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Sample records for heterogeneous ribonuclear proteins

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

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

    2007-01-01

    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

  2. Heterogeneity of protein hormones

    Rosselin, G; Bataille, D; Laburthe, M; Duran-Garcia, S [Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital Saint-Antoine, 75 - Paris (France)

    1975-12-01

    Radioimmunoassay measures antigenic determinants of hormonal molecules in the plasmas and tissues. These estimations carried out after fractionation in biological fluids, have revealed several immunological forms of the same hormone. The main problem is in the relationship of the various immunoreactive forms to the same hormonal sequence. The similar immunoreactive forms of high molecular weight usually have low biological activity and suggest the presence of prohormone; the suggestion of prohormonal nature depends on the chronology of the incorporation of labelled leucine and enzymatic transformation of prohormone with low biological into active hormone. The forms with high molecular weight and similar immunological activity may be of another nature. Thus, it has been shown that the biosynthetic nature of a compound such as big big insulin in the rat is doubtful owing to the absence of specific incorporation of labelled leucine into the immunoprecipitate of this fraction. The significance of low molecular weight form is still little known. An example of these forms is supplied by the existence of an alpha sub-unit of gonadotrophin present in the plasma of menopausal women. The interest of analytical methods by radio-receptor, simulation of cyclase activity in the identification of biological activity of immunoreactive forms, is discussed in relation to immunological forms ofenteroglucagon. An unusual aspect of the evolutive and adaptative character of hormonal heterogeneity is given by the gastro-intestinal hormones.

  3. Sequence heterogeneity accelerates protein search for targets on DNA

    Shvets, Alexey A.; Kolomeisky, Anatoly B.

    2015-01-01

    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

  4. Sequence heterogeneity accelerates protein search for targets on DNA

    Shvets, Alexey A.; Kolomeisky, Anatoly B., E-mail: tolya@rice.edu [Department of Chemistry and Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005 (United States)

    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.

  5. Heterogeneity mapping of protein expression in tumors using quantitative immunofluorescence.

    Faratian, Dana; Christiansen, Jason; Gustavson, Mark; Jones, Christine; Scott, Christopher; Um, InHwa; Harrison, David J

    2011-10-25

    Morphologic heterogeneity within an individual tumor is well-recognized by histopathologists in surgical practice. While this often takes the form of areas of distinct differentiation into recognized histological subtypes, or different pathological grade, often there are more subtle differences in phenotype which defy accurate classification (Figure 1). Ultimately, since morphology is dictated by the underlying molecular phenotype, areas with visible differences are likely to be accompanied by differences in the expression of proteins which orchestrate cellular function and behavior, and therefore, appearance. The significance of visible and invisible (molecular) heterogeneity for prognosis is unknown, but recent evidence suggests that, at least at the genetic level, heterogeneity exists in the primary tumor(1,2), and some of these sub-clones give rise to metastatic (and therefore lethal) disease. Moreover, some proteins are measured as biomarkers because they are the targets of therapy (for instance ER and HER2 for tamoxifen and trastuzumab (Herceptin), respectively). If these proteins show variable expression within a tumor then therapeutic responses may also be variable. The widely used histopathologic scoring schemes for immunohistochemistry either ignore, or numerically homogenize the quantification of protein expression. Similarly, in destructive techniques, where the tumor samples are homogenized (such as gene expression profiling), quantitative information can be elucidated, but spatial information is lost. Genetic heterogeneity mapping approaches in pancreatic cancer have relied either on generation of a single cell suspension(3), or on macrodissection(4). A recent study has used quantum dots in order to map morphologic and molecular heterogeneity in prostate cancer tissue(5), providing proof of principle that morphology and molecular mapping is feasible, but falling short of quantifying the heterogeneity. Since immunohistochemistry is, at best, only semi

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

    Keita Ino

    Full Text Available 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.

  7. Heterogeneity of proteins expressed by Brazilian Sporothrix schenckii isolates.

    Fernandes, Geisa Ferreira; Do Amaral, Cristiane Candida; Sasaki, Alexandre; Godoy, Patrício Martinez; De Camargo, Zoilo Pires

    2009-12-01

    The profiles of proteins present in the exoantigens of Brazilian Sporothrix schenckii isolates were studied and compared by electrophoresis (SDS-PAGE). Thirteen isolates from five different regions of Brazil (1,000 to 2,000 km apart) and ten from a more limited region (200 to 400 km apart within the state of São Paulo) were cultured in Sabouraud, M199 and minimum (MM) media. Qualitative and quantitative differences in the expression of proteins, which varied according to the medium and the isolate, were observed. Fractions with the same MW but varying in intensity were detected, as well as fractions present in 1 isolate but absent in others. Dendrograms were constructed and isolates grouped based on the fractions obtained, irrespective of the intensity. The results showed that Brazilian S. schenckii isolates express different protein profiles, a feature also present in isolates from a more restricted region. The exoantigens were found to have a maximum of 15 protein fractions, ranging in MW from 19-220 KDaltons depending on the medium used for the cultures. These data show the great heterogeneity of Brazilian S. schenckii protein expression.

  8. Enhancing Accuracy in Molecular Weight Determination of Highly Heterogeneously Glycosylated Proteins by Native Tandem Mass Spectrometry

    Wang, Guanbo; de Jong, Rob N; van den Bremer, Ewald T J; Parren, Paul W H I; Heck, Albert J R

    2017-01-01

    The determination of molecular weights (MWs) of heavily glycosylated proteins is seriously hampered by the physicochemical characteristics and heterogeneity of the attached carbohydrates. Glycosylation impacts protein migration during sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis

  9. Is dynamic heterogeneity of water in presence of a protein ...

    Abstract. Rotational and translational dynamic heterogeneities (DHs) of ambient aqueous solutions of trimethylamine-N-oxide (TMAO) and tetramethylurea (TMU) at several solute concentrations have been inves- tigated and compared. Motional characteristics of water molecules at solute interfaces and in bulk solutions.

  10. Proteins are secreted from heterogeneous prestored sources in the exocrine pancreas

    Miller, P.E.; Adelson, J.W.

    1987-01-01

    Recent studies demonstrating nonparallel regulated secretion of prestored digestive enzymes in tightly linked groups consistent with the exocytosis mechanisms led the authors to predict that digestive enzymes would be found to be secreted from heterogeneous sources within the exocrine pancreas. They explored whether the gland was heterogeneous with respect to its sources of prestored secretory proteins with a double isotopic label method not dependent on activity of secreted digestive enzymes. Rabbit pancreatic proteins were double labeled in vivo by injection of each animal with chemically identical but isotopically distinct mixtures of 3 H- and 14 C-labeled amino acids, which were administered separately or together on consecutive days after partial depletion of prestored proteins by administration of cholecystokinin (CCK), methacholine chloride, or saline in a protocol in which order of both isotope and secretagogue administration was varied. Three days after labeling, proteins were recovered by collection from cannulated pancreatic ducts of anesthetized animals after stimulation with alternating increasing doses of CCK and methacholine chloride. Correlation and regression analysis of isotopic outputs and variance analysis of specific radioactivities of secreted proteins showed sequestration into and secretion from heterogeneous pools of secretory proteins, directly confirming the hypothesis. These results provide a cell biological mechanism explaining regulated nonparallel secretion of digestive enzymes

  11. Addressing challenges of heterogeneous tumor treatment through bispecific protein-mediated pretargeted drug delivery.

    Yang, Qi; Parker, Christina L; McCallen, Justin D; Lai, Samuel K

    2015-12-28

    Tumors are frequently characterized by genomically and phenotypically distinct cancer cell subpopulations within the same tumor or between tumor lesions, a phenomenon termed tumor heterogeneity. These diverse cancer cell populations pose a major challenge to targeted delivery of diagnostic and/or therapeutic agents, as the conventional approach of conjugating individual ligands to nanoparticles is often unable to facilitate intracellular delivery to the full spectrum of cancer cells present in a given tumor lesion or patient. As a result, many cancers are only partially suppressed, leading to eventual tumor regrowth and/or the development of drug-resistant tumors. Pretargeting (multistep targeting) approaches involving the administration of 1) a cocktail of bispecific proteins that can collectively bind to the entirety of a mixed tumor population followed by 2) nanoparticles containing therapeutic and/or diagnostic agents that can bind to the bispecific proteins accumulated on the surface of target cells offer the potential to overcome many of the challenges associated with drug delivery to heterogeneous tumors. Despite its considerable success in improving the efficacy of radioimmunotherapy, the pretargeting strategy remains underexplored for a majority of nanoparticle therapeutic applications, especially for targeted delivery to heterogeneous tumors. In this review, we will present concepts in tumor heterogeneity, the shortcomings of conventional targeted systems, lessons learned from pretargeted radioimmunotherapy, and important considerations for harnessing the pretargeting strategy to improve nanoparticle delivery to heterogeneous tumors. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Intrafocal heterogeneity of ERG protein expression and gene fusion pattern in prostate cancer.

    Suh, Ja Hee; Park, Jeong Hwan; Lee, Cheol; Moon, Kyung Chul

    2017-10-01

    Prostate cancer is considered to be highly heterogeneous, with various morphologic features and biologic behaviors. The TMPRSS2-ERG gene fusion is the most frequently observed genetic aberration in prostate cancer. The aim of this study was to elucidate the intrafocal heterogeneity of ERG gene fusion status. ERG immunohistochemistry (IHC) was performed in samples from 168 prostate cancer patients who had undergone radical prostatectomy, and 40 cases showing ERG-positive IHC staining were selected for tissue microarray (TMA) construction. Two to six representative cores were selected from each tumor focus. In the cases with heterogeneous ERG IHC staining intensity, the areas showing different intensities were separately selected. Using the TMA blocks, IHC and fluorescence in situ hybridization (FISH) were conducted to evaluate the heterogeneity of ERG protein expression and ERG fusion gene patterns, respectively, in a single tumor focus. Heterogeneity of ERG IHC staining was defined as the simultaneous presence of negative and positive cores in the same tumor focus. Heterogeneity of ERG FISH was defined by the presence of cores with positive and negative FISH signals or cores with break-apart and interstitial deletion FISH signals in the same tumor focus. A total of 202 TMA cores were isolated from 40 ERG-positive cases. Of the 202 total cores, 19 were negative for ERG IHC staining, and 46 showed 1+, 52 showed 2+, and 85 showed 3+ ERG staining intensity. Eleven cores were negative for ERG FISH signal, 119 cores showed ERG break-apart FISH signals, and the remaining 72 cores revealed interstitial deletion. Intrafocal heterogeneity of ERG IHC staining was found in 20% (8/40) of cases, and intrafocal heterogeneity of ERG gene fusion pattern was found in 32.5% (13/40) of cases. In summary, this study showed significantly frequent intrafocal heterogeneity of ERG protein expression, gene fusion status and fusion pattern. This heterogeneity can be caused by the development

  13. Conformational Heterogeneity in Antibody-Protein Antigen Recognition IMPLICATIONS FOR HIGH AFFINITY PROTEIN COMPLEX FORMATION

    Addis, P. W.; Hall, c. J.; Bruton, S.; Veverka, Václav; Wilkinson, I. C.; Muskett, F. W.; Renshaw, P. S.; Prosser, C. E.; Carrington, B.; Lawson, A. D. G.; Griffin, R.; Taylor, R. J.; Waters, L. C.; Henry, A. J.; Carr, M. D.

    2014-01-01

    Roč. 289, č. 10 (2014), s. 7200-7210 ISSN 0021-9258 Institutional support: RVO:61388963 Keywords : NMR * antibody * protein-protein interaction * protein conformation Subject RIV: CE - Biochemistry Impact factor: 4.573, year: 2014

  14. Functional characterization of two paralogs that are novel RNA binding proteins influencing mitochondrial transcripts of Trypanosoma brucei

    Kafková, Lucie; Ammerman, M. L.; Faktorová, D.; Fisk, J. C.; Zimmer, S.L.; Sobotka, Roman; Read, L. K.; Lukeš, Julius; Hashimi, Hassan

    2012-01-01

    Roč. 18, č. 10 (2012), s. 1846-1861 ISSN 1355-8382 R&D Projects: GA ČR GA204/09/1667 Institutional support: RVO:60077344 ; RVO:61388971 Keywords : RNA editing * RNA binding protein * ribonuclear protein (RNP) * mitochondria * trypanosome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.088, year: 2012 http://rnajournal.cshlp.org/content/18/10/1846

  15. Protein fraction heterogeneity in donkey’s milk analysed by proteomic methods

    G. D'Urso

    2010-04-01

    Full Text Available Donkey’s milk is often well tolerate by patients affected by cow’s milk protein allergy, probably thanks to its protein composition. This empiric evidence, confirmed by some clinical trials, needs to be better investigated. A preliminary survey on the protein fraction of donkey’s milk was carried out: fifty-six individual milk samples have been collected and analysed by IEF and SDS-PAGE. Five different IEF patterns have been identified, showing a marked heterogeneity both in casein and whey protein fractions. A single IEF pattern showed an apparent reduced amount of casein fraction highlighted by SDS. Three of the five IEF patterns have been further investigated by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS.

  16. Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma

    Walderik W. Zomerman

    2018-03-01

    Full Text Available Summary: The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog, group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling. Integrative analysis demonstrated that heterogeneous transcriptional input converges on these protein-signaling profiles: all SHH and a subset of group 3 patients exhibited the MYC-like protein-signaling profile; the majority of the other group 3 subset and group 4 patients displayed the DNA damage/apoptotic/neuronal signaling profile. Functional analysis of enriched pathways highlighted cell-cycle progression and protein synthesis as therapeutic targets for MYC-like medulloblastoma. : Using peptide phosphorylation profiling, Zomerman et al. identify two medulloblastoma phosphoprotein-signaling profiles that have prognostic value and are potentially targetable. They find that these profiles extend across transcriptome-based subgroup borders. This suggests that diverse genetic information converges on common protein-signaling pathways and highlights protein-signaling as a unique information layer. Keywords: medulloblastoma, protein-signaling, protein synthesis, MYC, TP53, proteome, phosphoproteome

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

    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.

