to area), (2) fracture aperture (fracture porosity) and (3) hydraulic conductance (fracture permeability normalised to the pressure gradient and fluid properties). Our results show that fracture density and hydraulic conductance are poorly correlated and that fracture density does not fully represent the natural heterogeneity of fracture systems. Fracture aperture and hydraulic conductance indicate stronger degrees of flow localisation. Different types of structures also seem to display characteristic and predictable patterns of heterogeneity. Normal fault systems show the highest magnitude of localisation along the faults rather than in the relay ramps, while contractional and dilational strike-slip systems show very strong localisation in the faults and oversteps, respectively. In all cases the amount of damage in the oversteps can modify such patterns of heterogeneity.

  5. Phylogenetic Quantification of Intra-tumour Heterogeneity

    PubMed Central

    Schwarz, Roland F.; Trinh, Anne; Sipos, Botond; Brenton, James D.; Goldman, Nick; Markowetz, Florian

    2014-01-01

    Intra-tumour genetic heterogeneity is the result of ongoing evolutionary change within each cancer. The expansion of genetically distinct sub-clonal populations may explain the emergence of drug resistance, and if so, would have prognostic and predictive utility. However, methods for objectively quantifying tumour heterogeneity have been missing and are particularly difficult to establish in cancers where predominant copy number variation prevents accurate phylogenetic reconstruction owing to horizontal dependencies caused by long and cascading genomic rearrangements. To address these challenges, we present MEDICC, a method for phylogenetic reconstruction and heterogeneity quantification based on a Minimum Event Distance for Intra-tumour Copy-number Comparisons. Using a transducer-based pairwise comparison function, we determine optimal phasing of major and minor alleles, as well as evolutionary distances between samples, and are able to reconstruct ancestral genomes. Rigorous simulations and an extensive clinical study show the power of our method, which outperforms state-of-the-art competitors in reconstruction accuracy, and additionally allows unbiased numerical quantification of tumour heterogeneity. Accurate quantification and evolutionary inference are essential to understand the functional consequences of tumour heterogeneity. The MEDICC algorithms are independent of the experimental techniques used and are applicable to both next-generation sequencing and array CGH data. PMID:24743184

  6. Predicting cancer involvement of genes from heterogeneous data

    PubMed Central

    Aragues, Ramon; Sander, Chris; Oliva, Baldo

    2008-01-01

    Background Systematic approaches for identifying proteins involved in different types of cancer are needed. Experimental techniques such as microarrays are being used to characterize cancer, but validating their results can be a laborious task. Computational approaches are used to prioritize between genes putatively involved in cancer, usually based on further analyzing experimental data. Results We implemented a systematic method using the PIANA software that predicts cancer involvement of genes by integrating heterogeneous datasets. Specifically, we produced lists of genes likely to be involved in cancer by relying on: (i) protein-protein interactions; (ii) differential expression data; and (iii) structural and functional properties of cancer genes. The integrative approach that combines multiple sources of data obtained positive predictive values ranging from 23% (on a list of 811 genes) to 73% (on a list of 22 genes), outperforming the use of any of the data sources alone. We analyze a list of 20 cancer gene predictions, finding that most of them have been recently linked to cancer in literature. Conclusion Our approach to identifying and prioritizing candidate cancer genes can be used to produce lists of genes likely to be involved in cancer. Our results suggest that differential expression studies yielding high numbers of candidate cancer genes can be filtered using protein interaction networks. PMID:18371197

  7. Self-attracting walk on heterogeneous networks.

    PubMed

    Kim, Kanghun; Kyoung, Jaegu; Lee, D-S

    2016-05-01

    Understanding human mobility in cyberspace becomes increasingly important in this information era. While human mobility, memory-dependent and subdiffusive, is well understood in Euclidean space, it remains elusive in random heterogeneous networks like the World Wide Web. Here we study the diffusion characteristics of self-attracting walks, in which a walker is more likely to move to the locations visited previously than to unvisited ones, on scale-free networks. Under strong attraction, the number of distinct visited nodes grows linearly in time with larger coefficients in more heterogeneous networks. More interestingly, crossovers to sublinear growths occur in strongly heterogeneous networks. To understand these phenomena, we investigate the characteristic volumes and topology of the cluster of visited nodes and find that the reinforced attraction to hubs results in expediting exploration first but delaying later, as characterized by the scaling exponents that we derive. Our findings and analysis method can be useful for understanding various diffusion processes mediated by human.

  8. Self-attracting walk on heterogeneous networks

    NASA Astrophysics Data System (ADS)

    Kim, Kanghun; Kyoung, Jaegu; Lee, D.-S.

    2016-05-01

    Understanding human mobility in cyberspace becomes increasingly important in this information era. While human mobility, memory-dependent and subdiffusive, is well understood in Euclidean space, it remains elusive in random heterogeneous networks like the World Wide Web. Here we study the diffusion characteristics of self-attracting walks, in which a walker is more likely to move to the locations visited previously than to unvisited ones, on scale-free networks. Under strong attraction, the number of distinct visited nodes grows linearly in time with larger coefficients in more heterogeneous networks. More interestingly, crossovers to sublinear growths occur in strongly heterogeneous networks. To understand these phenomena, we investigate the characteristic volumes and topology of the cluster of visited nodes and find that the reinforced attraction to hubs results in expediting exploration first but delaying later, as characterized by the scaling exponents that we derive. Our findings and analysis method can be useful for understanding various diffusion processes mediated by human.

  9. Heterogeneity and thermal modeling of ground water.

    PubMed

    Ferguson, Grant

    2007-01-01

    Heat transport in aquifers is becoming an increasingly important topic due to recent growth in the use of ground water in thermal applications. However, the effect of heterogeneity on heat transport in aquifers has yet to be examined in the same detail as it has been for solute transport, and it is unclear what effect this may have on our ability to create accurate models. This study examines this issue through stochastic modeling using the geostatistics for two aquifers with low and high degrees of heterogeneity. The results indicate that there is considerable uncertainty in the distribution of heat associated with injection of warm water into an aquifer. Heterogeneity in the permeability field was also found to slightly reduce the ability to recover this introduced heat at a later time. These simulations also reveal that hydrodynamic macrodispersion is an important consideration in some heat flow problems.

  10. Multiple roles of graphene in heterogeneous catalysis.

    PubMed

    Fan, Xiaobin; Zhang, Guoliang; Zhang, Fengbao

    2015-05-21

    Scientific interest in graphene as a catalyst and as a catalyst support in heterogeneous catalytic reactions has grown dramatically over the past several years. The present critical review summarizes the multiple roles of graphene in heterogeneous catalysis and highlights the influence of defects, heteroatom-containing functionalities, and graphene's two-dimensional structure on catalytic performance. We first discuss the role and advantages of graphene as a catalyst support, with emphasis on its interactions with the catalytic phases and the influence of mass transfer processes. We then clarify the origin of the intrinsic catalytic activity of graphene in heterogeneous catalytic reactions. Finally we suggest challenges and potential practical applications for graphene in industrial processes.

  11. Microswimmers in Complex Environments with Heterogeneous Microstructure

    NASA Astrophysics Data System (ADS)

    Hyon, Yunkyong; Fu, Henry

    2011-11-01

    We will discuss the swimming of microorganisms in complex and heterogeneous environments. Microswimmers in biological complex fluids, for instance, bacteria and sperm, are often greatly influenced by heterogeneous medium microstructure with length scales comparable to themselves. We characterize the interaction between the microswimmer and the medium microstructure using the model Golestanian three-sphere swimmer, treating the hydrodynamic interaction with the microstructure through the Oseen tensor. In this investigation, the microstructure of the heterogeneous environment is modeled by fixed spheres representing obstacles, or chains consisting of spheres connected with elastic springs. We find that the swimming speed of the swimmer depends on the force and deformation exerted on micro-structure. Furthermore, we find that while short freely suspended chains and short chains anchored at their ends interact with swimmer quite differently, long enough chains interact similarly, that is, a long mobile chain acts like a anchored chain. We discuss the implications for swimmer interactions with polymer solutions and compliant networks.

  12. Metabolic heterogeneity in human lung tumors

    PubMed Central

    Hensley, Christopher T.; Faubert, Brandon; Yuan, Qing; Lev-Cohain, Naama; Jin, Eunsook; Kim, Jiyeon; Jiang, Lei; Ko, Bookyung; Skelton, Rachael; Loudat, Laurin; Wodzak, Michelle; Klimko, Claire; McMillan, Elizabeth; Butt, Yasmeen; Ni, Min; Oliver, Dwight; Torrealba, Jose; Malloy, Craig R.; Kernstine, Kemp; Lenkinski, Robert E.; DeBerardinis, Ralph J.

    2015-01-01

    SUMMARY Non-small cell lung cancer (NSCLC) is heterogeneous in the genetic and environmental parameters that influence cell metabolism in culture. Here, we assessed the impact of these factors on human NSCLC metabolism in vivo using intra-operative 13C-glucose infusions in nine NSCLC patients to compare metabolism between tumors and benign lung. While enhanced glycolysis and glucose oxidation were common among these tumors, we observed evidence for oxidation of multiple nutrients in each of them, including lactate as a potential carbon source. Moreover, metabolically heterogeneous regions were identified within and between tumors, and surprisingly, our data suggested potential contributions of non-glucose nutrients in well-perfused tumor areas. Our findings not only demonstrate the heterogeneity in tumor metabolism in vivo but also highlight the strong influence of the microenvironment on this feature. PMID:26853473

  13. Heterogeneous Chemistry Related to Stratospheric Aircraft

    NASA Technical Reports Server (NTRS)

    Tolbert, Margaret A.

    1995-01-01

    Emissions from stratospheric aircraft that may directly or indirectly affect ozone include NO(y), H2O, soot and sulfuric acid. To fully assess the impact of such emissions, it is necessary to have a full understanding of both the homogeneous and heterogeneous transformations that may occur in the stratosphere. Heterogeneous reactions on stratospheric particles play a key role in partitioning ozone-destroying species between their active and reservoir forms. In particular, heterogeneous reactions tend to activate odd chlorine while deactivating odd nitrogen. Accurate modeling of the net atmospheric effects of stratospheric aircraft requires a thorough understanding of the competing effects of this activation/deactivation. In addition, a full understanding of the potential aircraft impacts requires that the abundance, composition and formation mechanisms of the particles themselves be established. Over the last three years with support from the High Speed Research Program, we have performed laboratory experiments to determine the chemical composition, formation mechanism, and reactivity of stratospheric aerosols.

  14. Heterogeneous Distributed Computing for Computational Aerosciences

    NASA Technical Reports Server (NTRS)

    Sunderam, Vaidy S.

    1998-01-01

    The research supported under this award focuses on heterogeneous distributed computing for high-performance applications, with particular emphasis on computational aerosciences. The overall goal of this project was to and investigate issues in, and develop solutions to, efficient execution of computational aeroscience codes in heterogeneous concurrent computing environments. In particular, we worked in the context of the PVM[1] system and, subsequent to detailed conversion efforts and performance benchmarking, devising novel techniques to increase the efficacy of heterogeneous networked environments for computational aerosciences. Our work has been based upon the NAS Parallel Benchmark suite, but has also recently expanded in scope to include the NAS I/O benchmarks as specified in the NHT-1 document. In this report we summarize our research accomplishments under the auspices of the grant.

  15. Information flow in heterogeneously interacting systems.

    PubMed

    Yamaguti, Yutaka; Tsuda, Ichiro; Takahashi, Yoichiro

    2014-02-01

    Motivated by studies on the dynamics of heterogeneously interacting systems in neocortical neural networks, we studied heterogeneously-coupled chaotic systems. We used information-theoretic measures to investigate directions of information flow in heterogeneously coupled Rössler systems, which we selected as a typical chaotic system. In bi-directionally coupled systems, spontaneous and irregular switchings of the phase difference between two chaotic oscillators were observed. The direction of information transmission spontaneously switched in an intermittent manner, depending on the phase difference between the two systems. When two further oscillatory inputs are added to the coupled systems, this system dynamically selects one of the two inputs by synchronizing, selection depending on the internal phase differences between the two systems. These results indicate that the effective direction of information transmission dynamically changes, induced by a switching of phase differences between the two systems.

  16. Deconstructing transcriptional heterogeneity in pluripotent stem cells.

    PubMed

    Kumar, Roshan M; Cahan, Patrick; Shalek, Alex K; Satija, Rahul; DaleyKeyser, A Jay; Li, Hu; Zhang, Jin; Pardee, Keith; Gennert, David; Trombetta, John J; Ferrante, Thomas C; Regev, Aviv; Daley, George Q; Collins, James J

    2014-12-04

    Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates; however, the regulatory circuits specifying these states and enabling transitions between them are not well understood. Here we set out to characterize transcriptional heterogeneity in mouse PSCs by single-cell expression profiling under different chemical and genetic perturbations. Signalling factors and developmental regulators show highly variable expression, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signalling pathways and chromatin regulators. Notably, either removal of mature microRNAs or pharmacological blockage of signalling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency network, enhanced self-renewal and a distinct chromatin state, an effect mediated by opposing microRNA families acting on the Myc/Lin28/let-7 axis. These data provide insight into the nature of transcriptional heterogeneity in PSCs.

  17. Deconstructing transcriptional heterogeneity in pluripotent stem cells

    PubMed Central

    Shalek, Alex K.; Satija, Rahul; DaleyKeyser, AJay; Li, Hu; Zhang, Jin; Pardee, Keith; Gennert, David; Trombetta, John J.; Ferrante, Thomas C.; Regev, Aviv; Daley, George Q.; Collins, James J.

    2014-01-01

    SUMMARY Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates, but the regulatory circuits specifying these states and enabling transitions between them are not well understood. We set out to characterize transcriptional heterogeneity in PSCs by single-cell expression profiling under different chemical and genetic perturbations. Signaling factors and developmental regulators show highly variable expression, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signaling pathways and chromatin regulators. Strikingly, either removal of mature miRNAs or pharmacologic blockage of signaling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency network, enhanced self-renewal, and a distinct chromatin state, an effect mediated by opposing miRNA families acting on the c-myc / Lin28 / let-7 axis. These data illuminate the nature of transcriptional heterogeneity in PSCs. PMID:25471879

  18. Characterizing hydrogeologic heterogeneity using lithologic data

    SciTech Connect

    Flach, G.; Hamm, LL.L.; Harris, M.K.; Thayer, P.A.; Haselow, J.S.; Smits, A.D.

    1997-06-13

    Large-scale (>1 m) variability in hydraulic conductivity is usually the main influence on field-scale groundwater flow patterns and dispersive transport. Incorporating realistic hydraulic conductivity heterogeneity into flow and transport models is paramount to accurate simulations, particularly for contaminant migration. Sediment lithologic descriptions and geophysical logs typically offer finer spatial resolution, and therefore more potential information about site-scale heterogeneity, than other site characterization data. In this study, a technique for generating a heterogeneous, three- dimensional hydraulic conductivity field from sediment lithologic descriptions is presented. The approach involves creating a three-dimensional, fine-scale representation of mud (silt and clay) percentage using a stratified interpolation algorithm. Mud percentage is then translated into horizontal and vertical conductivity using direct correlations derived from measured data and inverse groundwater flow modeling. Lastly, the fine-scale conductivity fields are averaged to create a coarser grid for use in groundwater flow and transport modeling.

  19. Temperature dependent heterogeneous rotational correlation in lipids

    NASA Astrophysics Data System (ADS)

    Dadashvand, Neda; Othon, Christina M.

    2016-12-01

    Lipid structures exhibit complex and highly dynamic lateral structure; and changes in lipid density and fluidity are believed to play an essential role in membrane targeting and function. The dynamic structure of liquids on the molecular scale can exhibit complex transient density fluctuations. Here the lateral heterogeneity of lipid dynamics is explored in free standing lipid monolayers. As the temperature is lowered the probes exhibit increasingly broad and heterogeneous rotational correlation. This increase in heterogeneity appears to exhibit a critical onset, similar to those observed for glass forming fluids. We explore heterogeneous relaxation in in a single constituent lipid monolayer of 1, 2-dimyristoyl-sn-glycero-3-phosphocholine by measuring the rotational diffusion of a fluorescent probe (1-palmitoyl-2-[1]-sn-glycero-3-phosphocholine), which is embedded in the lipid monolayer at low labeling density. Dynamic distributions are measured using wide-field time-resolved fluorescence anisotropy. The observed relaxation exhibits a narrow, liquid-like distribution at high temperatures (τ ˜ 2.4 ns), consistent with previous experimental measures (Dadashvand et al 2014 Struct. Dyn. 1 054701, Loura and Ramalho 2007 Biochim. Biophys. Acta 1768 467-478). However, as the temperature is quenched, the distribution broadens, and we observe the appearance of a long relaxation population (τ ˜ 16.5 ns). This supports the heterogeneity observed for lipids at high packing densities, and demonstrates that the nanoscale diffusion and reorganization in lipid structures can be significantly complex, even in the simplest amorphous architectures. Dynamical heterogeneity of this form can have a significant impact on the organization, permeability and energetics of lipid membrane structures.

  20. Temperature dependent heterogeneous rotational correlation in lipids.

    PubMed

    Dadashvand, Neda; Othon, Christina M

    2016-11-15

    Lipid structures exhibit complex and highly dynamic lateral structure; and changes in lipid density and fluidity are believed to play an essential role in membrane targeting and function. The dynamic structure of liquids on the molecular scale can exhibit complex transient density fluctuations. Here the lateral heterogeneity of lipid dynamics is explored in free standing lipid monolayers. As the temperature is lowered the probes exhibit increasingly broad and heterogeneous rotational correlation. This increase in heterogeneity appears to exhibit a critical onset, similar to those observed for glass forming fluids. We explore heterogeneous relaxation in in a single constituent lipid monolayer of 1, 2-dimyristoyl-sn-glycero-3-phosphocholine  by measuring the rotational diffusion of a fluorescent probe (1-palmitoyl-2-[1]-sn-glycero-3-phosphocholine), which is embedded in the lipid monolayer at low labeling density. Dynamic distributions are measured using wide-field time-resolved fluorescence anisotropy. The observed relaxation exhibits a narrow, liquid-like distribution at high temperatures (τ ∼ 2.4 ns), consistent with previous experimental measures (Dadashvand et al 2014 Struct. Dyn. 1 054701, Loura and Ramalho 2007 Biochim. Biophys. Acta 1768 467-478). However, as the temperature is quenched, the distribution broadens, and we observe the appearance of a long relaxation population (τ ∼ 16.5 ns). This supports the heterogeneity observed for lipids at high packing densities, and demonstrates that the nanoscale diffusion and reorganization in lipid structures can be significantly complex, even in the simplest amorphous architectures. Dynamical heterogeneity of this form can have a significant impact on the organization, permeability and energetics of lipid membrane structures.

  1. Genetic heterogeneity among kindreds with Alport syndrome.

    PubMed Central

    Hasstedt, S J; Atkin, C L; San Juan, A C

    1986-01-01

    Twenty-three kindreds were ascertained through patients at renal clinics at University of Utah Associated Hospitals. Urinalysis indicated glomerulonephritis in 231 of 997 examined kindred members; medical records documented kidney disease consistent with glomerulonephritis in 88 unexamined kindred members. Renal biopsies of 35 persons in a subset of 14 kindreds showed ultrastructural changes and absence of immune phenomena consistent with the diagnosis of Alport syndrome. End-stage renal disease (ESRD) had occurred in 72 (49%) of 148 known affected males and in 13 (8%) of 171 known affected females. No father-son affected pairs occurred in any of the kindreds; 84% of daughters of affected fathers were affected, and 49% of sons and 48% of daughters of affected mothers were affected. One of three phenotypes (juvenile Alport syndrome with deafness, adult Alport syndrome with deafness, or adult Alport syndrome without deafness or other defects) occurred in each of the 23 kindreds. We applied likelihood analysis to test for genetic heterogeneity underlying the phenotypic heterogeneity. In the first application (the admixture test), we tested for the occurrence of two forms of the disease without specifying which kindred had which form; we found insufficient evidence of admixture. In the second application (the predivided-sample test), we tested for genetic heterogeneity expressed as phenotypic heterogeneity. Kindreds were successively divided into two subgroups, with admission to the first subgroup dependent upon: (1) having greater than or equal to 2 males with ESRD, (2) occurrence of deafness in most nephrologically affected male family members, and (3) intrakindred mean age of ESRD in males later than age 31. Weak evidence of heterogeneity was found for category (1); stronger evidence of heterogeneity was found for category (3). Penetrance of microscopic hematuria in female heterozygotes was estimated as 82% overall, 85% for adult Alport syndrome, and 28% for

  2. Aspergillus fumigatus Photobiology Illuminates the Marked Heterogeneity between Isolates

    PubMed Central

    Fuller, Kevin K.; Cramer, Robert A.; Zegans, Michael E.

    2016-01-01

    ABSTRACT The given strain of Aspergillus fumigatus under study varies across laboratories, ranging from a few widely used “standards,” e.g., Af293 or CEA10, to locally acquired isolates that may be unique to one investigator. Since experiments concerning physiology or gene function are seldom replicated by others, i.e., in a different A. fumigatus background, the extent to which behavioral heterogeneity exists within the species is poorly understood. As a proxy for assessing such intraspecies variability, we analyzed the light response of 15 A. fumigatus isolates and observed striking quantitative and qualitative heterogeneity among them. The majority of the isolates fell into one of two seemingly mutually exclusive groups: (i) “photopigmenters” that robustly accumulate hyphal melanin in the light and (ii) “photoconidiators” that induce sporulation in the light. These two distinct responses were both governed by the same upstream blue light receptor, LreA, indicating that a specific protein’s contribution can vary in a strain-dependent manner. Indeed, while LreA played no apparent role in regulating cell wall homeostasis in strain Af293, it was essential in that regard in strain CEA10. The manifest heterogeneity in the photoresponses led us to compare the virulence levels of selected isolates in a murine model; remarkably, the virulence did vary greatly, although not in a manner that correlated with their overt light response. Taken together, these data highlight the extent to which isolates of A. fumigatus can vary, with respect to both broad physiological characteristics (e.g., virulence and photoresponse) and specific protein functionality (e.g., LreA-dependent phenotypes). PMID:27651362

  3. Strip and microstrip line periodic heterogeneities

    NASA Astrophysics Data System (ADS)

    Lerer, A. M.; Lerer, B. M.; Ryazanov, V. D.; Sledkov, V. A.

    1985-04-01

    A quasistatic method is described for analyzing periodic heterogeneities in single and coupled strip lines and microstrip lines. An ALGOL program on a BESM-6 computer calculated the running inductance and capacitance, wave impedances and delay coefficients for single and coupled strip lines and microstrip lines with periodic heterogeneities of arbitrary form. The analyzed quantities are investigated as a function of distance (from side shield to the strip), number of terms in the series and number of approximated functions. The method demonstrates good convergence and requires little machine time and results were verified experimentally.

  4. Atmospheric pressure microwave assisted heterogeneous catalytic reactions.

    PubMed

    Chemat-Djenni, Zoubida; Hamada, Boudjema; Chemat, Farid

    2007-07-11

    The purpose of the study was to investigate microwave selective heating phenomena and their impact on heterogeneous chemical reactions. We also present a tool which will help microwave chemists to answer to such questions as "My reaction yields 90% after 7 days at reflux; is it possible to obtain the same yield after a few minutes under microwaves?" and to have an approximation of their reactions when conducted under microwaves with different heterogeneous procedures. This model predicting reaction kinetics and yields under microwave heating is based on the Arrhenius equation, in agreement with experimental data and procedures.

  5. Micro- and nanorobots swimming in heterogeneous liquids.

    PubMed

    Nelson, Bradley J; Peyer, Kathrin E

    2014-09-23

    Essentially all experimental investigations of swimming micro- and nanorobots have focused on swimming in homogeneous Newtonian liquids. In this issue of ACS Nano, Schamel et al. investigate the actuation of "nanopropellers" in a viscoelastic biological gel that illustrates the importance of the size of the nanostructure relative to the gel mesh size. In this Perspective, we shed further light on the swimming performance of larger microrobots swimming in heterogeneous liquids. One of the interesting results of our work is that earlier findings on the swimming performance of motile bacteria in heterogeneous liquids agree, in principle, with our results. We also discuss future research directions that should be pursued in this fascinating interdisciplinary field.

  6. Stabilizing metal nanoparticles for heterogeneous catalysis.

    PubMed

    Cao, Anmin; Lu, Rongwen; Veser, Götz

    2010-11-07

    Metal nanoparticles hold great promise for heterogeneous catalysis due to their high dispersion, large concentration of highly undercoordinated surface sites, and the presence of quantum confinement effects, which can drastically alter their reactivity. However, the poor thermal stability of nano-sized particles limits their use to low temperature conditions and constitutes one of the key hurdles towards industrial application. The present perspective paper briefly reviews the mechanisms underlying nanoparticle sintering, and then gives an overview of emerging approaches towards stabilizing metal nanoparticles for heterogeneous catalysis. We conclude by highlighting the current needs for further developments in the field.

  7. Heterogeneity and Scaling in Geologic Media

    SciTech Connect

    Gregory N. Boitnott; Gilles Y. Bussod; Paul N. Hagin; Stephen R. Brown

    2005-04-18

    The accurate characterization and remediation of contaminated subsurface environments requires the detailed knowledge of subsurface structures and flow paths. Enormous resources are invested in scoping and characterizing sites using core sampling, 3-D geophysical surveys, well tests, etc.... Unfortunately, much of the information acquired is lost to compromises and simplifications made in constructing numerical grids for the simulators used to predict flow and transport from the contaminated area to the accessible environment. In rocks and soils, the bulk geophysical and transport properties of the matrix and of fracture systems are determined by the juxtaposition of geometric features at many length scales. In the interest of computational efficiency, recognized heterogeneities are simplified, averaged out, or entirely ignored in spite of recent studies that recognize that: (1) Structural and lithologic heterogeneities exist on all scales in rocks. (2) Small heterogeneities influence, and can control the physical and chemical properties of rocks. In this work we propose a physically based approach for the description and treatment of heterogeneities, that highlights the use of laboratory equipment designed to measure the effect on physical properties of fine scale heterogeneities observed in rocks and soils. We then discuss the development of an integration methodology that uses these measurements to develop and upscale flow and transport models. Predictive simulations are 'calibrated' to the measured heterogeneity data, and subsequently upscaled in a way that is consistent with the transport physics and the efficient use of environmental geophysics. This methodology provides a more accurate interpretation and representation of the subsurface for both environmental engineering and remediation. We show through examples, (i) the important influence of even subtle heterogeneity in the interpreting of geophysical data, and (ii) how physically based upscaling can lead

  8. Method for Accessing Distributed Heterogeneous Databases

    NASA Technical Reports Server (NTRS)

    Jacobs, B. E.

    1984-01-01

    A scenario of relational, hierarchial, and network data bases is presented and a distributed access view integrated data base system (DAVID) is described for uniformly accessing data bases which are heterogeneous and physically distributed. The DAVID system is based on data base logic so that the relational approach is generalized to the heterogeneous approach. The global data manager is explained as are global data manipulation languages which can operate on all the data bases and can query the data dictionary and the data directory.

  9. Retinal regionalization and heterogeneity of butterfly eyes

    NASA Astrophysics Data System (ADS)

    Stavenga, D.; Kinoshita, M.; Yang, E.-C.; Arikawa, K.

    2001-11-01

    The regional characteristics of the eyes of butterflies from different families have been surveyed using epi-illumination microscopy, utilizing the eyeshine visible due to the tapetum situated proximally to the rhabdom. All butterflies studied have a high spatial acuity in the frontal region. The facet diameter varies slightly across the eye, and the interommatidial angle and the eye parameter p are especially large dorsally. Whereas the ommatidial lattice is generally highly regular, the eyeshine colours distinctly depend on the species. Sometimes the eyeshine is locally uniform, but often it is heterogeneous. It is hypothesized that the regional characteristics as well as the local heterogeneity are adaptations that optimize spectral discrimination.

  10. Retinal regionalization and heterogeneity of butterfly eyes.

    PubMed

    Stavenga, D G; Kinoshita, M; Yang, E C; Arikawa, K

    2001-11-01

    The regional characteristics of the eyes of butterflies from different families have been surveyed using epi-illumination microscopy, utilizing the eyeshine visible due to the tapetum situated proximally to the rhabdom. All butterflies studied have a high spatial acuity in the frontal region. The facet diameter varies slightly across the eye, and the interommatidial angle and the eye parameter p are especially large dorsally. Whereas the ommatidial lattice is generally highly regular, the eyeshine colours distinctly depend on the species. Sometimes the eyeshine is locally uniform, but often it is heterogeneous. It is hypothesized that the regional characteristics as well as the local heterogeneity are adaptations that optimize spectral discrimination.

  11. Overcoming semantic heterogeneity in spatial data infrastructures

    NASA Astrophysics Data System (ADS)

    Lutz, M.; Sprado, J.; Klien, E.; Schubert, C.; Christ, I.

    2009-04-01

    In current spatial data infrastructures (SDIs), it is still often difficult to effectively exchange or re-use geographic data sets. A main reason for this is semantic heterogeneity, which occurs at different levels: at the metadata, the schema and the data content level. It is the goal of the work presented in this paper to overcome the problems caused by semantic heterogeneity on all three levels. We present a method based on ontologies and logical reasoning, which enhances the discovery, retrieval, interpretation and integration of geographic data in SDIs. Its benefits and practical use are illustrated with examples from the domains of geology and hydrology.

