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Sample records for heterogeneous ribonuclear proteins

  1. Heterogeneous nuclear ribonuclear protein U associates with YAP and regulates its co-activation of Bax transcription.

    PubMed

    Howell, Michael; Borchers, Christoph; Milgram, Sharon L

    2004-06-18

    Although initially described as a cytosolic scaffolding protein, YAP (Yes-associated protein of 65 kDa) is known to associate with multiple transcription factors in the nucleus. Using affinity chromatography and mass spectrometry, we show that YAP interacts with heterogeneous nuclear ribonuclear protein U (hnRNP U), an RNA- and DNA-binding protein enriched in the nuclear matrix that also plays a role in the regulation of gene expression. hnRNP U interacts specifically with the proline-rich amino terminus of YAP, a region of YAP that is not found in the related protein TAZ. Although hnRNP U and YAP localize to both the nucleus and the cytoplasm, YAP does not translocate to the nucleus in an hnRNP U-dependent manner. Furthermore, hnRNP U and YAP only interact in the nucleus, suggesting that the association between the two proteins is regulated. Co-expression of hnRNP U attenuates the ability of YAP to increase the activity of a p73-driven Bax-luciferase reporter plasmid. In contrast, hnRNP U has no effect when co-expressed with a truncated YAP protein lacking the hnRNP U-binding site. Because YAP is distinguished from the homologue TAZ by its proline-rich amino terminus, the YAP-hnRNP U interaction may uniquely regulate the nuclear function(s) of YAP. The YAP-hnRNP U interaction provides another mechanism of YAP transcriptional regulation. PMID:15096513

  2. Heterogeneous nuclear ribonuclear protein K interacts with Sindbis virus nonstructural proteins and viral subgenomic mRNA

    SciTech Connect

    Burnham, Andrew J.; Gong, Lei; Hardy, Richard W.

    2007-10-10

    Alphaviruses are a group of arthropod-borne human and animal pathogens that can cause epidemics of significant public health and economic consequence. Alphavirus RNA synthesis requires four virally encoded nonstructural proteins and probably a number of cellular proteins. Using comparative two-dimensional electrophoresis we were able to identify proteins enriched in cytoplasmic membrane fractions containing viral RNA synthetic complexes following infection with Sindbis virus. Our studies demonstrated the following: (i) the host protein hnRNP K is enriched in cytoplasmic membrane fractions following Sindbis virus infection, (ii) viral nonstructural proteins co-immunoprecipitate with hnRNP K, (iii) nsP2 and hnRNP K co-localize in the cytoplasm of Sindbis virus infected cells, (iv) Sindbis virus subgenomic mRNA, but not genomic RNA co-immunoprecipitates with hnRNP K, (v) viral RNA does not appear to be required for the interaction of hnRNP K with the nonstructural proteins. Potential functions of hnRNP K during virus replication are discussed.

  3. 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

  4. 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. PMID:18653337

  5. Heterogeneous surfaces to repel proteins.

    PubMed

    Shen, Lei; Zhu, Jintao

    2016-02-01

    The nonspecific adsorption of proteins is usually undesirable on solid surfaces as it induces adverse responses, such as platelet adhesion on medical devices, negative signals of biosensors and contamination blockage of filtration membranes. Thus, an important scheme in material science is to design and fabricate protein-repulsive surfaces. Early approaches in this field focused on homogeneous surfaces comprised of single type functionality. Yet, recent researches have demonstrated that surfaces with heterogeneities (chemistry and topography) show promising performance against protein adsorption. In this review, we will summarize the recent achievements and discuss the new perspectives in the research of developing and characterizing heterogeneous surfaces to repel proteins. The protein repulsion mechanisms of different heterogeneous surfaces will also be discussed in details, followed by the perspective and challenge of this emerging field. PMID:26691416

  6. 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. PMID:26157136

  7. 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.

  8. 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.

  9. 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.

  10. 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).

  11. Heterogeneity of zein mRNA and protein in maize.

    PubMed

    Park, W D; Lewis, E D; Rubenstein, I

    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. PMID:16661153

  12. Information transfer by leaky, heterogeneous, protein kinase signaling systems

    PubMed Central

    Voliotis, Margaritis; Perrett, Rebecca M.; McWilliams, Chris; McArdle, Craig A.; Bowsher, Clive G.

    2014-01-01

    Cells must sense extracellular signals and transfer the information contained about their environment reliably to make appropriate decisions. To perform these tasks, cells use signal transduction networks that are subject to various sources of noise. Here, we study the effects on information transfer of two particular types of noise: basal (leaky) network activity and cell-to-cell variability in the componentry of the network. Basal activity is the propensity for activation of the network output in the absence of the signal of interest. We show, using theoretical models of protein kinase signaling, that the combined effect of the two types of noise makes information transfer by such networks highly vulnerable to the loss of negative feedback. In an experimental study of ERK signaling by single cells with heterogeneous ERK expression levels, we verify our theoretical prediction: In the presence of basal network activity, negative feedback substantially increases information transfer to the nucleus by both preventing a near-flat average response curve and reducing sensitivity to variation in substrate expression levels. The interplay between basal network activity, heterogeneity in network componentry, and feedback is thus critical for the effectiveness of protein kinase signaling. Basal activity is widespread in signaling systems under physiological conditions, has phenotypic consequences, and is often raised in disease. Our results reveal an important role for negative feedback mechanisms in protecting the information transfer function of saturable, heterogeneous cell signaling systems from basal activity. PMID:24395805

  13. Probabilistic Protein Function Prediction from Heterogeneous Genome-Wide Data

    PubMed Central

    Nariai, Naoki; Kolaczyk, Eric D.; Kasif, Simon

    2007-01-01

    Dramatic improvements in high throughput sequencing technologies have led to a staggering growth in the number of predicted genes. However, a large fraction of these newly discovered genes do not have a functional assignment. Fortunately, a variety of novel high-throughput genome-wide functional screening technologies provide important clues that shed light on gene function. The integration of heterogeneous data to predict protein function has been shown to improve the accuracy of automated gene annotation systems. In this paper, we propose and evaluate a probabilistic approach for protein function prediction that integrates protein-protein interaction (PPI) data, gene expression data, protein motif information, mutant phenotype data, and protein localization data. First, functional linkage graphs are constructed from PPI data and gene expression data, in which an edge between nodes (proteins) represents evidence for functional similarity. The assumption here is that graph neighbors are more likely to share protein function, compared to proteins that are not neighbors. The functional linkage graph model is then used in concert with protein domain, mutant phenotype and protein localization data to produce a functional prediction. Our method is applied to the functional prediction of Saccharomyces cerevisiae genes, using Gene Ontology (GO) terms as the basis of our annotation. In a cross validation study we show that the integrated model increases recall by 18%, compared to using PPI data alone at the 50% precision. We also show that the integrated predictor is significantly better than each individual predictor. However, the observed improvement vs. PPI depends on both the new source of data and the functional category to be predicted. Surprisingly, in some contexts integration hurts overall prediction accuracy. Lastly, we provide a comprehensive assignment of putative GO terms to 463 proteins that currently have no assigned function. PMID:17396164

  14. 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

  15. Heterogeneous nucleation of protein crystals on fluorinated layered silicate.

    PubMed

    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

  16. Locus heterogeneity disease genes encode proteins with high interconnectivity in the human protein interaction network

    PubMed Central

    Keith, Benjamin P.; Robertson, David L.; Hentges, Kathryn E.

    2014-01-01

    Mutations in genes potentially lead to a number of genetic diseases with differing severity. These disease genes have been the focus of research in recent years showing that the disease gene population as a whole is not homogeneous, and can be categorized according to their interactions. Locus heterogeneity describes a single disorder caused by mutations in different genes each acting individually to cause the same disease. Using datasets of experimentally derived human disease genes and protein interactions, we created a protein interaction network to investigate the relationships between the products of genes associated with a disease displaying locus heterogeneity, and use network parameters to suggest properties that distinguish these disease genes from the overall disease gene population. Through the manual curation of known causative genes of 100 diseases displaying locus heterogeneity and 397 single-gene Mendelian disorders, we use network parameters to show that our locus heterogeneity network displays distinct properties from the global disease network and a Mendelian network. Using the global human proteome, through random simulation of the network we show that heterogeneous genes display significant interconnectivity. Further topological analysis of this network revealed clustering of locus heterogeneity genes that cause identical disorders, indicating that these disease genes are involved in similar biological processes. We then use this information to suggest additional genes that may contribute to diseases with locus heterogeneity. PMID:25538735

  17. Investigating heterogeneous protein annotations toward cross-corpora utilization

    PubMed Central

    2009-01-01

    Background The number of corpora, collections of structured texts, has been increasing, as a result of the growing interest in the application of natural language processing methods to biological texts. Many named entity recognition (NER) systems have been developed based on these corpora. However, in the biomedical community, there is yet no general consensus regarding named entity annotation; thus, the resources are largely incompatible, and it is difficult to compare the performance of systems developed on resources that were divergently annotated. On the other hand, from a practical application perspective, it is desirable to utilize as many existing annotated resources as possible, because annotation is costly. Thus, it becomes a task of interest to integrate the heterogeneous annotations in these resources. Results We explore the potential sources of incompatibility among gene and protein annotations that were made for three common corpora: GENIA, GENETAG and AIMed. To show the inconsistency in the corpora annotations, we first tackle the incompatibility problem caused by corpus integration, and we quantitatively measure the effect of this incompatibility on protein mention recognition. We find that the F-score performance declines tremendously when training with integrated data, instead of training with pure data; in some cases, the performance drops nearly 12%. This degradation may be caused by the newly added heterogeneous annotations, and cannot be fixed without an understanding of the heterogeneities that exist among the corpora. Motivated by the result of this preliminary experiment, we further qualitatively analyze a number of possible sources for these differences, and investigate the factors that would explain the inconsistencies, by performing a series of well-designed experiments. Our analyses indicate that incompatibilities in the gene/protein annotations exist mainly in the following four areas: the boundary annotation conventions, the scope of

  18. A new heterogeneous family of telomerically encoded Cryptosporidium proteins

    PubMed Central

    Bouzid, Maha; Hunter, Paul R; McDonald, Vincent; Elwin, Kristin; Chalmers, Rachel M; Tyler, Kevin M

    2013-01-01

    Cryptosporidiosis is predominantly caused by two closely related species of protozoan parasites the zoonotic Cryptosporidium parvum and anthroponotic Cryptosporidium hominis which diverge phenotypically in respect to host range and virulence. Using comparative genomics we identified two genes displaying overt heterogeneity between species. Although initial work suggested both were species specific, Cops-1 for C. parvum and Chos-1 for C. hominis, subsequent study identified an abridged ortholog of Cops-1 in C. hominis. Cops-1 and Chos-1 showed limited, but significant, similarity to each other and share common features: (i) telomeric location: Cops-1 is the last gene on chromosome 2, whilst Chos-1 is the first gene on chromosome 5, (ii) encode circa 50-kDa secreted proteins with isoelectric points above 10, (iii) are serine rich, and (iv) contain internal nucleotide repeats. Importantly, Cops-1 sequence contains specific SNPs with good discriminatory power useful epidemiologically. C. parvum-infected patient sera recognized a 50-kDa protein in antigen preparations of C. parvum but not C. hominis, consistent with Cops-1 being antigenic for patients. Interestingly, anti-Cops-1 monoclonal antibody (9E1) stained oocyst content and sporozoite surface of C. parvum only. This study provides a new example of protozoan telomeres as rapidly evolving contingency loci encoding putative virulence factors. PMID:23467513

  19. Heterogeneous distribution of TRPC proteins in the embryonic cortex.

    PubMed

    Boisseau, Sylvie; Kunert-Keil, Christiane; Lucke, Silke; Bouron, Alexandre

    2009-03-01

    The present study was initiated to gain some information about the tissue distribution of transient receptor potential proteins of C-type (TRPC), a family of voltage-independent cation channels, at the beginning of neurogenesis in the telencephalon of embryonic mice. The mRNAs of all known TRPCs (TRPC1-TRPC7) could be found in the cortex at E13. TRPC1, TRPC3 and TRPC5 were the main isoforms, whereas the mRNAs for TRPC2, TRPC4, TRPC6 and TRPC7 were less abundant. The distribution throughout the cortical wall of TRPC1, TRPC3 and TRPC6 was studied by means of immuno-histochemistry. The data collected pointed to a heterogeneous expression of the channels. Three groups were identified. The first one comprises TRPC1, specifically found in the preplate but only in some post-mitotic neurons. It was mainly observed in a subset of cells distinct from the Cajal-Retzius cells. The second group is composed of TRPC3. It was found in non-neuronal cells and also in dividing (5-bromo-2'-deoxyuridine-positive) cells, indicating that TRPC3 is present in precursor cells. The third group contains TRPC6 detected in neuronal and in dividing non-neuronal cells. Double immunostaining experiments showed that TRPC3-positive cells also express TRPC6. Collectively, this report highlights a specific TRPC expression pattern in the immature cortical wall. PMID:18989690

  20. Computational prediction of virus-human protein-protein interactions using embedding kernelized heterogeneous data.

    PubMed

    Nourani, Esmaeil; Khunjush, Farshad; Durmuş, Saliha

    2016-05-24

    Pathogenic microorganisms exploit host cellular mechanisms and evade host defense mechanisms through molecular pathogen-host interactions (PHIs). Therefore, comprehensive analysis of these PHI networks should be an initial step for developing effective therapeutics against infectious diseases. Computational prediction of PHI data is gaining increasing demand because of scarcity of experimental data. Prediction of protein-protein interactions (PPIs) within PHI systems can be formulated as a classification problem, which requires the knowledge of non-interacting protein pairs. This is a restricting requirement since we lack datasets that report non-interacting protein pairs. In this study, we formulated the "computational prediction of PHI data" problem using kernel embedding of heterogeneous data. This eliminates the abovementioned requirement and enables us to predict new interactions without randomly labeling protein pairs as non-interacting. Domain-domain associations are used to filter the predicted results leading to 175 novel PHIs between 170 human proteins and 105 viral proteins. To compare our results with the state-of-the-art studies that use a binary classification formulation, we modified our settings to consider the same formulation. Detailed evaluations are conducted and our results provide more than 10 percent improvements for accuracy and AUC (area under the receiving operating curve) results in comparison with state-of-the-art methods. PMID:27072625

  1. Colloidal graphenes as heterogeneous additives to enhance protein crystal yield

    NASA Astrophysics Data System (ADS)

    Gully, Benjamin S.; Zou, Jianli; Cadby, Gemma; Passon, Daniel M.; Iyer, K. Swaminathan; Bond, Charles S.

    2012-08-01

    In the structural analysis of proteins via X-ray diffraction, a rate-limiting step is in favourable nucleation, a problematic obstacle in successful generation of protein crystals. Here graphene and graphene oxide were applied to protein crystallisation trials, offering improvements in crystalline output and nucleation.In the structural analysis of proteins via X-ray diffraction, a rate-limiting step is in favourable nucleation, a problematic obstacle in successful generation of protein crystals. Here graphene and graphene oxide were applied to protein crystallisation trials, offering improvements in crystalline output and nucleation. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr31150j

  2. 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.

  3. Colloidal graphenes as heterogeneous additives to enhance protein crystal yield.

    PubMed

    Gully, Benjamin S; Zou, Jianli; Cadby, Gemma; Passon, Daniel M; Iyer, K Swaminathan; Bond, Charles S

    2012-09-01

    In the structural analysis of proteins via X-ray diffraction, a rate-limiting step is in favourable nucleation, a problematic obstacle in successful generation of protein crystals. Here graphene and graphene oxide were applied to protein crystallisation trials, offering improvements in crystalline output and nucleation. PMID:22833181

  4. Protein Dynamics and Conformational Heterogeneity Characterized with Two-Dimensional Infrared Spectroscopy

    NASA Astrophysics Data System (ADS)

    Thielges, Megan; Basom, Edward; Spearman, James

    2014-06-01

    Conformational heterogeneity and dynamics impact protein function, but their investigation is limited by the availability of methods for characterizing rapidly fluctuating protein states with both high spatial and temporal resolution. Multidimensional infrared spectroscopy is emerging as a powerful technique that directly probes the structural dynamics on fast timescales. To overcome the spectral congestion inherent to protein spectra that restricts application of infrared spectroscopy to protein systems, we incorporate into proteins vibrational probes with spectrally isolated frequencies and local-mode character that make possible rigorous analysis of protein environments and dynamics with infrared spectroscopy. In particular, both heme-bound carbon monoxide and nitriles selectively incorporated as unnatural amino acids are used as probes of cytochrome P450. 2D IR spectroscopy is used to investigate the impact of protein dynamics and conformational heterogeneity on the selectivity of its catalytic activity. Comparative studies of mutants of cytochrome P450 are used to unravel the contribution of specific residues to the protein's dynamics.

  5. Effects of surface compositional and structural heterogeneity on nanoparticle-protein interactions: different protein configurations.

    PubMed

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

    2014-06-24

    As nanoparticles (NPs) enter into biological systems, they are immediately exposed to a variety and concentration of proteins. The physicochemical interactions between proteins and NPs are influenced by the surface properties of the NPs. To identify the effects of NP surface heterogeneity, the interactions between bovine serum albumin (BSA) and gold NPs (AuNPs) with similar chemical composition but different surface structures were investigated. Different interaction modes and BSA conformations were studied by dynamic light scattering, circular dichroism spectroscopy, fluorescence quenching and isothermal titration calorimetry (ITC). Depending on the surface structure of AuNPs, BSA seems to adopt either a "side-on" or an "end-on" conformation on AuNPs. ITC demonstrated that the adsorption of BSA onto AuNPs with randomly distributed polar and nonpolar groups was primarily driven by electrostatic interaction, and all BSA were adsorbed in the same process. The adsorption of BSA onto AuNPs covered with alternating domains of polar and nonpolar groups was a combination of different interactions. Overall, the results of this study point to the potential for utilizing nanoscale manipulation of NP surfaces to control the resulting NP-protein interactions. PMID:24882660

  6. 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. PMID:26116677

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

    PubMed Central

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

    2015-01-01

    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. PMID:26116677

  8. Lateral heterogeneity of plant thylakoid protein complexes: early reminiscences

    PubMed Central

    Anderson, Jan M.

    2012-01-01

    The concept that the two photosystems of photosynthesis cooperate in series, immortalized in Hill and Bendall's Z scheme, was still a black box that defined neither the structural nor the molecular organization of the thylakoid membrane network into grana and stroma thylakoids. The differentiation of the continuous thylakoid membrane into stacked grana thylakoids interconnected by single stroma thylakoids is a morphological reflection of the non-random distribution of photosystem II/light-harvesting complex of photosystem II, photosystem I and ATP synthase, which became known as lateral heterogeneity. PMID:23148264

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

    NASA Astrophysics Data System (ADS)

    Liu, Chuang; Xie, Liping; Zhang, Rongqing

    2015-12-01

    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.

  10. Heterogeneity of presynaptic proteins: do not forget isoforms

    PubMed Central

    Bragina, Luca; Fattorini, Giorgia; Giovedì, Silvia; Bosco, Federica; Benfenati, Fabio; Conti, Fiorenzo

    2013-01-01

    Analysis of presynaptic protein expression in glutamatergic and GABAergic central synapses performed in several laboratories and with different techniques is unveiling a complex scenario, largely because each presynaptic protein exists in several isoforms. The interpretation of these findings is generally based on the notion that each synapse and each synaptic vesicle contains one of the isoforms of each family of presynaptic proteins. We verified whether this interpretation is tenable by performing triple labeling and immunoisolation studies with the aim of detecting two isoforms of a given presynaptic protein in glutamatergic or GABAergic axon terminals and/or synaptic vesicles (SVs). Here, we show that: (1) the possibility that not all families of presynaptic proteins are expressed in all terminals must be taken into serious account; (2) the expression of a given protein isoform in a terminal does not exclude the expression of other isoforms of the same protein in the same terminal and in the same vesicle. These conclusions open new and interesting problems; their experimental analysis might improve our understanding of the physiology and pathophysiology of central synapses. PMID:23382710

  11. DETECTION OF HETEROGENEOUS DRUG-PROTEIN BINDING BY FRONTAL ANALYSIS AND HIGH-PERFORMANCE AFFINITY CHROMATOGRAPHY

    PubMed Central

    Tong, Zenghan; Joseph, K.S.; Hage, David S.

    2011-01-01

    This study examined the use of frontal analysis and high-performance affinity chromatography for detecting heterogeneous binding in biomolecular interactions, using the binding of acetohexamide with human serum albumin (HSA) as a model. It was found through the use of this model system and chromatographic theory that double-reciprocal plots could be used more easily than traditional isotherms for the initial detection of binding site heterogeneity. The deviations from linearity that were seen in double-reciprocal plots as a result of heterogeneity were a function of the analyte concentration, the relative affinities of the binding sites in the system and the amount of each type of site that was present. The size of these deviations was determined and compared under various conditions. Plots were also generated to show what experimental conditions would be needed to observe these deviations for general heterogeneous systems or for cases in which some preliminary information was available on the extent of binding heterogeneity. The methods developed in this work for the detection of binding heterogeneity are not limited to drug interactions with HSA but could be applied to other types of drug-protein binding or to additional biological systems with heterogeneous binding. PMID:21612784

  12. Specific Adhesion of Lipid Membranes Can Simultaneously Produce Two Types of Lipid and Protein Heterogeneities

    NASA Astrophysics Data System (ADS)

    Shindell, Orrin; Micah, Natalie; Ritzer, Max; Gordon, Vernita

    2015-03-01

    Living cells adhere to one another and their environment. Adhesion is associated with re-organization of the lipid and protein components of the cell membrane. The resulting heterogeneities are functional structures involved in biological processes. We use artificial lipid membranes that contain a single type of binding protein. Before adhesion, the lipid, protein, and dye components in the membrane are well-mixed and constitute a single disordered-liquid phase (Ld) . After adhesion, two distinct types of heterogeneities coexist in the adhesion zone: a central domain of ordered lipid phase that excludes both binding proteins and membrane dye, and a peripheral domain of disordered lipid phase that is densely packed with adhesion proteins and enriched in membrane dye relative to the non-adhered portion of the vesicle. Thus, we show that adhesion that is mediated by only one type of protein can organize the lipid and protein components of the membranes into heterogeneities that resemble those found in biology, for example the immune synapse.

  13. Effect of protein crystal hydration on side chain conformational heterogeneity

    NASA Astrophysics Data System (ADS)

    Atakisi, Hakan; Moreau, David; Hopkins, Jesse; Thorne, Robert; Robert Thorne's group Team

    The structure of protein crystals is determined in part by water-mediated interactions involving both protein surface-ordered (hydration) and bulk water, and so is sensitive to the relative humidity of the environment. Monoclinic lysozyme provides a remarkable model for studying structural changes induced by dehydration, as it maintains excellent order for relative humidities (r.h.) down to 5%, corresponding to solvent content of 9% by volume, much smaller than the 88% (22% by volume) at which lysozyme loses its enzymatic activity. Although the main chain conformation does not change significantly, the effect of dehydration on side chain conformations has not been systematically studied. High resolution (1.1 to 1.7 A) structural data sets for monoclinic lysozyme at r.h. between 99% and 11% have been analyzed to identify major and minor side chain conformers at each humidity, and to map out how the side chain conformational ensemble evolves with hydration. Modest dehydration produces comparable overall effects to cooling to T =100 K, but with conformational changes largely confined to solvent-exposed residues. The largest side chain conformation changes occur at humidities that deplete water within the first two hydration shells.

  14. The use of heterogeneous and epitaxial nucleants to promote the growth of protein crystals

    NASA Technical Reports Server (NTRS)

    Mcpherson, Alexander; Shlichta, P.

    1988-01-01

    Fifty different mineral samples were tested as potential heterogeneous or epitaxial nucleants for four commonly crystallized proteins. It was found, using conventional protein crystallization techniques, that for each protein there was a set of mineral substrates that promoted nucleation of crystals at lower critical levels of supersaturation than required for spontaneous growth. In at least one case, the growth of lysozyme on the mineral apophyllite, it was shown by lattice analysis and X-ray diffraction that the nucleation and growth of the protein crystal on the mineral was likely to be truly epitaxial.

  15. 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.

  16. Exploring protein solution structure: Second moments of fluorescent spectra report heterogeneity of tryptophan rotamers.

    PubMed

    Gasymov, Oktay K; Abduragimov, Adil R; Glasgow, Ben J

    2015-11-01

    Trp fluorescent spectra appear as a log-normal function but are usually analyzed with λmax, full width at half maximum, and the first moment of incomplete spectra. Log-normal analyses have successfully separated fluorescence contributions from some multi-Trp proteins but deviations were observed in single Trp proteins. The possibility that disparate rotamer environments might account for these deviations was explored by moment spectral analysis of single Trp mutants spanning the sequence of tear lipocalin as a model. The analysis required full width Trp spectra. Composite spectra were constructed using log-normal analysis to derive the inaccessible blue edge, and the experimentally obtained spectra for the remainder. First moments of the composite spectra reflected the site-resolved secondary structure. Second moments were most sensitive for spectral deviations. A novel parameter, derived from the difference of the second moments of composite and simulated log-normal spectra correlated with known multiple heterogeneous rotamer conformations. Buried and restricted side chains showed the most heterogeneity. Analyses applied to other proteins further validated the method. The rotamer heterogeneity values could be rationalized by known conformational properties of Trp residues and the distribution of nearby charged groups according to the internal Stark effect. Spectral heterogeneity fits the rotamer model but does not preclude other contributing factors. Spectral moment analysis of full width Trp emission spectra is accessible to most laboratories. The calculations are informative of protein structure and can be adapted to study dynamic processes. PMID:26119357

  17. Classification and purification of proteins of heterogeneous nuclear ribonucleoprotein particles by RNA-binding specificities

    SciTech Connect

    Swanson, M.S.; Dreyfuss, G.

    1988-05-01

    Several proteins of heterogeneous nuclear ribonucleoprotein (hnRNP) particles display very high binding affinities for different ribonucleotide homopolymers. The specificity of some of these proteins at high salt concentrations and in the presence of heparin allows for their rapid one-step purification from HeLa nucleoplasm. The authors show that the hnRNP proteins are poly(U)-binding proteins and compare their specificity to that of the previously described cytoplasmic poly(A)-binding protein. These findings provide a useful tool for the classification and purification of hnRNP proteins from various tissues and organisms and indicate that different hnRNP proteins have different RNA-binding specificities.

  18. 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.

  19. Identifying Human Kinase-Specific Protein Phosphorylation Sites by Integrating Heterogeneous Information from Various Sources

    PubMed Central

    Li, Tingting; Du, Pufeng; Xu, Nanfang

    2010-01-01

    Phosphorylation is an important type of protein post-translational modification. Identification of possible phosphorylation sites of a protein is important for understanding its functions. Unbiased screening for phosphorylation sites by in vitro or in vivo experiments is time consuming and expensive; in silico prediction can provide functional candidates and help narrow down the experimental efforts. Most of the existing prediction algorithms take only the polypeptide sequence around the phosphorylation sites into consideration. However, protein phosphorylation is a very complex biological process in vivo. The polypeptide sequences around the potential sites are not sufficient to determine the phosphorylation status of those residues. In the current work, we integrated various data sources such as protein functional domains, protein subcellular location and protein-protein interactions, along with the polypeptide sequences to predict protein phosphorylation sites. The heterogeneous information significantly boosted the prediction accuracy for some kinase families. To demonstrate potential application of our method, we scanned a set of human proteins and predicted putative phosphorylation sites for Cyclin-dependent kinases, Casein kinase 2, Glycogen synthase kinase 3, Mitogen-activated protein kinases, protein kinase A, and protein kinase C families (avaiable at http://cmbi.bjmu.edu.cn/huphospho). The predicted phosphorylation sites can serve as candidates for further experimental validation. Our strategy may also be applicable for the in silico identification of other post-translational modification substrates. PMID:21085571

  20. 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

  1. Small angle neutron scattering contrast variation reveals heterogeneities of interactions in protein gels.

    PubMed

    Banc, A; Charbonneau, C; Dahesh, M; Appavou, M-S; Fu, Z; Morel, M-H; Ramos, L

    2016-06-28

    We propose a quantitative approach to probe the spatial heterogeneities of interactions in macromolecular gels, based on a combination of small angle X-ray (SAXS) and neutrons (SANS) scattering. We investigate the structure of model gluten protein gels and show that the gels display radically different SAXS and SANS profiles when the solvent is (at least partially) deuterated. The detailed analysis of the SANS signal as a function of the solvent deuteration demonstrates heterogeneities of sample deuteration at different length scales. The progressive exchange between the protons (H) of the proteins and the deuteriums (D) of the solvent is inhomogeneous and 60 nm large zones that are enriched in H are evidenced. In addition, at low protein concentration, in the sol state, solvent deuteration induces a liquid/liquid phase separation. Complementary biochemical and structure analyses show that the denser protein phase is more protonated and specifically enriched in glutenin, the polymeric fraction of gluten proteins. These findings suggest that the presence of H-rich zones in gluten gels would arise from the preferential interaction of glutenin polymers through a tight network of non-exchangeable intermolecular hydrogen bonds. PMID:27198847

  2. 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.

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

    PubMed

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

    2009-02-18

    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 elicit 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 tRNA(lys) precharged with lysine-epsilon-biotin followed by solid phase immobilization on 384-well neutravidin-coated plates. The generated array is highly specific and sensitive in a micro-ELISA 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

  4. Molecular crowding causes narrowing of population heterogeneity and restricts internal dynamics in a protein

    NASA Astrophysics Data System (ADS)

    Mondal, Samsuzzoha; Kallianpur, Mamata V.; Udgaonkar, Jayant B.; Krishnamoorthy, G.

    2016-03-01

    Macromolecular crowding is a distinguishing property of intracellular media. Knowledge on the structure and dynamics of a protein in a crowded environment is essential for a complete understanding of its function. Reduction in intermolecular space could cause structural and functional alterations. Here, we have studied a model protein barstar to see how polyethylene glycol (PEG)-induced crowding affects its various structural states (native, unfolded and molten-globule-like) with different extents of change in conformational heterogeneity. Intramolecular distances and distance distributions were determined by time-resolved Förster resonance energy transfer from Trp53 to several acceptor sites by analysis of fluorescence decay kinetics using the Maximum Entropy Method. We observed PEG-induced narrowing of population distributions along with shifting of populations towards more compact states. Structural compactness also resulted in the slowing down of internal dynamics of the protein as revealed by fluorescence anisotropy decay kinetics of the fluorophore IAEDANS attached at several sites.

  5. 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

  6. 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

  7. Directly measuring single molecule heterogeneity in proteins and RNA using force spectroscopy

    NASA Astrophysics Data System (ADS)

    Hinczewski, Michael; Hyeon, Changbong; Thirumalai, Devarajan

    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 stochastic interconversions occurring only at macroscopic timescales, fractions of a second or longer. Though we now have proof of functional heterogeneity in a handful of systems--enzymes, motors, adhesion complexes--identifying and measuring it remains a formidable challenge. 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: AFM 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. Our work suggests experimental approaches for estimating the timescales of these fluctuations with unprecedented accuracy.

  8. Heterogeneity of a Campylobacter jejuni Protein That Is Secreted through the Flagellar Filament▿

    PubMed Central

    Poly, Frédéric; Ewing, Cheryl; Goon, Scarlett; Hickey, Thomas E.; Rockabrand, David; Majam, Gary; Lee, Lanfong; Phan, Julie; Savarino, Nicholas J.; Guerry, Patricia

    2007-01-01

    Cj0859c, or FspA, is a small, acidic protein of Campylobacter jejuni that is expressed by a σ28 promoter. Analysis of the fspA gene in 41 isolates of C. jejuni revealed two overall variants of the predicted protein, FspA1 and FspA2. Secretion of FspA occurs in broth-grown bacteria and requires a minimum flagellar structure. The addition of recombinant FspA2, but not FspA1, to INT407 cells in vitro resulted in a rapid induction of apoptosis. These data define a novel C. jejuni virulence factor, and the observed heterogeneity among fspA alleles suggests alternate virulence potential among different strains. PMID:17517862

  9. Improved Success of Sparse Matrix Protein Crystallization Screening with Heterogeneous Nucleating Agents

    PubMed Central

    Thakur, Anil S.; Robin, Gautier; Guncar, Gregor; Saunders, Neil F. W.; Newman, Janet; Martin, Jennifer L.; Kobe, Bostjan

    2007-01-01

    Background Crystallization is a major bottleneck in the process of macromolecular structure determination by X-ray crystallography. Successful crystallization requires the formation of nuclei and their subsequent growth to crystals of suitable size. Crystal growth generally occurs spontaneously in a supersaturated solution as a result of homogenous nucleation. However, in a typical sparse matrix screening experiment, precipitant and protein concentration are not sampled extensively, and supersaturation conditions suitable for nucleation are often missed. Methodology/Principal Findings We tested the effect of nine potential heterogenous nucleating agents on crystallization of ten test proteins in a sparse matrix screen. Several nucleating agents induced crystal formation under conditions where no crystallization occurred in the absence of the nucleating agent. Four nucleating agents: dried seaweed; horse hair; cellulose and hydroxyapatite, had a considerable overall positive effect on crystallization success. This effect was further enhanced when these nucleating agents were used in combination with each other. Conclusions/Significance Our results suggest that the addition of heterogeneous nucleating agents increases the chances of crystal formation when using sparse matrix screens. PMID:17971854

  10. 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

  11. Heterogeneous nuclear ribonucleoprotein B1 protein impairs DNA repair mediated through the inhibition of DNA-dependent protein kinase activity

    SciTech Connect

    Iwanaga, Kentaro; Sueoka, Naoko; Sato, Akemi; Hayashi, Shinichiro; Sueoka, Eisaburo . E-mail: sueokae@post.saga-med.ac.jp

    2005-08-05

    Heterogeneous nuclear ribonucleoprotein B1, an RNA binding protein, is overexpressed from the early stage of lung cancers; it is evident even in bronchial dysplasia, a premalignant lesion. We evaluated the proteins bound with hnRNP B1 and found that hnRNP B1 interacted with DNA-dependent protein kinase (DNA-PK) complex, and recombinant hnRNP B1 protein dose-dependently inhibited DNA-PK activity in vitro. To test the effect of hnRNP B1 on DNA repair, we performed comet assay after irradiation, using normal human bronchial epithelial (HBE) cells treated with siRNA for hnRNP A2/B1: reduction of hnRNP B1 treated with siRNA for hnRNP A2/B1 induced faster DNA repair in normal HBE cells. Considering these results, we assume that overexpression of hnRNP B1 occurring in the early stage of carcinogenesis inhibits DNA-PK activity, resulting in subsequent accumulation of erroneous rejoining of DNA double-strand breaks, causing tumor progression.

  12. 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

  13. Heterogeneity of p53-pathway Protein Expression in Chemosensitive Chronic Lymphocytic Leukemia: A Pilot Study

    PubMed Central

    Groves, Michael J; MacCallum, Stephanie F; Boylan, Michael T; Haydock, Sally; Cunningham, Joan; Gelly, Keith; Gowans, Duncan; Kerr, Ron; Coates, Philip J; Tauro, Sudhir

    2012-01-01

    The presence of p53-pathway dysfunction in chronic lymphocytic leukemia (CLL) can be used to identify patients with chemotherapy-refractory disease. Therapeutic responses are known to vary between patients with chemosensitive CLL and may relate to differences in p53-pathway activity. We hypothesized that the magnitude or type of p53-pathway protein expression is heterogeneous in patients with chemosensitive disease and could associate with white cell responses. In this pilot study, changes in p53 and its transcriptional targets, p21/waf1 and MDM2 were analyzed by immunoblotting and densitometry in CLL cells from 10 patients immediately prior to the start of chemotherapy, and after culture for 24 hours (h) with fludarabine (n=7) or chlorambucil (n=3). The in vitro response was also compared to that in vivo in circulating cells pre-treatment, and at 24h and 96h of chemotherapy. Disease responses were evident in all patients after the first treatment-cycle. Significant p53 induction was observed in CLL cells treated in vitro and in vivo. Greater heterogeneity in the expression-intensity was observed in vivo (σ2=45.15) than in vitro (σ2=1.33) and the results failed to correlate (r2=0.18, p=0.22). p21/waf1 and MDM2 expression-profiles were also dissimilar in vitro and in vivo. Higher in vivo (but not in vitro) responses associated with changes in white cell count (p=0.026). Thus, heterogeneity of p53-pathway activity exists in chemosensitive CLL; in unselected patients, in vivo changes do not correlate with those in vitro, but may associate with post-treatment white cell responses. PMID:22962562

  14. 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

  15. Comprehensive assessment of chamber-specific and transmural heterogeneity in myofilament protein phosphorylation by top-down mass spectrometry.

    PubMed

    Gregorich, Zachery R; Peng, Ying; Lane, Nicole M; Wolff, Jeremy J; Wang, Sijian; Guo, Wei; Guner, Huseyin; Doop, Justin; Hacker, Timothy A; Ge, Ying

    2015-10-01

    The heart is characterized by a remarkable degree of heterogeneity, the basis of which is a subject of active investigation. Myofilament protein post-translational modifications (PTMs) represent a critical mechanism regulating cardiac contractility, and emerging evidence shows that pathological cardiac conditions induce contractile heterogeneity that correlates with transmural variations in the modification status of myofilament proteins. Nevertheless, whether there exists basal heterogeneity in myofilament protein PTMs in the heart remains unclear. Here we have systematically assessed chamber-specific and transmural variations in myofilament protein PTMs, specifically, the phosphorylation of cardiac troponin I (cTnI), cardiac troponin T (cTnT), tropomyosin (Tpm), and myosin light chain 2 (MLC2). We show that the phosphorylation of cTnI and αTm vary in the different chambers of the heart, whereas the phosphorylation of MLC2 and cTnT does not. In contrast, no significant transmural differences were observed in the phosphorylation of any of the myofilament proteins analyzed. These results highlight the importance of appropriate tissue sampling-particularly for studies aimed at elucidating disease mechanisms and biomarker discovery-in order to minimize potential variations arising from basal heterogeneity in myofilament PTMs in the heart. PMID:26268593

  16. Structure of nuclear ribonucleoprotein: heterogeneous nuclear RNA is complexed with a major sextet of proteins in vivo.

    PubMed Central

    Economidis, I V; Pederson, T

    1983-01-01

    Mouse erythroleukemia cells were pulse-labeled with [3H]uridine and irradiated with 254-nm light to produce covalent crosslinks between RNA and proteins in close proximity to one another in vivo. Nuclear ribonucleoprotein particles containing heterogeneous nuclear RNA were isolated and digested with nucleases, and the resulting proteins were subjected to gel electrophoresis. Proteins carrying covalently crosslinked [3H]uridine nucleotides were identified by fluorography. The results demonstrate that heterogeneous nuclear RNA is complexed in vivo with a set of six major proteins having molecular weights between 32,500 and 41,500. Analysis of chromatin fractions indicates that nascent heterogeneous nuclear RNA chains assemble with these six proteins as a very early post-transcriptional event. These data, and other results [Nevins, J. R. & Darnell, J. E. (1981) Cell 15, 1477-1493], lead us to propose the usual order of post-transcriptional events to be: heterogeneous nuclear RNA-ribonucleoprotein particle assembly leads to poly(A) addition leads to splicing. Images PMID:6572923

  17. Microsecond acquisition of heterogeneous structure in the folding of a TIM barrel protein

    SciTech Connect

    Wu, Ying; Kondrashkina, Elena; Kayatekin, Can; Matthews, C. Robert; Bilsel, Osman

    2008-09-29

    The earliest kinetic folding events for ({beta}{alpha}){sub 8} barrels reflect the appearance of off-pathway intermediates. Continuous-flow microchannel mixing methods interfaced to small-angle x-ray scattering (SAXS), circular dichroism (CD), time-resolved Foerster resonant energy transfer (trFRET), and time-resolved fluorescence anisotropy (trFLAN) have been used to directly monitor global and specific dimensional properties of the partially folded state in the microsecond time range for a representative ({beta}{alpha}){sub 8} barrel protein. Within 150 {micro}s, the {alpha}-subunit of Trp synthase ({alpha}TS) experiences a global collapse and the partial formation of secondary structure. The time resolution of the folding reaction was enhanced with trFRET and trFLAN to show that, within 30 {micro}s, a distinct and autonomous partially collapsed structure has already formed in the N-terminal and central regions but not in the C-terminal region. A distance distribution analysis of the trFRET data confirmed the presence of a heterogeneous ensemble that persists for several hundreds of microseconds. Ready access to locally folded, stable substructures may be a hallmark of repeat-module proteins and the source of early kinetic traps in these very common motifs. Their folding free-energy landscapes should be elaborated to capture this source of frustration.