  18. Quantitative Evaluation of Protein Heterogeneity within Herpes Simplex Virus 1 Particles.

    El Bilali, Nabil; Duron, Johanne; Gingras, Diane; Lippé, Roger

    2017-05-15

    Several virulence genes have been identified thus far in the herpes simplex virus 1 genome. It is also generally accepted that protein heterogeneity among virions further impacts viral fitness. However, linking this variability directly with infectivity has been challenging at the individual viral particle level. To address this issue, we resorted to flow cytometry (flow virometry), a powerful approach we recently employed to analyze individual viral particles, to identify which tegument proteins vary and directly address if such variability is biologically relevant. We found that the stoichiometry of the U L 37, ICP0, and VP11/12 tegument proteins in virions is more stable than the VP16 and VP22 tegument proteins, which varied significantly among viral particles. Most interestingly, viruses sorted for their high VP16 or VP22 content yielded modest but reproducible increases in infectivity compared to their corresponding counterparts containing low VP16 or VP22 content. These findings were corroborated for VP16 in short interfering RNA experiments but proved intriguingly more complex for VP22. An analysis by quantitative Western blotting revealed substantial alterations of virion composition upon manipulation of individual tegument proteins and suggests that VP22 protein levels acted indirectly on viral fitness. These findings reaffirm the interdependence of the virion components and corroborate that viral fitness is influenced not only by the genome of viruses but also by the stoichiometry of proteins within each virion. IMPORTANCE The ability of viruses to spread in animals has been mapped to several viral genes, but other factors are clearly involved, including virion heterogeneity. To directly probe whether the latter influences viral fitness, we analyzed the protein content of individual herpes simplex virus 1 particles using an innovative flow cytometry approach. The data confirm that some viral proteins are incorporated in more controlled amounts, while

  19. MEGADOCK 4.0: an ultra-high-performance protein-protein docking software for heterogeneous supercomputers.

    Ohue, Masahito; Shimoda, Takehiro; Suzuki, Shuji; Matsuzaki, Yuri; Ishida, Takashi; Akiyama, Yutaka

    2014-11-15

    The application of protein-protein docking in large-scale interactome analysis is a major challenge in structural bioinformatics and requires huge computing resources. In this work, we present MEGADOCK 4.0, an FFT-based docking software that makes extensive use of recent heterogeneous supercomputers and shows powerful, scalable performance of >97% strong scaling. MEGADOCK 4.0 is written in C++ with OpenMPI and NVIDIA CUDA 5.0 (or later) and is freely available to all academic and non-profit users at: http://www.bi.cs.titech.ac.jp/megadock. akiyama@cs.titech.ac.jp Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

  20. Semi-supervised drug-protein interaction prediction from heterogeneous biological spaces.

    Xia, Zheng; Wu, Ling-Yun; Zhou, Xiaobo; Wong, Stephen T C

    2010-09-13

    Predicting drug-protein interactions from heterogeneous biological data sources is a key step for in silico drug discovery. The difficulty of this prediction task lies in the rarity of known drug-protein interactions and myriad unknown interactions to be predicted. To meet this challenge, a manifold regularization semi-supervised learning method is presented to tackle this issue by using labeled and unlabeled information which often generates better results than using the labeled data alone. Furthermore, our semi-supervised learning method integrates known drug-protein interaction network information as well as chemical structure and genomic sequence data. Using the proposed method, we predicted certain drug-protein interactions on the enzyme, ion channel, GPCRs, and nuclear receptor data sets. Some of them are confirmed by the latest publicly available drug targets databases such as KEGG. We report encouraging results of using our method for drug-protein interaction network reconstruction which may shed light on the molecular interaction inference and new uses of marketed drugs.

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

    Gao, Feng-Hou [NO.3 People' s Hospital affiliated to Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 201900 (China); The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Wu, Ying-Li [The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Zhao, Meng [Institute of Health Science, SJTU-SM/Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai (China); Liu, Chuan-Xu; Wang, Li-Shun [The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Chen, Guo-Qiang, E-mail: chengq@shsmu.edu.cn [The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Institute of Health Science, SJTU-SM/Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai (China)

    2009-11-15

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

  2. Improved success of sparse matrix protein crystallization screening with heterogeneous nucleating agents.

    Anil S Thakur

    2007-10-01

    Full Text Available 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.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.Our results suggest that the addition of heterogeneous nucleating agents increases the chances of crystal formation when using sparse matrix screens.

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

    Iwanaga, Kentaro; Sueoka, Naoko; Sato, Akemi; Hayashi, Shinichiro; Sueoka, Eisaburo

    2005-01-01

    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

  4. Phenotypic heterogeneity associated with a novel mutation (Gly112Glu) in the Norrie disease protein.

    Allen, R C; Russell, S R; Streb, L M; Alsheikheh, A; Stone, E M

    2006-02-01

    To determine the molecular pathology and clinical severity of two pedigrees with a history of early retinal detachment and peripheral retinal vascular abnormalities. Longitudinal cohort study. A longitudinal clinical study and DNA analysis was performed on 49 family members of two pedigrees. Nine individuals were found to be hemizygous for a mutation at codon 112 (Gly112Glu) of the Norrie disease protein (NDP) in one pedigree. Significant phenotypic heterogeneity was found. The proband presented with a unilateral subtotal retinal detachment at the age of 3 years, and subsequently developed a slowly progressive tractional retinal detachment involving the macula in the contralateral eye at the age of 4 years. One individual had only mild peripheral retinal pigmentary changes with normal vision at the age of 79 years. The remaining seven individuals had varying degrees of peripheral retinal vascular abnormalities and anterior segment findings. Seven affected members of a second pedigree affected by a previously reported mutation, Arg74Cys, also demonstrated wide ocular phenotypic variation. A novel mutation (Gly112Glu), which represents the most carboxy located, NDP mutation reported, results in significant phenotypic heterogeneity. These data support the contention that the spectrum of ocular disease severity associated with these NDP mutations is broad. Use of terms that characterize this entity by phenotypic appearance, such as familial exudative vitreoretinopathy, do not adequately communicate the potential spectrum of severity of this disorder to affected or carrier family members.

  5. The Significance of Protein Components in Heterogeneous Eggs for Embrionic Development and Larvas Persistence of Cyprinidae

    Zalepukhin Valeriy Vladimirovich

    2014-12-01

    Full Text Available Endogenous heterogeneity of females and their eggs is one of the most important factors of annual generation’s formation in nature-spawn and incubative centers. Its assessment is significant for comprehending the notion of biochemical changes in proximate prespawn period. Between the shares of egg’s biochemical composition of Cyprinidae species only protein and b-lipoproteids levels are incovering constant and authentic correlations with embrionic development and larval survival in the conditions of artificial reproduction. The promotion of protein’s level to 20 – 24 % (in wet weigth in percolating eggs positively affects the fertilization and larvae vitality. This trend is fair for the domesticated and nature-spawn fish. The same significance is important for the b-lipoproteids level in ovular eggs of grass carp (Ctenopharyngodon idella Val.. The optimal concentration is 100-200 mg % in wet weight.

  6. Modeling heterogeneous (co)variances from adjacent-SNP groups improves genomic prediction for milk protein composition traits

    Gebreyesus, Grum; Lund, Mogens Sandø; Buitenhuis, Albert Johannes

    2017-01-01

    Accurate genomic prediction requires a large reference population, which is problematic for traits that are expensive to measure. Traits related to milk protein composition are not routinely recorded due to costly procedures and are considered to be controlled by a few quantitative trait loci...... of large effect. The amount of variation explained may vary between regions leading to heterogeneous (co)variance patterns across the genome. Genomic prediction models that can efficiently take such heterogeneity of (co)variances into account can result in improved prediction reliability. In this study, we...... developed and implemented novel univariate and bivariate Bayesian prediction models, based on estimates of heterogeneous (co)variances for genome segments (BayesAS). Available data consisted of milk protein composition traits measured on cows and de-regressed proofs of total protein yield derived for bulls...

  7. A branch-heterogeneous model of protein evolution for efficient inference of ancestral sequences.

    Groussin, M; Boussau, B; Gouy, M

    2013-07-01

    Most models of nucleotide or amino acid substitution used in phylogenetic studies assume that the evolutionary process has been homogeneous across lineages and that composition of nucleotides or amino acids has remained the same throughout the tree. These oversimplified assumptions are refuted by the observation that compositional variability characterizes extant biological sequences. Branch-heterogeneous models of protein evolution that account for compositional variability have been developed, but are not yet in common use because of the large number of parameters required, leading to high computational costs and potential overparameterization. Here, we present a new branch-nonhomogeneous and nonstationary model of protein evolution that captures more accurately the high complexity of sequence evolution. This model, henceforth called Correspondence and likelihood analysis (COaLA), makes use of a correspondence analysis to reduce the number of parameters to be optimized through maximum likelihood, focusing on most of the compositional variation observed in the data. The model was thoroughly tested on both simulated and biological data sets to show its high performance in terms of data fitting and CPU time. COaLA efficiently estimates ancestral amino acid frequencies and sequences, making it relevant for studies aiming at reconstructing and resurrecting ancestral amino acid sequences. Finally, we applied COaLA on a concatenate of universal amino acid sequences to confirm previous results obtained with a nonhomogeneous Bayesian model regarding the early pattern of adaptation to optimal growth temperature, supporting the mesophilic nature of the Last Universal Common Ancestor.

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

    Mannello, Ferdinando; Ligi, Daniela

    2013-01-01

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

  9. High-throughput simultaneous analysis of RNA, protein, and lipid biomarkers in heterogeneous tissue samples.

    Reiser, Vladimír; Smith, Ryan C; Xue, Jiyan; Kurtz, Marc M; Liu, Rong; Legrand, Cheryl; He, Xuanmin; Yu, Xiang; Wong, Peggy; Hinchcliffe, John S; Tanen, Michael R; Lazar, Gloria; Zieba, Renata; Ichetovkin, Marina; Chen, Zhu; O'Neill, Edward A; Tanaka, Wesley K; Marton, Matthew J; Liao, Jason; Morris, Mark; Hailman, Eric; Tokiwa, George Y; Plump, Andrew S

    2011-11-01

    With expanding biomarker discovery efforts and increasing costs of drug development, it is critical to maximize the value of mass-limited clinical samples. The main limitation of available methods is the inability to isolate and analyze, from a single sample, molecules requiring incompatible extraction methods. Thus, we developed a novel semiautomated method for tissue processing and tissue milling and division (TMAD). We used a SilverHawk atherectomy catheter to collect atherosclerotic plaques from patients requiring peripheral atherectomy. Tissue preservation by flash freezing was compared with immersion in RNAlater®, and tissue grinding by traditional mortar and pestle was compared with TMAD. Comparators were protein, RNA, and lipid yield and quality. Reproducibility of analyte yield from aliquots of the same tissue sample processed by TMAD was also measured. The quantity and quality of biomarkers extracted from tissue prepared by TMAD was at least as good as that extracted from tissue stored and prepared by traditional means. TMAD enabled parallel analysis of gene expression (quantitative reverse-transcription PCR, microarray), protein composition (ELISA), and lipid content (biochemical assay) from as little as 20 mg of tissue. The mean correlation was r = 0.97 in molecular composition (RNA, protein, or lipid) between aliquots of individual samples generated by TMAD. We also demonstrated that it is feasible to use TMAD in a large-scale clinical study setting. The TMAD methodology described here enables semiautomated, high-throughput sampling of small amounts of heterogeneous tissue specimens by multiple analytical techniques with generally improved quality of recovered biomolecules.

  10. Machines vs. ensembles: effective MAPK signaling through heterogeneous sets of protein complexes.

    Ryan Suderman

    Full Text Available Despite the importance of intracellular signaling networks, there is currently no consensus regarding the fundamental nature of the protein complexes such networks employ. One prominent view involves stable signaling machines with well-defined quaternary structures. The combinatorial complexity of signaling networks has led to an opposing perspective, namely that signaling proceeds via heterogeneous pleiomorphic ensembles of transient complexes. Since many hypotheses regarding network function rely on how we conceptualize signaling complexes, resolving this issue is a central problem in systems biology. Unfortunately, direct experimental characterization of these complexes has proven technologically difficult, while combinatorial complexity has prevented traditional modeling methods from approaching this question. Here we employ rule-based modeling, a technique that overcomes these limitations, to construct a model of the yeast pheromone signaling network. We found that this model exhibits significant ensemble character while generating reliable responses that match experimental observations. To contrast the ensemble behavior, we constructed a model that employs hierarchical assembly pathways to produce scaffold-based signaling machines. We found that this machine model could not replicate the experimentally observed combinatorial inhibition that arises when the scaffold is overexpressed. This finding provides evidence against the hierarchical assembly of machines in the pheromone signaling network and suggests that machines and ensembles may serve distinct purposes in vivo. In some cases, e.g. core enzymatic activities like protein synthesis and degradation, machines assembled via hierarchical energy landscapes may provide functional stability for the cell. In other cases, such as signaling, ensembles may represent a form of weak linkage, facilitating variation and plasticity in network evolution. The capacity of ensembles to signal effectively

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

    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. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

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

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

    2013-06-03

    Epidemiological studies have proposed that depression may increase the risk for Alzheimer's disease (AD), even in patients with early-onset depression. Although metabolism of amyloid β protein (Aβ) in elderly depression received attention in terms of their correlation, there is a serious heterogeneity in elderly depression in terms of age at onset of depression. Moreover, it is unknown whether early-onset major depressive disorder (MDD) has a long-term effect on the involvement of Aβ metabolism and later development of AD. Thus, we evaluated serum Aβ40 and Aβ42 levels, the Aβ40/Aβ42 ratio in 89 elderly (≥60 years of age) inpatients with MDD and 81 age-matched healthy controls, and compared them among patients with early-onset (great interest that the serum Aβ40/Aβ42 ratio was negatively correlated with the age at MDD onset (R=-0.201, p=0.032). These results suggest that an earlier onset of MDD may have a more serious abnormality in Aβ metabolism, possibly explaining a biological mechanism underlying the link between depression and AD. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Novel somatic single nucleotide variants within the RNA binding protein hnRNP A1 in multiple sclerosis patients [v2; ref status: indexed, http://f1000r.es/4dh

    Sangmin Lee

    2014-09-01

    Full Text Available Some somatic single nucleotide variants (SNVs are thought to be pathogenic, leading to neurological disease. We hypothesized that heterogeneous nuclear ribonuclear protein A1 (hnRNP A1, an autoantigen associated with multiple sclerosis (MS would contain SNVs. MS patients develop antibodies to hnRNP A1293-304, an epitope within the M9 domain (AA268-305 of hnRNP A1. M9 is hnRNP A1’s nucleocytoplasmic transport domain, which binds transportin-1 (TPNO-1 and allows for hnRNP A1’s transport into and out of the nucleus. Genomic DNA sequencing of M9 revealed nine novel SNVs that resulted in an amino acid substitution in MS patients that were not present in controls. SNVs occurred within the TPNO-1 binding domain (hnRNP A1268-289 and the MS IgG epitope (hnRNP A1293-304, within M9.  In contrast to the nuclear localization of wild type (WT hnRNP A1, mutant hnRNP A1 mis-localized to the cytoplasm, co-localized with stress granules and caused cellular apoptosis. Whilst WT hnRNP A1 bound TPNO-1, mutant hnRNP A1 showed reduced TPNO-1 binding. These data suggest SNVs in hnRNP A1 might contribute to pathogenesis of MS.

  14. Novel somatic single nucleotide variants within the RNA binding protein hnRNP A1 in multiple sclerosis patients [v1; ref status: indexed, http://f1000r.es/3nv

    Sangmin Lee

    2014-06-01

    Full Text Available Some somatic single nucleotide variants (SNVs are thought to be pathogenic, leading to neurological disease. We hypothesized that heterogeneous nuclear ribonuclear protein A1 (hnRNP A1, an autoantigen associated with multiple sclerosis (MS would contain SNVs. MS patients develop antibodies to hnRNP A1293-304, an epitope within the M9 domain (AA268-305 of hnRNP A1. M9 is hnRNP A1’s nucleocytoplasmic transport domain, which binds transportin-1 (TPNO-1 and allows for hnRNP A1’s transport into and out of the nucleus. Genomic DNA sequencing of M9 revealed nine novel SNVs that resulted in an amino acid substitution in MS patients that were not present in controls. SNVs occurred within the TPNO-1 binding domain (hnRNP A1268-289 and the MS IgG epitope (hnRNP A1293-304, within M9.  In contrast to the nuclear localization of wild type (WT hnRNP A1, mutant hnRNP A1 mis-localized to the cytoplasm, co-localized with stress granules and caused cellular apoptosis. Whilst WT hnRNP A1 bound TPNO-1, mutant hnRNP A1 showed reduced TPNO-1 binding. These data suggest SNVs in hnRNP A1 might contribute to pathogenesis of MS.

  15. Marker Protein Expression Combined With Expression Heterogeneity is a Powerful Indicator of Malignancy in Acral Lentiginous Melanomas.