  12. Heterogeneity of group A streptococcal pyrogenic exotoxin type B.

    PubMed Central

    Barsumian, E L; Cunningham, C M; Schlievert, P M; Watson, D W

    1978-01-01

    Streptococcal pyrogenic exotoxin type B purified from culture filtrates of either the NY-5 or T-19 strain of group A streptococcus was found to be heterogeneous in charge. Three protein fractions with isoelectric points of 8.0, 8.4, and 9.0 were isolated by differential solubility in ethanol and acetate-buffered saline followed by isoelectric focusing and shown to be antigenically identical to streptococcal pyrogenic exotoxin type B. The molecular weights of all three fractions were approximately 17,500, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with aggregates forming in the presence of hyaluronic acid. Only the pI 8.4 fraction showed the characteristic activities of streptococcal pyrogenic exotoxin in rabbits: pyrogenicity and ability to enhance susceptibility to lethal endotoxin shock. The pI 8.0 and pI 9.0 fractions were not pyrogenic, but could be used to immunize against pyrogenicity. These two fractions failed either to enhance lethal endotoxin shock or to immunize against enhancement activity. When the isolated fractions were electrofocused again they appeared heterogeneous, suggesting an instability of the B toxin molecular forms. Images PMID:352946

  13. Heterogeneity of lipoprotein particles in hepatic Golgi fractions

    PubMed Central

    1982-01-01

    Newly synthesized phospholipids, labeled with either [14C]choline, [3H]myo-inositol, or [33P]phosphate, partioned preferentially (greater than 80% of total incorporated radioactivity) in a Golgi membrane subfraction, although the cognate content subfraction contained a relatively large amount of secretory lipoproteins. The labeling pattern was the same for all phospholipids tested in the two subfractions. An active exchange process of polar lipids between Golgi membranes and Golgi secretory lipoproteins is postulated as a plausible explanation for these findings. Less than half of all Golgi lipoprotein particles have the density of serum VLDLs and a similar, but not identical, biochemical composition. The remaining lipoprotein particles are characterized by a continuous spectrum of sizes, and (to the extent tested) by a lipid and protein composition different from that of serum VLDLs and HDLs. Results obtained in control experiments rule out the possibility that the heterogeneous population of Golgi lipoprotein particles is an artefact caused by our preparation procedures. It is assumed that these heterogeneous particles are immature precursors of both VLDLs and HDLs. PMID:7085757

  14. Compositional Heterogeneity in Ternary Models for the Cell Membrane

    NASA Astrophysics Data System (ADS)

    Smith, Robin; Heberle, Frederick; Wu, Jing; Feigenson, Gerald

    2010-03-01

    Ternary models for the cell membrane comprised of cholesterol (Chol) plus high and low melting temperature lipids exhibit rich phase behavior as a function of temperature and composition. Of particular interest is a region of coexisting disordered and ordered fluid phases that is thought to indicate how lipids organize to promote protein function in the cell membrane. We have used fluorescence resonance energy transfer to investigate the ternary mixtures DOPC(1,2-dioleoyl-sn-glycero-3-phosphocholine)/bSM (porcine brainsphingomyelin)/Chol and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)/bSM/Chol at high compositional resolution. We confirmed liquid coexistence for DOPC/bSM/Chol at 15 and 25C that melts by 35C, but in contrast to previous studies we detected no fluid-phase compositional heterogeneity for POPC/bSM/Chol from 5-35C. If domains exist, they must be smaller than the approximately 5 nm sensitivity provided by the fluorescent lipid analogs employed. We propose electron spin resonance and x-ray scattering for measuring whether liquid-phase compositional heterogeneity occurs for POPC/bSM/Chol. Understanding POPC/bSM/Chol phase behavior will provide a framework for investigating peptide/lipid interactions in a biologically relevant lipid mixture.

  15. Macrophages heterogeneity in atherosclerosis – implications for therapy

    PubMed Central

    Wilson, Heather M

    2010-01-01

    Abstract Atherosclerosis is a chronic inflammatory disease occurring within the artery wall and is an underlying cause of cardiovascular complications, including myocardial infarction, stroke and peripheral vascular disease. Its pathogenesis involves many immune cell types with a well accepted role for monocyte/macrophages. Cholesterol-loaded macrophages are a characteristic feature of plaques and are major players in all stages of plaque development. As well as modulating lipid metabolism, macrophages secrete inflammatory cytokines, chemokines and reactive oxygen and nitrogen species that drive pathogenesis. They also produce proteases and tissue factor that contribute to plaque rupture and thrombosis. Macrophages are however heterogeneous cells and when appropriately activated, they phagocytose cytotoxic lipoproteins, clear apoptotic bodies, secrete anti-inflammatory cytokines and synthesize matrix repair proteins that stabilize vulnerable plaques. Pharmacological modulation of macrophage activity therefore represents a potential therapeutic strategy for atherosclerosis. The aim of this review is to provide an overview of the current understanding of the different macrophage subsets and their monocyte precursors, and, the implications of these subsets for atherosclerosis. This will present a foundation for highlighting novel opportunities to exploit the heterogeneity of macrophages as important diagnostic and therapeutic targets for atherosclerosis and its associated diseases. PMID:20629993

  16. Molecular and clinical heterogeneity in palmoplantar keratoderma (PPK)

    SciTech Connect

    Hennis, H.C.; Sperling, K.; Reis, A.

    1994-09-01

    Palmoplantar keratoderma (PPK) is a frequent hereditary disorder of keratinization in man. Various clinically, histopathologically, and genetically distinct phenotypes can be diagnosed. Recently, we have identified mutations in the keratin 9 gene on chromosome 17q21 in a number of patients with the epidermolytic form of palmoplantar keratoderma (EPPK). We have now investigated three large families with clinically different types of PPK for linkage to either the type II keratin gene cluster on chromosome 12q or the type I keratin gene cluster on chromosome 17q using microsatellites and polymorphisms in several keratin genes. One family each with diffuse PPK associated with carcinoma of the esophagus (type Clarke-Howel-Evans-McConnell), PPK associated with sensorineural hearing loss, and keratolytic winter erythema (Oudtshoorn skin disease) was analyzed. We were able to exclude both type I and type II keratin genes as candidate genes for all these genodermatoses. In addition, linkage to a number of further candidate regions could also be excluded in these three families; the gene for transglutaminase 1 on chromosome 14q11, chromosome 1q21 containing a cluster of genes encoding intermediate filament-associated and cell envelope-associated proteins, and chromosome 18q12 with several genes for desmosomal glycoproteins. These findings reveal that mutations in genes other than keratin genes can be involved in the etiology of hyperkeratosis of palms and soles. Thus, the clinical heterogeneity in PPK is mirrored by heterogeneity at the molecular level.

  17. Increasing silk fibre strength through heterogeneity of bundled fibrils.

    PubMed

    Cranford, Steven W

    2013-05-06

    Can naturally arising disorder in biological materials be beneficial? Materials scientists are continuously attempting to replicate the exemplary performance of materials such as spider silk, with detailed techniques and assembly procedures. At the same time, a spider does not precisely machine silk-imaging indicates that its fibrils are heterogeneous and irregular in cross section. While past investigations either focused on the building material (e.g. the molecular scale protein sequence and behaviour) or on the ultimate structural component (e.g. silk threads and spider webs), the bundled structure of fibrils that compose spider threads has been frequently overlooked. Herein, I exploit a molecular dynamics-based coarse-grain model to construct a fully three-dimensional fibril bundle, with a length on the order of micrometres. I probe the mechanical behaviour of bundled silk fibrils with variable density of heterogenic protrusions or globules, ranging from ideally homogeneous to a saturated distribution. Subject to stretching, the model indicates that cooperativity is enhanced by contact through low-force deformation and shear 'locking' between globules, increasing shear stress transfer by up to 200 per cent. In effect, introduction of a random and disordered structure can serve to improve mechanical performance. Moreover, addition of globules allows a tuning of free volume, and thus the wettability of silk (with implications for supercontraction). These findings support the ability of silk to maintain near-molecular-level strength at the scale of silk threads, and the mechanism could be easily adopted as a strategy for synthetic fibres.

  18. Passive cutaneous anaphylaxis inhibition: evidence for heterogeneity in IgE mast cell interaction.

    PubMed Central

    Lehrer, S B; McCants, M L; Farris, P N; Bazin, H

    1981-01-01

    Recent evidence suggests that IgE molecules are heterogeneous with respect to ability to compete with IgE myeloma for sensitization of histamine release from chopped human lung and ability to passively sensitize human basophils for antigen-induced histamine release. These observations prompted further investigation of the possibility that there exists a functional heterogeneity in the IgE molecules with respect to mast-cell binding properties. Using eight different purified rat IgE myeloma proteins, we found that they differ in their ability to inhibit the passive cutaneous anaphylaxis (PCA) reaction of mouse reaginic antisera. This suggests that IgE molecules differ in their ability to bind to mast cell receptors. Since maximal inhibition of different mouse reaginic antisera and mouse IgE hybridomas is achieved with different IgE myelomas, there may exist a functional heterogeneity in mast-cell binding receptors as well. PMID:7319556

  19. Programming Models for Heterogeneous Multicore Systems

    DTIC Science & Technology

    2011-08-08

    Badia, F.D. Igual, J. Labarta, R. Mayo and E.S. Quintana- Orti . “An extension of the StarSs Programming Model for Platforms with Multiple GPUs...R. Mayo, J.M. Perez, J. Planas, E.S. Quintana- Orti . “A Proposal to Extend the OpenMP Tasking Model for Heterogeneous Architectures ” LNCS Vol. 5568

  20. Synthesis of RNA oligomers on heterogeneous templates

    NASA Technical Reports Server (NTRS)

    Ertem, G.; Ferris, J. P.

    1996-01-01

    The concept of an RNA world in the chemical origin of life is appealing, as nucleic acids are capable of both information storage and acting as templates that catalyse the synthesis of complementary molecules. Template-directed synthesis has been demonstrated for homogeneous oligonucleotides that, like natural nucleic acids, have 3',5' linkages between the nucleotide monomers. But it seems likely that prebiotic routes to RNA-like molecules would have produced heterogeneous molecules with various kinds of phosphodiester linkages and both linear and cyclic nucleotide chains. Here we show that such heterogeneity need be no obstacle to the templating of complementary molecules. Specifically, we show that heterogeneous oligocytidylates, formed by the montmorillonite clay-catalysed condensation of actuated monomers, can serve as templates for the synthesis of oligoguanylates. Furthermore, we show that oligocytidylates that are exclusively 2',5'-linked can also direct synthesis of oligoguanylates. Such heterogeneous templating reactions could have increased the diversity of the pool of protonucleic acids from which life ultimately emerged.

  1. Colloid Straining within Saturated Heterogeneous Porous Media

    NASA Astrophysics Data System (ADS)

    Porubcan, A.; Walczak, J.; Xu, S.

    2008-12-01

    A thorough understanding of colloid movement in the subsurface system is critical to the assessment of groundwater pollution by pathogenic bacteria and colloid-bound contaminants. It is increasingly recognized that straining, a process that occurs when the pore space is too small to allow for a particle's passage, represents an important process in colloid immobilization within groundwater systems. Previously published studies have focused on the kinetics of colloid straining within sand packs composed of uniform mineral grains. Natural aquifers, however, are usually characterized by physically heterogeneous sediments. In this study, we conducted column transport experiments with carboxylated latex particles and quartz sand to investigate the impact of sediment texture (i.e., the size distribution of mineral grains) on colloid straining kinetics. The quartz sands used in the experiment were thoroughly cleaned and the strong repulsive interactions between colloid particles and quartz sands resulted in minimal physicochemical deposition so the straining kinetics can be quantified unambiguously. Sand packs of different textures were prepared by mixing sands of various sizes (mesh sizes of 20-25, 35-40 and 60-70). Our results suggested that the ratio of colloid size and the median sand grain size was insufficient to predict colloid straining within heterogeneous sediments. Soil texture, which was related to the size distribution of the sand grains, must be considered. A relationship between colloid straining kinetics and the heterogeneity of porous media that can be useful for the prediction of colloid transport within heterogeneous sediments was presented.

  2. Towards inverse modeling of intratumor heterogeneity

    NASA Astrophysics Data System (ADS)

    Brutovsky, Branislav; Horvath, Denis

    2015-08-01

    Development of resistance limits efficiency of present anticancer therapies and preventing it remains a big challenge in cancer research. It is accepted, at the intuitive level, that resistance emerges as a consequence of the heterogeneity of cancer cells at the molecular, genetic and cellular levels. Produced by many sources, tumor heterogeneity is extremely complex time dependent statistical characteristics which may be quantified by measures defined in many different ways, most of them coming from statistical mechanics. In this paper, we apply the Markovian framework to relate population heterogeneity to the statistics of the environment. As, from an evolutionary viewpoint, therapy corresponds to a purposeful modi- fication of the cells' fitness landscape, we assume that understanding general relationship between the spatiotemporal statistics of a tumor microenvironment and intratumor heterogeneity will allow to conceive the therapy as an inverse problem and to solve it by optimization techniques. To account for the inherent stochasticity of biological processes at cellular scale, the generalized distancebased concept was applied to express distances between probabilistically described cell states and environmental conditions, respectively.

  3. Heterogeneous catalysis: More than skimming the surface

    NASA Astrophysics Data System (ADS)

    (Feng) Tao, Franklin; Tang, Yu

    2016-10-01

    The high temperatures and pressures used in heterogeneous catalysis make it difficult to observe catalysts using conventional techniques. Now, adsorbed product molecules on the surface of a single-crystal model catalyst have been observed during catalysis using a custom-built scanning tunnelling microscope that can work in situ.

  4. Reactor heterogeneity with saccharopolyspora erythraea airlift fermentations

    PubMed

    Pollard; Ison; Shamlou; Lilly

    1998-06-05

    Bioreactor heterogeneity has been studied in a multiconfigurable pilot-scale airlift reactor (0.25 m3) which created different degrees of heterogeneity. The impact of the two sparger configurations, i.e. in the draft tube or the annulus, in conjunction with a marine propeller fitted at the base of the downcomer, on the physiology of Saccharopolyspora erythraea was studied. Cellular growth, morphology, and productivity were compared between airlift and stirred tank reactors. Dissolved oxygen tension heterogeneity caused by differences in dissolved oxygen tension around the vessel did not affect growth, but the reduction of heterogeneity improved the specific erythromycin production rate and final specific production. Erythromycin production was shown to be proportional to the energy dissipation rate. The enhancement of bubble coalescence with increasing apparent viscosity led to the reduction of the sectional gas holdups and the improvement of liquid mixing. The extent of the changes with increasing apparent viscosity was dependent on the broth morphology, reactor configurations, and operating conditions. Copyright 1998 John Wiley & Sons, Inc.

  5. Heterogeneous multidimensional scaling for complex networks

    NASA Astrophysics Data System (ADS)

    Xuan, Qi; Ma, Xiaodi; Fu, Chenbo; Dong, Hui; Zhang, Guijun; Yu, Li

    2015-07-01

    Many real-world networks are essentially heterogeneous, where the nodes have different abilities to gain connections. Such networks are difficult to be embedded into low-dimensional Euclidean space if we ignore the heterogeneity and treat all the nodes equally. In this paper, based on a newly defined heterogeneous distance and a generalized network distance under the constraints of network and triangle inequalities, respectively, we propose a new heterogeneous multidimensional scaling method (HMDS) to embed different networks into proper Euclidean spaces. We find that HMDS behaves much better than the traditional multidimensional scaling method (MDS) in embedding different artificial and real-world networks into Euclidean spaces. Besides, we also propose a method to estimate the appropriate dimensions of Euclidean spaces for different networks, and find that the estimated dimensions are quite close to the real dimensions for those geometrical networks under study. These methods thus can help to better understand the evolution of real-world networks, and have practical importance in network visualization, community detection, link prediction and localization of wireless sensors.

  6. Scale Reliability Evaluation with Heterogeneous Populations

    ERIC Educational Resources Information Center

    Raykov, Tenko; Marcoulides, George A.

    2015-01-01

    A latent variable modeling approach for scale reliability evaluation in heterogeneous populations is discussed. The method can be used for point and interval estimation of reliability of multicomponent measuring instruments in populations representing mixtures of an unknown number of latent classes or subpopulations. The procedure is helpful also…

  7. Heterogeneity: The key to failure forecasting

    PubMed Central

    Vasseur, Jérémie; Wadsworth, Fabian B.; Lavallée, Yan; Bell, Andrew F.; Main, Ian G.; Dingwell, Donald B.

    2015-01-01

    Elastic waves are generated when brittle materials are subjected to increasing strain. Their number and energy increase non-linearly, ending in a system-sized catastrophic failure event. Accelerating rates of geophysical signals (e.g., seismicity and deformation) preceding large-scale dynamic failure can serve as proxies for damage accumulation in the Failure Forecast Method (FFM). Here we test the hypothesis that the style and mechanisms of deformation, and the accuracy of the FFM, are both tightly controlled by the degree of microstructural heterogeneity of the material under stress. We generate a suite of synthetic samples with variable heterogeneity, controlled by the gas volume fraction. We experimentally demonstrate that the accuracy of failure prediction increases drastically with the degree of material heterogeneity. These results have significant implications in a broad range of material-based disciplines for which failure forecasting is of central importance. In particular, the FFM has been used with only variable success to forecast failure scenarios both in the field (volcanic eruptions and landslides) and in the laboratory (rock and magma failure). Our results show that this variability may be explained, and the reliability and accuracy of forecast quantified significantly improved, by accounting for material heterogeneity as a first-order control on forecasting power. PMID:26307196

  8. Heterogeneous photocatalytic oxidation of atmospheric trace contaminants

    NASA Technical Reports Server (NTRS)

    Ollis, David F.

    1993-01-01

    The progress report on heterogeneous photocatalytic oxidation of atmospheric trace contaminants covering the period from 1 May - 31 Oct. 1992 is presented. The two topics discussed are photoreactor monolith fundamental studies and monolith reactor operation: batch recirculation system. Concentration profiles are shown.

  9. Fragmentation of metal particles during heterogeneous explosion

    NASA Astrophysics Data System (ADS)

    Ripley, R. C.; Donahue, L.; Zhang, F.

    2015-03-01

    Heterogeneous explosives contain a mixture of standard explosive material and reactive metal particles. The inclusion of metal particles alters the energy density and energy release timescales involved in the blast event. Available experimental evidence indicates that metal particles may be damaged or fragmented during heterogeneous blast, altering the distribution of particle sizes from their initial state. This paper discusses adaptation and application of fragmentation theory and physical models for particle damage during condensed matter detonation, aerodynamic breakup of molten particles, and particle impact fragmentation with nearby structures. The shock compression and impact fragmentation models are based on the energy methods for dynamic fragmentation by Grady and Kipp, while aerodynamic breakup is treated according to Weber number stability criteria for droplets. These particle fragmentation models are validated against fundamental test cases from the literature. The models are then applied to heterogeneous blast scenarios including free field and wall reflection in a semi-confined urban street. Comparison with experimental records of pressure shows good agreement despite challenges inherent in the complexity of heterogeneous blast measurement and multiphase simulation.

  10. Diffusion and Surface Reaction in Heterogeneous Catalysis

    ERIC Educational Resources Information Center

    Baiker, A.; Richarz, W.

    1978-01-01

    Ethylene hydrogenation on a platinum catalyst, electrolytically applied to a tube wall, is a good system for the study of the interactions between diffusion and surface reaction in heterogeneous catalysis. Theoretical background, apparatus, procedure, and student performance of this experiment are discussed. (BB)

  11. [Single-cell sequencing and tumour heterogeneity].

    PubMed

    Jordan, Bertrand

    2014-12-01

    The heterogeneity of tumours is now beginning to be documented precisely by single-cell new-generation sequencing. Recently published results on breast tumours show that each of the cells analysed displays a unique pattern of point mutations. This extensive genetic diversity is present before any treatment, and is likely to cause resistance to initially successful targeted therapies.

  12. Forecasting the failure of heterogeneous magmas

    NASA Astrophysics Data System (ADS)

    Vasseur, J.; Wadsworth, F. B.; Lavallée, Y.; Bell, A. F.; Main, I. G.; Dingwell, D. B.

    2015-12-01

    Eruption prediction is a long-sought-after goal of volcanology. Yet applying existing techniques retrospectively (hindcasting), we fail to predict events more often than we success. As much of the seismicity associated with intermediate to silicic volcanic eruptions comes from the brittle response of the ascending magma itself, we clearly require a good understanding of the parameters that control the ability to forecast magma failure itself. Here, we present suites of controlled experiments at magmatic temperatures using a range of synthetic magmas to investigate the control of microstructures on the efficacy of forecast models for material failure. We find that the failure of magmas with very little microstructural heterogeneity - such as melts - is very challenging to predict; whereas, the failure of very heterogeneous magmas is always well-predicted. To shed further light on this issue, we provide a scaling law based on the relationship between the microstructural heterogeneity in a magma and the error in the prediction of its failure time. We propose this method be used to elucidate the variable success rate of predicting volcanic predictions. We discuss this scaling in the context of the birth, life and death of structural heterogeneity during magma ascent with specific emphasis on obsidian-forming eruptions such as Chaitèn, 2008. During such eruptions, the repetitive creation and destruction of fractures filled with granular magma, which are thought to be the in situ remnants of seismogenic fracturing itself, are expressions of the life-cycle of heterogeneity in an otherwise coherent, melt-rich magma. We conclude that the next generation of failure forecast tools available to monitoring teams should incorporate some acknowledgment of the magma microstructure and not be solely based on the geophysical signals prior to eruption.

  13. Characterization of oil and gas reservoir heterogeneity

    SciTech Connect

    Tyler, N.; Barton, M.D.; Bebout, D.G.; Fisher, R.S.; Grigsby, J.D.; Guevara, E.; Holtz, M.; Kerans, C.; Nance, H.S.; Levey, R.A.

    1992-10-01

    Research described In this report addresses the internal architecture of two specific reservoir types: restricted-platform carbonates and fluvial-deltaic sandstones. Together, these two reservoir types contain more than two-thirds of the unrecovered mobile oil remaining ill Texas. The approach followed in this study was to develop a strong understanding of the styles of heterogeneity of these reservoir types based on a detailed outcrop description and a translation of these findings into optimized recovery strategies in select subsurface analogs. Research targeted Grayburg Formation restricted-platform carbonate outcrops along the Algerita Escarpment and In Stone Canyon In southeastern New Mexico and Ferron deltaic sandstones in central Utah as analogs for the North Foster (Grayburg) and Lake Creek (Wilcox) units, respectively. In both settings, sequence-stratigraphic style profoundly influenced between-well architectural fabric and permeability structure. It is concluded that reservoirs of different depositional origins can therefore be categorized Into a heterogeneity matrix'' based on varying intensity of vertical and lateral heterogeneity. The utility of the matrix is that it allows prediction of the nature and location of remaining mobile oil. Highly stratified reservoirs such as the Grayburg, for example, will contain a large proportion of vertically bypassed oil; thus, an appropriate recovery strategy will be waterflood optimization and profile modification. Laterally heterogeneous reservoirs such as deltaic distributary systems would benefit from targeted infill drilling (possibly with horizontal wells) and improved areal sweep efficiency. Potential for advanced recovery of remaining mobile oil through heterogeneity-based advanced secondary recovery strategies In Texas is projected to be an Incremental 16 Bbbl. In the Lower 48 States this target may be as much as 45 Bbbl at low to moderate oil prices over the near- to mid-term.

  14. The biology of myelodysplastic syndromes: unity despite heterogeneity

    PubMed Central

    Raza, Azra; Cruz, Raymond; Latif, Tahir; Mukherjee, Siddhartha; Galili, Naomi

    2010-01-01

    Myelodysplastic syndromes (MDS) traditionally have been grouped together as a disease entity based on clinical phenomena seen in association. Despite the similarities, there is great heterogeneity among the syndromes. Recent insights have shown, however, that there exists a biologically cohesive theme that unifies and thereby validates the conceptual interconnectedness. The first suggestion that such a relationship existed where biology could directly explain the observed cytopenias was the finding of excessive premature apoptosis of hematopoietic cells in MDS marrows. This apoptosis was mediated by paracrine as well as autocrine factors implicating both the seed and the soil in the pathology of the disease. Pro-inflammatory cytokines in the marrow microenvironment were mainly the paracrine mediators of apoptosis, but how the clonal cells committed suicide because of autocrine stimulation had remained a mystery for more than a decade. It has been shown now that deregulation of ribosome biogenesis can initiate a stress response in the cell through the p53 signaling pathway. Congenital anemias had been associated with mutations in ribosomal protein genes. The surprise came with the investigation of 5q- syndrome patients where haplo-insufficiency of the ribosomal protein gene RPS14 was found to be the cause of this MDS subtype. Similar ribosomal deregulation was shown to be present in all varieties of MDS patients, serving as another unifying characteristic. In addition to these findings, there are other DNA-related abnormalities such as uniparental disomy, mutations in the TET2 gene, and epigenetic phenomena that are associated with and occur across all types of MDS. This paper summarizes the themes unifying this heterogeneous group of diseases. PMID:22184517

  15. Mechanical Heterogeneity Favors Fragmentation of Strained Actin Filaments

    PubMed Central

    De La Cruz, Enrique M.; Martiel, Jean-Louis; Blanchoin, Laurent

    2015-01-01

    We present a general model of actin filament deformation and fragmentation in response to compressive forces. The elastic free energy density along filaments is determined by their shape and mechanical properties, which were modeled in terms of bending, twisting, and twist-bend coupling elasticities. The elastic energy stored in filament deformation (i.e., strain) tilts the fragmentation-annealing reaction free-energy profile to favor fragmentation. The energy gradient introduces a local shear force that accelerates filament intersubunit bond rupture. The severing protein, cofilin, renders filaments more compliant in bending and twisting. As a result, filaments that are partially decorated with cofilin are mechanically heterogeneous (i.e., nonuniform) and display asymmetric shape deformations and energy profiles distinct from mechanically homogenous (i.e., uniform), bare actin, or saturated cofilactin filaments. The local buckling strain depends on the relative size of the compliant segment as well as the bending and twisting rigidities of flanking regions. Filaments with a single bare/cofilin-decorated boundary localize energy and force adjacent to the boundary, within the compliant cofilactin segment. Filaments with small cofilin clusters were predicted to fragment within the compliant cofilactin rather than at boundaries. Neglecting contributions from twist-bend coupling elasticity underestimates the energy density and gradients along filaments, and thus the net effects of filament strain to fragmentation. Spatial confinement causes compliant cofilactin segments and filaments to adopt higher deformation modes and store more elastic energy, thereby promoting fragmentation. The theory and simulations presented here establish a quantitative relationship between actin filament fragmentation thermodynamics and elasticity, and reveal how local discontinuities in filament mechanical properties introduced by regulatory proteins can modulate both the severing efficiency

  16. Spatial heterogeneity of local blood flow and metabolite content in dog hearts

    SciTech Connect

    Franzen, D.; Conway, R.S.; Zhang, H.; Sonnenblick, E.H.; Eng, C. )

    1988-02-01

    Spatial variation (heterogeneity) of myocardial blood flow was studied under basal conditions in relation to four biochemical markers: creatine kinase (CK), lactate dehydrogenase (LDH), ATP, and glycogen. A total of 508 individual 0.5-g samples from the left ventricular free wall was studied in 12 dogs. Myocardial blood flow was measured by radioactive microspheres injected via a pigtail catheter into the left ventricle during light sedation; following thoracotomy, a second set of microspheres was injected via a catheter into the left atrium. In 27-54 samples/heart, myocardial blood flow, CK, LDH, protein, ATP, and glycogen were determined, permitting a direct correspondence between local blood flow and metabolic markers in each sample and an assessment of the spatial heterogeneity of flow and metabolite content. The coefficient of variation, which defines the extent of spatial heterogeneity, averaged 20% for closed-chest flow measurement, 19% for open-chest flow measurement, 22% for CK, 17% for LDH, 15% for protein, 8% for ATP, and 18% for glycogen. The correlation between local blood flow and the studied metabolities can only explain a minor portion of the spatial heterogeneity of myocardial blood flow. Although a physiological link between blood flow and metabolite content for small regions of the heart is demonstrated, the true local variability of blood flow may be modulated predominantly by other factors.

  17. Modeling mechanical response of heterogeneous materials

    NASA Astrophysics Data System (ADS)

    Pal, Siladitya

    Heterogeneous materials are ubiquitous in nature and as synthetic materials. These materials provide unique combination of desirable mechanical properties emerging from its heterogeneities at different length scales. Future structural and technological applications will require the development of advanced light weight materials with superior strength and toughness. Cost effective design of the advanced high performance synthetic materials by tailoring their microstructure is the challenge facing the materials design community. Prior knowledge of structure-property relationships for these materials is imperative for optimal design. Thus, understanding such relationships for heterogeneous materials is of primary interest. Furthermore, computational burden is becoming critical concern in several areas of heterogeneous materials design. Therefore, computationally efficient and accurate predictive tools are highly essential. In the present study, we mainly focus on mechanical behavior of soft cellular materials and tough biological material such as mussel byssus thread. Cellular materials exhibit microstructural heterogeneity by interconnected network of same material phase. However, mussel byssus thread comprises of two distinct material phases. A robust numerical framework is developed to investigate the micromechanisms behind the macroscopic response of both of these materials. Using this framework, effect of microstuctural parameters has been addressed on the stress state of cellular specimens during split Hopkinson pressure bar test. A voronoi tessellation based algorithm has been developed to simulate the cellular microstructure. Micromechanisms (microinertia, microbuckling and microbending) governing macroscopic behavior of cellular solids are investigated thoroughly with respect to various microstructural and loading parameters. To understand the origin of high toughness of mussel byssus thread, a Genetic Algorithm (GA) based optimization framework has been

  18. Molecular Heterogeneity in Aldosterone-Producing Adenomas

    PubMed Central

    Nanba, Kazutaka; Chen, Andrew X.; Omata, Kei; Vinco, Michelle; Giordano, Thomas J.; Else, Tobias; Hammer, Gary D.