  18. 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. PMID:20722697

  19. Isolation and characterization of a Xenopus laevis C protein cDNA: structure and expression of a heterogeneous nuclear ribonucleoprotein core protein.

    PubMed Central

    Preugschat, F; Wold, B

    1988-01-01

    The C proteins are major components of heterogeneous nuclear ribonucleoprotein complexes in nuclei of vertebrate cells. To begin to describe their structure, expression, and function we isolated and determined the DNA sequence of Xenopus laevis C protein cDNA clones. The protein predicted from the DNA sequence has a molecular mass of 30,916 kDa and is very similar to its human counterpart. Although mammalian genomes contain many copies of C protein sequence, the Xenopus genome contains few copies. When C protein RNA was synthesized in vitro and microinjected into stage-VI Xenopus oocytes, newly synthesized C proteins were efficiently localized in the nucleus. In vitro rabbit reticulocyte lysate and in vivo Xenopus oocyte translation systems both produce from a single mRNA two discrete polypeptide species that accumulate in a ratio similar to that of mammalian C1 and C2 proteins in vivo. Images PMID:2904678

  20. The Drosophila Hrb98DE locus encodes four protein isoforms homologous to the A1 protein of mammalian heterogeneous nuclear ribonucleoprotein complexes.

    PubMed Central

    Haynes, S R; Raychaudhuri, G; Beyer, A L

    1990-01-01

    The Drosophila Hrb98DE locus encodes proteins that are highly homologous to the mammalian A1 protein, a major component of heterogeneous nuclear ribonucleoprotein (RNP) particles. The Hrb98DE locus is transcribed throughout development, with the highest transcript levels found in ovaries, early embryos, and pupae. Eight different transcripts are produced by the use of combinations of alternative promoters, exons, and splice acceptor sites; the various species are not all equally abundant. The 3'-most exon is unusual in that it is completely noncoding. These transcripts can potentially generate four protein isoforms that differ in their N-terminal 16 to 21 amino acids but are identical in the remainder of the protein, including the RNP consensus motif domain and the glycine-rich domain characteristic of the mammalian A1 protein. We suggest that these sequence differences could affect the affinities of the proteins for RNA or other protein components of heterogeneous nuclear RNP complexes, leading to differences in function. Images PMID:2104660

  1. Nucleolin and heterogeneous nuclear ribonucleoprotein C proteins specifically interact with the 3'-untranslated region of amyloid protein precursor mRNA.

    PubMed

    Zaidi, S H; Malter, J S

    1995-07-21

    The central nervous system deposition by neurons and glia of beta A4 amyloid protein is an important contributing factor to the development of Alzheimer's disease. Amyloidogenic cells overexpress amyloid precursor protein (APP) mRNAs suggesting a transcriptional or post-transcriptional defect may contribute to this process. We have previously shown that APP mRNAs display regulated stability which is dependent on a 29-base element within the 3'-untranslated region (UTR). This domain specifically interacted with several cytoplasmic RNA-binding proteins. We have purified these APP RNA-binding proteins from a human T-cell leukemia and demonstrate that five cytoplasmic proteins of 70, 48, 47, 39, and 38 kDa form the previously observed APP RNA protein complexes. Amino acid sequence analyses showed that the 70-, 48-, and 47-kDa proteins were fragments of nucleolin and that the 39- and 38-kDa proteins were heterogeneous nuclear ribonucleoprotein (hnRNP) C protein. Northwestern and Western blot analyses of purified material further confirmed these data. Nucleolin protein is known to shuttle between the nucleus and cytoplasm but hnRNP C has not been reported within the cytoplasm. This report of sequence specific, mRNA binding by nucleolin and hnRNP C suggests that these proteins participate in the post-transcriptional regulation of APP mRNA through 3'-UTR, site-specific interactions. PMID:7615529

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

    PubMed Central

    Mitchell, Rod T; Camacho-Moll, Maria; Macdonald, Joni; Anderson, Richard A; Kelnar, Christopher JH; O’Donnell, Marie; Sharpe, Richard M; Smith, Lee B; Grigor, Ken M; Wallace, W Hamish B; Stoop, Hans; Wolffenbuttel, Katja P; Donat, Roland

    2014-01-01

    Testicular germ cell cancer develops from pre-malignant 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 hypothesised that cells expressing an immature (OCT4+/MAGEA4−) germ cell profile would exhibit an increased proliferation rate compared to 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 pre-invasive 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 v 3.4%, p<0.0001) irrespective of histological tumour type, reflected in the predominance of OCT4+/MAGEA4− cells in the invasive tumour component. Surprisingly, OCT4+/MAGEA4− cells in patients with pre-invasive disease showed significantly higher proliferation compared to those with seminoma or non-seminoma (18.1 v 10.2 v 7.2%, p<0.05 respectively). In conclusion, this study has demonstrated that OCT4+/MAGEA4

  3. Identification of two RNA-binding proteins in Balbiani ring premessenger ribonucleoprotein granules and presence of these proteins in specific subsets of heterogeneous nuclear ribonucleoprotein particles.

    PubMed Central

    Wurtz-T; Kiseleva, E; Nacheva, G; Alzhanova-Ericcson, A; Rosén, A; Daneholt, B

    1996-01-01

    Balbiani ring (BR) granules are premessenger ribonucleoprotein particles (RNPs) generated in giant chromosomal puffs, the BRs, in the larval salivary glands of the dipteran chironomus tentans. Monoclonal antibodies were raised against nuclear proteins collected on a single-stranded-DNA-agarose affinity column, and two of them were used to identify RNA-binding proteins in BR granules. First, in Western blots (immunoblots), one of the antibodies recognized a 36-kDa protein and the other recognized a 45-KDa protein. Second, both antibodies bound to the BRs in immunocytological experiments. It was shown in cross-linking experiments that the two proteins are associated with heterogeneous nuclear RNP (hnRNP) complexes extracted from C. tentans nuclei. By immunoelectron microscopy of isolated and partly unfolded BR RNPs, it was specifically demonstrated that the BR granules contain the two proteins and, in addition, that both proteins are distributed frequently along the RNP fiber of the particles. Thus, the 36- and 45-KDa proteins are likely to be abundant, RNA-binding proteins in the BR particles. To elucidate to what extent the two proteins are also present in other hnRNPs, we studied the binding of the antibodies to chromosomal puffs in general. It was observed that many puffs in addition to the BRs harbor the two proteins, but there are also puffs containing only one of the components, either the 36- or the 45-kDa protein. We conclude that the two proteins are not randomly bound to all hnRNPs but that each of them seems to be linked to a specific subset of the particles. PMID:8657116

  4. 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

  5. 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

  6. A Map of Dielectric Heterogeneity in a Membrane Protein: the Hetero-Oligomeric Cytochrome b6f Complex

    PubMed Central

    2015-01-01

    The cytochrome b6f complex, a member of the cytochrome bc family that mediates energy transduction in photosynthetic and respiratory membranes, is a hetero-oligomeric complex that utilizes two pairs of b-hemes in a symmetric dimer to accomplish trans-membrane electron transfer, quinone oxidation–reduction, and generation of a proton electrochemical potential. Analysis of electron storage in this pathway, utilizing simultaneous measurement of heme reduction, and of circular dichroism (CD) spectra, to assay heme–heme interactions, implies a heterogeneous distribution of the dielectric constants that mediate electrostatic interactions between the four hemes in the complex. Crystallographic information was used to determine the identity of the interacting hemes. The Soret band CD signal is dominated by excitonic interaction between the intramonomer b-hemes, bn and bp, on the electrochemically negative and positive sides of the complex. Kinetic data imply that the most probable pathway for transfer of the two electrons needed for quinone oxidation–reduction utilizes this intramonomer heme pair, contradicting the expectation based on heme redox potentials and thermodynamics, that the two higher potential hemes bn on different monomers would be preferentially reduced. Energetically preferred intramonomer electron storage of electrons on the intramonomer b-hemes is found to require heterogeneity of interheme dielectric constants. Relative to the medium separating the two higher potential hemes bn, a relatively large dielectric constant must exist between the intramonomer b-hemes, allowing a smaller electrostatic repulsion between the reduced hemes. Heterogeneity of dielectric constants is an additional structure–function parameter of membrane protein complexes. PMID:24867491

  7. 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

  8. Intrinsic Linear Heterogeneity of Amyloid β Protein Fibrils Revealed by Higher Resolution Mass-per-length Determinations*

    PubMed Central

    Komatsu, Hiroaki; Feingold-Link, Elana; Sharp, Kim A.; Rastogi, Tanvi; Axelsen, Paul H.

    2010-01-01

    Amyloid β proteins spontaneously form fibrils in vitro that vary in their thermodynamic stability and in morphological characteristics such as length, width, shape, longitudinal twist, and the number of component filaments. It is vitally important to determine which variant best represents the type of fibril that accumulates in Alzheimer disease. In the present study, the nature of morphological variation was examined by dark-field and transmission electron microscopy in a preparation of seeded amyloid β protein fibrils that formed at relatively low protein concentrations and exhibited remarkably high thermodynamic stability. The number of filaments comprising these fibrils changed frequently from two to six along their length, and these changes only became apparent when mass-per-length (MPL) determinations are made with sufficient resolution. The MPL results could be reproduced by a simple stochastic model with a single adjustable parameter. The presence of more than two primary filaments could not be discerned by transmission electron microscopy, and they had no apparent relationship to the longitudinal twist of the fibrils. However, the pitch of the twist was strongly affected by the pH of the negative stain. We conclude that highly stable amyloid fibrils may form in which a surprising amount of intrinsic linear heterogeneity may be obscured by MPL measurements of insufficient resolution, and by the negative stains used for imaging fibrils by electron microscopy. PMID:20940298

  9. 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.

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

    PubMed

    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

  11. 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.

  12. Heterogeneity of glutamatergic and GABAergic release machinery in cerebral cortex: analysis of synaptogyrin, vesicle-associated membrane protein, and syntaxin.

    PubMed

    Bragina, L; Giovedì, S; Barbaresi, P; Benfenati, F; Conti, F

    2010-02-01

    To define whether cortical glutamatergic and GABAergic release machineries can be differentiated on the basis of the nature and amount of proteins they express, we studied the degree of co-localization of synaptogyrin (SGYR) 1 and 3, vesicle-associated membrane protein (VAMP) 1 and 2, syntaxin (STX) 1A and 1B in vesicular glutamate transporter (VGLUT)1-, VGLUT2- and vesicular GABA transporter (VGAT)-positive (+) puncta and synaptic vesicles in the rat cerebral cortex. Co-localization studies showed that SGYR1 and 3 were expressed in about 90% of VGLUT1+, 70% of VGLUT2+ and 80% of VGAT+ puncta; VAMP1 was expressed in approximately 45% of VGLUT1+, 55% of VGLUT2+, and 80% of VGAT+ puncta; VAMP2 in about 95% of VGLUT1+, 75% of VGLUT2+, and 80% of VGAT+ puncta; STX1A in about 65% of VGLUT1+, 30% of VGLUT2+, and 3% of VGAT+ puncta, and STX1B in approximately 45% of VGLUT1+, 35% of VGLUT2+, and 70% of VGAT+ puncta. Immunoisolation studies showed that while STX1A was completely segregated and virtually absent from VGAT synaptic vesicles, STX1B, VAMP1/VAMP2, SGYR1/SGYR3 showed a similar pattern with the highest expression in VGLUT1 immunoisolated vesicles and the lowest in VGAT immunoisolated vesicles. Moreover, we studied the localization of STX1B at the electron microscope and found that a population of axon terminals forming symmetric synapses were STX1B-positive.These results extend our previous observations on the differential expression of presynaptic proteins involved in neurotransmitter release in GABAergic and glutamatergic terminals and indicate that heterogeneity of glutamatergic and GABAergic release machinery can be contributed by both the presence or absence of a given protein in a nerve terminal and the amount of protein expressed by synaptic vesicles. PMID:19909789

  13. 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. PMID:23543276

  14. Mapping protein conformational heterogeneity under pressure with site-directed spin labeling and double electron-electron resonance.

    PubMed

    Lerch, Michael T; Yang, Zhongyu; Brooks, Evan K; Hubbell, Wayne L

    2014-04-01

    The dominance of a single native state for most proteins under ambient conditions belies the functional importance of higher-energy conformational states (excited states), which often are too sparsely populated to allow spectroscopic investigation. Application of high hydrostatic pressure increases the population of excited states for study, but structural characterization is not trivial because of the multiplicity of states in the ensemble and rapid (microsecond to millisecond) exchange between them. Site-directed spin labeling in combination with double electron-electron resonance (DEER) provides long-range (20-80 Å) distance distributions with angstrom-level resolution and thus is ideally suited to resolve conformational heterogeneity in an excited state populated under high pressure. DEER currently is performed at cryogenic temperatures. Therefore, a method was developed for rapidly freezing spin-labeled proteins under pressure to kinetically trap the high-pressure conformational ensemble for subsequent DEER data collection at atmospheric pressure. The methodology was evaluated using seven doubly-labeled mutants of myoglobin designed to monitor selected interhelical distances. For holomyoglobin, the distance distributions are narrow and relatively insensitive to pressure. In apomyoglobin, on the other hand, the distributions reveal a striking conformational heterogeneity involving specific helices in the pressure range of 0-3 kbar, where a molten globule state is formed. The data directly reveal the amplitude of helical fluctuations, information unique to the DEER method that complements previous rate determinations. Comparison of the distance distributions for pressure- and pH-populated molten globules shows them to be remarkably similar despite a lower helical content in the latter. PMID:24707053

  15. Mapping protein conformational heterogeneity under pressure with site-directed spin labeling and double electron–electron resonance

    PubMed Central

    Lerch, Michael T.; Yang, Zhongyu; Brooks, Evan K.; Hubbell, Wayne L.

    2014-01-01

    The dominance of a single native state for most proteins under ambient conditions belies the functional importance of higher-energy conformational states (excited states), which often are too sparsely populated to allow spectroscopic investigation. Application of high hydrostatic pressure increases the population of excited states for study, but structural characterization is not trivial because of the multiplicity of states in the ensemble and rapid (microsecond to millisecond) exchange between them. Site-directed spin labeling in combination with double electron–electron resonance (DEER) provides long-range (20–80 Å) distance distributions with angstrom-level resolution and thus is ideally suited to resolve conformational heterogeneity in an excited state populated under high pressure. DEER currently is performed at cryogenic temperatures. Therefore, a method was developed for rapidly freezing spin-labeled proteins under pressure to kinetically trap the high-pressure conformational ensemble for subsequent DEER data collection at atmospheric pressure. The methodology was evaluated using seven doubly-labeled mutants of myoglobin designed to monitor selected interhelical distances. For holomyoglobin, the distance distributions are narrow and relatively insensitive to pressure. In apomyoglobin, on the other hand, the distributions reveal a striking conformational heterogeneity involving specific helices in the pressure range of 0–3 kbar, where a molten globule state is formed. The data directly reveal the amplitude of helical fluctuations, information unique to the DEER method that complements previous rate determinations. Comparison of the distance distributions for pressure- and pH-populated molten globules shows them to be remarkably similar despite a lower helical content in the latter. PMID:24707053

  16. Overexpression of Desulfovibrio vulgaris Hildenborough cytochrome c553 in Desulfovibrio desulfuricans G200. Evidence of conformational heterogeneity in the oxidized protein by NMR.

    PubMed

    Blanchard, L; Marion, D; Pollock, B; Voordouw, G; Wall, J; Bruschi, M; Guerlesquin, F

    1993-12-01

    Plasmid pRC41, containing the cyf gene encoding cytochrome c533 from Desulfovibrio vulgaris Hildenborough, was transferred by conjugation from Escherichia coli to Desulfovibrio desulfuricans G200. The structural properties of the purified protein were studied by one-dimensional and two-dimensional NMR. A heterogeneity in the folding of the cytochrome isolated from D. vulgaris Hildenborough and from D. desulfuricans G200 was observed for the oxidized from. Temperature, pH and salt-dependence studies indicated that the heterogeneity does not result from an intermediate in the protein unfolding process, but derives from two conformations which are not in dynamic equilibrium. PMID:8269917

  17. 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. PMID:27437115

  18. 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

  19. 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

  20. Structural Heterogeneity in Transmembrane Amyloid Precursor Protein Homodimer Is a Consequence of Environmental Selection

    PubMed Central

    2015-01-01

    The 99 amino acid C-terminal fragment of amyloid precursor protein (C99), consisting of a single transmembrane (TM) helix, is known to form homodimers. Homodimers can be processed by γ-secretase to produce amyloid-β (Aβ) protein, which is implicated in Alzheimer’s disease (AD). While knowledge of the structure of C99 homodimers is of great importance, experimental NMR studies and simulations have produced varying structural models, including right-handed and left-handed coiled-coils. In order to investigate the structure of this critical protein complex, simulations of the C9915–55 homodimer in POPC membrane bilayer and DPC surfactant micelle environments were performed using a multiscale approach that blends atomistic and coarse-grained models. The C9915–55 homodimer adopts a dominant right-handed coiled-coil topology consisting of three characteristic structural states in a bilayer, only one of which is dominant in the micelle. Our structural study, which provides a self-consistent framework for understanding a number of experiments, shows that the energy landscape of the C99 homodimer supports a variety of slowly interconverting structural states. The relative importance of any given state can be modulated through environmental selection realized by altering the membrane or micelle characteristics. PMID:24926593

  1. Heterogeneity among Homologs of Cutinase-Like Protein Cut5 in Mycobacteria

    PubMed Central

    Gambhir, Vandana; Dikshit, Kanak Lata; Varshney, Grish C.

    2015-01-01

    The study of genomic variability within various pathogenic and non-pathogenic strains of mycobacteria provides insight into their evolution and pathogenesis. The mycobacterial genome encodes seven cutinase-like proteins and each one of these exhibit distinct characteristics. We describe the presence of Cut5, a member of the cutinase family, in mycobacteria and the existence of a unique genomic arrangement in the cut5 gene of M. tuberculosis (Mtb) strains. A single nucleotide (T) insertion is observed in the cut5 gene, which is specific for Mtb strains. Using in silico analysis and RT-PCR, we demonstrate the transcription of Rv3724/cut5 as Rv3724a/cut5a and Rv3724b/cut5b in Mtb H37Rv and as full length cut5 in M. bovis. Cut5b protein of Mtb H37Rv (MtbCut5b) was found to be antigenically similar to its homologs in M. bovis and M. smegmatis, without any observed cross-reactivity with other Mtb cutinases. Also, the presence of Cut5b in Mtb and its homologs in M. bovis and M. smegmatis were confirmed by western blotting using antibodies raised against recombinant Cut5b. In Mtb H37Rv, Cut5b was found to be localized in the cell wall, cytosol and membrane fractions. We also report the vast prevalence of Cut5 homologs in pathogenic and non pathogenic species of mycobacteria. In silico analysis revealed that this protein has three possible organizations in mycobacteria. Also, a single nucleotide (T) insertion in Mtb strains and varied genomic arrangements within mycobacterial species make Rv3724/Cut5 a potential candidate that can be exploited as a biomarker in Mtb infection. PMID:26177502

  2. Free-Propagator Reweighting Integrator for Single-Particle Dynamics in Reaction-Diffusion Models of Heterogeneous Protein-Protein Interaction Systems

    NASA Astrophysics Data System (ADS)

    Johnson, Margaret E.; Hummer, Gerhard

    2014-07-01

    We present a new algorithm for simulating reaction-diffusion equations at single-particle resolution. Our algorithm is designed to be both accurate and simple to implement, and to be applicable to large and heterogeneous systems, including those arising in systems biology applications. We combine the use of the exact Green's function for a pair of reacting particles with the approximate free-diffusion propagator for position updates to particles. Trajectory reweighting in our free-propagator reweighting (FPR) method recovers the exact association rates for a pair of interacting particles at all times. FPR simulations of many-body systems accurately reproduce the theoretically known dynamic behavior for a variety of different reaction types. FPR does not suffer from the loss of efficiency common to other path-reweighting schemes, first, because corrections apply only in the immediate vicinity of reacting particles and, second, because by construction the average weight factor equals one upon leaving this reaction zone. FPR applications include the modeling of pathways and networks of protein-driven processes where reaction rates can vary widely and thousands of proteins may participate in the formation of large assemblies. With a limited amount of bookkeeping necessary to ensure proper association rates for each reactant pair, FPR can account for changes to reaction rates or diffusion constants as a result of reaction events. Importantly, FPR can also be extended to physical descriptions of protein interactions with long-range forces, as we demonstrate here for Coulombic interactions.

  3. HER2 intratumoral heterogeneity analyses by concurrent HER2 gene and protein assessment for the prognosis of HER2 negative invasive breast cancer patients.

    PubMed

    Kurozumi, Sasagu; Padilla, Mary; Kurosumi, Masafumi; Matsumoto, Hiroshi; Inoue, Kenichi; Horiguchi, Jun; Takeyoshi, Izumi; Oyama, Tetsunari; Ranger-Moore, Jim; Allred, D Craig; Dennis, Eslie; Nitta, Hiroaki

    2016-07-01

    HER2 gene-protein assay (GPA) is a new method for the simultaneous evaluation of HER2 immunohistochemistry (IHC) and HER2 dual in situ hybridization (DISH) on single tissue sections of breast cancer. We investigated the presence of HER2 gene and protein discrepancy and HER2-heterogeneity using HER2-GPA. HER2 status was analyzed for the correlation between the presence of HER2-heterogeneity and patient prognosis. Consecutive 280 invasive breast cancer were examined. Statuses of HER2 protein and gene were evaluated in whole tumor sections of HER2 GPA slides. HER2 protein and gene combination patterns were classified to six phenotypic and genotypic types for each case, as well as at individual cell levels: (A) IHC and DISH positive; (B) IHC positive and DISH negative; (C) IHC equivocal and DISH positive; (D) IHC equivocal and DISH negative; (E) IHC negative and DISH positive; and (F) IHC and DISH negative. The presence of HER2-heterogeneity was determined by the existence of at least two of six types within one tumor. HER2-IHC positive patients had significantly worse survival than IHC negative patients and HER2-DISH positive patients had significantly worse survival than DISH negative patients. HER2 IHC negative and DISH positive patients had significantly worse recurrence-free survival than IHC and DISH negative patients. In the HER2 IHC and DISH negative group, the HER2 heterogeneous group had significantly worse survival than the nonheterogeneous group. Notably, among triple negative breast cancer (TNBC), the HER2 heterogeneous group had significantly worse survival than the nonheterogeneous group. Our study suggests that the presence of HER2-heterogeneity might be a prognostic factor in HER2 negative breast cancer patients, especially in TNBC. PMID:27318853

  4. [Heterogeneity of leucinosis. Correlations between clinical manifestations, protein tolerance and enzyme deficiency].

    PubMed

    Saudubray, J M; Amédée-Manesme, O; Munnich, A; Ogier, H; Depondt, E; Charpentier, C; Coudé, F X; Rey, F; Frézal, J

    1982-12-01

    Maple syrup urine disease (MSUD) is an inborn error of branched-chain aminoacid (BCAA) catabolism due to a defect of BC ketoacid decarboxylation. Beside the classical form of the disease, general variant forms have been recently reported. From our personal experience in 21 patients consisting of 14 patients with classical MSUD and 7 patients with "variant" forms (1 intermittent, 2 subacute forms, 1 lipoamide dehydrogenase deficiency and 3 composite heterozygotes), we tried to correlate clinical features with protein tolerance and enzyme activity. All classical forms share an acute neonatal presentation, with a low leucine tolerance (m +/- SD = 465 +/- 88 mg per day), and a very low enzyme activity (m +/- SD = 2.5 +/- 1.5% of controls), mild variations being consistent with a possible polyallelism within this group. All "variant" forms share a late onset with a reasonable leucine tolerance (2-3 grams per day) and a fair enzyme activity, ranging from 7 to 20% of controls. However, no strict correlation could be found between the severity of the outcome and the extent of the residual enzyme activity, since acute episodes or chronic deterioration occurred even in "variants", irrespective of the level of their enzyme activity. Finally, our data suggest that variant forms could result from a composite heterozygotism, combining heterozygotism for the gene of classical MSUD and heterozygotism for a "petite" mutation, undetectable when isolated. The occurrence of classical MSUD and "variant" forms of the disease within a single family of our series further supports this hypothesis. PMID:6897702

  5. Heterogeneity of microtubule-associated protein 2 during rat brain development.

    PubMed Central

    Binder, L I; Frankfurter, A; Kim, H; Caceres, A; Payne, M R; Rebhun, L I

    1984-01-01

    The electrophoretic pattern of the large microtubule-associated protein, MAP2, changes during rat brain development. Immunoblots of NaDodSO4 extracts obtained from the cerebral cortex, cerebellum, and thalamus at 10-15 days after birth reveal only a single electrophoretic species when probed with any of three MAP2 monoclonal antibodies. By contrast, adult MAP2 contains two immunoreactive species, MAP2a and MAP2b. The single band of MAP2 from immature brain electrophoretically comigrates with adult MAP2b. Between postnatal days 17 and 18, immature MAP2 simultaneously resolves into two species in both the cerebellum and cerebral cortex. Immunoblots of NaDodSO4 extracts from spinal cord demonstrate the adult complement of MAP2 by day 10, indicating that MAP2 does not change coordinately throughout the entire central nervous system. In vitro cAMP-dependent phosphorylation of immature MAP2 causes a band split reminiscent of that seen during brain development in vivo. The possibility that the developmentally regulated changes observed in MAP2 during brain maturation are due to timed phosphorylation events is discussed. Images PMID:6591209

  6. Heterogeneity of binding subunits of the human 150K insulin-like growth factor binding protein.

    PubMed

    Gelato, M C; Gaynes, L A; Greenstein, L A; Nissley, S P

    1990-04-01

    Models for the structure of the GH-dependent 150K insulin-like growth factor-binding protein (IGF-BP) complex include 1) a binding subunit of 40-60K mol wt associated with a larger nonbinding component, and 2) an oligomeric structure simply made up of six 25-28K monomeric IGF-BP complexes. To evaluate these alternative models we examined the IGF-binding characteristics and behavior on an SP-Sephadex ion exchange column of BP species identified by chemically cross-linking [125I]IGF-I and [125I]IGF-II. In addition, human serum was gel filtered on Sephadex G-200 in 0.05 M NH4HCO3, pH 8.0, and the 150K BP identified by binding of [125I]IGF-II to column fractions. When [125I]IGF-I or [125I]IGF-II was cross-linked to the 150K BP with disuccinimidyl suberate and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (10-15%) and autoradiography, four specifically labeled complexes of 20K, 24K, 33K, and 47K mol wt were identified. We examined the IGF-binding characteristics of these species by cross-linking [125I]IGF-I and [125I]IGF-II after incubation in the presence of increasing concentrations of unlabeled IGF-I or IGF-II. Formation of the 24K complex was inhibited more potently by IGF-II than IGF-I, whereas the relative potency of IGF-I vs. IGF-II for inhibition of the formation of the other complexes depended upon whether [125I]IGF-II or [125I]IGF-I was used. When the 150K BP complex generated from gel filtration on Sephadex G-200 was acid stripped, the only species seen with chemical cross-linking of either [125I]IGF-I or [125I]IGF-II was the 47K complex. By both conventional competitive binding studies and cross-linking [125I]IGF-I and [125I]IGF-II after incubation with increasing concentrations of unlabeled IGF-I or IGF-II, the formation of the 47K complex was usually more potently inhibited by IGF-I than IGF-II. When Cohn fraction IV extract was chromatographed on a SP-Sephadex column (pH 3) and cross-linking performed on the flow-through, the 47K

  7. An Eriophyid Mite-Transmitted Plant Virus Contains Eight Genomic RNA Segments with Unusual Heterogeneity in the Nucleocapsid Protein

    PubMed Central

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

    2014-01-01

    ABSTRACT 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

  8. 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

  9. A Thermodynamic-Based Interpretation of Protein Expression Heterogeneity in Different Glioblastoma Multiforme Tumors Identifies Tumor-Specific Unbalanced Processes.

    PubMed

    Kravchenko-Balasha, Nataly; Johnson, Hannah; White, Forest M; Heath, James R; Levine, R D

    2016-07-01

    We describe a thermodynamic-motivated, information theoretic analysis of proteomic data collected from a series of 8 glioblastoma multiforme (GBM) tumors. GBMs are considered here as prototypes of heterogeneous cancers. That heterogeneity is viewed here as manifesting in different unbalanced biological processes that are associated with thermodynamic-like constraints. The analysis yields a molecular description of a stable steady state that is common across all tumors. It also resolves molecular descriptions of unbalanced processes that are shared by several tumors, such as hyperactivated phosphoprotein signaling networks. Further, it resolves unbalanced processes that provide unique classifiers of tumor subgroups. The results of the theoretical interpretation are compared against those of statistical multivariate methods and are shown to provide a superior level of resolution for identifying unbalanced processes in GBM tumors. The identification of specific constraints for each GBM tumor suggests tumor-specific combination therapies that may reverse this imbalance. PMID:27035264

  10. The rice RING finger E3 ligase, OsHCI1, drives nuclear export of multiple substrate proteins and its heterogeneous overexpression enhances acquired thermotolerance

    PubMed Central

    Lim, Sung Don; Cho, Hyun Yong; Park, Yong Chan; Ham, Deok Jae; Lee, Ju Kyong; Jang, Cheol Seong

    2013-01-01

    Thermotolerance is very important for plant survival when plants are subjected to lethally high temperature. However, thus far little is known about the functions of RING E3 ligase in response to heat shock in plants. This study found that one rice gene encoding the RING finger protein was specifically induced by heat and cold stress treatments but not by salinity or dehydration and named it OsHCI1 (Oryza sativa heat and cold induced 1). Subcellular localization results showed that OsHCI1 was mainly associated with the Golgi apparatus and moved rapidly and extensively along the cytoskeleton. In contrast, OsHCI1 may have accumulated in the nucleus under high temperatures. OsHCI1 physically interacted with nuclear substrate proteins including a basic helix-loop-helix transcription factor. Transient co-overexpression of OsHCI1 and each of three nuclear proteins showed that their fluorescent signals moved into the cytoplasm as punctuate formations. Heterogeneous overexpression of OsHCI1 in Arabidopsis highly increased survival rate through acquired thermotolerance. It is proposed that OsHCI1 mediates nuclear–cytoplasmic trafficking of nuclear substrate proteins via monoubiquitination and drives an inactivation device for the nuclear proteins under heat shock. PMID:23698632

  11. Primary structure of human nuclear ribonucleoprotein particle C proteins: conservation of sequence and domain structures in heterogeneous nuclear RNA, mRNA, and pre-rRNA-binding proteins.

    PubMed Central

    Swanson, M S; Nakagawa, T Y; LeVan, K; Dreyfuss, G

    1987-01-01

    In the eucaryotic nucleus, heterogeneous nuclear RNAs exist in a complex with a specific set of proteins to form heterogeneous nuclear ribonucleoprotein particles (hnRNPs). The C proteins, C1 and C2, are major constituents of hnRNPs and appear to play a role in RNA splicing as suggested by antibody inhibition and immunodepletion experiments. With the use of a previously described partial cDNA clone as a hybridization probe, full-length cDNAs for the human C proteins were isolated. All of the cDNAs isolated hybridized to two poly(A)+ RNAs of 1.9 and 1.4 kilobases (kb). DNA sequencing of a cDNA clone for the 1.9-kb mRNA (pHC12) revealed a single open reading frame of 290 amino acids coding for a protein of 31,931 daltons and two polyadenylation signals, AAUAAA, approximately 400 base pairs apart in the 3' untranslated region of the mRNA. DNA sequencing of a clone corresponding to the 1.4-kb mRNA (pHC5) indicated that the sequence of this mRNA is identical to that of the 1.9-kb mRNA up to the first polyadenylation signal which it uses. Both mRNAs therefore have the same coding capacity and are probably transcribed from a single gene. Translation in vitro of the 1.9-kb mRNA selected by hybridization with a 3'-end subfragment of pHC12 demonstrated that it by itself can direct the synthesis of both C1 and C2. The difference between the C1 and C2 proteins which results in their electrophoretic separation is not known, but most likely one of them is generated from the other posttranslationally. Since several hnRNP proteins appeared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis as multiple antigenically related polypeptides, this raises the possibility that some of these other groups of hnRNP proteins are also each produced from a single mRNA. The predicted amino acid sequence of the protein indicates that it is composed of two distinct domains: an amino terminus that contains what we have recently described as a RNP consensus sequence, which is the putative

  12. Evolution of eutherian cytochrome c oxidase subunit II: heterogeneous rates of protein evolution and altered interaction with cytochrome c.

    PubMed

    Adkins, R M; Honeycutt, R L; Disotell, T R

    1996-12-01

    Cytochrome c oxidase subunit II (COII), encoded by the mitochondrial genome, exhibits one of the most heterogeneous rates of amino acid replacement among placental mammals. Moreover, it has been demonstrated that cytochrome c oxidase has undergone a structural change in higher primates which has altered its physical interaction with cytochrome c. We collected a large data set of COII sequences from several orders of mammals with emphasis on primates, rodents, and artiodactyls. Using phylogenetic hypotheses based on data independent of the COII gene, we demonstrated that an increased number of amino acid replacements are concentrated among higher primates. Incorporating approximate divergence dates derived from the fossil record, we find that most of the change occurred independently along the New World monkey lineage and in a rapid burst before apes and Old World monkeys diverged. There is some evidence that Old World monkeys have undergone a faster rate of nonsynonymous substitution than have apes. Rates of substitution at four-fold degenerate sites in primates are relatively homogeneous, indicating that the rate heterogeneity is restricted to nondegenerate sites. Excluding the rate acceleration mentioned above, primates, rodents, and artiodactyls have remarkably similar nonsynonymous replacement rates. A different pattern is observed for transversions at four-fold degenerate sites, for which rodents exhibit a higher rate of replacement than do primates and artiodactyls. Finally, we hypothesize specific amino acid replacements which may account for much of the structural difference in cytochrome c oxidase between higher primates and other mammals. PMID:8952084

  13. Identification of the methylation preference region in heterogeneous nuclear ribonucleoprotein K by protein arginine methyltransferase 1 and its implication in regulating nuclear/cytoplasmic distribution

    SciTech Connect

    Chang, Yuan-I; Hsu, Sheng-Chieh; Chau, Gar-Yang; Huang, Chi-Ying F.; Sung, Jung-Sung; Hua, Wei-Kai; Lin, Wey-Jinq

    2011-01-21

    Research highlights: {yields} Verifying by direct methylation assay the substrate sites of PRMT1 in the hnRNP K protein. {yields} Identifying the preferred PMRT1 methylation regions in hnRNP K by kinetic analysis. {yields} Linking methylation in regulating nuclear localization of hnRNP K. -- Abstract: Protein arginine methylation plays crucial roles in numerous cellular processes. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multi-functional protein participating in a variety of cellular functions including transcription and RNA processing. HnRNP K is methylated at multiple sites in the glycine- and arginine-rich (RGG) motif. Using various RGG domain deletion mutants of hnRNP K as substrates, here we show by direct methylation assay that protein arginine methyltransferase 1 (PRMT1) methylated preferentially in a.a. 280-307 of the RGG motif. Kinetic analysis revealed that deletion of a.a. 280-307, but not a.a. 308-327, significantly inhibited rate of methylation. Importantly, nuclear localization of hnRNP K was significantly impaired in mutant hnRNP K lacking the PRMT1 methylation region or upon pharmacological inhibition of methylation. Together our results identify preferred PRMT1 methylation sequences of hnRNP K by direct methylation assay and implicate a role of arginine methylation in regulating intracellular distribution of hnRNP K.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25348392

  15. 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.

  16. 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

  17. 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

  18. Chemical heterogeneity as a result of hydroxylamine cleavage of a fusion protein of human insulin-like growth factor I.

    PubMed Central

    Canova-Davis, E; Eng, M; Mukku, V; Reifsnyder, D H; Olson, C V; Ling, V T

    1992-01-01

    Recombinant DNA techniques were used to biosynthesize human insulin-like growth factor I (hIGF-I) as a fusion protein wherein the fusion polypeptide is an IgG-binding moiety derived from staphylococcal protein A. This fusion protein is produced in Escherichia coli and secreted into the fermentation broth. In order to release mature recombinant-derived hIGF-I (rhIGF-I), the fusion protein is treated with hydroxylamine, which cleaves a susceptible Asn-Gly bond that has been engineered into the fusion protein gene. Reversed-phase h.p.l.c. was used to estimate the purity of the rhIGF-I preparations, especially for the quantification of the methionine sulphoxide-containing variant. It was determined that hydroxylamine cleavage of the fusion protein produced, as a side reaction, hydroxamates of the asparagine and glutamine residues in rhIGF-I. Although isoelectric focusing was effective in detecting, and reversed-phase h.p.l.c. for producing enriched fractions of the hydroxamate variants, ion-exchange chromatography was a more definitive procedure, as it allowed quantification and facile removal of these variants. The identity of the variants as hydroxamates was established by Staphylococcus aureus V8 proteinase digestion, followed by m.s., as the modification was transparent to amino acid and N-terminal sequence analyses. The biological activity of rhIGF-I was established by its ability to incorporate [3H]thymidine into the DNA of BALB/c373 cells and by a radioreceptor assay utilizing human placental membranes. Both assays demonstrate that the native, recombinant and methionine sulphoxide and hydroxamate IGF-I variants are essentially equipotent. Images Fig. 2. PMID:1637301

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

    PubMed Central

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

    2016-01-01

    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. PMID:26824423

  20. 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. PMID:26824423

  1. 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

  2. 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)

  3. 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

  4. Functional heterogeneity as reflected by topological parameters in a classical protein molecular model: t4 phage lysozyme.

    PubMed

    Caruso, Lisa Beatrice; Giuliani, Alessandro; Colosimo, Alfredo

    2016-01-01

    A systematic comparison with the Wild-Type (WT) of one-point mutants of bacteriophage T4 lysozyme was carried out using as difference markers the topological parameters of the protein contact networks corresponding to each crystallographic structure. The investigation concerned changes at the resolution level of single residue along the protein sequence. The results were correlated with (reported) changes in functional properties and (observed) changes in the information provided by the energy dissipation algorithm of the "Turbine" software simulation tool. The critical factor leading to significant difference among mutants and WT is in most cases associated to the sensitivity towards mutation of relatively short windows in the amino acidic sequence not necessarily contiguous to the active site. PMID:26412794

  5. The Coxiella burnetii Ankyrin Repeat Domain-Containing Protein Family Is Heterogeneous, with C-Terminal Truncations That Influence Dot/Icm-Mediated Secretion ▿

    PubMed Central

    Voth, Daniel E.; Howe, Dale; Beare, Paul A.; Vogel, Joseph P.; Unsworth, Nathan; Samuel, James E.; Heinzen, Robert A.

    2009-01-01

    Coxiella burnetii is an obligate intracellular bacterium that directs biogenesis of a parasitophorous vacuole (PV) for replication. Effectors of PV maturation are likely translocated into the host cytosol by a type IV secretion system (T4SS) with homology to the Dot/Icm apparatus of Legionella pneumophila. Since secreted bacterial virulence factors often functionally mimic the activities of host proteins, prokaryotic proteins with eukaryotic features are considered candidate T4SS substrates. Genes encoding proteins with eukaryotic-type ankyrin repeat domains (Anks) were identified upon genome sequencing of the C. burnetii Nine Mile reference isolate, which is associated with a case of human acute Q fever. Interestingly, recent genome sequencing of the G and K isolates, derived from human chronic endocarditis patients, and of the Dugway rodent isolate revealed remarkable heterogeneity in the Ank gene family, with the Dugway isolate harboring the largest number of full-length Ank genes. Using L. pneumophila as a surrogate host, we identified 10 Dugway Anks and 1 Ank specific to the G and K endocarditis isolates translocated into the host cytosol in a Dot/Icm-dependent fashion. A 10-amino-acid C-terminal region appeared to be necessary for translocation, with some Anks also requiring the chaperone IcmS for secretion. Ectopically expressed Anks localized to a variety of subcellular regions in mammalian cells, including microtubules, mitochondria, and the PV membrane. Collectively, these data suggest that C. burnetii isolates translocate distinct subsets of the Ank protein family into the host cytosol, where they modulate diverse functions, some of which may be unique to C. burnetii pathotypes. PMID:19411324

  6. Facilitation of hammerhead ribozyme catalysis by the nucleocapsid protein of HIV-1 and the heterogeneous nuclear ribonucleoprotein A1.