    Cintra Lopes Carapeto, Fernando; Neves Comodo, Andréia; Germano, Andressa; Pereira Guimarães, Daiane; Barcelos, Denise; Fernandes, Mariana; Landman, Gilles

    2017-02-01

    Samples of acral lentiginous melanomas (ALMs) were obtained from the Department of Pathology at Escola Paulista de Medicina-Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Demographic, clinical, and follow-up data were obtained from the charts of Hospital São Paulo. From 2 tissue microarrays containing 60 nevi and quadruplicate samples of ≥1.0-mm of 49 ALM, sections were stained to evaluate SCF, KIT, BRAF, CYCLIND1, MYC, and PTEN immunohistochemical protein expression. Nevi and ALM from 2006 to 2010 were reviewed and collected. All specimens were in the vertical growth phase, and histopathological parameters indicated that tumors were at an advanced stage at diagnosis. Average tumor thickness was 6.95 mm, 63% were ulcerated, average mitotic index was 5 mitotic cells per mm, and 43% were at Clark's level V. Compared with nevi, the χ test showed that ALM significantly correlated with SCF protein expression (P = 0.001) and expression heterogeneity (P < 0.000). Similar findings were observed for KIT (P = 0.005, P = 0.003, respectively), MYC (P < 0.000, P < 0.000), and PTEN (P = 0.005, P < 0.000). Malignancy did not correlate with BRAF and CYCLIN D1 expression (P = 0.053 and P = 0.259, respectively), but it did significantly correlate with their heterogeneous expression (P < 0.000, P = 0.024, respectively). Combined protein expression had an odds ratio of greater malignancy when BRAF and MYC were positive and/or heterogeneously expressed (OR of 78 and 95, respectively). We show that marker protein expression, when combined with heterogeneous expression as shown by immunohistochemistry, is a powerful indicator of malignancy in ALMs, especially, when protein pairs are combined.

  16. Single-molecule resolution of protein dynamics on polymeric membrane surfaces: the roles of spatial and population heterogeneity.

    Langdon, Blake B; Mirhossaini, Roya B; Mabry, Joshua N; Sriram, Indira; Lajmi, Ajay; Zhang, Yanxia; Rojas, Orlando J; Schwartz, Daniel K

    2015-02-18

    Although polymeric membranes are widely used in the purification of protein pharmaceuticals, interactions between biomolecules and membrane surfaces can lead to reduced membrane performance and damage to the product. In this study, single-molecule fluorescence microscopy provided direct observation of bovine serum albumin (BSA) and human monoclonal antibody (IgG) dynamics at the interface between aqueous buffer and polymeric membrane materials including regenerated cellulose and unmodified poly(ether sulfone) (PES) blended with either polyvinylpyrrolidone (PVP), polyvinyl acetate-co-polyvinylpyrrolidone (PVAc-PVP), or polyethylene glycol methacrylate (PEGM) before casting. These polymer surfaces were compared with model surfaces composed of hydrophilic bare fused silica and hydrophobic trimethylsilane-coated fused silica. At extremely dilute protein concentrations (10(-3)-10(-7) mg/mL), protein surface exchange was highly dynamic with protein monomers desorbing from the surface within ∼1 s after adsorption. Protein oligomers (e.g., nonspecific dimers, trimers, or larger aggregates), although less common, remained on the surface for 5 times longer than monomers. Using newly developed super-resolution methods, we could localize adsorption sites with ∼50 nm resolution and quantify the spatial heterogeneity of the various surfaces. On a small anomalous subset of the adsorption sites, proteins adsorbed preferentially and tended to reside for significantly longer times (i.e., on "strong" sites). Proteins resided for shorter times overall on surfaces that were more homogeneous and exhibited fewer strong sites (e.g., PVAc-PVP/PES). We propose that strong surface sites may nucleate protein aggregation, initiated preferentially by protein oligomers, and accelerate ultrafiltration membrane fouling. At high protein concentrations (0.3-1.0 mg/mL), fewer strong adsorption sites were observed, and surface residence times were reduced. This suggests that at high concentrations

  17. Antigenic heterogeneity of capsid protein VP1 in foot-and-mouth disease virus (FMDV serotype Asia1

    Alam SM

    2013-08-01

    Full Text Available SM Sabbir Alam,1 Ruhul Amin,1 Mohammed Ziaur Rahman,2 M Anwar Hossain,1 Munawar Sultana11Department of Microbiology, University of Dhaka, Dhaka, Bangladesh; 2International Centre for Diarrhoeal Disease Research, Dhaka, BangladeshAbstract: Foot and mouth disease virus (FMDV, with its seven serotypes, is a highly contagious virus infecting mainly cloven-hoofed animals. The serotype Asia1 occurs mainly in Asian regions. An in-silico approach was taken to reveal the antigenic heterogeneities within the capsid protein VP1 of Asia1. A total of 47 VP1 sequences of Asia1 isolates from different countries of South Asian regions were selected, retrieved from database, and were aligned. The structure of VP1 protein was modeled using a homology modeling approach. Several antigenic sites were identified and mapped onto the three-dimensional protein structure. Variations at these antigenic sites were analyzed by calculating the protein variability index and finding mutation combinations. The data suggested that vaccine escape mutants have derived from only few mutations at several antigenic sites. Five antigenic peptides have been identified as the least variable epitopes, with just fewer amino acid substitutions. Only a limited number of serotype Asia1 antigenic variants were found to be circulated within the South Asian region. This emphasizes a possibility of formulating synthetic vaccines for controlling foot-and-mouth disease by Asia1 serotypes.Keywords: protein modeling, antigenic sites, sequence variation

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

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

    2017-01-01

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

  19. Extreme heterogeneity of polyadenylation sites in mRNAs encoding chloroplast RNA-binding proteins in Nicotiana plumbaginifolia.

    Klahre, U; Hemmings-Mieszczak, M; Filipowicz, W

    1995-06-01

    We have previously characterized nuclear cDNA clones encoding two RNA binding proteins, CP-RBP30 and CP-RBP-31, which are targeted to chloroplasts in Nicotiana plumbaginifolia. In this report we describe the analysis of the 3'-untranslated regions (3'-UTRs) in 22 CP-RBP30 and 8 CP-RBP31 clones which reveals that mRNAs encoding both proteins have a very complex polyadenylation pattern. Fourteen distinct poly(A) sites were identified among CP-RBP30 clones and four sites among the CP-RBP31 clones. The authenticity of the sites was confirmed by RNase A/T1 mapping of N. plumbaginifolia RNA. CP-RBP30 provides an extreme example of the heterogeneity known to be a feature of mRNA polyadenylation in higher plants. Using PCR we have demonstrated that CP-RBP genes in N. plumbaginifolia and N. sylvestris, in addition to the previously described introns interrupting the coding region, contain an intron located in the 3' non-coding part of the gene. In the case of the CP-RBP31, we have identified one polyadenylation event occurring in this intron.

  20. Deep Sequencing Reveals Uncharted Isoform Heterogeneity of the Protein-Coding Transcriptome in Cerebral Ischemia.

    Bhattarai, Sunil; Aly, Ahmed; Garcia, Kristy; Ruiz, Diandra; Pontarelli, Fabrizio; Dharap, Ashutosh

    2018-06-03

    Gene expression in cerebral ischemia has been a subject of intense investigations for several years. Studies utilizing probe-based high-throughput methodologies such as microarrays have contributed significantly to our existing knowledge but lacked the capacity to dissect the transcriptome in detail. Genome-wide RNA-sequencing (RNA-seq) enables comprehensive examinations of transcriptomes for attributes such as strandedness, alternative splicing, alternative transcription start/stop sites, and sequence composition, thus providing a very detailed account of gene expression. Leveraging this capability, we conducted an in-depth, genome-wide evaluation of the protein-coding transcriptome of the adult mouse cortex after transient focal ischemia at 6, 12, or 24 h of reperfusion using RNA-seq. We identified a total of 1007 transcripts at 6 h, 1878 transcripts at 12 h, and 1618 transcripts at 24 h of reperfusion that were significantly altered as compared to sham controls. With isoform-level resolution, we identified 23 splice variants arising from 23 genes that were novel mRNA isoforms. For a subset of genes, we detected reperfusion time-point-dependent splice isoform switching, indicating an expression and/or functional switch for these genes. Finally, for 286 genes across all three reperfusion time-points, we discovered multiple, distinct, simultaneously expressed and differentially altered isoforms per gene that were generated via alternative transcription start/stop sites. Of these, 165 isoforms derived from 109 genes were novel mRNAs. Together, our data unravel the protein-coding transcriptome of the cerebral cortex at an unprecedented depth to provide several new insights into the flexibility and complexity of stroke-related gene transcription and transcript organization.

  1. Heterogeneous genetic diversity pattern in Plasmodium vivax genes encoding merozoite surface proteins (MSP) -7E, -7F and -7L.

    Garzón-Ospina, Diego; Forero-Rodríguez, Johanna; Patarroyo, Manuel A

    2014-12-13

    The msp-7 gene has become differentially expanded in the Plasmodium genus; Plasmodium vivax has the highest copy number of this gene, several of which encode antigenic proteins in merozoites. DNA sequences from thirty-six Colombian clinical isolates from P. vivax (pv) msp-7E, -7F and -7L genes were analysed for characterizing and studying the genetic diversity of these pvmsp-7 members which are expressed during the intra-erythrocyte stage; natural selection signals producing the variation pattern so observed were evaluated. The pvmsp-7E gene was highly polymorphic compared to pvmsp-7F and pvmsp-7L which were seen to have limited genetic diversity; pvmsp-7E polymorphism was seen to have been maintained by different types of positive selection. Even though these copies seemed to be species-specific duplications, a search in the Plasmodium cynomolgi genome (P. vivax sister taxon) showed that both species shared the whole msp-7 repertoire. This led to exploring the long-term effect of natural selection by comparing the orthologous sequences which led to finding signatures for lineage-specific positive selection. The results confirmed that the P. vivax msp-7 family has a heterogeneous genetic diversity pattern; some members are highly conserved whilst others are highly diverse. The results suggested that the 3'-end of these genes encode MSP-7 proteins' functional region whilst the central region of pvmsp-7E has evolved rapidly. The lineage-specific positive selection signals found suggested that mutations occurring in msp-7s genes during host switch may have succeeded in adapting the ancestral P. vivax parasite population to humans.

  2. Genetic heterogeneity of retinitis pigmentosa

    Hartono, Hartono

    2015-01-01

    Genetic heterogeneity is a phenomenon in which a genetic disease can be transmitted by several modes of inheritance. The understanding of genetic heterogeneity is important in giving genetic counselling.The presence of genetic heterogeneity can be explained by the existence of:1.different mutant alleles at a single locus, and2.mutant alleles at different loci affecting the same enzyme or protein, or affecting different enzymes or proteins.To have an overall understanding of genetic heterogene...

  3. Heterogeneous electron transfer of a two-centered heme protein: redox and electrocatalytic properties of surface-immobilized cytochrome C(4).

    Monari, Stefano; Battistuzzi, Gianantonio; Borsari, Marco; Di Rocco, Giulia; Martini, Laura; Ranieri, Antonio; Sola, Marco

    2009-10-15

    The recombinant diheme cytochrome c(4) from the psycrophilic bacterium Pseudoalteromonas haloplanktis TAC 125 and its Met64Ala and Met164Ala variants, which feature a hydroxide ion axially bound to the heme iron at the N- and C-terminal domains, respectively, were found to exchange electrons efficiently with a gold electrode coated with a SAM of 11-mercapto-1-undecanoic acid. The mutation-induced removal of the redox equivalence of the two heme groups and changes in the net charge of the protein lobes yield two-centered protein systems with unprecedented properties in the electrode-immobilized state. The heterogeneous and intraheme electron transfer processes were characterized for these species in which the high- and low-potential heme groups are swapped over in the bilobal protein framework and experience a constrained (M64A) and unconstrained (M164A) orientation toward the electrode. The reduction thermodynamics for the native and mutated hemes were measured for the first time for a diheme cytochrome c. In the diffusing regime, they reproduce closely those for the corresponding centers in single-heme class-I cytochromes c, despite the low sequence identity. Larger differences are observed in the thermodynamics of the immobilized species and in the heterogeneous electron transfer rate constants. T-dependent kinetic measurements show that the proteins are positioned approximately 7 A from the HOOC-terminated SAM-coated electrode. Protein-electrode orientation and efficient intraheme ET enable the His,OH(-)-ligated heme A of the immobilized Met64Ala variant to carry out the reductive electrocatalysis of molecular oxygen. This system therefore constitutes a novel two-centered heme-based biocatalytic interface to be exploited for "third-generation" amperometric biosensing.

  4. Heterogeneous nuclear ribonucleoproteins H, H', and F are members of a ubiquitously expressed subfamily of related but distinct proteins encoded by genes mapping to different chromosomes

    Honoré, B; Rasmussen, H H; Vorum, H

    1995-01-01

    Molecular cDNA cloning, two-dimensional gel immunoblotting, and amino acid microsequencing identified three sequence-unique and distinct proteins that constitute a subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins corresponding to hnRNPs H, H', and F. These proteins share...... epitopes and sequence identity with two other proteins, isoelectric focusing sample spot numbers 2222 (37.6 kDa; pI 6.5) and 2326 (39.5 kDa; pI 6.6), indicating that the subfamily may contain additional members. The identity between hnRNPs H and H' is 96%, between H and F 78%, and between H' and F 75......%, respectively. The three proteins contain three repeats, which we denote quasi-RRMs (qRRMs) since they have a remote similarity to the RNA recognition motif (RRM). The three qRRMs of hnRNP H, with a few additional NH2-terminal amino acids, were constructed by polymerase chain reaction amplification and used...

  5. Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry: implications for IgA nephropathy

    Renfrow, MB; Mackay, CL; Chalmers, MJ

    2007-01-01

    deficiency in IgA1 proteins occurs randomly or preferentially at specific sites. We have previously demonstrated the first direct localization of multiple O-glycosylation sites on a single IgA1 myeloma protein by use of activated ion-electron capture dissociation (AI-ECD) Fourier transform ion cyclotron...... resonance (FT-ICR) tandem mass spectrometry. Here, we report the analysis of IgA1 O-glycan heterogeneity by use of FT-ICR MS and liquid chromatography FT-ICR MS to obtain unbiased accurate mass profiles of IgA1 HR glycopeptides from three different IgA1 myeloma proteins. Additionally, we report the first AI......-ECD fragmentation on an individual IgA1 O-glycopeptide from an IgA1 HR preparation that is reproducible for each IgA1 myeloma protein. These results suggest that future analysis of IgA1 HR from IgAN patients and normal healthy controls should be feasible....