    2016-01-01

    Context: The use of next-generation sequencing has resulted in the identification of recurrent somatic mutations underlying primary aldosteronism (PA). However, significant gaps remain in our understanding of the relationship between tumor aldosterone synthase (CYP11B2) expression and somatic mutation status. Objective: The objective of the study was to investigate tumor CYP11B2 expression and somatic aldosterone-driver gene mutation heterogeneity. Methods: Fifty-one adrenals from 51 PA patients were studied. Immunohistochemistry for CYP11B2 was performed. Aldosterone-producing adenomas with intratumor CYP11B2 heterogeneity were analyzed for mutation status using targeted next-generation sequencing. DNA was isolated from CYP11B2-positive, CYP11B2-negative, and adjacent normal areas from formalin-fixed, paraffin-embedded sections. Results: Of 51 adrenals, seven (14 %) showed distinct heterogeneity in CYP11B2 by immunohistochemistry, including six adenomas with intratumor heterogeneity and one multinodular hyperplastic adrenal with both CYP11B2-positive and -negative nodules. Of the six adrenocortical adenomas with CYP11B2 heterogeneity, three had aldosterone-regulating mutations (CACNA1D p.F747C, KCNJ5 p.L168R, ATP1A1 p.L104R) only in CYP11B2-positive regions, and one had two different mutations localized to two histologically distinct CYP11B2-positive regions (ATP2B3 p.L424_V425del, KCNJ5 p.G151R). Lastly, one adrenal with multiple CYP11B2-expressing nodules showed different mutations in each (CACNA1D p.F747V and ATP1A1 p.L104R), and no mutations were identified in CYP11B2-negative nodule or adjacent normal adrenal. Conclusions: Adrenal tumors in patients with PA can demonstrate clear heterogeneity in CYP11B2 expression and somatic mutations in driver genes for aldosterone production. These findings suggest that aldosterone-producing adenoma tumorigenesis can occur within preexisting nodules through the acquisition of somatic mutations that drive aldosterone

  19. Heterogeneous Organo-Catalysis: Sustainable Pathways to ...

    EPA Pesticide Factsheets

    Glucose and fructose are among the most abundant plant-derived materials1 and have been converted into useful building units often used in the drug discovery and polymer architecture.2 Unfortunately, most of these conversions require mineral acids and complex heterogeneous catalysis systems which suffer from the diminished activity and recyclability issues.3 Herein, we report a highly reactive and inexpensive heterogeneous sulfonated graphitic carbon nitride (Sg-CN), endowed with strong acidity that readily transforms carbohydrates to furanics. The ready availability and benign nature of the material and its stability over the several reaction cycles renders this catalyst very useful in organic synthesis, polymer industry and in the preparation of drug precursors. Poster presentation at the 253rd American Chemical Society (ACS) National meeting in San Francisco, CA

  20. Heterogeneous Drying Stresses in Stratum Corneum

    PubMed Central

    German, G.K.; Engl, W.C.; Pashkovski, E.; Banerjee, S.; Xu, Y.; Mertz, A.F.; Hyland, C.; Dufresne, E.R.

    2012-01-01

    We study the drying of stratum corneum, the skin's outermost layer and an essential barrier to mechanical and chemical stresses from the environment. Even though stratum corneum exhibits structural features across multiple length-scales, contemporary understanding of the mechanical properties of stratum corneum is based on the assumption that its thickness and composition are homogeneous. We quantify spatially resolved in-plane traction stress and deformation at the interface between a macroscopic sample of porcine stratum corneum and an adherent deformable elastomer substrate. At length-scales greater than a millimeter, the skin behaves as a homogeneous elastic material. At this scale, a linear elastic model captures the spatial distribution of traction stresses and the dependence of drying behavior on the elastic modulus of the substrate. At smaller scales, the traction stresses are strikingly heterogeneous and dominated by the heterogeneous structure of the stratum corneum. PMID:22713557

  1. Heterogeneous chemistry of HBr and HF

    SciTech Connect

    Hanson, D.R.; Ravishankara, A.R.

    1992-11-12

    The authors present information on heterogeneous chemistry of HF and HBr on glass and ice surfaces at a temperature of 200K. Their objective is to study whether heterogeneous reactions of these species could be important in the atmospheric chemistry occuring on NAT particles or cloud condensation nuclei, and be a contributor to ozone depletion. HF showed no significant uptake or reactions with ClONO{sub 2} or HOCl. HBr was found to adsorb on these surfaces, and did not exhibit saturation for even relative high concentrations. In addition it showed reactivity with ClONO{sub 2}, Cl{sub 2} and N{sub 2}O{sub 5} on ice surfaces.

  2. Heterogeneous physicochemistry of the polar ozone hole

    NASA Technical Reports Server (NTRS)

    Turco, Richard P.; Toon, Owen B.; Hamill, Patrick

    1989-01-01

    Processes occurring in the polar winter stratosphere, which involve polar stratospheric clouds (PSCs), are investigated using observations from the Airborne Antarctic Ozone Experiment. In particular, data on the properties of PSCs and their physical chemistry, the microphysical processes and time constants for cloud processes, the heterogeneous chemical processes and their time constants, and nonlinearities in the long-term ozone trend associated with physical and chemical processes are examined. The chemical reactions leading to the depletion of the inert chlorine reservoir in a presence of type I PSCs are established, and it is shown that type II PSCs contribute to chemical processing that sustains the chemical imbalance of the polar stratosphere. It is shown that, using a simple model, the decadal evolution of the Antarctic ozone hole may be understood through nonlinearities in the heterogeneous chemistry, with possible contributing effects of variations in stratospheric temperatures and water vapor concentrations.

  3. The lunar seismic tomography and internal heterogeneity

    NASA Astrophysics Data System (ADS)

    Zhao, N.; Zhu, P.; Yuan, Y.; Zhang, J.

    2012-12-01

    A seismic tomography is presented to show the internal lateral heterogeneities of moon. The lunar seismic tomography is made from the moonquake arrival-time data acquired by the Apollo program during 1971 to 1977. The seismic records obtained from the four seismic station of Apollo Lunar Surface Experiments Package on the moon. The research target covers the surround of Apollo-12, 14, 15 and 16 landing sites. A preliminary image of three-dimensional P- and S-wave velocity structures of lunar interior have been calculated using hundreds of arrival-times of moonquake events from surface to deep mantle. These results show that some evidences of lateral heterogeneities in the lunar mantle and crust, which implies the existence of complex structure inside the moon.

  4. Dynamics of Adaptation in Spatially Heterogeneous Metapopulations

    PubMed Central

    Papaïx, Julien; David, Olivier; Lannou, Christian; Monod, Hervé

    2013-01-01

    The selection pressure experienced by organisms often varies across the species range. It is hence crucial to characterise the link between environmental spatial heterogeneity and the adaptive dynamics of species or populations. We address this issue by studying the phenotypic evolution of a spatial metapopulation using an adaptive dynamics approach. The singular strategy is found to be the mean of the optimal phenotypes in each habitat with larger weights for habitats present in large and well connected patches. The presence of spatial clusters of habitats in the metapopulation is found to facilitate specialisation and to increase both the level of adaptation and the evolutionary speed of the population when dispersal is limited. By showing that spatial structures are crucial in determining the specialisation level and the evolutionary speed of a population, our results give insight into the influence of spatial heterogeneity on the niche breadth of species. PMID:23424618

  5. Heterogeneous growth of single crystals on polycrystals

    NASA Astrophysics Data System (ADS)

    Wang, Zumin; Jeurgens, Lars P. H.; Gu, Lin; Mittemeijer, Eric J.

    2017-03-01

    This work discloses a surprising, previously unknown heterogeneous growth mode. Namely, large-area, thin sheets of single-crystalline Ge were observed to grow laterally on top of a polycrystalline Al substrate, covering as many as tens of differently oriented Al grains at low temperatures. The observation of the Ge crystal-growth process by in situ heating transmission electron microscopy demonstrates an intriguing type of "faceted" growth: the growth of single-crystalline Ge thin sheets proceeding Al-grain by Al-grain on top of the polycrystalline Al substrate. The crystalline Ge growth front tends to align along the lines of intersection of the Al grain boundaries with the Al surface. Such an unusual heterogeneous growth mode has been shown to be a consequence of the strong anisotropy of the energy of the crystalline/crystalline (here: c-Ge/c-Al) interfaces.

  6. Simple model to study heterogeneous electrocatalysts

    NASA Astrophysics Data System (ADS)

    Franco-Junior, Edison; Lopes, Ana Carolina G.; Suffredini, Hugo B.; Homem-de-Mello, Paula

    2015-01-01

    New electrocatalyst materials have been proposed to increase the performance of fuel cells. Experimental studies show that Pt and Pb metallic and oxide materials are quite efficient in the oxidation of alcohols and small organic molecules such as formic acid in advanced fuel cells. This work proposes a model for studying morphologically heterogeneous catalysts through quantum chemistry methods such as density functional calculations. For testing the model, we have experimentally studied the adsorption of small organic molecules, namely formic acid and methanol, on Pt and Pb electrodes. All methodologies we have tested can be employed for this kind of study, but M06 functional results correlate best with previous simulations of homogeneous catalysts and with experimental data obtained for homogeneous and heterogeneous electrodes. Our model indicates that the presence of a Pt-Pb interface is responsible for higher adsorption energies of these molecules, most likely due to the orientation of the organic molecules that should facilitate the oxidation process.

  7. Multiparametric imaging with heterogeneous radiofrequency fields

    PubMed Central

    Cloos, Martijn A.; Knoll, Florian; Zhao, Tiejun; Block, Kai T.; Bruno, Mary; Wiggins, Graham C.; Sodickson, Daniel K.

    2016-01-01

    Magnetic resonance imaging (MRI) has become an unrivalled medical diagnostic technique able to map tissue anatomy and physiology non-invasively. MRI measurements are meticulously engineered to control experimental conditions across the sample. However, residual radiofrequency (RF) field inhomogeneities are often unavoidable, leading to artefacts that degrade the diagnostic and scientific value of the images. Here we show that, paradoxically, these artefacts can be eliminated by deliberately interweaving freely varying heterogeneous RF fields into a magnetic resonance fingerprinting data-acquisition process. Observations made based on simulations are experimentally confirmed at 7 Tesla (T), and the clinical implications of this new paradigm are illustrated with in vivo measurements near an orthopaedic implant at 3T. These results show that it is possible to perform quantitative multiparametric imaging with heterogeneous RF fields, and to liberate MRI from the traditional struggle for control over the RF field uniformity. PMID:27526996

  8. Multiparametric imaging with heterogeneous radiofrequency fields

    NASA Astrophysics Data System (ADS)

    Cloos, Martijn A.; Knoll, Florian; Zhao, Tiejun; Block, Kai T.; Bruno, Mary; Wiggins, Graham C.; Sodickson, Daniel K.

    2016-08-01

    Magnetic resonance imaging (MRI) has become an unrivalled medical diagnostic technique able to map tissue anatomy and physiology non-invasively. MRI measurements are meticulously engineered to control experimental conditions across the sample. However, residual radiofrequency (RF) field inhomogeneities are often unavoidable, leading to artefacts that degrade the diagnostic and scientific value of the images. Here we show that, paradoxically, these artefacts can be eliminated by deliberately interweaving freely varying heterogeneous RF fields into a magnetic resonance fingerprinting data-acquisition process. Observations made based on simulations are experimentally confirmed at 7 Tesla (T), and the clinical implications of this new paradigm are illustrated with in vivo measurements near an orthopaedic implant at 3T. These results show that it is possible to perform quantitative multiparametric imaging with heterogeneous RF fields, and to liberate MRI from the traditional struggle for control over the RF field uniformity.

  9. Microgrids and Heterogeneous Power Quality and Reliability

    SciTech Connect

    LaCommare, Kristina; Marnay, Chris

    2007-10-01

    This paper describes two stylized alternative visions of how the power system might evolve to meet future requirements for the high quality electricity service that modern digital economies demand, a supergrids paradigm and a dispersed paradigm. Some of the economics of the dispersed vision are explored, and perspectives are presented on both the choice of homogeneous universal power quality upstream in the electricity supply chain and on the extremely heterogeneous requirements of end-use loads. It is argued that meeting the demanding requirements of sensitive loads by local provision of high quality power may be more cost effective than increasing the quality of universal homogeneous supply upstream in the legacy grid. Finally, the potential role of microgrids in delivering heterogeneous power quality is demonstrated by reference to two ongoing microgrid tests in the U.S. and Japan.

  10. Modeling vaccination in a heterogeneous metapopulation system

    NASA Astrophysics Data System (ADS)

    Lachiany, Menachem

    2016-09-01

    We present here a multicity SIS epidemic model with vaccination. The model describes the dynamics of heterogeneous metapopulations that contain imperfectly vaccinated individuals. The effect of vaccination on heterogeneous multicity models has not been previously studied. We show that under very generic conditions, the epidemic threshold does not depend on the diffusion coefficient of the vaccinated individuals, but it does depend on the diffusion coefficient of the infected population. We then show, using a novel methodology, that the reproduction number is determined by the homogeneous model parameters and by the maximal number of neighbors a city can have, when the diffusion coefficient of the infected population is low. Finally, we present numerical simulations to support the analytical results.

  11. Population dynamics on heterogeneous bacterial substrates

    NASA Astrophysics Data System (ADS)

    Mobius, Wolfram; Murray, Andrew W.; Nelson, David R.

    2012-02-01

    How species invade new territories and how these range expansions influence the population's genotypes are important questions in the field of population genetics. The majority of work addressing these questions focuses on homogeneous environments. Much less is known about the population dynamics and population genetics when the environmental conditions are heterogeneous in space. To better understand range expansions in two-dimensional heterogeneous environments, we employ a system of bacteria and bacteriophage, the viruses of bacteria. Thereby, the bacteria constitute the environment in which a population of bacteriophages expands. The spread of phage constitutes itself in lysis of bacteria and thus formation of clear regions on bacterial lawns, called plaques. We study the population dynamics and genetics of the expanding page for various patterns of environments.

  12. Heterogeneous propellant internal ballistics: criticism and regeneration

    NASA Astrophysics Data System (ADS)

    Glick, R. L.

    2011-10-01

    Although heterogeneous propellant and its innately nondeterministic, chemically discrete morphology dominates applications, ballisticcharacterization deterministic time-mean burning rate and acoustic admittance measures' absence of explicit, nondeterministic information requires homogeneous propellant with a smooth, uniformly regressing burning surface: inadequate boundary conditions for heterogeneous propellant grained applications. The past age overcame this dichotomy with one-dimensional (1D) models and empirical knowledge from numerous, adequately supported motor developments and supplementary experiments. However, current cost and risk constraints inhibit this approach. Moreover, its fundamental science approach is more sensitive to incomplete boundary condition information (garbage-in still equals garbage-out) and more is expected. This work critiques this situation and sketches a path forward based on enhanced ballistic and motor characterizations in the workplace and approximate model and apparatus developments mentored by CSAR DNS capabilities (or equivalent).

  13. Heterogeneous concurrent computing with exportable services

    NASA Technical Reports Server (NTRS)

    Sunderam, Vaidy

    1995-01-01

    Heterogeneous concurrent computing, based on the traditional process-oriented model, is approaching its functionality and performance limits. An alternative paradigm, based on the concept of services, supporting data driven computation, and built on a lightweight process infrastructure, is proposed to enhance the functional capabilities and the operational efficiency of heterogeneous network-based concurrent computing. TPVM is an experimental prototype system supporting exportable services, thread-based computation, and remote memory operations that is built as an extension of and an enhancement to the PVM concurrent computing system. TPVM offers a significantly different computing paradigm for network-based computing, while maintaining a close resemblance to the conventional PVM model in the interest of compatibility and ease of transition Preliminary experiences have demonstrated that the TPVM framework presents a natural yet powerful concurrent programming interface, while being capable of delivering performance improvements of upto thirty percent.

  14. Multiparametric imaging with heterogeneous radiofrequency fields.

    PubMed

    Cloos, Martijn A; Knoll, Florian; Zhao, Tiejun; Block, Kai T; Bruno, Mary; Wiggins, Graham C; Sodickson, Daniel K

    2016-08-16

    Magnetic resonance imaging (MRI) has become an unrivalled medical diagnostic technique able to map tissue anatomy and physiology non-invasively. MRI measurements are meticulously engineered to control experimental conditions across the sample. However, residual radiofrequency (RF) field inhomogeneities are often unavoidable, leading to artefacts that degrade the diagnostic and scientific value of the images. Here we show that, paradoxically, these artefacts can be eliminated by deliberately interweaving freely varying heterogeneous RF fields into a magnetic resonance fingerprinting data-acquisition process. Observations made based on simulations are experimentally confirmed at 7 Tesla (T), and the clinical implications of this new paradigm are illustrated with in vivo measurements near an orthopaedic implant at 3T. These results show that it is possible to perform quantitative multiparametric imaging with heterogeneous RF fields, and to liberate MRI from the traditional struggle for control over the RF field uniformity.

  15. Trophic mismatch requires seasonal heterogeneity of warming.

    PubMed

    Straile, Dietmar; Kerimoglu, Onur; Peeters, Frank

    2015-10-01

    Climate warming has been shown to advance the phenology of species. Asynchronous changes in phenology between interacting species may disrupt feeding interactions (phenological mismatch), which could have tremendous consequences for ecosystem functioning. Long-term field observations have suggested asynchronous shifts in phenology with warming, whereas experimental studies have not been conclusive. Using proxy-based modeling of three trophic levels (algae, herbivores, and fish), we .show that asynchronous changes in phenology only occur if warming is seasonally heterogeneous, but not if warming is constant throughout the year. If warming is seasonally heterogeneous, the degree and even direction of asynchrony depends on the specific seasonality of the warming. Conclusions about phenological mismatches in food web interactions may therefore produce controversial results if the analyses do not distinguish between seasonally constant and seasonal specific warming. Furthermore, our results suggest that predicting asynchrony between interacting species requires reliable warming predictions that resolve sub-seasonal time scales.

  16. Sparse covariance estimation in heterogeneous samples*

    PubMed Central

    Rodríguez, Abel; Lenkoski, Alex; Dobra, Adrian

    2015-01-01

    Standard Gaussian graphical models implicitly assume that the conditional independence among variables is common to all observations in the sample. However, in practice, observations are usually collected from heterogeneous populations where such an assumption is not satisfied, leading in turn to nonlinear relationships among variables. To address such situations we explore mixtures of Gaussian graphical models; in particular, we consider both infinite mixtures and infinite hidden Markov models where the emission distributions correspond to Gaussian graphical models. Such models allow us to divide a heterogeneous population into homogenous groups, with each cluster having its own conditional independence structure. As an illustration, we study the trends in foreign exchange rate fluctuations in the pre-Euro era. PMID:26925189

  17. Integrating CLIPS applications into heterogeneous distributed systems

    NASA Technical Reports Server (NTRS)

    Adler, Richard M.

    1991-01-01

    SOCIAL is an advanced, object-oriented development tool for integrating intelligent and conventional applications across heterogeneous hardware and software platforms. SOCIAL defines a family of 'wrapper' objects called agents, which incorporate predefined capabilities for distributed communication and control. Developers embed applications within agents and establish interactions between distributed agents via non-intrusive message-based interfaces. This paper describes a predefined SOCIAL agent that is specialized for integrating C Language Integrated Production System (CLIPS)-based applications. The agent's high-level Application Programming Interface supports bidirectional flow of data, knowledge, and commands to other agents, enabling CLIPS applications to initiate interactions autonomously, and respond to requests and results from heterogeneous remote systems. The design and operation of CLIPS agents are illustrated with two distributed applications that integrate CLIPS-based expert systems with other intelligent systems for isolating and mapping problems in the Space Shuttle Launch Processing System at the NASA Kennedy Space Center.

  18. Dedicated heterogeneous node scheduling including backfill scheduling

    DOEpatents

    Wood, Robert R.; Eckert, Philip D.; Hommes, Gregg

    2006-07-25

    A method and system for job backfill scheduling dedicated heterogeneous nodes in a multi-node computing environment. Heterogeneous nodes are grouped into homogeneous node sub-pools. For each sub-pool, a free node schedule (FNS) is created so that the number of to chart the free nodes over time. For each prioritized job, using the FNS of sub-pools having nodes useable by a particular job, to determine the earliest time range (ETR) capable of running the job. Once determined for a particular job, scheduling the job to run in that ETR. If the ETR determined for a lower priority job (LPJ) has a start time earlier than a higher priority job (HPJ), then the LPJ is scheduled in that ETR if it would not disturb the anticipated start times of any HPJ previously scheduled for a future time. Thus, efficient utilization and throughput of such computing environments may be increased by utilizing resources otherwise remaining idle.

  19. MICROSITE AND HERBACEOUS VEGETATION HETEROGENEITY AFTER BURNING ARTEMISIA TRIDENTATA STEPPE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Woody vegetation can create distinct subcanopy and interspace microsites, which often results in resource islands in subcanopies compared to interspaces. This heterogeneity in soil resources contributes to herbaceous vegetation heterogeneity in plant communities. However, information detailing the...

  20. Genetic Manipulation of Outer Membrane Permeability: Generating Porous Heterogeneous Catalyst Analogs in Escherichia coli

    SciTech Connect

    Patel, TN; Park, AHA; Bantat, S

    2014-12-01

    The limited permeability of the E. coli outer membrane can significantly hinder whole-cell biocatalyst performance. In this study, the SARS coronavirus small envelope protein (SCVE) was expressed in E. coli cells previously engineered for periplasmic expression of carbonic anhydrase (CA) activity. This maneuver increased small molecule uptake by the cells, resulting in increased apparent CA activity of the biocatalysts. The enhancements in activity were quantified using methods developed for traditional heterogeneous catalysis. The expression of the SCVE protein was found to significantly reduce the Thiele moduli (phi), as well as increase the effectiveness factors (eta), effective diffusivities (D-e), and permeabilities (P) of the biocatalysts. These catalytic improvements translated into superior performance of the biocatalysts for the precipitation of calcium carbonate from solution which is an attractive strategy for long-term sequestration of captured carbon dioxide. Overall, these results demonstrate that synthetic biology approaches can be used to enhance heterogeneous catalysts incorporated into microbial whole-cell scaffolds.

  1. Heterogeneity Effects in Plutonium Contaminated Soil

    DTIC Science & Technology

    2009-03-01

    lodged in the lung, a partition coefficient specific to the BOMARC missile site contamination might be developed. The question of long-term...activity heterogeneity using dual counting methods with gamma spectroscopy using a hyper pure germanium (HpGe) counter. Each sample was partitioned ... partition off onto bone surfaces and to the liver with the remaining fraction distributing to other tissues in the body (Cember, 1996). As the routes of

  2. Evolution of altruistic punishment in heterogeneous populations.

    PubMed

    de Weerd, Harmen; Verbrugge, Rineke

    2011-12-07

    Evolutionary models for altruistic behavior typically make the assumption of homogeneity: each individual has the same costs and benefits associated with cooperating with each other and punishing for selfish behavior. In this paper, we relax this assumption by separating the population into heterogeneous classes, such that individuals from different classes differ in their ability to punish for selfishness. We compare the effects of introducing heterogeneity this way across two population models, that each represents a different type of population: the infinite and well-mixed population describes the way workers of social insects such as ants are organized, while a spatially structured population is more related to the way social norms evolve and are maintained in a social network. We find that heterogeneity in the effectiveness of punishment by itself has little to no effect on whether or not altruistic behavior will stabilize in a population. In contrast, heterogeneity in the cost that individuals pay to punish for selfish behavior allows altruistic behavior to be maintained more easily. Fewer punishers are needed to deter selfish behavior, and the individuals that punish will mostly belong to the class that pays a lower cost to do so. This effect is amplified when individuals that pay a lower cost for punishing inflict a higher punishment. The two population models differ when individuals that pay a low cost for punishing also inflict a lower punishment. In this situation, altruistic behavior becomes harder to maintain in an infinite and well-mixed population. However, this effect does not occur when the population is spatially structured.

  3. Heterogeneous photocatalytic oxidation of atmospheric trace contaminants

    NASA Technical Reports Server (NTRS)

    Ollis, David F.; Peral, Jose

    1992-01-01

    A two year study to examine the feasibility of using heterogeneous photocatalysis for spacecraft air purification was begun at North Carolina State University on November 1, 1990. The original grant proposal included examination of the rates of destruction of anticipated spacecraft-generated air contaminants, including alcohols, aldehydes, chlorinated compounds, as well as trace levels of volatile compounds containing nitrogen, sulfur, and silicon. The progress made in the second six month period of 5/1/91-11/1/91 is discussed.

  4. Method of assessing heterogeneity in images

    SciTech Connect

    Jacob, Richard E.; Carson, James P.

    2016-08-23

    A method of assessing heterogeneity in images is disclosed. 3D images of an object are acquired. The acquired images may be filtered and masked. Iterative decomposition is performed on the masked images to obtain image subdivisions that are relatively homogeneous. Comparative analysis, such as variogram analysis or correlogram analysis, is performed of the decomposed images to determine spatial relationships between regions of the images that are relatively homogeneous.

  5. Phenotype heterogeneity in cancer cell populations

    NASA Astrophysics Data System (ADS)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-06-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as "bet hedging" of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  6. Evidence for surface heterogeneity on Titan

    NASA Astrophysics Data System (ADS)

    Griffith, C. A.

    1993-08-01

    Observational results are presented for two rotational periods of Titan which exhibit the albedo difference noted by Lemmon et al. (1993) between this moon's positions at eastern and western elongation relative to Saturn. The persistence of this difference indicates that this heterogeneity is unlikely to be associated with transient features, and must be intrinsic to the surface. The results presented also indicate that Titan is locked in a synchronous orbit around Saturn.

  7. A 1998 Workshop on Heterogeneous Computing

    DTIC Science & Technology

    2007-11-02

    Servers: A small number of nodes read and store simulation data, forwarding it to the SAF- Sim nodes through SPP messages. Routers: The movement of data...NetSolve: A Network-Enabled Solver; Examples and Users 19 H. Casanova and J.J. Dongarra Implementing Distributed Synthetic Forces Simulations in...Heuristic, and Simulation Study for a Basic Data Staging Problem in a Heterogeneous Networking Environment 115 M. Tan, M.D. Theys, H.J. Siegel, N.B. Beck

  8. Heterogeneous processes: Laboratory, field, and modeling studies

    NASA Technical Reports Server (NTRS)

    Poole, Lamont R.; Kurylo, Michael J.; Jones, Rod L.; Wahner, Andreas; Calvert, Jack G.; Leu, M.-T.; Fried, A.; Molina, Mario J.; Hampson, Robert F.; Pitts, M. C.

    1991-01-01

    The efficiencies of chemical families such as ClO(x) and NO(x) for altering the total abundance and distribution of stratospheric ozone are controlled by a partitioning between reactive (active) and nonreactive (reservoir) compounds within each family. Gas phase thermodynamics, photochemistry, and kinetics would dictate, for example, that only about 1 percent of the chlorine resident in the lower stratosphere would be in the form of active Cl or ClO, the remainder existing in the reservoir compounds HCl and ClONO2. The consistency of this picture was recently challenged by the recognition that important chemical transformations take place on polar regions: the Airborne Antarctic Ozone Experiment (AAOE) and the Airborne Arctic Stratospheric Expedition (AASA). Following the discovery of the Antarctic ozone hole, Solomon et al. suggested that the heterogeneous chemical reaction: ClONO2(g)+HCl(s) yields Cl2(g)+HNO3(s) could play a key role in converting chlorine from inactive forms into a species (Cl2) that would rapidly dissociate in sunlight to liberate atomic chlorine and initiate ozone depletion. The symbols (s) and (g) denote solid phase, or adsorbed onto a solid surface, and gas phase, respectively, and represent the approach by which such a reaction is modeled rather than the microscopic details of the reaction. The reaction was expected to be most important at altitudes where PSC's were most prevalent (10 to 25 km), thereby extending the altitude range over which chlorine compounds can efficiently destroy ozone from the 35 to 45 km region (where concentrations of active chlorine are usually highest) to lower altitudes where the ozone concentration is at its peak. This chapter will briefly review the current state of knowledge of heterogeneous processes in the stratosphere, emphasizing those results obtained since the World Meteorological Organization (WMO) conference. Sections are included on laboratory investigations of heterogeneous reactions, the

  9. Coordinated Deployment of Multiple, Heterogeneous Robots

    DTIC Science & Technology

    2000-01-01

    Coordinated Deployment of Multiple, Heterogeneous Robots Reid Simmons1, David Apfelbaum1, Dieter Fox1, Robert P. Goldman2, Karen Zita Haigh2, David J...Drive Pittsburgh PA 15213 Minneapolis MN 55418 Abstract To be truly useful, mobile robots need to be fairly autonomous and easy to control. This is...especially true in situations where multiple robots are used, due to the increase in sensory information and the fact that the robots can interfere with

  10. Cluster formation in a heterogeneous metapopulation model.

    PubMed

    Silva, Jacques A L

    2016-05-01

    A spatially explicit heterogeneous metapopulation model with two different patch types is analyzed. Some network topologies support a partially synchronized dynamics, a state where two different clusters of patches are formed. Within each cluster the dynamics of all patches are synchronized. The linearized asymptotic stability of the partially synchronized attractor is studied. The transversal stability is analyzed and a simple expression for the transversal Lyapunov number of partially synchronized attractors is obtained.

  11. Statistical methods for studying disease subtype heterogeneity.

    PubMed

    Wang, Molin; Spiegelman, Donna; Kuchiba, Aya; Lochhead, Paul; Kim, Sehee; Chan, Andrew T; Poole, Elizabeth M; Tamimi, Rulla; Tworoger, Shelley S; Giovannucci, Edward; Rosner, Bernard; Ogino, Shuji

    2016-02-28

    A fundamental goal of epidemiologic research is to investigate the relationship between exposures and disease risk. Cases of the disease are often considered a single outcome and assumed to share a common etiology. However, evidence indicates that many human diseases arise and evolve through a range of heterogeneous molecular pathologic processes, influenced by diverse exposures. Pathogenic heterogeneity has been considered in various neoplasms such as colorectal, lung, prostate, and breast cancers, leukemia and lymphoma, and non-neoplastic diseases, including obesity, type II diabetes, glaucoma, stroke, cardiovascular disease, autism, and autoimmune disease. In this article, we discuss analytic options for studying disease subtype heterogeneity, emphasizing methods for evaluating whether the association of a potential risk factor with disease varies by disease subtype. Methods are described for scenarios where disease subtypes are categorical and ordinal and for cohort studies, matched and unmatched case-control studies, and case-case study designs. For illustration, we apply the methods to a molecular pathological epidemiology study of alcohol intake and colon cancer risk by tumor LINE-1 methylation subtypes. User-friendly software to implement the methods is publicly available.

  12. Genetic heterogeneity of familial hemiplegic migraine

    SciTech Connect

    Joutel, A.; Ducros, A.; Delrieu, O.; Maziaceck, J.; Tournier-Lasserve, E.; Vahedi, K. |; Bousser, M.G.; Ponsot, G.; Gouttiere, F.; Labauge, P.; Mancini, J.