    PubMed Central

    Bertrand, E L; Rossi, J J

    1994-01-01

    In order to improve the activity of hammerhead ribozymes in vivo, we have analyzed the effect of several prototypical RNA binding proteins on the ribozyme cleavage reaction: bacteriophage T4 gene 32 protein (gp32), hnRNP A1 (A1) and the nucleocapsid protein of HIV-1 (NCp7). We show that, while gp32 has no effect on the cleavage reaction, A1 and NCp7 affect different steps of the reaction. Moreover, some of these effects depend upon the ribozyme-substrate hybrid length. A1 and NCp7 inhibit the reaction of the least stable ribozyme-substrate complexes, which have 12 bp of duplex. NCp7, but not A1, inhibits the cleavage of substrates that have long ribozyme-substrate duplexes (17 or 20 bp), while cleavage of complexes having shorter duplexes (13 or 14 bp) is not affected. NCp7 and A1 enhance the turnover of ribozymes by increasing the rate of product dissociation, but only when both cleavage products are bound with < or = 7 bp. A1 and NCp7 enhance ribozyme binding to long substrates, such as mRNAs, the structure of which otherwise limits ribozyme binding. Therefore, the effects of A1 or NCp7 on the different steps of the cleavage reaction define a length of the ribozyme-substrate duplex which allows enhancement of the rate of binding and product release without inhibiting the cleavage step. Interestingly, this duplex length (14 bases, or 7 on each side of the cleavage site) is identical for A1 and NCp7. Since A1 is thought to interact with most, if not all mRNAs in vivo, it may enhance the intracellular activity of ribozymes targeted against any mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8026475

  7. 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

  8. Heterogeneous nuclear ribonucleoprotein (hnRNP) F is a novel component of oligodendroglial RNA transport granules contributing to regulation of myelin basic protein (MBP) synthesis.

    PubMed

    White, Robin; Gonsior, Constantin; Bauer, Nina M; Krämer-Albers, Eva-Maria; Luhmann, Heiko J; Trotter, Jacqueline

    2012-01-13

    Myelin basic protein (MBP) is a major component of central nervous system (CNS) myelin. The absence of MBP results in the loss of almost all compact myelin in the CNS. MBP mRNA is sorted into RNA granules that are transported to the periphery of oligodendrocytes in a translationally inactive state. A central mediator of this transport process is the trans-acting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 that binds to the cis-acting A2-response element in the 3'UTR of MBP mRNA. Recently, we found that activation of the Src family nonreceptor tyrosine kinase Fyn in oligodendrocytes leads to phosphorylation of hnRNP A2 and to increased translation of MBP mRNA. Here, we identify the RNA-binding protein hnRNP F as a novel component of MBP mRNA transport granules. It is associated with hnRNP A2 and MBP mRNA in cytoplasmic granular structures and is involved in post-transcriptional regulation of MBP expression. Fyn kinase activity results in phosphorylation of hnRNP F in the cytoplasm and its release from MBP mRNA and RNA granules. Our results define hnRNP F as a regulatory element of MBP expression in oligodendrocytes and imply an important function of hnRNP F in the control of myelin synthesis. PMID:22128153

  9. Centromere Protein (CENP)-W Interacts with Heterogeneous Nuclear Ribonucleoprotein (hnRNP) U and May Contribute to Kinetochore-Microtubule Attachment in Mitotic Cells

    PubMed Central

    Chun, Younghwa; Kim, Raehyung; Lee, Soojin

    2016-01-01

    Background Recent studies have shown that heterogeneous nuclear ribonucleoprotein U (hnRNP U), a component of the hnRNP complex, contributes to stabilize the kinetochore-microtubule interaction during mitosis. CENP-W was identified as an inner centromere component that plays crucial roles in the formation of a functional kinetochore complex. Results We report that hnRNP U interacts with CENP-W, and the interaction between hnRNP U and CENP-W mutually increased each other’s protein stability by inhibiting the proteasome-mediated degradation. Further, their co-localization was observed chiefly in the nuclear matrix region and at the microtubule-kinetochore interface during interphase and mitosis, respectively. Both microtubule-stabilizing and microtubule-destabilizing agents significantly decreased the protein stability of CENP-W. Furthermore, loss of microtubules and defects in microtubule organization were observed in CENP-W-depleted cells. Conclusion Our data imply that CENP-W plays an important role in the attachment and interaction between microtubules and kinetochore during mitosis. PMID:26881882

  10. Heterogeneous Nuclear Ribonucleoprotein (hnRNP) F Is a Novel Component of Oligodendroglial RNA Transport Granules Contributing to Regulation of Myelin Basic Protein (MBP) Synthesis*

    PubMed Central

    White, Robin; Gonsior, Constantin; Bauer, Nina M.; Krämer-Albers, Eva-Maria; Luhmann, Heiko J.; Trotter, Jacqueline

    2012-01-01

    Myelin basic protein (MBP) is a major component of central nervous system (CNS) myelin. The absence of MBP results in the loss of almost all compact myelin in the CNS. MBP mRNA is sorted into RNA granules that are transported to the periphery of oligodendrocytes in a translationally inactive state. A central mediator of this transport process is the trans-acting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 that binds to the cis-acting A2-response element in the 3′UTR of MBP mRNA. Recently, we found that activation of the Src family nonreceptor tyrosine kinase Fyn in oligodendrocytes leads to phosphorylation of hnRNP A2 and to increased translation of MBP mRNA. Here, we identify the RNA-binding protein hnRNP F as a novel component of MBP mRNA transport granules. It is associated with hnRNP A2 and MBP mRNA in cytoplasmic granular structures and is involved in post-transcriptional regulation of MBP expression. Fyn kinase activity results in phosphorylation of hnRNP F in the cytoplasm and its release from MBP mRNA and RNA granules. Our results define hnRNP F as a regulatory element of MBP expression in oligodendrocytes and imply an important function of hnRNP F in the control of myelin synthesis. PMID:22128153

  11. 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.

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

    PubMed

    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. PMID:26291198

  13. Heterogeneous side chain conformation highlights a network of interactions implicated in hysteresis of the knotted protein, Minimal Tied Trefoil (MTTTm)

    PubMed Central

    Capraro, Dominique T.; Jennings, Patricia A.

    2015-01-01

    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. PMID:26291198

  14. 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.

  15. Antibodies to the RNA Binding Protein Heterogeneous Nuclear Ribonucleoprotein A1 Colocalize to Stress Granules Resulting in Altered RNA and Protein Levels in a Model of Neurodegeneration in Multiple Sclerosis

    PubMed Central

    Douglas, Joshua N.; Gardner, Lidia A.; Salapa, Hannah E; Levin, Michael C.

    2016-01-01

    Objective Multiple sclerosis (MS) is the most common demyelinating disorder of the central nervous system (CNS). Data suggest that antibodies to CNS targets contribute to the pathogenesis of MS. MS patients produce autoantibodies to heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). hnRNP A1 is an RNA binding protein (RBP) overexpressed in neurons that functions in pre-mRNA splicing, mRNA trafficking, and translation. Previously, we showed that anti-hnRNP A1 antibodies entered neuronal cells (in vitro) via clathrin-mediated endocytosis, caused mislocalization of endogenous hnRNP A1 protein and increased markers of neurodegeneration including decreased ATP concentration and apoptosis. In this study, we hypothesized that anti-hnRNP A1 antibodies might cause stress granule formation and altered levels of RNAs and proteins that bind hnRNP A1. Methods Neuronal cell lines were exposed to anti-hnRNP A1 and isotype-matched control antibodies in vitro and examined for neuronal granule formation, including stress granules, P bodies and transport granules. In addition, RNAs that bound hnRNP A1 were determined. Levels of RNA and their translated proteins were measured upon exposure to the anti-hnRNP A1 antibodies. Results Anti-hnRNP A1 antibodies induced and localized to stress granules, a marker of neurodegeneration, within a neuronal cell line. The anti-hnRNP A1 antibodies did not induce P bodies or neuronal granules. Clinically relevant RNAs were found to bind hnRNP A1. In addition, the anti-hnRNP A1 antibodies caused reduced levels of RNA and protein of the spinal paraplegia genes (SPGs) 4 and 7, which when mutated mimic progressive MS. Conclusions Taken together, these data suggest potential mechanisms by which autoantibodies may contribute to neurodegeneration in MS. PMID:27375925

  16. 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.

  17. Molecular Insights into the Coding Region Determinant-binding Protein-RNA Interaction through Site-directed Mutagenesis in the Heterogeneous Nuclear Ribonucleoprotein-K-homology Domains*

    PubMed Central

    Barnes, Mark; van Rensburg, Gerrit; Li, Wai-Ming; Mehmood, Kashif; Mackedenski, Sebastian; Chan, Ching-Man; King, Dustin T.; Miller, Andrew L.; Lee, Chow H.

    2015-01-01

    The ability of its four heterogeneous nuclear RNP-K-homology (KH) domains to physically associate with oncogenic mRNAs is a major criterion for the function of the coding region determinant-binding protein (CRD-BP). However, the particular RNA-binding role of each of the KH domains remains largely unresolved. Here, we mutated the first glycine to an aspartate in the universally conserved GXXG motif of the KH domain as an approach to investigate their role. Our results show that mutation of a single GXXG motif generally had no effect on binding, but the mutation in any two KH domains, with the exception of the combination of KH3 and KH4 domains, completely abrogated RNA binding in vitro and significantly retarded granule formation in zebrafish embryos, suggesting that any combination of at least two KH domains cooperate in tandem to bind RNA efficiently. Interestingly, we found that any single point mutation in one of the four KH domains significantly impacted CRD-BP binding to mRNAs in HeLa cells, suggesting that the dynamics of the CRD-BP-mRNA interaction vary over time in vivo. Furthermore, our results suggest that different mRNAs bind preferentially to distinct CRD-BP KH domains. The novel insights revealed in this study have important implications on the understanding of the oncogenic mechanism of CRD-BP as well as in the future design of inhibitors against CRD-BP function. PMID:25389298

  18. Epidermal growth factor increases the interaction between nucleolin and heterogeneous nuclear ribonucleoprotein K/poly(C) binding protein 1 complex to regulate the gastrin mRNA turnover.

    PubMed

    Lee, Pin-Tse; Liao, Pao-Chi; Chang, Wen-Chang; Tseng, Joseph T

    2007-12-01

    Gastrin, a gastrointestinal hormone responsible for gastric acid secretion, has been confirmed as a growth factor for gastrointestinal tract malignancies. High expression of gastrin mRNA was observed in pancreatic and colorectal cancer; however, the mechanism is unclear. Epidermal growth factor (EGF) was found to increase gastrin mRNA stability, indicating mRNA turnover regulation mechanism is involved in the control of gastrin mRNA expression. Using biotin-labeled RNA probe pull-down assay combined with mass spectrometry analysis, we identified the heterogeneous nuclear ribonucleoprotein K (hnRNP K) and poly(C) binding protein 1 (PCBP1) bound with the C-rich region in gastrin mRNA 3' untranslated region. Nucleolin bound with the AGCCCU motif and interacted with hnRNP K were also demonstrated. Under EGF treatment, we observed the amount of nucleolin interacting with hnRNP K and gastrin mRNA increased. Using small interfering RNA technology to define their functional roles, we found hnRNP K, PCBP1, and nucleolin were all responsible for stabilizing gastrin mRNA. Moreover, nucleolin plays a crucial role in mediating the increased gastrin mRNA stability induced by EGF signaling. Besides, we also observed hnRNP K/PCBP1 complex bound with the C-rich region in the gastrin mRNA increased nucleolin binding with gastrin mRNA. Finally, a novel binding model was proposed. PMID:17928403

  19. Heterogeneity of protein–polysaccharides of porcine articular cartilage. The sequential extraction of chondroitin sulphate–proteins with iso-osmotic neutral sodium acetate

    PubMed Central

    Brandt, Kenneth D.; Muir, Helen

    1971-01-01

    Protein–polysaccharides of knee-joint cartilage of 9-month-old pigs were extracted sequentially with neutral iso-osmotic sodium acetate after five repeated homogenizations. One-third of the uronic acid originally present in the tissue was brought into solution, about half being in the first extract. The protein–polysaccharides, which were purified by precipitation with 9-aminoacridine, were heterogeneous in size on gel chromatography. The smallest (retarded by 6% agarose) were the most easily extracted since they were most prevalent in the initial extracts and absent from later ones, whereas the proportion of larger molecules increased progressively in successive extracts. Nevertheless a small proportion of the largest molecules (excluded from Sepharose 2B) was present even in the first extract. None of the protein–polysaccharide preparations contained hydroxyproline, and the analyses of their constituent sugars were the same, although there was a progressive increase in the protein content and in the glucosamine/galactosamine molar ratio of successive extracts. In each preparation this molar ratio was invariably greater in larger than in smaller molecules separated by gel filtration. From galactosamine/pentose molar ratios it appeared that the chondroitin sulphate chains were on average about 29 disaccharide units in length in the protein–polysaccharides of each extract, although gel-chromatography and cetylpyridinium chloride elution profiles showed that a somewhat higher proportion of shorter chondroitin sulphate chains occurred in the larger protein–polysaccharides. In the last extract, where the largest molecules predominated, about half could be reversibly dissociated by urea, whereas this had no effect on the protein–polysaccharides of earlier extracts even though these contained some large molecules. PMID:5117031

  20. Impact of heterogeneity within cultured cells on bacterial invasion: analysis of Pseudomonas aeruginosa and Salmonella enterica serovar typhi entry into MDCK cells by using a green fluorescent protein-labelled cystic fibrosis transmembrane conductance regulator receptor.

    PubMed

    Gerçeker, A A; Zaidi, T; Marks, P; Golan, D E; Pier, G B

    2000-02-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel that also serves as a receptor for entry of Pseudomonas aeruginosa and Salmonella enterica serovar Typhi into epithelial cells. To evaluate heterogeneity in CFTR protein expression in cultured cells and the effect of heterogeneity on internalization of different P. aeruginosa and serovar Typhi strains, we used two-color flow cytometry and confocal laser microscopy to study bacterial uptake by Madin-Darby canine kidney (MDCK) type I epithelial cells stably expressing a green fluorescent protein (GFP)-CFTR fusion construct (MDCK-GFP-CFTR cells). We found a strong correlation between cell size and GFP-CFTR protein expression, with 60 to 70% of cells expressing low levels of GFP-CFTR protein, 20 to 30% expressing intermediate levels, and <10% expressing high levels. The cells were sorted into low-, intermediate-, or high-level producers of CFTR protein; in vitro growth of each sorted population yielded the same distribution of CFTR protein expression as that in the original population. Cells expressing either low or high levels of CFTR protein internalized bacteria poorly; maximal bacterial uptake occurred in the cells expressing intermediate levels of CFTR protein. Treatment of MDCK cells with sodium butyrate markedly enhanced the production of CFTR protein without increasing cell size; butyrate treatment also increased the proportion of cells with internalized bacteria. However, there were fewer bacteria per butyrate-treated cell and, for P. aeruginosa, there was an overall decrease in the total level of bacterial uptake. The most highly ingested bacterial strains were internalized by fewer total MDCK-GFP-CFTR cells, indicating preferential bacterial uptake by a minority of epithelial cells within a given culture. Confocal fluorescence microscopy showed that P. aeruginosa and serovar Typhi induced cytoplasmic accumulation of CFTR protein close to the plasma membrane where the

  1. The proliferation potential protein-related (P2P-R) gene with domains encoding heterogeneous nuclear ribonucleoprotein association and Rb1 binding shows repressed expression during terminal differentiation.

    PubMed

    Witte, M M; Scott, R E

    1997-02-18

    Terminal differentiation is associated with repression in the expression of the proliferation potential proteins (P2P) subset of heterogeneous nuclear ribonucleoprotein (hnRNP) proteins. We report here the cloning and characterization of a 5173-bp P2P-related (P2P-R) cDNA that contains a 4214-bp open reading frame. Probes to this cDNA detect a single 8-kb mRNA in multiple murine tissues and in proliferating 3T3T cells, but not in terminally differentiated 3T3T adipocytes. Evidence that this cDNA can encode peptides with domains for hnRNP association was established by showing that such peptides are recognized by two monoclonal antibodies known to detect core hnRNP proteins, and by showing that the C130 monoclonal antibody, produced against a cDNA-derived fusion protein, also selectively detects native P2P hnRNP proteins. In addition, P2P-R cDNA-derived fusion proteins bind single-stranded nucleic acids, and a P2P-R cDNA-derived antisense oligonucleotide selectively represses P2P expression. Because terminal differentiation is associated with modulation in Rb1 function, we assayed if products of this cDNA might interact with Rb1. Evidence that the P2P-R cDNA encodes a protein domain that binds Rb1 was established using a glutathione S-transferase fusion protein to selectively precipitate Rb1 from cellular extracts. Data also show that this binding is reduced by competition with the adenovirus E1a protein, indicating that binding occurs through the "pocket" domain of Rb1. These results establish that the P2P-R cDNA encodes protein domains involved in both hnRNP association and Rb1 binding and complement recent reports that localize Rb1 to sites of RNA processing in the nucleus. PMID:9037032

  2. A physical mechanism of cancer heterogeneity

    PubMed Central

    Chen, Cong; Wang, Jin

    2016-01-01

    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. PMID:26854017

  3. 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.

  4. Treponema pallidum subsp. pallidum TP0136 protein is heterogeneous among isolates and binds cellular and plasma fibronectin via its NH2-terminal end.

    PubMed

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

    2015-03-01

    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

  5. 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

  6. 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

  7. 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).

  8. Outer Membrane Protein Heterogeneity within Pseudomonas fluorescens and P. putida and Use of an OprF Antibody as a Probe for rRNA Homology Group I Pseudomonads

    PubMed Central

    Kragelund, L.; Leopold, K.; Nybroe, O.

    1996-01-01

    The electrophoretic patterns of outer membrane proteins of strains representing the biovars of Pseudomonas fluorescens and Pseudomonas putida were analyzed by gel electrophoresis. The outer membrane protein profiles were variable, and they were not useful for assigning strains to a specific biovar. However, three or four predominant outer membrane proteins migrating at 42 to 46 kDa, 33 to 38 kDa, and 20 to 22 kDa were conserved among the strains. They could be tentatively identified as OprE (44 kDa), OprF (38 kDa), OprH (21 kDa), and OprL (20.5 kDa), which are known proteins from Pseudomonas aeruginosa. A 37-kDa OprF-like protein was purified from P. fluorescens DF57 and used to raise a polyclonal antibody. In Western blot (immunoblot) analysis, this antibody reacted with OprF proteins from members of Pseudomonas rRNA homology group I but not with proteins from nonpseudomonads. The heterogeneity in M(infr) of OprF was greater among P. fluorescens strains than among P. putida strains. Immunofluorescence microscopy of intact cells demonstrated that the antibody recognized epitopes that were accessible only after unmasking by EDTA treatment. The antibody was used in a colony blotting assay to determine the percentage of rRNA homology group I pseudomonads among bacteria from the rhizosphere of barley. The bacteria were isolated on 10% tryptic soy agar, King's B agar, and the pseudomonad-specific medium Gould S1 agar. The estimate of OprF-containing CFU in rhizosphere soil obtained by colony blotting on 10% tryptic soy agar was about 2 and 14 times higher than the values obtained from King's agar and Gould S1 agar, respectively, indicating that not all fluorescent pseudomonads are scored on more specific media. The colonies reacting with the OprF antibody were verified as being rRNA homology group I pseudomonads by using the API 20NE system. PMID:16535235

  9. Outer Membrane Protein Heterogeneity within Pseudomonas fluorescens and P. putida and Use of an OprF Antibody as a Probe for rRNA Homology Group I Pseudomonads.

    PubMed

    Kragelund, L; Leopold, K; Nybroe, O

    1996-02-01

    The electrophoretic patterns of outer membrane proteins of strains representing the biovars of Pseudomonas fluorescens and Pseudomonas putida were analyzed by gel electrophoresis. The outer membrane protein profiles were variable, and they were not useful for assigning strains to a specific biovar. However, three or four predominant outer membrane proteins migrating at 42 to 46 kDa, 33 to 38 kDa, and 20 to 22 kDa were conserved among the strains. They could be tentatively identified as OprE (44 kDa), OprF (38 kDa), OprH (21 kDa), and OprL (20.5 kDa), which are known proteins from Pseudomonas aeruginosa. A 37-kDa OprF-like protein was purified from P. fluorescens DF57 and used to raise a polyclonal antibody. In Western blot (immunoblot) analysis, this antibody reacted with OprF proteins from members of Pseudomonas rRNA homology group I but not with proteins from nonpseudomonads. The heterogeneity in M(infr) of OprF was greater among P. fluorescens strains than among P. putida strains. Immunofluorescence microscopy of intact cells demonstrated that the antibody recognized epitopes that were accessible only after unmasking by EDTA treatment. The antibody was used in a colony blotting assay to determine the percentage of rRNA homology group I pseudomonads among bacteria from the rhizosphere of barley. The bacteria were isolated on 10% tryptic soy agar, King's B agar, and the pseudomonad-specific medium Gould S1 agar. The estimate of OprF-containing CFU in rhizosphere soil obtained by colony blotting on 10% tryptic soy agar was about 2 and 14 times higher than the values obtained from King's agar and Gould S1 agar, respectively, indicating that not all fluorescent pseudomonads are scored on more specific media. The colonies reacting with the OprF antibody were verified as being rRNA homology group I pseudomonads by using the API 20NE system. PMID:16535235

  10. 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

  11. Heterogeneous Nuclear Ribonucleoprotein C Proteins Interact with the Human Papillomavirus Type 16 (HPV16) Early 3′-Untranslated Region and Alleviate Suppression of HPV16 Late L1 mRNA Splicing*

    PubMed Central

    Dhanjal, Soniya; Kajitani, Naoko; Glahder, Jacob; Mossberg, Ann-Kristin; Johansson, Cecilia; Schwartz, Stefan

    2015-01-01

    In order to identify cellular factors that regulate human papillomavirus type 16 (HPV16) gene expression, cervical cancer cells permissive for HPV16 late gene expression were identified and characterized. These cells either contained a novel spliced variant of the L1 mRNAs that bypassed the suppressed HPV16 late, 5′-splice site SD3632; produced elevated levels of RNA-binding proteins SRSF1 (ASF/SF2), SRSF9 (SRp30c), and HuR that are known to regulate HPV16 late gene expression; or were shown by a gene expression array analysis to overexpress the RALYL RNA-binding protein of the heterogeneous nuclear ribonucleoprotein C (hnRNP C) family. Overexpression of RALYL or hnRNP C1 induced HPV16 late gene expression from HPV16 subgenomic plasmids and from episomal forms of the full-length HPV16 genome. This induction was dependent on the HPV16 early untranslated region. Binding of hnRNP C1 to the HPV16 early, untranslated region activated HPV16 late 5′-splice site SD3632 and resulted in production of HPV16 L1 mRNAs. Our results suggested that hnRNP C1 controls HPV16 late gene expression. PMID:25878250

  12. Heterogeneous Nuclear Ribonucleoprotein C Proteins Interact with the Human Papillomavirus Type 16 (HPV16) Early 3'-Untranslated Region and Alleviate Suppression of HPV16 Late L1 mRNA Splicing.

    PubMed

    Dhanjal, Soniya; Kajitani, Naoko; Glahder, Jacob; Mossberg, Ann-Kristin; Johansson, Cecilia; Schwartz, Stefan

    2015-05-22

    In order to identify cellular factors that regulate human papillomavirus type 16 (HPV16) gene expression, cervical cancer cells permissive for HPV16 late gene expression were identified and characterized. These cells either contained a novel spliced variant of the L1 mRNAs that bypassed the suppressed HPV16 late, 5'-splice site SD3632; produced elevated levels of RNA-binding proteins SRSF1 (ASF/SF2), SRSF9 (SRp30c), and HuR that are known to regulate HPV16 late gene expression; or were shown by a gene expression array analysis to overexpress the RALYL RNA-binding protein of the heterogeneous nuclear ribonucleoprotein C (hnRNP C) family. Overexpression of RALYL or hnRNP C1 induced HPV16 late gene expression from HPV16 subgenomic plasmids and from episomal forms of the full-length HPV16 genome. This induction was dependent on the HPV16 early untranslated region. Binding of hnRNP C1 to the HPV16 early, untranslated region activated HPV16 late 5'-splice site SD3632 and resulted in production of HPV16 L1 mRNAs. Our results suggested that hnRNP C1 controls HPV16 late gene expression. PMID:25878250

  13. 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.

  14. Multispecific and heterogeneous recognition of the gag protein by cytotoxic T lymphocytes (CTL) from HIV-infected patients: factors other than the MHC control the epitopic specificities.

    PubMed Central

    Buseyne, F; Janvier, G; Fleury, B; Schmidt, D; Rivière, Y

    1994-01-01

    The HIV gag polyprotein is a major target for recognition by CTL in infected humans. Using recombinant vaccinia viruses (rVV) expressing truncations of the p24gag, and the p18gag, p15gag and HIV-2 p56gag proteins, the characterization of epitope regions recognized by in vitro-stimulated peripheral blood mononuclear cells (PBMC) from 18 infected patients has been studied. The gag-specific response of most individuals is polyclonal and multispecific, and interindividual variations between target epitope regions were frequently observed, despite shared MHC alleles. As CTL may play an important role in the control of HIV replication in infected hosts, these results have important implications for designing vaccine strategies. PMID:7521806

  15. 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

  16. Immunophenotype Heterogeneity in Nasal Glomangiopericytoma

    PubMed Central

    Handra-Luca, Adriana; Abd Elmageed, Zakaria Y.; Magkou, Christina; Lae, Marick

    2015-01-01

    Nasal glomangiopericytoma is rare. The immunophenotype is heterogeneous, more frequently smooth-muscle-actin and CD34-positive. We report expression patterns for several vascular-related proteins such as CD99, CD146, Bcl2, and WT1 as well as for treatment-related proteins such as mTOR and EGFR in a nasal glomangiopericytoma. The patient (woman, 86 years) presented with a left nasal tumefaction. The resected specimen (1.5-cm) showed a glomangiopericytoma. Tumor cells expressed smooth-muscle-actin, CD31, CD34, and progesterone receptor. They also expressed the vascular-cell-related proteins Bcl2, CD99, CD146, and WT1, as well as mTOR and EGFR. Nasal glomangiopericytomas show immunohistochemical heterogeneity for vascular-related markers, suggesting a possible extensive pericytic differentiation. The expression of potential targets for drug treatments such as mTOR and EGFR may impact on the clinical follow-up of these tumors occurring at advanced ages, which may require complex surgery. PMID:26351605

  17. Protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Proteins are the major structural and functional components of all cells in the body. They are macromolecules that comprise 1 or more chains of amino acids that vary in their sequence and length and are folded into specific 3-dimensional structures. The sizes and conformations of proteins, therefor...

  18. 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)

  19. Tumor heterogeneity and circulating tumor cells.

    PubMed

    Zhang, Chufeng; Guan, Yan; Sun, Yulan; Ai, Dan; Guo, Qisen

    2016-05-01

    In patients with cancer, individualized treatment strategies are generally guided by an analysis of molecular biomarkers. However, genetic instability allows tumor cells to lose monoclonality and acquire genetic heterogeneity, an important characteristic of tumors, during disease progression. Researchers have found that there is tumor heterogeneity between the primary tumor and metastatic lesions, between different metastatic lesions, and even within a single tumor (either primary or metastatic). Tumor heterogeneity is associated with heterogeneous protein functions, which lowers diagnostic precision and consequently becomes an obstacle to determining the appropriate therapeutic strategies for individual cancer patients. With the development of novel testing technologies, an increasing number of studies have attempted to explore tumor heterogeneity by examining circulating tumor cells (CTCs), with the expectation that CTCs may comprehensively represent the full spectrum of mutations and/or protein expression alterations present in the cancer. In addition, this strategy represents a minimally invasive approach compared to traditional tissue biopsies that can be used to dynamically monitor tumor evolution. The present article reviews the potential efficacy of using CTCs to identify both spatial and temporal tumor heterogeneity. This review also highlights current issues in this field and provides an outlook toward future applications of CTCs. PMID:26902424

  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 in rhesus macaque complement factor H binding to meningococcal factor H binding protein (FHbp) informs selection of primates to assess immunogenicity of FHbp-based vaccines.

    PubMed

    Beernink, Peter T; Shaughnessy, Jutamas; Stefek, Heather; Ram, Sanjay; Granoff, Dan M

    2014-11-01

    Neisseria meningitidis causes disease only in humans. An important mechanism underlying this host specificity is the ability of the organism to resist complement by recruiting the complement downregulator factor H (FH) to the bacterial surface. In previous studies, binding of FH to one of the major meningococcal FH ligands, factor H binding protein (FHbp), was reported to be specific for human FH. Here we report that sera from 23 of 73 rhesus macaques (32%) tested had high FH binding to FHbp. Similar to human FH, binding of macaque FH to the meningococcal cell surface inhibited the complement alternative pathway by decreasing deposition of C3b. FH contains 20 domains (or short consensus repeats), with domains 6 and 7 being responsible for binding of human FH to FHbp. DNA sequence analyses of FH domains 6 and 7 from macaques with high or low FH binding showed a polymorphism at residue 352 in domain 6, with Tyr being associated with high binding and His with low binding. A recombinant macaque FH 6,7/Fc fragment with Tyr352 showed higher binding to FHbp than the corresponding fragment with His352. In previous studies in human FH transgenic mice, binding of FH to FHbp vaccines decreased protective antibody responses, and mutant FHbp vaccines with decreased FH binding elicited serum antibodies with greater protective activity. Thus, macaques with high FH binding to FHbp represent an attractive nonhuman primate model to investigate further the effects of FH binding on the immunogenicity of FHbp vaccines. PMID:25185576

  2. Heterogeneity in Rhesus Macaque Complement Factor H Binding to Meningococcal Factor H Binding Protein (FHbp) Informs Selection of Primates To Assess Immunogenicity of FHbp-Based Vaccines

    PubMed Central

    Beernink, Peter T.; Shaughnessy, Jutamas; Stefek, Heather; Ram, Sanjay

    2014-01-01

    Neisseria meningitidis causes disease only in humans. An important mechanism underlying this host specificity is the ability of the organism to resist complement by recruiting the complement downregulator factor H (FH) to the bacterial surface. In previous studies, binding of FH to one of the major meningococcal FH ligands, factor H binding protein (FHbp), was reported to be specific for human FH. Here we report that sera from 23 of 73 rhesus macaques (32%) tested had high FH binding to FHbp. Similar to human FH, binding of macaque FH to the meningococcal cell surface inhibited the complement alternative pathway by decreasing deposition of C3b. FH contains 20 domains (or short consensus repeats), with domains 6 and 7 being responsible for binding of human FH to FHbp. DNA sequence analyses of FH domains 6 and 7 from macaques with high or low FH binding showed a polymorphism at residue 352 in domain 6, with Tyr being associated with high binding and His with low binding. A recombinant macaque FH 6,7/Fc fragment with Tyr352 showed higher binding to FHbp than the corresponding fragment with His352. In previous studies in human FH transgenic mice, binding of FH to FHbp vaccines decreased protective antibody responses, and mutant FHbp vaccines with decreased FH binding elicited serum antibodies with greater protective activity. Thus, macaques with high FH binding to FHbp represent an attractive nonhuman primate model to investigate further the effects of FH binding on the immunogenicity of FHbp vaccines. PMID:25185576

  3. Affinity and catalytic heterogeneity of polyclonal myelin basic protein-hydrolyzing IgGs from sera of patients with multiple sclerosis

    PubMed Central

    Legostaeva, Galina A; Polosukhina, Dar’ya I; Bezuglova, Anna M; Doronin, Boris M; Buneva, Valentina N; Nevinsky, Georgy A

    2010-01-01

    Abstract Human myelin basic protein (hMBP)-hydrolyzing activity was recently shown to be an intrinsic property of antibodies (Abs) from multiple sclerosis (MS) patients. Here, we present the first evidence demonstrating a significant diversity of different fractions of polyclonal IgGs (pIgGs) from MS patients in their affinity for hMBP and in the ability of pIgGs to hydrolyze hBMP at different optimal pHs (3–10.5). IgGs containing λ- and κ-types of light chains demonstrated comparable relative activities in the hydrolysis of hMBP. IgGs of IgG1–IgG4 sub-classes were analyzed for catalytic activity. IgGs of all four sub-classes were catalytically active, with their contribution to the total activity of Abzs in the hydrolysis of hMBP and its 19-mer oligopeptide increasing in the order: IgG1 (1.5–2.1%) < IgG2 (4.9–12.8%) < IgG3 (14.7–25.0%) < IgG4 (71–78%). Our findings suggest that the immune systems of individual MS patients generate a variety of anti-hMBP abzymes with different catalytic properties, which can attack hMBP of myelin-proteolipid shell of axons, playing an important role in MS pathogenesis. PMID:19438809

  4. Cellular Heterogeneity During Embryonic Stem Cell Differentiation to Epiblast Stem Cells is Revealed by the ShcD/RaLP Adaptor Protein

    PubMed Central

    Turco, Margherita Y; Furia, Laura; Dietze, Anja; Fernandez Diaz, Luis; Ronzoni, Simona; Sciullo, Anna; Simeone, Antonio; Constam, Daniel; Faretta, Mario; Lanfrancone, Luisa

    2012-01-01

    The Shc family of adaptor proteins are crucial mediators of a plethora of receptors such as the tyrosine kinase receptors, cytokine receptors, and integrins that drive signaling pathways governing proliferation, differentiation, and migration. Here, we report the role of the newly identified family member, ShcD/RaLP, whose expression in vitro and in vivo suggests a function in embryonic stem cell (ESC) to epiblast stem cells (EpiSCs) transition. The transition from the naïve (ESC) to the primed (EpiSC) pluripotent state is the initial important step for ESCs to commit to differentiation and the mechanisms underlying this process are still largely unknown. Using a novel approach to simultaneously assess pluripotency, apoptosis, and proliferation by multiparameter flow cytometry, we show that ESC to EpiSC transition is a process involving a tight coordination between the modulation of the Oct4 expression, cell cycle progression, and cell death. We also describe, by high-content immunofluorescence analysis and time-lapse microscopy, the emergence of cells expressing caudal-related homeobox 2 (Cdx2) transcription factor during ESC to EpiSC transition. The use of the ShcD knockout ESCs allowed the unmasking of this process as they presented deregulated Oct4 modulation and an enrichment in Oct4-negative Cdx2-positive cells with increased MAPK/extracellular-regulated kinases 1/2 activation, within the differentiating population. Collectively, our data reveal ShcD as an important modulator in the switch of key pathway(s) involved in determining EpiSC identity. Stem Cells2012;30:2423–2436 PMID:22948967

  5. Modeling blood flow heterogeneity.

    PubMed

    King, R B; Raymond, G M; Bassingthwaighte, J B

    1996-01-01

    It has been known for some time that regional blood flows within an organ are not uniform. Useful measures of heterogeneity of regional blood flows are the standard deviation and coefficient of variation or relative dispersion of the probability density function (PDF) of regional flows obtained from the regional concentrations of tracers that are deposited in proportion to blood flow. When a mathematical model is used to analyze dilution curves after tracer solute administration, for many solutes it is important to account for flow heterogeneity and the wide range of transit times through multiple pathways in parallel. Failure to do so leads to bias in the estimates of volumes of distribution and membrane conductances. Since in practice the number of paths used should be relatively small, the analysis is sensitive to the choice of the individual elements used to approximate the distribution of flows or transit times. Presented here is a method for modeling heterogeneous flow through an organ using a scheme that covers both the high flow and long transit time extremes of the flow distribution. With this method, numerical experiments are performed to determine the errors made in estimating parameters when flow heterogeneity is ignored, in both the absence and presence of noise. The magnitude of the errors in the estimates depends upon the system parameters, the amount of flow heterogeneity present, and whether the shape of the input function is known. In some cases, some parameters may be estimated to within 10% when heterogeneity is ignored (homogeneous model), but errors of 15-20% may result, even when the level of heterogeneity is modest. In repeated trials in the presence of 5% noise, the mean of the estimates was always closer to the true value with the heterogeneous model than when heterogeneity was ignored, but the distributions of the estimates from the homogeneous and heterogeneous models overlapped for some parameters when outflow dilution curves were

  6. 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.

  7. Teaching Heterogeneous Classes.

    ERIC Educational Resources Information Center

    Millrood, Radislav

    2002-01-01

    Discusses an approach to teaching heterogeneous English-as-a-Second/Foreign-Language classes. Draws on classroom research data to describe the features of a success-building lesson context. (Author/VWL)

  8. 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.

  9. 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.

  10. Heterogeneity of packing: structural approach.

    PubMed Central

    Kurochkina, N.; Privalov, G.

    1998-01-01

    Analysis of the heterogeneity of packing in proteins showed that different groups of the protein preferentially contribute to low- or high-density regions. Statistical distribution reveals the two preferable values for packing density in the form of two peaks. One peak occurs in the range of densities 0.55-0.65, the other occurs in the range 0.75-0.8. The high-density peak is originated primarily by high packing inside the hydrogen bonded backbone and to some extent by side chains. Polar/charged and apolar side chains both contribute to the low-density peak. The average packing density values of individual atomic groups significantly vary for backbone atoms as well as for side chain atoms. The carbonyl oxygen atoms of protein backbone and the end groups of side chains show lower packing density than the rest of the protein. The side-chain atomic groups of a secondary structure element when packed against the neighboring secondary structure element form stronger contacts with the side chains of this element than with its backbone. Analysis of the low-density regions around each buried peptide group was done for the set of proteins with different types of packing, including alpha-alpha, alpha-beta, and beta-beta packing. It was shown that cavities are regularly situated in the groove of secondary structure element packed against neighboring elements for all types of packing. Low density in the regions surrounding the peptide groups and the end groups of side chains can be explained by their positioning next to a cavity formed upon the association of secondary structure elements. The model proposed can be applied to the analysis of protein internal motions, mechanisms of cellular signal transduction, diffusion through protein matrix, and other events. PMID:9568896

  11. 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

  12. 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.

  13. Managing Power Heterogeneity

    NASA Astrophysics Data System (ADS)

    Pruhs, Kirk

    A particularly important emergent technology is heterogeneous processors (or cores), which many computer architects believe will be the dominant architectural design in the future. The main advantage of a heterogeneous architecture, relative to an architecture of identical processors, is that it allows for the inclusion of processors whose design is specialized for particular types of jobs, and for jobs to be assigned to a processor best suited for that job. Most notably, it is envisioned that these heterogeneous architectures will consist of a small number of high-power high-performance processors for critical jobs, and a larger number of lower-power lower-performance processors for less critical jobs. Naturally, the lower-power processors would be more energy efficient in terms of the computation performed per unit of energy expended, and would generate less heat per unit of computation. For a given area and power budget, heterogeneous designs can give significantly better performance for standard workloads. Moreover, even processors that were designed to be homogeneous, are increasingly likely to be heterogeneous at run time: the dominant underlying cause is the increasing variability in the fabrication process as the feature size is scaled down (although run time faults will also play a role). Since manufacturing yields would be unacceptably low if every processor/core was required to be perfect, and since there would be significant performance loss from derating the entire chip to the functioning of the least functional processor (which is what would be required in order to attain processor homogeneity), some processor heterogeneity seems inevitable in chips with many processors/cores.

  14. 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

  15. Evaluating foam heterogeneity

    NASA Technical Reports Server (NTRS)

    Liou, D. W.; Lee, W. M.

    1972-01-01

    New analytical tool is available to calculate the degree of foam heterogeneity based on the measurement of gas diffusivity values. Diffusion characteristics of plastic foam are described by a system of differential equations based on conventional diffusion theory. This approach saves research and computation time in studying mass or heat diffusion problems.

  16. 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.

  17. Heterogeneities in granular dynamics.

    PubMed

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

    2008-06-17

    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

  18. Atmospheric Heterogeneous Stereochemistry

    NASA Astrophysics Data System (ADS)

    Stokes, G. Y.; Buchbinder, A. M.; Geiger, F. M.

    2009-12-01

    This paper addresses the timescale and mechanism of heterogeneous interactions of laboratory models of organic-coated mineral dust and ozone. We are particularly interested in investigating the role of stereochemistry in heterogeneous oxidation reactions involving chiral biogenic VOCs. Using the surface-specific nonlinear optical spectroscopy, sum frequency generation, we tracked terpene diastereomers during exposure to 10^11 to 10^13 molecules of ozone per cm^3 in 1 atm helium to model ozone-limited and ozone-rich tropospheric conditions. Our kinetic data indicate that the diastereomers which orient their reactive C=C double bonds towards the gas phase exhibit heterogeneous ozonolysis rate constants that are two times faster than diastereomers that orient their C=C double bonds away from the gas phase. Insofar as our laboratory model studies are representative of real world environments, our studies suggest that the propensity of aerosol particles coated with chiral semivolatile organic compounds to react with ozone may depend on stereochemistry. Implications of these results for chiral markers that would allow for source appointment of anthropogenic versus biogenic carbon emissions will be discussed.