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

    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

  7. Constrained Maximum Likelihood Estimation of Relative Abundances of Protein Conformation in a Heterogeneous Mixture from Small Angle X-Ray Scattering Intensity Measurements

    Onuk, A. Emre; Akcakaya, Murat; Bardhan, Jaydeep P.; Erdogmus, Deniz; Brooks, Dana H.; Makowski, Lee

    2015-01-01

    In this paper, we describe a model for maximum likelihood estimation (MLE) of the relative abundances of different conformations of a protein in a heterogeneous mixture from small angle X-ray scattering (SAXS) intensities. To consider cases where the solution includes intermediate or unknown conformations, we develop a subset selection method based on k-means clustering and the Cramér-Rao bound on the mixture coefficient estimation error to find a sparse basis set that represents the space spanned by the measured SAXS intensities of the known conformations of a protein. Then, using the selected basis set and the assumptions on the model for the intensity measurements, we show that the MLE model can be expressed as a constrained convex optimization problem. Employing the adenylate kinase (ADK) protein and its known conformations as an example, and using Monte Carlo simulations, we demonstrate the performance of the proposed estimation scheme. Here, although we use 45 crystallographically determined experimental structures and we could generate many more using, for instance, molecular dynamics calculations, the clustering technique indicates that the data cannot support the determination of relative abundances for more than 5 conformations. The estimation of this maximum number of conformations is intrinsic to the methodology we have used here. PMID:26924916

  8. Surface Induced Dissociation Coupled with High Resolution Mass Spectrometry Unveils Heterogeneity of a 211 kDa Multicopper Oxidase Protein Complex

    Zhou, Mowei; Yan, Jing; Romano, Christine A.; Tebo, Bradley M.; Wysocki, Vicki H.; Paša-Tolić, Ljiljana

    2018-01-01

    Manganese oxidation is an important biogeochemical process that is largely regulated by bacteria through enzymatic reactions. However, the detailed mechanism is poorly understood due to challenges in isolating and characterizing these unknown enzymes. A manganese oxidase, Mnx, from Bacillus sp. PL-12 has been successfully overexpressed in active form as a protein complex with a molecular mass of 211 kDa. We have recently used surface induced dissociation (SID) and ion mobility-mass spectrometry (IM-MS) to release and detect folded subcomplexes for determining subunit connectivity and quaternary structure. The data from the native mass spectrometry experiments led to a plausible structural model of this multicopper oxidase, which has been difficult to study by conventional structural biology methods. It was also revealed that each Mnx subunit binds a variable number of copper ions. Becasue of the heterogeneity of the protein and limited mass resolution, ambiguities in assigning some of the observed peaks remained as a barrier to fully understanding the role of metals and potential unknown ligands in Mnx. In this study, we performed SID in a modified Fourier transform-ion cyclotron resonance (FTICR) mass spectrometer. The high mass accuracy and resolution offered by FTICR unveiled unexpected artificial modifications on the protein that had been previously thought to be iron bound species based on lower resolution spectra. Additionally, isotopically resolved spectra of the released subcomplexes revealed the metal binding stoichiometry at different structural levels. This method holds great potential for in-depth characterization of metalloproteins and protein-ligand complexes. [Figure not available: see fulltext.

  9. PredPPCrys: accurate prediction of sequence cloning, protein production, purification and crystallization propensity from protein sequences using multi-step heterogeneous feature fusion and selection.

    Huilin Wang

    Full Text Available X-ray crystallography is the primary approach to solve the three-dimensional structure of a protein. However, a major bottleneck of this method is the failure of multi-step experimental procedures to yield diffraction-quality crystals, including sequence cloning, protein material production, purification, crystallization and ultimately, structural determination. Accordingly, prediction of the propensity of a protein to successfully undergo these experimental procedures based on the protein sequence may help narrow down laborious experimental efforts and facilitate target selection. A number of bioinformatics methods based on protein sequence information have been developed for this purpose. However, our knowledge on the important determinants of propensity for a protein sequence to produce high diffraction-quality crystals remains largely incomplete. In practice, most of the existing methods display poorer performance when evaluated on larger and updated datasets. To address this problem, we constructed an up-to-date dataset as the benchmark, and subsequently developed a new approach termed 'PredPPCrys' using the support vector machine (SVM. Using a comprehensive set of multifaceted sequence-derived features in combination with a novel multi-step feature selection strategy, we identified and characterized the relative importance and contribution of each feature type to the prediction performance of five individual experimental steps required for successful crystallization. The resulting optimal candidate features were used as inputs to build the first-level SVM predictor (PredPPCrys I. Next, prediction outputs of PredPPCrys I were used as the input to build second-level SVM classifiers (PredPPCrys II, which led to significantly enhanced prediction performance. Benchmarking experiments indicated that our PredPPCrys method outperforms most existing procedures on both up-to-date and previous datasets. In addition, the predicted crystallization

  10. [Levels and molecular heterogeneity of serotonin transporter protein in platelets of patients with different mental diseases: a comparative analysis with the use of monoclonal and polyclonal antibodies].

    Brusov, O S; Faktor, M I; Zlobina, G P; Bologov, P V; Kaleda, V G; Oleĭchik, I V; Korenev, A N; Piatnitskiĭ, A N; Dupin, A M; Katasonov, A B; Morozova, M A; Beniashvili, A G; Lozier, R Kh; Pavlova, E V; Segal, O L; Massino, Iu S; Dmitriev, A D

    2001-01-01

    Polyclonal (PAb) and monoclonal (MAb) antibodies to CT2-epitope of the C-terminal fragment of serotonin transporter (SERT) protein were used to study the levels and molecular heterogeneity of platelet SERT in healthy donors and patients with affective (AD) and somatoform (SD) disorders, schizoaffective disorder (SAD) and schizophrenia. SERT was found to exist as high molecular wight (HMW) and low molecular weight (LMW) forms separated after electrophoresis. The levels of HMW and LMW forms of SERT were significantly, decreased in mentally ill patients as compared to healthy individuals. Unlike PAb, horse radish peroxidase (HRP)-conjugated MAbs were more sensitive and specific to SERT and could detect the LMW form of SERT as a duplet protein form with MW about 40 and 43 kDa. The MAb to CT2 C-terminal fragment of SERT conjugated with HRP is considered to be a new valuable tool for further investigation of SERT expression, properties, and posttranslation modification in the controls and in patients with different psychopathology.

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

    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

  12. Epigenetics targeted protein-vorinostat nanomedicine inducing apoptosis in heterogeneous population of primary acute myeloid leukemia cells including refractory and relapsed cases.

    Chandran, Parwathy; Kavalakatt, Anu; Malarvizhi, Giridharan Loghanathan; Vasanthakumari, Divya Rani Vikraman Nair; Retnakumari, Archana Payickattu; Sidharthan, Neeraj; Pavithran, Keechilat; Nair, Shantikumar; Koyakutty, Manzoor

    2014-05-01

    Aberrant epigenetics play a key role in the onset and progression of acute myeloid leukemia (AML). Herein we report in silico modelling based development of a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti-leukemic activity against heterogeneous population of AML patient samples (n=9), including refractory and relapsed cases, and three representative cell lines expressing CD34(+)/CD38(-) stem cell phenotype (KG-1a), promyelocytic phenotype (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having ~100nm size exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell lines and patient samples, and induced enhanced HDAC inhibition, oxidative injury, cell cycle arrest and apoptosis compared to free vorinostat. Most importantly, nanomedicine showed exceptional single-agent activity against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. Collectively, this epigenetics targeted nanomedicine appears to be a promising therapeutic strategy against various French-American-British (FAB) classes of AML. Through the use of a protein-vorinostat agent, exceptional single-agent activity was demonstrated against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. The studied epigenetics targeted nanomedicine approach is a promising therapeutic strategy against various French-American-British classes of acute myeloid leukemia. © 2014 Elsevier Inc. All rights reserved.

  13. Heterogeneous reactors

    Moura Neto, C. de; Nair, R.P.K.

    1979-08-01

    The microscopic study of a cell is meant for the determination of the infinite multiplication factor of the cell, which is given by the four factor formula: K(infinite) = n(epsilon)pf. The analysis of an homogeneous reactor is similar to that of an heterogeneous reactor, but each factor of the four factor formula can not be calculated by the formulas developed in the case of an homogeneous reactor. A great number of methods was developed for the calculation of heterogeneous reactors and some of them are discussed. (Author) [pt

  14. Heterogeneity in recombinant protein production

    Schalén, Martin; Johanson, Ted; Lundin, Luisa

    2012-01-01

    A crucial step in biotechnology is the scale-up process. Normally, lab scale verification and optimization of production processes and strains are performed in small reactors with perfect mixing and hence the cells experience a homogenous environment. The gradients that occur in industrial scale ...

  15. Heterogeneous Gossip

    Frey, Davide; Guerraoui, Rachid; Kermarrec, Anne-Marie; Koldehofe, Boris; Mogensen, Martin; Monod, Maxime; Quéma, Vivien

    Gossip-based information dissemination protocols are considered easy to deploy, scalable and resilient to network dynamics. Load-balancing is inherent in these protocols as the dissemination work is evenly spread among all nodes. Yet, large-scale distributed systems are usually heterogeneous with respect to network capabilities such as bandwidth. In practice, a blind load-balancing strategy might significantly hamper the performance of the gossip dissemination.

  16. A Heterogeneous Nuclear Ribonucleoprotein A/B-Related Protein Binds to Single-Stranded DNA near the 5′ End or within the Genome of Feline Parvovirus and Can Modify Virus Replication

    Wang, Dai; Parrish, Colin R.

    1999-01-01

    Phage display of cDNA clones prepared from feline cells was used to identify host cell proteins that bound to DNA-containing feline panleukopenia virus (FPV) capsids but not to empty capsids. One gene found in several clones encoded a heterogeneous nuclear ribonucleoprotein (hnRNP)-related protein (DBP40) that was very similar in sequence to the A/B-type hnRNP proteins. DBP40 bound specifically to oligonucleotides representing a sequence near the 5′ end of the genome which is exposed on the outside of the full capsid but did not bind most other terminal sequences. Adding purified DBP40 to an in vitro fill-in reaction using viral DNA as a template inhibited the production of the second strand after nucleotide (nt) 289 but prior to nt 469. DBP40 bound to various regions of the viral genome, including a region between nt 295 and 330 of the viral genome which has been associated with transcriptional attenuation of the parvovirus minute virus of mice, which is mediated by a stem-loop structure of the DNA and cellular proteins. Overexpression of the protein in feline cells from a plasmid vector made them largely resistant to FPV infection. Mutagenesis of the protein binding site within the 5′ end viral genome did not affect replication of the virus. PMID:10438866

  17. Variants of beta-microglobulin cleaved at lysine-58 retain the main conformational features of the native protein but are more conformationally heterogeneous and unstable at physiological temperature

    Mimmi, Maria C; Jørgensen, Thomas J D; Pettirossi, Fabio

    2006-01-01

    -58 is removed. We find that the solution stability of both variants, especially of beta2-microglobulin from which lysine-58 is removed, is much reduced compared to wild-type beta2-microglobulin and is strongly dependent on temperature and protein concentration. 1H-NMR spectroscopy and amide hydrogen......Cleavage of the small amyloidogenic protein beta2-microglobulin after lysine-58 renders it more prone to unfolding and aggregation. This is important for dialysis-related beta2-microglobulin amyloidosis, since elevated levels of cleaved beta2-microglobulin may be found in the circulation...

  18. Immunophenotype Heterogeneity in Nasal Glomangiopericytoma

    Adriana Handra-Luca

    2015-01-01

    Full Text Available 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.

  19. Heterogeneous network architectures

    Christiansen, Henrik Lehrmann

    2006-01-01

    is flexibility. This thesis investigates such heterogeneous network architectures and how to make them flexible. A survey of algorithms for network design is presented, and it is described how using heuristics can increase the speed. A hierarchical, MPLS based network architecture is described......Future networks will be heterogeneous! Due to the sheer size of networks (e.g., the Internet) upgrades cannot be instantaneous and thus heterogeneity appears. This means that instead of trying to find the olution, networks hould be designed as being heterogeneous. One of the key equirements here...... and it is discussed that it is advantageous to heterogeneous networks and illustrated by a number of examples. Modeling and simulation is a well-known way of doing performance evaluation. An approach to event-driven simulation of communication networks is presented and mixed complexity modeling, which can simplify...

  20. Heterogeneity of reward mechanisms.

    Lajtha, A; Sershen, H

    2010-06-01

    The finding that many drugs that have abuse potential and other natural stimuli such as food or sexual activity cause similar chemical changes in the brain, an increase in extracellular dopamine (DA) in the shell of the nucleus accumbens (NAccS), indicated some time ago that the reward mechanism is at least very similar for all stimuli and that the mechanism is relatively simple. The presently available information shows that the mechanisms involved are more complex and have multiple elements. Multiple brain regions, multiple receptors, multiple distinct neurons, multiple transmitters, multiple transporters, circuits, peptides, proteins, metabolism of transmitters, and phosphorylation, all participate in reward mechanisms. The system is variable, is changed during development, is sex-dependent, and is influenced by genetic differences. Not all of the elements participate in the reward of all stimuli. Different set of mechanisms are involved in the reward of different drugs of abuse, yet different mechanisms in the reward of natural stimuli such as food or sexual activity; thus there are different systems that distinguish different stimuli. Separate functions of the reward system such as anticipation, evaluation, consummation and identification; all contain function-specific elements. The level of the stimulus also influences the participation of the elements of the reward system, there are possible reactions to even below threshold stimuli, and excessive stimuli can change reward to aversion involving parts of the system. Learning and memory of past reward is an important integral element of reward and addictive behavior. Many of the reward elements are altered by repeated or chronic stimuli, and chronic exposure to one drug is likely to alter the response to another stimulus. To evaluate and identify the reward stimulus thus requires heterogeneity of the reward components in the brain.

  1. Targeting population heterogeneity for optimal cell factories

    Heins, Anna-Lena; Carlqvist, Magnus; Helmark, S.

    the heterogeneity level of the population. To further investigate these phenomena and gain a deeper understanding of population heterogeneity, Saccharomyces cerevisiae growth reporter strains based on the expression of green fluorescent protein (GFP) were constructed which enabled us to perform single cell level...... analysis, and thereby created the possibility to map population heterogeneity. A factorial design with pH, glucose concentration and oxygen level was performed in batch cultivations using the growth reporter strains to evaluate the effect of those environmental factors on heterogeneity level and amount......To achieve an efficient production process, it is essential to optimize both the strain and the cultivation conditions. Traditionally, a microbial population has been considered homogeneous in optimization studies of fermentation processes. However, research has shown that a typical microbial...

  2. Heterogeneous cellular networks

    Hu, Rose Qingyang

    2013-01-01

    A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

  3. Neurobiological heterogeneity in ADHD

    de Zeeuw, P.

    2011-01-01

    Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly heterogeneous disorder clinically. Symptoms take many forms, from subtle but pervasive attention problems or dreaminess up to disruptive and unpredictable behavior. Interestingly, early neuroscientific work on ADHD assumed either a

  4. Heterogeneous Calculation of {epsilon}

    Jonsson, Alf

    1961-02-15

    A heterogeneous method of calculating the fast fission factor given by Naudet has been applied to the Carlvik - Pershagen definition of {epsilon}. An exact calculation of the collision probabilities is included in the programme developed for the Ferranti - Mercury computer.

  5. Heterogeneous Calculation of ε

    Jonsson, Alf

    1961-02-01

    A heterogeneous method of calculating the fast fission factor given by Naudet has been applied to the Carlvik - Pershagen definition of ε. An exact calculation of the collision probabilities is included in the programme developed for the Ferranti - Mercury computer

  6. HETEROGENEOUS INTEGRATION TECHNOLOGY

    2017-08-24

    AFRL-RY-WP-TR-2017-0168 HETEROGENEOUS INTEGRATION TECHNOLOGY Dr. Burhan Bayraktaroglu Devices for Sensing Branch Aerospace Components & Subsystems...Final September 1, 2016 – May 1, 2017 4. TITLE AND SUBTITLE HETEROGENEOUS INTEGRATION TECHNOLOGY 5a. CONTRACT NUMBER In-house 5b. GRANT NUMBER N/A...provide a structure for this review. The history and the current status of integration technologies in each category are examined and product examples are

  7. Heterogeneous gas core reactor

    Han, K.I.