    1994-12-01

    Familial hemiplegic migraine (FHM) is an autosomal dominant variety of migraine with aura. We previously mapped a gene for this disorder to the short arm of chromosome 19, within a 30-cM interval bracketed by D19S216 and D19S215. Linkage analysis conducted on two large pedigrees did not show any evidence of heterogeneity, despite their clinical differences due to the presence, in one family, of cerebellar ataxia and nystagmus. Herein we report linkage data on seven additional FHM families including another one with cerebellar ataxia. Analysis was conducted with a set of seven markers spanning the D19S216-D19S215 interval. Two-point and multipoint strong evidence for genetic heterogeneity. Strong evidence of linkage was obtained in two families and of absence of linkage in four families. The posterior probability of being of the linked type was >.95 in the first two families and <.01 in four other ones. It was not possible to draw any firm conclusion for the last family. Thus, within the nine families so far tested, four were linked, including those with associated cerebellar ataxia. We could not find any clinical difference between the pure FHM families regardless of whether they were linked. In addition to the demonstration of genetic heterogeneity of FHM, this study also allowed us to establish that the most likely location of the gene was within an interval of 12 cM between D19S413 and D19S226.

  13. Measuring statistical heterogeneity: The Pietra index

    NASA Astrophysics Data System (ADS)

    Eliazar, Iddo I.; Sokolov, Igor M.

    2010-01-01

    There are various ways of quantifying the statistical heterogeneity of a given probability law: Statistics uses variance - which measures the law’s dispersion around its mean; Physics and Information Theory use entropy - which measures the law’s randomness; Economics uses the Gini index - which measures the law’s egalitarianism. In this research we explore an alternative to the Gini index-the Pietra index-which is a counterpart of the Kolmogorov-Smirnov statistic. The Pietra index is shown to be a natural and elemental measure of statistical heterogeneity, which is especially useful in the case of asymmetric and skewed probability laws, and in the case of asymptotically Paretian laws with finite mean and infinite variance. Moreover, the Pietra index is shown to have immediate and fundamental interpretations within the following applications: renewal processes and continuous time random walks; infinite-server queueing systems and shot noise processes; financial derivatives. The interpretation of the Pietra index within the context of financial derivatives implies that derivative markets, in effect, use the Pietra index as their benchmark measure of statistical heterogeneity.

  14. Bridge monitoring using heterogeneous wireless sensor network

    NASA Astrophysics Data System (ADS)

    Haran, Shivan; Kher, Shubhalaxmi; Mehndiratta, Vandana

    2010-03-01

    Wireless sensor networks (WSN) are proving to be a good fit where real time monitoring of multiple physical parameters is required. In many applications such as structural health monitoring, patient data monitoring, traffic accident monitoring and analysis, sensor networks may involve interface with conventional P2P systems and it is challenging to handle heterogeneous network systems. Heterogeneous deployments will become increasingly prevalent as it allows for systems to seamlessly integrate and interoperate especially when it comes to applications involving monitoring of large infrastructures. Such networks may have wireless sensor network overlaid on a conventional computer network to pick up data from one distant location and carry out the analysis after relaying it over to another distant location. This paper discusses monitoring of bridges using WSN. As a test bed, a heterogeneous network of WSN and conventional P2P together with a combination of sensing devices (including vibration and strain) is to be used on a bridge model. Issues related to condition assessment of the bridge for situations including faults, overloads, etc., as well as analysis of network and system performance will be discussed. When conducted under controlled conditions, this is an important step towards fine tuning the monitoring system for recommendation of permanent mounting of sensors and collecting data that can help in the development of new methods for inspection and evaluation of bridges. The proposed model, design, and issues therein will be discussed, along with its implementation and results.

  15. Site occupancy models with heterogeneous detection probabilities

    USGS Publications Warehouse

    Royle, J. Andrew

    2006-01-01

    Models for estimating the probability of occurrence of a species in the presence of imperfect detection are important in many ecological disciplines. In these ?site occupancy? models, the possibility of heterogeneity in detection probabilities among sites must be considered because variation in abundance (and other factors) among sampled sites induces variation in detection probability (p). In this article, I develop occurrence probability models that allow for heterogeneous detection probabilities by considering several common classes of mixture distributions for p. For any mixing distribution, the likelihood has the general form of a zero-inflated binomial mixture for which inference based upon integrated likelihood is straightforward. A recent paper by Link (2003, Biometrics 59, 1123?1130) demonstrates that in closed population models used for estimating population size, different classes of mixture distributions are indistinguishable from data, yet can produce very different inferences about population size. I demonstrate that this problem can also arise in models for estimating site occupancy in the presence of heterogeneous detection probabilities. The implications of this are discussed in the context of an application to avian survey data and the development of animal monitoring programs.

  16. Assessing local outcomes in heterogeneous gliomas

    NASA Astrophysics Data System (ADS)

    Dowson, Nicholas; Thomas, Paul; Gal, Yaniv; Fay, Michael; Jeffree, Rosalind L.; Winter, Craig; Coulthard, Alan; Smith, Jye; Bourgeat, Pierrick; Salvado, Olivier; Crozier, Stuart; Rose, Stephen

    2014-03-01

    Tumours are known to be heterogeneous, yet typical treatment plans consider them as a single unit. This may influence treatment outcomes. However, treatment cannot be customised to intra-tumour variation without a method to establish outcomes at an intra-tumour scale. This work proposes a method to both assess and measure outcomes locally within tumours. Methods: Four patients were scanned at two post-surgery time points using contrast enhanced MRI and 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) PET. The shell of active tumour tissue is divided into a set of small subregions at both time points. Local outcome is measured from changes in subregion volume over time. The utility of the proposed approach is evaluated by measuring the correlation between PET uptake and documented growth. Correlation with overall survival time was also examined. Results: Local outcomes were heterogeneous and evidence of a positive correlation between local 18F-DOPA uptake and local progression was observed. Conclusions: Given that intra-tumour outcomes are heterogeneous the consistently positive correlation between FDOPA uptake and progression, local analysis of tumours could prove useful for treatment planning.

  17. Soil Porous Structure as Heterogeneous Networks

    NASA Astrophysics Data System (ADS)

    Cárdenas, J. P.; Santiago, A.; Losada, J. C.; Borondo, F.; Benito, R. M.

    2010-05-01

    In this paper we present an application of the Complex Network theory to Geosciences. In particular, we show the implementation of the Heterogeneous Preferential Attachment (HPA) model [1] as a new way to quantify the structure of porous soils and closer relate them with soil texture. In the HPA model, already introduced in this context [2], pores are considered as nodes and their properties, such as position and size, are described by fixed states in a metric space. An affinity function is introduced in the HPA soil model in order to bias the attachment probabilities of links between pores according to their properties and soil texture. We perform an analytical study of the connectivity distributions of pores, P(k), and develop a numerical analysis for the HPA soil model considering a combination of parameters corresponding to eleven empirical soil samples with different physical properties and five different textures. [1] A. Santiago and R. M. Benito, An extended formalism for preferential attachment in heterogeneous complex networks, Europhysics Letters, 82 (2008) 58004. [2] A. Santiago, J.P. Cárdenas, J.C. Losada, R.M. Benito, A.M. Tarquis and F. Borondo, Multiscaling of porous soils as heterogeneous complex networks, Nonlinear Processes in Geophysics, 15 (2008) 893-902.

  18. {sup 48}Ca HETEROGENEITY IN DIFFERENTIATED METEORITES

    SciTech Connect

    Chen, Hsin-Wei; Lee, Typhoon; Lee, Der-Chuen; Shen, Jason Jiun-San; Chen, Jiang-Chang

    2011-12-10

    Isotopic heterogeneities of {sup 48}Ca have been found in numerous bulk meteorites that are correlated with {sup 50}Ti and {sup 54}Cr anomalies among differentiated planetary bodies, and the results suggest that a rare subset of neutron-rich Type Ia supernova (nSN Ia) was responsible for contributing these neutron-rich iron-group isotopes into the solar system (SS). The heterogeneity of these isotopes found in differentiated meteorites indicates that the isotopic compositions of the bulk SS are not uniform, and there are significant amounts of nSNe Ia dust incompletely mixed with the rest of SS materials during planetary formation. Combined with the data of now-extinct short-lived nuclide {sup 60}Fe, which can be produced more efficiently from an nSN Ia than a Type II supernova ejecta, the observed planetary-scale isotopic heterogeneity probably reflects a late input of stellar dust grains with neutron-rich nuclear statistical equilibrium nuclides into the early SS.

  19. Altering Emulsion Stability with Heterogeneous Surface Wettability

    PubMed Central

    Meng, Qiang; Zhang, Yali; Li, Jiang; Lammertink, Rob G. H.; Chen, Haosheng; Tsai, Peichun Amy

    2016-01-01

    Emulsions–liquid droplets dispersed in another immiscible liquid–are widely used in a broad spectrum of applications, including food, personal care, agrochemical, and pharmaceutical products. Emulsions are also commonly present in natural crude oil, hampering the production and quality of petroleum fuels. The stability of emulsions plays a crucial role in their applications, but controlling the stability without external driving forces has been proven to be difficult. Here we show how heterogeneous surface wettability can alter the stability and dynamics of oil-in-water emulsions, generated by a co-flow microfluidic device. We designed a useful methodology that can modify a micro-capillary of desired heterogeneous wettability (e.g., alternating hydrophilic and hydrophobic regions) without changing the hydraulic diameter. We subsequently investigated the effects of flow rates and heterogeneous wettability on the emulsion morphology and motion. The experimental data revealed a universal critical timescale of advective emulsions, above which the microfluidic emulsions remain stable and intact, whereas below they become adhesive or inverse. A simple theoretical model based on a force balance can be used to explain this critical transition of emulsion dynamics, depending on the droplet size and the Capillary number–the ratio of viscous to surface effects. These results give insight into how to control the stability and dynamics of emulsions in microfluidics with flow velocity and different wettability. PMID:27256703

  20. Heterogeneity of the Pancreatic Beta Cell

    PubMed Central

    Gutierrez, Giselle Dominguez; Gromada, Jesper; Sussel, Lori

    2017-01-01

    The pancreatic beta cell functions as a key regulator of blood glucose levels by integrating a variety of signals in response to changing metabolic demands. Variations in beta cell identity that translate into functionally different subpopulations represent an interesting mechanism to allow beta cells to efficiently respond to diverse physiological and pathophysiological conditions. Recently, there is emerging evidence that morphological and functional differences between beta cells exist. Furthermore, the ability of novel single cell technologies to characterize the molecular identity of individual beta cells has created a new era in the beta cell field. These studies are providing important novel information about the origin of beta cell heterogeneity, the type and proportions of the different beta cell subpopulations, as well as their intrinsic properties. Furthermore, characterization of different beta cell subpopulations that could variably offer protection from or drive progression of diabetes has important clinical implications in diabetes prevention, beta cell regeneration and stem cell treatments. In this review, we will assess the evidence that supports the existence of heterogeneous populations of beta cells and the factors that could influence their formation. We will also address novel studies using islet single cell analysis that have provided important information toward understanding beta cell heterogeneity and discuss the caveats that may be associated with these new technologies. PMID:28321233

  1. Heterogeneous nanofluids: natural convection heat transfer enhancement

    PubMed Central

    2011-01-01

    Convective heat transfer using different nanofluid types is investigated. The domain is differentially heated and nanofluids are treated as heterogeneous mixtures with weak solutal diffusivity and possible Soret separation. Owing to the pronounced Soret effect of these materials in combination with a considerable solutal expansion, the resulting solutal buoyancy forces could be significant and interact with the initial thermal convection. A modified formulation taking into account the thermal conductivity, viscosity versus nanofluids type and concentration and the spatial heterogeneous concentration induced by the Soret effect is presented. The obtained results, by solving numerically the full governing equations, are found to be in good agreement with the developed solution based on the scale analysis approach. The resulting convective flows are found to be dependent on the local particle concentration φ and the corresponding solutal to thermal buoyancy ratio N. The induced nanofluid heterogeneity showed a significant heat transfer modification. The heat transfer in natural convection increases with nanoparticle concentration but remains less than the enhancement previously underlined in forced convection case. PMID:21711755

  2. Soft random solids and their heterogeneous elasticity

    NASA Astrophysics Data System (ADS)

    Mao, Xiaoming; Goldbart, Paul M.; Xing, Xiangjun; Zippelius, Annette

    2009-09-01

    Spatial heterogeneity in the elastic properties of soft random solids is examined via vulcanization theory. The spatial heterogeneity in the structure of soft random solids is a result of the fluctuations locked-in at their synthesis, which also brings heterogeneity in their elastic properties. Vulcanization theory studies semimicroscopic models of random-solid-forming systems and applies replica field theory to deal with their quenched disorder and thermal fluctuations. The elastic deformations of soft random solids are argued to be described by the Goldstone sector of fluctuations contained in vulcanization theory, associated with a subtle form of spontaneous symmetry breaking that is associated with the liquid-to-random-solid transition. The resulting free energy of this Goldstone sector can be reinterpreted as arising from a phenomenological description of an elastic medium with quenched disorder. Through this comparison, we arrive at the statistics of the quenched disorder of the elasticity of soft random solids in terms of residual stress and Lamé-coefficient fields. In particular, there are large residual stresses in the equilibrium reference state, and the disorder correlators involving the residual stress are found to be long ranged and governed by a universal parameter that also gives the mean shear modulus.

  3. Soft random solids and their heterogeneous elasticity.

    PubMed

    Mao, Xiaoming; Goldbart, Paul M; Xing, Xiangjun; Zippelius, Annette

    2009-09-01

    Spatial heterogeneity in the elastic properties of soft random solids is examined via vulcanization theory. The spatial heterogeneity in the structure of soft random solids is a result of the fluctuations locked-in at their synthesis, which also brings heterogeneity in their elastic properties. Vulcanization theory studies semimicroscopic models of random-solid-forming systems and applies replica field theory to deal with their quenched disorder and thermal fluctuations. The elastic deformations of soft random solids are argued to be described by the Goldstone sector of fluctuations contained in vulcanization theory, associated with a subtle form of spontaneous symmetry breaking that is associated with the liquid-to-random-solid transition. The resulting free energy of this Goldstone sector can be reinterpreted as arising from a phenomenological description of an elastic medium with quenched disorder. Through this comparison, we arrive at the statistics of the quenched disorder of the elasticity of soft random solids in terms of residual stress and Lamé-coefficient fields. In particular, there are large residual stresses in the equilibrium reference state, and the disorder correlators involving the residual stress are found to be long ranged and governed by a universal parameter that also gives the mean shear modulus.

  4. Altering Emulsion Stability with Heterogeneous Surface Wettability

    NASA Astrophysics Data System (ADS)

    Meng, Qiang; Zhang, Yali; Li, Jiang; Lammertink, Rob G. H.; Chen, Haosheng; Tsai, Peichun Amy

    2016-06-01

    Emulsions–liquid droplets dispersed in another immiscible liquid–are widely used in a broad spectrum of applications, including food, personal care, agrochemical, and pharmaceutical products. Emulsions are also commonly present in natural crude oil, hampering the production and quality of petroleum fuels. The stability of emulsions plays a crucial role in their applications, but controlling the stability without external driving forces has been proven to be difficult. Here we show how heterogeneous surface wettability can alter the stability and dynamics of oil-in-water emulsions, generated by a co-flow microfluidic device. We designed a useful methodology that can modify a micro-capillary of desired heterogeneous wettability (e.g., alternating hydrophilic and hydrophobic regions) without changing the hydraulic diameter. We subsequently investigated the effects of flow rates and heterogeneous wettability on the emulsion morphology and motion. The experimental data revealed a universal critical timescale of advective emulsions, above which the microfluidic emulsions remain stable and intact, whereas below they become adhesive or inverse. A simple theoretical model based on a force balance can be used to explain this critical transition of emulsion dynamics, depending on the droplet size and the Capillary number–the ratio of viscous to surface effects. These results give insight into how to control the stability and dynamics of emulsions in microfluidics with flow velocity and different wettability.

  5. Genetic Heterogeneity in Algerian Human Populations

    PubMed Central

    Deba, Tahria; Calafell, Francesc; Benhamamouch, Soraya; Comas, David

    2015-01-01

    The demographic history of human populations in North Africa has been characterized by complex processes of admixture and isolation that have modeled its current gene pool. Diverse genetic ancestral components with different origins (autochthonous, European, Middle Eastern, and sub-Saharan) and genetic heterogeneity in the region have been described. In this complex genetic landscape, Algeria, the largest country in Africa, has been poorly covered, with most of the studies using a single Algerian sample. In order to evaluate the genetic heterogeneity of Algeria, Y-chromosome, mtDNA and autosomal genome-wide makers have been analyzed in several Berber- and Arab-speaking groups. Our results show that the genetic heterogeneity found in Algeria is not correlated with geography or linguistics, challenging the idea of Berber groups being genetically isolated and Arab groups open to gene flow. In addition, we have found that external sources of gene flow into North Africa have been carried more often by females than males, while the North African autochthonous component is more frequent in paternally transmitted genome regions. Our results highlight the different demographic history revealed by different markers and urge to be cautious when deriving general conclusions from partial genomic information or from single samples as representatives of the total population of a region. PMID:26402429

  6. Coordinating the Design and Management of Heterogeneous Datacenter Resources

    ERIC Educational Resources Information Center

    Guevara, Marisabel

    2014-01-01

    Heterogeneous design presents an opportunity to improve energy efficiency but raises a challenge in management. Whereas prior work separates the two, we coordinate heterogeneous design and management. We present a market-based resource allocation mechanism that navigates the performance and power trade-offs of heterogeneous architectures. Given…

  7. Effects of Population Heterogeneity on Accuracy of DIF Detection

    ERIC Educational Resources Information Center

    Oliveri, María Elena; Ercikan, Kadriye; Zumbo, Bruno D.

    2014-01-01

    Heterogeneity within English language learners (ELLs) groups has been documented. Previous research on differential item functioning (DIF) analyses suggests that accurate DIF detection rates are reduced greatly when groups are heterogeneous. In this simulation study, we investigated the effects of heterogeneity within linguistic (ELL) groups on…

  8. Small Regulatory RNA-Induced Growth Rate Heterogeneity of Bacillus subtilis

    PubMed Central

    Mars, Ruben A. T.; Nicolas, Pierre; Ciccolini, Mariano; Reilman, Ewoud; Reder, Alexander; Schaffer, Marc; Mäder, Ulrike; Völker, Uwe; van Dijl, Jan Maarten; Denham, Emma L.

    2015-01-01

    Isogenic bacterial populations can consist of cells displaying heterogeneous physiological traits. Small regulatory RNAs (sRNAs) could affect this heterogeneity since they act by fine-tuning mRNA or protein levels to coordinate the appropriate cellular behavior. Here we show that the sRNA RnaC/S1022 from the Gram-positive bacterium Bacillus subtilis can suppress exponential growth by modulation of the transcriptional regulator AbrB. Specifically, the post-transcriptional abrB-RnaC/S1022 interaction allows B. subtilis to increase the cell-to-cell variation in AbrB protein levels, despite strong negative autoregulation of the abrB promoter. This behavior is consistent with existing mathematical models of sRNA action, thus suggesting that induction of protein expression noise could be a new general aspect of sRNA regulation. Importantly, we show that the sRNA-induced diversity in AbrB levels generates heterogeneity in growth rates during the exponential growth phase. Based on these findings, we hypothesize that the resulting subpopulations of fast- and slow-growing B. subtilis cells reflect a bet-hedging strategy for enhanced survival of unfavorable conditions. PMID:25790031

  9. Small regulatory RNA-induced growth rate heterogeneity of Bacillus subtilis.

    PubMed

    Mars, Ruben A T; Nicolas, Pierre; Ciccolini, Mariano; Reilman, Ewoud; Reder, Alexander; Schaffer, Marc; Mäder, Ulrike; Völker, Uwe; van Dijl, Jan Maarten; Denham, Emma L

    2015-03-01

    Isogenic bacterial populations can consist of cells displaying heterogeneous physiological traits. Small regulatory RNAs (sRNAs) could affect this heterogeneity since they act by fine-tuning mRNA or protein levels to coordinate the appropriate cellular behavior. Here we show that the sRNA RnaC/S1022 from the Gram-positive bacterium Bacillus subtilis can suppress exponential growth by modulation of the transcriptional regulator AbrB. Specifically, the post-transcriptional abrB-RnaC/S1022 interaction allows B. subtilis to increase the cell-to-cell variation in AbrB protein levels, despite strong negative autoregulation of the abrB promoter. This behavior is consistent with existing mathematical models of sRNA action, thus suggesting that induction of protein expression noise could be a new general aspect of sRNA regulation. Importantly, we show that the sRNA-induced diversity in AbrB levels generates heterogeneity in growth rates during the exponential growth phase. Based on these findings, we hypothesize that the resulting subpopulations of fast- and slow-growing B. subtilis cells reflect a bet-hedging strategy for enhanced survival of unfavorable conditions.

  10. Examining the Heterogeneous Genome Content of Multipartite Viruses BMV and CCMV by Native Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    van de Waterbeemd, Michiel; Snijder, Joost; Tsvetkova, Irina B.; Dragnea, Bogdan G.; Cornelissen, Jeroen J.; Heck, Albert J. R.

    2016-06-01

    Since the concept was first introduced by Brian Chait and co-workers in 1991, mass spectrometry of proteins and protein complexes under non-denaturing conditions (native MS) has strongly developed, through parallel advances in instrumentation, sample preparation, and data analysis tools. However, the success rate of native MS analysis, particularly in heterogeneous mega-Dalton (MDa) protein complexes, still strongly depends on careful instrument modification. Here, we further explore these boundaries in native mass spectrometry, analyzing two related endogenous multipartite viruses: the Brome Mosaic Virus (BMV) and the Cowpea Chlorotic Mottle Virus (CCMV). Both CCMV and BMV are approximately 4.6 megadalton (MDa) in mass, of which approximately 1 MDA originates from the genomic content of the virion. Both viruses are produced as mixtures of three particles carrying different segments of the genome, varying by approximately 0.1 MDA in mass (~2%). This mixture of particles poses a challenging analytical problem for high-resolution native MS analysis, given the large mass scales involved. We attempt to unravel the particle heterogeneity using both Q-TOF and Orbitrap mass spectrometers extensively modified for analysis of very large assemblies. We show that manipulation of the charging behavior can provide assistance in assigning the correct charge states. Despite their challenging size and heterogeneity, we obtained native mass spectra with resolved series of charge states for both BMV and CCMV, demonstrating that native MS of endogenous multipartite virions is feasible.

  11. Fluorescence quenching in proteins: some applications to protein-DNA and protein-lipid interactions

    NASA Astrophysics Data System (ADS)

    Knutson, Jay R.; Chen, Raymond F.; Porter, D. K.; Hensley, Preston; Han, Myun K.; Kim, S. J.; Wilson, Samuel H.; Clague, M.; Williamson, Cynthia K.

    1992-04-01

    The authors outline some examples of the advantages found in subdividing overall quenching into heterogeneous contributions. Subdivision is accomplished by overdetermination (global) and association (DAS, decay associated spectral) methods. In some cases, the subdivision of fluorescence leads to the unique identification of different fluorophores in different sites. Alternatively, the recovered components may reflect conformational heterogeneity at each site. For intrinsic protein fluorescence, it is often noted in the literature that single Trp proteins may be multiexponential. Genetic substitution in multi-Trp proteins, however, often leads to very strong (if not complete) lifetime-to-Trp assignment. Even if a single Trp experiences two or more microenvironments, it can be a useful reporter. The linkage of multiple lifetimes and amplitudes to changes in global conformation often reveals a more `sensitive' subpopulation or lifetime component that becomes a better indicator for important conformational states than aggregate intensity can provide. This has proven useful in studying pH transitions of proteins both in solution and embedded in membranes. Energy transfer is particularly useful in differentiating sites at different distances. Further, the disclosure of heterogeneity in distance is clearly superior to the reporting of a mean distance. This report surveys several systems that have been examined via emission DAS techniques, showing how each protein is better understood when viewed in terms of discrete spectral contributions. We conclude with an overview and some details about our construction of an EDAS (excitation-DAS) instrument; i.e., how excitation scans can be incorporated into a time-resolved instrument.

  12. Increasing silk fibre strength through heterogeneity of bundled fibrils

    PubMed Central

    Cranford, Steven W.

    2013-01-01

    Can naturally arising disorder in biological materials be beneficial? Materials scientists are continuously attempting to replicate the exemplary performance of materials such as spider silk, with detailed techniques and assembly procedures. At the same time, a spider does not precisely machine silk—imaging indicates that its fibrils are heterogeneous and irregular in cross section. While past investigations either focused on the building material (e.g. the molecular scale protein sequence and behaviour) or on the ultimate structural component (e.g. silk threads and spider webs), the bundled structure of fibrils that compose spider threads has been frequently overlooked. Herein, I exploit a molecular dynamics-based coarse-grain model to construct a fully three-dimensional fibril bundle, with a length on the order of micrometres. I probe the mechanical behaviour of bundled silk fibrils with variable density of heterogenic protrusions or globules, ranging from ideally homogeneous to a saturated distribution. Subject to stretching, the model indicates that cooperativity is enhanced by contact through low-force deformation and shear ‘locking’ between globules, increasing shear stress transfer by up to 200 per cent. In effect, introduction of a random and disordered structure can serve to improve mechanical performance. Moreover, addition of globules allows a tuning of free volume, and thus the wettability of silk (with implications for supercontraction). These findings support the ability of silk to maintain near-molecular-level strength at the scale of silk threads, and the mechanism could be easily adopted as a strategy for synthetic fibres. PMID:23486175

  13. Heterogeneity of link weight and the evolution of cooperation

    NASA Astrophysics Data System (ADS)

    Iwata, Manabu; Akiyama, Eizo

    2016-04-01

    In this paper, we investigate the effect of heterogeneity of link weight, heterogeneity of the frequency or amount of interactions among individuals, on the evolution of cooperation. Based on an analysis of the evolutionary prisoner's dilemma game on a weighted one-dimensional lattice network with intra-individual heterogeneity, we confirm that moderate level of link-weight heterogeneity can facilitate cooperation. Furthermore, we identify two key mechanisms by which link-weight heterogeneity promotes the evolution of cooperation: mechanisms for spread and maintenance of cooperation. We also derive the corresponding conditions under which the mechanisms can work through evolutionary dynamics.

  14. Heterogeneity in pineapple fruit quality results from plant heterogeneity at flower induction

    PubMed Central

    Fassinou Hotegni, V. Nicodème; Lommen, Willemien J. M.; Agbossou, Euloge K.; Struik, Paul C.

    2014-01-01

    Heterogeneity in fruit quality constitutes a major constraint in agri-food chains. In this paper the sources of the heterogeneity in pineapple in the field were studied in four experiments in commercial pineapple fields. The aims were to determine (a) whether differences in pineapple fruit quality among individual fruits are associated with differences in vigor of the individual plants within the crop at the time of artificial flower induction; and (b) whether the side shoots produced by the plant during the generative phase account for the fruit quality heterogeneity. Two pineapple cultivars were considered: cv. Sugarloaf and cv. Smooth Cayenne. Plant vigor at the time of artificial flower induction was measured by three variates: the number of functional leaves, the D-leaf length and their cross product. Fruit quality attributes measured at harvest time included external attributes (weight and height of fruit, infructescence and crown) and internal quality attributes [total soluble solids (TSS), pH, translucent flesh]. Results showed that the heterogeneity in fruit weight was a consequence of the heterogeneity in vigor of the plants at the moment of flower induction; that effect was mainly on the infructescence weight and less or not on the crown weight. The associations between plant vigor variates at flower induction and the internal quality attributes of the fruit were poor and/or not consistent across experiments. The weight of the slips (side shoots) explained part of the heterogeneity in fruit weight, infructescence weight and fruit height in cv. Sugarloaf. Possibilities for reducing the variation in fruit quality by precise cultural practices are discussed. PMID:25538714

  15. DNA Methylation Heterogeneity Patterns in Breast Cancer Cell Lines

    PubMed Central

    Tian, Sunny; Bertelsmann, Karina; Yu, Linda; Sun, Shuying

    2016-01-01

    Heterogeneous DNA methylation patterns are linked to tumor growth. In order to study DNA methylation heterogeneity patterns for breast cancer cell lines, we comparatively study four metrics: variance, I2 statistic, entropy, and methylation state. Using the categorical metric methylation state, we select the two most heterogeneous states to identify genes that directly affect tumor suppressor genes and high- or moderate-risk breast cancer genes. Utilizing the Gene Set Enrichment Analysis software and the ConsensusPath Database visualization tool, we generate integrated gene networks to study biological relations of heterogeneous genes. This analysis has allowed us to contribute 19 potential breast cancer biomarker genes to cancer databases by locating “hub genes” – heterogeneous genes of significant biological interactions, selected from numerous cancer modules. We have discovered a considerable relationship between these hub genes and heterogeneously methylated oncogenes. Our results have many implications for further heterogeneity analyses of methylation patterns and early detection of breast cancer susceptibility. PMID:27688708

  16. Hydrological heterogeneity in agricultural riparian buffer strips

    NASA Astrophysics Data System (ADS)

    Hénault-Ethier, Louise; Larocque, Marie; Perron, Rachel; Wiseman, Natalie; Labrecque, Michel

    2017-03-01

    Riparian buffer strips (RBS) may protect surface water and groundwater in agricultural settings, although their effectiveness, observed in field-scale studies, may not extend to a watershed scale. Hydrologically-controlled leaching plots have often shown RBS to be effective at buffering nutrients and pesticides, but uncontrolled field studies have sometimes suggested limited effectiveness. The limited RBS effectiveness may be explained by the spatiotemporal hydrological heterogeneity near non-irrigated fields. This hypothesis was tested in conventional corn and soy fields in the St. Lawrence Lowlands of southern Quebec (Canada), where spring melt brings heavy and rapid runoff, while summer months are hot and dry. One field with a mineral soil (Saint-Roch-de-l'Achigan) and another with an organic-rich soil (Boisbriand) were equipped with passive runoff collectors, suction cup lysimeters, and piezometers placed before and after a 3 m-wide RBS, and monitored from 2011 to 2014. Soil topography of the RBS was mapped to a 1 cm vertical precision and a 50 cm sampling grid. On average, surface runoff intersects the RBS perpendicularly, but is subject to substantial local heterogeneity. Groundwater saturates the root zones, but flows little at the time of snowmelt. Groundwater flow is not consistently perpendicular to the RBS, and may reverse, flowing from stream to field under low water flow regimes with stream-aquifer connectivity, thus affecting RBS effectiveness calculations. Groundwater flow direction can be influenced by stratigraphy, local soil hydraulic properties, and historical modification of the agricultural stream beds. Understanding the spatiotemporal heterogeneity of surface and groundwater flows is essential to correctly assess the effectiveness of RBS in intercepting agro-chemical pollution. The implicit assumption that water flows across vegetated RBS, from the field to the stream, should always be verified.