  19. Heterogeneity in Melanoma.

    PubMed

    Shannan, Batool; Perego, Michela; Somasundaram, Rajasekharan; Herlyn, Meenhard

    2016-01-01

    Melanoma is among the most aggressive and therapy-resistant human cancers. While great strides in therapy have generated enthusiasm, many challenges remain. Heterogeneity is the most pressing issue for all types of therapy. This chapter summarizes the clinical classification of melanoma, of which the research community now adds additional layers of classifications for better diagnosis and prediction of therapy response. As the search for new biomarkers increases, we expect that biomarker analyses will be essential for all clinical trials to better select patient populations for optimal therapy. While individualized therapy that is based on extensive biomarker analyses is an option, we expect in the future genetic and biologic biomarkers will allow grouping of melanomas in such a way that we can predict therapy outcome. At this time, tumor heterogeneity continues to be the major challenge leading inevitably to relapse. To address heterogeneity therapeutically, we need to develop complex therapies that eliminate the bulk of the tumor and, at the same time, the critical subpopulations. PMID:26601857

  20. Cell heterogeneity during the cell cycle

    SciTech Connect

    Darzynkiewicz, Z.; Crissman, H.; Traganos, F.; Steinkamp, J.

    1982-12-01

    Using flow cytometry, populations of Chinese hamster ovary cells, asynchronous and synchronized in the cycle, were measured with respect to cellular RNA- and protein-content, as well as cell light scatter properties. Heterogeneities of cell populations were expressed as coefficients of variation (c.v.) in percent of the respective mean values. Populations of cells immediately after mitosis have about 15% higher c.v. than mitotic cell populations, regardless of whether RNA, proteins, or light scatter are measured. These data indicate that cytoplasmic constituents are unequally distributed into the daughter cells during cytokinesis and that unequal cytokinesis generates intercellular metabolic variability during the cycle. An additional increase in heterogeneity, although of smaller degree, occurs during G/sub 2/ phase. Populations of S-phase cells are the most uniform, having 20-30% lower c.v. than the postmitotic cells. Cell progression through S does not involve any significant increase in intercellular variability with respect to RNA or protein content. In unperturbed exponentially growing cultures a critical RNA content is required for G/sub 1/ cells prior to their entrance into S. The cell residence times in the equalization compartments are exponentially distributed, which may reflect the randomness generated by the uneven division of metabolic constituents to daughter cells during cytokinesis. The cell heterogeneities were presently estimated at two metabolic levels, transcription (RNA content) and translation (proteins). The most uniform were populations stained for RNA and the highest variability was observed after staining of proteins. This suggests that the regulatory mechanisms equalizing cells in the cell cycle may operate primarily at the level of DNA transcription.

  1. 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

  2. Interfacial Protein-Protein Associations

    PubMed Central

    Langdon, Blake B.; Kastantin, Mark; Walder, Robert; Schwartz, Daniel K.

    2014-01-01

    While traditional models of protein adsorption focus primarily on direct protein-surface interactions, recent findings suggest that protein-protein interactions may play a central role. Using high-throughput intermolecular resonance energy transfer (RET) tracking, we directly observed dynamic, protein-protein associations of bovine serum albumin on poly(ethylene glycol) modified surfaces. The associations were heterogeneous and reversible, and associating molecules resided on the surface for longer times. The appearance of three distinct RET states suggested a spatially heterogeneous surface – with areas of high protein density (i.e. strongly-interacting clusters) coexisting with mobile monomers. Distinct association states exhibited characteristic behavior, i.e. partial-RET (monomer-monomer) associations were shorter-lived than complete-RET (protein-cluster) associations. While the fractional surface area covered by regions with high protein density (i.e. clusters) increased with increasing concentration, the distribution of contact times between monomers and clusters was independent of solution concentration, suggesting that associations were a local phenomenon, and independent of the global surface coverage. PMID:24274729

  3. Heterogeneity in expected longevities.

    PubMed

    Pijoan-Mas, Josep; Ríos-Rull, José-Víctor

    2014-12-01

    We develop a new methodology to compute differences in the expected longevity of individuals of a given cohort who are in different socioeconomic groups at a certain age. We address the two main problems associated with the standard use of life expectancy: (1) that people's socioeconomic characteristics change, and (2) that mortality has decreased over time. Our methodology uncovers substantial heterogeneity in expected longevities, yet much less heterogeneity than what arises from the naive application of life expectancy formulae. We decompose the longevity differences into differences in health at age 50, differences in the evolution of health with age, and differences in mortality conditional on health. Remarkably, education, wealth, and income are health-protecting but have very little impact on two-year mortality rates conditional on health. Married people and nonsmokers, however, benefit directly in their immediate mortality. Finally, we document an increasing time trend of the socioeconomic gradient of longevity in the period 1992-2008, and we predict an increase in the socioeconomic gradient of mortality rates for the coming years. PMID:25391225

  4. Biclustering with heterogeneous variance.

    PubMed

    Chen, Guanhua; Sullivan, Patrick F; Kosorok, Michael R

    2013-07-23

    In cancer research, as in all of medicine, it is important to classify patients into etiologically and therapeutically relevant subtypes to improve diagnosis and treatment. One way to do this is to use clustering methods to find subgroups of homogeneous individuals based on genetic profiles together with heuristic clinical analysis. A notable drawback of existing clustering methods is that they ignore the possibility that the variance of gene expression profile measurements can be heterogeneous across subgroups, and methods that do not consider heterogeneity of variance can lead to inaccurate subgroup prediction. Research has shown that hypervariability is a common feature among cancer subtypes. In this paper, we present a statistical approach that can capture both mean and variance structure in genetic data. We demonstrate the strength of our method in both synthetic data and in two cancer data sets. In particular, our method confirms the hypervariability of methylation level in cancer patients, and it detects clearer subgroup patterns in lung cancer data. PMID:23836637

  5. Heterogeneous broadband network

    NASA Astrophysics Data System (ADS)

    Dittmann, Lars

    1995-11-01

    Although the vision for the future Integrated Broadband Communication Network (IBCN) is an all optical network, it is certain that for a long period to come, the network will remain very heterogeneous, with a mixture of different physical media (fiber, coax and twisted pair), transmission systems (PDH, SDH, ADSL) and transport protocols (TCP/IP, AAL/ATM, frame relay). In the current work towards the IBCN, the ATM concept is considered the generic network protocol for both public and private network, with the ability to use different underlying transmission protocols and, through adaptation protocols, provide the appropriate services (old as well as new) to the customer. One of the major difficulties of heterogeneous network is the restriction that is usually given by the lowest common denominator, e.g. in terms of single channel capacity. A possible way to overcome these limitations is by extending the ATM concept with a multilink capability, that allows us to use separate resources as one common. The improved flexibility obtained by this protocol extension further allows a real time optimization of network and call configuration, without any impact on the quality of service seen from the user. This paper describes an example of an ATM based multilink protocol that has been experimentally implemented within the RACE project 'STRATOSPHERIC'. The paper outlines the complexity of introducing an extra network functionality compared with the added value, such as an improved ability to recover an error due to a malfunctioning network component.

  6. 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

  7. Large epidemic thresholds emerge in heterogeneous networks of heterogeneous nodes

    NASA Astrophysics Data System (ADS)

    Yang, Hui; Tang, Ming; Gross, Thilo

    2015-08-01

    One of the famous results of network science states that networks with heterogeneous connectivity are more susceptible to epidemic spreading than their more homogeneous counterparts. In particular, in networks of identical nodes it has been shown that network heterogeneity, i.e. a broad degree distribution, can lower the epidemic threshold at which epidemics can invade the system. Network heterogeneity can thus allow diseases with lower transmission probabilities to persist and spread. However, it has been pointed out that networks in which the properties of nodes are intrinsically heterogeneous can be very resilient to disease spreading. Heterogeneity in structure can enhance or diminish the resilience of networks with heterogeneous nodes, depending on the correlations between the topological and intrinsic properties. Here, we consider a plausible scenario where people have intrinsic differences in susceptibility and adapt their social network structure to the presence of the disease. We show that the resilience of networks with heterogeneous connectivity can surpass those of networks with homogeneous connectivity. For epidemiology, this implies that network heterogeneity should not be studied in isolation, it is instead the heterogeneity of infection risk that determines the likelihood of outbreaks.

  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. 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. PMID:27253725

  10. 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.

  11. [Neutrophilic functional heterogeneity].

    PubMed

    2006-02-01

    Blood neutrophilic functional heterogeneity is under discussion. The neutrophils of one subpopulation, namely killer neutrophils (Nk), potential phagocytes, constitute a marginal pool and a part of the circulating pool, intensively produce active oxygen forms (AOF) and they are adherent to the substrate. The neutrophils of another subpopulation, cager neutrophils (Nc), seem to perform a transport function of delivering foreign particles to the competent organs, to form about half of the circulating pool, to produce APC to a lesser extent, exclusively for self-defense and, probably, in usual conditions, to fail to interact with substrate. Analysis of the experimental findings suggests that the phylogenetic age of Nk is older than that of Nc and Nk has predominantly a tendency to spontaneous apoptosis under physiological conditions. PMID:16610631

  12. Multipartite entanglement in heterogeneous systems

    NASA Astrophysics Data System (ADS)

    Goyeneche, Dardo; Bielawski, Jakub; Życzkowski, Karol

    2016-07-01

    Heterogeneous bipartite quantum pure states, composed of two subsystems with a different number of levels, cannot have both reductions maximally mixed. In this work, we demonstrate the existence of a wide range of highly entangled states of heterogeneous multipartite systems consisting of N >2 parties such that every reduction to one and two parties is maximally mixed. Two constructions of generating genuinely multipartite maximally entangled states of heterogeneous systems for an arbitrary number of subsystems are presented. Such states are related to quantum error correction codes over mixed alphabets and mixed orthogonal arrays. Additionally, we show the advantages of considering heterogeneous systems in practical implementations of multipartite steering.

  13. 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.

  14. Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

    PubMed Central

    Math, M.; Tarpey, Patrick; Varela, Ignacio; Phillimore, Benjamin; Begum, Sharmin; McDonald, Neil Q.; Butler, Adam; Jones, David; Raine, Keiran; Latimer, Calli; Santos, Claudio R.; Nohadani, Mahrokh; Eklund, Aron C.; Spencer-Dene, Bradley; Clark, Graham; Pickering, Lisa; Stamp, Gordon; Gore, Martin; Szallasi, Zoltan; Downward, Julian; Futreal, P. Andrew

    2016-01-01

    Background Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples. Methods To examine intratumor heterogeneity, we performed exome sequencing, chromosome aberration analysis, and ploidy profiling on multiple spatially separated samples obtained from primary renal carcinomas and associated metastatic sites. We characterized the consequences of intratumor heterogeneity using immunohistochemical analysis, mutation functional analysis, and profiling of messenger RNA expression. Results Phylogenetic reconstruction revealed branched evolutionary tumor growth, with 63 to 69% of all somatic mutations not detectable across every tumor region. Intratumor heterogeneity was observed for a mutation within an autoinhibitory domain of the mammalian target of rapamycin (mTOR) kinase, correlating with S6 and 4EBP phosphorylation in vivo and constitutive activation of mTOR kinase activity in vitro. Mutational intratumor heterogeneity was seen for multiple tumor-suppressor genes converging on loss of function; SETD2, PTEN, and KDM5C underwent multiple distinct and spatially separated inactivating mutations within a single tumor, suggesting convergent phenotypic evolution. Gene-expression signatures of good and poor prognosis were detected in different regions of the same tumor. Allelic composition and ploidy profiling analysis revealed extensive intratumor heterogeneity, with 26 of 30 tumor samples from four tumors harboring divergent allelic-imbalance profiles and with ploidy heterogeneity in two of four tumors. Conclusions Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development. Intratumor heterogeneity, associated with heterogeneous protein function, may foster tumor adaptation and therapeutic failure through

  15. Heterogenous mismatch-repair status in colorectal cancer

    PubMed Central

    2014-01-01

    Abstract Background Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. Methods Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative expression patterns macro-dissected and micro-dissected tumor areas were separately analyzed for microsatellite instability and MLH1 promoter methylation. Results Heterogenous retained/lost mismatch repair protein expression could be classified as intraglandular (within or in-between glandular formations), clonal (in whole glands or groups of glands) and compartmental (in larger tumor areas/compartments or in between different tumor blocks). These patterns coexisted in 9/14 tumors and in the majority of the tumors correlated with differences in microsatellite instability/MLH1 methylation status. Conclusions Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1771940323126788 PMID:24968821

  16. Political Jurisdictions in Heterogeneous Communities.

    ERIC Educational Resources Information Center

    Alesina, Alberto; Baqir, Reza; Hoxby, Caroline

    2004-01-01

    We investigate whether political jurisdictions form in response to the trade-off between economies of scale and the costs of a heterogeneous population. We consider heterogeneity in income, race, ethnicity, and religion, and we test the model using American school districts, school attendance areas, municipalities, and special districts. We find…

  17. Biomarker Discovery for Heterogeneous Diseases

    PubMed Central

    Wallstrom, Garrick; Anderson, Karen S.; LaBaer, Joshua

    2013-01-01

    Background Modern genomic and proteomic studies reveal that many diseases are heterogeneous, comprising multiple different subtypes. The common notion that one biomarker can be predictive for all patients may need to be replaced by an understanding that each subtype has its own set of unique biomarkers, affecting how discovery studies are designed and analyzed. Methods We used Monte Carlo simulation to measure and compare the performance of eight selection methods with homogeneous and heterogeneous diseases using both single-stage and two-stage designs. We also applied the selection methods in an actual proteomic biomarker screening study of heterogeneous breast cancer cases. Results Different selection methods were optimal and more than 2-fold larger sample sizes were needed for heterogeneous diseases compared with homogeneous diseases. We also found that for larger studies, two-stage designs can achieve nearly the same statistical power as single-stage designs at significantly reduced cost. Conclusions We found that disease heterogeneity profoundly affected biomarker performance. We report sample size requirements and provide guidance on the design and analysis of biomarker discovery studies for both homogeneous and heterogeneous diseases. Impact We have shown that studies to identify biomarkers for the early detection of heterogeneous disease require different statistical selection methods and larger sample sizes than if the disease were homogeneous. These findings provide a methodological platform for biomarker discovery of heterogeneous diseases. PMID:23462916

  18. Heterogeneity of an earth

    NASA Astrophysics Data System (ADS)

    Litvinova, T.; Petrova, A.

    2009-04-01

    The study of magnetic anomaly field structure of the Barents Sea water area along seismic and extended profiles intersecting known fields is carried out. Geomagnetic and density sections down to 40 km depth are constructed. This allowed the estimation of heterogeneities of the Barents Sea water area deep structure. The analysis of geomagnetic and density sections along extended profiles showed the confinedness of oil-and-gas bearing provinces to deep permeable zones characterized by reduced magnetic and density features. Based on the analysis of permeable zones, regional diagnostic features similar to those obtained earlier in oil-and-gas bearing provinces in other regions, for example, in Timan-Pechora, Volga-Urals and Siberian, as well as in the Northern and Norwegian seas water areas, are revealed. The analysis of magnetic and gravity fields over the region area allowed the delineation of weakened zones as intersection areas of weakly magnetic areals with reduced density. Within the Barents Sea water area, permeable areas with lenticular-laminated structure of the upper and lower Earth's crust containing weakly magnetic areals with reduced rock density within the depth range of 8-12 and 15-20 km are revealed. Such ratio of magnetic and density heterogeneities in the Earth's crust is characteristic for zones with proved oil-and-gas content in the European part of the Atlantic Ocean water area. North Kildin field on 1 AR profile is confined to a trough with thick weakly magnetic stratum discontinuously traced to a depth of 6-10 km. At a depth of approximately 15 km, a lens of weakly magnetic and porous formations is observed. Ludlov field in the North Barents trough is confined to a zone of weakly magnetic rocks with reduced density traced to a depth of 8-9 km. Deeper, at Н=15 km, a lenticular areal of weakly magnetic formations with reduced density is observed. The profile transecting the Stockman field shows that it is located in the central part of a permeable

  19. 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.

  20. 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.

  1. 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

  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. Node assignment in heterogeneous computing

    NASA Technical Reports Server (NTRS)

    Som, Sukhamoy

    1993-01-01

    A number of node assignment schemes, both static and dynamic, are explored for the Algorithm to Architecture Mapping Model (ATAMM). The architecture under consideration consists of heterogeneous processors and implements dataflow models of real-time applications. Terminology is developed for heterogeneous computing. New definitions are added to the ATAMM for token and assignment classifications. It is proved that a periodic execution is possible for dataflow graphs. Assignment algorithms are developed and proved. A design procedure is described for satisfying an objective function in an heterogeneous architecture. Several examples are provided for illustration.

  4. Spatial heterogeneity in the heart: recent insights and open questions.

    PubMed

    Decking, Ulrich K M

    2002-12-01

    Within the left ventricular myocardium and despite its rather homogeneous structure, local myocardial perfusion varies substantially. Areas of low and high local flow differ with regard to substrate uptake, energy turnover, and demand. This spatial heterogeneity is related to distinct differences in local protein expression, forming the basis of a novel homeostatic mechanism. PMID:12433979

  5. Heterogeneous Oxidation of Catechol.

    PubMed

    Pillar, Elizabeth A; Zhou, Ruixin; Guzman, Marcelo I

    2015-10-15

    Natural and anthropogenic emissions of aromatic hydrocarbons from biomass burning, agro-industrial settings, and fossil fuel combustion contribute precursors to secondary aerosol formation (SOA). How these compounds are processed under humid tropospheric conditions is the focus of current attention to understand their environmental fate. This work shows how catechol thin films, a model for oxygenated aromatic hydrocarbons present in biomass burning and combustion aerosols, undergo heterogeneous oxidation at the air-solid interface under variable relative humidity (RH = 0-90%). The maximum reactive uptake coefficient of O3(g) by catechol γO3 = (7.49 ± 0.35) × 10(-6) occurs for 90% RH. Upon exposure of ca. 104-μm thick catechol films to O3(g) mixing ratios between 230 ppbv and 25 ppmv, three main reaction pathways are observed. (1) The cleavage of the 1,2 carbon-carbon bond at the air-solid interface resulting in the formation of cis,cis-muconic acid via primary ozonide and hydroperoxide intermediates. Further direct ozonolysis of cis,cis-muconic yields glyoxylic, oxalic, crotonic, and maleic acids. (2) A second pathway is evidenced by the presence of Baeyer-Villiger oxidation products including glutaconic 4-hydroxy-2-butenoic and 5-oxo-2-pentenoic acids during electrospray ionization mass spectrometry (MS) and ion chromatography MS analyses. (3) Finally, indirect oxidation by in situ produced hydroxyl radical (HO(•)) results in the generation of semiquinone radical intermediates toward the synthesis of polyhydoxylated aromatic rings such as tri-, tetra-, and penta-hydroxybenzene. Remarkably, heavier polyhydroxylated biphenyl and terphenyl products present in the extracted oxidized films result from coupling reactions of semiquinones of catechol and its polyhydroxylated rings. The direct ozonolysis of 1,2,3- and 1,2,4-trihydroxybenezene yields 2- and 3-hydroxy-cis,cis-muconic acid, respectively. The production of 2,4- or 3,4-dihdroxyhex-2-enedioic acid is

  6. 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)

  7. 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.

  8. Ribosome heterogeneity in tumorigenesis: the rRNA point of view

    PubMed Central

    Marcel, Virginie; Catez, Frédéric; Diaz, Jean-Jacques

    2015-01-01

    The "specialized ribosome" concept proposes that ribosome variants are produced and differentially regulate translation. Examples supporting this notion demonstrated heterogeneity of ribosomal protein composition. However, ribosome translational activity is carried out by rRNA. We, and others, recently showed that rRNA heterogeneity regulates translation to generate distinct translatomes promoting tumorigenesis. PMID:27305893

  9. Analysis of active renin heterogeneity.

    PubMed

    Katz, S A; Malvin, R L; Lee, J; Kim, S H; Murray, R D; Opsahl, J A; Abraham, P A

    1991-09-01

    Active renin is a heterogeneous enzyme that can be separated into multiple forms with high-resolution isoelectric focusing. The isoelectric heterogeneity may result from differences in glycosylation between the different forms. In order to determine the relationship between active renin heterogeneity and differences in composition or attachment of oligosaccharides, two separate experiments were performed: (i) Tunicamycin, which interferes with normal glycosylation processing, increased the proportion of relatively basic renin forms secreted into the incubation media by rat renal cortical slices. (ii) Endoglycosidase F, which enzymatically removes carbohydrate from some classes of glycoprotein, similarly increased the proportion of relatively basic forms when incubated with active human recombinant renin. In addition, further studies with inhibitors of human renin activity revealed that the heterogeneous renin forms were similarly inhibited by two separate renin inhibitors. These results are consistent with the hypothesis that renin isoelectric heterogeneity is due in part to differences in carbohydrate moiety attachment and that the heterogeneity of renin does not influence access of direct renin inhibitors to the active site of renin. PMID:1908097

  10. Directly measuring single-molecule heterogeneity using force spectroscopy.

    PubMed

    Hinczewski, Michael; Hyeon, Changbong; Thirumalai, D

    2016-07-01

    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

  11. Proteins and glasses

    SciTech Connect

    Frauenfelder, H.

    1997-12-31

    The structure, the energy landscape, and the dynamics of proteins and glasses are similar. Both types of systems display characteristic nonexponential time dependencies of relaxation phenomena. Experiments suggest that both, proteins and glasses, are heterogeneous and that this fact causes the observed time dependence. This result is discussed in terms of the rough energy landscape characteristic of complex systems.

  12. Kinetics of electron transfer in the complex of cytochrome P450 3A4 with the flavin domain of cytochrome P450BM-3 as evidence of functional heterogeneity of the heme protein

    PubMed Central

    Fernando, Harshica; Halpert, James R.; Davydov, Dmitri R.

    2008-01-01

    We used a rapid scanning stop-flow technique to study the kinetics of reduction of cytochrome P450 3A4 (CYP3A4) by the flavin domain of cytochrome P450-BM3 (BMR), which was shown to form a stoichiometric complex (KD = 0.48 µM) with CYP3A4. In the absence of substrates only about 50% of CYP3A4 was able to accept electrons from BMR. Whereas the high-spin fraction was completely reducible, the reducibility of the low-spin fraction did not exceed 42%. Among four substrates tested (testosterone, 1-pyrenebutanol, bromocriptine, or α-naphthoflavone (ANF)) only ANF is capable of increasing the reducibility of the low-spin fraction to 75%. Our results demonstrate that the pool of CYP3A4 is heterogeneous, and not all P450 is competent for electron transfer in the complex with reductase. The increase in the reducibility of the enzyme in the presence of ANF may represent an important element of the mechanism of action of this activator. PMID:18086551

  13. Novel Genetic and Phenotypic Heterogeneity in Bordetella bronchiseptica Pertactin

    PubMed Central

    Register, Karen B.

    2001-01-01

    The Bordetella bronchiseptica outer membrane protein pertactin is believed to function as an adhesin and is an important protective immunogen. Previous sequence analysis of the pertactin gene identified two regions predicted to encode amino acid repeat motifs. Recent studies have documented DNA sequence heterogeneity in both regions. The present study describes additional variants in these regions, which form the basis for six novel pertactin types. Immunoblotting demonstrated phenotypic heterogeneity in pertactin consistent with the predicted combined sizes of the repeat regions. A revised system for classifying B. bronchiseptica pertactin variants is proposed. PMID:11179374

  14. Heterogeneous Preferential Solvation of Water and Trifluoroethanol in Homologous Lysozymes

    PubMed Central

    2015-01-01

    Cytoplasmic osmolytes can significantly alter the thermodynamic and kinetic properties of proteins relative to those under dilute solution conditions. Spectroscopic experiments of lysozymes in cosolvents indicate that such changes may arise from the heterogeneous, site-specific hydrophobic interactions between protein surface residues and individual solvent molecules. In pursuit of an accurate and predictive model for explaining biomolecular interactions, we study the averaged structural characteristics of mixed solvents with homologous lysozyme solutes using all-atom molecular dynamics. By observing the time-averaged densities of different aqueous solutions of trifluoroethanol, we deduce trends in the heterogeneous solvent interactions over each protein’s surface, and investigate how the homology of protein structure does not necessarily translate to similarities in solvent structure and composition—even when observing identical side chains. PMID:24823618

  15. 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

  16. 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

  17. 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.

  18. Quantifying tumour heterogeneity with CT

    PubMed Central

    Miles, Kenneth A.

    2013-01-01

    Abstract Heterogeneity is a key feature of malignancy associated with adverse tumour biology. Quantifying heterogeneity could provide a useful non-invasive imaging biomarker. Heterogeneity on computed tomography (CT) can be quantified using texture analysis which extracts spatial information from CT images (unenhanced, contrast-enhanced and derived images such as CT perfusion) that may not be perceptible to the naked eye. The main components of texture analysis can be categorized into image transformation and quantification. Image transformation filters the conventional image into its basic components (spatial, frequency, etc.) to produce derived subimages. Texture quantification techniques include structural-, model- (fractal dimensions), statistical- and frequency-based methods. The underlying tumour biology that CT texture analysis may reflect includes (but is not limited to) tumour hypoxia and angiogenesis. Emerging studies show that CT texture analysis has the potential to be a useful adjunct in clinical oncologic imaging, providing important information about tumour characterization, prognosis and treatment prediction and response. PMID:23545171

  19. Resource heterogeneity can facilitate cooperation

    PubMed Central

    Kun, Ádám; Dieckmann, Ulf

    2013-01-01

    Although social structure is known to promote cooperation, by locally exposing selfish agents to their own deeds, studies to date assumed that all agents have access to the same level of resources. This is clearly unrealistic. Here we find that cooperation can be maintained when some agents have access to more resources than others. Cooperation can then emerge even in populations in which the temptation to defect is so strong that players would act fully selfishly if their resources were distributed uniformly. Resource heterogeneity can thus be crucial for the emergence and maintenance of cooperation. We also show that resource heterogeneity can hinder cooperation once the temptation to defect is significantly lowered. In all cases, the level of cooperation can be maximized by managing resource heterogeneity. PMID:24088665

  20. 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.

  1. 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.

  2. Single-cell profiling approaches to probing tumor heterogeneity.

    PubMed

    Khoo, Bee Luan; Chaudhuri, Parthiv Kant; Ramalingam, Naveen; Tan, Daniel Shao Weng; Lim, Chwee Teck; Warkiani, Majid Ebrahimi

    2016-07-15

    Tumor heterogeneity is a major hindrance in cancer classification, diagnosis and treatment. Recent technological advances have begun to reveal the true extent of its heterogeneity. Single-cell analysis (SCA) is emerging as an important approach to detect variations in morphology, genetic or proteomic expression. In this review, we revisit the issue of inter- and intra-tumor heterogeneity, and list various modes of SCA techniques (cell-based, nucleic acid-based, protein-based, metabolite-based and lipid-based) presently used for cancer characterization. We further discuss the advantages of SCA over pooled cell analysis, as well as the limitations of conventional techniques. Emerging trends, such as high-throughput sequencing, are also mentioned as improved means for cancer profiling. Collectively, these applications have the potential for breakthroughs in cancer treatment. PMID:26789729

  3. Morphological and molecular heterogeneity in release sites of single neurons.

    PubMed

    Morgenthaler, Florence D; Knott, Graham W; Floyd Sarria, J-C; Wang, Xin; Staple, Julie K; Catsicas, Stefan; Hirling, Harald

    2003-04-01

    We have previously shown that labelling intensities for synaptic proteins vary strongly among synaptic boutons. Here we addressed the questions as to whether there are heterogeneous levels of integral membrane synaptic vesicle proteins at distinct active release sites of single neurons and if these sites possess the ultrastructural features of synapses. By double-immunostaining with specific antibodies against synaptophysin, synaptotagmin I, VAMP1 and VAMP2, we identified different relative levels of these integral membrane proteins of synaptic vesicles in comparison to boutons of the same rat cortical neuron. This heterogeneity could also be observed between the two isoforms VAMP1 and VAMP2. By studying pairs of these proteins implicated in neurotransmitter release, including both VAMP isoforms, we also show that the sites that contained predominantly one protein were nevertheless functional, as they internalized and released FM1-43 upon potassium stimulation. Using electron microscopy, we show that these active sites could have either synaptic specializations, or the features of vesicle-containing varicosities without a postsynaptic target. Different varicosities of the same neuron showed different intensities for synaptic vesicle proteins; some varicosities were capable of internalizing and releasing FM1-43, while others were silent. These results show that integral membrane synaptic vesicle proteins are differentially distributed among functional release sites of the same neuron. PMID:12713639

  4. Heterogeneous expression of transketolase in rat brain.

    PubMed

    Calingasan, N Y; Sheu, K F; Baker, H; Jung, E H; Paoletti, F; Gibson, G E

    1995-03-01

    Transketolase (TK; EC 2.2.1.1) is a key pentose phosphate shunt enzyme that plays an important role in the production of reducing equivalents and pentose sugars. TK activity declines in the brains of patients with Alzheimer's disease or Wernicke-Korsakoff syndrome, as well as in thiamine-deficient rats. Understanding the role of TK in the pathophysiology of these neurodegenerative conditions requires knowledge of its regional, cellular, and subcellular distribution within the brain. The current study employed in situ hybridization and immunocytochemistry to examine the distribution of TK mRNA and its encoded protein in adult rat brain. TK mRNA and protein were widely distributed throughout the brain. However, they were enriched in selective perikarya in the piriform cortex, nucleus of the diagonal band, red nucleus, dorsal raphe, pontine nucleus, locus coeruleus, trapezoid, inferior olive, and several cranial nerve nuclei. Lower expression of TK mRNA and protein occurred in layer V of cortex, olfactory tubercle, ventral pallidum, medial septal nucleus, hippocampus, thalamic and hypothalamic nuclei, mammillary body, central gray, and the substantia nigra. TK immunoreactivity also occurred in the nuclei of ubiquitously distributed glial cells, as well as ependymal cells. The heterogeneous distribution of TK may reflect a variety of metabolic activities among different brain regions but does not provide a simple molecular explanation for selective cell death in either thiamine deficiency or other conditions where TK is reduced. PMID:7861132

  5. NERVOUS-SYSTEM SPECIFIC PROTEINS AS BIOCHEMICAL INDICATORS OF NEUROTOXICITY

    EPA Science Inventory

    Recent advances in neuroimmunology and protein purification methodology have led to the identification of nervous-system specific proteins. Their intimate relationship to the cellular and functional heterogeneity of the nervous system, makes these proteins ideal biochemical marke...

  6. Heterogeneous chiral catalysis: Past, present, and future

    SciTech Connect

    Brenner, J.R.

    1996-12-31

    In order to improve the scalability of the synthesis of chiral compounds, considerable effort has been devoted to the design of heterogeneous chiral catalysts. The attachment of {open_quotes}curved{close_quotes} chiral ligands, such as cinchona alkaloids, to supported metal complexes has permitted enantioselectivities approaching those in homogeneous solution. While the nature of the support has received less attention, the increased pore structure control gained during the gradual shift from polymeric supports to pillared clays, and finally to mesoporous zeolites and controlled pore glasses will hopefully allow better molecular size and shape control. Future work in this area likely will entail the use of polymeric templates as molecular imprints for protein synthesis and for antibody delivery systems.

  7. 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

  8. Metabolomic Heterogeneity of Pulmonary Arterial Hypertension

    PubMed Central

    Zhao, Yidan; Peng, Jenny; Lu, Catherine; Hsin, Michael; Mura, Marco; Wu, Licun; Chu, Lei; Zamel, Ricardo; Machuca, Tiago; Waddell, Thomas; Liu, Mingyao; Keshavjee, Shaf; Granton, John; de Perrot, Marc

    2014-01-01

    Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. PMID:24533144

  9. Heterogeneity of the translational machinery: Variations on a common theme

    PubMed Central

    Moll, Isabella

    2016-01-01

    In all organisms the universal process of protein synthesis is performed by the ribosome, a complex multi-component assembly composed of RNA and protein elements. Although ribosome heterogeneity was observed already more than 40 years ago, the ribosome is still traditionally viewed as an unchangeable entity that has to be equipped with all ribosomal components and translation factors in order to precisely accomplish all steps in protein synthesis. In the recent years this concept was challenged by several studies highlighting a broad variation in the composition of the translational machinery in response to environmental signals, which leads to its adaptation and functional specialization. Here, we summarize recent reports on the variability of the protein synthesis apparatus in diverse organisms and discuss the multiple mechanisms and possibilities that can lead to functional ribosome heterogeneity. Collectively, these results indicate that all cells are equipped with a remarkable toolbox to fine tune gene expression at the level of translation and emphasize the physiological importance of ribosome heterogeneity for the immediate implementation of environmental information. PMID:25542647

  10. 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…

  11. 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...

  12. 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…

  13. Electoral Competition in Heterogeneous Districts

    ERIC Educational Resources Information Center

    Callander, Steven

    2005-01-01

    This paper considers a model of elections in which parties compete simultaneously for multiple districts. I show that if districts are heterogeneous, then a unique two-party equilibrium exists under plurality rule in which further entry is deterred. The equilibrium requires that parties choose noncentrist policy platforms and not converge to the…

  14. Genomic Heterogeneity and Structural Variation in Soybean Near Isogenic Lines

    PubMed Central

    Stec, Adrian O.; Bhaskar, Pudota B.; Bolon, Yung-Tsi; Nolan, Rebecca; Shoemaker, Randy C.; Vance, Carroll P.; Stupar, Robert M.

    2013-01-01

    Near isogenic lines (NILs) are a critical genetic resource for the soybean research community. The ability to identify and characterize the genes driving the phenotypic differences between NILs is limited by the degree to which differential genetic introgressions can be resolved. Furthermore, the genetic heterogeneity extant among NIL sub-lines is an unaddressed research topic that might have implications for how genomic and phenotypic data from NILs are utilized. In this study, a recently developed high-resolution comparative genomic hybridization (CGH) platform was used to investigate the structure and diversity of genetic introgressions in two classical soybean NIL populations, respectively varying in protein content and iron deficiency chlorosis (IDC) susceptibility. There were three objectives: assess the capacity for CGH to resolve genomic introgressions, identify introgressions that are heterogeneous among NIL sub-lines, and associate heterogeneous introgressions with susceptibility to IDC. Using the CGH approach, introgression boundaries were refined and previously unknown introgressions were revealed. Furthermore, heterogeneous introgressions were identified within seven sub-lines of the IDC NIL “IsoClark.” This included three distinct introgression haplotypes linked to the major iron susceptible locus on chromosome 03. A phenotypic assessment of the seven sub-lines did not reveal any differences in IDC susceptibility, indicating that the genetic heterogeneity among the lines does not have a significant impact on the primary NIL phenotype. PMID:23630538

  15. 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

  16. 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.

  17. Heterogeneous Viscoelasticity: A Combined Theory of Dynamic and Elastic Heterogeneity.

    PubMed

    Schirmacher, Walter; Ruocco, Giancarlo; Mazzone, Valerio

    2015-07-01

    We present a heterogeneous version of Maxwell's theory of viscoelasticity based on the assumption of spatially fluctuating local viscoelastic coefficients. The model is solved in coherent-potential approximation. The theory predicts an Arrhenius-type temperature dependence of the viscosity in the vanishing-frequency limit, independent of the distribution of the activation energies. It is shown that this activation energy is generally different from that of a diffusing particle with the same barrier-height distribution, which explains the violation of the Stokes-Einstein relation observed frequently in glasses. At finite but low frequencies, the theory describes low-temperature asymmetric alpha relaxation. As examples, we report the good agreement obtained for selected inorganic, metallic, and organic glasses. At high frequencies, the theory reduces to heterogeneous elasticity theory, which explains the occurrence of the boson peak and related vibrational anomalies. PMID:26182108

  18. Heterogeneity of adenovirus type 5 E1A proteins: multiple serine phosphorylations induce slow-migrating electrophoretic variants but do not affect E1A-induced transcriptional activation or transformation.

    PubMed Central

    Richter, J D; Slavicek, J M; Schneider, J F; Jones, N C

    1988-01-01

    The 289-amino-acid product encoded by the adenovirus E1A 13S mRNA has several pleiotropic activities, including transcriptional activation, transcriptional repression, and when acting in concert with certain oncogene products, cell transformation. In all cell types in which E1A has been introduced (except bacteria), E1A protein is extensively posttranslationally modified to yield several isoelectric and molecular weight variants. The most striking variant is one that has a retarded mobility, by about Mr = 2,000, in sodium dodecyl sulfate gels. We have investigated the nature of this modification and have assessed its importance for E1A activity. Phosphorylation is responsible for the altered mobility of E1A, since acid phosphatase treatment eliminates the higher apparent molecular weight products. By using several E1A deletion mutants, we show that at least two seryl residues, residing between residues 86 and 120 and 224 and 289, are the sites of phosphorylation and that each phosphorylation can independently induce the mobility shift. However, E1A mutants lacking these seryl residues transcriptionally activate the adenovirus E3 and E2A promoters and transform baby rat kidney cells to near wild-type levels. Images PMID:2835499

  19. 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.

  20. 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. PMID:21106371

  1. Heterogeneous, weakly coupled map lattices

    NASA Astrophysics Data System (ADS)

    Sotelo Herrera, M.a. Dolores; San Martín, Jesús; Porter, Mason A.

    2016-07-01

    Coupled map lattices (CMLs) are often used to study emergent phenomena in nature. It is typically assumed (unrealistically) that each component is described by the same map, and it is important to relax this assumption. In this paper, we characterize periodic orbits and the laminar regime of type-I intermittency in heterogeneous weakly coupled map lattices (HWCMLs). We show that the period of a cycle in an HWCML is preserved for arbitrarily small coupling strengths even when an associated uncoupled oscillator would experience a period-doubling cascade. Our results characterize periodic orbits both near and far from saddle-node bifurcations, and we thereby provide a key step for examining the bifurcation structure of heterogeneous CMLs.

  2. Specialization and Bet Hedging in Heterogeneous Populations

    NASA Astrophysics Data System (ADS)

    Rulands, Steffen; Jahn, David; Frey, Erwin

    2014-09-01

    Phenotypic heterogeneity is a strategy commonly used by bacteria to rapidly adapt to changing environmental conditions. Here, we study the interplay between phenotypic heterogeneity and genetic diversity in spatially extended populations. By analyzing the spatiotemporal dynamics, we show that the level of mobility and the type of competition qualitatively influence the persistence of phenotypic heterogeneity. While direct competition generally promotes persistence of phenotypic heterogeneity, specialization dominates in models with indirect competition irrespective of the degree of mobility.

  3. On comparing heterogeneity across biomarkers

    PubMed Central

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

    2015-01-01

    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 co-staining 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 co-staining. 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. PMID:25425168

  4. Translational Implications of Tumor Heterogeneity

    PubMed Central

    Jamal-Hanjani, Mariam; Quezada, Sergio A.; Larkin, James; Swanton, Charles

    2015-01-01

    Advances in next-generation sequencing and bioinformatics have led to an unprecedented view of the cancer genome and its evolution. Genomic studies have demonstrated the complex and heterogeneous clonal landscape of tumors of different origins, and the potential impact of intratumor heterogeneity on treatment response and resistance, cancer progression and the risk of disease relapse. However, the significance of subclonal mutations, in particular mutations in driver genes, and their evolution through time and their dynamics in response to cancer therapies, is yet to be determined. The necessary tools are now available to prospectively determine whether clonal heterogeneity can be used as a biomarker of clinical outcome, and to what extent subclonal somatic alterations might influence clinical outcome. Studies that employ longitudinal tissue sampling, integrating both genomic and clinical data, have the potential to reveal the subclonal composition and track the evolution of tumors in order to address these questions, and to begin to define the breadth of genetic diversity in different tumor types, and its relevance to patient outcome. Such studies may provide further evidence for novel drug resistance mechanisms informing novel combinatorial, adaptive and tumour immune-therapies placed within the context of tumor evolution. PMID:25770293

  5. Heterogeneous nucleation or homogeneous nucleation?

    NASA Astrophysics Data System (ADS)

    Liu, X. Y.