    1977-01-01

    Preliminary investigations of a heterogeneous gas core reactor (HGCR) concept suggest that this potential power reactor offers distinct advantages over other existing or conceptual reactor power plants. One of the most favorable features of the HGCR is the flexibility of the power producing system which allows it to be efficiently designed to conform to a desired optimum condition without major conceptual changes. The arrangement of bundles of moderator/coolant channels in a fissionable gas or mixture of gases makes a truly heterogeneous nuclear reactor core. It is this full heterogeneity for a gas-fueled reactor core which accounts for the novelty of the heterogeneous gas core reactor concept and leads to noted significant advantages over previous gas core systems with respect to neutron and fuel economy, power density, and heat transfer characteristics. The purpose of this work is to provide an insight into the design, operating characteristics, and safety of a heterogeneous gas core reactor system. The studies consist mainly of neutronic, energetic and kinetic analyses of the power producing and conversion systems as a preliminary assessment of the heterogeneous gas core reactor concept and basic design. The results of the conducted research indicate a high potential for the heterogeneous gas core reactor system as an electrical power generating unit (either large or small), with an overall efficiency as high as 40 to 45%. The HGCR system is found to be stable and safe, under the conditions imposed upon the analyses conducted in this work, due to the inherent safety of ann expanding gaseous fuel and the intrinsic feedback effects of the gas and water coolant

  8. Green heterogeneous wireless networks

    Ismail, Muhammad; Nee, Hans-Peter; Qaraqe, Khalid A; Serpedin, Erchin

    2016-01-01

    This book focuses on the emerging research topic "green (energy efficient) wireless networks" which has drawn huge attention recently from both academia and industry. This topic is highly motivated due to important environmental, financial, and quality-of-experience (QoE) considerations. Specifically, the high energy consumption of the wireless networks manifests in approximately 2% of all CO2 emissions worldwide. This book presents the authors’ visions and solutions for deployment of energy efficient (green) heterogeneous wireless communication networks. The book consists of three major parts. The first part provides an introduction to the "green networks" concept, the second part targets the green multi-homing resource allocation problem, and the third chapter presents a novel deployment of device-to-device (D2D) communications and its successful integration in Heterogeneous Networks (HetNets). The book is novel in that it specifically targets green networking in a heterogeneous wireless medium, which re...

  9. Isotopes in heterogeneous catalysis

    Hargreaves, Justin SJ

    2006-01-01

    The purpose of this book is to review the current, state-of-the-art application of isotopic methods to the field of heterogeneous catalysis. Isotopic studies are arguably the ultimate technique in in situ methods for heterogeneous catalysis. In this review volume, chapters have been contributed by experts in the field and the coverage includes both the application of specific isotopes - Deuterium, Tritium, Carbon-14, Sulfur-35 and Oxygen-18 - as well as isotopic techniques - determination of surface mobility, steady state transient isotope kinetic analysis, and positron emission profiling.

  10. Cancer heterogeneity and imaging.

    O'Connor, James P B

    2017-04-01

    There is interest in identifying and quantifying tumor heterogeneity at the genomic, tissue pathology and clinical imaging scales, as this may help better understand tumor biology and may yield useful biomarkers for guiding therapy-based decision making. This review focuses on the role and value of using x-ray, CT, MRI and PET based imaging methods that identify, measure and map tumor heterogeneity. In particular we highlight the potential value of these techniques and the key challenges required to validate and qualify these biomarkers for clinical use. Copyright © 2016. Published by Elsevier Ltd.

  11. Heterogeneity and Networks

    Goyal, S.

    2018-01-01

    This chapter shows that networks can have large and differentiated effects on behavior and then argues that social and economic pressures facilitate the formation of heterogenous networks. Thus networks can play an important role in understanding the wide diversity in human behaviour and in economic outcomes.

  12. Heterogeneous Computing in Economics

    Dziubinski, M.P.; Grassi, S.

    2014-01-01

    This paper shows the potential of heterogeneous computing in solving dynamic equilibrium models in economics. We illustrate the power and simplicity of C++ Accelerated Massive Parallelism (C++ AMP) recently introduced by Microsoft. Starting from the same exercise as Aldrich et al. (J Econ Dyn...

  13. Heterogeneity of Dutch rainfall

    Witter, J.V.

    1984-01-01

    Rainfall data for the Netherlands have been used in this study to investigate aspects of heterogeneity of rainfall, in particular local differences in rainfall levels, time trends in rainfall, and local differences in rainfall trend. The possible effect of urbanization and industrialization on the

  14. in Heterogeneous Media

    Saeed Balouchi

    2013-01-01

    Full Text Available Fractured reservoirs contain about 85 and 90 percent of oil and gas resources respectively in Iran. A comprehensive study and investigation of fractures as the main factor affecting fluid flow or perhaps barrier seems necessary for reservoir development studies. High degrees of heterogeneity and sparseness of data have incapacitated conventional deterministic methods in fracture network modeling. Recently, simulated annealing (SA has been applied to generate stochastic realizations of spatially correlated fracture networks by assuming that the elastic energy of fractures follows Boltzmann distribution. Although SA honors local variability, the objective function of geometrical fracture modeling is defined for homogeneous conditions. In this study, after the introduction of SA and the derivation of the energy function, a novel technique is presented to adjust the model with highly heterogeneous data for a fractured field from the southwest of Iran. To this end, the regular object-based model is combined with a grid-based technique to cover the heterogeneity of reservoir properties. The original SA algorithm is also modified by being constrained in different directions and weighting the energy function to make it appropriate for heterogeneous conditions. The simulation results of the presented approach are in good agreement with the observed field data.

  15. Heterogeneous chromium catalysts

    2005-01-01

    The present invention relates to a heterogeneous chromium catalyst system for the polymerisation of ethylene and/or alpha olefins prepared by the steps of: (a) providing a silica-containing support, (b) treating the silica-containing support with a chromium compound to form a chromium-based

  16. Why does heterogeneity matter?

    K.B. Pierce

    2007-01-01

    This is a review of the book "Ecosystem function in heterogeneous landscapes" published in 2005. The authors are G. Lovett, C. Jones, M.G. Turner, and K.C. Weathers. It was published by Springer, New York. The book is a synthesis of the 10th Gary conference held at the Institute of Ecosystem Studies in Millbrook, New York, in 2003.

  17. Heterogeneity and option pricing

    Benninga, Simon; Mayshar, Joram

    2000-01-01

    An economy with agents having constant yet heterogeneous degrees of relative risk aversion prices assets as though there were a single decreasing relative risk aversion pricing representative agent. The pricing kernel has fat tails and option prices do not conform to the Black-Scholes formula.

  18. Heterogeneous Materials I and Heterogeneous Materials II

    Knowles, K M

    2004-01-01

    In these two volumes the author provides a comprehensive survey of the various mathematically-based models used in the research literature to predict the mechanical, thermal and electrical properties of hetereogeneous materials, i.e., materials containing two or more phases such as fibre-reinforced polymers, cast iron and porous ceramic kiln furniture. Volume I covers linear properties such as linear dielectric constant, effective electrical conductivity and elastic moduli, while Volume II covers nonlinear properties, fracture and atomistic and multiscale modelling. Where appropriate, particular attention is paid to the use of fractal geometry and percolation theory in describing the structure and properties of these materials. The books are advanced level texts reflecting the research interests of the author which will be of significant interest to research scientists working at the forefront of the areas covered by the books. Others working more generally in the field of materials science interested in comparing predictions of properties with experimental results may well find the mathematical level quite daunting initially, as it is apparent that the author assumes a level of mathematics consistent with that taught in final year undergraduate and graduate theoretical physics courses. However, for such readers it is well worth persevering because of the in-depth coverage to which the various models are subjected, and also because of the extensive reference lists at the back of both volumes which direct readers to the various source references in the scientific literature. Thus, for the wider materials science scientific community the two volumes will be a valuable library resource. While I would have liked to see more comparison with experimental data on both ideal and 'real' heterogeneous materials than is provided by the author and a discussion of how to model strong nonlinear current--voltage behaviour in systems such as zinc oxide varistors, my overall

  19. Information and Heterogeneous Beliefs

    Christensen, Peter Ove; Qin, Zhenjiang

    2014-01-01

    In an incomplete market with heterogeneous prior beliefs, we show public information can have a substantial impact on the ex ante cost of capital, trading volume, and investor welfare. The Pareto effcient public information system is the system enjoying the maximum ex ante cost of capital...... and the maximum expected abnormal trading volume. Imperfect public information increases the gains-to-trade based on heterogeneously updated posterior beliefs. In an exchange economy, this leads to higher growth in the investors' certainty equivalents and, thus, a higher equilibrium interest rate, whereas the ex...... ante risk premium is unaffected by the informativeness of the public information system. Similar results are obtained in a production economy, but the impact on the ex ante cost of capital is dampened compared to the exchange economy due to welfare improving reductions in real investments to smooth...

  20. Micromechanics of heterogeneous materials

    Buryachenko, Valeriy

    2007-01-01

    Here is an accurate and timely account of micromechanics, which spans materials science, mechanical engineering, applied mathematics, technical physics, geophysics, and biology. The book features rigorous and unified theoretical methods of applied mathematics and statistical physics in the material science of microheterogeneous media. Uniquely, it offers a useful demonstration of the systematic and fundamental research of the microstructure of the wide class of heterogeneous materials of natural and synthetic nature.

  1. Percolation in Heterogeneous Media

    Vocka, Radim

    1999-01-01

    This work is a theoretical reflection on the problematic of the modeling of heterogeneous media, that is on the way of their simple representation conserving their characteristic features. Two particular problems are addressed in this thesis. Firstly, we study the transport in porous media, that is in a heterogeneous media which structure is quenched. A pore space is represented in a simple way - a pore is symbolized as a tube of a given length and a given diameter. The fact that the correlations in the distribution of pore sizes are taken into account by a construction of a hierarchical network makes possible the modeling of porous media with a porosity distributed over several length scales. The transport in the hierarchical network shows qualitatively different phenomena from those observed in simpler models. A comparison of numerical results with experimental data shows that the hierarchical network gives a good qualitative representation of the structure of real porous media. Secondly, we study a problem of the transport in a heterogeneous media which structure is evolving during the time. The models where the evolution of the structure is not influenced by the transport are studied in detail. These models present a phase transition of the same nature as that observed on the percolation networks. We propose a new theoretical description of this transition, and we express critical exponents describing the evolution of the conductivity as a function of fundamental exponents of percolation theory. (author) [fr

  2. Dynamic heterogeneity in life histories

    Tuljapurkar, Shripad; Steiner, Uli; Orzack, Steven Hecht

    2009-01-01

    or no fixed heterogeneity influences this trait. We propose that dynamic heterogeneity provides a 'neutral' model for assessing the possible role of unobserved 'quality' differences between individuals. We discuss fitness for dynamic life histories, and the implications of dynamic heterogeneity...... generate dynamic heterogeneity: life-history differences produced by stochastic stratum dynamics. We characterize dynamic heterogeneity in a range of species across taxa by properties of the Markov chain: the entropy, which describes the extent of heterogeneity, and the subdominant eigenvalue, which...... distributions of lifetime reproductive success. Dynamic heterogeneity contrasts with fixed heterogeneity: unobserved differences that generate variation between life histories. We show by an example that observed distributions of lifetime reproductive success are often consistent with the claim that little...

  3. Heterogeneous nuclear ribonucleoprotein D/AUF1 interacts with ...

    SEARCHU

    Ribonucleic acids (RNAs) in cells are bound to proteins. Heterogeneous nuclear ribonucleoprotein (hnRNP) is one of the representative proteins bound to RNAs in eukaryotic cells. More than 30 hnRNPs have been determined to exist in human nuclei, and are referred to as hnRNPs A1 through U (Choi and Dreyfuss 1984; ...

  4. Heterogenous mismatch-repair status in colorectal cancer

    Joost, Patrick; Veurink, Nynke; Holck, Susanne

    2014-01-01

    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....... 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...

  5. Heterogeneous chromatin target model

    Watanabe, Makoto

    1996-01-01

    The higher order structure of the entangled chromatin fibers in a chromosome plays a key role in molecular control mechanism involved in chromosome mutation due to ionizing radiations or chemical mutagens. The condensed superstructure of chromatin is not so rigid and regular as has been postulated in general. We have proposed a rheological explanation for the flexible network system ('chromatin network') that consists of the fluctuating assembly of nucleosome clusters linked with supertwisting DNA in a chromatin fiber ('Supertwisting Particulate Model'). We have proposed a 'Heterosensitive Target Model' for cellular radiosensitivity that is a modification of 'Heterogeneous Target Model'. The heterogeneity of chromatin target is derived from the highly condensed organization of chromatin segments consist of unstable and fragile sites in the fluctuating assembly of nucleosome clusters, namely 'supranucleosomal particles' or 'superbeads'. The models have been principally supported by our electron microscopic experiments employing 'surface - spreading whole - mount technique' since 1967. However, some deformation and artifacts in the chromatin structure are inevitable with these electron microscopic procedures. On the contrary, the 'atomic force microscope (AFM)' can be operated in liquid as well as in the air. A living specimen can be examined without any preparative procedures. Micromanipulation of the isolated chromosome is also possible by the precise positional control of a cantilever on the nanometer scale. The living human chromosomes were submerged in a solution of culture medium and observed by AFM using a liquid immersion cell. The surface - spreading whole - mount technique was applicable for this observation. The particulate chromatin segments of nucleosome clusters were clearly observed within mitotic human chromosomes in a living hydrated condition. These findings support the heterogeneity of chromatin target in a living cell. (J.P.N.)

  6. Heterogeneous Active Matter

    Kolb, Thomas; Klotsa, Daphne

    Active systems are composed of self-propelled (active) particles that locally convert energy into motion and exhibit emergent collective behaviors, such as fish schooling and bird flocking. Most works so far have focused on monodisperse, one-component active systems. However, real systems are heterogeneous, and consist of several active components. We perform molecular dynamics simulations of multi-component active matter systems and report on their emergent behavior. We discuss the phase diagram of dynamic states as well as parameters where we see mixing versus segregation.

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

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

    Yang, Hui; Tang, Ming; Gross, Thilo

    2015-08-21

    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.

  9. Heterogeneous gas core reactor

    Diaz, N.J.; Dugan, E.T.

    1983-01-01

    A heterogeneous gas core nuclear reactor is disclosed comprising a core barrel provided interiorly with an array of moderator-containing tubes and being otherwise filled with a fissile and/or fertile gaseous fuel medium. The fuel medium may be flowed through the chamber and through an external circuit in which heat is extracted. The moderator may be a fluid which is flowed through the tubes and through an external circuit in which heat is extracted. The moderator may be a solid which may be cooled by a fluid flowing within the tubes and through an external heat extraction circuit. The core barrel is surrounded by moderator/coolant material. Fissionable blanket material may be disposed inwardly or outwardly of the core barrel

  10. Heterogeneity in Waardenburg syndrome.

    Hageman, M J; Delleman, J W

    1977-01-01

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

  11. Quantifying hidden individual heterogeneity

    Steiner, Ulrich; Lenart, Adam; Vaupel, James W.

    Aging is assumed to be driven by the accumulation of damage or some other aging factor which shapes demographic patterns, including the classical late age mortality plateaus. However to date, heterogeneity in these damage stages is not observed. Here, we estimate underlying stage distributions...... and stage dynamics, based on observed survival patterns of isoclonal bacteria. Our results reveal demographic dynamics being dominated by low damage stages and transmission of damage from mother to daughters is low. Still, our models are too simplistic and deterministic. Explaining the observed data...... requires more stochastic processes as our current models includes. We are only at the beginning of understanding the diverse mechanism behind aging and the shaping of senescence....