  17. Pb isotopic heterogeneity in basaltic phenocrysts

    SciTech Connect

    Bryce, Julia G.; DePaolo, Donald J.

    2002-06-01

    The Pb isotopic compositions of phenocrystic phases in young basaltic lavas have been investigated using the Getty-DePaolo method (Getty S. J. and DePaolo D. J. [1995] Quaternary geochronology by the U-Th-Pb method. Geochim. Cosmochim. Acta 59, 3267 3272), which allows for the resolution of small isotopic differences. Phenocryst, matrix, and whole rock analyses were made on samples from the 17 Myr-old Imnaha basalts of the Columbia River Group, a zero-age MORB from the Mid-Atlantic Ridge, and a ca. 260 kyr-old tholeiite from Mount Etna. Plagioclase feldspar phenocrysts have low-(U, Th)/Pb, and in each sample the plagioclase has significantly lower 206Pb/207Pb and 208Pb/207Pb values than whole rock, matrix, and magnetite-rich separates. The Pb isotopic contrast between plagioclase and matrix/whole rock is found in three samples with varying grain sizes (0.5 2 cm for the Imnaha basalt and MORB and <1 mm for the Etna sample) from different tectonic settings, suggesting that these results are not unique. The isotopic contrasts are only slightly smaller in magnitude than the variations exhibited by whole rock samples from the region. The Imnaha basalts also have Sr isotopic heterogeneity evident only in plagioclase phenocrysts, but the MORB and Etna lavas do not. The isotopic heterogeneities reflect magma mixing, and indicate that isotopically diverse magmas were mixed together just prior to eruption. The results reinforce indications from melt inclusion studies that magma source region isotopic heterogeneities have large amplitudes at short length scales, and that the isotopic variations imparted to the magmas are not entirely homogenized during segregation and transport processes.

  18. Thermal and compositional contributions to mantle heterogeneity

    NASA Astrophysics Data System (ADS)

    Simmons, N. A.; Grand, S. P.; Forte, A. M.

    2007-12-01

    We have integrated seismic, geodynamic and mineral physics constraints to obtain models of mantle heterogeneity. The seismic constraints primarily consist of teleseismic shear body wave travel times and the geodynamic constraints include the global free-air gravity field, tectonic plate divergences, dynamic surface topography and the excess ellipticity of the core-mantle boundary. The geodynamic observations are interpreted with viscous flow response kernels and velocity-to-density scaling relationships for thermally-varying mantle material. Considering the viscosity model from Mitrovica & Forte (2004) and an optimal thermal density-velocity scaling relationship, we have found a single velocity/density model capable of satisfying the combined dataset to high degrees. The implication is that thermal variations dominate and compositional contributions are secondary throughout most of the non-cratonic mantle (Simmons et al. 2007). This modeling approach inherently minimizes potential non-thermal contributions to the density field and thus establishes a minimal estimate of the influence of composition needed to reconcile the observations. This is due to the fact that we use optimal viscosity and density-velocity scaling relationships to model the data with the initial assumption that all heterogeneity is generated by thermal variations. Therefore, we test other possibilities including simplified viscosity profiles and alternative thermal density-velocity relationships in order to evaluate how these input parameters increase the level of compositional influence required to satisfy the combined dataset. We also demonstrate the potential downfall of scaling a purely seismically-derived shear velocity model to obtain density heterogeneity in the mantle. This work was performed under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under Contract No. W-7405-Eng-48. UCRL-ABS-233968

  19. Features and heterogeneities in growing network models

    NASA Astrophysics Data System (ADS)

    Ferretti, Luca; Cortelezzi, Michele; Yang, Bin; Marmorini, Giacomo; Bianconi, Ginestra

    2012-06-01

    Many complex networks from the World Wide Web to biological networks grow taking into account the heterogeneous features of the nodes. The feature of a node might be a discrete quantity such as a classification of a URL document such as personal page, thematic website, news, blog, search engine, social network, etc., or the classification of a gene in a functional module. Moreover the feature of a node can be a continuous variable such as the position of a node in the embedding space. In order to account for these properties, in this paper we provide a generalization of growing network models with preferential attachment that includes the effect of heterogeneous features of the nodes. The main effect of heterogeneity is the emergence of an “effective fitness” for each class of nodes, determining the rate at which nodes acquire new links. The degree distribution exhibits a multiscaling behavior analogous to the the fitness model. This property is robust with respect to variations in the model, as long as links are assigned through effective preferential attachment. Beyond the degree distribution, in this paper we give a full characterization of the other relevant properties of the model. We evaluate the clustering coefficient and show that it disappears for large network size, a property shared with the Barabási-Albert model. Negative degree correlations are also present in this class of models, along with nontrivial mixing patterns among features. We therefore conclude that both small clustering coefficients and disassortative mixing are outcomes of the preferential attachment mechanism in general growing networks.

  20. Reporting Tumor Molecular Heterogeneity in Histopathological Diagnosis

    PubMed Central

    Mafficini, Andrea; Amato, Eliana; Fassan, Matteo; Simbolo, Michele; Antonello, Davide; Vicentini, Caterina; Scardoni, Maria; Bersani, Samantha; Gottardi, Marisa; Rusev, Borislav; Malpeli, Giorgio; Corbo, Vincenzo; Barbi, Stefano; Sikora, Katarzyna O.; Lawlor, Rita T.; Tortora, Giampaolo; Scarpa, Aldo

    2014-01-01

    Background Detection of molecular tumor heterogeneity has become of paramount importance with the advent of targeted therapies. Analysis for detection should be comprehensive, timely and based on routinely available tumor samples. Aim To evaluate the diagnostic potential of targeted multigene next-generation sequencing (TM-NGS) in characterizing gastrointestinal cancer molecular heterogeneity. Methods 35 gastrointestinal tract tumors, five of each intestinal type gastric carcinomas, pancreatic ductal adenocarcinomas, pancreatic intraductal papillary mucinous neoplasms, ampulla of Vater carcinomas, hepatocellular carcinomas, cholangiocarcinomas, pancreatic solid pseudopapillary tumors were assessed for mutations in 46 cancer-associated genes, using Ion Torrent semiconductor-based TM-NGS. One ampulla of Vater carcinoma cell line and one hepatic carcinosarcoma served to assess assay sensitivity. TP53, PIK3CA, KRAS, and BRAF mutations were validated by conventional Sanger sequencing. Results TM-NGS yielded overlapping results on matched fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues, with a mutation detection limit of 1% for fresh-frozen high molecular weight DNA and 2% for FFPE partially degraded DNA. At least one somatic mutation was observed in all tumors tested; multiple alterations were detected in 20/35 (57%) tumors. Seven cancers displayed significant differences in allelic frequencies for distinct mutations, indicating the presence of intratumor molecular heterogeneity; this was confirmed on selected samples by immunohistochemistry of p53 and Smad4, showing concordance with mutational analysis. Conclusions TM-NGS is able to detect and quantitate multiple gene alterations from limited amounts of DNA, moving one step closer to a next-generation histopathologic diagnosis that integrates morphologic, immunophenotypic, and multigene mutational analysis on routinely processed tissues, essential for personalized cancer therapy. PMID:25127237

  1. Type-curve estimation of statistical heterogeneity

    NASA Astrophysics Data System (ADS)

    Neuman, Shlomo P.; Guadagnini, Alberto; Riva, Monica

    2004-04-01

    The analysis of pumping tests has traditionally relied on analytical solutions of groundwater flow equations in relatively simple domains, consisting of one or at most a few units having uniform hydraulic properties. Recently, attention has been shifting toward methods and solutions that would allow one to characterize subsurface heterogeneities in greater detail. On one hand, geostatistical inverse methods are being used to assess the spatial variability of parameters, such as permeability and porosity, on the basis of multiple cross-hole pressure interference tests. On the other hand, analytical solutions are being developed to describe the mean and variance (first and second statistical moments) of flow to a well in a randomly heterogeneous medium. We explore numerically the feasibility of using a simple graphical approach (without numerical inversion) to estimate the geometric mean, integral scale, and variance of local log transmissivity on the basis of quasi steady state head data when a randomly heterogeneous confined aquifer is pumped at a constant rate. By local log transmissivity we mean a function varying randomly over horizontal distances that are small in comparison with a characteristic spacing between pumping and observation wells during a test. Experimental evidence and hydrogeologic scaling theory suggest that such a function would tend to exhibit an integral scale well below the maximum well spacing. This is in contrast to equivalent transmissivities derived from pumping tests by treating the aquifer as being locally uniform (on the scale of each test), which tend to exhibit regional-scale spatial correlations. We show that whereas the mean and integral scale of local log transmissivity can be estimated reasonably well based on theoretical ensemble mean variations of head and drawdown with radial distance from a pumping well, estimating the log transmissivity variance is more difficult. We obtain reasonable estimates of the latter based on

  2. Mathematical analysis of epidemiological models with heterogeneity

    SciTech Connect

    Van Ark, J.W.

    1992-01-01

    For many diseases in human populations the disease shows dissimilar characteristics in separate subgroups of the population; for example, the probability of disease transmission for gonorrhea or AIDS is much higher from male to female than from female to male. There is reason to construct and analyze epidemiological models which allow this heterogeneity of population, and to use these models to run computer simulations of the disease to predict the incidence and prevalence of the disease. In the models considered here the heterogeneous population is separated into subpopulations whose internal and external interactions are homogeneous in the sense that each person in the population can be assumed to have all average actions for the people of that subpopulation. The first model considered is an SIRS models; i.e., the Susceptible can become Infected, and if so he eventually Recovers with temporary immunity, and after a period of time becomes Susceptible again. Special cases allow for permanent immunity or other variations. This model is analyzed and threshold conditions are given which determine whether the disease dies out or persists. A deterministic model is presented; this model is constructed using difference equations, and it has been used in computer simulations for the AIDS epidemic in the homosexual population in San Francisco. The homogeneous version and the heterogeneous version of the differential-equations and difference-equations versions of the deterministic model are analyzed mathematically. In the analysis, equilibria are identified and threshold conditions are set forth for the disease to die out if the disease is below the threshold so that the disease-free equilibrium is globally asymptotically stable. Above the threshold the disease persists so that the disease-free equilibrium is unstable and there is a unique endemic equilibrium.

  3. Macrophage heterogeneity in liver injury and fibrosis.

    PubMed

    Tacke, Frank; Zimmermann, Henning W

    2014-05-01

    Hepatic macrophages are central in the pathogenesis of chronic liver injury and have been proposed as potential targets in combatting fibrosis. Recent experimental studies in animal models revealed that hepatic macrophages are a remarkably heterogeneous population of immune cells that fulfill diverse functions in homeostasis, disease progression, and regression from injury. These range from clearance of pathogens or cellular debris and maintenance of immunological tolerance in steady state conditions; central roles in initiating and perpetuating inflammation in response to injury; promoting liver fibrosis via activating hepatic stellate cells in chronic liver damage; and, finally, resolution of inflammation and fibrosis by degradation of extracellular matrix and release of anti-inflammatory cytokines. Cellular heterogeneity in the liver is partly explained by the origin of macrophages. Hepatic macrophages can either arise from circulating monocytes, which are recruited to the injured liver via chemokine signals, or from self-renewing embryo-derived local macrophages, termed Kupffer cells. Kupffer cells appear essential for sensing tissue injury and initiating inflammatory responses, while infiltrating Ly-6C(+) monocyte-derived macrophages are linked to chronic inflammation and fibrogenesis. In addition, proliferation of local or recruited macrophages may possibly further contribute to their accumulation in injured liver. During fibrosis regression, monocyte-derived cells differentiate into Ly-6C (Ly6C, Gr1) low expressing 'restorative' macrophages and promote resolution from injury. Understanding the mechanisms that regulate hepatic macrophage heterogeneity, either by monocyte subset recruitment, by promoting restorative macrophage polarization or by impacting distinctive macrophage effector functions, may help to develop novel macrophage subset-targeted therapies for liver injury and fibrosis.

  4. Dual compile strategy for parallel heterogeneous execution.

    SciTech Connect

    Smith, Tyler Barratt; Perry, James Thomas

    2012-06-01

    The purpose of the Dual Compile Strategy is to increase our trust in the Compute Engine during its execution of instructions. This is accomplished by introducing a heterogeneous Monitor Engine that checks the execution of the Compute Engine. This leads to the production of a second and custom set of instructions designed for monitoring the execution of the Compute Engine at runtime. This use of multiple engines differs from redundancy in that one engine is working on the application while the other engine is monitoring and checking in parallel instead of both applications (and engines) performing the same work at the same time.

  5. Nonlinear lattice waves in heterogeneous media

    NASA Astrophysics Data System (ADS)

    Laptyeva, T. V.; Ivanchenko, M. V.; Flach, S.

    2014-12-01

    We discuss recent advances in the understanding of the dynamics of nonlinear lattice waves in heterogeneous media, which enforce complete wave localization in the linear wave equation limit, especially Anderson localization for random potentials, and Aubry-André localization for quasiperiodic potentials. Additional nonlinear terms in the wave equations can either preserve the phase-coherent localization of waves, or destroy it through nonintegrability and deterministic chaos. Spreading wave packets are observed to show universal features in their dynamics which are related to properties of nonlinear diffusion equations.

  6. Characterization of mechanical heterogeneity in amorphous solids

    NASA Astrophysics Data System (ADS)

    Peng, H. L.; Li, M. Z.; Sun, B. A.; Wang, W. H.

    2012-07-01

    The structural geometry and size distribution of the local atomic rearrangements induced by external stress in amorphous solids are investigated by molecular dynamics studies. We find that the size distribution exhibits a generic power-law behavior and their structural geometry shows fractal feature. This indicates that the local atomic rearrangements in amorphous solids are self-organized during deformation. A simple theoretical model based on the interaction of the heterogeneous elastic field sources is proposed which predicts the power-law scaling and characterizes the properties of the local atomic rearrangements in amorphous solids.

  7. HIGH TEMPERATURE, HIGH POWER HETEROGENEOUS NUCLEAR REACTOR

    DOEpatents

    Hammond, R.P.; Wykoff, W.R.; Busey, H.M.

    1960-06-14

    A heterogeneous nuclear reactor is designed comprising a stationary housing and a rotatable annular core being supported for rotation about a vertical axis in the housing, the core containing a plurality of radial fuel- element supporting channels, the cylindrical empty space along the axis of the core providing a central plenum for the disposal of spent fuel elements, the core cross section outer periphery being vertically gradated in radius one end from the other to provide a coolant duct between the core and the housing, and means for inserting fresh fuel elements in the supporting channels under pressure and while the reactor is in operation.

  8. Evolutionary Dynamics on Degree-Heterogeneous Graphs

    NASA Astrophysics Data System (ADS)

    Antal, T.; Redner, S.; Sood, V.

    2006-05-01

    The evolution of two species with different fitness is investigated on degree-heterogeneous graphs. The population evolves either by one individual dying and being replaced by the offspring of a random neighbor (voter model dynamics) or by an individual giving birth to an offspring that takes over a random neighbor node (invasion process dynamics). The fixation probability for one species to take over a population of N individuals depends crucially on the dynamics and on the local environment. Starting with a single fitter mutant at a node of degree k, the fixation probability is proportional to k for voter model dynamics and to 1/k for invasion process dynamics.

  9. Wind resource assessment in heterogeneous terrain.

    PubMed

    Vanderwel, C; Placidi, M; Ganapathisubramani, B

    2017-04-13

    High-resolution particle image velocimetry data obtained in rough-wall boundary layer experiments are re-analysed to examine the influence of surface roughness heterogeneities on wind resource. Two different types of heterogeneities are examined: (i) surfaces with repeating roughness units of the order of the boundary layer thickness (Placidi & Ganapathisubramani. 2015 J. Fluid Mech.782, 541-566. (doi:10.1017/jfm.2015.552)) and (ii) surfaces with streamwise-aligned elevated strips that mimic adjacent hills and valleys (Vanderwel & Ganapathisubramani. 2015 J. Fluid Mech.774, 1-12. (doi:10.1017/jfm.2015.228)). For the first case, the data show that the power extraction potential is highly dependent on the surface morphology with a variation of up to 20% in the available wind resource across the different surfaces examined. A strong correlation is shown to exist between the frontal and plan solidities of the rough surfaces and the equivalent wind speed, and hence the wind resource potential. These differences are also found in profiles of [Formula: see text] and [Formula: see text] (where U is the streamwise velocity), which act as proxies for thrust and power output. For the second case, the secondary flows that cause low- and high-momentum pathways when the spacing between adjacent hills is beyond a critical value result in significant variations in wind resource availability. Contour maps of [Formula: see text] and [Formula: see text] show a large difference in thrust and power potential (over 50%) between hills and valleys (at a fixed vertical height). These variations do not seem to be present when adjacent hills are close to each other (i.e. when the spacing is much less than the boundary layer thickness). The variance in thrust and power also appears to be significant in the presence of secondary flows. Finally, there are substantial differences in the dispersive and turbulent stresses across the terrain, which could lead to variable fatigue life depending on

  10. Treatment of Organic Pollutants by Heterogeneous Photocatalysis

    NASA Astrophysics Data System (ADS)

    Feroz, S.; Jesil, A.

    2012-08-01

    An experimental investigation was carried out in the area of heterogeneous catalysis using TiO2 as a catalyst for the removal of the model organic compounds (benzoic acid and phenol) in three different photocatalytic reactors. Natural and artificial UV source of radiation were used and the performance of the reactors were studied in the present investigation. The extent of degradation/removal of the organic compounds was found by varying the initial concentration, flow rate, pipe diameter, TiO2 concentration and exposure time.

  11. Heterogeneous distributed query processing: The DAVID system

    NASA Technical Reports Server (NTRS)

    Jacobs, Barry E.

    1985-01-01

    The objective of the Distributed Access View Integrated Database (DAVID) project is the development of an easy to use computer system with which NASA scientists, engineers and administrators can uniformly access distributed heterogeneous databases. Basically, DAVID will be a database management system that sits alongside already existing database and file management systems. Its function is to enable users to access the data in other languages and file systems without having to learn the data manipulation languages. Given here is an outline of a talk on the DAVID project and several charts.

  12. Understanding as Integration of Heterogeneous Representations

    NASA Astrophysics Data System (ADS)

    Martínez, Sergio F.

    2014-03-01

    The search for understanding is a major aim of science. Traditionally, understanding has been undervalued in the philosophy of science because of its psychological underpinnings; nowadays, however, it is widely recognized that epistemology cannot be divorced from psychology as sharp as traditional epistemology required. This eliminates the main obstacle to give scientific understanding due attention in philosophy of science. My aim in this paper is to describe an account of scientific understanding as an emergent feature of our mastering of different (causal) explanatory frameworks that takes place through the mastering of scientific practices. Different practices lead to different kinds of representations. Such representations are often heterogeneous. The integration of such representations constitute understanding.

  13. Heterogeneous parallel programming capability. Final report

    SciTech Connect

    Flower, J.W.; Kolawa, A.

    1990-11-30

    In creating a heterogeneous parallel processing capability we are really trying to approach three basic problems with current systems: (1) Supercomputer and parallel computer hardware architectures vary widely but need to support one or two fairly standard programming languages and programming models. A particularly important issue concerns the short life cycle of individual hardware designs; (2) Many algorithms require capabilities beyond the reach of single superconducters but could be approached by several machines working together; and (3) Performing a given task requires integration of a system that may contain many components in addition to the super or parallel computer itself. Peripherals from many different manufacturers must be incorporated.

  14. Heterogeneity versus homogeneity of multiple sclerosis

    PubMed Central

    Sato, Fumitaka; Martinez, Nicholas E; Omura, Seiichi; Tsunoda, Ikuo

    2011-01-01

    The 10th International Congress of Neuroimmunology, including the 10th European School of Neuroimmunology Course, was held by the International Society of Neuroimmunology in Sitges (Barcelona, Spain) on 26–30 October 2010. The conference covered a wide spectrum of issues and challenges in both basic science and clinical aspects of neuroimmunology. Data and ideas were shared through a variety of programs, including review talks and poster sessions. One of the topics of the congress was whether multiple sclerosis is a homogenous or heterogenous disease, clinically and pathologically, throughout its course. PMID:21426254

  15. Markovian Search Games in Heterogeneous Spaces

    SciTech Connect

    Griffin, Christopher H

    2009-01-01

    We consider how to search for a mobile evader in a large heterogeneous region when sensors are used for detection. Sensors are modeled using probability of detection. Due to environmental effects, this probability will not be constant over the entire region. We map this problem to a graph search problem and, even though deterministic graph search is NP-complete, we derive a tractable, optimal, probabilistic search strategy. We do this by defining the problem as a differential game played on a Markov chain. We prove that this strategy is optimal in the sense of Nash. Simulations of an example problem illustrate our approach and verify our claims.

  16. Heterogeneous Vapor Condensation in Boundary Layers

    SciTech Connect

    Bonilla, L. L.; Carpio, A.; Neu, J. C.

    2008-09-01

    We consider heterogeneous condensation of vapors mixed with a carrier gas in stagnation point boundary layer flow near a cold wall in the presence of solid particles much larger than the mean free path of vapor particles. The supersaturated vapor condenses on the particles by diffusion, particles and droplets are thermophoretically attracted to the wall. We sketch three asymptotic theories of the condensation process, calculate the flow-induced shift in the dew point interface, vapor density profile and deposition rates at the wall, and compare them to direct numerical simulation.

  17. Nanoparticles for heterogeneous catalysis: new mechanistic insights.

    PubMed

    Schauermann, Swetlana; Nilius, Niklas; Shaikhutdinov, Shamil; Freund, Hans-Joachim

    2013-08-20

    Metallic nanoparticles finely dispersed over oxide supports have found use as heterogeneous catalysts in many industries including chemical manufacturing, energy-related applications and environmental remediation. The compositional and structural complexity of such nanosized systems offers many degrees of freedom for tuning their catalytic properties. However, fully rational design of heterogeneous catalysts based on an atomic-level understanding of surface processes remains an unattained goal in catalysis research. Researchers have used surface science methods and metal single crystals to explore elementary processes in heterogeneous catalysis. In this Account, we use more realistic materials that capture part of the complexity inherent to industrial catalysts. We assess the impacts on the overall catalytic performance of characteristics such as finite particle size, particle structure, particle chemical composition, flexibility of atoms in clusters, and metal-support interactions. To prepare these materials, we grew thin oxide films on metal single crystals under ultrahigh vacuum conditions and used these films as supports for metallic nanoparticles. We present four case studies on specifically designed materials with properties that expand our atomic-level understanding of surface chemistry. Specifically, we address (1) the effect of dopants in the oxide support on the growth of metal nanoclusters; (2) the effects of size and structural flexibility of metal clusters on the binding energy of gas-phase adsorbates and their catalytic activity; (3) the role of surface modifiers, such as carbon, on catalytic activity and selectivity; and (4) the structural and compositional changes of the active surface as a result of strong metal-support interaction. Using these examples, we demonstrate how studies of complex nanostructured materials can help revealing atomic processes at the solid-gas interface of heterogeneous catalysts. Among our findings is that doping of oxide

  18. Thermal conductivity of heterogeneous LWR MOX fuels

    NASA Astrophysics Data System (ADS)

    Staicu, D.; Barker, M.

    2013-11-01

    It is generally observed that the thermal conductivity of LWR MOX fuel is lower than that of pure UO2. For MOX, the degradation is usually only interpreted as an effect of the substitution of U atoms by Pu. This hypothesis is however in contradiction with the observations of Duriez and Philiponneau showing that the thermal conductivity of MOX is independent of the Pu content in the ranges 3-15 and 15-30 wt.% PuO2 respectively. Attributing this degradation to Pu only implies that stoichiometric heterogeneous MOX can be obtained, while we show that any heterogeneity in the plutonium distribution in the sample introduces a variation in the local stoichiometry which in turn has a strong impact on the thermal conductivity. A model quantifying this effect is obtained and a new set of experimental results for homogeneous and heterogeneous MOX fuels is presented and used to validate the proposed model. In irradiated fuels, this effect is predicted to disappear early during irradiation. The 3, 6 and 10 wt.% Pu samples have a similar thermal conductivity. Comparison of the results for this homogeneous microstructure with MIMAS (heterogeneous) fuel of the same composition showed no difference for the Pu contents of 3, 5.9, 6, 7.87 and 10 wt.%. A small increase of the thermal conductivity was obtained for 15 wt.% Pu. This increase is of about 6% when compared to the average of the values obtained for 3, 6 and 10 wt.% Pu. For comparison purposes, Duriez also measured the thermal conductivity of FBR MOX with 21.4 wt.% Pu with O/M = 1.982 and a density close to 95% TD and found a value in good agreement with the estimation obtained using the formula of Philipponneau [8] for FBR MOX, and significantly lower than his results corresponding to the range 3-15 wt.% Pu. This difference in thermal conductivity is of about 20%, i.e. higher than the measurement uncertainties.Thus, a significant difference was observed between FBR and PWR MOX fuels, but was not explained. This difference

  19. Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila

    SciTech Connect

    Stoiber, Marcus H.; Olson, Sara; May, Gemma E.; Duff, Michael O.; Manent, Jan; Obar, Robert; Guruharsha, K. G.; Bickel, Peter J.; Artavanis-Tsakonas, Spyros; Brown, James B.; Graveley, Brenton R.; Celniker, Susan E.

    2015-08-20

    In eukaryotic cells, RNAs exist as ribonucleoprotein particles (RNPs). Despite the importance of these complexes in many biological processes, including splicing, polyadenylation, stability, transportation, localization, and translation, their compositions are largely unknown. We affinity-purified 20 distinct RNA-binding proteins (RBPs) from cultured Drosophila melanogaster cells under native conditions and identified both the RNA and protein compositions of these RNP complexes. We identified “high occupancy target” (HOT) RNAs that interact with the majority of the RBPs we surveyed. HOT RNAs encode components of the nonsense-mediated decay and splicing machinery, as well as RNA-binding and translation initiation proteins. The RNP complexes contain proteins and mRNAs involved in RNA binding and post-transcriptional regulation. Genes with the capacity to produce hundreds of mRNA isoforms, ultracomplex genes, interact extensively with heterogeneous nuclear ribonuclear proteins (hnRNPs). Our data are consistent with a model in which subsets of RNPs include mRNA and protein products from the same gene, indicating the widespread existence of auto-regulatory RNPs. Lastly, from the simultaneous acquisition and integrative analysis of protein and RNA constituents of RNPs, we identify extensive cross-regulatory and hierarchical interactions in post-transcriptional control.

  20. Network-Informed Gene Ranking Tackles Genetic Heterogeneity in Exome-Sequencing Studies of Monogenic Disease.

    PubMed

    Dand, Nick; Schulz, Reiner; Weale, Michael E; Southgate, Laura; Oakey, Rebecca J; Simpson, Michael A; Schlitt, Thomas

    2015-12-01

    Genetic heterogeneity presents a significant challenge for the identification of monogenic disease genes. Whole-exome sequencing generates a large number of candidate disease-causing variants and typical analyses rely on deleterious variants being observed in the same gene across several unrelated affected individuals. This is less likely to occur for genetically heterogeneous diseases, making more advanced analysis methods necessary. To address this need, we present HetRank, a flexible gene-ranking method that incorporates interaction network data. We first show that different genes underlying the same monogenic disease are frequently connected in protein interaction networks. This motivates the central premise of HetRank: those genes carrying potentially pathogenic variants and whose network neighbors do so in other affected individuals are strong candidates for follow-up study. By simulating 1,000 exome sequencing studies (20,000 exomes in total), we model varying degrees of genetic heterogeneity and show that HetRank consistently prioritizes more disease-causing genes than existing analysis methods. We also demonstrate a proof-of-principle application of the method to prioritize genes causing Adams-Oliver syndrome, a genetically heterogeneous rare disease. An implementation of HetRank in R is available via the Website http://sourceforge.net/p/hetrank/.

  1. Measuring intratumor heterogeneity by network entropy using RNA-seq data

    PubMed Central

    Park, Youngjune; Lim, Sangsoo; Nam, Jin-Wu; Kim, Sun

    2016-01-01

    Intratumor heterogeneity (ITH) is observed at different stages of tumor progression, metastasis and reouccurence, which can be important for clinical applications. We used RNA-sequencing data from tumor samples, and measured the level of ITH in terms of biological network states. To model complex relationships among genes, we used a protein interaction network to consider gene-gene dependency. ITH was measured by using an entropy-based distance metric between two networks, nJSD, with Jensen-Shannon Divergence (JSD). With nJSD, we defined transcriptome-based ITH (tITH). The effectiveness of tITH was extensively tested for the issues related with ITH using real biological data sets. Human cancer cell line data and single-cell sequencing data were investigated to verify our approach. Then, we analyzed TCGA pan-cancer 6,320 patients. Our result was in agreement with widely used genome-based ITH inference methods, while showed better performance at survival analysis. Analysis of mouse clonal evolution data further confirmed that our transcriptome-based ITH was consistent with genetic heterogeneity at different clonal evolution stages. Additionally, we found that cell cycle related pathways have significant contribution to increasing heterogeneity on the network during clonal evolution. We believe that the proposed transcriptome-based ITH is useful to characterize heterogeneity of a tumor sample at RNA level. PMID:27883053

  2. Measuring intratumor heterogeneity by network entropy using RNA-seq data.

    PubMed

    Park, Youngjune; Lim, Sangsoo; Nam, Jin-Wu; Kim, Sun

    2016-11-24

    Intratumor heterogeneity (ITH) is observed at different stages of tumor progression, metastasis and reouccurence, which can be important for clinical applications. We used RNA-sequencing data from tumor samples, and measured the level of ITH in terms of biological network states. To model complex relationships among genes, we used a protein interaction network to consider gene-gene dependency. ITH was measured by using an entropy-based distance metric between two networks, nJSD, with Jensen-Shannon Divergence (JSD). With nJSD, we defined transcriptome-based ITH (tITH). The effectiveness of tITH was extensively tested for the issues related with ITH using real biological data sets. Human cancer cell line data and single-cell sequencing data were investigated to verify our approach. Then, we analyzed TCGA pan-cancer 6,320 patients. Our result was in agreement with widely used genome-based ITH inference methods, while showed better performance at survival analysis. Analysis of mouse clonal evolution data further confirmed that our transcriptome-based ITH was consistent with genetic heterogeneity at different clonal evolution stages. Additionally, we found that cell cycle related pathways have significant contribution to increasing heterogeneity on the network during clonal evolution. We believe that the proposed transcriptome-based ITH is useful to characterize heterogeneity of a tumor sample at RNA level.