    2000-06-01

    The generic heterogeneous effect of foreign particles on three dimensional nucleation was examined both theoretically and experimentally. It shows that the nucleation observed under normal conditions includes a sequence of progressive heterogeneous processes, characterized by different interfacial correlation function f(m,x)s. At low supersaturations, nucleation will be controlled by the process with a small interfacial correlation function f(m,x), which results from a strong interaction and good structural match between the foreign bodies and the crystallizing phase. At high supersaturations, nucleation on foreign particles having a weak interaction and poor structural match with the crystallizing phase (f(m,x)→1) will govern the kinetics. This frequently leads to the false identification of homogeneous nucleation. Genuine homogeneous nucleation, which is the up-limit of heterogeneous nucleation, may not be easily achievable under gravity. In order to check these results, the prediction is confronted with nucleation experiments of some organic and inorganic crystals. The results are in excellent agreement with the theory.

  6. 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.

  7. 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.

  8. Investigating Population Heterogeneity With Factor Mixture Models

    ERIC Educational Resources Information Center

    Lubke, Gitta H.; Muthen, Bengt

    2005-01-01

    Sources of population heterogeneity may or may not be observed. If the sources of heterogeneity are observed (e.g., gender), the sample can be split into groups and the data analyzed with methods for multiple groups. If the sources of population heterogeneity are unobserved, the data can be analyzed with latent class models. Factor mixture models…

  9. Polygenic dissection of major depression clinical heterogeneity.

    PubMed

    Milaneschi, Y; Lamers, F; Peyrot, W J; Abdellaoui, A; Willemsen, G; Hottenga, J-J; Jansen, R; Mbarek, H; Dehghan, A; Lu, C; Boomsma, D I; Penninx, B W J H

    2016-04-01

    The molecular mechanisms underlying major depressive disorder (MDD) are largely unknown. Limited success of previous genetics studies may be attributable to heterogeneity of MDD, aggregating biologically different subtypes. We examined the polygenic features of MDD and two common clinical subtypes (typical and atypical) defined by symptom profiles in a large sample of adults with established diagnoses. Data were from 1530 patients of the Netherlands Study of Depression and Anxiety (NESDA) and 1700 controls mainly from the Netherlands Twin Register (NTR). Diagnoses of MDD and its subtypes were based on DSM-IV symptoms. Genetic overlap of MDD and subtypes with psychiatric (MDD, bipolar disorder, schizophrenia) and metabolic (body mass index (BMI), C-reactive protein, triglycerides) traits was evaluated via genomic profile risk scores (GPRS) generated from meta-analysis results of large international consortia. Single nucleotide polymorphism (SNP)-heritability of MDD and subtypes was also estimated. MDD was associated with psychiatric GPRS, while no association was found for GPRS of metabolic traits. MDD subtypes had differential polygenic signatures: typical was strongly associated with schizophrenia GPRS (odds ratio (OR)=1.54, P=7.8e-9), while atypical was additionally associated with BMI (OR=1.29, P=2.7e-4) and triglycerides (OR=1.21, P=0.006) GPRS. Similar results were found when only the highly discriminatory symptoms of appetite/weight were used to define subtypes. SNP-heritability was 32% for MDD, 38% and 43% for subtypes with, respectively, decreased (typical) and increased (atypical) appetite/weight. In conclusion, MDD subtypes are characterized by partially distinct polygenic liabilities and may represent more homogeneous phenotypes. Disentangling MDD heterogeneity may help the psychiatric field moving forward in the search for molecular roots of depression. PMID:26122587

  10. Irreversible adsorption of particles on heterogeneous surfaces.

    PubMed

    Adamczyk, Zbigniew; Jaszczółt, Katarzyna; Michna, Aneta; Siwek, Barbara; Szyk-Warszyńska, Lilianna; Zembala, Maria

    2005-12-30

    Methods of theoretical and experimental evaluation of irreversible adsorption of particles, e.g., colloids and globular proteins at heterogeneous surfaces were reviewed. The theoretical models were based on the generalized random sequential adsorption (RSA) approach. Within the scope of these models, localized adsorption of particles occurring as a result of short-ranged attractive interactions with discrete adsorption sites was analyzed. Monte-Carlo type simulations performed according to this model enabled one to determine the initial flux, adsorption kinetics, jamming coverage and the structure of the particle monolayer as a function of the site coverage and the particle/site size ratio, denoted by lambda. It was revealed that the initial flux increased significantly with the site coverage theta(s) and the lambda parameter. This behavior was quantitatively interpreted in terms of the scaled particle theory. It also was demonstrated that particle adsorption kinetics and the jamming coverage increased significantly, at fixed site coverage, when the lambda parameter increased. Practically, for alpha = lambda2theta(s) > 1 the jamming coverage at the heterogeneous surfaces attained the value pertinent to continuous surfaces. The results obtained prove unequivocally that spherically shaped sites were more efficient in binding particles in comparison with disk-shaped sites. It also was predicted that for particle size ratio lambda < 4 the site multiplicity effect plays a dominant role, affecting significantly the structure of particle monolayers and the jamming coverage. Experimental results validating main aspects of these theoretical predictions also have been reviewed. These results were derived by using monodisperse latex particles adsorbing on substrates produced by covering uniform surface by adsorption sites of a desired size, coverage and surface charge. Particle deposition occurred under diffusion-controlled transport conditions and their coverage was

  11. 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. PMID:24123408

  12. 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.

  13. Root Patterns in Heterogeneous Soils

    NASA Astrophysics Data System (ADS)

    Dara, A.; Moradi, A. B.; Carminati, A.; Oswald, S. E.

    2010-12-01

    Heterogeneous water availability is a typical characteristic of soils in which plant roots grow. Despite the intrinsic heterogeneity of soil-plant water relations, we know little about the ways how plants respond to local environmental quality. Furthermore, increasing use of soil amendments as partial water reservoirs in agriculture calls for a better understanding of plant response to soil heterogeneity. Neutron radiography is a non-invasive imaging that is highly sensitive to water and root distribution and that has high capability for monitoring spatial and temporal soil-plant water relations in heterogeneous systems. Maize plants were grown in 25 x 30 x 1 cm aluminum slabs filled with sandy soil. On the right side of the compartments a commercial water absorbent (Geohumus) was mixed with the soil. Geohumus was distributed with two patterns: mixed homogeneously with the soil, and arranged as 1-cm diameter aggregates (Fig. 1). Two irrigation treatments were applied: sufficient water irrigation and moderate water stress. Neutron radiography started 10 days after planting and has been performed twice a day for one week. At the end of the experiment, the containers were opened, the root were removed and dry root weight in different soil segments were measured. Neutron radiography showed root growth tendency towards Geohumus treated parts and preferential water uptake from Geohumus aggregates. Number and length of fine lateral roots were lower in treated areas compared to the non-treated zone and to control soil. Although corn plants showed an overall high proliferation towards the soil water sources, they decreased production of branches and fine root when water was more available near the main root parts. However there was 50% higher C allocation in roots grown in Geohumus compartments, as derived by the relative dry weight of root. The preferential C allocation in treated regions was higher when plants grew under water stress. We conclude that in addition to the

  14. Force spectroscopy of complex biopolymers with heterogeneous elasticity.

    PubMed

    Valdman, David; Lopez, Benjamin J; Valentine, Megan T; Atzberger, Paul J

    2013-01-21

    Cellular biopolymers can exhibit significant compositional heterogeneities as a result of the non-uniform binding of associated proteins, the formation of microstructural defects during filament assembly, or the imperfect bundling of filaments into composite structures of variable diameter. These can lead to significant variations in the local mechanical properties of biopolymers along their length. Existing spectral analysis methods assume filament homogeneity and therefore report only a single average stiffness for the entire filament. However, understanding how local effects modulate biopolymer mechanics in a spatially resolved manner is essential to understanding how binding and bundling proteins regulate biopolymer stiffness and function in cellular contexts. Here, we present a new method to determine the spatially varying material properties of individual complex biopolymers from the observation of passive thermal fluctuations of the filament conformation. We develop new statistical mechanics-based approaches for heterogeneous filaments that estimate local bending elasticities as a function of the filament arc-length. We validate this methodology using simulated polymers with known stiffness distributions, and find excellent agreement between derived and expected values. We then determine the bending elasticity of microtubule filaments of variable composition generated by repeated rounds of tubulin polymerization using either GTP or GMPCPP, a nonhydrolyzable GTP analog. Again, we find excellent agreement between mechanical and compositional heterogeneities. PMID:24049545

  15. Heterogeneity of Aspergillus niger Microcolonies in Liquid Shaken Cultures▿ †

    PubMed Central

    de Bekker, Charissa; van Veluw, G. Jerre; Vinck, Arman; Wiebenga, L. Ad; Wösten, Han A. B.

    2011-01-01

    The fungus Aspergillus niger forms (sub)millimeter microcolonies within a liquid shaken culture. Here, we show that such microcolonies are heterogeneous with respect to size and gene expression. Microcolonies of strains expressing green fluorescent protein (GFP) from the promoter of the glucoamlyase gene glaA or the ferulic acid esterase gene faeA were sorted on the basis of diameter and fluorescence using the Complex Object Parametric Analyzer and Sorter (COPAS) technology. Statistical analysis revealed that the liquid shaken culture consisted of two populations of microcolonies that differ by 90 μm in diameter. The population of small microcolonies of strains expressing GFP from the glaA or faeA promoter comprised 39% and 25% of the culture, respectively. Two populations of microcolonies could also be distinguished when the expression of GFP in these strains was analyzed. The population expressing a low level of GFP consisted of 68% and 44% of the culture, respectively. We also show that mRNA accumulation is heterogeneous within microcolonies of A. niger. Central and peripheral parts of the mycelium were isolated with laser microdissection and pressure catapulting (LMPC), and RNA from these samples was used for quantitative PCR analysis. This analysis showed that the RNA content per hypha was about 45 times higher at the periphery than in the center of the microcolony. Our data imply that the protein production of A. niger can be improved in industrial fermentations by reducing the heterogeneity within the culture. PMID:21169437

  16. 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

  17. Socially Aware Heterogeneous Wireless Networks.

    PubMed

    Kosmides, Pavlos; Adamopoulou, Evgenia; Demestichas, Konstantinos; Theologou, Michael; Anagnostou, Miltiades; Rouskas, Angelos

    2015-01-01

    The development of smart cities has been the epicentre of many researchers' efforts during the past decade. One of the key requirements for smart city networks is mobility and this is the reason stable, reliable and high-quality wireless communications are needed in order to connect people and devices. Most research efforts so far, have used different kinds of wireless and sensor networks, making interoperability rather difficult to accomplish in smart cities. One common solution proposed in the recent literature is the use of software defined networks (SDNs), in order to enhance interoperability among the various heterogeneous wireless networks. In addition, SDNs can take advantage of the data retrieved from available sensors and use them as part of the intelligent decision making process contacted during the resource allocation procedure. In this paper, we propose an architecture combining heterogeneous wireless networks with social networks using SDNs. Specifically, we exploit the information retrieved from location based social networks regarding users' locations and we attempt to predict areas that will be crowded by using specially-designed machine learning techniques. By recognizing possible crowded areas, we can provide mobile operators with recommendations about areas requiring datacell activation or deactivation. PMID:26110402

  18. On evolutionary spatial heterogeneous games

    NASA Astrophysics Data System (ADS)

    Fort, H.

    2008-03-01

    How cooperation between self-interested individuals evolve is a crucial problem, both in biology and in social sciences, that is far from being well understood. Evolutionary game theory is a useful approach to this issue. The simplest model to take into account the spatial dimension in evolutionary games is in terms of cellular automata with just a one-parameter payoff matrix. Here, the effects of spatial heterogeneities of the environment and/or asymmetries in the interactions among the individuals are analysed through different extensions of this model. Instead of using the same universal payoff matrix, bimatrix games in which each cell at site ( i, j) has its own different ‘temptation to defect’ parameter T(i,j) are considered. First, the case in which these individual payoffs are constant in time is studied. Second, an evolving evolutionary spatial game such that T=T(i,j;t), i.e. besides depending on the position evolves (by natural selection), is used to explore the combination of spatial heterogeneity and natural selection of payoff matrices.

  19. 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.

  20. 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.

  1. 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.

  2. Heterogeneous catalytic transesterification of phosphatidylcholine.

    PubMed

    Balasubramanian, Rajesh Kumar; Obbard, Jeffrey Philip

    2011-01-01

    The transesterification of phosphatidylcholine (PC) via homogeneous and heterogeneous catalysis was investigated for the production of fatty acid methyl esters (FAME) i.e. biodiesel. Calcium methoxide and calcium oxide were used as heterogeneous catalysts, and KOH as a homogeneous catalyst for the transesterification of phosphatidylcholine (PC)--a polar phospholipid prevalent in eukaryotic organisms. The initial reaction rate was higher for KOH (24.23 g of FAME/g of catalyst.min) than for calcium methoxide (17.06 g of FAME/g of catalyst.min) and calcium oxide (1.06 g of FAME/g of catalyst.min). PC was then mixed with soybean oil at different proportions (i.e. 10%, 30% and 50%, PC10, PC30 and PC50, respectively) which was then used as the feedstock for transesterification using calcium methoxide. When the mass fraction of PC was increased in the feedstock reaction rate also increased. Phosphorus content of the FAME layer of PC100, PC50, PC30 and PC10 was 0.081, 0.041, 0.035 and 0.028% (w/w), respectively. PMID:20832299

  3. Socially Aware Heterogeneous Wireless Networks

    PubMed Central

    Kosmides, Pavlos; Adamopoulou, Evgenia; Demestichas, Konstantinos; Theologou, Michael; Anagnostou, Miltiades; Rouskas, Angelos

    2015-01-01

    The development of smart cities has been the epicentre of many researchers’ efforts during the past decade. One of the key requirements for smart city networks is mobility and this is the reason stable, reliable and high-quality wireless communications are needed in order to connect people and devices. Most research efforts so far, have used different kinds of wireless and sensor networks, making interoperability rather difficult to accomplish in smart cities. One common solution proposed in the recent literature is the use of software defined networks (SDNs), in order to enhance interoperability among the various heterogeneous wireless networks. In addition, SDNs can take advantage of the data retrieved from available sensors and use them as part of the intelligent decision making process contacted during the resource allocation procedure. In this paper, we propose an architecture combining heterogeneous wireless networks with social networks using SDNs. Specifically, we exploit the information retrieved from location based social networks regarding users’ locations and we attempt to predict areas that will be crowded by using specially-designed machine learning techniques. By recognizing possible crowded areas, we can provide mobile operators with recommendations about areas requiring datacell activation or deactivation. PMID:26110402

  4. Thermal properties of heterogeneous grains

    NASA Technical Reports Server (NTRS)

    Lien, David J.

    1988-01-01

    Cometary dust is not spherical nor homogeneous, yet these are the assumptions used to model its thermal, optical, and dynamical properties. To better understand the effects of heterogeneity on the thermal and optical properties of dust grains, the effective dielectric constant for an admixture of magnetite and a silicate were calculated using two different effective medium theories: the Maxwell-Garnett theory and the Bruggeman theory. In concept, the MG theory describes the effective dielectric constant of a matrix material into which is embedded a large number of very small inclusions of a second material. The Bruggeman theory describes the dielectric constant of a well mixed aggregate of two or more types of materials. Both theories assume that the individual particles are much smaller than the wavelength of the incident radiation. The refractivity for a heterogeneous grain using the MG theory is very similar to the refractivity of the matrix material, even for large volume fractions of the inclusion. The equilibrium grain temperature for spherical particles sized from .001 to 100 microns in radius at 1 astronomical unit from the sun was calculated. Further explanation is given.

  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. Groundwater pumping by heterogeneous users

    NASA Astrophysics Data System (ADS)

    Saak, Alexander E.; Peterson, Jeffrey M.

    2012-08-01

    Farm size is a significant determinant of both groundwater-irrigated farm acreage and groundwater-irrigation-application rates per unit land area. This paper analyzes the patterns of groundwater exploitation when resource users in the area overlying a common aquifer are heterogeneous. In the presence of user heterogeneity, the common resource problem consists of inefficient dynamic and spatial allocation of groundwater because it impacts income distribution not only across periods but also across farmers. Under competitive allocation, smaller farmers pump groundwater faster if farmers have a constant marginal periodic utility of income. However, it is possible that larger farmers pump faster if the Arrow-Pratt coefficient of relative risk-aversion is sufficiently decreasing in income. A greater farm-size inequality may either moderate or amplify income inequality among farmers. Its effect on welfare depends on the curvature properties of the agricultural output function and the farmer utility of income. Also, it is shown that a flat-rate quota policy that limits the quantity of groundwater extraction per unit land area may have unintended consequences for the income distribution among farmers.

  7. 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

  8. Heterogeneous Nuclear Ribonucleoprotein M Facilitates Enterovirus Infection

    PubMed Central

    Jagdeo, Julienne M.; Dufour, Antoine; Fung, Gabriel; Luo, Honglin; Kleifeld, Oded; Overall, Christopher M.

    2015-01-01

    ABSTRACT Picornavirus infection involves a dynamic interplay of host and viral protein interactions that modulates cellular processes to facilitate virus infection and evade host antiviral defenses. Here, using a proteomics-based approach known as TAILS to identify protease-generated neo-N-terminal peptides, we identify a novel target of the poliovirus 3C proteinase, the heterogeneous nuclear ribonucleoprotein M (hnRNP M), a nucleocytoplasmic shuttling RNA-binding protein that is primarily known for its role in pre-mRNA splicing. hnRNP M is cleaved in vitro by poliovirus and coxsackievirus B3 (CVB3) 3C proteinases and is targeted in poliovirus- and CVB3-infected HeLa cells and in the hearts of CVB3-infected mice. hnRNP M relocalizes from the nucleus to the cytoplasm during poliovirus infection. Finally, depletion of hnRNP M using small interfering RNA knockdown approaches decreases poliovirus and CVB3 infections in HeLa cells and does not affect poliovirus internal ribosome entry site translation and viral RNA stability. We propose that cleavage of and subverting the function of hnRNP M is a general strategy utilized by picornaviruses to facilitate viral infection. IMPORTANCE Enteroviruses, a member of the picornavirus family, are RNA viruses that cause a range of diseases, including respiratory ailments, dilated cardiomyopathy, and paralysis. Although enteroviruses have been studied for several decades, the molecular basis of infection and the pathogenic mechanisms leading to disease are still poorly understood. Here, we identify hnRNP M as a novel target of a viral proteinase. We demonstrate that the virus subverts the function of hnRNP M and redirects it to a step in the viral life cycle. We propose that cleavage of hnRNP M is a general strategy that picornaviruses use to facilitate infection. PMID:25926642

  9. Weakly bound states in heterogeneous waveguides

    NASA Astrophysics Data System (ADS)

    Amore, Paolo; Fernández, Francisco M.; Hofmann, Christoph P.

    2016-07-01

    We study the spectrum of the Helmholtz equation in a two-dimensional infinite waveguide, containing a weak heterogeneity localized at an internal point, and obeying Dirichlet boundary conditions at its border. We use the variational theorem to derive the condition for which the lowest eigenvalue of the spectrum falls below the continuum threshold and a bound state appears, localized at the heterogeneity. We devise a rigorous perturbation scheme and derive the exact expression for the energy to third order in the heterogeneity.

  10. Inferring Diffusion Dynamics from FCS in Heterogeneous Nuclear Environments

    PubMed Central

    Tsekouras, Konstantinos; Siegel, Amanda P.; Day, Richard N.; Pressé, Steve

    2015-01-01

    Fluorescence correlation spectroscopy (FCS) is a noninvasive technique that probes the diffusion dynamics of proteins down to single-molecule sensitivity in living cells. Critical mechanistic insight is often drawn from FCS experiments by fitting the resulting time-intensity correlation function, G(t), to known diffusion models. When simple models fail, the complex diffusion dynamics of proteins within heterogeneous cellular environments can be fit to anomalous diffusion models with adjustable anomalous exponents. Here, we take a different approach. We use the maximum entropy method to show—first using synthetic data—that a model for proteins diffusing while stochastically binding/unbinding to various affinity sites in living cells gives rise to a G(t) that could otherwise be equally well fit using anomalous diffusion models. We explain the mechanistic insight derived from our method. In particular, using real FCS data, we describe how the effects of cell crowding and binding to affinity sites manifest themselves in the behavior of G(t). Our focus is on the diffusive behavior of an engineered protein in 1) the heterochromatin region of the cell’s nucleus as well as 2) in the cell’s cytoplasm and 3) in solution. The protein consists of the basic region-leucine zipper (BZip) domain of the CCAAT/enhancer-binding protein (C/EBP) fused to fluorescent proteins. PMID:26153697

  11. 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.

  12. 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.

  13. 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.

  14. Mesoscale poroelasticity of heterogeneous media

    NASA Astrophysics Data System (ADS)

    Monfared, Siavash; Laubie, Hadrien; Radjai, Farhang; Pellenq, Roland; Ulm, Franz-Josef

    Poroelastic behavior of heterogeneous media is revisited. Lattice Element Method (LEM) is used to model interaction between solid constituents due to a pressurized pore space. Exploring beyond mean-field based theories in continuum microporomechanics, local textural variations and its contribution to the global anisotropic poroelastic behavior of real multiphase porous media are captured. To this end, statistical distributions of mesoscale poroelastic coefficients from numerical simulations on X-ray microscopy scans of two different organic-rich shales with different microtextures are presented. The results are compared with predictions using mean-field based tools of continuum micromechanics. The textural dependency of strain localization and stress chain formation captured in this framework promises a powerful tool for modeling poroelastic response of complex porous composites and a path to incorporate local textural and elastic variations into a continuum description. Visiting Scientist, CNRS-MIT, MIT.

  15. Heterogeneous fuel for hybrid rocket

    NASA Technical Reports Server (NTRS)

    Stickler, David B. (Inventor)

    1996-01-01

    Heterogeneous fuel compositions suitable for use in hybrid rocket engines and solid-fuel ramjet engines, The compositions include mixtures of a continuous phase, which forms a solid matrix, and a dispersed phase permanently distributed therein. The dispersed phase or the matrix vaporizes (or melts) and disperses into the gas flow much more rapidly than the other, creating depressions, voids and bumps within and on the surface of the remaining bulk material that continuously roughen its surface, This effect substantially enhances heat transfer from the combusting gas flow to the fuel surface, producing a correspondingly high burning rate, The dispersed phase may include solid particles, entrained liquid droplets, or gas-phase voids having dimensions roughly similar to the displacement scale height of the gas-flow boundary layer generated during combustion.

  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. [Systemic mastocytosis: a heterogeneous disease].

    PubMed

    Hermans, M A W; Verburg, M; van Laar, J A M; van Hagen, P M; Pasmans, S G M A; van Daele, P L A

    2016-01-01

    Systemic mastocytosis (SM) is an acquired myeloproliferative disease, which is caused by an uncontrolled proliferation of aberrant mast cells. SM patients can have very different clinical phenotypes and may therefore initially present to different specialties. Diagnosis is often delayed because many physicians are unfamiliar with this illness. This can lead to substantial morbidity and puts patients at risk of complications such as severe anaphylaxis. Measurement of serum tryptase levels is always a sensible first step in the diagnostic work-up, but a normal serum tryptase does not rule out SM completely, and a bone marrow biopsy is essential for a conclusive diagnosis. Here, we describe two patient cases to illustrate the heterogeneous nature of this disease, and provide an overview of the symptoms, diagnostic work-up and current treatments options for SM. PMID:27229688

  18. Toward understanding and exploiting tumor heterogeneity

    PubMed Central

    Alizadeh, Ash A; Aranda, Victoria; Bardelli, Alberto; Blanpain, Cedric; Bock, Christoph; Borowski, Christine; Caldas, Carlos; Califano, Andrea; Doherty, Michael; Elsner, Markus; Esteller, Manel; Fitzgerald, Rebecca; Korbel, Jan O; Lichter, Peter; Mason, Christopher E; Navin, Nicholas; Pe’er, Dana; Polyak, Kornelia; Roberts, Charles W M; Siu, Lillian; Snyder, Alexandra; Stower, Hannah; Swanton, Charles; Verhaak, Roel G W; Zenklusen, Jean C; Zuber, Johannes; Zucman-Rossi, Jessica

    2016-01-01

    The extent of tumor heterogeneity is an emerging theme that researchers are only beginning to understand. How genetic and epigenetic heterogeneity affects tumor evolution and clinical progression is unknown. The precise nature of the environmental factors that influence this heterogeneity is also yet to be characterized. Nature Medicine, Nature Biotechnology and the Volkswagen Foundation organized a meeting focused on identifying the obstacles that need to be overcome to advance translational research in and tumor heterogeneity. Once these key questions were established, the attendees devised potential solutions. Their ideas are presented here. PMID:26248267

  19. Toward understanding and exploiting tumor heterogeneity.

    PubMed

    Alizadeh, Ash A; Aranda, Victoria; Bardelli, Alberto; Blanpain, Cedric; Bock, Christoph; Borowski, Christine; Caldas, Carlos; Califano, Andrea; Doherty, Michael; Elsner, Markus; Esteller, Manel; Fitzgerald, Rebecca; Korbel, Jan O; Lichter, Peter; Mason, Christopher E; Navin, Nicholas; Pe'er, Dana; Polyak, Kornelia; Roberts, Charles W M; Siu, Lillian; Snyder, Alexandra; Stower, Hannah; Swanton, Charles; Verhaak, Roel G W; Zenklusen, Jean C; Zuber, Johannes; Zucman-Rossi, Jessica

    2015-08-01

    The extent of tumor heterogeneity is an emerging theme that researchers are only beginning to understand. How genetic and epigenetic heterogeneity affects tumor evolution and clinical progression is unknown. The precise nature of the environmental factors that influence this heterogeneity is also yet to be characterized. Nature Medicine, Nature Biotechnology and the Volkswagen Foundation organized a meeting focused on identifying the obstacles that need to be overcome to advance translational research in and tumor heterogeneity. Once these key questions were established, the attendees devised potential solutions. Their ideas are presented here. PMID:26248267

  20. [Amino acid composition of rice grain proteins].

    PubMed

    Peruanskiĭ, Iu V; Savich, I M

    1976-01-01

    The composition of the major reserve proteins of rice grain--globulins, prolamines and glutelins--was examined in four rice varieties (Dubovsky 129, Kuban 3, Alakul, Ushtobinsky). Globulins proved to be most heterogeneous whereas glutelins appeared to be least heterogeneous. In regards to the ratio of components globulins showed high variability and glutelins displayed high stability. PMID:1005365

  1. 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. PMID:12460477

  2. Heterogeneous Factor Analysis Models: A Bayesian Approach.

    ERIC Educational Resources Information Center

    Ansari, Asim; Jedidi, Kamel; Dube, Laurette

    2002-01-01

    Developed Markov Chain Monte Carlo procedures to perform Bayesian inference, model checking, and model comparison in heterogeneous factor analysis. Tested the approach with synthetic data and data from a consumption emotion study involving 54 consumers. Results show that traditional psychometric methods cannot fully capture the heterogeneity in…

  3. 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…

  4. Heterogeneity in Health Care Computing Environments

    PubMed Central

    Sengupta, Soumitra

    1989-01-01

    This paper discusses issues of heterogeneity in computer systems, networks, databases, and presentation techniques, and the problems it creates in developing integrated medical information systems. The need for institutional, comprehensive goals are emphasized. Using the Columbia-Presbyterian Medical Center's computing environment as the case study, various steps to solve the heterogeneity problem are presented.

  5. 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

  6. 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. PMID:27175778

  7. 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

  8. Potentiation of mycovirus transmission by zinc compounds via attenuation of heterogenic incompatibility in Rosellinia necatrix.

    PubMed

    Ikeda, Kenichi; Inoue, Kanako; Kida, Chiaki; Uwamori, Takahiro; Sasaki, Atsuko; Kanematsu, Satoko; Park, Pyoyun

    2013-06-01

    Heterogenic incompatibility is considered a defense mechanism against deleterious intruders such as mycovirus. Rosellinia necatrix shows strong heterogenic incompatibility. In the heterogenic incompatibility reaction, the approaching hyphae hardly anastomosed, a distinctive barrage line formed, and green fluorescent protein (GFP)-labeled hyphae quickly lost their fluorescence when encountering incompatible hyphae. In this study, transmission of a hypovirulence-conferring mycovirus to strains with different genetic backgrounds was attempted. Various chemical reagents considered to affect the programmed cell death pathway or cell wall modification were examined. Treatment with zinc compounds was shown to aid in transmission of mycoviruses to strains with different genetic backgrounds. In incompatible pairings, treatment with zinc compounds accelerated hyphal anastomosis; moreover, cytosolic GFP was transmitted to the newly joined hyphae. These results suggest that zinc compounds not only increase hyphal anastomosis but also attenuate heterogenic incompatibility. PMID:23563943

  9. Quantification of heterogeneity observed in medical images

    PubMed Central

    2013-01-01

    Background There has been much recent interest in the quantification of visually evident heterogeneity within functional grayscale medical images, such as those obtained via magnetic resonance or positron emission tomography. In the case of images of cancerous tumors, variations in grayscale intensity imply variations in crucial tumor biology. Despite these considerable clinical implications, there is as yet no standardized method for measuring the heterogeneity observed via these imaging modalities. Methods In this work, we motivate and derive a statistical measure of image heterogeneity. This statistic measures the distance-dependent average deviation from the smoothest intensity gradation feasible. We show how this statistic may be used to automatically rank images of in vivo human tumors in order of increasing heterogeneity. We test this method against the current practice of ranking images via expert visual inspection. Results We find that this statistic provides a means of heterogeneity quantification beyond that given by other statistics traditionally used for the same purpose. We demonstrate the effect of tumor shape upon our ranking method and find the method applicable to a wide variety of clinically relevant tumor images. We find that the automated heterogeneity rankings agree very closely with those performed visually by experts. Conclusions These results indicate that our automated method may be used reliably to rank, in order of increasing heterogeneity, tumor images whether or not object shape is considered to contribute to that heterogeneity. Automated heterogeneity ranking yields objective results which are more consistent than visual rankings. Reducing variability in image interpretation will enable more researchers to better study potential clinical implications of observed tumor heterogeneity. PMID:23453000

  10. Heterogeneous Chemistry in Global Chemistry Transport Models

    NASA Astrophysics Data System (ADS)

    Stadtler, Scarlet; Simpson, David; Schultz, Martin; Bott, Andreas

    2016-04-01

    The impact of six tropospheric heterogeneous reactions on ozone and nitrogen species was studied using two chemical transport models EMEP MSC-W and ECHAM6-HAMMOZ. Since heterogeneous reactions depend on reactant concentrations (in this study these are N_2O_5, NO_3, NO_2, O_3, HNO_3, HO_2) and aerosol surface area S_a, the modeled surface area of both models was compared to a satellite product retrieving the surface area. This comparison shows a good agreement in global pattern and especially the capability of both models to capture the extreme aerosol loadings in East Asia. Further, the impact of the heterogeneous reactions was evaluated by the simulation of a reference run containing all heterogeneous reactions and several sensitivity runs. One reaction was turned off in each sensitivity run to compare it with the reference run. As previously shown, the analysis of the sensitivity runs shows that the globally most important heterogeneous reaction is the one of N_2O_5. Nevertheless, NO_2, NO_3, HNO3 and HO2 heterogeneous reactions gain relevance particular in East China due to presence of high NOx concentrations and high Sa in the same region. The heterogeneous reaction of O3 itself on dust is compared to the other heterogeneous reactions of minor relevance. Evaluation of the models with northern hemispheric ozone surface observations yields a better agreement of the models with observations when the heterogeneous reactions are incorporated. Impacts of emission changes on the importance of the heterogeneous chemistry will be discussed.

  11. 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.

  12. 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.

  13. Heterogeneity of the Tumor Vasculature

    PubMed Central

    Nagy, Janice A.; Chang, Sung-Hee; Shih, Shou-Ching; Dvorak, Ann M.; Dvorak, Harold F.

    2012-01-01

    The blood vessels supplying tumors are strikingly heterogeneous and differ from their normal counterparts with respect to organization, structure, and function. Six distinctly different tumor vessel types have been identified, and much has been learned about the steps and mechanisms by which they form. Four of the six vessel types (mother vessels, capillaries, glomeruloid microvascular proliferations, and vascular malformations) develop from preexisting normal venules and capillaries by angiogenesis. The two remaining vessel types (feeder arteries and draining veins) develop from arterio-venogenesis, a parallel, poorly understood process that involves the remodeling of preexisting arteries and veins. All six of these tumor vessel types can be induced to form sequentially in normal mouse tissues by an adenoviral vector expressing vascular endothelial growth factor (VEGF)-A164. Current antiangiogenic cancer therapies directed at VEGF-A or its receptors have been of only limited benefit to cancer patients, perhaps because they target only the endothelial cells of the tumor blood vessel subset that requires exogenous VEGF-A for maintenance. A goal of future work is to identify therapeutic targets on tumor blood vessel endothelial cells that have lost this requirement. PMID:20490982

  14. 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.

  15. Adaptation Driven by Spatial Heterogeneities

    NASA Astrophysics Data System (ADS)

    Hermsen, Rutger

    2011-03-01

    Biological evolution and ecology are intimately linked, because the reproductive success or ``fitness'' of an organism depends crucially on its ecosystem. Yet, most models of evolution (or population genetics) consider homogeneous, fixed-size populations subjected to a constant selection pressure. To move one step beyond such ``mean field'' descriptions, we discuss stochastic models of evolution driven by spatial heterogeneity. We imagine a population whose range is limited by a spatially varying environmental parameter, such as a temperature or the concentration of an antibiotic drug. Individuals in the population replicate, die and migrate stochastically. Also, by mutation, they can adapt to the environmental stress and expand their range. This way, adaptation and niche expansion go hand in hand. This mode of evolution is qualitatively different from the usual notion of a population climbing a fitness gradient. We analytically calculate the rate of adaptation by solving a first passage time problem. Interestingly, the joint effects of reproduction, death, mutation and migration result in two distinct parameter regimes depending on the relative time scales of mutation and migration. We argue that the proposed scenario may be relevant for the rapid evolution of antibiotic resistance. This work was supported by the Center for Theoretical Biological Physics sponsored by the National Science Foundation (NSF) (Grant PHY-0822283).

  16. Bedload sheets in heterogeneous sediment

    SciTech Connect

    Whiting, P.J.; Dietrich, W.E.; Leopold, L.B.; Drake, T.G.; Shreve, R.L.

    1988-02-01

    Field observations in streams with beds of coarse sand and fine gravel have revealed that bedload moves primarily as thin, migrating accumulations of sediment, and coarse grains cluster at their leading edge. These accumulations are one or two coarse grains high and are much longer (0.2-0.6 m long in sand; 0.5-2.0 m in fine gravel) than their height. The authors propose the term bedload sheet for these features, and the authors argue that they result from an instability inherent to bedload movement of moderately and poorly sorted sediment. In essence, coarse particles in the bedload slow or stop each other, trap finer particles in their interstices, and thus cause the coarse particles to become mobile again. Bedload sheets develop on the stoss side of dunes, causing the dune to advance incrementally with the arrival of each sheet. Successive deposition of coarse sediment from the leading edge followed by fine sediment may generate the grain-size sorting that distinguishes cross-bedding. Available flume experiments and field observations indicate that bedload sheets are a common, but generally unrecognized, feature of heterogeneous sediment transport.

  17. Surface area controlled heterogeneous nucleation

    NASA Astrophysics Data System (ADS)

    Steer, Brian; Gorbunov, Boris; Rowles, Jonathan; Green, David

    2012-02-01

    Heterogeneous nucleation of liquid from a gas phase on nanoparticles has been studied under various saturation ratios and nuclei size. The probability of liquid droplet nucleation, especially at a low degree of deviation from equilibrium, was measured for both atmospheric aerosol particles and engineered nanoparticles Cr2O3. The concept of a critical saturation ratio and the validity of the one-to-one relationship between the nuclei number and the number of droplets were examined. A transient zone between no nucleation and established nucleation termed the surface area controlled nucleation was observed. In this zone, the probability of stable phase formation is determined by the surface area of nuclei. There are two distinctive features of the surface area controlled nucleation: the nucleation probability is much less than 1 and is proportional to the surface area of nuclei. For condensation particle counters (CPCs) counting nanoparticles, these features mean that counts measured are proportional to the surface area of nanoparticles and, therefore, the CPCs counts can be calibrated to measure the surface area.

  18. Anatomical heterogeneity of Alzheimer disease

    PubMed Central

    Noh, Young; Jeon, Seun; Seo, Sang Won; Kim, Geon Ha; Cho, Hanna; Ye, Byoung Seok; Yoon, Cindy W.; Kim, Hee Jin; Chin, Juhee; Park, Kee Hyung; Heilman, Kenneth M.

    2014-01-01

    Objective: Because the signs associated with dementia due to Alzheimer disease (AD) can be heterogeneous, the goal of this study was to use 3-dimensional MRI to examine the various patterns of cortical atrophy that can be associated with dementia of AD type, and to investigate whether AD dementia can be categorized into anatomical subtypes. Methods: High-resolution T1-weighted volumetric MRIs were taken of 152 patients in their earlier stages of AD dementia. The images were processed to measure cortical thickness, and hierarchical agglomerative cluster analysis was performed using Ward's clustering linkage. The identified clusters of patients were compared with an age- and sex-matched control group using a general linear model. Results: There were several distinct patterns of cortical atrophy and the number of patterns varied according to the level of cluster analyses. At the 3-cluster level, patients were divided into (1) bilateral medial temporal–dominant atrophy subtype (n = 52, ∼34.2%), (2) parietal-dominant subtype (n = 28, ∼18.4%) in which the bilateral parietal lobes, the precuneus, along with bilateral dorsolateral frontal lobes, were atrophic, and (3) diffuse atrophy subtype (n = 72, ∼47.4%) in which nearly all association cortices revealed atrophy. These 3 subtypes also differed in their demographic and clinical features. Conclusions: This cluster analysis of cortical thickness of the entire brain showed that AD dementia in the earlier stages can be categorized into various anatomical subtypes, with distinct clinical features. PMID:25344382

  19. Transmission imaging in heterogeneous media

    NASA Astrophysics Data System (ADS)

    Bongajum, E. L.; Meng, Y.; Milkereit, B.

    2010-12-01

    Wave propagation in heterogeneous media is characterized by amplitude, traveltime, and spectral fluctuations that reflect the variations in elastic properties (e.g. Vp, Vs, density). Variations in physical rock properties exist at different scales and occasionally result in effective anisotropy in medium parameters. If the variations in rock properties can be characterized from existing information such as logs, then it becomes possible to incorporate this information in wave modeling algorithms to understand its impact on acquisition design, processing of seismic waves for velocity information, AVO analysis as well as reverse time migration (RTM) routines. This study evaluates some of these aspects by using transmitted (direct) waves. When the variations exist over large scale lengths, RTM can be successfully implemented on Vertical Seismic Profiling (VSP) data in order to image the interface between two inhomogeneities as well as characterize the velocity distribution beyond the borehole location. However, when the existing geology causes anisotropy in the variability of the physical rock properties, the use of transmitted waves becomes strongly dependent on the acquisition geometry. In this circumstance, travel time fluctuations are influenced by the strength of the perturbations of the elastic parameters and the direction with the least variability (large scale lengths) in these parameters. This has according implications for seismic imaging in hardrock environment as well microseismic imaging applications.