  12. Receiver Heterogeneity Helps

    Kovács, Erika R.; Pedersen, Morten Videbæk; Roetter, Daniel Enrique Lucani

    2014-01-01

    Heterogeneity amongst devices and desired service are commonly seen as a source of additional challenges for setting up an efficient multi-layer multicast service. In particular, devices requiring only the base layer can become a key bottleneck to the performance for other devices. This paper...... studies the case of a wireless multi-layer multicast setting and shows that the judicious use of network coding allows devices with different computational capabilities to trade-off processing complexity for an improved quality of service. As a consequence, individual devices can determine their required...... effort, while bringing significant advantages to the system as a whole. Network coding is used as a key element to reduce signaling in order to deliver the multicast service. More importantly, our proposed approach focuses on creating some structure in the transmitted stream by allowing inter-layer...

  13. Interconnecting heterogeneous database management systems

    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. Heterogeneity in kinesin function

    Reddy, Babu J N; Tripathy, Suvranta; Vershinin, Michael; Tanenbaum, Marvin E; Xu, Jing; Mattson-Hoss, Michelle; Arabi, Karim; Chapman, Dail; Doolin, Tory; Hyeon, Changbong; Gross, Steven P

    2017-01-01

    The kinesin family proteins are often studied as prototypical molecular motors; a deeper understanding of them can illuminate regulation of intracellular transport. It is typically assumed that they function identically. Here we find that this assumption of homogeneous function appears incorrect:

  15. Heterogeneity: multilingualism and democracy

    Hans-Jürgen Krumm

    2004-01-01

    Full Text Available Linguistic diversity and multilingualism on the part of individuals are aprerequisite and a constitutive condition of enabling people to live togetherin a world of growing heterogeneity. Foreign language teaching plays animportant part in democratic education because it can be seen as a trainingin respecting otherness and developing an intercultural, non-ethnocentricperception and attitude. This is all the more important because of the neces-sity of integrating children from migrant families into school life.My article argues that language education policy has to take this per-spective into account, i.e., of establishing a planned diversification so thatpupils (and their parents will not feel satisfied with learning English only,but also become motivated to learn languages of their own neighbourhood,such as migrant and minority languages. However, in order to make use ofthe linguistic resources in the classroom, relating it to the democratic impetusof foreign language education, it is necessary to revise existing languagepolicies and to develop a multilingual perspective for all educational institutions.

  16. Heterogeneous burnable poisons:

    Leiva, Sergio; Agueda, Horacio; Russo, Diego

    1989-01-01

    The use of materials possessing high neutron absorption cross-section commonly known as 'burnable poisons' have its origin in BWR reactors with the purpose of improving the efficiency of the first fuel load. Later on, it was extended to PWR to compensate of initial reactivity without infringing the requirement of maintaining a negative moderator coefficient. The present tendency is to increase the use of solid burnable poisons to extend the fuel cycle life and discharge burnup. There are two concepts for the burnable poisons utilization: 1) heterogeneously distributions in the form of rods, plates, etc. and 2) homogeneous dispersions of burnable poisons in the fuel. The purpose of this work is to present the results of sinterability studies, performed on Al 2 O 3 -B 4 C and Al 2 O 3 -Gd 2 O 3 systems. Experiments were carried on pressing at room temperature mixtures of powders containing up to 5 wt % of B 4 C or Gd 2 O 3 in Al 2 O 3 and subsequently sintering at 1750 deg C in reducing atmosphere. Evaluation of density, porosity and microstructures were done and a comparison with previous experiences is shown. (Author) [es

  17. Parsing Heterogeneous Striatal Activity

    Kae Nakamura

    2017-05-01

    Full Text Available The striatum is an input channel of the basal ganglia and is well known to be involved in reward-based decision making and learning. At the macroscopic level, the striatum has been postulated to contain parallel functional modules, each of which includes neurons that perform similar computations to support selection of appropriate actions for different task contexts. At the single-neuron level, however, recent studies in monkeys and rodents have revealed heterogeneity in neuronal activity even within restricted modules of the striatum. Looking for generality in the complex striatal activity patterns, here we briefly survey several types of striatal activity, focusing on their usefulness for mediating behaviors. In particular, we focus on two types of behavioral tasks: reward-based tasks that use salient sensory cues and manipulate outcomes associated with the cues; and perceptual decision tasks that manipulate the quality of noisy sensory cues and associate all correct decisions with the same outcome. Guided by previous insights on the modular organization and general selection-related functions of the basal ganglia, we relate striatal activity patterns on these tasks to two types of computations: implementation of selection and evaluation. We suggest that a parsing with the selection/evaluation categories encourages a focus on the functional commonalities revealed by studies with different animal models and behavioral tasks, instead of a focus on aspects of striatal activity that may be specific to a particular task setting. We then highlight several questions in the selection-evaluation framework for future explorations.

  18. Quantifying spatial heterogeneity from images

    Pomerantz, Andrew E; Song Yiqiao

    2008-01-01

    Visualization techniques are extremely useful for characterizing natural materials with complex spatial structure. Although many powerful imaging modalities exist, simple display of the images often does not convey the underlying spatial structure. Instead, quantitative image analysis can extract the most important features of the imaged object in a manner that is easier to comprehend and to compare from sample to sample. This paper describes the formulation of the heterogeneity spectrum to show the extent of spatial heterogeneity as a function of length scale for all length scales to which a particular measurement is sensitive. This technique is especially relevant for describing materials that simultaneously present spatial heterogeneity at multiple length scales. In this paper, the heterogeneity spectrum is applied for the first time to images from optical microscopy. The spectrum is measured for thin section images of complex carbonate rock cores showing heterogeneity at several length scales in the range 10-10 000 μm.

  19. Emerging understanding of multiscale tumor heterogeneity

    Michael J Gerdes

    2014-12-01

    Full Text Available 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 ten 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.

  20. Heterogeneous ice nucleation

    Bogdan, A. [Helsinki Univ. (Finland). Dept. of Physics

    1994-12-31

    The classical theory of heterogenous ice nucleation is reviewed in detail. The modelling of ice nucleation in the adsorbed water films on natural particles by analogous ice nucleation in adsorbed water films on the walls of porous media is discussed. Ice nucleation in adsorbed films of purewater and the HNO{sub 3}/H{sub 2}0 binary system on the surface of porous aerosol (SiO{sub 2}) was investigated using the method of NMR spectroscopy. The median freezing temperature and freezing temperature region were shown to be highly sensitive both to the average thickness of the adsorbed films and to the amount of adsorbed nitric acid. The character of the ice phase formation tends to approach that of bulk liquid with increasing adsorbed film thickness. Under the given conditions the thickness of the adsorbed films decreases with an increasing amount of adsorbed nitric acid molecules The molar concentration of nitric acid in the adsorbed films is very small (of the order of 10{sup -}3 10{sup -}2 (M/l)). Nitric acid molecules tend to adsorb on the surface of aerosol to a greater extent than in subsequent layers. The concentration is greatest in layers situated close to the surface and sharply decreases with the distance from the surface. The difference between the median freezing temperatures for adsorbed pure water and for the binary system was found to be about 9 K for films of equal thickness. This is about 150 times greater than the difference between the median freezing temperatures of bulk pure water and a solution with the same concentration of nitric acid. (orig.)

  1. Heterogeneous dissipative composite structures

    Ryabov, Victor; Yartsev, Boris; Parshina, Ludmila

    2018-05-01

    The paper suggests mathematical models of decaying vibrations in layered anisotropic plates and orthotropic rods based on Hamilton variation principle, first-order shear deformation laminated plate theory (FSDT), as well as on the viscous-elastic correspondence principle of the linear viscoelasticity theory. In the description of the physical relationships between the materials of the layers forming stiff polymeric composites, the effect of vibration frequency and ambient temperature is assumed as negligible, whereas for the viscous-elastic polymer layer, temperature-frequency relationship of elastic dissipation and stiffness properties is considered by means of the experimentally determined generalized curves. Mitigation of Hamilton functional makes it possible to describe decaying vibration of anisotropic structures by an algebraic problem of complex eigenvalues. The system of algebraic equation is generated through Ritz method using Legendre polynomials as coordinate functions. First, real solutions are found. To find complex natural frequencies of the system, the obtained real natural frequencies are taken as input values, and then, by means of the 3rd order iteration method, complex natural frequencies are calculated. The paper provides convergence estimates for the numerical procedures. Reliability of the obtained results is confirmed by a good correlation between analytical and experimental values of natural frequencies and loss factors in the lower vibration tones for the two series of unsupported orthotropic rods formed by stiff GRP and CRP layers and a viscoelastic polymer layer. Analysis of the numerical test data has shown the dissipation & stiffness properties of heterogeneous composite plates and rods to considerably depend on relative thickness of the viscoelastic polymer layer, orientation of stiff composite layers, vibration frequency and ambient temperature.

  2. Heterogeneity of rabbit platelets

    Karpatkin, S.

    1978-01-01

    Rabbits were injected intravenously with a cohort platelet label, 75 Se-selenomethionine. Platelet-rich plasma was separated into five different platelet density fractions on each of seven days by repetitively centrifuging the same sample of platelet-rich plasma at increasing gravitational force. The heaviest platelet sediment fraction was enriched with larger platelets. The lightest platelet sediment fraction was enriched with smaller platelets. Incorporation of isotope into the heaviest platelet fraction was considerably greater than incorporation into the lightest platelet fraction. The mean platelet survival of the lightest two fractions was significantly shorter than that of the heaviest three fractions. SDS-polyacrylamide gel electrophoresis of the platelet cell sap generally revealed 10 prominent protein bands for the heaviest platelet fractions. The lightest platelet fraction had six absent to markedly diminished platelet proteins. The data are compatible with two models, (1) heavy-large platelets are, on average, young platelets which become lighter-smaller platelets while losing platelet membranes and cell sap components with time. (2) Heavy-large platelets and light-small platelets are produced independently by specific megakarocytes. The heavy-large platelets incorporate more isotope that lighter-smaller platelets (possibly because of their megakarocyte precursor). However, they are released earlier into the circulation than lighter-smaller platelets and are therefore younger platelets. The light-smaller platelets which are released later into the circulation have a shorter survival. (author)

  3. Imaging metabolic heterogeneity in cancer.

    Sengupta, Debanti; Pratx, Guillem

    2016-01-06

    As our knowledge of cancer metabolism has increased, it has become apparent that cancer metabolic processes are extremely heterogeneous. The reasons behind this heterogeneity include genetic diversity, the existence of multiple and redundant metabolic pathways, altered microenvironmental conditions, and so on. As a result, methods in the clinic and beyond have been developed in order to image and study tumor metabolism in the in vivo and in vitro regimes. Both regimes provide unique advantages and challenges, and may be used to provide a picture of tumor metabolic heterogeneity that is spatially and temporally comprehensive. Taken together, these methods may hold the key to appropriate cancer diagnoses and treatments in the future.

  4. Evidence for nonallelic genetic heterogeneity in autosomal recessive retinitis pigmentosa

    Bleeker-Wagemakers, L. M.; Gal, A.; Kumar-Singh, R.; van den Born, L. I.; Li, Y.; Schwinger, E.; Sandkuijl, L. A.; Bergen, A. A.; Kenna, P.; Humphries, P.

    1992-01-01

    Recent evidence suggesting the involvement of mutant rhodopsin proteins in the pathogenesis of autosomal recessive retinitis pigmentosa has prompted us to investigate whether this form of the disease shows non-allelic genetic heterogeneity, as has previously been shown to be the case in autosomal

  5. High Content Analysis of Compositional Heterogeneities to Study GPCR Oligomerization

    Walsh, Samuel McEwen

    In this thesis I demonstrate how the natural compositional heterogeneities of synthetic and living cell model systems can be used to quantitate the mechanics of G-protein coupled receptor (GPCR) oligomerization with Förster resonance energy transfer (FRET). The thesis is structured around three a...

  6. Viscous fingering with permeability heterogeneity

    Tan, C.; Homsy, G.M.

    1992-01-01

    Viscous fingering in miscible displacements in the presence of permeability heterogeneities is studied using two-dimensional simulations. The heterogeneities are modeled as stationary random functions of space with finite correlation scale. Both the variance and scale of the heterogeneities are varied over modest ranges. It is found that the fingered zone grows linearly in time in a fashion analogous to that found in homogeneous media by Tan and Homsy [Phys. Fluids 31, 1330 (1988)], indicating a close coupling between viscous fingering on the one hand and flow through preferentially more permeable paths on the other. The growth rate of the mixing zone increases monotonically with the variance of the heterogeneity, as expected, but shows a maximum as the correlation scale is varied. The latter is explained as a ''resonance'' between the natural scale of fingers in homogeneous media and the correlation scale

  7. Tumor Heterogeneity and Drug Resistance

    Kucerova, L.; Skolekova, S.; Kozovska, Z.

    2015-01-01

    New generation of sequencing methodologies revealed unexpected complexity and genomic alterations linked with the tumor subtypes. This diversity exists across the tumor types, histologic tumor subtypes and subsets of the tumor cells within the same tumor. This phenomenon is termed tumor heterogeneity. Regardless of its origin and mechanisms of development it has a major impact in the clinical setting. Genetic, phenotypic and expression pattern diversity of tumors plays critical role in the selection of suitable treatment and also in the prognosis prediction. Intratumoral heterogeneity plays a key role in the intrinsic and acquired chemoresistance to cytotoxic and targeted therapies. In this review we focus on the mechanisms of intratumoral and inter tumoral heterogeneity and their relationship to the drug resistance. Understanding of the mechanisms and spatiotemporal dynamics of tumor heterogeneity development before and during the therapy is important for the ability to design individual treatment protocols suitable in the given molecular context. (author)

  8. Aggregation Algorithms in Heterogeneous Tables

    Titus Felix FURTUNA

    2006-01-01

    Full Text Available The heterogeneous tables are most used in the problem of aggregation. A solution for this problem is to standardize these tables of figures. In this paper, we proposed some methods of aggregation based on the hierarchical algorithms.

  9. Homogenisation of heterogeneous viscoplastic materials.

    Sluis, van der O.; Schreurs, P.J.G.; Meijer, H.E.H.; Anderson, P.D.; Kruijt, P.G.M.

    1999-01-01

    Heterogeneous materials have been used extensively in the past few decades, since their mechanical properties, such as strength, stiffness and toughness are being improved continuously. Experimental work has clearly demonstrated the significant influence of the micromechanical phenomena on the

  10. Dealing with spatial heterogeneity

    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

  11. Optimal Control of Heterogeneous Systems with Endogenous Domain of Heterogeneity

    Belyakov, Anton O.; Tsachev, Tsvetomir; Veliov, Vladimir M.

    2011-01-01

    The paper deals with optimal control of heterogeneous systems, that is, families of controlled ODEs parameterized by a parameter running over a domain called domain of heterogeneity. The main novelty in the paper is that the domain of heterogeneity is endogenous: it may depend on the control and on the state of the system. This extension is crucial for several economic applications and turns out to rise interesting mathematical problems. A necessary optimality condition is derived, where one of the adjoint variables satisfies a differential inclusion (instead of equation) and the maximization of the Hamiltonian takes the form of “min-max”. As a consequence, a Pontryagin-type maximum principle is obtained under certain regularity conditions for the optimal control. A formula for the derivative of the objective function with respect to the control from L ∞ is presented together with a sufficient condition for its existence. A stylized economic example is investigated analytically and numerically.