  3. Heterogeneous processes at the intersection of chemistry and biology: A computational approach

    SciTech Connect

    Kuo, I W; Mundy, C J

    2008-02-11

    Heterogeneous processes hold the key to understanding many problems in biology and atmospheric science. In particular, recent experiments have shown that heterogeneous chemistry at the surface of sea-salt aerosols plays a large role in important atmospheric processes with far reaching implications towards understanding of the fate and transport of aerosolized chemical weapons (i.e. organophosphates such as sarin and VX). Unfortunately, the precise mechanistic details of the simplest surface enhanced chemical reactions remain unknown. Understanding heterogeneous processes also has implications in the biological sciences. Traditionally, it is accepted that enzymes catalyze reactions by stabilizing the transition state, thereby lowering the free energy barrier. However, recent findings have shown that a multitude of phenomena likely contribute to the efficiency of enzymes, such as coupled protein motion, quantum mechanical tunneling, or strong electrostatic binding. The objective of this project was to develop and validate a single computational framework based on first principles simulations using tera-scale computational resources to answer fundamental scientific questions about heterogeneous chemical processes relevant to atmospheric chemistry and biological sciences.

  4. Collective action problem in heterogeneous groups

    PubMed Central

    Gavrilets, Sergey

    2015-01-01

    I review the theoretical and experimental literature on the collective action problem in groups whose members differ in various characteristics affecting individual costs, benefits and preferences in collective actions. I focus on evolutionary models that predict how individual efforts and fitnesses, group efforts and the amount of produced collective goods depend on the group's size and heterogeneity, as well as on the benefit and cost functions and parameters. I consider collective actions that aim to overcome the challenges from nature or win competition with neighbouring groups of co-specifics. I show that the largest contributors towards production of collective goods will typically be group members with the highest stake in it or for whom the effort is least costly, or those who have the largest capability or initial endowment. Under some conditions, such group members end up with smaller net pay-offs than the rest of the group. That is, they effectively behave as altruists. With weak nonlinearity in benefit and cost functions, the group effort typically decreases with group size and increases with within-group heterogeneity. With strong nonlinearity in benefit and cost functions, these patterns are reversed. I discuss the implications of theoretical results for animal behaviour, human origins and psychology. PMID:26503689

  5. Deformation field heterogeneity in punch indentation

    PubMed Central

    Murthy, Tejas G.; Saldana, Christopher; Hudspeth, Matthew; M'Saoubi, Rachid

    2014-01-01

    Plastic heterogeneity in indentation is fundamental for understanding mechanics of hardness testing and impression-based deformation processing methods. The heterogeneous deformation underlying plane-strain indentation was investigated in plastic loading of copper by a flat punch. Deformation parameters were measured, in situ, by tracking the motion of asperities in high-speed optical imaging. These measurements were coupled with multi-scale analyses of strength, microstructure and crystallographic texture in the vicinity of the indentation. Self-consistency is demonstrated in description of the deformation field using the in situ mechanics-based measurements and post-mortem materials characterization. Salient features of the punch indentation process elucidated include, among others, the presence of a dead-metal zone underneath the indenter, regions of intense strain rate (e.g. slip lines) and extent of the plastic flow field. Perhaps more intriguing are the transitions between shear-type and compression-type deformation modes over the indentation region that were quantified by the high-resolution crystallographic texture measurements. The evolution of the field concomitant to the progress of indentation is discussed and primary differences between the mechanics of indentation for a rigid perfectly plastic material and a strain-hardening material are described. PMID:24910521

  6. Mitochondrial DNA heterogeneity in Tunisian Berbers.

    PubMed

    Fadhlaoui-Zid, K; Plaza, S; Calafell, F; Ben Amor, M; Comas, D; Bennamar El gaaied, A

    2004-05-01

    Berbers live in groups scattered across North Africa whose origins and genetic relationships with their neighbours are not well established. The first hypervariable segment of the mitochondrial DNA (mtDNA) control region was sequenced in a total of 155 individuals from three Tunisian Berber groups and compared to other North Africans. The mtDNA lineages found belong to a common set of mtDNA haplogroups already described in North Africa. Besides the autochthonous North African U6 haplogroup, a group of L3 lineages characterized by the transition at position 16041 seems to be restricted to North Africans, suggesting that an expansion of this group of lineages took place around 10500 years ago in North Africa, and spread to neighbouring populations. Principal components and the coordinate analyses show that some Berber groups (the Tuareg, the Mozabite, and the Chenini-Douiret) are outliers within the North African genetic landscape. This outlier position is consistent with an isolation process followed by genetic drift in haplotype frequencies, and with the high heterogeneity displayed by Berbers compared to Arab samples as shown in the AMOVA. Despite this Berber heterogeneity, no significant differences were found between Berber and Arab samples, suggesting that the Arabization was mainly a cultural process rather than a demographic replacement.

  7. Learning probabilistic phenotypes from heterogeneous EHR data.

    PubMed

    Pivovarov, Rimma; Perotte, Adler J; Grave, Edouard; Angiolillo, John; Wiggins, Chris H; Elhadad, Noémie

    2015-12-01

    We present the Unsupervised Phenome Model (UPhenome), a probabilistic graphical model for large-scale discovery of computational models of disease, or phenotypes. We tackle this challenge through the joint modeling of a large set of diseases and a large set of clinical observations. The observations are drawn directly from heterogeneous patient record data (notes, laboratory tests, medications, and diagnosis codes), and the diseases are modeled in an unsupervised fashion. We apply UPhenome to two qualitatively different mixtures of patients and diseases: records of extremely sick patients in the intensive care unit with constant monitoring, and records of outpatients regularly followed by care providers over multiple years. We demonstrate that the UPhenome model can learn from these different care settings, without any additional adaptation. Our experiments show that (i) the learned phenotypes combine the heterogeneous data types more coherently than baseline LDA-based phenotypes; (ii) they each represent single diseases rather than a mix of diseases more often than the baseline ones; and (iii) when applied to unseen patient records, they are correlated with the patients' ground-truth disorders. Code for training, inference, and quantitative evaluation is made available to the research community.

  8. Genetic heterogeneity of familial hemiplegic migraine

    SciTech Connect

    Ophoff, R.A.; Van Eijk, R.; Sandkuijl, L.A.

    1994-07-01

    Familial hemiplegic migraine (FHM) is a distinctive form of migraine with an autosomal dominant mode of inheritance. The migraine-like attacks are associated with transient hemiparesis. A locus for FHM has recently been assigned to chromosome 19 by linkage mapping. In the present study, five unrelated pedigrees with multiple members suffering from hemiplegic migraine were investigated. In two of the pedigrees additional symptoms, cerebellar ataxia and benign neonatal convulsions, respectively, were observed in affected members. Three pedigrees showed linkage to loci D19S391, D19S221, and D19S226 at chromosome 19p13. Haplotyping suggested a location of a FHM gene between D19S391 and D19S221. In the two remaining families, evidence against linkage was found. These results confirm the localization of a gene for familial hemiplegic migraine to the short arm of chromosome 19, but locus heterogeneity not corresponding to the observed clinical heterogeneity is likely to exist. 19 refs., 3 figs., 3 tabs.

  9. Genetic heterogeneity of familial hemiplegic migraine

    SciTech Connect

    Joutel, A.; Ducros, A.; Vahedi, K.

    1994-09-01

    Familial hemiplegic migraine (FHM) is an autosomal dominant subtype of migraine with aura, characterized by the occurrence of a transient hemiplegia during the aura. We previously mapped the affected gene to the short arm of chromosome 19, within a 30 cM interval bracketed by D19S216 and D19S215. Linkage analysis conducted on 2 large FHM pedigrees did not show evidence of heterogeneity, despite their clinical differences due to the presence in one family of a cerebellar ataxia and a nystagmus. Herein we report linkage data on 9 additional FHM families including 2 other ones with cerebellar ataxia. Analysis was conducted with a set of 7 markers spanning the D19S216-D19S215 interval. Two point and multipoint lodscores analysis as well as HOMOG testing provided significant evidence for genetic heterogenity. Strong evidence of linkage was obtained in 3 families and absence of linkage in 6 families. Thus within the 11 families so far tested, 5 were linked, including those with an associated cerebellar ataxia. We could not find any clinical difference between the {open_quotes}pure{close_quotes} FHM families whether or not they were linked. This study also allowed us to establish that the most likely location of the gene is a 12 cM interval bracketed by D19S413 and D19S226. One of the unlinked family was large enough to conduct genetic mapping of the affected gene. Data will be presented at the meeting.

  10. PDF-based heterogeneous multiscale filtration model.

    PubMed

    Gong, Jian; Rutland, Christopher J

    2015-04-21

    Motivated by modeling of gasoline particulate filters (GPFs), a probability density function (PDF) based heterogeneous multiscale filtration (HMF) model is developed to calculate filtration efficiency of clean particulate filters. A new methodology based on statistical theory and classic filtration theory is developed in the HMF model. Based on the analysis of experimental porosimetry data, a pore size probability density function is introduced to represent heterogeneity and multiscale characteristics of the porous wall. The filtration efficiency of a filter can be calculated as the sum of the contributions of individual collectors. The resulting HMF model overcomes the limitations of classic mean filtration models which rely on tuning of the mean collector size. Sensitivity analysis shows that the HMF model recovers the classical mean model when the pore size variance is very small. The HMF model is validated by fundamental filtration experimental data from different scales of filter samples. The model shows a good agreement with experimental data at various operating conditions. The effects of the microstructure of filters on filtration efficiency as well as the most penetrating particle size are correctly predicted by the model.

  11. Heterogeneous chemistry in the atmosphere of Mars.

    PubMed

    Lefèvre, Franck; Bertaux, Jean-Loup; Clancy, R Todd; Encrenaz, Thérèse; Fast, Kelly; Forget, François; Lebonnois, Sébastien; Montmessin, Franck; Perrier, Séverine

    2008-08-21

    Hydrogen radicals are produced in the martian atmosphere by the photolysis of water vapour and subsequently initiate catalytic cycles that recycle carbon dioxide from its photolysis product carbon monoxide. These processes provide a qualitative explanation for the stability of the atmosphere of Mars, which contains 95 per cent carbon dioxide. Balancing carbon dioxide production and loss based on our current understanding of the gas-phase chemistry in the martian atmosphere has, however, proven to be difficult. Interactions between gaseous chemical species and ice cloud particles have been shown to be key factors in the loss of polar ozone observed in the Earth's stratosphere, and may significantly perturb the chemistry of the Earth's upper troposphere. Water-ice clouds are also commonly observed in the atmosphere of Mars and it has been suggested previously that heterogeneous chemistry could have an important impact on the composition of the martian atmosphere. Here we use a state-of-the-art general circulation model together with new observations of the martian ozone layer to show that model simulations that include chemical reactions occurring on ice clouds lead to much improved quantitative agreement with observed martian ozone levels in comparison with model simulations based on gas-phase chemistry alone. Ozone is readily destroyed by hydrogen radicals and is therefore a sensitive tracer of the chemistry that regulates the atmosphere of Mars. Our results suggest that heterogeneous chemistry on ice clouds plays an important role in controlling the stability and composition of the martian atmosphere.

  12. Semiclassical approach to heterogeneous vacuum decay

    NASA Astrophysics Data System (ADS)

    Grinstein, Benjamín; Murphy, Christopher W.

    2015-12-01

    We derive the decay rate of an unstable phase of a quantum field theory in the presence of an impurity in the thin-wall approximation. This derivation is based on the how the impurity changes the (flat spacetime) geometry relative to case of pure false vacuum. Two examples are given that show how to estimate some of the additional parameters that enter into this heterogeneous decay rate. This formalism is then applied to the Higgs vacuum of the Standard Model (SM), where baryonic matter acts as an impurity in the electroweak Higgs vacuum. We find that the probability for heterogeneous vacuum decay to occur is suppressed with respect to the homogeneous case. That is to say, the conclusions drawn from the homogeneous case are not modified by the inclusion of baryonic matter in the calculation. On the other hand, we show that Beyond the Standard Model physics with a characteristic scale comparable to the scale that governs the homogeneous decay rate in the SM, can in principle lead to an enhanced decay rate.

  13. Dynamic contact angle cycling homogenizes heterogeneous surfaces.

    PubMed

    Belibel, R; Barbaud, C; Mora, L

    2016-12-01

    In order to reduce restenosis, the necessity to develop the appropriate coating material of metallic stent is a challenge for biomedicine and scientific research over the past decade. Therefore, biodegradable copolymers of poly((R,S)-3,3 dimethylmalic acid) (PDMMLA) were prepared in order to develop a new coating exhibiting different custom groups in its side chain and being able to carry a drug. This material will be in direct contact with cells and blood. It consists of carboxylic acid and hexylic groups used for hydrophilic and hydrophobic character, respectively. The study of this material wettability and dynamic surface properties is of importance due to the influence of the chemistry and the potential motility of these chemical groups on cell adhesion and polymer kinetic hydrolysis. Cassie theory was used for the theoretical correction of contact angles of these chemical heterogeneous surfaces coatings. Dynamic Surface Analysis was used as practical homogenizer of chemical heterogeneous surfaces by cycling during many cycles in water. In this work, we confirmed that, unlike receding contact angle, advancing contact angle is influenced by the difference of only 10% of acidic groups (%A) in side-chain of polymers. It linearly decreases with increasing acidity percentage. Hysteresis (H) is also a sensitive parameter which is discussed in this paper. Finally, we conclude that cycling provides real information, thus avoiding theoretical Cassie correction. H(10)is the most sensible parameter to %A.

  14. [Phenotypic heterogeneity of chronic obstructive pulmonary disease].

    PubMed

    Garcia-Aymerich, Judith; Agustí, Alvar; Barberà, Joan A; Belda, José; Farrero, Eva; Ferrer, Antoni; Ferrer, Jaume; Gáldiz, Juan B; Gea, Joaquim; Gómez, Federico P; Monsó, Eduard; Morera, Josep; Roca, Josep; Sauleda, Jaume; Antó, Josep M

    2009-03-01

    A functional definition of chronic obstructive pulmonary disease (COPD) based on airflow limitation has largely dominated the field. However, a view has emerged that COPD involves a complex array of cellular, organic, functional, and clinical events, with a growing interest in disentangling the phenotypic heterogeneity of COPD. The present review is based on the opinion of the authors, who have extensive research experience in several aspects of COPD. The starting assumption of the review is that current knowledge on the pathophysiology and clinical features of COPD allows us to classify phenotypic information in terms of the following dimensions: respiratory symptoms and health status, acute exacerbations, lung function, structural changes, local and systemic inflammation, and systemic effects. Twenty-six phenotypic traits were identified and assigned to one of the 6 dimensions. For each dimension, a summary is provided of the best evidence on the relationships among phenotypic traits, in particular among those corresponding to different dimensions, and on the relationship between these traits and relevant events in the natural history of COPD. The information has been organized graphically into a phenotypic matrix where each cell representing a pair of phenotypic traits is linked to relevant references. The information provided has the potential to increase our understanding of the heterogeneity of COPD phenotypes and help us plan future studies on aspects that are as yet unexplored.

  15. Heterogeneous Participant Recruitment for Comprehensive Vehicle Sensing

    PubMed Central

    Liu, Yazhi; Li, Xiong

    2015-01-01

    Widely distributed mobile vehicles wherein various sensing devices and wireless communication interfaces are installed bring vehicular participatory sensing into practice. However, the heterogeneity of vehicles in terms of sensing capability and mobility, and the participants’ expectations on the incentives blackmake the collection of comprehensive sensing data a challenging task. A sensing data quality-oriented optimal heterogeneous participant recruitment strategy is proposed in this paper for vehicular participatory sensing. In the proposed strategy, the differences between the sensing data requirements and the collected sensing data are modeled. An optimization formula is established to model the optimal participant recruitment problem, and a participant utility analysis scheme is built based on the sensing and mobility features of vehicles. Besides, a greedy algorithm is then designed according to the utility of vehicles to recruit the most efficient vehicles with a limited total incentive budget. Real trace-driven simulations show that the proposed strategy can collect 85.4% of available sensing data with 34% incentive budget. PMID:26407102

  16. Monocyte heterogeneity in human cardiovascular disease.

    PubMed

    Zawada, Adam M; Rogacev, Kyrill S; Schirmer, Stephan H; Sester, Martina; Böhm, Michael; Fliser, Danilo; Heine, Gunnar H

    2012-12-01

    Atherosclerosis has been characterized as an inflammatory process, in which monocytes and monocyte-derived macrophages are of paramount importance. Contrasting with their established role in atherosclerosis, monocytes have not unanimously been found to predict cardiovascular events in large epidemiological studies. However, in these studies human monocyte heterogeneity has been largely overlooked so far. Three human monocyte subsets can be distinguished: classical CD14(++)CD16(-), intermediate CD14(++)CD16(+) and nonclassical CD14(+)CD16(++) monocytes. Of note, correct enumeration of subset counts requires appropriate staining and gating strategies that encompass a pan-monocytic marker (e.g. HLA-DR or CD86). In experimental studies on murine atherogenesis a monocyte subset-specific contribution to atherosclerosis has been established. However, major interspecies differences in atherogenesis itself, as well as in the immune system (including monocyte subset phenotype and distribution) preclude a direct extrapolation to human pathology. Experimental and pilot clinical studies point to a prominent involvement of intermediate CD14(++)CD16(+) monocytes in human atherosclerosis. Future clinical studies should analyze monocyte heterogeneity in cardiovascular disease. If a specific contribution of intermediate monocytes should be confirmed, immunomodulation of this monocyte subset could represent a future therapeutic target in atherosclerosis.

  17. Heterogeneous nucleation of aspartame from aqueous solutions

    NASA Astrophysics Data System (ADS)

    Kubota, Noriaki; Kinno, Hiroaki; Shimizu, Kenji

    1990-03-01

    Waiting times, the time from the instant of quenching needed for a first nucleus to appear, were measured at constant supercoolings for primary nucleation of aspartame (α-L-aspartyl-L-phenylalanine methylester) from aqueous solutions, which were sealed into glass ampoules (solution volume = 3.16 cm 3). Since the waiting time became shorter by filtering the solution prior to quenching, the nucleation was concluded to be heterogeneously induced. The measured waiting time consisted of two parts: time needed for the nucleus to grow to a detactable size (growth time) and stochastic time needed for nucleation (true waiting time). The distribution of the true waiting time, is well explained by a stochastic model, in which nucleation is regarded to occur heterogeneously and in a stochastic manner by two kinds of active sites. The active sites are estimated to be located on foreign particles in which such elements as Si, Al and Mg were contained. The amount of each element is very small in the order of magnitude of ppb (mass basis) of the whole solution. The growth time was correlated with the degree of supercooling.

  18. Heterogeneity in styrene-butadiene latex films.

    PubMed

    Santos, Juliane P; Corpart, Pascale; Wong, Kenneth; Galembeck, Fernando

    2004-11-23

    Low-Tg styrene-butadiene (SB) latex films were investigated by noncontact atomic force microscopy and scanning electric potential microscopy, revealing a number of different morphologies and electric potential patterns across films cast from the same SB latex dispersions under the same conditions. Surface leveling and charge dispersion throughout the films are, thus, restrained even at temperatures above Tg and the minimum film-formation temperature. An unprecedented electric pattern is observed, in which the particle cores are more positive than the contacting particle outer layers. Different packing patterns, including cubic and hexagonal arrays, coexist in neighboring areas. Zonal centrifugation of the SB latex in sucrose density gradient shows that particles cover a broad range of densities. Thus, film surface heterogeneity is at least partly due to particle heterogeneity. Fractal dimensions of topographic profiles are lower than those of the electric potential profiles, showing that charge mobility is much more restrained than polymer chain motion at the film surface and that it imposes a limit to the charged chain-ends motion.

  19. Characterizing hydrogeologic heterogeneity using lithologic data

    SciTech Connect

    Flach, G.P.; Hamm, L.L.; Harris, M.K.; Thayer, P.A.; Haselow, J.S.; Smits, A.D.

    1995-12-31

    Large-scale (> 1 m) variability in hydraulic conductivity is usually the main influence on field-scale groundwater flow patterns and dispersive transport. Sediment lithologic descriptions and geophysical logs typically offer finer spatial resolution, and therefore more potential information about site-scale heterogeneity, than other site characterization data. In this study, a technique for generating a heterogeneous, three-dimensional hydraulic conductivity field from sediment lithologic descriptions is presented. The approach involves creating a three-dimensional, fine-scale representation of mud (silt + clay) percentage using a stratified interpolation algorithm. Mud percentage is then translated into horizontal and vertical conductivity using direct correlations derived from measured data and inverse groundwater flow modeling. Lastly, the fine-scale conductivity fields are averaged to create a coarser grid for use in groundwater flow and transport modeling. The approach is demonstrated using a finite-element groundwater flow model of a Savannah River Site solid radioactive and hazardous waste burial ground. Hydrostratigraphic units in the area consist of fluvial, deltaic, and shallow marine sand, mud and calcareous sediment that exhibit abrupt facies changes over short distances.

  20. Heterogeneous photocatalytic reactions of sulfur aromatic compounds.

    PubMed

    Samokhvalov, Alexander

    2011-11-18

    Sulfur aromatic compounds, such as mono-, di-, tri-, and tetraalkyl-substituted thiophene, benzothiophenes, dibenzothiophenes, are the molecular components of many fossils (petroleum, oil shale, tar sands, bitumen). Structural units of natural, cross-linked heteroaromatic polymers present in brown coals, turf, and soil are similar to those of sulfur aromatic compounds. Many sulfur aromatic compounds are found in the streams of petroleum refining and upgrading (naphthas, gas oils) and in the consumer products (gasoline, diesel, jet fuels, heating fuels). Besides fossils, the structural fragments of sulfur aromatic compounds are present in molecules of certain organic semiconductors, pesticides, small molecule drugs, and in certain biomolecules present in human body (pheomelanin pigments). Photocatalysis is the frontier area of physical chemistry that studies chemical reactions initiated by absorption of photons by photocatalysts, that is, upon electronic rather than thermal activation, under "green" ambient conditions. This review provides systematization and critical review of the fundamental chemical and physicochemical information on heterogeneous photocatalysis of sulfur aromatic compounds accumulated in the last 20-30 years. Specifically, the following topics are covered: physicochemical properties of sulfur aromatic compounds, major classes of heterogeneous photocatalysts, mechanisms and reactive intermediates of photocatalytic reactions of sulfur aromatic compounds, and the selectivity of these reactions. Quantum chemical calculations of properties and structures of sulfur aromatic compounds, their reactive intermediates, and the structure of adsorption complexes formed on the surface of the photocatalysts are also discussed.

  1. Groundwater flow in heterogeneous composite aquifers

    NASA Astrophysics Data System (ADS)

    Winter, C. L.; Tartakovsky, Daniel M.

    2002-08-01

    We introduce a stochastic model of flow through highly heterogeneous, composite porous media that greatly improves estimates of pressure head statistics. Composite porous media consist of disjoint blocks of permeable materials, each block comprising a single material type. Within a composite medium, hydraulic conductivity can be represented through a pair of random processes: (1) a boundary process that determines block arrangement and extent and (2) a stationary process that defines conductivity within a given block. We obtain second-order statistics for hydraulic conductivity in the composite model and then contrast them with statistics obtained from a standard univariate model that ignores the boundary process and treats a composite medium as if it were statistically homogeneous. Next, we develop perturbation expansions for the first two moments of head and contrast them with expansions based on the homogeneous approximation. In most cases the bivariate model leads to much sharper perturbation approximations than does the usual model of flow through an undifferentiated material when both are applied to highly heterogeneous media. We make this statement precise. We illustrate the composite model with examples of one-dimensional flows which are interesting in their own right and which allow us to compare the accuracy of perturbation approximations of head statistics to exact analytical solutions. We also show the boundary process of our bivariate model is equivalent to the indicator functions often used to represent composite media in Monte Carlo simulations.

  2. Repeatability and randomness in heterogeneous freezing nucleation

    NASA Astrophysics Data System (ADS)

    Vali, G.

    2008-08-01

    This study is aimed at clarifying the relative importance of the specific character of the nuclei and of the duration of supercooling in heterogeneous freezing nucleation by immersed impurities. Laboratory experiments were carried out in which sets of water drops underwent multiple cycles of freezing and melting. The drops contained suspended particles of mixtures of materials; the resulting freezing temperatures ranged from -6°C to -24°C. Rank correlation coefficients between observed freezing temperatures of the drops in successive runs were >0.9 with very high statistical significance, and thus provide strong support for the modified singular model of heterogeneous immersion freezing nucleation. For given drops, changes in freezing temperatures between cycles were relatively small (<1°C) for the majority of the events. These frequent small fluctuations in freezing temperatures are interpreted as reflections of the random nature of embryo growth and are associated with a nucleation rate that is a function of a temperature difference from the characteristic temperatures of nuclei. About a sixth of the changes were larger, up to ±5°C, and exhibited some systematic patterns. These are thought to arise from alterations of the nuclei, some being permanent and some transitory. The results are used to suggest ways of describing ice initiation in cloud models that account for both the temperature and the time dependence of freezing nucleation.

  3. Repeatability and randomness in heterogeneous freezing nucleation

    NASA Astrophysics Data System (ADS)

    Vali, G.

    2008-02-01

    This study is aimed at clarifying the relative importance of the specific character of the nuclei and of the duration of supercooling in heterogeneous freezing nucleation by immersed impurities. Laboratory experiments were carried out in which sets of water drops underwent multiple cycles of freezing and melting. The drops contained suspended particles of mixtures of materials; the resulting freezing temperatures ranged from -6°C to -24°C. Rank correlation coefficients between observed freezing temperatures of the drops in successive runs were >0.9 with very high statistical significance, and thus provide strong support for the modified singular model of heterogeneous immersion freezing nucleation. For given drops, changes in freezing temperatures between cycles were relatively small (<1°C) for the majority of the events. These frequent small fluctuations in freezing temperatures are interpreted as reflections of the random nature of embryo growth and are associated with a nucleation rate that is a function of a temperature difference from the characteristic temperatures of nuclei. About a sixth of the changes were larger, up to ±5°C, and exhibited some systematic patterns. These are thought to arise from alterations of the nuclei, some being permanent and some transitory. The results are used to suggest ways of describing ice initiation in cloud models that account for both the temperature and the time dependence of freezing nucleation.

  4. Heterogeneous Participant Recruitment for Comprehensive Vehicle Sensing.

    PubMed

    Liu, Yazhi; Li, Xiong

    2015-01-01

    Widely distributed mobile vehicles wherein various sensing devices and wireless communication interfaces are installed bring vehicular participatory sensing into practice. However, the heterogeneity of vehicles in terms of sensing capability and mobility, and the participants' expectations on the incentives blackmake the collection of comprehensive sensing data a challenging task. A sensing data quality-oriented optimal heterogeneous participant recruitment strategy is proposed in this paper for vehicular participatory sensing. In the proposed strategy, the differences between the sensing data requirements and the collected sensing data are modeled. An optimization formula is established to model the optimal participant recruitment problem, and a participant utility analysis scheme is built based on the sensing and mobility features of vehicles. Besides, a greedy algorithm is then designed according to the utility of vehicles to recruit the most efficient vehicles with a limited total incentive budget. Real trace-driven simulations show that the proposed strategy can collect 85.4% of available sensing data with 34% incentive budget.

  5. Improving network utilization over heterogeneous airborne networks

    NASA Astrophysics Data System (ADS)

    Griffin, Peter H.; Rickenbach, Brent L.; Rush, Jason A.

    2011-06-01

    Existing and future military networks vary widely in bandwidth and other network characteristics, potentially challenging deployment of services and applications across heterogeneous data links. To address this challenge, General Dynamics and Naval Research Laboratory created network services to allow applications to use wireless data links more efficiently. The basis for the network services are hooks into the data links and transport protocols providing status about the airborne networking environment. The network service can monitor heterogeneous data links on a platform and report on link availability and parameters such as latency and bandwidth. The network service then presents the network characteristics to other services and applications. These services and applications are then able to tune parameters and content based on network parameters. The technology has been demonstrated in several live-flight experiments sponsored by the United States Air Force and United States Navy. The technology was housed on several aircraft with a variety of data links ranging from directional, high-bandwidth systems to omnidirectional, medium-bandwidth systems to stable but low-bandwidth satellite systems. In each of these experiments, image and video data was successfully delivered over tactical data links that varied greatly in bandwidth and delay.

  6. Spreading of persistent infections in heterogeneous populations

    NASA Astrophysics Data System (ADS)

    Sanz, J.; Floría, L. M.; Moreno, Y.

    2010-05-01

    Up to now, the effects of having heterogeneous networks of contacts have been studied mostly for diseases which are not persistent in time, i.e., for diseases where the infectious period can be considered very small compared to the lifetime of an individual. Moreover, all these previous results have been obtained for closed populations, where the number of individuals does not change during the whole duration of the epidemics. Here, we go one step further and analyze, both analytically and numerically, a radically different kind of diseases: those that are persistent and can last for an individual’s lifetime. To be more specific, we particularize to the case of tuberculosis’ (TB) infection dynamics, where the infection remains latent for a period of time before showing up and spreading to other individuals. We introduce an epidemiological model for TB-like persistent infections taking into account the heterogeneity inherent to the population structure. This sort of dynamics introduces new analytical and numerical challenges that we are able to sort out. Our results show that also for persistent diseases the epidemic threshold depends on the ratio of the first two moments of the degree distribution so that it goes to zero in a class of scale-free networks when the system approaches the thermodynamic limit.