  20. Clinical significance of monocyte heterogeneity.

    PubMed

    Stansfield, Brian K; Ingram, David A

    2015-01-01

    Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. Until recently, human monocytes were subdivided based on expression of the surface marker CD16. "Classical" monocytes express surface markers denoted as CD14(++)CD16(-) and account for greater than 70% of total monocyte count, while "non-classical" monocytes express the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition of an intermediate population identified as CD14(++)CD16(+) supports the new paradigm that monocytes are a true heterogeneous population and careful identification of specific subpopulations is necessary for understanding monocyte function in human disease. Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen. In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis. PMID:25852821

  1. Transcriptional and phenotypical heterogeneity of Trypanosoma cruzi cell populations.

    PubMed

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

    2015-12-01

    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

  2. Analysis of heterogeneity in nonspecific PEGylation reactions of biomolecules.

    PubMed

    Hakem, Ilhem F; Leech, Anna M; Bohn, Justin; Walker, Jeremy P; Bockstaller, Michael R

    2013-07-01

    The compositional heterogeneity associated with polymer conjugation reactions of biomolecules is analyzed for the particular case of nonspecific PEGylation reactions. It is shown that the distribution of the number of PEG moieties grafted to biomolecules such as proteins is a binomial-type function of two parameters-the reaction efficiency as well as the number of binding sites per biomolecule. The nature of this distribution implies that uniform compositions are favored for increasing number of coupling sites per biomolecule as well as for increasing efficiency of the modification process. Therefore, the binomial distribution provides a rationale for the pronounced heterogeneity that is observed for PEGylated small enzyme systems even at high coupling efficiencies. For the particular case of PEGylated trypsin it is shown that the heterogeneity results in a broad distribution of deactivation times that is captured by a stretched exponential decay model. The presented analysis is expected to apply to general modification processes of compounds in which partial functionalization of a fixed number of reactive sites is achieved by means of a nonspecific coupling reaction. PMID:23616211

  3. 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

  4. Quantifying the Heterogeneous Dynamics of a Simulated Dipalmitoylphosphatidylcholine (DPPC) Membrane.

    PubMed

    Shafique, Neha; Kennedy, Kiley E; Douglas, Jack F; Starr, Francis W

    2016-06-16

    Heterogeneity of dynamics plays a vital role in membrane function, but the methods for quantifying this heterogeneity are still being developed. Here we examine membrane dynamical heterogeneity via molecular simulations of a single-component dipalmitoylphosphatidylcholine (DPPC) lipid bilayer using the MARTINI force field. We draw upon well-established analysis methods developed in the study of glass-forming fluids and find significant changes in lipid dynamics between the fluid (Lα), and gel (Lβ) phases. In particular, we distinguish two mobility groups in the more ordered Lβ phase: (i) lipids that are transiently trapped by their neighbors and (ii) lipids with displacements on the scale of the intermolecular spacing. These distinct mobility groups spatially segregate, forming dynamic clusters that have characteristic time (1-2 μs) and length (1-10 nm) scales comparable to those of proteins and other biomolecules. We suggest that these dynamic clusters could couple to biomolecules within the membrane and thus may play a role in many membrane functions. In the equilibrium membrane, lipid molecules dynamically exchange between the mobility groups, and the resulting clusters are not associated with a thermodynamic phase separation. Dynamical clusters having similar characteristics arise in many other condensed phase materials, placing membranes in a broad class of materials with strong intermolecular interactions. PMID:27223339

  5. Roles for lipid heterogeneity in immunoreceptor signaling.

    PubMed

    Holowka, David; Baird, Barbara

    2016-08-01

    Immune receptors that specifically recognize foreign antigens to activate leukocytes in adaptive immune responses belong to a family of multichain cell surface proteins. All of these contain immunoreceptor tyrosine-based activation motifs in one or more subunits that initiate signaling cascades following stimulated tyrosine phosphorylation by Src-family kinases. As highlighted in this review, lipids participate in this initial activation step, as well as in more downstream signaling steps. We summarize evidence for cholesterol-dependent ordered lipids serving to regulate the store-operated Ca(2+) channel, Orai1, and we describe the sensitivity of Orai1 coupling to the ER Ca(2+) sensor, STIM1, to inhibition by polyunsaturated fatty acids. Phosphoinositides play key roles in regulating STIM1-Orai1 coupling, as well as in the stimulated Ca(2+) oscillations that are a consequence of IgE receptor signaling in mast cells. They also participate in the coupling between the plasma membrane and the actin cytoskeleton, which regulates immune receptor responses in T cells, B cells, and mast cells, both positively and negatively, depending on the cellular context. Recent studies show that other phospholipids with mostly saturated acylation also participate in coupling between receptors and the actin cytoskeleton. Lipid heterogeneity is a central feature of the intimate relationship between the plasma membrane and the actin cytoskeleton. The detailed nature of these interactions and how they are dynamically regulated to initiate and propagate receptor-mediated cell signaling are challenging questions for further investigation. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID:26995463

  6. Molecular heterogeneity of glioblastomas: does location matter?

    PubMed

    Denicolaï, Emilie; Tabouret, Emeline; Colin, Carole; Metellus, Philippe; Nanni, Isabelle; Boucard, Celine; Tchoghandjian, Aurélie; Meyronet, David; Baeza-Kallee, Nathalie; Chinot, Olivier; Figarella-Branger, Dominique

    2016-01-01

    Glioblastomas in adults are highly heterogeneous tumors that can develop throughout the brain. To date no predictive-location marker has been identified. We previously derived two glioblastoma cell lines from cortical and periventricular locations and demonstrated distinct transcriptomic profiles. Based on these preliminary results, the aim of this study was to correlate glioblastoma locations with the expression of ten selected genes (VEGFC, FLT4, MET, HGF, CHI3L1, PROM1, NOTCH1, DLL3, PDGFRA, BCAN). Fifty nine patients with newly diagnosed glioblastomas were retrospectively included. Tumors were classified into cortical and periventricular locations, which were subsequently segregated according to cerebral lobes involved: cortical fronto-parietal (C-FP), cortical temporal (C-T), periventricular fronto-parietal (PV-FP), periventricular temporal (PV-T), and periventricular occipital (PV-O). Gene expression levels were determined using RT-qPCR. Compared to cortical glioblastomas, periventricular glioblastomas were characterized by a higher expression of two mesenchymal genes, VEGFC (p = 0.001) and HGF (p = 0.001). Among cortical locations, gene expressions were homogeneous. In contrast, periventricular locations exhibited distinct expression profiles. PV-T tumors were associated with higher expression of two proneural and cancer stem cell genes, NOTCH1 (p = 0.028) and PROM1 (p = 0.033) while PV-FP tumors were characterized by high expression of a mesenchymal gene, CHI3L1 (p = 0.006). Protein expression of NOTCH1 was correlated with RNA expression levels. PV-O glioblastomas were associated with lower expression of VEGFC (p = 0.032) than other periventricular locations, whereas MET overexpression remained exceptional. These data suggest a differential gene expression profile according to initial glioblastoma location. PMID:26637806

  7. Breast cancer intra-tumor heterogeneity

    PubMed Central

    2014-01-01

    In recent years it has become clear that cancer cells within a single tumor can display striking morphological, genetic and behavioral variability. Burgeoning genetic, epigenetic and phenomenological data support the existence of intra-tumor genetic heterogeneity in breast cancers; however, its basis is yet to be fully defined. Two of the most widely evoked concepts to explain the origin of heterogeneity within tumors are the cancer stem cell hypothesis and the clonal evolution model. Although the cancer stem cell model appeared to provide an explanation for the variability among the neoplastic cells within a given cancer, advances in massively parallel sequencing have provided several lines of evidence to suggest that intra-tumor genetic heterogeneity likely plays a fundamental role in the phenotypic heterogeneity observed in cancers. Many challenges remain, however, in the interpretation of the next generation sequencing results obtained so far. Here we review the models that explain tumor heterogeneity, the causes of intra-tumor genetic diversity and their impact on our understanding and management of breast cancer, methods to study intra-tumor heterogeneity and the assessment of intra-tumor genetic heterogeneity in the clinic. PMID:25928070

  8. 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.

  9. 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.

  10. Graphene-Si heterogeneous nanotechnology

    NASA Astrophysics Data System (ADS)

    Akinwande, Deji; Tao, Li

    2013-05-01

    It is widely envisioned that graphene, an atomic sheet of carbon that has generated very broad interest has the largest prospects for flexible smart systems and for integrated graphene-silicon (G-Si) heterogeneous very large-scale integrated (VLSI) nanoelectronics. In this work, we focus on the latter and elucidate the research progress that has been achieved for integration of graphene with Si-CMOS including: wafer-scale graphene growth by chemical vapor deposition on Cu/SiO2/Si substrates, wafer-scale graphene transfer that afforded the fabrication of over 10,000 devices, wafer-scalable mitigation strategies to restore graphene's device characteristics via fluoropolymer interaction, and demonstrations of graphene integrated with commercial Si- CMOS chips for hybrid nanoelectronics and sensors. Metrology at the wafer-scale has led to the development of custom Raman processing software (GRISP) now available on the nanohub portal. The metrology reveals that graphene grown on 4-in substrates have monolayer quality comparable to exfoliated flakes. At room temperature, the high-performance passivated graphene devices on SiO2/Si can afford average mobilities 3000cm2/V-s and gate modulation that exceeds an order of magnitude. The latest growth research has yielded graphene with high mobilities greater than 10,000cm2/V-s on oxidized silicon. Further progress requires track compatible graphene-Si integration via wafer bonding in order to translate graphene research from basic to applied research in commercial R and D laboratories to ultimately yield a viable nanotechnology.

  11. 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.

  12. 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.

  13. Neural Field Dynamics with Heterogeneous Connection Topology

    NASA Astrophysics Data System (ADS)

    Qubbaj, Murad R.; Jirsa, Viktor K.

    2007-06-01

    Neural fields receive inputs from local and nonlocal sources. Notably in a biologically realistic architecture the latter vary under spatial translations (heterogeneous), the former do not (homogeneous). To understand the mutual effects of homogeneous and heterogeneous connectivity, we study the stability of the steady state activity of a neural field as a function of its connectivity and transmission speed. We show that myelination, a developmentally relevant change of the heterogeneous connectivity, always results in the stabilization of the steady state via oscillatory instabilities, independent of the local connectivity. Nonoscillatory instabilities are shown to be independent of any influences of time delay.

  14. Thermodynamic equilibrium at heterogeneous pressure

    NASA Astrophysics Data System (ADS)

    Vrijmoed, Johannes C.; Podladchikov, Yuri Y.

    2014-05-01

    Recent advances in metamorphic petrology point out the importance of grain-scale pressure variations in high-temperature metamorphic rocks. Pressures derived from chemical zonation using unconventional geobarometry based on equal chemical potentials fit mechanically feasible pressure variations. Here a thermodynamic equilibrium method is presented that predicts chemical zoning as a result of pressure variations by Gibbs energy minimization. Equilibrium thermodynamic prediction of the chemical zoning in the case of pressure heterogeneity is done by constraint Gibbs minimization using linear programming techniques. Compositions of phases considered in the calculation are discretized into 'pseudo-compounds' spanning the entire compositional space. Gibbs energies of these discrete compounds are generated for a given range and resolution of pressures for example derived by barometry or from mechanical model predictions. Gibbs energy minimization is subsequently performed considering all compounds of different composition and pressure. In addition to constraining the system composition a certain proportion of the system is constraint at a specified pressure. Input pressure variations need to be discretized and each discrete pressure defines an additional constraint for the minimization. The proportion of the system at each different pressure is equally distributed over the number of input pressures. For example if two input pressures P1 and P2 are specified, two constraints are added: 50 percent of the system is constraint at P1 while the remaining 50 percent is constraint at P2. The method has been tested for a set of 10 input pressures obtained by Tajčmanová et al. (2014) using their unconventional geobarometry method in a plagioclase rim around kyanite. Each input pressure is added as constraint to the minimization (1/10 percent of the system for each discrete pressure). Constraining the system composition to the average composition of the plagioclase rim

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Changing Emulsion Dynamics with Heterogeneous Surface Wettability

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

    We elucidate the effect of heterogeneous surface wettability on the morphology and dynamics of microfluidic emulsions, generated by a co-flowing device. We first design a useful methodology of modifying a micro-capillary with desired heterogeneous wettability, such as alternating hydrophilic and hydrophobic regions. Subsequently, the effects of flow rates and heterogeneous wettability on the emulsion morphology and motion in the micro-capillary are investigated. Our experimental data reveal a universal critical time scale of advective emulsions, above which the microfluidic emulsions remain intact, whereas below this time-scale emulsions become adhesive or inverse. A simple model based on a force balance can be used to explain this critical transition. These results show a control of emulsion dynamics by tuning the droplet size and the Capillary number, the ratio of viscous to surface effects, with heterogeneous surface wettability.

  20. 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.

  1. Wetting of a chemically heterogeneous surface

    SciTech Connect

    Frink, L.J.; Salinger, A.G.

    1999-03-01

    Theories for inhomogeneous fluids have focused in recent years on wetting, capillary condensation, and solvation forces for model systems where the surface(s) is(are) smooth homogeneous parallel plates, cylinders, or spherical drops. Unfortunately natural systems are more likely to be heterogeneous both in surface shape and surface chemistry. In this paper we discuss the consequences of chemical heterogeneity on wetting. Specifically, a two-dimensional (2D) implementation of a nonlocal density-functional theory is solved for a striped surface model. Both the strength and range of the heterogeneity are varied. Contact angles are calculated, and phase transitions (both the wetting transition and a local layering transition) are located. The wetting properties of the surface are shown to be strongly dependent on the nature of the surface heterogeneity. In addition highly ordered nanoscopic phases are found, and the operational limits for formation of ordered or crystalline phases of nanoscopic extent are discussed. {copyright} {ital 1999 American Institute of Physics.}

  2. 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.

  3. Dehydrogenation of Formic Acid by Heterogeneous Catalysts.

    PubMed

    Li, Jun; Zhu, Qi-Long; Xu, Qiang

    2015-01-01

    Formic acid has recently been considered as one of the most promising hydrogen storage materials. The basic concept is briefly discussed and the research progress is detailledly reviewed on the dehydrogenation of aqueous formic acid by heterogeneous catalysts. PMID:26507481

  4. HETEROGENOUS PHOTOREACTION OF FORMALDEHYDE WITH HYDROXYL RADICALS

    EPA Science Inventory

    Atmospheric heterogeneous photoreactions occur between formaldehyde and hydroxyl radicals to produce formic acid. hese photoreactions not only occur in clouds, but also in other tropospheric hydrometeors such as precipitation and dew droplets. xperiments were performed by irradia...

  5. 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. PMID:24932226

  6. A High Throughput Micro-Chamber Array Device for Single Cell Clonal Cultivation and Tumor Heterogeneity Analysis

    PubMed Central

    Shen, Feng-Min; Zhu, Lian; Ye, Heng; Yang, Yu-Jun; Pang, Dai-Wen; Zhang, Zhi-Ling

    2015-01-01

    Recently, single cell cloning techniques have been gradually developed benefited from their important roles in monoclonal antibody screening, tumor heterogeneity research fields, etc. In this study, we developed a high throughput device containing 1400 lateral chambers to efficiently isolate single cells and carry out long-term single cell clonal cultivation as well as tumor heterogeneity studies. Most of the isolated single cells could proliferate normally nearly as long as three weeks and hundreds of clones could be formed once with one device, which made it possible to study tumor heterogeneity at single cell level. The device was further used to examine tumor heterogeneity such as morphology, growth rate, anti-cancer drug tolerance as well as adenosine triphosphate-binding cassette (ABC) transporter ABCG2 protein expression level. Except for the single cell isolation and tumor heterogeneity studies, the device is expected to be used as an excellent platform for drug screening, tumor biomarker discovering and tumor metastasis assay. PMID:26149707

  7. Heterogeneous reactions in aircraft gas turbine engines

    NASA Astrophysics Data System (ADS)

    Brown, R. C.; Miake-Lye, R. C.; Lukachko, S. P.; Waitz, I. A.

    2002-05-01

    One-dimensional flow models and unity probability heterogeneous rate parameters are used to estimate the maximum effect of heterogeneous reactions on trace species evolution in aircraft gas turbines. The analysis includes reactions on soot particulates and turbine/nozzle material surfaces. Results for a representative advanced subsonic engine indicate the net change in reactant mixing ratios due to heterogeneous reactions is <10-6 for O2, CO2, and H2O, and <10-10 for minor combustion products such as SO2 and NO2. The change in the mixing ratios relative to the initial values is <0.01%. Since these estimates are based on heterogeneous reaction probabilities of unity, the actual changes will be even lower. Thus, heterogeneous chemistry within the engine cannot explain the high conversion of SO2 to SO3 which some wake models require to explain the observed levels of volatile aerosols. Furthermore, turbine heterogeneous processes will not effect exhaust NOx or NOy levels.

  8. 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. PMID:25807041

  9. Regional Heterogenity In Ceres' Subsurface

    NASA Astrophysics Data System (ADS)

    Raymond, Carol A.; Marchi, Simone; Bland, Michael T.; Castillo-Rogez, Julie C.; Park, Ryan S.; Russell, Christopher T.; Hughson, Kynan G.; Scully, Jennifer E. C.

    2016-04-01

    subdued or degraded rims. Regional-scale variations in roughness and cratering could be caused by varia-bility in the viscosity of the volatile-rich shell, or could reflect a resurfacing process. However, these two processes would yield differences that would help to distinguish them. In the case of relaxation, the degree of crater obilitera-tion would be a function of crater size and age, and possibly would vary with latitude (temperature). If caused by resurfacing, the crater size frequency distribution would be similar to but offset with respect to that of the surround-ing terrains. Some correlation is seen between variations in the visible spectrum and the areas of smooth terrain. In either case, relaxation or resurfacing would indicate an internal process that resulted in primordial heterogeneity in the volatile-rich shell, or subsequent convective processes that drove regional resurfacing.

  10. Overview of medium heterogeneity and transport processes

    SciTech Connect

    Tsang, Y.; Tsang, C.F.

    1993-11-01

    Medium heterogeneity can have significant impact on the behavior of solute transport. Tracer breakthrough curves from transport in a heterogeneous medium are distinctly different from that in a homogeneous porous medium. Usually the shape of the breakthrough curves are highly non-symmetrical with a fast rise at early times and very long tail at late times, and often, they consist of multiple peaks. Moreover, unlike transport in a homogeneous medium where the same transport parameters describe the entire medium, transport through heterogeneous media gives rise to breakthrough curves which have strong spatial dependence. These inherent characteristics of transport in heterogeneous medium present special challenge to the performance assessment of a potential high level nuclear waste repository with respect to the possible release of radio nuclides to the accessible environment. Since an inherently desirable site characteristic for a waste repository is that flow and transport should be slow, then transport measurements in site characterization efforts will necessarily be spatially small and temporally short compare to the scales which are of relevance to performance assessment predictions. In this paper we discuss the role of medium heterogeneity in site characterization and performance assessment. Our discussion will be based on a specific example of a 3D heterogeneous stochastic model of a site generally similar to, the Aespoe Island, the site of the Hard Rock Laboratory in Southern Sweden. For our study, alternative 3D stochastic fields of hydraulic conductivities conditioned on ``point`` measurements shall be generated. Results of stochastic flow and transport simulations would be used to address the issues of (1) the relationship of tracer breakthrough with the structure of heterogeneity, and (2) the inference from small scale testing results to large scale and long term predictions.

  11. Natural heterogeneity of α2-antiplasmin: functional and clinical consequences.

    PubMed

    Abdul, Shiraazkhan; Leebeek, Frank W G; Rijken, Dingeman C; Uitte de Willige, Shirley

    2016-02-01

    Human α2-antiplasmin (α2AP, also called α2-plasmin inhibitor) is the main physiological inhibitor of the fibrinolytic enzyme plasmin. α2AP inhibits plasmin on the fibrin clot or in the circulation by forming plasmin-antiplasmin complexes. Severely reduced α2AP levels in hereditary α2AP deficiency may lead to bleeding symptoms, whereas increased α2AP levels have been associated with increased thrombotic risk. α2AP is a very heterogeneous protein. In the circulation, α2AP undergoes both amino terminal (N-terminal) and carboxyl terminal (C-terminal) proteolytic modifications that significantly modify its activities. About 70% of α2AP is cleaved at the N terminus by antiplasmin-cleaving enzyme (or soluble fibroblast activation protein), resulting in a 12-amino-acid residue shorter form. The glutamine residue that serves as a substrate for activated factor XIII becomes more efficient after removal of the N terminus, leading to faster crosslinking of α2AP to fibrin and consequently prolonged clot lysis. In approximately 35% of circulating α2AP, the C terminus is absent. This C terminus contains the binding site for plasmin(ogen), the key component necessary for the rapid and efficient inhibitory mechanism of α2AP. Without its C terminus, α2AP can no longer bind to the lysine binding sites of plasmin(ogen) and is only a kinetically slow plasmin inhibitor. Thus, proteolytic modifications of the N and C termini of α2AP constitute major regulatory mechanisms for the inhibitory function of the protein and may therefore have clinical consequences. This review presents recent findings regarding the main aspects of the natural heterogeneity of α2AP with particular focus on the functional and possible clinical implications. PMID:26626994

  12. Heterogeneous physicochemistry of the winter polar stratosphere

    NASA Technical Reports Server (NTRS)

    Turco, R. P.; Toon, O. B.

    1988-01-01

    Present chemical theories of the Antarctic ozone hole assume that heterogeneous reactions involving polar stratospheric clouds (PSCs) are the precursor of springtime ozone depletions. However, none of the theories quantify the rates of proposed heterogeneous processed, and none utilize the extensive data base on PSC's. Thus, all of the theories must be considered incomplete until the heterogeneous mechanisms are properly defined. A unified treatment developed of the cloud related processes, both physical and chemical, and the importance of these processes using observation data is calibrated. The rates are compared competitive heterogeneous processes to place reasonable limits on critical mechanisms such as the denitrification and dechlorination of the polar winter stratosphere. Among the subjects addressed here are the physical/chemical properties of PSC's including their relevant microphysical, optical and compositional characteristics, mass transfer rates of gaseous constituents to cloud particles, adsorption, accommodation and sticking coefficients on cloud particles, time constants for condensation, absorption and other microphysical processes, effects of solubility and vapor pressure on cloud composition, the statistics of cloud processing of chemically active condensible species, rate limiting steps in heterogeneous chemical reactions, and the nonlinear dependence of ozone loss on physical and chemical parameters.

  13. 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.

  14. 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. PMID:26213370

  15. On the origin of sperm epigenetic heterogeneity.

    PubMed

    Laurentino, Sandra; Borgmann, Jennifer; Gromoll, Jörg

    2016-05-01

    The influence of epigenetic modifications on reproduction and on the function of male germ cells has been thoroughly demonstrated. In particular, aberrant DNA methylation levels in sperm have been associated with abnormal sperm parameters, lower fertilization rates and impaired embryo development. Recent reports have indicated that human sperm might be epigenetically heterogeneous and that abnormal DNA methylation levels found in the sperm of infertile men could be due to the presence of sperm populations with different epigenetic quality. However, the origin and the contribution of different germ cell types to this suspected heterogeneity remain unclear. In this review, we focus on sperm epigenetics at the DNA methylation level and its importance in reproduction. We take into account the latest developments and hypotheses concerning the functional significance of epigenetic heterogeneity coming from the field of stem cell and cancer biology and discuss the potential importance and consequences of sperm epigenetic heterogeneity for reproduction, male (in)fertility and assisted reproductive technologies (ART). Based on the current information, we propose a model in which spermatogonial stem cell variability, either intrinsic or due to external factors (such as endocrine action and environmental stimuli), can lead to epigenetic sperm heterogeneity, sperm epimutations and male infertility. The elucidation of the precise causes for epimutations, the conception of adequate therapeutic options and the development of sperm selection technologies based on epigenetic quality should be regarded as crucial to the improvement of ART outcome in the near future. PMID:26884419

  16. Implications of Heterogeneity in Multiple Myeloma

    PubMed Central

    de Mel, Sanjay; Lim, Su Hong; Tung, Moon Ley; Chng, Wee-Joo

    2014-01-01

    Multiple myeloma is the second most common hematologic malignancy in the world. Despite improvement in outcome, the disease is still incurable for most patients. However, not all myeloma are the same. With the same treatment, some patients can have very long survival whereas others can have very short survival. This suggests that there is underlying heterogeneity in myeloma. Studies over the years have revealed multiple layers of heterogeneity. First, clinical parameters such as age and tumor burden could significantly affect outcome. At the genetic level, there are also significant heterogeneity ranging for chromosome numbers, genetic translocations, and genetic mutations. At the clonal level, there appears to be significant clonal heterogeneity with multiple clones coexisting in the same patient. At the cell differentiation level, there appears to be a hierarchy of clonally related cells that have different clonogenic potential and sensitivity to therapies. These levels of complexities present challenges in terms of treatment and prognostication as well as monitoring of treatment. However, if we can clearly delineate and dissect this heterogeneity, we may also be presented with unique opportunities for precision and personalized treatment of myeloma. Some proof of concepts of such approaches has been demonstrated. PMID:25101266

  17. Multiscale hyporheic exchange through strongly heterogeneous sediments

    NASA Astrophysics Data System (ADS)

    Pryshlak, Timothy T.; Sawyer, Audrey H.; Stonedahl, Susa H.; Soltanian, Mohamad Reza

    2015-11-01

    Heterogeneity in hydraulic conductivity (K) and channel morphology both control surface water-groundwater exchange (hyporheic exchange), which influences stream ecosystem processes and biogeochemical cycles. Here we show that heterogeneity in K is the dominant control on exchange rates, residence times, and patterns in hyporheic zones with abrupt lithologic contrasts. We simulated hyporheic exchange in a representative low-gradient stream with 300 different bimodal K fields composed of sand and silt. Simulations span five sets of sand-silt ratios and two sets of low and high K contrasts (1 and 3 orders of magnitude). Heterogeneity increases interfacial flux by an order of magnitude relative to homogeneous cases, drastically changes the shape of residence time distributions, and decreases median residence times. The positioning of highly permeable sand bodies controls patterns of interfacial flux and flow paths. These results are remarkably different from previous studies of smooth, continuous K fields that indicate only moderate effects on hyporheic exchange. Our results also show that hyporheic residence times are least predictable when sand body connectivity is low. As sand body connectivity increases, the expected residence time distribution (ensemble average for a given sand-silt ratio) remains approximately constant, but the uncertainty around the expectation decreases. Including strong heterogeneity in hyporheic models is imperative for understanding hyporheic fluxes and solute transport. In streams with strongly heterogeneous sediments, characterizing lithologic structure is more critical for predicting hyporheic exchange metrics than characterizing channel morphology.

  18. Integrated Design and Analysis for Heterogeneous Objects

    NASA Astrophysics Data System (ADS)

    Qian, Xiaoping; Yang, Pinghai

    2008-02-01

    The recent advancement of solid freeform fabrication, design techniques and fundamental understanding of material properties in functionally graded material objects has made it possible to design and fabricate multifunctional heterogeneous objects. In this paper, we present an integrated design and analysis approach for heterogeneous object realization, which employs a unified design and analysis model based on B-splines and allows for direct interaction between the design and analysis model without a laborious meshing operation. In the design module, a new approach for intuitively modeling multi-material objects, termed heterogeneous lofting, is presented. In the analysis module, a novel graded B-spline finite element solution procedure is described, which gives orders of magnitude better convergence rate in comparison with current methods, as demonstrated in several case studies. Further advantages of this approach include simplified mesh construction, exact geometry/material composition representation and easy extraction of iso-material surface for manufacturing process planning.

  19. 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.

  20. Seismoelectric effects due to mesoscopic heterogeneities

    NASA Astrophysics Data System (ADS)

    Jougnot, Damien; Rubino, J. GermáN.; Carbajal, Marina Rosas; Linde, Niklas; Holliger, Klaus

    2013-05-01

    While the seismic effects of wave-induced fluid flow due to mesoscopic heterogeneities have been studied for several decades, the role played by these types of heterogeneities on seismoelectric phenomena is largely unexplored. To address this issue, we have developed a novel methodological framework which allows for the coupling of wave-induced fluid flow, as inferred through numerical oscillatory compressibility tests, with the pertinent seismoelectric conversion mechanisms. Simulating the corresponding response of a water-saturated sandstone sample containing mesoscopic fractures, we demonstrate for the first time that these kinds of heterogeneities can produce measurable seismoelectric signals under typical laboratory conditions. Given that this phenomenon is sensitive to key hydraulic and mechanical properties, we expect that the results of this pilot study will stimulate further exploration on this topic in several domains of the Earth, environmental, and engineering sciences.

  1. 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.

  2. Correlation between spatial heterogeneity and local dynamics

    NASA Astrophysics Data System (ADS)

    Bhatia, Ritwik; Medvedev, Grigori; Corti, David; Caruthers, James

    2003-03-01

    Spatially correlated dynamic heterogeneity has been observed in binary Lennard-Jones mixtures [1]; however, the properites that cause the dynamic heterogeneity are not completely understood. In order to investigate the origin of the dynamic heterogeneity, we have examined the correlation of various thermodynamic properties in the region surrounding the mobile particles. Specifically, the simulation box is divided into a number of sub-volumes and the autocorrelation functions of the density, potential energy and thermal energy are determioned for each sub-volume. A comparison of autocorrelation functions of the sub-volumes containing a large number of mobile particles to sub-volumes containing no mobile particles is reported. [1] Donati et. al., Phys Rev E. v60, n3, p3107, 1999.

  3. 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.

  4. 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. PMID:25777748

  5. Stretchable heterogeneous composites with extreme mechanical gradients.

    PubMed

    Libanori, Rafael; Erb, Randall M; Reiser, Alain; Le Ferrand, Hortense; Süess, Martin J; Spolenak, Ralph; Studart, André R

    2012-01-01

    Heterogeneous composite materials with variable local stiffness are widespread in nature, but are far less explored in engineering structural applications. The development of heterogeneous synthetic composites with locally tuned elastic properties would allow us to extend the lifetime of functional devices with mechanically incompatible interfaces, and to create new enabling materials for applications ranging from flexible electronics to regenerative medicine. Here we show that heterogeneous composites with local elastic moduli tunable over five orders of magnitude can be prepared through the site-specific reinforcement of an entangled elastomeric matrix at progressively larger length scales. Using such a hierarchical reinforcement approach, we designed and produced composites exhibiting regions with extreme soft-to-hard transitions, while still being reversibly stretchable up to 350%. The implementation of the proposed methodology in a mechanically challenging application is illustrated here with the development of locally stiff and globally stretchable substrates for flexible electronics. PMID:23232395

  6. Dynamical robustness of coupled heterogeneous oscillators

    NASA Astrophysics Data System (ADS)

    Tanaka, Gouhei; Morino, Kai; Daido, Hiroaki; Aihara, Kazuyuki

    2014-05-01

    We study tolerance of dynamic behavior in networks of coupled heterogeneous oscillators to deterioration of the individual oscillator components. As the deterioration proceeds with reduction in dynamic behavior of the oscillators, an order parameter evaluating the level of global oscillation decreases and then vanishes at a certain critical point. We present a method to analytically derive a general formula for this critical point and an approximate formula for the order parameter in the vicinity of the critical point in networks of coupled Stuart-Landau oscillators. Using the critical point as a measure for dynamical robustness of oscillator networks, we show that the more heterogeneous the oscillator components are, the more robust the oscillatory behavior of the network is to the component deterioration. This property is confirmed also in networks of Morris-Lecar neuron models coupled through electrical synapses. Our approach could provide a useful framework for theoretically understanding the role of population heterogeneity in robustness of biological networks.

  7. Impact of Aquifer Heterogeneities on Autotrophic Denitrification.

    NASA Astrophysics Data System (ADS)

    McCarthy, A.; Roques, C.; Selker, J. S.; Istok, J. D.; Pett-Ridge, J. C.

    2015-12-01

    Nitrate contamination in groundwater is a big challenge that will need to be addressed by hydrogeologists throughout the world. With a drinking water standard of 10mg/L of NO3-, innovative techniques will need to be pursued to ensure a decrease in drinking water nitrate concentration. At the pumping site scale, the influence and relationship between heterogeneous flow, mixing, and reactivity is not well understood. The purpose of this project is to incorporate both physical and chemical modeling techniques to better understand the effect of aquifer heterogeneities on autotrophic denitrification. We will investigate the link between heterogeneous hydraulic properties, transport, and the rate of autotrophic denitrification. Data collected in previous studies in laboratory experiments and pumping site scale experiments will be used to validate the models. The ultimate objective of this project is to develop a model in which such coupled processes are better understood resulting in best management practices of groundwater.

  8. 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. PMID:27300913

  9. Stretchable heterogeneous composites with extreme mechanical gradients

    NASA Astrophysics Data System (ADS)

    Libanori, Rafael; Erb, Randall M.; Reiser, Alain; Le Ferrand, Hortense; Süess, Martin J.; Spolenak, Ralph; Studart, André R.

    2012-12-01

    Heterogeneous composite materials with variable local stiffness are widespread in nature, but are far less explored in engineering structural applications. The development of heterogeneous synthetic composites with locally tuned elastic properties would allow us to extend the lifetime of functional devices with mechanically incompatible interfaces, and to create new enabling materials for applications ranging from flexible electronics to regenerative medicine. Here we show that heterogeneous composites with local elastic moduli tunable over five orders of magnitude can be prepared through the site-specific reinforcement of an entangled elastomeric matrix at progressively larger length scales. Using such a hierarchical reinforcement approach, we designed and produced composites exhibiting regions with extreme soft-to-hard transitions, while still being reversibly stretchable up to 350%. The implementation of the proposed methodology in a mechanically challenging application is illustrated here with the development of locally stiff and globally stretchable substrates for flexible electronics.

  10. 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.

  11. 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. PMID:24465282

  12. Spatial Heterogeneity in the Tumor Microenvironment.

    PubMed

    Yuan, Yinyin

    2016-01-01

    Recent developments in studies of tumor heterogeneity have provoked new thoughts on cancer management. There is a desperate need to understand influence of the tumor microenvironment on cancer development and evolution. Applying principles and quantitative methods from ecology can suggest novel solutions to fulfil this need. We discuss spatial heterogeneity as a fundamental biological feature of the microenvironment, which has been largely ignored. Histological samples can provide spatial context of diverse cell types coexisting within the microenvironment. Advanced computer-vision techniques have been developed for spatial mapping of cells in histological samples. This has enabled the applications of experimental and analytical tools from ecology to cancer research, generating system-level knowledge of microenvironmental spatial heterogeneity. We focus on studies of immune infiltrate and tumor resource distribution, and highlight statistical approaches for addressing the emerging challenges based on these new approaches. PMID:27481837

  13. 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

  14. PDA based control of multiple heterogeneous robots

    NASA Astrophysics Data System (ADS)

    Kim, Tae Geun; Suk, Sung Youn; Park, Jae Suk; Kim, Sung Rock; Jeon, You Ju; Lee, Suk Gyu

    2005-12-01

    This paper proposed PDA based control of multiple heterogeneous robots by sharing information to perform surveillance and reconnaissance. Since heterogeneous groups were equipped with different sensor systems, they in particular allow a potentially greater degree of fault-tolerance compared to homogeneous groups. In this paper, unknown environment around robots was recognized efficiently by multiple robots using internet based PDA, where communication between PDA(user interface) and host PC(a controller for robots) is based on TCP/IP protocol. Each of the robots collects sensor data regarding its own motion and environment to share this information with the rest of he team during he update cycles.

  15. A framework for querying heterogeneous images repositories

    NASA Astrophysics Data System (ADS)

    Albanesi, Maria G.; Falchero, Emanuele; Guerrini, Federico; Ferretti, Marco

    2003-12-01

    In this paper we describe a new system for storing annotated images in a large database and querying by means of a dynamical retrieval of images through use of metadata. It is based on a three-tier architecture suitable for building a common gateway for accessing heterogeneous data. Based on XML schema of documents, the extraction of metadata is used for successive querying. We give an example on a database of astronomical and geographical images, but the method is quite general and can be applied to more general case of large heterogeneous databases.

  16. Heterogeneity in the muscle satellite cell population

    PubMed Central

    Biressi, Stefano; Rando, Thomas A.

    2010-01-01

    Satellite cells, the adult stem cells responsible for skeletal muscle regeneration, are defined by their location between the basal lamina and the fiber sarcolemma. Increasing evidence suggests that satellite cells represent a heterogeneous population of cells with distinct embryological origin and multiple levels of biochemical and functional diversity. This review focuses on the rich diversity of the satellite cell population based on studies across species. Ultimately, a more complete characterization of the heterogeneity of satellite cells will be essential to understand the functional significance in terms of muscle growth, homeostasis, tissue repair, and aging. PMID:20849971

  17. Effective permeabilities for model heterogeneous porous media

    SciTech Connect

    Otevo, C.; Rusinek, I. ); Saez, A.E. )

    1990-01-01

    This paper presents a technique to evaluate effective absolute permeabilities for heterogeneous porous media. The technique is based on a perturbation analysis of the equations of motion of a slightly compressible fluid in a homogeneous porous medium at low Reynolds numbers. The effective permeabilities can be calculated once the local geometry of the heterogeneous medium is specified. The technique is used to evaluate two- and three-dimensional effective vertical permeabilities in porous media with shale intercalations, including the case in which the porous matrix is anisotropic.

  18. 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.

  19. Random sphere packing model of heterogeneous propellants

    NASA Astrophysics Data System (ADS)

    Kochevets, Sergei Victorovich

    It is well recognized that combustion of heterogeneous propellants is strongly dependent on the propellant morphology. Recent developments in computing systems make it possible to start three-dimensional modeling of heterogeneous propellant combustion. A key component of such large scale computations is a realistic model of industrial propellants which retains the true morphology---a goal never achieved before. The research presented develops the Random Sphere Packing Model of heterogeneous propellants and generates numerical samples of actual industrial propellants. This is done by developing a sphere packing algorithm which randomly packs a large number of spheres with a polydisperse size distribution within a rectangular domain. First, the packing code is developed, optimized for performance, and parallelized using the OpenMP shared memory architecture. Second, the morphology and packing fraction of two simple cases of unimodal and bimodal packs are investigated computationally and analytically. It is shown that both the Loose Random Packing and Dense Random Packing limits are not well defined and the growth rate of the spheres is identified as the key parameter controlling the efficiency of the packing. For a properly chosen growth rate, computational results are found to be in excellent agreement with experimental data. Third, two strategies are developed to define numerical samples of polydisperse heterogeneous propellants: the Deterministic Strategy and the Random Selection Strategy. Using these strategies, numerical samples of industrial propellants are generated. The packing fraction is investigated and it is shown that the experimental values of the packing fraction can be achieved computationally. It is strongly believed that this Random Sphere Packing Model of propellants is a major step forward in the realistic computational modeling of heterogeneous propellant of combustion. In addition, a method of analysis of the morphology of heterogeneous

  20. Atmospheric pressure microwave assisted heterogeneous catalytic reactions.

    PubMed

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

    2007-01-01

    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. PMID:17909495

  1. 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.

  2. Metainference: A Bayesian inference method for heterogeneous systems

    PubMed Central

    Bonomi, Massimiliano; Camilloni, Carlo; Cavalli, Andrea; Vendruscolo, Michele

    2016-01-01

    Modeling a complex system is almost invariably a challenging task. The incorporation of experimental observations can be used to improve the quality of a model and thus to obtain better predictions about the behavior of the corresponding system. This approach, however, is affected by a variety of different errors, especially when a system simultaneously populates an ensemble of different states and experimental data are measured as averages over such states. To address this problem, we present a Bayesian inference method, called “metainference,” that is able to deal with errors in experimental measurements and with experimental measurements averaged over multiple states. To achieve this goal, metainference models a finite sample of the distribution of models using a replica approach, in the spirit of the replica-averaging modeling based on the maximum entropy principle. To illustrate the method, we present its application to a heterogeneous model system and to the determination of an ensemble of structures corresponding to the thermal fluctuations of a protein molecule. Metainference thus provides an approach to modeling complex systems with heterogeneous components and interconverting between different states by taking into account all possible sources of errors. PMID:26844300

  3. The Tyrosine Kinome Dictates Breast Cancer Heterogeneity and Therapeutic Responsiveness.

    PubMed

    Ha, Jacqueline R; Siegel, Peter M; Ursini-Siegel, Josie

    2016-09-01

    Phospho-tyrosine signaling networks control numerous biological processes including cellular differentiation, cell growth and survival, motility, and invasion. Aberrant regulation of the tyrosine kinome is a hallmark of malignancy and influences all stages of breast cancer progression, from initiation to the development of metastatic disease. The success of specific tyrosine kinase inhibitors strongly validates the clinical relevance of tyrosine phosphorylation networks in breast cancer pathology. However, a significant degree of redundancy exists within the tyrosine kinome. Numerous receptor and cytoplasmic tyrosine kinases converge on a core set of signaling regulators, including adaptor proteins and tyrosine phosphatases, to amplify pro-tumorigenic signal transduction pathways. Mutational activation, amplification, or overexpression of one or more components of the tyrosine kinome represents key contributing events responsible for the tumor heterogeneity that is observed in breast cancers. It is this molecular heterogeneity that has become the most significant barrier to durable clinical responses due to the development of therapeutic resistance. This review focuses on recent literature that supports a prominent role for specific components of the tyrosine kinome in the emergence of unique breast cancer subtypes and in shaping breast cancer plasticity, sensitivity to targeted therapies, and the eventual emergence of acquired resistance. J. Cell. Biochem. 117: 1971-1990, 2016. © 2016 Wiley Periodicals, Inc. PMID:27392311

  4. Metainference: A Bayesian inference method for heterogeneous systems.

    PubMed

    Bonomi, Massimiliano; Camilloni, Carlo; Cavalli, Andrea; Vendruscolo, Michele

    2016-01-01

    Modeling a complex system is almost invariably a challenging task. The incorporation of experimental observations can be used to improve the quality of a model and thus to obtain better predictions about the behavior of the corresponding system. This approach, however, is affected by a variety of different errors, especially when a system simultaneously populates an ensemble of different states and experimental data are measured as averages over such states. To address this problem, we present a Bayesian inference method, called "metainference," that is able to deal with errors in experimental measurements and with experimental measurements averaged over multiple states. To achieve this goal, metainference models a finite sample of the distribution of models using a replica approach, in the spirit of the replica-averaging modeling based on the maximum entropy principle. To illustrate the method, we present its application to a heterogeneous model system and to the determination of an ensemble of structures corresponding to the thermal fluctuations of a protein molecule. Metainference thus provides an approach to modeling complex systems with heterogeneous components and interconverting between different states by taking into account all possible sources of errors. PMID:26844300

  5. 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.