  12. Organizational heterogeneity of vertebrate genomes.

    Frenkel, Svetlana; Kirzhner, Valery; Korol, Abraham

    2012-01-01

    Genomes of higher eukaryotes are mosaics of segments with various structural, functional, and evolutionary properties. The availability of whole-genome sequences allows the investigation of their structure as "texts" using different statistical and computational methods. One such method, referred to as Compositional Spectra (CS) analysis, is based on scoring the occurrences of fixed-length oligonucleotides (k-mers) in the target DNA sequence. CS analysis allows generating species- or region-specific characteristics of the genome, regardless of their length and the presence of coding DNA. In this study, we consider the heterogeneity of vertebrate genomes as a joint effect of regional variation in sequence organization superimposed on the differences in nucleotide composition. We estimated compositional and organizational heterogeneity of genome and chromosome sequences separately and found that both heterogeneity types vary widely among genomes as well as among chromosomes in all investigated taxonomic groups. The high correspondence of heterogeneity scores obtained on three genome fractions, coding, repetitive, and the remaining part of the noncoding DNA (the genome dark matter--GDM) allows the assumption that CS-heterogeneity may have functional relevance to genome regulation. Of special interest for such interpretation is the fact that natural GDM sequences display the highest deviation from the corresponding reshuffled sequences.

  13. Organizational heterogeneity of vertebrate genomes.

    Svetlana Frenkel

    Full Text Available Genomes of higher eukaryotes are mosaics of segments with various structural, functional, and evolutionary properties. The availability of whole-genome sequences allows the investigation of their structure as "texts" using different statistical and computational methods. One such method, referred to as Compositional Spectra (CS analysis, is based on scoring the occurrences of fixed-length oligonucleotides (k-mers in the target DNA sequence. CS analysis allows generating species- or region-specific characteristics of the genome, regardless of their length and the presence of coding DNA. In this study, we consider the heterogeneity of vertebrate genomes as a joint effect of regional variation in sequence organization superimposed on the differences in nucleotide composition. We estimated compositional and organizational heterogeneity of genome and chromosome sequences separately and found that both heterogeneity types vary widely among genomes as well as among chromosomes in all investigated taxonomic groups. The high correspondence of heterogeneity scores obtained on three genome fractions, coding, repetitive, and the remaining part of the noncoding DNA (the genome dark matter--GDM allows the assumption that CS-heterogeneity may have functional relevance to genome regulation. Of special interest for such interpretation is the fact that natural GDM sequences display the highest deviation from the corresponding reshuffled sequences.

  14. Nanoscale high-content analysis using compositional heterogeneities of single proteoliposomes

    Mathiasen, Signe; Christensen, Sune M.; Fung, Juan José

    2014-01-01

    Proteoliposome reconstitution is a standard method to stabilize purified transmembrane proteins in membranes for structural and functional assays. Here we quantified intrareconstitution heterogeneities in single proteoliposomes using fluorescence microscopy. Our results suggest that compositional...... heterogeneities can severely skew ensemble-average proteoliposome measurements but also enable ultraminiaturized high-content screens. We took advantage of this screening capability to map the oligomerization energy of the β2-adrenergic receptor using ∼10(9)-fold less protein than conventional assays....

  15. How to measure genetic heterogeneity

    Yamada, Ryo

    2009-01-01

    Genetic information of organisms is coded as a string of four letters, A, T, G and C, a sequence in macromolecules called deoxyribonucleic acid (DNA). DNA sequence offers blueprint of organisms and its heterogeneity determines identity and variation of species. The quantitation of this genetic heterogeneity is fundamental to understand biology. We compared previously-reported three measures, covariance matrix expression of list of loci (pair-wise r 2 ), the most popular index in genetics, and its multi-dimensional form, Ψ, and entropy-based index, ε. Thereafter we proposed two methods so that we could handle the diplotypic heterogeneity and quantitate the conditions where the number of DNA sequence samples is much smaller than the number of possible variants.

  16. Heterogeneity in Preferences and Productivity

    Gørtz, Mette

    This paper discusses the determinants of the retirement decision and the implications of retirement on economic well-being. The main contribution of the paper is to formulate the role of individual heterogeneity explicitly. We argue that individual heterogeneity in 1) productivity of market work...... choices of expenditure, household production and leisure for people in and around retirement. The unobserved individual heterogeneity factor is isolated by comparing cross-sectional evidence and panel data estimates of the effects of retirement on consumption and time allocation. Based on cross......-section data, we can identify a difference in consumption due to retirement status, but when the panel nature of the data is exploited, the effect of retirement on consumption is small and insignificant. Moreover, the analyses point at a large positive effect of retirement on household production. Our results...

  17. Job Heterogeneity and Coordination Frictions

    Kennes, John; le Maire, Daniel

    We develop a new directed search model of a frictional labor market with a continuum of heterogenous workers and firms. We estimate two versions of the model - auction and price posting - using Danish data on wages and productivities. Assuming heterogenous workers with no comparative advantage, we...... the job ladder, how the identification of assortative matching is fundamentally different in directed and undirected search models, how our theory accounts for business cycle facts related to inter-temporal changes in job offer distributions, and how our model could also be used to identify...

  18. Majority rule on heterogeneous networks

    Lambiotte, R

    2008-01-01

    We focus on the majority rule (MR) applied on heterogeneous networks. When the underlying topology is homogeneous, the system is shown to exhibit a transition from an ordered regime to a disordered regime when the noise is increased. When the network exhibits modular structures, in contrast, the system may also exhibit an asymmetric regime, where the nodes in each community reach an opposite average opinion. Finally, the node degree heterogeneity is shown to play an important role by displacing the location of the order-disorder transition and by making the system exhibit non-equipartition of the average spin

  19. Heterogeneity in isogenic populations of microorganisms

    Pedersen, Anne Egholm

    heterogeneity was detected when the culture had been propagated according to the guidelines of the Copenhagen School of Bacterial Growth Physiology. The L. lactis GFP reporter strain was more challenging to analyze. The population profile for this reporter strain was shown to be dependent on the type of medium...... values for quantifiable variables are used. The reproducibility of an experiment could thus be affected by the presence of subpopulations or high levels of phenotypic variations. Ole Maaløe and colleagues did in the late 1950’ties observe that the growth rate, RNA, DNA and protein synthesis and cell...... factor per unit of time. The use of a balanced growing culture is a cornerstone in the Copenhagen School of Bacterial Growth Physiology headed by Ole Maaløe. Due to the size of the microorganism it is challenging to measure a quantifiable variable in a single cell. However, fluorescence, whether being...

  20. Electronic Energy Transfer in Polarizable Heterogeneous Environments

    Svendsen, Casper Steinmann; Kongsted, Jacob

    2015-01-01

    such couplings provide important insight into the strength of interaction between photo-active pigments in protein-pigment complexes. Recently, attention has been payed to how the environment modifies or even controls the electronic couplings. To enable such theoretical predictions, a fully polarizable embedding......-order multipole moments. We use this extended model to systematically examine three different ways of obtaining EET couplings in a heterogeneous medium ranging from use of the exact transition density to a point-dipole approximation. Several interesting observations are made including that explicit use...... of transition densities in the calculation of the electronic couplings - also when including the explicit environment contribution - can be replaced by a much simpler transition point charge description without comprising the quality of the model predictions....

  1. Molecular ingredients of heterogeneous catalysis

    Somorjai, G.A.

    1982-06-01

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

  2. Behavioral heterogeneity in stock prices

    Boswijk, H.P.; Hommes, C.H.; Manzan, S.

    2007-01-01

    We estimate a dynamic asset pricing model characterized by heterogeneous boundedly rational agents. The fundamental value of the risky asset is publicly available to all agents, but they have different beliefs about the persistence of deviations of stock prices from the fundamental benchmark. An

  3. Prices and heterogeneous search costs

    Luis Moraga-Gonzalez, Jose; Sandor, Zsolt; Wildenbeest, Matthijs R.

    2017-01-01

    We study price formation in a model of consumer search for differentiated products in which consumers have heterogeneous search costs. We provide conditions under which a pure-strategy symmetric Nash equilibrium exists and is unique. Search costs affect two margins-the intensive search margin (or

  4. Communicating to heterogeneous target groups

    Pedersen, Karsten

    very often have to communicate to rather heterogeneous target groups that have little more in common than a certain geographical habitat. That goes against most schoolbook teaching in the field of communication, but is none the less the terms with which that kind of communication has to live...

  5. Morphology stabilization of heterogeneous blends

    1980-01-01

    A heterogeneous elastomer blend is described, consisting of at least two elastomer components which are cross-linkable by irradiation and having a stabilized morphology formed by subjecting the blend to high energy radiation to a point from below to slightly above the gel dose of the blend. (author)

  6. Heterogeneous Beliefs and Climate Catastrophes

    Kiseleva, T.

    2016-01-01

    We study how heterogeneous beliefs about the causes and extent of global warming affect local mitigation and adaptation strategies and therefore global climate dynamics. Local policies are determined by expectations of policy makers about future climate. There are three types of expectations: strong

  7. Molecular ingredients of heterogeneous catalysis

    Somorjai, G.A.

    1982-06-01

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

  8. Chloride Transport in Heterogeneous Formation

    Mukherjee, A.; Holt, R. M.

    2017-12-01

    The chloride mass balance (CMB) is a commonly-used method for estimating groundwater recharge. Observations of the vertical distribution of pore-water chloride are related to the groundwater infiltration rates (i.e. recharge rates). In CMB method, the chloride distribution is attributed mainly to the assumption of one dimensional piston flow. In many places, however, the vertical distribution of chloride will be influenced by heterogeneity, leading to horizontal movement of infiltrating waters. The impact of heterogeneity will be particularly important when recharge is locally focused. When recharge is focused in an area, horizontal movement of chloride-bearing waters, coupled with upward movement driven by evapotranspiration, may lead to chloride bulges that could be misinterpreted if the CMB method is used to estimate recharge. We numerically simulate chloride transport and evaluate the validity of the CMB method in highly heterogeneous systems. This simulation is conducted for the unsaturated zone of Ogallala, Antlers, and Gatuna (OAG) formations in Andrews County, Texas. A two dimensional finite element model will show the movement of chloride through heterogeneous systems. We expect to see chloride bulges not only close to the surface but also at depths characterized by horizontal or upward movement. A comparative study of focused recharge estimates in this study with available recharge data will be presented.

  9. A Heterogeneous Quantum Computer Architecture

    Fu, X.; Riesebos, L.; Lao, L.; Garcia Almudever, C.; Sebastiano, F.; Versluis, R.; Charbon, E.; Bertels, K.

    2016-01-01

    In this paper, we present a high level view of the heterogeneous quantum computer architecture as any future quantum computer will consist of both a classical and quantum computing part. The classical part is needed for error correction as well as for the execution of algorithms that contain both

  10. Social capital and community heterogeneity

    Coffé, Hilde R.

    2009-01-01

    Abstract 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

  11. Replikasi Unidirectional pada Heterogen Database

    Hendro Nindito

    2013-12-01

    Full Text Available The use of diverse database technology in enterprise today can not be avoided. Thus, technology is needed to generate information in real time. The purpose of this research is to discuss a database replication technology that can be applied in heterogeneous database environments. In this study we use Windows-based MS SQL Server database to Linux-based Oracle database as the goal. The research method used is prototyping where development can be done quickly and testing of working models of the interaction process is done through repeated. From this research it is obtained that the database replication technolgy using Oracle Golden Gate can be applied in heterogeneous environments in real time as well.

  12. Clinical heterogeneity in Fabry disease

    G. N. Salogub

    2015-01-01

    Full Text Available Fabry disease is an X-linked, lysosomal storage disease (OMIM: 301500, caused by α-galactosidase A deficiency, resulting in accumulation of its substrates, glycosphingolipids, primarily – globotriaosylceramide, in the lysosomes of multiple cell types with multi-system clinical manifestations, even within the same family, including abnormalities of the central and peripheral nervous system, kidneys, heart, gastrointestinal tract, lungs, organ of vision. Clinical heterogeneity is often the reason of the delayed diagnosis. Nowadays enzyme replacement therapy has proved its efficiency in the treatment of Fabry disease. Including Fabry disease in the differential diagnosis of a large range of disorders is important because of its wide clinical heterogeneity and the possibility of an earlier intervention with a beneficial treatment.

  13. Thermal properties of heterogeneous fuels

    Staicu, D.; Beauvy, M.

    1998-01-01

    Fresh or irradiated nuclear fuels are composites or solid solutions more or less heterogeneous, and their thermal conductivities are strongly dependent on the microstructure. The effective thermal conductivities of these heterogeneous solids must be determined for the modelling of the behaviour under irradiation. Different methods (analytical or numerical) published in the literature can be used for the calculation of this effective thermal conductivity. They are analysed and discussed, but finally only few of them are really useful because the assumptions selected are often not compatible with the complex microstructures observed in the fuels. Numerical calculations of the effective thermal conductivity of various fuels based on the microstructure information provided in our laboratory by optical microscopy or electron micro-probe analysis images, have been done for the validation of these methods. The conditions necessary for accurate results on effective thermal conductivity through these numerical calculations are discussed. (author)

  14. Renewal-anomalous-heterogeneous files

    Flomenbom, Ophir

    2010-01-01

    Renewal-anomalous-heterogeneous files are solved. A simple file is made of Brownian hard spheres that diffuse stochastically in an effective 1D channel. Generally, Brownian files are heterogeneous: the spheres' diffusion coefficients are distributed and the initial spheres' density is non-uniform. In renewal-anomalous files, the distribution of waiting times for individual jumps is not exponential as in Brownian files, yet obeys: ψ α (t)∼t -1-α , 0 2 >, obeys, 2 >∼ 2 > nrml α , where 2 > nrml is the MSD in the corresponding Brownian file. This scaling is an outcome of an exact relation (derived here) connecting probability density functions of Brownian files and renewal-anomalous files. It is also shown that non-renewal-anomalous files are slower than the corresponding renewal ones.

  15. Interference, heterogeneity and disease gene mapping

    Keats, B. [Louisiana State Univ. Medical Center, New Orleans, LA (United States)

    1996-12-31

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

  16. Hyphal heterogeneity in Aspergillus niger

    de Bekker, A.M.

    2011-01-01

    Mycelial fungi use hyphae to colonize substrates. These hyphae secrete enzymes that convert complex polymers into breakdown products that can be taken up to serve as nutrients. Using GFP as a reporter it has been shown that exploring hyphae of Aspergillus niger are heterogenic with respect to expression of the glucoamylase gene glaA; some hyphae strongly express the glucoamylase gene glaA, while others express it lowly. This was a surprising finding considering the fact that all hyphae were e...

  17. Macroeconomic Policies and Agent Heterogeneity

    GOTTLIEB, Charles

    2012-01-01

    Defence date: 24 February 2012 Examining Board: Giancarlo Corsetti, Arpad Abraham, Juan Carlos Conesa, Jonathan Heathcote. This thesis contributes to the understanding of macroeconomic policies’ impact on the distribution of wealth. It belongs to the strand of literature that departs from the representative agent assumption and perceives agent heterogeneity and the induced disparities in wealth accumulation, as an important dimension of economic policy-making. Within such economic envir...

  18. Heterogeneous inflation expectations and learning

    Madeira, Carlos; Zafar, Basit

    2012-01-01

    Using the panel component of the Michigan Survey of Consumers, we estimate a learning model of inflation expectations, allowing for heterogeneous use of both private information and lifetime inflation experience. “Life-experience inflation” has a significant impact on individual expectations, but only for one-year-ahead inflation. Public information is substantially more relevant for longer-horizon expectations. Even controlling for life-experience inflation and public information, idiosyncra...