  7. Metapopulation dynamics and spatial heterogeneity in cancer.

    PubMed

    González-García, Isabel; Solé, Ricard V; Costa, José

    2002-10-01

    With the advent of drugs targeting specific molecular defects in cancerous cells [Gorre, M. E., et al. (2001) Science 293, 876-880], it is important to understand the degree of genetic heterogeneity present in tumor cell populations and the rules that govern microdiversity in human cancer. Here, we first show that populations with different genotypes in genes influencing cell growth and programmed cell death coexist in advanced malignant tumors of the colon, exhibiting microsatellite instability. Detailed, physical mapping of the diverse populations shows them to be arranged in small, intermingling areas, resulting in a variegated pattern of diversity. Using computational modeling of the experimental data, we find that the coexistence between similar competitors is enhanced, instead of deterred, by spatial dynamics [Hanski, I. (1999) Metapopulation Dynamics (Oxford Univ. Press, New York)]. The model suggests a simple and plausible scenario for the generation of spatial heterogeneity during tumor progression. The emergence and persistence of the patterns of diversity encountered in the tumors can be generated without a need to invoke differences in mutation rates, neutrality of interactions, or separated time scales. We posit that the rules that apply to spatial ecology and explain the maintenance of diversity are also at work in tumors and may underlie tumor microheterogeneity.

  8. Genetic heterogeneity of Usher syndrome type II.

    PubMed Central

    Pieke Dahl, S; Kimberling, W J; Gorin, M B; Weston, M D; Furman, J M; Pikus, A; Möller, C

    1993-01-01

    Usher syndrome is an autosomal recessive disorder characterised by retinitis pigmentosa and congenital sensorineural hearing loss. A gene for Usher syndrome type II (USH2) has been localised to chromosome 1q32-q41. DNA from a family with four of seven sibs affected with clinical characteristics of Usher syndrome type II was genotyped using markers spanning the 1q32-1q41 region. These included D1S70 and D1S81, which are believed to flank USH2. Genotypic results and subsequent linkage analysis indicated non-linkage of this family to these markers. The A test analysis for heterogeneity with this family and 32 other Usher type II families was statistically significant at p < 0.05. Further clinical evaluation of this family was done in light of the linkage results to determine if any phenotypic characteristics would allow for clinical identification of the unlinked type. No clear phenotypic differences were observed; however, this unlinked family may represent a previously unreported subtype of Usher type II characterised by a milder form of retinitis pigmentosa and mild vestibular abnormalities. Heterogeneity of Usher syndrome type II complicates efforts to isolate and clone Usher syndrome genes using linkage analysis and limits the use of DNA markers in early detection of Usher type II. Images PMID:7901420

  9. Heterogeneous information-based artificial stock market

    NASA Astrophysics Data System (ADS)

    Pastore, S.; Ponta, L.; Cincotti, S.

    2010-05-01

    In this paper, an information-based artificial stock market is considered. The market is populated by heterogeneous agents that are seen as nodes of a sparsely connected graph. Agents trade a risky asset in exchange for cash. Besides the amount of cash and assets owned, each agent is characterized by a sentiment. Moreover, agents share their sentiments by means of interactions that are identified by the graph. Interactions are unidirectional and are supplied with heterogeneous weights. The agent's trading decision is based on sentiment and, consequently, the stock price process depends on the propagation of information among the interacting agents, on budget constraints and on market feedback. A central market maker (clearing house mechanism) determines the price process at the intersection of the demand and supply curves. Both closed- and open-market conditions are considered. The results point out the validity of the proposed model of information exchange among agents and are helpful for understanding the role of information in real markets. Under closed market conditions, the interaction among agents' sentiments yields a price process that reproduces the main stylized facts of real markets, e.g. the fat tails of the returns distributions and the clustering of volatility. Within open-market conditions, i.e. with an external cash inflow that results in asset price inflation, also the unitary root stylized fact is reproduced by the artificial stock market. Finally, the effects of model parameters on the properties of the artificial stock market are also addressed.

  10. Effects of microstructural heterogeneity on BGA reliability

    SciTech Connect

    Neilsen, M.K.; Burchett, S.N.; Fang, H.E.; Vianco, P.T.

    1998-07-01

    The near eutectic 60Sn-40Pb alloy is the most commonly used solder for electrical interconnections in electronic packages. This alloy has a number of processing advantages (suitable melting point of 183 C and good wetting behavior). However, under conditions of cyclic strain and temperature (thermomechanical fatigue), the microstructure of this alloy undergoes a heterogeneous coarsening and failure process that makes the prediction of solder joint lifetime complex. A viscoplastic constitutive model for solder with an internal state variable that tracks microstructural evolution is currently under development. This constitutive model was implemented in to several finite element codes. With this computational capability, the thermomechanical response of solder interconnects, including microstructural evolution, can be predicted. This capability was applied to predict the thermomechanical response of a ball grid array (BGA) solder interconnect. BGAs with both homogeneous and heterogeneous initial microstructures were evaluated. In this paper, the constitutive model used to describe the solder will first be briefly discussed. The results of computational studies to determine the thermomechanical response of BGA solder interconnects will then be presented.

  11. Heterogeneity in nanoparticles influences biodistribution and targeting

    PubMed Central

    Adjei, Isaac M; Peetla, Chiranjeevi; Labhasetwar, Vinod

    2013-01-01

    Aim A large fraction of the administered dose of nanoparticles (NPs) localizes into nontarget tissue, which could be due to the heterogeneous population of NPs. Materials & methods To investigate the impact of the above issue, we simultaneously tracked the biodistribution using optical imaging of two different sized poly (d,l-lactide co-glycolide) NPs, which also varied in their surface charge and texture, in a prostate tumor xenograft mouse model. Results Although formulated using the same polymer and emulsifier concentration, small NPs were neutral (S-neutral-NPs) whereas large NPs were anionic (L-anionic-NPs). Simultaneous injection of these NPs, representing heterogeneity, shows significantly different biodistribution. S-neutral-NPs demonstrated longer circulation time than L-anionic-NPs (t1/2 = 96 vs 13 min); accounted for 75% of total NPs accumulated in the tumor, and showed 13-fold greater tumor to liver signal intensity ratio than L-anionic-NPs. Conclusion The data underscore the importance of formulating nanocarriers of specific properties to enhance their targeting efficacy. PMID:23799984

  12. Fluid dynamics of active heterogeneities in a mantle plume conduit

    NASA Astrophysics Data System (ADS)

    Farnetani, C. G.; Limare, A.; Hofmann, A. W.

    2015-12-01

    Laboratory experiments and numerical simulations indicate that the flow of a purely thermal plume preserves the azimuthal zonation of the source region, thus providing a framework to attribute a deep origin to the isotopic zonation of Hawaiian lavas. However, previous studies were limited to passive heterogeneities not affecting the flow. We go beyond this simplification by considering active heterogeneities which are compositionally denser, or more viscous, and we address the following questions: (1) How do active heterogeneities modify the axially symmetric velocity field of the plume conduit? (2) Under which conditions is the azimuthal zonation of the source region no longer preserved in the plume stem? (3) How do active heterogeneities deform during upwelling and what is their shape once at sublithospheric depths? We conducted both laboratory experiments, using a Particle Image Velocimetry (PIV) to calculate the velocity field, and high resolution three-dimensional simulations where millions of tracers keep track of the heterogeneous fluid. For compositionally denser heterogeneities we cover a range of buoyancy ratios 0heterogeneities, the range of viscosity ratios is 0<λ<20, where λ=ηheterogeneity/ηfluid and η is viscosity. The initial heterogeneity has the arbitrary shape of a sphere and we vary its volume and its distance from the plume axis. We find that by increasing λ, the shape of the heterogeneity changes from filament-like to blob-like characterized by internal rotation and little stretching. By increasing B the heterogeneity tends to spread at the base of the plume stem and to rise as a tendril close to the axis, so that the initial zonation may be poorly preserved. We also find that the plume velocity field can be profoundly modified by active heterogeneities, and we explore the relation between strain rates and the evolving shape of the upwelling heterogeneity.

  13. Mutation-selection models of coding sequence evolution with site-heterogeneous amino acid fitness profiles

    PubMed Central

    Rodrigue, Nicolas; Philippe, Hervé; Lartillot, Nicolas

    2010-01-01

    Modeling the interplay between mutation and selection at the molecular level is key to evolutionary studies. To this end, codon-based evolutionary models have been proposed as pertinent means of studying long-range evolutionary patterns and are widely used. However, these approaches have not yet consolidated results from amino acid level phylogenetic studies showing that selection acting on proteins displays strong site-specific effects, which translate into heterogeneous amino acid propensities across the columns of alignments; related codon-level studies have instead focused on either modeling a single selective context for all codon columns, or a separate selective context for each codon column, with the former strategy deemed too simplistic and the latter deemed overparameterized. Here, we integrate recent developments in nonparametric statistical approaches to propose a probabilistic model that accounts for the heterogeneity of amino acid fitness profiles across the coding positions of a gene. We apply the model to a dozen real protein-coding gene alignments and find it to produce biologically plausible inferences, for instance, as pertaining to site-specific amino acid constraints, as well as distributions of scaled selection coefficients. In their account of mutational features as well as the heterogeneous regimes of selection at the amino acid level, the modeling approaches studied here can form a backdrop for several extensions, accounting for other selective features, for variable population size, or for subtleties of mutational features, all with parameterizations couched within population-genetic theory. PMID:20176949

  14. Phenotypic Heterogeneity Enables Uropathogenic Escherichia coli To Evade Killing by Antibiotics and Serum Complement

    PubMed Central

    Putrinš, Marta; Kogermann, Karin; Lukk, Eliisa; Lippus, Markus; Varik, Vallo

    2015-01-01

    Uropathogenic strains of Escherichia coli (UPEC) are the major cause of bacteremic urinary tract infections. Survival in the bloodstream is associated with different mechanisms that help to resist serum complement-mediated killing. While the phenotypic heterogeneity of bacteria has been shown to influence antibiotic tolerance, the possibility that it makes cells refractory to killing by the immune system has not been experimentally tested. In the present study we sought to determine whether the heterogeneity of bacterial cultures is relevant to bacterial targeting by the serum complement system. We monitored cell divisions in the UPEC strain CFT073 with fluorescent reporter protein. Stationary-phase cells were incubated in active or heat-inactivated human serum in the presence or absence of different antibiotics (ampicillin, norfloxacin, and amikacin), and cell division and complement protein C3 binding were measured by flow cytometry and immunofluorescence microscopy. Heterogeneity in the doubling times of CFT073 cells in serum enabled three phenotypically different subpopulations to be distinguished, all of them being recognized by the C3 component of the complement system. The population of rapidly growing cells resists serum complement-mediated lysis. The dominant subpopulation of cells with intermediate growth rate is susceptible to serum. The third population, which does not resume growth upon dilution from stationary phase, is simultaneously protected from serum complement and antibiotics. PMID:25561706

  15. Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila

    DOE PAGES

    Stoiber, Marcus H.; Olson, Sara; May, Gemma E.; ...

    2015-08-20

    In eukaryotic cells, RNAs exist as ribonucleoprotein particles (RNPs). Despite the importance of these complexes in many biological processes, including splicing, polyadenylation, stability, transportation, localization, and translation, their compositions are largely unknown. We affinity-purified 20 distinct RNA-binding proteins (RBPs) from cultured Drosophila melanogaster cells under native conditions and identified both the RNA and protein compositions of these RNP complexes. We identified “high occupancy target” (HOT) RNAs that interact with the majority of the RBPs we surveyed. HOT RNAs encode components of the nonsense-mediated decay and splicing machinery, as well as RNA-binding and translation initiation proteins. The RNP complexes contain proteinsmore » and mRNAs involved in RNA binding and post-transcriptional regulation. Genes with the capacity to produce hundreds of mRNA isoforms, ultracomplex genes, interact extensively with heterogeneous nuclear ribonuclear proteins (hnRNPs). Our data are consistent with a model in which subsets of RNPs include mRNA and protein products from the same gene, indicating the widespread existence of auto-regulatory RNPs. Lastly, from the simultaneous acquisition and integrative analysis of protein and RNA constituents of RNPs, we identify extensive cross-regulatory and hierarchical interactions in post-transcriptional control.« less

  16. Harvesting geographic features from heterogeneous raster maps

    NASA Astrophysics Data System (ADS)

    Chiang, Yao-Yi

    2010-11-01

    Raster maps offer a great deal of geospatial information and are easily accessible compared to other geospatial data. However, harvesting geographic features locked in heterogeneous raster maps to obtain the geospatial information is challenging. This is because of the varying image quality of raster maps (e.g., scanned maps with poor image quality and computer-generated maps with good image quality), the overlapping geographic features in maps, and the typical lack of metadata (e.g., map geocoordinates, map source, and original vector data). Previous work on map processing is typically limited to a specific type of map and often relies on intensive manual work. In contrast, this thesis investigates a general approach that does not rely on any prior knowledge and requires minimal user effort to process heterogeneous raster maps. This approach includes automatic and supervised techniques to process raster maps for separating individual layers of geographic features from the maps and recognizing geographic features in the separated layers (i.e., detecting road intersections, generating and vectorizing road geometry, and recognizing text labels). The automatic technique eliminates user intervention by exploiting common map properties of how road lines and text labels are drawn in raster maps. For example, the road lines are elongated linear objects and the characters are small connected-objects. The supervised technique utilizes labels of road and text areas to handle complex raster maps, or maps with poor image quality, and can process a variety of raster maps with minimal user input. The results show that the general approach can handle raster maps with varying map complexity, color usage, and image quality. By matching extracted road intersections to another geospatial dataset, we can identify the geocoordinates of a raster map and further align the raster map, separated feature layers from the map, and recognized features from the layers with the geospatial

  17. [Phenomenon of polyembryony. Genetic heterogeneity of seeds].

    PubMed

    Batygina, T B; Vinogradova, G Iu

    2007-01-01

    Different concepts of polyembryony and genetic heterogeneity of seeds in flower plants have been reviewed. Different types, ways, and forms of plant reproduction appeared in the course of evolution as a consequences of the attached mode of life and autotrophy. This is ascribed to totipotency, "stemminess" of plant cells, and presence of constantly functioning meristems, which determined to a great extent the system of plant safety. There are two ways of formation of a new individual: sexual process --> gamospermy involving meiosis and gamete fusion and asexual process --> agamospermy without meiosis and gamete fusion and two types of reproduction: seed and vegetative. Both processes may take place simultaneously in one seed, as a result of which many embryos of different origins are formed: uniparental and biparental inheritance. Traditionally, this phenomenon is called polyembryony. It comprises embryoidogeny (a new category of vegetative reproduction): formation of somatic embryos (= embryoids) in the flower, seed, and on vegetative organs. Genetic heterogeneity is one of the most important characteristics of seeds, which is based on different phenomena, such as embryogeny, embryoidogeny, and gametophytic and sporophytic apomixes. When describing two types of polyembryony, sporophytic (nucellar, integumental, cleavage) and gametophytic (synergidal, antipodal), a great attention is paid to characterization of initial cells of the sexual and adventive embryos. A new concept of apogamety is developed from new positions (totipotency and "stemminess"), which is based on different genesis of cells of the egg and antipodal systems. Five possible pathways of formation of the adventive embryos have been proposed from cells of the egg apparatus. Specific features of the formation of adventive embryos in the case of gametophytic apomixis, such as androgenesis and semigamy, are discussed. Morphogenesis of the sexual and adventive embryos proceeds in the mother organism and

  18. OH initiated heterogeneous degradation of organophosphorus compounds

    NASA Astrophysics Data System (ADS)

    Liggio, J.; Liu, Y.; Harner, T.; Jantunen, L.; Shoeib, M.; Li, S.

    2013-12-01

    Organophosphorus compounds (OPs) have been extensively used worldwide as flame retardants, plasticizers, antifoaming agents, and additives because of their favorable physicochemical characteristics. The global consumption of OPs is likely to greatly increase due to the phasing out of bromine-containing flame retardants (BFRs) with OPs identified as possible substitutes. In most applications, OPs easily leach out of the material into the environment via volatilization, abrasion, and dissolution and have been observed widely in atmospheric particles even in polar regions. However, little is known about their atmospheric fate. The Canadian Chemicals Management Plan (CMP) has targeted OP FRs for risk assessment, including assessing stability and atmospheric transport potential of OP FRs and other priority chemicals that are associated primarily with particles. In the current study, OH initiated heterogeneous reaction kinetics of tris(1,3-dichloro-2-propyl) phosphate (TDCPP), tris-2-ethylhexyl-phosphate (TEHP), tris-2-butoxyethyl-phosphate (TBEP), and tri-phenyl phosphate (TPhP) coated on (NH4)2SO4 were investigated using a photo-chemical flow tube which was coupled to an Aerosol Mass Spectrometer (AMS) and Proton Transfer Reaction Mass Spectrometer (PTR-MS). second-order rate constants (k2) for the heterogeneous loss of TPhP, TEHP and TDCPP were (2.07×0.19)×10-12, (2.69×0.63)×10-12 and (9.22×0.92)×10-13 cm3 molecule-1 s-1, respectively, from which approximate atmospheric lifetimes were estimated to be 5.6 (5.2-6.0), 4.3 (3.5-5.6), and 12.6 (11.4-14.0) days. These results represent the first reported estimates of heterogeneous rate constants for these species, and suggest that particle bound OPEs will be highly persistent in the atmosphere, supporting the assumption that OPEs can undergo medium or long-range transport, as proposed on the basis of field measurements.

  19. "Heterogeneity within order" in metal-organic frameworks.

    PubMed

    Furukawa, Hiroyasu; Müller, Ulrich; Yaghi, Omar M

    2015-03-09

    Metal-organic frameworks (MOFs) are constructed by linking inorganic units with organic linkers to make extended networks. Though more than 20 000 MOF structures have been reported most of these are ordered and largely composed of a limited number of different kinds building units, and very few have multiple different building units (heterogeneous). Although heterogeneity and multiplicity is a fundamental characteristic of biological systems, very few synthetic materials incorporate heterogeneity without losing crystalline order. Thus, the question arises: how do we introduce heterogeneity into MOFs without losing their ordered structure? This Review outlines strategies for varying the building units within both the backbone of the MOF and its pores to produce the heterogeneity that is sought after. The impact this heterogeneity imparts on the properties of a MOF is highlighted. We also provide an update on the MOF industry as part of this themed issue for the 150th anniversary of BASF.

  20. Role of epigenetics in lung cancer heterogeneity and clinical implication.

    PubMed

    Dong, Nian; Shi, Lin; Wang, Diane C; Chen, Chengshui; Wang, Xiangdong

    2016-08-26

    Lung cancer, as a highly heterogeneous disease, can be initiated and progressed through the interaction between permanent genetic mutations and dynamic epigenetic alterations. However, the mediating mechanisms of epigenetics in cancer heterogeneity remain unclear. The evolution of cancer, the existence of cancer stem cells (CSCs) and the phenomenon of epithelial-mesenchymal transition (EMT) have been reported to be involved in lung cancer heterogeneity. In this review, we briefly recap the definition of heterogeneity and concept of epigenetics, highlight the potential roles and mechanisms of epigenetic regulation in heterogeneity of lung cancer, and summarize the diagnostic and therapeutic implications of epigenetic alterations in lung cancer, especially the role of DNA methylation and histone acetylation. Deep understanding of epigenetic regulation in cancer heterogeneity is instrumental to the design of novel therapeutic approaches that target lung cancer.

  1. Mining Functional Modules in Heterogeneous Biological Networks Using Multiplex PageRank Approach

    PubMed Central

    Li, Jun; Zhao, Patrick X.

    2016-01-01

    Identification of functional modules/sub-networks in large-scale biological networks is one of the important research challenges in current bioinformatics and systems biology. Approaches have been developed to identify functional modules in single-class biological networks; however, methods for systematically and interactively mining multiple classes of heterogeneous biological networks are lacking. In this paper, we present a novel algorithm (called mPageRank) that utilizes the Multiplex PageRank approach to mine functional modules from two classes of biological networks. We demonstrate the capabilities of our approach by successfully mining functional biological modules through integrating expression-based gene-gene association networks and protein-protein interaction networks. We first compared the performance of our method with that of other methods using simulated data. We then applied our method to identify the cell division cycle related functional module and plant signaling defense-related functional module in the model plant Arabidopsis thaliana. Our results demonstrated that the mPageRank method is effective for mining sub-networks in both expression-based gene-gene association networks and protein-protein interaction networks, and has the potential to be adapted for the discovery of functional modules/sub-networks in other heterogeneous biological networks. The mPageRank executable program, source code, the datasets and results of the presented two case studies are publicly and freely available at http://plantgrn.noble.org/MPageRank/. PMID:27446133

  2. At-Resin Research: Biotechnical Support and Heterogeneous Catalysis

    DTIC Science & Technology

    1990-07-20

    Heterogeneous Catalysis 12. PERSONAL AUTHOR(S) Sachdeva, Yesh P. 13a. TYPE OF REPORT 113b. TIME COVERED T14. DATE OF REPORT (Year’MonthDay) 11S. PAGE...chiofh SECURITY CLASSIFICATION OF THIS PAGE UNCLASSIFIED AT-RESIN RESEARCH: BIOTECHNICAL SUPPORT AND HETEROGENEOUS CATALYSIS -ffE’i Technical Report...September 1, 1989 to July 15, 1990 c. .. AT-RESIN RESEARCH: BIOTECHNICAL SUPPORT AND HETEROGENEOUS CATALYSIS Contract #: FQ8671-8900317 Subject: Ilfr=N

  3. Molecular Heterogeneity in Primary and Metastatic Prostate Tumor Tissue

    DTIC Science & Technology

    2015-06-01

    AWARD NUMBER: W81XWH-12-1-0072 TITLE: Molecular Heterogeneity in Primary and Metastatic Prostate Tumor Tissue PRINCIPAL INVESTIGATOR: Dr. Julie...Molecular Heterogeneity in Primary and Metastatic Prostate Tumor Tissue 5a. CONTRACT NUMBER W81XWH-12-1-0072 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...heterogeneity in PTEN loss in tumor tissue and prostate cancer prognosis. Aim 2 aimed to compare gene expression profiles between primary and lymph

  4. Spatially heterogeneous wastage of Himalayan glaciers.

    PubMed

    Fujita, Koji; Nuimura, Takayuki

    2011-08-23

    We describe volumetric changes in three benchmark glaciers in the Nepal Himalayas on which observations have been made since the 1970s. Compared with the global mean of glacier mass balance, the Himalayan glaciers showed rapid wastage in the 1970s-1990s, but similar wastage in the last decade. In the last decade, a glacier in an arid climate showed negative but suppressed mass balance compared with the period 1970s-1990s, whereas two glaciers in a humid climate showed accelerated wastage. A mass balance model with downscaled gridded datasets depicts the fate of the observed glaciers. We also show a spatially heterogeneous distribution of glacier wastage in the Asian highlands, even under the present-day climate warming.

  5. Chinese Immigrant Wealth: Heterogeneity in Adaptation

    PubMed Central

    Agius Vallejo, Jody; Aronson, Brian

    2016-01-01

    Chinese immigrants are a diverse and growing group whose members provide a unique opportunity to examine within-immigrant group differences in adaptation. In this paper, we move beyond thinking of national-origin groups as homogenous and study variation among Chinese immigrants in wealth ownership, a critical indicator of adaptation that attracts relatively little attention in the immigration literature. We develop an analytical approach that considers national origin, tenure in the U.S., and age to examine heterogeneity in economic adaptation among the immigrant generation. Our results show that variations among Chinese immigrants explain within-group differences in net worth, asset ownership, and debt. These differences also account for important variation between Chinese immigrants, natives, and other immigrant groups and provide important, new insight into the processes that lead to immigrant adaptation and long-term class stability. PMID:27977737

  6. Electrokinetic transport of heterogeneous particles in suspension

    NASA Technical Reports Server (NTRS)

    Velegol, D.; Garoff, Stephen; Anderson, John L.

    1994-01-01

    The Smoluchowski equation for electrophoresis predicts that the electrophoretic velocity of a particle is proportional to its zeta potential but not its size, shape, or orientation. Furthermore, the equation predicts that the rotation rate is identically zero. The Smoluchowski equation fails for heterogeneous particles (i.e., those with nonuniform zeta potentials). Recent theories and experiments show that particles with a dipole moment of zeta potential rotate into alignment with an externally applied electric field. For doublets (particles composed of two spheres) the rotation rate depends on (1) whether the spheres are rigidly rocked or freely rotating, and (2) the gap distance between the spheres. The relative configuration of two coagulated spheres is determined by the colloidal forces of the system. The goal of our research is to use measurements of electrophoretic rotation to determine the gap between two spheres of a colloidal doublet and also to determine whether or not the doublet is rigid.

  7. Heterogeneous reaction of ozone with aluminum oxide

    NASA Technical Reports Server (NTRS)

    Keyser, L. F.

    1976-01-01

    Rates and collision efficiencies for ozone decomposition on aluminum oxide surfaces were determined. Samples were characterized by BET surface area, X-ray diffraction, particle size, and chemical analysis. Collision efficiencies were found to be between 2 times 10 to the -10 power and 2 times 10 to the -9 power. This is many orders of magnitude below the value of 0.000001 to 0.00001 needed for appreciable long-term ozone loss in the stratosphere. An activation energy of 7.2 kcal/mole was found for the heterogeneous reaction between -40 C and 40 C. Effects of pore diffusion, outgassing and treatment of the aluminum oxide with several chemical species were also investigated.

  8. Job Scheduling in a Heterogeneous Grid Environment

    NASA Technical Reports Server (NTRS)

    Shan, Hong-Zhang; Smith, Warren; Oliker, Leonid; Biswas, Rupak

    2004-01-01

    Computational grids have the potential for solving large-scale scientific problems using heterogeneous and geographically distributed resources. However, a number of major technical hurdles must be overcome before this potential can be realized. One problem that is critical to effective utilization of computational grids is the efficient scheduling of jobs. This work addresses this problem by describing and evaluating a grid scheduling architecture and three job migration algorithms. The architecture is scalable and does not assume control of local site resources. The job migration policies use the availability and performance of computer systems, the network bandwidth available between systems, and the volume of input and output data associated with each job. An extensive performance comparison is presented using real workloads from leading computational centers. The results, based on several key metrics, demonstrate that the performance of our distributed migration algorithms is significantly greater than that of a local scheduling framework and comparable to a non-scalable global scheduling approach.

  9. Heterogeneous distributed databases: A case study

    NASA Technical Reports Server (NTRS)

    Stewart, Tracy R.; Mukkamala, Ravi

    1991-01-01

    Alternatives are reviewed for accessing distributed heterogeneous databases and a recommended solution is proposed. The current study is limited to the Automated Information Systems Center at the Naval Sea Combat Systems Engineering Station at Norfolk, VA. This center maintains two databases located on Digital Equipment Corporation's VAX computers running under the VMS operating system. The first data base, ICMS, resides on a VAX11/780 and has been implemented using VAX DBMS, a CODASYL based system. The second database, CSA, resides on a VAX 6460 and has been implemented using the ORACLE relational database management system (RDBMS). Both databases are used for configuration management within the U.S. Navy. Different customer bases are supported by each database. ICMS tracks U.S. Navy ships and major systems (anti-sub, sonar, etc.). Even though the major systems on ships and submarines have totally different functions, some of the equipment within the major systems are common to both ships and submarines.

  10. Metastable dynamics in heterogeneous neural fields

    PubMed Central

    Schwappach, Cordula; Hutt, Axel; beim Graben, Peter

    2015-01-01

    We present numerical simulations of metastable states in heterogeneous neural fields that are connected along heteroclinic orbits. Such trajectories are possible representations of transient neural activity as observed, for example, in the electroencephalogram. Based on previous theoretical findings on learning algorithms for neural fields, we directly construct synaptic weight kernels from Lotka-Volterra neural population dynamics without supervised training approaches. We deliver a MATLAB neural field toolbox validated by two examples of one- and two-dimensional neural fields. We demonstrate trial-to-trial variability and distributed representations in our simulations which might therefore be regarded as a proof-of-concept for more advanced neural field models of metastable dynamics in neurophysiological data. PMID:26175671

  11. Tunable Assembly of Heterogeneously Charged Colloids

    PubMed Central

    2014-01-01

    The self-assembly of colloidal particles is a route to designed materials production that combines high flexibility, cost effectiveness, and the opportunity to create ordered structures at length scales ranging from nano- to micrometers. For many practical applications in electronics, photovoltaics, and biomimetic material synthesis, ordered mono- and bilayers are often needed. Here we present a novel and simple way to tune via external parameters the ordering of heterogeneously charged colloids into quasi two-dimensional structures. Depending on the charges of the underlying substrate and of the particles, a rich and versatile assembly scenario takes place, resulting from the complex interplay between directional attractive and repulsive particle–particle and particle–substrate interactions. Upon subtle variations of the relative charge of the system components, emerging via pH modification, reversible changes either from extended aggregates to a monomeric phase or from triangular to square domains are observed. PMID:24842542

  12. Cancer heterogeneity--a multifaceted view.

    PubMed

    De Sousa E Melo, Felipe; Vermeulen, Louis; Fessler, Evelyn; Medema, Jan Paul

    2013-08-01

    Cancers of various organs have been categorized into distinct subtypes after increasingly sophisticated taxonomies. Additionally, within a seemingly homogeneous subclass, individual cancers contain diverse tumour cell populations that vary in important cancer-specific traits such as clonogenicity and invasive potential. Differences that exist between and within a given tumour type have hampered significantly both the proper selection of patients that might benefit from therapy, as well as the development of new targeted agents. In this review, we discuss the differences associated with organ-specific cancer subtypes and the factors that contribute to intra-tumour heterogeneity. It is of utmost importance to understand the biological causes that distinguish tumours as well as distinct tumour cell populations within malignancies, as these will ultimately point the way to more rational anti-cancer treatments.

  13. Stochastic epidemic dynamics on extremely heterogeneous networks

    NASA Astrophysics Data System (ADS)

    Parra-Rojas, César; House, Thomas; McKane, Alan J.