  6. Heterogeneous Hydration of p53/MDM2 Complex

    PubMed Central

    2015-01-01

    Water-mediated interactions play critical roles in biomolecular recognition processes. Explicit solvent molecular dynamics (MD) simulations and the variational implicit-solvent model (VISM) are used to study those hydration properties during binding for the biologically important p53/MDM2 complex. Unlike simple model solutes, in such a realistic and heterogeneous solute–solvent system with both geometrical and chemical complexity, the local water distribution sensitively depends on nearby amino acid properties and the geometric shape of the protein. We show that the VISM can accurately describe the locations of high and low density solvation shells identified by the MD simulations and can explain them by a local coupling balance of solvent–solute interaction potentials and curvature. In particular, capillary transitions between local dry and wet hydration states in the binding pocket are captured for interdomain distance between 4 to 6 Å, right at the onset of binding. The underlying physical connection between geometry and polarity is illustrated and quantified. Our study offers a microscopic and physical insight into the heterogeneous hydration behavior of the biologically highly relevant p53/MDM2 system and demonstrates the fundamental importance of hydrophobic effects for biological binding processes. We hope our study can help to establish new design rules for drugs and medical substances. PMID:24803860

  7. 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

  8. Integrating heterogeneous gene expression data for gene regulatory network modelling.

    PubMed

    Sîrbu, Alina; Ruskin, Heather J; Crane, Martin

    2012-06-01

    Gene regulatory networks (GRNs) are complex biological systems that have a large impact on protein levels, so that discovering network interactions is a major objective of systems biology. Quantitative GRN models have been inferred, to date, from time series measurements of gene expression, but at small scale, and with limited application to real data. Time series experiments are typically short (number of time points of the order of ten), whereas regulatory networks can be very large (containing hundreds of genes). This creates an under-determination problem, which negatively influences the results of any inferential algorithm. Presented here is an integrative approach to model inference, which has not been previously discussed to the authors' knowledge. Multiple heterogeneous expression time series are used to infer the same model, and results are shown to be more robust to noise and parameter perturbation. Additionally, a wavelet analysis shows that these models display limited noise over-fitting within the individual datasets. PMID:21948152

  9. The heterogeneity of store-operated calcium entry in melanoma

    PubMed Central

    Hooper, Robert; Zaidi, M. Raza; Soboloff, Jonathan

    2016-01-01

    Calcium is a key regulator of many physiological processes that are perturbed in cancer, such as migration, proliferation and apoptosis. The proteins STIM and Orai mediate store-operated calcium entry (SOCE), the main pathway for calcium entry in non-excitable cells. Changes in the expression and function of STIM and Orai have been found in a range of cancer types and thus implicated in disease progression. Here we discuss the role of STIM, Orai and the SOCE pathway in the progression of melanoma and explore how the heterogeneous nature of melanoma may explain the lack of consensus in the field regarding the role of SOCE in the progression of this disease. PMID:27417567

  10. Dynamic heterogeneity controls diffusion and viscosity near biological interfaces

    PubMed Central

    Pronk, Sander; Lindahl, Erik

    2014-01-01

    At a nanometer scale, the behavior of biological fluids is largely governed by interfacial physical chemistry. This may manifest as slowed or anomalous diffusion. Here we describe how measures developed for studying glassy systems allow quantitative measurement of interfacial effects on water dynamics, showing that correlated motions of particles near a surface result in a viscosity greater than anticipated from individual particle motions. This effect arises as a fundamental consequence of spatial heterogeneity on nanometer length scales and applies to any fluid near any surface. Increased interfacial viscosity also causes the classic finding that large solutes such as proteins diffuse much more slowly than predicted in bulk water. This has previously been treated via an empirical correction to the solute size: the hydrodynamic radius. Using measurements of quantities from theories of glass dynamics, we can now calculate diffusion constants from molecular details alone, eliminating the empirical correction factor. PMID:24398864

  11. A 'green' chitosan silver nanoparticle composite as a heterogeneous as well as micro-heterogeneous catalyst

    NASA Astrophysics Data System (ADS)

    Murugadoss, A.; Chattopadhyay, Arun

    2008-01-01

    In this paper, we report on the catalytic activity of a new metal nanoparticle-polymer composite consisting of Ag nanoparticles (NPs) and environmentally friendly ('green') chitosan. The polymer (chitosan) not only acted as the reducing agent for the metal ions, but also stabilized the product NPs by anchoring them. The majority of the particles produced in this way had sizes less than 5 nm. The catalytic activity of the composite was investigated photometrically by monitoring the reduction of 4-nitrophenol (4NP) in the presence of excess NaBH4 in water, under both heterogeneous and micro-heterogeneous conditions. The reaction was first order with respect to the concentration of 4NP. We also observed that the apparent rate constant, kapp, for the reaction was linearly dependent on the amount of Ag NPs present in the composite. Moreover, the turn-over frequency (TOF) of the catalyst was found to be (1.5 ± 0.3) × 10-3 s-1, when the reaction was carried out under heterogeneous conditions. The Ag NPs in the composite retained their catalytic activities even after using them for ten cycles. Our observations also suggest that the catalytic efficiency under micro-heterogeneous conditions is much higher than under heterogeneous conditions. Thus the composite we have represents an ideal case of an environmentally friendly and stable catalyst, which works under heterogeneous as well as micro-heterogeneous conditions with the advantage of nanoscopic particles as the catalyst.

  12. Uncovering the genomic heterogeneity of multifocal breast cancer

    PubMed Central

    Desmedt, Christine; Fumagalli, Debora; Pietri, Elisabetta; Zoppoli, Gabriele; Brown, David; Nik-Zainal, Serena; Gundem, Gunes; Rothé, Françoise; Majjaj, Samira; Garuti, Anna; Carminati, Enrico; Loi, Sherene; Van Brussel, Thomas; Boeckx, Bram; Maetens, Marion; Mudie, Laura; Vincent, Delphine; Kheddoumi, Naima; Serra, Luigi; Massa, Ilaria; Ballestrero, Alberto; Amadori, Dino; Salgado, Roberto; de Wind, Alexandre; Lambrechts, Diether; Piccart, Martine; Larsimont, Denis; Campbell, Peter J; Sotiriou, Christos

    2015-01-01

    Multifocal breast cancer (MFBC), defined as multiple synchronous unilateral lesions of invasive breast cancer, is relatively frequent and has been associated with more aggressive features than unifocal cancer. Here, we aimed to investigate the genomic heterogeneity between MFBC lesions sharing similar histopathological parameters. Characterization of different lesions from 36 patients with ductal MFBC involved the identification of non-silent coding mutations in 360 protein-coding genes (171 tumour and 36 matched normal samples). We selected only patients with lesions presenting the same grade, ER, and HER2 status. Mutations were classified as ‘oncogenic’ in the case of recurrent substitutions reported in COSMIC or truncating mutations affecting tumour suppressor genes. All mutations identified in a given patient were further interrogated in all samples from that patient through deep resequencing using an orthogonal platform. Whole-genome rearrangement screen was further conducted in 8/36 patients. Twenty-four patients (67%) had substitutions/indels shared by all their lesions, of which 11 carried the same mutations in all lesions, and 13 had lesions with both common and private mutations. Three-quarters of those 24 patients shared oncogenic variants. The remaining 12 patients (33%) did not share any substitution/indels, with inter-lesion heterogeneity observed for oncogenic mutation(s) in genes such as PIK3CA, TP53, GATA3, and PTEN. Genomically heterogeneous lesions tended to be further apart in the mammary gland than homogeneous lesions. Genome-wide analyses of a limited number of patients identified a common somatic background in all studied MFBCs, including those with no mutation in common between the lesions. To conclude, as the number of molecular targeted therapies increases and trials driven by genomic screening are ongoing, our findings highlight the presence of genomic inter-lesion heterogeneity in one-third, despite similar pathological features

  13. Intratumor Heterogeneity of ALK-Rearrangements and Homogeneity of EGFR-Mutations in Mixed Lung Adenocarcinoma

    PubMed Central

    Marino, Federica Zito; Liguori, Giuseppina; Aquino, Gabriella; La Mantia, Elvira; Bosari, Silvano; Ferrero, Stefano; Rosso, Lorenzo; Gaudioso, Gabriella; De Rosa, Nicla; Scrima, Marianna; Martucci, Nicola; La Rocca, Antonello; Normanno, Nicola; Morabito, Alessandro; Rocco, Gaetano; Botti, Gerardo; Franco, Renato

    2015-01-01

    Background Non Small Cell Lung Cancer is a highly heterogeneous tumor. Histologic intratumor heterogeneity could be ‘major’, characterized by a single tumor showing two different histologic types, and ‘minor’, due to at least 2 different growth patterns in the same tumor. Therefore, a morphological heterogeneity could reflect an intratumor molecular heterogeneity. To date, few data are reported in literature about molecular features of the mixed adenocarcinoma. The aim of our study was to assess EGFR-mutations and ALK-rearrangements in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas and adenosquamous carcinomas. Methods 590 Non Small Cell Lung Carcinomas tumor samples were revised in order to select mixed adenocarcinomas with available tumor components. Finally, only 105 mixed adenocarcinomas and 17 adenosquamous carcinomas were included in the study for further analyses. Two TMAs were built selecting the different intratumor histotypes. ALK-rearrangements were detected through FISH and IHC, and EGFR-mutations were detected through IHC and confirmed by RT-PCR. Results 10/122 cases were ALK-rearranged and 7 from those 10 showing an intratumor heterogeneity of the rearrangements. 12/122 cases were EGFR-mutated, uniformly expressing the EGFR-mutated protein in all histologic components. Conclusion Our data suggests that EGFR-mutations is generally homogeneously expressed. On the contrary, ALK-rearrangement showed an intratumor heterogeneity in both mixed adenocarcinomas and adenosquamous carcinomas. The intratumor heterogeneity of ALK-rearrangements could lead to a possible impact on the therapeutic responses and the disease outcomes. PMID:26422230

  14. 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

  15. Heterogeneous calretinin expression in the avian cochlear nucleus angularis.

    PubMed

    Bloom, S; Williams, A; MacLeod, K M

    2014-08-01

    Multiple calcium-binding proteins (CaBPs) are expressed at high levels and in complementary patterns in the auditory pathways of birds, mammals, and other vertebrates, but whether specific members of the CaBP family can be used to identify neuronal subpopulations is unclear. We used double immunofluorescence labeling of calretinin (CR) in combination with neuronal markers to investigate the distribution of CR-expressing neurons in brainstem sections of the cochlear nucleus in the chicken (Gallus gallus domesticus). While CR was homogeneously expressed in cochlear nucleus magnocellularis, CR expression was highly heterogeneous in cochlear nucleus angularis (NA), a nucleus with diverse cell types analogous in function to neurons in the mammalian ventral cochlear nucleus. To quantify the distribution of CR in the total NA cell population, we used antibodies against neuronal nuclear protein (NeuN), a postmitotic neuron-specific nuclear marker. In NA neurons, NeuN label was variably localized to the cell nucleus and the cytoplasm, and the intensity of NeuN immunoreactivity was inversely correlated with the intensity of CR immunoreactivity. The percentage of CR + neurons in NA increased from 31 % in embryonic (E)17/18 chicks, to 44 % around hatching (E21), to 51 % in postnatal day (P) 8 chicks. By P8, the distribution of CR + neurons was uniform, both rostrocaudal and in the tonotopic (dorsoventral) axis. Immunoreactivity for the voltage-gated potassium ion channel Kv1.1, used as a marker for physiological type, showed broad and heterogeneous postsynaptic expression in NA, but did not correlate with CR expression. These results suggest that CR may define a subpopulation of neurons within nucleus angularis. PMID:24752525

  16. 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.

  17. Heterogeneous nucleation in hypermonotectic aluminum alloys

    NASA Astrophysics Data System (ADS)

    Köhler, M.; Ratke, L.; Kaban, I.; Hoyer, W.

    2012-01-01

    Simple casting experiments were set up to solve the question, if heterogeneous nucleation of the liquid-liquid decomposition in monotectic systems is possible. Al-Pb alloys with different inoculants were solidified, and the resulting microstructure was analysed by SEM and X-ray microtomography. Pronounced changes in the distribution of the lead precipitations indicate that it is possible to trigger the nucleation.

  18. Heterogeneity: The key to failure forecasting

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    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.

  19. 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.

  20. Heterogeneity: The key to failure forecasting.

    PubMed

    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

  1. 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

  2. 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)

  3. 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…

  4. 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.

  5. Burning Fat Fuels Leukemic Stem Cell Heterogeneity.

    PubMed

    Thomas, Daniel; Majeti, Ravindra

    2016-07-01

    Obese leukemia patients exhibit reduced survival after chemotherapy, suggesting an important role of adipose tissue in disease progression. In this issue of Cell Stem Cell, Ye et al. (2016) reveal metabolic heterogeneity in leukemic stem cell (LSC) subpopulations and show that chemotherapy-resistant CD36+ LSCs co-opt gonadal adipose tissue to support their metabolism and survival. PMID:27392217

  6. Electron beam sterilisation of heterogeneous medical devices

    NASA Astrophysics Data System (ADS)

    Sadat, T.; Morisseau, MrD.; Ross, MissA.

    1993-07-01

    Electron beam radiation is used in the sterilisation of medical disposable devices. High energy, 10 MeV, electron beam linear accelerators are in use worldwide for this purpose. The dose distribution achieved in the products treated influences the efficiency of treatment. This paper looks at the dose distribution achieved with such machines and the methods used to define it in heterogeneous products.

  7. Mapping the Structure of Heterogeneous Materials

    NASA Technical Reports Server (NTRS)

    Strand, L. D.; Cohen, N. S.; Hernan, M. A.

    1986-01-01

    Image-processing microdensitometer/Fourier analyzer yields statistics of subcomponent distribution. Nondestructive method for studying structure heterogeneous materials uses energy-dispersive X-ray analysis in scanning electron microscope. Scanning microdensitometer/Fourier analyzer (SMFA) is applied to SEM images to obtain statistics about sample structure. Method originally developed for studying effect on combustion of fine structure of composite solid propellants.

  8. Sampling designs for heterogeneous snow distributions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Intensive snow surveys of mountain basins are the most accurate means of characterizing the heterogeneous mosaic of snow distribution typically present. The collection of survey data is however costly and time-consuming and important decisions are required to adequately sample larger basins. In this...

  9. Accelerating Mathematics Achievement Using Heterogeneous Grouping

    ERIC Educational Resources Information Center

    Burris, Carol Corbett; Heubert, Jay P.; Levin, Henry M.

    2006-01-01

    This longitudinal study examined the effects of providing an accelerated mathematics curriculum in heterogeneously grouped middle school classes in a diverse suburban school district. A quasi-experimental cohort design was used to evaluate subsequent completion of advanced high school math courses as well as academic achievement. Results showed…

  10. Phenotypic heterogeneity of Streptococcus mutans in dentin.

    PubMed

    Rupf, S; Hannig, M; Breitung, K; Schellenberger, W; Eschrich, K; Remmerbach, T; Kneist, S

    2008-12-01

    Information concerning phenotypic heterogeneity of Streptococcus mutans in carious dentin is sparse. Matrix-assisted laser-desorption/ionization-time-of-flight mass-spectrometry (MALDI-TOF-MS) facilitates the phenotypic differentiation of bacteria to the subspecies level. To verify a supposed influence of restorative treatment on the phenotypic heterogeneity of S. mutans, we isolated and compared a total of 222 S. mutans strains from dentin samples of 21 human deciduous molars during caries excavation (T(1)) and 8 wks (T(2)) after removal of the temporary restoration. Phenotypic heterogeneity was determined by MALDI-TOF-MS and hierarchical clustering. Thirty-six distinct S. mutans phenotypes could be identified. Although indistinguishable phenotypes were found in the same teeth at T(1) and T(2), as well as in different teeth of individual participants, the phenotypic heterogeneity increased significantly, from 1.4 phenotypes per S. mutans-positive dentin sample at T(1) to 2.2 phenotypes at T(2). We attribute this to an adaptation of S. mutans to the modified environment under the restoration following caries excavation. PMID:19029088

  11. Multilingual Federated Searching Across Heterogeneous Collections.

    ERIC Educational Resources Information Center

    Powell, James; Fox, Edward A.

    1998-01-01

    Describes a scalable system for searching heterogeneous multilingual collections on the World Wide Web. Details Searchable Database Markup Language (SearchDB-ML) for describing the characteristics of a search engine and its interface, and a protocol for requesting word translations between languages. (Author)

  12. 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.

  13. Heterogeneity of FFA responses or multiplexing?

    PubMed Central

    Ross, David A.; McGugin, Rankin W.; Gauthier, Isabel

    2014-01-01

    Recent work using cluster analysis of brain activity during movies revealed distinct clusters that respond to faces and different non-face categories in the fusiform face area (FFA). Because of the limited heterogeneity observed, these results could mean that FFA contains one population of cells capable of representing multiple categories. PMID:24360882

  14. 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.

  15. 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.

  16. Scaling the heterogeneously heated convective boundary layer

    NASA Astrophysics Data System (ADS)

    Van Heerwaarden, C.; Mellado, J.; De Lozar, A.

    2013-12-01

    We have studied the heterogeneously heated convective boundary layer (CBL) by means of large-eddy simulations (LES) and direct numerical simulations (DNS). What makes our study different from previous studies on this subject are our very long simulations in which the system travels through multiple states and that from there we have derived scaling laws. In our setup, a stratified atmosphere is heated from below by square patches with a high surface buoyancy flux, surrounded by regions with no or little flux. By letting a boundary layer grow in time we let the system evolve from the so-called meso-scale to the micro-scale regime. In the former the heterogeneity is large and strong circulations can develop, while in the latter the heterogeneity is small and does no longer influence the boundary layer structure. Within each simulation we can now observe the formation of a peak in kinetic energy, which represents the 'optimal' heterogeneity size in the meso-scale, and the subsequent decay of the peak and the development towards the transition to the micro-scale. We have created a non-dimensional parameter space that describes all properties of this system. By studying the previously described evolution for different combinations of parameters, we have derived three important conclusions. First, there exists a horizontal length scale of the heterogeneity (L) that is a function of the boundary layer height (h) and the Richardson (Ri) number of the inversion at the top of the boundary layer. This relationship has the form L = h Ri^(3/8). Second, this horizontal length scale L allows for expressing the time evolution, and thus the state of the system, as a ratio of this length scale and the distance between two patches Xp. This ratio thus describes to which extent the circulation fills up the space that exists between two patch centers. The timings of the transition from the meso- to the micro-scale collapse under this scaling for all simulations sharing the same flux

  17. 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.

  18. 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...

  19. Heterogeneity and the genetics of autism.

    PubMed Central

    Szatmari, P

    1999-01-01

    The objective of this review is to summarize recent data on the genetics of autism, highlight the evidence for genetic heterogeneity and extend the implications of these findings for the identification of susceptibility genes in this disorder. Family studies have shown that autism runs in families and twin studies indicate that the basis of that familial aggregation is genetic. As a result the prospects for the identification of susceptibility genes using either linkage or association studies are quite good. However, recent evidence is accumulating suggesting that the disorder is genetically heterogeneous; higher functioning individuals with autism may arise from separate genetic mechanisms that lower functioning ones. If true, this will make the detection of linkage and association much more difficult. PMID:10212560

  20. 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.

  1. Deciphering intratumor heterogeneity using cancer genome analysis.

    PubMed

    Ryu, Daeun; Joung, Je-Gun; Kim, Nayoung K D; Kim, Kyu-Tae; Park, Woong-Yang

    2016-06-01

    Intratumor heterogeneity within individual cancer tissues underlies the numerous phenotypes of cancer. Tumor subclones ultimately affect therapeutic outcomes due to their distinct molecular features. Drug-resistant subclones are present at a low frequency in tissues at the time of biopsy, but can also arise as a result of acquired somatic mutations. A number of different approaches have been utilized to understand the nature of intratumor heterogeneity. Clonal analysis using whole exome or genome sequencing data can help monitor subclones in the context of tumor progression. Multiregional biopsies permit the molecular characterization of subclones within tumors. Deep sequencing has also provided researchers with the ability to measure the low allele fraction variant within a small number of cells. Ultimately, single-cell sequencing will enable the identification of every minor population within a tumor microenvironment. In the clinical context, the ability to identify and monitor the subclonal architecture of a tumor is valuable for the development of precise cancer therapeutic methods. PMID:27126234

  2. Modeling heterogeneous polymer-grafted nanoparticle networks

    NASA Astrophysics Data System (ADS)

    Zhang, Tao; Mbanga, Badel; Yashin, Victor; Balazs, Anna

    Via a dynamic 3D computational approach, we simulate the heterogeneous polymer-grafted nanoparticle networks. The nanoparticles rigid cores are decorated with a corona of grafted polymers, which contain reactive functional groups at the chain ends. With the overlap of grafted polymers, these reactive groups can form weak labile bonds, which can reform after breakage, or stronger bonds, which rupture irreversibly and thus, the nanoparticles are interconnected by dual cross-links. Previous work has been done on homogeneous networks, while we introduce the heterogeneity by considering two types of particles having different reactive functional groups, so that the labile bond energy varies depending on types of the two end reactive groups. We study the effect of tensile and rotational deformations on the network morphology, and observe, in particular, the phase separation of two types of particles. Our results will provide guidelines for designing transformable material that can controllably change structure under mechanical action.

  3. Blind and myopic ants in heterogeneous networks.

    PubMed

    Hwang, S; Lee, D-S; Kahng, B

    2014-11-01

    The diffusion processes on complex networks may be described by different Laplacian matrices due to heterogeneous connectivity. Here we investigate the random walks of blind ants and myopic ants on heterogeneous networks: While a myopic ant hops to a neighbor node every step, a blind ant may stay or hop with probabilities that depend on node connectivity. By analyzing the trajectories of blind ants, we show that the asymptotic behaviors of both random walks are related by rescaling time and probability with node connectivity. Using this result, we show how the small eigenvalues of the Laplacian matrices generating the two random walks are related. As an application, we show how the return-to-origin probability of a myopic ant can be used to compute the scaling behaviors of the Edwards-Wilkinson model, a representative model of load balancing on networks. PMID:25493841

  4. Blind and myopic ants in heterogeneous networks

    NASA Astrophysics Data System (ADS)

    Hwang, S.; Lee, D.-S.; Kahng, B.

    2014-11-01

    The diffusion processes on complex networks may be described by different Laplacian matrices due to heterogeneous connectivity. Here we investigate the random walks of blind ants and myopic ants on heterogeneous networks: While a myopic ant hops to a neighbor node every step, a blind ant may stay or hop with probabilities that depend on node connectivity. By analyzing the trajectories of blind ants, we show that the asymptotic behaviors of both random walks are related by rescaling time and probability with node connectivity. Using this result, we show how the small eigenvalues of the Laplacian matrices generating the two random walks are related. As an application, we show how the return-to-origin probability of a myopic ant can be used to compute the scaling behaviors of the Edwards-Wilkinson model, a representative model of load balancing on networks.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Beyond relationships between homogeneous and heterogeneous catalysis

    SciTech Connect

    Dixon, David A.; Katz, Alexander; Arslan, Ilke; Gates, Bruce C.

    2014-08-13

    Scientists who regard catalysis as a coherent field have been striving for decades to articulate the fundamental unifying principles. But because these principles seem to be broader than chemistry, chemical engineering, and materials science combined, catalytic scientists commonly interact within the sub-domains of homogeneous, heterogeneous, and bio-catalysis, and increasingly within even narrower domains such as organocatalysis, phase-transfer catalysis, acid-base catalysis, zeolite catalysis, etc. Attempts to unify catalysis have motivated researchers to find relationships between homogeneous and heterogeneous catalysis and to mimic enzymes. These themes have inspired vibrant international meetings and workshops, and we have benefited from the idea exchanges and have some thoughts about a path forward.

  10. 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.

  11. 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.

  12. Maintaining robust connectivity in heterogeneous robotic networks

    NASA Astrophysics Data System (ADS)

    Cruz, P.; Fierro, R.; Lu, W.; Ferrari, S.

    2013-05-01

    In this paper, we are interested in exploiting the heterogeneity of a robotic network made of ground and aerial agents to sense multiple targets in a cluttered environment. Maintaining wireless communication on this type of networks is fundamentally important specially for cooperative purposes. The proposed heterogeneous network consists of ground sensors, e.g., OctoRoACHes, and aerial routers, e.g., quadrotors. Adaptive potential field methods are used to coordinate the ground mobile sensors. Moreover, a reward function for the aerial mobile wireless routers is formulated to guarantee communication coverage among the ground sensors and a fixed base station. A sub-optimal controller is proposed based on an approximate control policy iteration technique. Simulation results of a case study are presented to illustrate the proposed methodology.

  13. Fluorescence lifetime measurements in heterogeneous scattering medium

    NASA Astrophysics Data System (ADS)

    Nishimura, Goro; Awasthi, Kamlesh; Furukawa, Daisuke

    2016-07-01

    Fluorescence lifetime in heterogeneous multiple light scattering systems is analyzed by an algorithm without solving the diffusion or radiative transfer equations. The algorithm assumes that the optical properties of medium are constant in the excitation and emission wavelength regions. If the assumption is correct and the fluorophore is a single species, the fluorescence lifetime can be determined by a set of measurements of temporal point-spread function of the excitation light and fluorescence at two different concentrations of the fluorophore. This method is not dependent on the heterogeneity of the optical properties of the medium as well as the geometry of the excitation-detection on an arbitrary shape of the sample. The algorithm was validated by an indocyanine green fluorescence in phantom measurements and demonstrated by an in vivo measurement.

  14. Satellite Cell Heterogeneity in Skeletal Muscle Homeostasis.

    PubMed

    Tierney, Matthew T; Sacco, Alessandra

    2016-06-01

    The cellular turnover required for skeletal muscle maintenance and repair is mediated by resident stem cells, also termed satellite cells. Satellite cells normally reside in a quiescent state, intermittently entering the cell cycle to fuse with neighboring myofibers and replenish the stem cell pool. However, the mechanisms by which satellite cells maintain the precise balance between self-renewal and differentiation necessary for long-term homeostasis remain unclear. Recent work has supported a previously unappreciated heterogeneity in the satellite cell compartment that may underlie the observed variability in cell fate and function. In this review, we examine the work supporting this notion as well as the potential governing principles, developmental origins, and principal determinants of satellite cell heterogeneity. PMID:26948993

  15. Heterogeneous distribution of metabolites across plant species

    NASA Astrophysics Data System (ADS)

    Takemoto, Kazuhiro; Arita, Masanori

    2009-07-01

    We investigate the distribution of flavonoids, a major category of plant secondary metabolites, across species. Flavonoids are known to show high species specificity, and were once considered as chemical markers for understanding adaptive evolution and characterization of living organisms. We investigate the distribution among species using bipartite networks, and find that two heterogeneous distributions are conserved among several families: the power-law distributions of the number of flavonoids in a species and the number of shared species of a particular flavonoid. In order to explain the possible origin of the heterogeneity, we propose a simple model with, essentially, a single parameter. As a result, we show that two respective power-law statistics emerge from simple evolutionary mechanisms based on a multiplicative process. These findings provide insights into the evolution of metabolite diversity and characterization of living organisms that defy genome sequence analysis for different reasons.

  16. Psoriatic arthritis: embracing pathogenetic and clinical heterogeneity?

    PubMed

    McInnes, Iain B

    2016-01-01

    Psoriatic arthritis (PsA) is a clinically heterogeneous condition of skin, joint, enthesis and bone that provides considerable unmet therapeutic need. Recent treatment advances have offered new opportunities to improve quality of life and long term well being for afflicted patients. It is timely therefore, to consider the underlying heterogeneity inherent in the disease from a pathologic aspect so as to best optimise the choice and order of therapeutic application over time. Herein I will discuss the various contributions made by immune pathways to discrete tissue compartments that in turn might allow a more targeted approach to the management of PsA in which different tissues express variable severity of involvement. PMID:27586796

  17. 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

  18. 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).

  19. Heterogeneous differential evolution for numerical optimization.

    PubMed

    Wang, Hui; Wang, Wenjun; Cui, Zhihua; Sun, Hui; Rahnamayan, Shahryar

    2014-01-01

    Differential evolution (DE) is a population-based stochastic search algorithm which has shown a good performance in solving many benchmarks and real-world optimization problems. Individuals in the standard DE, and most of its modifications, exhibit the same search characteristics because of the use of the same DE scheme. This paper proposes a simple and effective heterogeneous DE (HDE) to balance exploration and exploitation. In HDE, individuals are allowed to follow different search behaviors randomly selected from a DE scheme pool. Experiments are conducted on a comprehensive set of benchmark functions, including classical problems and shifted large-scale problems. The results show that heterogeneous DE achieves promising performance on a majority of the test problems. PMID:24683329

  20. Heterogeneously-Catalyzed Conversion of Carbohydrates

    NASA Astrophysics Data System (ADS)

    Vigier, Karine De Oliveira; Jérôme, François

    Polyfunctionality of carbohydrates and their low solubility in conventional organic solvents make rather complex their conversion to higher value added chemicals. Therefore, innovative processes are now strongly needed in order to increase the selectivity of these reactions. Here, we report an overview of the different heterogeneously-catalyzed processes described in the literature. In particular, hydrolysis, dehydration, oxidation, esterification, and etherification of carbohydrates are presented. We shall discuss the main structural parameters that need to be controlled and that permit the conversion of carbohydrates to bioproducts with good selectivity. The conversion of monosaccharides and disaccharides over solid catalysts, as well as recent advances in the heterogeneously-catalyzed conversion of cellulose, will be presented.

  1. 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

  2. Micromechanical modeling of heterogeneous energetic materials

    SciTech Connect

    Baer, M.R.; Kipp, M.E.; Swol, F. van

    1998-09-01

    In this work, the mesoscale processes of consolidation, deformation and reaction of shocked porous energetic materials are studied using shock physics analysis of impact on a collection of discrete HMX crystals. High resolution three-dimensional CTH simulations indicate that rapid deformation occurs at material contact points causing large amplitude fluctuations of stress states having wavelengths of the order of several particle diameters. Localization of energy produces hot-spots due to shock focusing and plastic work near grain boundaries as material flows to interstitial regions. These numerical experiments demonstrate that hot-spots are strongly influenced by multiple crystal interactions. Chemical reaction processes also produce multiple wave structures associated with particle distribution effects. This study provides new insights into the micromechanical behavior of heterogeneous energetic materials strongly suggesting that initiation and reaction of shocked heterogeneous materials involves states distinctly different than single jump state descriptions.

  3. Scroll waves pinned to moving heterogeneities

    NASA Astrophysics Data System (ADS)

    Ke, Hua; Zhang, Zhihui; Steinbock, Oliver

    2015-03-01

    Three-dimensional excitable systems can self-organize vortex patterns that rotate around one-dimensional phase singularities called filaments. In experiments with the Belousov-Zhabotinsky reaction and numerical simulations, we pin these scroll waves to translating inert cylinders and demonstrate the controlled repositioning of their rotation centers. If the pinning site extends only along a portion of the filament, the phase singularity is stretched out along the trajectory of the heterogeneity, which effectively writes the singularity into the system. Its trailing end point follows the heterogeneity with a lower velocity. This velocity, its dependence on the placement of the anchor, and the shape of the filament are explained by a curvature flow model.

  4. 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

    2016-01-01

    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

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

    PubMed

    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. Graphical Abstract ᅟ. PMID:26926442

  6. 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.

    2016-02-01

    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.

  7. 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. PMID:25790031

  8. 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.

  9. Method of assessing heterogeneity in images

    DOEpatents

    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.

  10. Mutational Heterogeneity in Melanoma: An Inconvenient Truth.

    PubMed

    Chang, Gregory A; Polsky, David

    2015-12-01

    Identification of oncogenic BRAF mutations in primary and metastatic melanomas supports a linear model of clonal evolution in cancer. Some mutational studies, however, have failed to identify BRAF mutations in metastatic tumors from patients with BRAFmutant primary melanomas. Using a combination of methods, Riveiro-Falkenbach et al. (2015) assert that technical issues, and not clonal heterogeneity, may explain prior discordant mutational results. PMID:26569584

  11. 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.

  12. [Heterogeneity of parasitic contamination of megalopolis soils].

    PubMed

    Aliautdinova, L V; Semenova, T A; Zavoĭkin, V D

    2011-01-01

    A morphological group ofwhipworm (Trichuris trichiura) eggs, which is detectable in the soil samples from the city's different control lands, shows that their origin is heterogeneous and it is possible to differentiate them by morphometric signs. At the same time is necessary to consider the specific biological factors contributing to soil contamination. Priority in parasitic soil contamination should be given to animals, dogs in particular, which is supported by the fact that the dog walking grounds exhibit the highest contamination rates. PMID:21797059

  13. 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.

  14. Bromine heterogenous chemistry in the troposhere

    SciTech Connect

    Abbatt, J.P.D.

    1996-10-01

    Motivated by the observations of boundary layer ozone loss which is correlated with high levels of bromine in the Arctic springtime, we have studied a number of heterogeneous interactions of tropospheric bromine species. The goal of this work is both to better define the source of inorganic bromine during this time of year and to determine the primary mechanism which keeps bromine in a photochemically active form.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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

  20. Heterogeneous nanofluids: natural convection heat transfer enhancement.

    PubMed

    Oueslati, Fakhreddine Segni; Bennacer, Rachid

    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

  1. Heterogeneous nanofluids: natural convection heat transfer enhancement

    NASA Astrophysics Data System (ADS)

    Oueslati, Fakhreddine Segni; Bennacer, Rachid

    2011-12-01

    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.

  2. {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.

  3. 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.

  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. Altering Emulsion Stability with Heterogeneous Surface Wettability.

    PubMed

    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

  6. Dynamical Heterogeneity in Glass-Forming Liquids

    NASA Astrophysics Data System (ADS)

    Glotzer, S. C.; Donati, C.

    1998-03-01

    The dynamical properties of cold, dense liquids differ dramatically from what is expected from extrapolation of their high temperature behavior. Recently, it has been proposed that such liquids may be dynamically heterogeneous over time scales which increase as the liquid cools. It has been suggested that, e.g., this is a mechanism for the stretched exponential decay of relaxation functions. Using extensive molecular dynamics simulations, we have investigated several supercooled liquids [1-4] ([1] W. Kob, C. Donati, S.J. Plimpton, P.H. Poole and S.C. Glotzer, PRL) 79 2827 (1997); [2] C. Donati, S.J. Plimpton, J.F. Douglas, W. Kob, P.H. Poole, and S.C. Glotzer, preprint; [3] Glotzer, Donati, Sciortino, unpublished; [4] Donati, Mountain, Glotzer, unpublished. to determine the extent and character of their dynamical heterogeneity. In the case of a binary Lennard-Jones mixture, e.g., we find [1] that particles of similar mobility form highly ramified clusters which grow with decreasing temperature [1]. Remarkably, their size appears to diverge as a power law at the mode coupling dynamical critical point [2]. We further find that the dynamical heterogeneity is related to the local potential energy landscape [2].

  7. Evidence for heterogeneous reactions in the atmosphere

    NASA Astrophysics Data System (ADS)

    Hidy, George M.

    Verification of heterogeneous reactions in the atmosphere through observations has remained a difficult, perhaps unachievable task because of the diversity and complexity of simultaneous chemical interactions which are suspected to occur. However, recent measurements combined with data analysis show promise for supplying both direct and indirect evidence of heterogeneous sulfur oxide and nitrogen oxide chemistry. Examples of useful methods are provided, which include (1) direct interpretation of observations in and near clouds and inference from thermodynamic properties, (2) inspection of combinations of aerometric data, (3) inference from statistical analysis, (4) comparison of observations with a validated air quality model, and (5) differences in particle size/composition distributions. An example involving thermodynamics is dry ammonium nitrate undergoing equilibrium transformation to the vapor phase, which is very sensitive to temperature. The other sample results presented suggest that heterogeneous oxidation of SO2 to sulfate may occur in the presence of suspended liquid water, particularly in winter, either through media buffered by absorbed ammonia or via suspended soot in droplets. No observational evidence has been found supporting metal-oxide- or ion-catalyzed reactions of sulfur dioxide or nitrogen oxides under atmospheric conditions.

  8. Heterogeneity and plasticity of T helper cells.

    PubMed

    Zhu, Jinfang; Paul, William E

    2010-01-01

    CD4 T helper (Th) cells play critical roles in adaptive immune responses. They recruit and activate other immune cells including B cells, CD8 T cells, macrophages, mast cells, neutrophils, eosinophils and basophils. Based on their functions, their pattern of cytokine secretion and their expression of specific transcription factors, Th cells, differentiated from naïve CD4 T cells, are classified into four major lineages, Th1, Th2, Th17 and T regulatory (Treg) cells, although other Th lineages may exist. Subsets of the same lineage may express different effector cytokines, reside at different locations or give rise to cells with different fates, whereas cells from different lineages may secrete common cytokines, such as IL-2, IL-9 and IL-10, resulting in massive heterogeneity of the Th cell population. In addition, the pattern of cytokine secretion may switch from that of one lineage toward another under certain circumstances, suggesting that Th cells are plastic. Tregs are also more heterogeneous and plastic than were originally thought. In this review, we summarize recent reports on heterogeneity and plasticity of Th cells, and discuss potential mechanisms and implications of such features that Th cells display. PMID:20010916

  9. Nanoscale Spatial Heterogeneity in Deep Eutectic Solvents.

    PubMed

    Kaur, Supreet; Gupta, Aditya; Kashyap, Hemant K

    2016-07-14

    In this article, we report a molecular dynamics simulation study on the X-ray and neutron scattering structures of deep eutectic solvents (DESs) and show that the DESs studied possess unique spatial heterogeneity on molecular length scales. The simulated X-ray and neutron scattering structure functions (S(q)s) of the DESs made of alkylamide + Li(+)/ClO4(-) display two peaks in the intermolecular region of the S(q)s. As a signature of nanoscale structural organization/heterogeneity, a prepeak is observed at 0.1 < q/Å(-1) < 0.4. The principal peak observed at around 1.2 < q/Å(-1) < 2 is rendered by short-distance inter- and intraspecies correlations. For the DESs studied, we demonstrate that nanoscale spatial heterogeneity is exhibited profoundly by the segregated domains of the constituent electrolyte, and the principal peak in S(q) is because of all sorts of close-contact correlations. The extent of nanoscale morphology as well as the strength of ion pairing is enhanced for the longer-tail alkylamide DES. PMID:27314310

  10. 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. PMID:19905095

  11. 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.

  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. 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

  14. Evolutionary optimization of cooperative heterogeneous teams

    NASA Astrophysics Data System (ADS)

    Soule, Terence; Heckendorn, Robert B.

    2007-04-01

    There is considerable interest in developing teams of autonomous, unmanned vehicles that can function in hostile environments without endangering human lives. However, heterogeneous teams, teams of units with specialized roles and/or specialized capabilities, have received relatively little attention. Specialized roles and capabilities can significantly increase team effectiveness and efficiency. Unfortunately, developing effective cooperation mechanisms is much more difficult in heterogeneous teams. Units with specialized roles or capabilities require specialized software that take into account the role and capabilities of both itself and its neighbors. Evolutionary algorithms, algorithms modeled on the principles of natural selection, have a proven track record in generating successful teams for a wide variety of problem domains. Using classification problems as a prototype, we have shown that typical evolutionary algorithms either generate highly effective teams members that cooperate poorly or poorly performing individuals that cooperate well. To overcome these weaknesses we have developed a novel class of evolutionary algorithms. In this paper we apply these algorithms to the problem of controlling simulated, heterogeneous teams of "scouts" and "investigators". Our test problem requires producing a map of an area and to further investigate "areas of interest". We compare several evolutionary algorithms for their ability to generate individually effective members and high levels of cooperation.

  15. Molecular heterogeneity of meningioma with INI1 mutation

    PubMed Central

    Rieske, P; Zakrzewska, M; Piaskowski, S; Jaskólski, D; Sikorska, B; Papierz, W; Zakrzewski, K; Liberski, P P

    2003-01-01

    Background: INI1 (hSNF5) mutations are linked to rhabdoid tumours, but mutations in meningiomas with hot spot mutations in position 377 have also been reported. Aims: To analyse the INI1 gene in meningioma. Methods: Exons 1, 4, 5, and 9 of the INI1 gene were analysed by the polymerase chain reaction and direct sequencing in 80 meningiomas. For all cases, western blotting of the INI1 protein was performed. Results: Only one of the 80 samples showed a cytosine insertion in codon 376. This mutation changed the open reading frame in almost the whole exon 9 and resulted in a longer hSNF5 protein. Complex analysis of the above described tumour sample by western blotting, DNA sequencing, and loss of heterozygosity (LOH) analysis showed that this particular meningioma consisted of heterogeneic cellular components. One of these components had a mutated INI1 gene, whereas in the other component INI1 was intact. Conclusions: INI1 mutation is a rare event in the molecular pathology of meningiomas. It is possible for the INI1 gene to be mutated in only a proportion of meningioma cells. PMID:14514925

  16. Seismoelectric effects caused by mesoscopic heterogeneities

    NASA Astrophysics Data System (ADS)

    Germán Rubino, J.; Jougnot, Damien; Rosas Carbajal, Marina; Linde, Niklas; Holliger, Klaus

    2013-04-01

    When a seismic wave propagates through a fluid saturated porous medium, it produces a relative motion between the fluid phase and the rock matrix. In the presence of an electric double layer at the fluid-solid interface, this movement introduces a separation of electrical charges which in turn generates a time-varying electrical source current and a resulting distribution of electrical potential. The presence of mesoscopic heterogeneities, that is, heterogeneities having sizes larger than the typical pore size but smaller than the prevailing wavelength, can induce a significant oscillatory fluid flow in response to the propagation of seismic waves. Indeed, the energy dissipation related to this phenomenon is considered to be one of the most common and important seismic attenuation mechanisms operating in the shallow part of the crust. Given that the amount of fluid flow produced by this phenomenon can be significant, a potentially important seismoelectric signal is also expected in such media. However, to the best of the authors' knowledge, the role played by mesoscopic wave-induced fluid flow on seismoelectric phenomenon is so far largely unexplored. In this work, we propose a numerical approach for computing seismoelectric signals related to the presence of mesoscopic heterogeneities. To this end, we consider a two-dimensional representative rock sample containing mesoscopic heterogeneities and apply an oscillatory compression on its top boundary. The solid phase is neither allowed to move on the bottom boundary nor to have horizontal displacements on the lateral boundaries and the fluid is not allowed to flow into or out of the sample. The fluid velocity field is determined by solving the quasi-static poroelastic equations in the space-frequency domain under the governing boundary conditions. Next, the seismoelectric conversion is calculated using the so-called effective electrical excess charge approach, which has been recently developed in streaming potential

  17. 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

  18. Proteomic analysis of transducin beta-subunit structural heterogeneity.

    PubMed

    Clack, James W; Juhl, Martha; Rice, Carol A; Li, Junyu; Witzmann, Frank A

    2003-10-01

    Partially purified transducin was resolved using two-dimensional gel electrophoresis (2-DE). Peptide mass fingerprinting of several different spots believed to correspond to the 37 kDa beta-subunit of transducin (T(beta)) was performed. Spots were excised and proteolyzed using modified trypsin. Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) was performed on the peptide mixture resulting from each spot. As many as six spots with different pI, ranging from 5.2 to 6.1, were observed when separated using 2-DE. MALDI peptide mass fingerprinting determined with high probability that all of the spots were the same gene product, guanine nucleotide-binding protein G(I)/G(S)/G(T) beta-subunit 1 (GNB1; T(beta1)). This suggested that post-translational modification was responsible for the differences in pI. Phosphorylation experiments showed that at least one T(beta1) spot was phosphorylated in vitro with [gamma-(32)P]ATP by an endogenous kinase. Treatment of T(beta) with alkaline phosphatase caused a large change in the spot pattern of T(beta), suggesting that phosphorylated T(beta) is a substrate for alkaline phosphatase. We conclude that T(beta1) constitutes over 99% of the T(beta) expressed in bovine rod outer segments and displays structural heterogeneity that is due to post-translational modification. We also conclude that some, but not all, of the heterogeneity observed is due to phosphorylation of Tb1. PMID:14595696

  19. 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.

  20. Marked heterogeneity of ERG expression in large primary prostate cancers.

    PubMed

    Minner, Sarah; Gärtner, Michael; Freudenthaler, Fabian; Bauer, Melanie; Kluth, Martina; Salomon, Georg; Heinzer, Hans; Graefen, Markus; Bokemeyer, Carsten; Simon, Ronald; Sauter, Guido; Schlomm, Thorsten; Wilczak, Waldemar

    2013-01-01

    Approximately 50% of prostate cancers are characterized by TMPRSS2 (transmembrane protease serine 2)-ERG (avian v-ets erythroblastosis virus E26 oncogene homolog) gene fusions resulting in an androgen-regulated overexpression of the transcription factor ERG. Some studies have suggested prognostic or predictive relevance of ERG status in prostate cancer. Such concepts could be impaired by extensive ERG heterogeneity in analyzed tumors. The aim of this study was to analyze the extent of heterogeneity for TMPRSS2-ERG fusion in prostate cancer. To enable large-scale studies on the extent of heterogeneity of biomarkers in prostate cancer, a heterogeneity tissue microarray containing samples from 10 different tumor blocks of 190 large prostate cancers selected from a consecutive series of 480 radical prostatectomies was developed. ERG expression was analyzed by immunohistochemistry. Positive ERG immunostaining was found in arrayed cancer-containing samples from 103 of the 178 analyzable patients (58%). ERG immunostaining was homogeneously positive in 29 prostate cancers (16%), whereas heterogeneous ERG positivity was seen in 74 cancers (42%). ERG heterogeneity was within one tumor focus (intrafocal heterogeneity) in 69 cases (93% of heterogeneous cases) and between different tumor foci (interfocal heterogeneity) in 5 cases (7%). Marked intrafocal heterogeneity challenges the concept of TMPRSS2-ERG fusion always representing an early step in prostate cancer development. Marked heterogeneity also compromises the concept of analyzing ERG status for treatment decisions in diagnostic needle core biopsies. PMID:22899295

  1. The role of heterogeneity in structuring spatial hierarchies

    SciTech Connect

    O'Neill, R.V.

    1987-07-01

    Following a paradigm based on Statistics and Newtonian physics, ecology often emphasizes the central tendency of observations and considers heterogeneity as extraneous noise. This approach ignores heterogeneity as an important measure of ecological systems. The present paper discusses two ways that heterogeneity characterizes the spatial hierarchies we observe on a landscape. As an exogenous factor, heterogeneity transforms a uniform landscape into a diverse array of habitats. Topography, moisture gradients, etc., create a spectrum of opportunities for species establishment. Heterogeneity compresses space, allowing a larger number of species to survive in a given area. As an endogenous factor, heterogeneity results from competition and natural selection acting to fill the available niches. In either case, heterogeneity is critical to understanding spatial hierarchies and community structure.

  2. Defining heterogeneity within bacterial populations via single cell approaches.

    PubMed

    Davis, Kimberly M; Isberg, Ralph R

    2016-08-01

    Bacterial populations are heterogeneous, which in many cases can provide a selective advantage during changes in environmental conditions. In some instances, heterogeneity exists at the genetic level, in which significant allelic variation occurs within a population seeded by a single cell. In other cases, heterogeneity exists due to phenotypic differences within a clonal, genetically identical population. A variety of mechanisms can drive this latter strategy. Stochastic fluctuations can drive differential gene expression, but heterogeneity in gene expression can also be driven by environmental changes sensed by individual cells residing in distinct locales. Utilizing multiple single cell approaches, workers have started to uncover the extent of heterogeneity within bacterial populations. This review will first describe several examples of phenotypic and genetic heterogeneity, and then discuss many single cell approaches that have recently been applied to define heterogeneity within bacterial populations. PMID:27273675

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

    PubMed

    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

  4. 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

  5. Network‐Informed Gene Ranking Tackles Genetic Heterogeneity in Exome‐Sequencing Studies of Monogenic Disease

    PubMed Central

    Schulz, Reiner; Weale, Michael E.; Southgate, Laura; Oakey, Rebecca J.; Simpson, Michael A.; Schlitt, Thomas

    2015-01-01

    ABSTRACT 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/. PMID:26394720

  6. 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.

  7. Emerging heterogeneous integrated photonic platforms on silicon

    NASA Astrophysics Data System (ADS)

    Fathpour, Sasan

    2015-05-01

    Silicon photonics has been established as a mature and promising technology for optoelectronic integrated circuits, mostly based on the silicon-on-insulator (SOI) waveguide platform. However, not all optical functionalities can be satisfactorily achieved merely based on silicon, in general, and on the SOI platform, in particular. Long-known shortcomings of silicon-based integrated photonics are optical absorption (in the telecommunication wavelengths) and feasibility of electrically-injected lasers (at least at room temperature). More recently, high two-photon and free-carrier absorptions required at high optical intensities for third-order optical nonlinear effects, inherent lack of second-order optical nonlinearity, low extinction ratio of modulators based on the free-carrier plasma effect, and the loss of the buried oxide layer of the SOI waveguides at mid-infrared wavelengths have been recognized as other shortcomings. Accordingly, several novel waveguide platforms have been developing to address these shortcomings of the SOI platform. Most of these emerging platforms are based on heterogeneous integration of other material systems on silicon substrates, and in some cases silicon is integrated on other substrates. Germanium and its binary alloys with silicon, III-V compound semiconductors, silicon nitride, tantalum pentoxide and other high-index dielectric or glass materials, as well as lithium niobate are some of the materials heterogeneously integrated on silicon substrates. The materials are typically integrated by a variety of epitaxial growth, bonding, ion implantation and slicing, etch back, spin-on-glass or other techniques. These wide range of efforts are reviewed here holistically to stress that there is no pure silicon or even group IV photonics per se. Rather, the future of the field of integrated photonics appears to be one of heterogenization, where a variety of different materials and waveguide platforms will be used for different purposes with

  8. Is ventilation heterogeneity related to asthma control?

    PubMed

    Svenningsen, Sarah; Nair, Parameswaran; Guo, Fumin; McCormack, David G; Parraga, Grace

    2016-08-01

    In asthma patients, magnetic resonance imaging (MRI) and the lung clearance index (LCI) have revealed persistent ventilation heterogeneity, although its relationship to asthma control is not well understood. Therefore, our goal was to explore the relationship of MRI ventilation defects and the LCI with asthma control and quality of life in patients with severe, poorly controlled asthma.18 patients with severe, poorly controlled asthma (mean±sd 46±12 years, six males/12 females) provided written informed consent to an ethics board approved protocol, and underwent spirometry, LCI and (3)He MRI during a single 2-h visit. Asthma control and quality of life were evaluated using the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). Ventilation heterogeneity was quantified using the LCI and (3)He MRI ventilation defect percent (VDP).All participants reported poorly controlled disease (mean±sd ACQ score=2.3±0.9) and highly heterogeneous ventilation (mean±sd VDP=12±11% and LCI=10.5±3.0). While VDP and LCI were strongly correlated (r=0.86, p<0.0001), in a multivariate model that included forced expiratory volume in 1 s, VDP and LCI, VDP was the only independent predictor of asthma control (R(2)=0.38, p=0.01). There was also a significantly worse VDP, but not LCI in asthma patients with an ACQ score >2 (p=0.04) and AQLQ score <5 (p=0.04), and a trend towards worse VDP (p=0.053), but not LCI in asthma patients reporting ≥1 exacerbation in the past 6 months.In patients with poorly controlled, severe asthma MRI ventilation, but not LCI was significantly worse in those with worse ACQ and AQLQ. PMID:27174885

  9. Diffusion of hydrogen in heterogeneous systems

    NASA Astrophysics Data System (ADS)

    Herrmann, A.; Schimmele, L.; Mössinger, J.; Hirscher, M.; Kronmüller, H.

    2001-04-01

    The effective long-range long-time tracer diffusivity Deff for interstitial diffusion of hydrogen through heterogeneous systems was studied theoretically for model systems consisting of isolated grains of material G embedded in a matrix of material M. Different solubilities of hydrogen in these two materials as well as different diffusivities are allowed for. Additionally, modified diffusion barriers at the phase boundaries were included in the diffusion model. The effect of different sizes, arrangements, and forms of the grains was also considered. Deff was determined by Monte Carlo (MC) simulations on simple lattice models of the systems described above. An equilibrium distribution of hydrogen atoms among the two constituent materials was assumed. Our main interest was focused on whether and how Deff may be related to mesoscopic or macroscopic quantities characterizing the heterogeneous system and its constituent materials, such as the volume fractions of the two materials, the fraction of lattice sites in the immediate vicinity of the phase boundary, the hydrogen concentrations cG and cM in the grains and in the matrix and the respective hydrogen diffusivities DG(cG) and DM(cM). In order to obtain good estimates for these relations in terms of analytic formulas, we attempted to model a heterogeneous system by a network of diffusion elements connected in series and in parallel, in analogy to an electric network. The properties of the basic connections, in parallel and in series, were studied on layered structures, for which analytic expressions for Deff could be derived. The network formulas for different grain-matrix systems were tested by comparing with results of MC simulations. In general, the network formulas describe the corresponding MC results for Deff fairly well. It was found that differences in the hydrogen solubilities in the two phases as well as modified energy barriers at the phase boundaries may have dramatic effects on Deff.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. A heterogeneous multiscale method for poroelasticity

    NASA Astrophysics Data System (ADS)

    Delgado, Paul M.

    In this thesis, we develop and analyze a heterogeneous multiscale model for coupled fluid flow and solid deformation in porous media based on operator splitting and finite volume method. The splitting method results in two elliptic multiscale PDE's in the form of a reaction diffusion equation and a linear elasticity equation. We extend our previous multiscale method from 1D to higher dimensions and develop new approaches for the inclusion of mixed boundary conditions and source terms. We derive an error estimate for our multiscale method and analyze the stability of our splitting method. We also test the effectiveness of our method in the case of steady state linear poroelasticity.

  15. Heterogeneously integrated microsystem-on-a-chip

    DOEpatents

    Chanchani, Rajen

    2008-02-26

    A microsystem-on-a-chip comprises a bottom wafer of normal thickness and a series of thinned wafers can be stacked on the bottom wafer, glued and electrically interconnected. The interconnection layer comprises a compliant dielectric material, an interconnect structure, and can include embedded passives. The stacked wafer technology provides a heterogeneously integrated, ultra-miniaturized, higher performing, robust and cost-effective microsystem package. The highly integrated microsystem package, comprising electronics, sensors, optics, and MEMS, can be miniaturized both in volume and footprint to the size of a bottle-cap or less.

  16. Dynamical Heterogeneity of the Glassy State

    NASA Astrophysics Data System (ADS)

    Wisitsorasak, Apiwat

    The understanding and the complete description of the glass transition are impeded by the complexity of nature of the glass. Parts of this complexity come from the emergence of long-lived inherent structures of a liquid at a temperature below which the activated reconfiguration events play a dominant role. Molecules in a glass change their locations through the activated process at a rate which varies throughout the glass owing to these local and aperiodic structures. Motions in one location also cause or relieve constrains, thereby altering the rate of transitions of neighboring regions. The key to understanding this problem is the interplay between the activated events that generate mobility and the transport of mobility. In the following we explore fluctuating mobility generation and transport in glasses to understand the dynamics of the glassy state within the framework of the random first order transition theory of glass. Fluctuating mobility generation and transport in the glass that arise from there being a distribution of local stability and thus effective temperature are treated by numerically solving stochastic continuum equations for mobility and fictive temperature fields. Fluctuating spatiotemporal structures in aging and rejuvenating glasses lead to dynamical heterogeneity in glasses with characteristics that are distinct from those found in the equilibrium liquid. We illustrate in this thesis how the heterogeneity in glasses gives rises of a non-Gaussian distribution of activation free energies, the stretching exponent, and the growth of characteristic lengths. These are studied along with the four-point dynamic correlation function. Asymmetric thermodynamic responses upon heating and cooling are also predicted to be the results of the heterogeneity and the out-of-equilibrium behavior of glasses below the glass transition temperature. Moreover the dynamical heterogeneity can lead to a growth front of mobility in rejuvenating glasses that emanates

  17. Bridge mediated ultrafast heterogeneous electron transfer

    NASA Astrophysics Data System (ADS)

    Ramakrishna, S.; Willig, F.; May, V.

    2002-01-01

    Bridge mediated photoinduced ultrafast heterogeneous electron transfer (ET) from a molecularly anchored chromophore to a semiconductor surface is modelled theoretically. The continuum levels of the semiconductor substrate are taken into account in the numerical calculations via a polynomial expansion. Electron transfer for the direct injection case in the strong coupling limit is studied and compared with cases where intermediate bridging states are successively introduced to weaken the effective electronic coupling. The role of vibronic coherences in the strong electronic coupling limit as well as in off-resonant bridge mediated electron transfer is also discussed.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Fractures in heterogeneous two-dimensional systems

    NASA Astrophysics Data System (ADS)

    Politi, Antonio; Zei, Maria

    2001-05-01

    A two-dimensional triangular lattice with bond disorder is used as a testing ground for fracture behavior in heterogeneous materials in strain-controlled conditions. Simulations are performed with two interaction potentials (harmonic and Lennard-Jones types) and different breaking thresholds. We study the strain range where the fracture progressively develops from the first to the last breakdown. Scaling properties with the lattice size are investigated: no qualitative difference is found between the two interaction potentials. Clustering properties of the broken bonds are also studied by grouping them into disjoint sets of connected bonds. Finally, the role of kinetic energy is analyzed by comparing overdamped with dissipationless dynamics.

  3. 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.

  4. 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

  5. CHIP buffers heterogeneous Bcl-2 expression levels to prevent augmentation of anticancer drug-resistant cell population.

    PubMed

    Tsuchiya, M; Nakajima, Y; Waku, T; Hiyoshi, H; Morishita, T; Furumai, R; Hayashi, Y; Kishimoto, H; Kimura, K; Yanagisawa, J

    2015-08-27

    Many types of cancer display heterogeneity in various features, including gene expression and malignant potential. This heterogeneity is associated with drug resistance and cancer progression. Recent studies have shown that the expression of a major protein quality control ubiquitin ligase, carboxyl terminus of Hsc70-interacting protein (CHIP), is negatively correlated with breast cancer clinicopathological stages and poor overall survival. Here we show that CHIP acts as a capacitor of heterogeneous Bcl-2 expression levels and prevents an increase in the anticancer drug-resistant population in breast cancer cells. CHIP knockdown in breast cancer cells increased variation in Bcl-2 expression levels, an antiapoptotic protein, among the cells. Our results also showed that CHIP knockdown increased the proportion of anticancer drug-resistant cells. These findings suggest that CHIP buffers variation in gene expression levels, affecting resistance to anticancer drugs. In single-cell clones derived from breast cancer cell lines, CHIP knockdown did not alter the variation in Bcl-2 expression levels and the proportion of anticancer drug-resistant cells. In contrast, when clonal cells were treated with a mutagen, the variation in Bcl-2 expression levels and proportion of anticancer drug-resistant cells were altered by CHIP knockdown. These results suggest that CHIP masks genetic variations to suppress heterogeneous Bcl-2 expression levels and prevents augmentation of the anticancer drug-resistant population of breast cancer cells. Because genetic variation is a major driver of heterogeneity, our results suggest that the degree of heterogeneity in expression levels is decided by a balance between genetic variation and the buffering capacity of CHIP. PMID:25435366

  6. Protein Condensation

    NASA Astrophysics Data System (ADS)

    Gunton, James D.; Shiryayev, Andrey; Pagan, Daniel L.

    2007-09-01

    Preface; 1. Introduction; 2. Globular protein structure; 3. Experimental methods; 4. Thermodynamics and statistical mechanics; 5. Protein-protein interactions; 6. Theoretical studies of equilibrium; 7. Nucleation theory; 8. Experimental studies of nucleation; 9. Lysozyme; 10. Some other globular proteins; 11. Membrane proteins; 12. Crystallins and cataracts; 13. Sickle hemoglobin and sickle cell anemia; 14, Alzheimer's disease; Index.

  7. Protein Condensation

    NASA Astrophysics Data System (ADS)

    Gunton, James D.; Shiryayev, Andrey; Pagan, Daniel L.

    2014-07-01

    Preface; 1. Introduction; 2. Globular protein structure; 3. Experimental methods; 4. Thermodynamics and statistical mechanics; 5. Protein-protein interactions; 6. Theoretical studies of equilibrium; 7. Nucleation theory; 8. Experimental studies of nucleation; 9. Lysozyme; 10. Some other globular proteins; 11. Membrane proteins; 12. Crystallins and cataracts; 13. Sickle hemoglobin and sickle cell anemia; 14, Alzheimer's disease; Index.

  8. Mutation-selection models of coding sequence evolution with site-heterogeneous amino acid fitness profiles.

    PubMed

    Rodrigue, Nicolas; Philippe, Hervé; Lartillot, Nicolas

    2010-03-01

    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

  9. 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. PMID:26407102

  10. 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.

  11. Scaling of Waves in Heterogeneous Materials

    NASA Astrophysics Data System (ADS)

    Vogler, Tracy

    2011-06-01

    The fourth power scaling of strain rate with stress described by Swegle and Grady describes steady waves in many homogeneous materials, but heterogeneous materials can display different scaling relationships. In particular, layered materials exhibit a second power scaling of strain rate with stress, while first power scaling has been observed in granular materials. To better understand these scaling behaviors, numerical simulations of wave propagation in layered and granular materials are performed. The simulations demonstrate that the heterogeneous nature of these materials can cause behavior similar to what has historically been termed viscosity when observed in homogeneous materials. From these simulations, non-dimensional groups that control the scaling of the waves are identified. These groups collapse the available experimental data reasonably well onto a single curve. Finally, a simple model for the first power scaling in granular materials is proposed that illustrates the importance of void space between particles to the wave structure. Sandia National Laboratories is a multi-program laboratory operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin company, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  12. MULTIGRID HOMOGENIZATION OF HETEROGENEOUS POROUS MEDIA

    SciTech Connect

    Dendy, J.E.; Moulton, J.D.

    2000-10-01

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL); this report, however, reports on only two years research, since this project was terminated at the end of two years in response to the reduction in funding for the LDRD Program at LANL. The numerical simulation of flow through heterogeneous porous media has become a vital tool in forecasting reservoir performance, analyzing groundwater supply and predicting the subsurface flow of contaminants. Consequently, the computational efficiency and accuracy of these simulations is paramount. However, the parameters of the underlying mathematical models (e.g., permeability, conductivity) typically exhibit severe variations over a range of significantly different length scales. Thus the numerical treatment of these problems relies on a homogenization or upscaling procedure to define an approximate coarse-scale problem that adequately captures the influence of the fine-scale structure, with a resultant compromise between the competing objectives of computational efficiency and numerical accuracy. For homogenization in models of flow through heterogeneous porous media, We have developed new, efficient, numerical, multilevel methods, that offer a significant improvement in the compromise between accuracy and efficiency. We recently combined this approach with the work of Dvorak to compute bounded estimates of the homogenized permeability for such flows and demonstrated the effectiveness of this new algorithm with numerical examples.

  13. Dynamic Heterogeneity in Interacting Miscible Polymer Blends

    NASA Astrophysics Data System (ADS)

    Gaikwad, Ashish; Lodge, Timothy

    2008-03-01

    Dynamic heterogeneity leading to time-temperature superposition (tTS) failure has been widely reported in non-interacting/weakly interacting miscible polymer blends. However, coupling of the component dynamic response in blends, even with a huge dynamic asymmetry in the pure components, is possible with H-bonding interactions. This study is focused on finding the minimum level of interaction necessary for thermo-rheological simplicity in blends. Blends of styrene-co-vinylphenol (PSVPh) and poly(vinyl methyl ether) (PVME) were chosen. Incorporation of styrene provides an effective way to modulate H-bonding interactions in the system. Linear viscoelastic data indicate that tTS fails for PS/PVME blends, whereas data obtained for different PVPh/PVME blends showed that tTS was obeyed a over wide temperature range. For PSVPh/PVME blends with low PSVPh content, tTS was successful. This suggests that the presence of alternating styrene and vinyl phenol units was insufficient for dynamic response decoupling. Further studies are in progress, with varying vinyl phenol content in PSVPh, to explore the influence of H-bonding on dynamic heterogeneity and blend dynamics.

  14. Heterogeneous Photochemical Oxidation of Sulfur Dioxide

    NASA Astrophysics Data System (ADS)

    El-Zanan, H. S.; Stockwell, W. R.

    2007-12-01

    The gas phase oxidation of sulfur dioxide by the hydroxyl radical is a significant source of sulfate aerosol in the troposphere and stratosphere. Stockwell and Calvert (1983) performed fifteen chamber experiments where mixtures of HONO, NO, NO2, H2O, SO2 and CO were photolyzed in synthetic air or in nitrogen containing approximately 50 ppm oxygen. They found that the atmospheric oxidation of SO2 by hydroxyl radical was a chain process that occurs through the production of an HO2 radical followed by reaction with NO to reproduce HO. We have reanalyzed this dataset and we have found that a very large amount of the observed SO2 oxidation (70.0 ± 9.1 %) is not explained through the HO + SO2 reaction alone. The Regional Atmospheric Chemistry Mechanism (RACM2) was used to investigate additional chemical pathways for the oxidation of SO2. A mechanism consisting of photochemical heterogeneous reactions is proposed to account for the observed additional sulfur dioxide oxidation not accounted for by gas phase oxidation. The analysis showed that the measured time dependent SO2, CO2 and nitrogenous compound concentrations could be simulated by the photochemical heterogeneous mechanism in conjunction with the RACM2 mechanism.

  15. Adaptive load sharing in heterogeneous distributed systems

    NASA Astrophysics Data System (ADS)

    Mirchandaney, Ravi; Towsley, Don; Stankovic, John A.

    1990-08-01

    In this paper, we study the performance characteristics of simple load sharing algorithms for heterogeneous distributed systems. We assume that nonnegligible delays are encountered in transferring jobs from one node to another. We analyze the effects of these delays on the performance of two threshold-based algorithms called Forward and Reverse. We formulate queuing theoretic models for each of the algorithms operating in heterogeneous systems under the assumption that the job arrival process at each node in Poisson and the service times and job transfer times are exponentially distributed. The models are solved using the Matrix-Geometric solution technique. These models are used to study the effects of different parameters and algorithm variations on the mean job response time: e.g., the effects of varying the thresholds, the impact of changing the probe limit, the impact of biasing the probing, and the optimal response times over a large range of loads and delays. Wherever relevant, the results of the models are compared with the M/M/ 1 model, representing no load balancing (hereafter referred to as NLB), and the M/M/K model, which is an achievable lower bound (hereafter referred to as LB).

  16. Visual EKF-SLAM from Heterogeneous Landmarks.

    PubMed

    Esparza-Jiménez, Jorge Othón; Devy, Michel; Gordillo, José L

    2016-01-01

    Many applications require the localization of a moving object, e.g., a robot, using sensory data acquired from embedded devices. Simultaneous localization and mapping from vision performs both the spatial and temporal fusion of these data on a map when a camera moves in an unknown environment. Such a SLAM process executes two interleaved functions: the front-end detects and tracks features from images, while the back-end interprets features as landmark observations and estimates both the landmarks and the robot positions with respect to a selected reference frame. This paper describes a complete visual SLAM solution, combining both point and line landmarks on a single map. The proposed method has an impact on both the back-end and the front-end. The contributions comprehend the use of heterogeneous landmark-based EKF-SLAM (the management of a map composed of both point and line landmarks); from this perspective, the comparison between landmark parametrizations and the evaluation of how the heterogeneity improves the accuracy on the camera localization, the development of a front-end active-search process for linear landmarks integrated into SLAM and the experimentation methodology. PMID:27070602

  17. Integrating data from heterogeneous DNA microarray platforms.

    PubMed

    Valente, Eduardo; Rocha, Miguel

    2015-01-01

    DNA microarrays are one of the most used technologies for gene expression measurement. However, there are several distinct microarray platforms, from different manufacturers, each with its own measurement protocol, resulting in data that can hardly be compared or directly integrated. Data integration from multiple sources aims to improve the assertiveness of statistical tests, reducing the data dimensionality problem. The integration of heterogeneous DNA microarray platforms comprehends a set of tasks that range from the re-annotation of the features used on gene expression, to data normalization and batch effect elimination. In this work, a complete methodology for gene expression data integration and application is proposed, which comprehends a transcript-based re-annotation process and several methods for batch effect attenuation. The integrated data will be used to select the best feature set and learning algorithm for a brain tumor classification case study. The integration will consider data from heterogeneous Agilent and Affymetrix platforms, collected from public gene expression databases, such as The Cancer Genome Atlas and Gene Expression Omnibus. PMID:26673932

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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. PMID:27612817

  3. Infrared and Raman Imaging of Heterogeneous Catalysts

    SciTech Connect

    E Stavistki; B Weckhuysen

    2011-12-31

    The miniaturization of in situ spectroscopic tools has been recognized as a forefront instrumental development for the characterization of heterogeneous catalysts. With the multitude of micro-spectroscopic methods available fundamental insight into the structure-function relationships of catalytic processes can be obtained. Among these techniques vibrational spectroscopy is one of the most versatile methods and capable to shed insight into the molecular structure of reaction intermediates and products, the chemical state of catalyst materials during reaction as well as the nature of interactions between reactants/intermediates/products and the catalyst surface. In this tutorial review we discuss the recent developments in the field of infrared (IR) and Raman micro-spectroscopy and illustrate their potential. Showcase examples include (1) chemical imaging of spatial heterogeneities during catalyst preparation, (2) high-throughput catalyst screening, (3) transport and adsorption phenomena within catalytic solids and (4) reactivity studies of porous oxides, such as zeolites. Finally, new in situ spectroscopy tools based on vibrational spectroscopy and their potential in the catalysis domain are discussed.

  4. 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.

  5. Mining Functional Modules in Heterogeneous Biological Networks Using Multiplex PageRank Approach.

    PubMed

    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

  6. 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

  7. 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.

  8. Total protein

    MedlinePlus

    The total protein test measures the total amount of two classes of proteins found in the fluid portion of your ... nutritional problems, kidney disease or liver disease . If total protein is abnormal, you will need to have more ...

  9. Storage Proteins

    PubMed Central

    Fujiwara, Toru; Nambara, Eiji; Yamagishi, Kazutoshi; Goto, Derek B.; Naito, Satoshi

    2002-01-01

    Plants accumulate storage substances such as starch, lipids and proteins in certain phases of development. Storage proteins accumulate in both vegetative and reproductive tissues and serve as a reservoir to be used in later stages of plant development. The accumulation of storage protein is thus beneficial for the survival of plants. Storage proteins are also an important source of dietary plant proteins. Here, we summarize the genome organization and regulation of gene expression of storage protein genes in Arabidopsis. PMID:22303197

  10. Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity.

    PubMed

    Feng, Jin; Huang, Chao; Wren, Jonathan D; Wang, Dao-Wen; Yan, Jizhou; Zhang, Jiexin; Sun, Yujie; Han, Xiao; Zhang, Xin A

    2015-12-01

    Tetraspanin CD82 suppresses the progression and metastasis of a wide range of solid malignant tumors. However, its roles in tumorigenesis and hematopoietic malignancy remain unclear. Ubiquitously expressed CD82 restrains cell migration and cell invasion by modulating both cell-matrix and cell-cell adhesiveness and confining outside-in pro-motility signaling. This restraint at least contributes to, if not determines, the metastasis-suppressive activity and, also likely, the physiological functions of CD82. As a modulator of cell membrane heterogeneity, CD82 alters microdomains, trafficking, and topography of the membrane by changing the membrane molecular landscape. The functional activities of membrane molecules and the cytoskeletal interaction of the cell membrane are subsequently altered, followed by changes in cellular functions. Given its pathological and physiological importance, CD82 is a promising candidate for clinically predicting and blocking tumor progression and metastasis and also an emerging model protein for mechanistically understanding cell membrane organization and heterogeneity. PMID:26335499

  11. Probing the water on chemically heterogeneous surface: interfacial-structural analysis for surface charge distribution

    NASA Astrophysics Data System (ADS)

    Shin, Sucheol; Willard, Adam

    We introduce the novel method for predicting the charge distribution of chemically heterogeneous surface, but reconstructed from the perspective of the interfacial water molecules. Our approach is to analyze the response of water to a disordered surface and infer from that response the heterogeneous distribution of surface charge. We accomplish this using a framework that is based on a probabilistic description of water's interfacial molecular structure and maximum likelihood estimation. This framework allows to deduce the apparent charge that is most congruently represented by the set of water configurations over the particular region of a surface. We demonstrate that the estimated charge distribution is consistent to the actual distribution for a static model substrate and hence that our method can be applied to investigate a dynamic fluctuating substrate such as the surface of a hydrated protein. This novel technique provides the useful information that can reflect the influence of fluctuations in the structure of biomolecule.

  12. Fabrication and characterization of SiO2/Si heterogeneous nanopillar arrays

    NASA Astrophysics Data System (ADS)

    Wu, Wengang; Mao, Haiyang; Han, Xiang; Xu, Jun; Wang, Weibing

    2016-07-01

    This work presents arrays of heterogeneous nanopillars stacked with Si bodies and SiO2 heads for biomedical applications. Novel crossed and overlapped spacer techniques are proposed to fabricate the nanopillar arrays in controllable dimensions. For the nanopillars in the arrays, the minimum spacing, body diameter and head tip-radius reach 100 nm, 23 nm and 11 nm, respectively. The maximum height is 1.2 μm. In addition, because of hydrophilic/hydrophobic selectivity between the SiO2 heads and Si bodies, localized nanoliter water-droplet condensing, fluorescein solution extraction and protein capturing are observed on the SiO2 pillar heads. These experiments demonstrate the great potential of heterogeneous nanopillars in biomedical applications.

  13. Fabrication and characterization of SiO2/Si heterogeneous nanopillar arrays.

    PubMed

    Wu, Wengang; Mao, Haiyang; Han, Xiang; Xu, Jun; Wang, Weibing

    2016-07-29

    This work presents arrays of heterogeneous nanopillars stacked with Si bodies and SiO2 heads for biomedical applications. Novel crossed and overlapped spacer techniques are proposed to fabricate the nanopillar arrays in controllable dimensions. For the nanopillars in the arrays, the minimum spacing, body diameter and head tip-radius reach 100 nm, 23 nm and 11 nm, respectively. The maximum height is 1.2 μm. In addition, because of hydrophilic/hydrophobic selectivity between the SiO2 heads and Si bodies, localized nanoliter water-droplet condensing, fluorescein solution extraction and protein capturing are observed on the SiO2 pillar heads. These experiments demonstrate the great potential of heterogeneous nanopillars in biomedical applications. PMID:27319739

  14. Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila

    PubMed Central

    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.

    2015-01-01

    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. 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. PMID:26294687

  15. 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.

  16. A Mathematical and Computational Approach for Integrating the Major Sources of Cell Population Heterogeneity

    PubMed Central

    Stamatakis, Michail; Zygourakis, Kyriacos

    2010-01-01

    Several approaches have been used in the past to model heterogeneity in bacterial cell populations, with each approach focusing on different source(s) of heterogeneity. However, a holistic approach that integrates all the major sources into a comprehensive framework applicable to cell populations is still lacking. In this work we present the mathematical formulation of a cell population master equation (CPME) that describes cell population dynamics and takes into account the major sources of heterogeneity, namely stochasticity in reaction, DNA-duplication, and division, as well as the random partitioning of species contents into the two daughter cells. The formulation also takes into account cell growth and respects the discrete nature of the molecular contents and cell numbers. We further develop a Monte Carlo algorithm for the simulation of the stochastic processes considered here. To benchmark our new framework, we first use it to quantify the effect of each source of heterogeneity on the intrinsic and the extrinsic phenotypic variability for the well-known two-promoter system used experimentally by Elowitz et al. (2002). We finally apply our framework to a more complicated system and demonstrate how the interplay between noisy gene expression and growth inhibition due to protein accumulation at the single cell level can result in complex behavior at the cell population level. The generality of our framework makes it suitable for studying a vast array of artificial and natural genetic networks. Using our Monte Carlo algorithm, cell population distributions can be predicted for the genetic architecture of interest, thereby quantifying the effect of stochasticity in intracellular reactions or the variability in the rate of physiological processes such as growth and division. Such in silico experiments can give insight into the behavior of cell populations and reveal the major sources contributing to cell population heterogeneity. PMID:20685607

  17. Heterogeneity: The key to forecasting material failure?

    NASA Astrophysics Data System (ADS)

    Vasseur, J.; Wadsworth, F. B.; Lavallée, Y.; Dingwell, D. B.

    2014-12-01

    Empirical mechanistic models have been applied to the description of the stress and strain rate upon failure for heterogeneous materials. The behaviour of porous rocks and their analogous two-phase viscoelastic suspensions are particularly well-described by such models. Nevertheless, failure cannot yet be predicted forcing a reliance on other empirical prediction tools such as the Failure Forecast Method (FFM). Measurable, accelerating rates of physical signals (e.g., seismicity and deformation) preceding failure are often used as proxies for damage accumulation in the FFM. Previous studies have already statistically assessed the applicability and performance of the FFM, but none (to the best of our knowledge) has done so in terms of intrinsic material properties. Here we use a rheological standard glass, which has been powdered and then sintered for different times (up to 32 hours) at high temperature (675°C) in order to achieve a sample suite with porosities in the range of 0.10-0.45 gas volume fraction. This sample suite was then subjected to mechanical tests in a uniaxial press at a constant strain rate of 10-3 s-1 and a temperature in the region of the glass transition. A dual acoustic emission (AE) rig has been employed to test the success of the FFM in these materials of systematically varying porosity. The pore-emanating crack model describes well the peak stress at failure in the elastic regime for these materials. We show that the FFM predicts failure within 0-15% error at porosities >0.2. However, when porosities are <0.2, the forecast error associated with predicting the failure time increases to >100%. We interpret these results as a function of the low efficiency with which strain energy can be released in the scenario where there are few or no heterogeneities from which cracks can propagate. These observations shed light on questions surrounding the variable efficacy of the FFM applied to active volcanoes. In particular, they provide a systematic

  18. Spatial Heterogeneity Induces Scale Dependent Rock Friction

    NASA Astrophysics Data System (ADS)

    Yamashita, F.; Fukuyama, E.; Xu, S.; Takizawa, S.; Mizoguchi, K.; Kawakata, H.; Passelègue, F. X.; Schubnel, A.

    2014-12-01

    We carried out large-scale biaxial friction experiments (Fukuyama et al., 2012; 2014) using a pair of meter-sized Indian gabbro as specimens, whose contacting area was 1.5 × 0.1 m2, normal stress was up to 6.7 MPa and loading velocity was up to 3 × 10-2 m/s. After each experiment, we found localized damages (i.e. grooves) were generated on the fault surface and gouges were distributed around them. We confirmed work rate dependency of rock friction as revealed by centimeter-sized rock samples (Di Toro et al., 2011), but further found that the meter-sized rock friction starts to decrease at one order of magnitude smaller work rate than that of the centimeter sized rock (Yamashita et al., 2013, AGU fall meeting). Here, we concluded that this difference is caused by stress localization and associated increase in heterogeneity on the fault as shown by: 1) Total amount of deviations of each local shear stress from the average, which were monitored by strain gauge array, increased with the decrease in friction. 2) Friction coefficients were negatively correlated with degree of spatial heterogeneity evaluated from the distribution of grooves and gouges. 3) Melt textures were found in the collected gouges by microscopic observation using HRSEM. Based on these observations, we propose a stress localization model; the fault surfaces are composed of patched and non-patched areas with high and low normal stress, respectively. The high normal stress patch leads to high shear stress, high mechanical work and thus production of much wear material (gouge), which further causes additional increase in normal stress. Assuming that the local friction follows the results by centimeter-sized gabbro experiments, we numerically simulated a slip-dependent friction for both patched and non-patched areas, and successively reproduced a weakening in macroscopic friction. We confirmed that the work rate dependency of simulated friction was consistent with that of biaxial experiments (Fig. 1

  19. 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

  20. 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.