    2016-12-01

    Networks of contacts capable of spreading infectious diseases are often observed to be highly heterogeneous, with the majority of individuals having fewer contacts than the mean, and a significant minority having relatively very many contacts. We derive a two-dimensional diffusion model for the full temporal behavior of the stochastic susceptible-infectious-recovered (SIR) model on such a network, by making use of a time-scale separation in the deterministic limit of the dynamics. This low-dimensional process is an accurate approximation to the full model in the limit of large populations, even for cases when the time-scale separation is not too pronounced, provided the maximum degree is not of the order of the population size.

  14. Noise and heterogeneity in bacterial communication

    NASA Astrophysics Data System (ADS)

    Hagen, Stephen

    2010-10-01

    Many bacterial species engage in a sophisticated chemical communication behavior known as quorum sensing: Individual cells release small diffusible molecules into their environment while simultaneously detecting the local concentration of these molecules. Important collective behaviors of the bacterial population are triggered once the signal concentration accumulates to a certain level. Although quorum sensing is widespread in microbiology, the physical environment of bacteria is often very heterogeneous and diffusion may be inefficient. Meanwhile the genetic circuitry that generates and detects the chemical signal is microscopic and subject to stochasticity. This raises interesting physical questions about how much information is actually carried by these chemical signals, and what an individual cell can learn about its environment through this mechanism. I will present a general introduction to quorum sensing with emphasis on our experimental studies of the role of noise and microenvironment on this phenomenon.

  15. Ultrasound scatter in heterogeneous 3D microstructures

    NASA Astrophysics Data System (ADS)

    Engle, B. J.; Roberts, R. A.; Grandin, R. J.

    2017-02-01

    This paper reports on a computational study of ultrasound propagation in heterogeneous metal microstructures. Random spatial fluctuations in elastic properties over a range of length scales relative to ultrasound wavelength can give rise to scatter-induced attenuation, backscatter noise, and phase front aberration. It is of interest to quantify the dependence of these phenomena on the microstructure parameters, for the purpose of quantifying deleterious consequences on flaw detectability, and for the purpose of material characterization. Valuable tools for estimation of microstructure parameters (e.g. grain size) through analysis of ultrasound backscatter have been developed based on approximate weak-scattering models. While useful, it is understood that these tools display inherent inaccuracy when multiple scattering phenomena significantly contribute to the measurement. It is the goal of this work to supplement weak scattering model predictions with corrections derived through application of an exact computational scattering model to explicitly prescribed microstructures.

  16. Heterogeneous Interactions of Acetaldehyde and Sulfuric Acid

    NASA Technical Reports Server (NTRS)

    Michelsen, R. R.; Ashbourn, S. F. M.; Iraci, L. T.

    2004-01-01

    The uptake of acetaldehyde [CH3CHO] by aqueous sulfuric acid has been studied via Knudsen cell experiments over ranges of temperature (210-250 K) and acid concentration (40-80 wt. %) representative of the upper troposphere. The Henry's law constants for acetaldehyde calculated from these data range from 6 x 10(exp 2) M/atm for 40 wt. % H2SO4 at 228 K to 2 x 10(exp 5) M/atm for 80 wt. % H2SO4 at 212 K. In some instances, acetaldehyde uptake exhibits apparent steady-state loss. The possible sources of this behavior, including polymerization, will be explored. Furthermore, the implications for heterogeneous reactions of aldehydes in sulfate aerosols in the upper troposphere will be discussed.

  17. Applications of neutron scattering to heterogeneous catalysis

    NASA Astrophysics Data System (ADS)

    Parker, Stewart F.; Lennon, David

    2016-09-01

    Historically, most studies of heterogeneous catalysts that have used neutron vibrational spectroscopy have employed indirect geometry instruments with a low (<40 cm-1) final energy. In this paper we examine the reasons why this has been the case and highlight the advantages and disadvantages of this approach. We then show how some of these may be overcome by the use of direct geometry spectrometers. We illustrate the use of direct geometry spectrometers with examples from reforming of methane to synthesis gas (CO + H2) over Ni/Al2O3 catalysts and an operando study of CO oxidation. We conclude with a proposal for a unique instrument that combines both indirect and direct geometry spectrometers.

  18. Shock wave structure in heterogeneous reactive media

    SciTech Connect

    Baer, M.R.

    1997-06-01

    Continuum mixture theory and mesoscale modeling are applied to describe the behavior of shock-loaded heterogeneous media. One-dimensional simulations of gas-gun experiments demonstrate that the wave features are well described by mixture theory, including reflected wave behavior and conditions where significant reaction is initiated. Detailed wave fields are resolved in numerical simulations of impact on a lattice of discrete explosive {open_quotes}crystals{close_quotes}. It is shown that rapid distortion first occurs at material contact points; the nature of the dispersive fields includes large amplitude fluctuations of stress over several particle pathlengths. Localization of energy causes {open_quotes}hot-spots{close_quotes} due to shock focusing and plastic work as material flows into interstitial regions.

  19. Achondrogenesis II-hypochondrogenesis: variability versus heterogeneity.

    PubMed

    Borochowitz, Z; Ornoy, A; Lachman, R; Rimoin, D L

    1986-06-01

    Recently hypochondrogenesis was described as a form of neonatally lethal dwarfism said to resemble spondyloepiphyseal dysplasia congenita radiographically and achondrogenesis II morphologically. Because of the difficulty in distinguishing radiographically between mild achondrogenesis II and severe hypochondrogenesis, we performed a clinical, radiographic, and morphologic study of 24 cases originally classified as either achondrogenesis II or hypochondrogenesis, in an attempt to distinguish between heterogeneity and clinical variability. Review of the radiographic findings in these cases show a fairly continuous spectrum of bony defects, rather than two distinct radiographic syndromes. Chondro-osseous histology and ultrastructure was similar in all cases regardless of severity and was characterized by hypervascularity and hypercellularity of the cartilage with multiple small, round dilated cysternae of rough endoplasmic reticulum. These findings suggest that hypochondrogenesis and achondrogenesis type II represent a spectrum with marked phenotypic variability.

  20. Dynamics on modular networks with heterogeneous correlations

    SciTech Connect

    Melnik, Sergey; Porter, Mason A.; Mucha, Peter J.; Gleeson, James P.

    2014-06-15

    We develop a new ensemble of modular random graphs in which degree-degree correlations can be different in each module, and the inter-module connections are defined by the joint degree-degree distribution of nodes for each pair of modules. We present an analytical approach that allows one to analyze several types of binary dynamics operating on such networks, and we illustrate our approach using bond percolation, site percolation, and the Watts threshold model. The new network ensemble generalizes existing models (e.g., the well-known configuration model and Lancichinetti-Fortunato-Radicchi networks) by allowing a heterogeneous distribution of degree-degree correlations across modules, which is important for the consideration of nonidentical interacting networks.

  1. RMIX: A Dynamic, Heterogeneous, Reconfigurable Communication Framework

    SciTech Connect

    Engelmann, Christian; Geist, Al

    2006-01-01

    RMIX is a dynamic, heterogeneous, reconfigurable communication framework that allows software components to communicate using various RMI/RPC protocols, such as ONC RPC, Java RMI and SOAP, by facilitating dynamically loadable provider plug-ins to supply different protocol stacks. With this paper, we present a native (C-based), flexible, adaptable, multi-protocol RMI/RPC communication framework that complements the Java-based RMIX variant previously developed by our partner team at Emory University. Our approach offers the same multi-protocol RMI/RPC services and advanced invocation semantics via a C-based interface that does not require an object-oriented programming language. This paper provides a detailed description of our RMIX framework architecture and some of its features. It describes the general use case of the RMIX framework and its integration into the Harness metacomputing environment in form of a plug-in.

  2. Imaging plants dynamics in heterogenic environments.

    PubMed

    Fiorani, Fabio; Rascher, Uwe; Jahnke, Siegfried; Schurr, Ulrich

    2012-04-01

    Noninvasive imaging sensors and computer vision approaches are key technologies to quantify plant structure, physiological status, and performance. Today, imaging sensors exploit a wide range of the electromagnetic spectrum, and they can be deployed to measure a growing number of traits, also in heterogenic environments. Recent advances include the possibility to acquire high-resolution spectra by imaging spectroscopy and classify signatures that might be informative of plant development, nutrition, health, and disease. Three-dimensional (3D) reconstruction of surfaces and volume is of particular interest, enabling functional and mechanistic analyses. While taking pictures is relatively easy, quantitative interpretation often remains challenging and requires integrating knowledge of sensor physics, image analysis, and complex traits characterizing plant phenotypes.

  3. Does Environmental Heterogeneity Promote Cognitive Abilities?

    PubMed

    González-Gómez, Paulina L; Razeto-Barry, Pablo; Araya-Salas, Marcelo; Estades, Cristian F

    2015-09-01

    In the context of global change the possible loss of biodiversity has been identified as a major concern. Biodiversity could be seriously threatened as a direct consequence of changes in availability of food, changing thermal conditions, and loss and fragmentation of habitat. Considering the magnitude of global change, an understanding of the mechanisms involved in coping with a changing environment is urgent. We explore the hypothesis that species and individuals experiencing highly variable environments are more likely to develop a wider range of responses to handle the different and unpredictable conditions imposed by global change. In the case of vertebrates, the responses to the challenges imposed by unpredictable perturbations ultimately are linked to cognitive abilities allowing the solving of problems, and the maximization of energy intake. Our models were hummingbirds, which offer a particularly compelling group in which to examine the functional and mechanistic links between behavioral and energetic strategies in individuals experiencing different degrees of social and environmental heterogeneity.

  4. Comprehensive monitoring for heterogeneous geographically distributed storage

    SciTech Connect

    Ratnikova, Natalia; Karavakis, E.; Lammel, S.; Wildish, Tony

    2015-12-23

    Storage capacity at CMS Tier-1 and Tier-2 sites reached over 100 Petabytes in 2014, and will be substantially increased during Run 2 data taking. The allocation of storage for the individual users analysis data, which is not accounted as a centrally managed storage space, will be increased to up to 40%. For comprehensive tracking and monitoring of the storage utilization across all participating sites, CMS developed a space monitoring system, which provides a central view of the geographically dispersed heterogeneous storage systems. The first prototype was deployed at pilot sites in summer 2014, and has been substantially reworked since then. In this study, we discuss the functionality and our experience of system deployment and operation on the full CMS scale.

  5. Comprehensive Monitoring for Heterogeneous Geographically Distributed Storage

    SciTech Connect

    Ratnikova, N.; Karavakis, E.; Lammel, S.; Wildish, T.

    2015-12-23

    Storage capacity at CMS Tier-1 and Tier-2 sites reached over 100 Petabytes in 2014, and will be substantially increased during Run 2 data taking. The allocation of storage for the individual users analysis data, which is not accounted as a centrally managed storage space, will be increased to up to 40%. For comprehensive tracking and monitoring of the storage utilization across all participating sites, CMS developed a space monitoring system, which provides a central view of the geographically dispersed heterogeneous storage systems. The first prototype was deployed at pilot sites in summer 2014, and has been substantially reworked since then. In this paper we discuss the functionality and our experience of system deployment and operation on the full CMS scale.

  6. Comprehensive monitoring for heterogeneous geographically distributed storage

    DOE PAGES

    Ratnikova, Natalia; Karavakis, E.; Lammel, S.; ...

    2015-12-23

    Storage capacity at CMS Tier-1 and Tier-2 sites reached over 100 Petabytes in 2014, and will be substantially increased during Run 2 data taking. The allocation of storage for the individual users analysis data, which is not accounted as a centrally managed storage space, will be increased to up to 40%. For comprehensive tracking and monitoring of the storage utilization across all participating sites, CMS developed a space monitoring system, which provides a central view of the geographically dispersed heterogeneous storage systems. The first prototype was deployed at pilot sites in summer 2014, and has been substantially reworked since then.more » In this study, we discuss the functionality and our experience of system deployment and operation on the full CMS scale.« less

  7. Job scheduling in a heterogenous grid environment

    SciTech Connect

    Oliker, Leonid; Biswas, Rupak; Shan, Hongzhang; Smith, Warren

    2004-02-11

    Computational grids have the potential for solving large-scale scientific problems using heterogeneous and geographically distributed resources. However, a number of major technical hurdles must be overcome before this potential can be realized. One problem that is critical to effective utilization of computational grids is the efficient scheduling of jobs. This work addresses this problem by describing and evaluating a grid scheduling architecture and three job migration algorithms. The architecture is scalable and does not assume control of local site resources. The job migration policies use the availability and performance of computer systems, the network bandwidth available between systems, and the volume of input and output data associated with each job. An extensive performance comparison is presented using real workloads from leading computational centers. The results, based on several key metrics, demonstrate that the performance of our distributed migration algorithms is significantly greater than that of a local scheduling framework and comparable to a non-scalable global scheduling approach.

  8. Income distribution: An adaptive heterogeneous model

    NASA Astrophysics Data System (ADS)

    da Silva, L. C.; de Figueirêdo, P. H.

    2014-02-01

    In this communication an adaptive process is introduced into a many-agent model for closed economic system in order to establish general features of income distribution. In this new version agents are able to modify their exchange parameter ωi of resources through an adaptive process. The conclusions indicate that assuming an instantaneous learning behavior of all agents a Γ-distribution for income is reproduced while a frozen behavior establishes a Pareto’s distribution for income with an exponent ν=0.94±0.02. A third case occurs when a heterogeneous “inertia” behavior is introduced leading us to a Γ-distribution at the low income regime and a power-law decay for the large income values with an exponent ν=2.05±0.05. This method enables investigation of the resources flux in the economic environment and produces also bounding values for the Gini index comparable with data evidences.

  9. Seismic signal processing on heterogeneous supercomputers

    NASA Astrophysics Data System (ADS)

    Gokhberg, Alexey; Ermert, Laura; Fichtner, Andreas

    2015-04-01

    The processing of seismic signals - including the correlation of massive ambient noise data sets - represents an important part of a wide range of seismological applications. It is characterized by large data volumes as well as high computational input/output intensity. Development of efficient approaches towards seismic signal processing on emerging high performance computing systems is therefore essential. Heterogeneous supercomputing systems introduced in the recent years provide numerous computing nodes interconnected via high throughput networks, every node containing a mix of processing elements of different architectures, like several sequential processor cores and one or a few graphical processing units (GPU) serving as accelerators. A typical representative of such computing systems is "Piz Daint", a supercomputer of the Cray XC 30 family operated by the Swiss National Supercomputing Center (CSCS), which we used in this research. Heterogeneous supercomputers provide an opportunity for manifold application performance increase and are more energy-efficient, however they have much higher hardware complexity and are therefore much more difficult to program. The programming effort may be substantially reduced by the introduction of modular libraries of software components that can be reused for a wide class of seismology applications. The ultimate goal of this research is design of a prototype for such library suitable for implementing various seismic signal processing applications on heterogeneous systems. As a representative use case we have chosen an ambient noise correlation application. Ambient noise interferometry has developed into one of the most powerful tools to image and monitor the Earth's interior. Future applications will require the extraction of increasingly small details from noise recordings. To meet this demand, more advanced correlation techniques combined with very large data volumes are needed. This poses new computational problems that

  10. Heterogenous catalysis mediated by plasmon heating.

    PubMed

    Adleman, James R; Boyd, David A; Goodwin, David G; Psaltis, Demetri

    2009-12-01

    We introduce a new method for performing and miniaturizing many types of heterogeneous catalysis involving nanoparticles. The method makes use of the plasmon resonance present in nanoscale metal catalysts to provide the necessary heat of reaction when illuminated with a low-power laser. We demonstrate our approach by reforming a flowing, liquid mixture of ethanol and water over gold nanoparticle catalysts in a microfluidic channel. Plasmon heating of the nanoparticles provides not only the heat of reaction but the means to generate both water and ethanol vapor locally over the catalysts, which in turn allows the chip and the fluid lines to remain at room temperature. The measured products of the reaction, CO(2), CO, and H(2), are consistent with catalytic steam reforming of ethanol. The approach, which we refer to as plasmon-assisted catalysis, is general and can be used with a variety of endothermic catalytic processes involving nanoparticles.

  11. AXAF user interfaces for heterogeneous analysis environments

    NASA Technical Reports Server (NTRS)

    Mandel, Eric; Roll, John; Ackerman, Mark S.

    1992-01-01

    The AXAF Science Center (ASC) will develop software to support all facets of data center activities and user research for the AXAF X-ray Observatory, scheduled for launch in 1999. The goal is to provide astronomers with the ability to utilize heterogeneous data analysis packages, that is, to allow astronomers to pick the best packages for doing their scientific analysis. For example, ASC software will be based on IRAF, but non-IRAF programs will be incorporated into the data system where appropriate. Additionally, it is desired to allow AXAF users to mix ASC software with their own local software. The need to support heterogeneous analysis environments is not special to the AXAF project, and therefore finding mechanisms for coordinating heterogeneous programs is an important problem for astronomical software today. The approach to solving this problem has been to develop two interfaces that allow the scientific user to run heterogeneous programs together. The first is an IRAF-compatible parameter interface that provides non-IRAF programs with IRAF's parameter handling capabilities. Included in the interface is an application programming interface to manipulate parameters from within programs, and also a set of host programs to manipulate parameters at the command line or from within scripts. The parameter interface has been implemented to support parameter storage formats other than IRAF parameter files, allowing one, for example, to access parameters that are stored in data bases. An X Windows graphical user interface called 'agcl' has been developed, layered on top of the IRAF-compatible parameter interface, that provides a standard graphical mechanism for interacting with IRAF and non-IRAF programs. Users can edit parameters and run programs for both non-IRAF programs and IRAF tasks. The agcl interface allows one to communicate with any command line environment in a transparent manner and without any changes to the original environment. For example, the authors

  12. Heterogeneous Photocatalytic Oxidation of Atmospheric Trace Contaminants

    NASA Technical Reports Server (NTRS)

    Ollis, David F.

    1996-01-01

    Heterogeneous photocatalysis involves the use of a light-activated catalyst at room temperature in order to carry out a desired reaction. In the presence of molecular oxygen, illumination of the n-type semiconductor oxide titanium dioxide (TiO2) provides for production of highly active forms of oxygen, such as hydroxyl radicals, which are able to carry out the complete oxidative destruction of simple hydrocarbons such as methane, ethane, ethylene, propylene, and carbon monoxide. This broad oxidation potential, coupled with the ability with sufficient residence time to achieve complete oxidation of simple hydrocarbon contaminants to carbon dioxide and water, indicated that heterogeneous photocatalysis should be examined for its potential for purification of spacecraft air. If a successful catalyst and photoreactor could be demonstrated at the laboratory level, such results would allow consideration of photocatalysts as a partial or complete replacement of adsorption systems, thereby allowing for reduction in lift-off weight of a portion of the life support system for the spacecraft, or other related application such as a space station or a conventional commercial aircraft. The present research was undertaken to explore this potential through achievement of the following plan of work: (a) ascertain the intrinsic kinetics of conversion of pollutants of interest in spacecraft, (b) ascertain the expected lifetime of catalysts through examination of most likely routes of catalyst deactivation and regeneration, (c) model and explore experimentally the low pressure drop catalytic monolith, a commercial configuration for automotive exhaust control, and (d) examine the kinetics of multicomponent conversions. In the recent course of this work, we have also discovered how to increase catalyst activity via halide promotion which has allowed us to achieve approximately 100% conversion of an aromatic contaminant (toluene) in a very short residence time of 5-6 milliseconds.

  13. Heterogeneous Photocatalytic Oxidation of Atmospheric Trace Contaminants

    NASA Technical Reports Server (NTRS)

    Ollis, David F.

    1996-01-01

    Heterogeneous photocatalysis involves the use of a light-activated catalyst at room temperature in order to carry out a desired reaction. In the presence of molecular oxygen, illumination of the n-type semiconductor oxide titanium dioxide (TiO2) provides for production of highly active forms of oxygen, such as hydroxyl radicals, which are able to carry out the complete oxidative destruction of simple hydrocarbons such as methane, ethane, ethylene, propylene, and carbon monoxide. This broad oxidation potential, coupled with the ability with sufficient residence time to achieve complete oxidation of simple hydrocarbon contaminants to carbon dioxide and water, indicated that heterogeneous photocatalysis should be examined for its potential for purification of spacecraft air. If a successful catalyst and photoreactor could be demonstrated at the laboratory level, such results would allow consideration of photocatalysts as a partial or complete replacement of adsorption systems, thereby allowing for reduction in lift-off weight of a portion of the life support system for the spacecraft, or other related application such as a space station or a conventional commercial aircraft. The present research was undertaken to explore this potential through achievement of the following plan of work: (a) ascertain the intrinsic kinetics of conversion of pollutants of interest in spacecraft, (b) ascertain the expected lifetime of catalysts through examination of most likely routes of catalyst deactivation and regeneration (c) model and explore experimentally the low pressure drop catalytic monolith, a commercial configuration for automotive exhaust control (d) examine the kinetics of multicomponent conversions. In the recent course of this work, we have also discovered how to increase catalyst activity via halide promotion which has allowed us to achieve approximately 100% conversion of an aromatic contaminant (toluene) in a very short residence time of 5-6 milliseconds.

  14. Improved electrochemiluminescence labels for heterogeneous microbead immunoassay.

    PubMed

    Yu, Linpo; Liu, Yang; Zhou, Ming

    2016-10-01

    Ruthenium(II) complexes with carboxylic acid as a bioconjugatable group, i.e., [Ru(bathophenanthroline disulfonate)(2,2'-bipyridine)(4-methyl-4'-(3-carboxypropyl)-2,2'-bipyridine)](0), (C49H38N6O8S2Ru), and [Ru(bathophenanthroline disulfonate)2(4-methyl-4'-(3-carboxypropyl)-2,2'-bipyridine)](2-) · 2Na(+), (C63H44N6O14S4RuNa2) were characterized spectroscopically and electrochemically. As potential labels for electrochemiluminescence (ECL) immunoassays, the ECL intensities of the free labels in homogenous aqueous buffer solutions were compared under a condition that is similar to the one employed by a commercial clinical immunoassay system. The two labels were found to be more emissive and, thus, can be detected at 10(- 12) pM compared with 5× 10(-12) pM of the label currently used in the commercial ECL system. Furthermore, the improved ECL emission of the free labels in homogenous solutions was proven to be translated into more intense ECL signal in heterogeneous sandwich immunoassay and, thus, leading to a lower limit of detection in immunoassay. The data obtained from these ECL labels shed light on the further development of ECL-based clinical immunoassay technology. Graphical abstract Electrochemiluminescence immunoassays were carried out with three different ruthenium(II) complex labels. It was proved that the higher signal intensities found with the novel labels in homogeneous solutions were maintained in heterogeneous sandwich format.

  15. The Heterogeneous Dynamics of Economic Complexity

    PubMed Central

    Cristelli, Matthieu; Tacchella, Andrea; Pietronero, Luciano

    2015-01-01

    What will be the growth of the Gross Domestic Product (GDP) or the competitiveness of China, United States, and Vietnam in the next 3, 5 or 10 years? Despite this kind of questions has a large societal impact and an extreme value for economic policy making, providing a scientific basis for economic predictability is still a very challenging problem. Recent results of a new branch—Economic Complexity—have set the basis for a framework to approach such a challenge and to provide new perspectives to cast economic prediction into the conceptual scheme of forecasting the evolution of a dynamical system as in the case of weather dynamics. We argue that a recently introduced non-monetary metrics for country competitiveness (fitness) allows for quantifying the hidden growth potential of countries by the means of the comparison of this measure for intangible assets with monetary figures, such as GDP per capita. This comparison defines the fitness-income plane where we observe that country dynamics presents strongly heterogeneous patterns of evolution. The flow in some zones is found to be laminar while in others a chaotic behavior is instead observed. These two regimes correspond to very different predictability features for the evolution of countries: in the former regime, we find strong predictable pattern while the latter scenario exhibits a very low predictability. In such a framework, regressions, the usual tool used in economics, are no more the appropriate strategy to deal with such a heterogeneous scenario and new concepts, borrowed from dynamical systems theory, are mandatory. We therefore propose a data-driven method—the selective predictability scheme—in which we adopt a strategy similar to the methods of analogues, firstly introduced by Lorenz, to assess future evolution of countries. PMID:25671312

  16. Heterogeneous Superconducting Low-Noise Sensing Coils

    NASA Technical Reports Server (NTRS)

    Hahn, Inseob; Penanen, Konstantin I.; Ho Eom, Byeong

    2008-01-01

    A heterogeneous material construction has been devised for sensing coils of superconducting quantum interference device (SQUID) magnetometers that are subject to a combination of requirements peculiar to some advanced applications, notably including low-field magnetic resonance imaging for medical diagnosis. The requirements in question are the following: The sensing coils must be large enough (in some cases having dimensions of as much as tens of centimeters) to afford adequate sensitivity; The sensing coils must be made electrically superconductive to eliminate Johnson noise (thermally induced noise proportional to electrical resistance); and Although the sensing coils must be cooled to below their superconducting- transition temperatures with sufficient cooling power to overcome moderate ambient radiative heat leakage, they must not be immersed in cryogenic liquid baths. For a given superconducting sensing coil, this combination of requirements can be satisfied by providing a sufficiently thermally conductive link between the coil and a cold source. However, the superconducting coil material is not suitable as such a link because electrically superconductive materials are typically poor thermal conductors. The heterogeneous material construction makes it possible to solve both the electrical- and thermal-conductivity problems. The basic idea is to construct the coil as a skeleton made of a highly thermally conductive material (typically, annealed copper), then coat the skeleton with an electrically superconductive alloy (typically, a lead-tin solder) [see figure]. In operation, the copper skeleton provides the required thermally conductive connection to the cold source, while the electrically superconductive coating material shields against Johnson noise that originates in the copper skeleton.

  17. The heterogeneous dynamics of economic complexity.

    PubMed

    Cristelli, Matthieu; Tacchella, Andrea; Pietronero, Luciano

    2015-01-01

    What will be the growth of the Gross Domestic Product (GDP) or the competitiveness of China, United States, and Vietnam in the next 3, 5 or 10 years? Despite this kind of questions has a large societal impact and an extreme value for economic policy making, providing a scientific basis for economic predictability is still a very challenging problem. Recent results of a new branch--Economic Complexity--have set the basis for a framework to approach such a challenge and to provide new perspectives to cast economic prediction into the conceptual scheme of forecasting the evolution of a dynamical system as in the case of weather dynamics. We argue that a recently introduced non-monetary metrics for country competitiveness (fitness) allows for quantifying the hidden growth potential of countries by the means of the comparison of this measure for intangible assets with monetary figures, such as GDP per capita. This comparison defines the fitness-income plane where we observe that country dynamics presents strongly heterogeneous patterns of evolution. The flow in some zones is found to be laminar while in others a chaotic behavior is instead observed. These two regimes correspond to very different predictability features for the evolution of countries: in the former regime, we find strong predictable pattern while the latter scenario exhibits a very low predictability. In such a framework, regressions, the usual tool used in economics, are no more the appropriate strategy to deal with such a heterogeneous scenario and new concepts, borrowed from dynamical systems theory, are mandatory. We therefore propose a data-driven method--the selective predictability scheme--in which we adopt a strategy similar to the methods of analogues, firstly introduced by Lorenz, to assess future evolution of countries.

  18. Computational drug repositioning through heterogeneous network clustering

    PubMed Central

    2013-01-01

    Background Given the costly and time consuming process and high attrition rates in drug discovery and development, drug repositioning or drug repurposing is considered as a viable strategy both to replenish the drying out drug pipelines and to surmount the innovation gap. Although there is a growing recognition that mechanistic relationships from molecular to systems level should be integrated into drug discovery paradigms, relatively few studies have integrated information about heterogeneous networks into computational drug-repositioning candidate discovery platforms. Results Using known disease-gene and drug-target relationships from the KEGG database, we built a weighted disease and drug heterogeneous network. The nodes represent drugs or diseases while the edges represent shared gene, biological process, pathway, phenotype or a combination of these features. We clustered this weighted network to identify modules and then assembled all possible drug-disease pairs (putative drug repositioning candidates) from these modules. We validated our predictions by testing their robustness and evaluated them by their overlap with drug indications that were either reported in published literature or investigated in clinical trials. Conclusions Previous computational approaches for drug repositioning focused either on drug-drug and disease-disease similarity approaches whereas we have taken a more holistic approach by considering drug-disease relationships also. Further, we considered not only gene but also other features to build the disease drug networks. Despite the relative simplicity of our approach, based on the robustness analyses and the overlap of some of our predictions with drug indications that are under investigation, we believe our approach could complement the current computational approaches for drug repositioning candidate discovery. PMID:24564976

  19. Challenges of deciphering gastric cancer heterogeneity

    PubMed Central

    Hudler, Petra

    2015-01-01

    Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively. PMID:26457012

  20. Homogeneous and heterogenized iridium water oxidation catalysts

    NASA Astrophysics Data System (ADS)

    Macchioni, Alceo

    2014-10-01

    The development of an efficient catalyst for the oxidative splitting of water into molecular oxygen, protons and electrons is of key importance for producing solar fuels through artificial photosynthesis. We are facing the problem by means of a rational approach aimed at understanding how catalytic performance may be optimized by the knowledge of the reaction mechanism of water oxidation and the fate of the catalytic site under the inevitably harsh oxidative conditions. For the purposes of our study we selected iridium water oxidation catalysts, exhibiting remarkable performance (TOF > 5 s-1 and TON > 20000). In particular, we recently focused our attention on [Cp*Ir(N,O)X] (N,O = 2-pyridincarboxylate; X = Cl or NO3) and [IrCl(Hedta)]Na water oxidation catalysts. The former exhibited a remarkable TOF whereas the latter showed a very high TON. Furthermore, [IrCl(Hedta)]Na was heterogenized onto TiO2 taking advantage of the presence of a dandling -COOH functionality. The heterogenized catalyst maintained approximately the same catalytic activity of the homogeneous analogous with the advantage that could be reused many times. Mechanistic studies were performed in order to shed some light on the rate-determining step and the transformation of catalysts when exposed to "oxidative stress". It was found that the last oxidative step, preceding oxygen liberation, is the rate-determining step when a small excess of sacrificial oxidant is used. In addition, several intermediates of the oxidative transformation of the catalyst were intercepted and characterized by NMR, X-Ray diffractometry and ESI-MS.