  19. REPLIKASI UNIDIRECTIONAL PADA HETEROGEN DATABASE

    Hendro Nindito; Evaristus Didik Madyatmadja; Albert Verasius Dian Sano

    2013-01-01

    The use of diverse database technology in enterprise today can not be avoided. Thus, technology is needed to generate information in real time. The purpose of this research is to discuss a database replication technology that can be applied in heterogeneous database environments. In this study we use Windows-based MS SQL Server database to Linux-based Oracle database as the goal. The research method used is prototyping where development can be done quickly and testing of working models of the...

  20. DATABASE REPLICATION IN HETEROGENOUS PLATFORM

    Hendro Nindito; Evaristus Didik Madyatmadja; Albert Verasius Dian Sano

    2014-01-01

    The application of diverse database technologies in enterprises today is increasingly a common practice. To provide high availability and survavibality of real-time information, a database replication technology that has capability to replicate databases under heterogenous platforms is required. The purpose of this research is to find the technology with such capability. In this research, the data source is stored in MSSQL database server running on Windows. The data will be replicated to MyS...

  1. Surface fluxes in heterogeneous landscape

    Bay Hasager, C

    1997-01-01

    The surface fluxes in homogeneous landscapes are calculated by similarity scaling principles. The methodology is well establish. In heterogeneous landscapes with spatial changes in the micro scale range, i e from 100 m to 10 km, advective effects are significant. The present work focus on these effects in an agricultural countryside typical for the midlatitudes. Meteorological and satellite data from a highly heterogeneous landscape in the Rhine Valley, Germany was collected in the large-scale field experiment TRACT (Transport of pollutants over complex terrain) in 1992. Classified satellite images, Landsat TM and ERS SAR, are used as basis for roughness maps. The roughnesses were measured at meteorological masts in the various cover classes and assigned pixel by pixel to the images. The roughness maps are aggregated, i e spatially averaged, into so-called effective roughness lengths. This calculation is performed by a micro scale aggregation model. The model solves the linearized atmospheric flow equations by a numerical (Fast Fourier Transform) method. This model also calculate maps of friction velocity and momentum flux pixel wise in heterogeneous landscapes. It is indicated how the aggregation methodology can be used to calculate the heat fluxes based on the relevant satellite data i e temperature and soil moisture information. (au) 10 tabs., 49 ills., 223 refs.

  2. Interest rate rules with heterogeneous expectations

    Anufriev, M.; Assenza, T.; Hommes, C.; Massaro, D.

    2011-01-01

    The recent macroeconomic literature stresses the importance of managing heterogeneous expectations in the formulation of monetary policy. We use a simple frictionless DSGE model to investigate inflation dynamics under alternative interest rate rules when agents have heterogeneous expectations and

  3. Heterogeneity in the multiple myeloma tumor clone

    Guikema, Jeroen E. J.; Hovenga, Sjoerd; Vellenga, Edo; Bos, Nicolaas A.

    2004-01-01

    Multiple Myeloma (MM) is a plasma cell malignancy which is characterized by a very heterogeneous disease outcome. Heterogeneity in plasma cell characteristics, including morphology, maturation status, immunophenotype and genetic abnormalities partly account for the variable disease outcome. Although

  4. Heterogeneity in the multiple myeloma tumor clone

    Guikema, JEJ; Hovenga, S; Vellenga, E; Bos, NA

    Multiple Myeloma ( MM) is a plasma cell malignancy which is characterized by a very heterogeneous disease outcome. Heterogeneity in plasma cell characteristics, including morphology, maturation status, immunophenotype and genetic abnormalities partly account for the variable disease outcome.

  5. Transfers in heterogeneous environments; Transferts en milieux heterogenes

    Flesselles, J M [Saint-Gobain Recherche, 93 - Aubervilliers (France); Gouesbet, G; Mees, L; Roze, C; Girasole, Th; Grehan, G [Laboratoire d' Electromagnetisme et Systemes Particulaires (LESP), UMR CNRS 6614, CORIA. Universite de Rouen et INSA de Rouen, 76 - Saint-Etienne du Rouvray (France); Goyheneche, J M; Vignoles, G; Coindreau, O [Laboratoire des Composites Thermostructuraux (LCTS), UMR 5801, 33 - Pessac (France); Moyne, Ch [LEMTA (UMR 7563) CNRS-INPL-UHP, 54 - Vandoeuvre les Nancy (France); Coussy, O [Institut Navier - ENPC, 77 - Marne-la-Vallee (France); Lassabatere, Th [Electricite de France Les Renardieres, Dept. Materiaux Mecanique des Composants, 77 - Moret sur Loing (France); Tadrist, L [IUSTI - UMR 6595, 13 - Marseille (France)

    2004-07-01

    This document gathers the articles and transparencies of the invited talks given at the 2004 French congress of thermal engineering about transfers in heterogeneous environment. Content: transfer phenomena in industrial glass furnaces; simple and multiple scattering diagnosis by femto-second pulsed laser: application to particulate diagnoses; thermal modeling of thermo-structural composites; hybrid mixtures theory, average volumic measurement, periodical or stochastic homogenization: advance in scale change processes; thermo-hydro-chemical-mechanical coupling in porous medium: application to young concrete structures and to clay barriers of disposal facilities; transfers and flows in fluidization: recent advances and future challenges. (J.S.)

  6. Irreversible adsorption of particles on heterogeneous surfaces.

    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 charge. Particle deposition occurred under diffusion-controlled transport conditions and their coverage was evaluated by direct particle counting using the optical and electron microscopy. Adsorption kinetics was quantitatively interpreted in terms of numerical solutions of the governing diffusion equation with the non-linear boundary condition derived from Monte-Carlo simulations. It was proven that for site coverage as low as a few percent the initial flux at heterogeneous surfaces attained the maximum value pertinent to homogeneous

  7. Heterogeneous policies, heterogeneous technologies: The case of renewable energy

    Nicolli, Francesco; Vona, Francesco

    2016-01-01

    This paper investigates empirically the effect of market regulation and renewable energy policies on innovation activity in different renewable energy technologies. For the EU countries and the years 1980 to 2007, we built a unique dataset containing information on patent production in eight different technologies, proxies of market regulation and technology-specific renewable energy policies. Our main finding is that, compared to privatisation and unbundling, reducing entry barriers is a more significant driver of renewable energy innovation, but that its effect varies across technologies and is stronger in technologies characterised by potential entry of small, independent power producers. In addition, the inducement effect of renewable energy policies is heterogeneous and more pronounced for wind, which is the only technology that is mature and has high technological potential. Finally, ratification of the Kyoto protocol, which determined a more stable and less uncertain policy framework, amplifies the inducement effect of both energy policy and market liberalisation. - Highlights: • We study the effect of market regulation and energy policy on renewable technologies. • Reducing entry barriers is a significant driver of renewable energy innovation. • The Kyoto protocol amplifies the effect of both energy policy and liberalisation. • These effects are heterogeneous across technologies and stronger for wind.

  8. Mechanical heterogeneity in ionic liquids

    Veldhorst, Arno A.; Ribeiro, Mauro C. C.

    2018-05-01

    Molecular dynamics (MD) simulations of five ionic liquids based on 1-alkyl-3-methylimidazolium cations, [CnC1im]+, have been performed in order to calculate high-frequency elastic moduli and to evaluate heterogeneity of local elastic moduli. The MD simulations of [CnC1im][NO3], n = 2, 4, 6, and 8, assessed the effect of domain segregation when the alkyl chain length increases, and [C8C1im][PF6] assessed the effect of strength of anion-cation interaction. Dispersion curves of excitation energies of longitudinal and transverse acoustic, LA and TA, modes were obtained from time correlation functions of mass currents at different wavevectors. High-frequency sound velocity of LA modes depends on the alkyl chain length, but sound velocity for TA modes does not. High-frequency bulk and shear moduli, K∞ and G∞, depend on the alkyl chain length because of a density effect. Both K∞ and G∞ are strongly dependent on the anion. The calculation of local bulk and shear moduli was accomplished by performing bulk and shear deformations of the systems cooled to 0 K. The simulations showed a clear connection between structural and elastic modulus heterogeneities. The development of nano-heterogeneous structure with increasing length of the alkyl chain in [CnC1im][NO3] implies lower values for local bulk and shear moduli in the non-polar domains. The mean value and the standard deviations of distributions of local elastic moduli decrease when [NO3]- is replaced by the less coordinating [PF6]- anion.

  9. Heterogeneity effects in neutron transport computations

    Gelbard, E.M.

    1975-01-01

    A nuclear reactor is, generally, an intricate heterogeneous structure whose adjacent components may differ radically in their neutronic properties. The heterogeneities in the structure of the reactor complicate the work of the reactor analyst and tend to degrade the efficiency of the numerical methods used in reactor computations. Two types of heterogeneity effects are considered. First, certain singularities in the solution of the neutron transport equation, induced by heterogeneities, are briefly described. Second, the effect of heterogeneities on neutron leakage rates, and consequently on effective diffusion coefficients, are discussed. (5 figures) (U.S.)

  10. Kinetics of heterogeneous catalytic reactions

    Boudart, Michel

    2014-01-01

    This book is a critical account of the principles of the kinetics of heterogeneous catalytic reactions in the light of recent developments in surface science and catalysis science. Originally published in 1984. The Princeton Legacy Library uses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These paperback editions preserve the original texts of these important books while presenting them in durable paperback editions. The goal of the Princeton Legacy Library is to vastly increase acc

  11. Fundamental concepts in heterogeneous catalysis

    Norskov, Jens K; Abild-Pedersen, Frank; Bligaard, Thomas

    2014-01-01

    This book is based on a graduate course and suitable as a primer for any newcomer to the field, this book is a detailed introduction to the experimental and computational methods that are used to study how solid surfaces act as catalysts.   Features include:First comprehensive description of modern theory of heterogeneous catalysisBasis for understanding and designing experiments in the field   Allows reader to understand catalyst design principlesIntroduction to important elements of energy transformation technologyTest driven at Stanford University over several semesters

  12. Integrating heterogeneous healthcare call centers.

    Peschel, K M; Reed, W C; Salter, K

    1998-01-01

    In a relatively short period, OHS has absorbed multiple call centers supporting different LOBs from various acquisitions, functioning with diverse standards, processes, and technologies. However, customer and employee satisfaction is predicated on OHS's ability to thoroughly integrate these heterogeneous call centers. The integration was initiated and has successfully progressed through a balanced program of focused leadership and a defined strategy which includes site consolidation, sound performance management philosophies, and enabling technology. Benefits have already been achieved with even more substantive ones to occur as the integration continues to evolve.

  13. Heterogeneous Economic Integration Agreement Effects

    Baier, Scott L.; Bergstrand, Jeffrey H.; Clance, Matthew W.

    2015-01-01

    Gravity equations have been used for more than 50 years to estimate ex post the partial effects of trade costs on international trade flows, and the well-known - and traditionally presumed exogenous – "trade-cost elasticity" plays a central role in computing general equilibrium trade-flow and welfare effects of trade-cost changes. This paper addresses theoretically and empirically the influence of variable and fixed export costs in explaining the likely heterogeneity in the trade-cost elast...

  14. A Heterogeneous Medium Analytical Benchmark

    Ganapol, B.D.

    1999-01-01

    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

  15. Heterogeneity in magnetic complex oxides

    Arenholz, Elke

    Heterogeneity of quantum materials on the nanoscale can result from the spontaneous formation of regions with distinct atomic, electronic and/or magnetic order, and indicates coexistence of competing quantum phases. In complex oxides, the subtle interplay of lattice, charge, orbital, and spin degrees of freedom gives rise to especially rich phase diagrams. For example, coexisting conducting and insulating phases can occur near metal-insulator transitions, colossal magnetoresistance can emerge where ferromagnetic and antiferromagnetic domains compete, and charge-ordered and superconducting regions are present simultaneously in materials exhibiting high-temperature superconductivity. Additionally, externally applied fields (electric, magnetic, or strain) or other external excitations (light or heat) can tip the energy balance towards one phase, or support heterogeneity and phase coexistence and provide the means to perturb and tailor quantum heterogeneity at the nanoscale. Engineering nanomaterials, with structural, electronic and magnetic characteristics beyond what is found in bulk materials, is possible today through the technique of thin film epitaxy, effectively a method of `spray painting' atoms on single crystalline substrates to create precisely customized layered structures with atomic arrangements defined by the underlying substrate. Charge transfer and spin polarization across interfaces as well as imprinting nanoscale heterogeneity between adjacent layers lead to intriguing and important new phenomena testing our understanding of basic physics and creating new functionalities. Moreover, the abrupt change of orientation of an order parameter between nanoscale domains can lead to unique phases that are localized at domain walls, including conducting domain walls in insulating ferroelectrics, and ferromagnetic domain walls in antiferromagnets. Here we present our recent results on tailoring the electronic anisotropy of multiferroic heterostructures by

  16. Robust mechanobiological behavior emerges in heterogeneous myosin systems

    Egan, Paul F.; Moore, Jeffrey R.; Ehrlicher, Allen J.; Weitz, David A.; Schunn, Christian; Cagan, Jonathan; LeDuc, Philip

    2017-09-01

    Biological complexity presents challenges for understanding natural phenomenon and engineering new technologies, particularly in systems with molecular heterogeneity. Such complexity is present in myosin motor protein systems, and computational modeling is essential for determining how collective myosin interactions produce emergent system behavior. We develop a computational approach for altering myosin isoform parameters and their collective organization, and support predictions with in vitro experiments of motility assays with α-actinins as molecular force sensors. The computational approach models variations in single myosin molecular structure, system organization, and force stimuli to predict system behavior for filament velocity, energy consumption, and robustness. Robustness is the range of forces where a filament is expected to have continuous velocity and depends on used myosin system energy. Myosin systems are shown to have highly nonlinear behavior across force conditions that may be exploited at a systems level by combining slow and fast myosin isoforms heterogeneously. Results suggest some heterogeneous systems have lower energy use near stall conditions and greater energy consumption when unloaded, therefore promoting robustness. These heterogeneous system capabilities are unique in comparison with homogenous systems and potentially advantageous for high performance bionanotechnologies. Findings open doors at the intersections of mechanics and biology, particularly for understanding and treating myosin-related diseases and developing approaches for motor molecule-based technologies.

  17. Socially Aware Heterogeneous Wireless Networks.

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

    2015-06-11

    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.

  18. Dispersivity in heterogeneous permeable media

    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

  19. Dispersivity in heterogeneous permeable media

    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 (typically 80%) of this change occurs is defined as the mixing zone length, which increases with increasing average distance traveled by the displacement front. Alternatively, 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 classical 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

  20. Heterogeneous Policies, Heterogeneous Technologies: The Case of Renewable Energy

    Nicolli, Francesco; Vona, Francesco

    2014-07-01

    This paper investigates empirically the effect of market regulation and renewable energy policies on innovation activity in different renewable energy technologies. For the EU countries and the years 1980 to 2007, we built a unique dataset containing information on patent production in eight different technologies, proxies of market regulation and technology-specific renewable energy policies. Our main findings show that lowering entry barriers is a more significant driver of renewable energy innovation than privatisation and un-bundling, but its effect varies across technologies, being stronger in technologies characterised by the potential entry of small, independent power producers. Additionally, the inducement effect of renewable energy policies is heterogeneous and more pronounced for wind, which is the only technology that is mature and has high technological potential. Finally, the ratification of the Kyoto protocol - determining a more stable and less uncertain policy framework - amplifies the inducement effect of both energy policy and market liberalisation. (authors)

  1. Fine Mapping Seronegative and Seropositive Rheumatoid Arthritis to Shared and Distinct HLA Alleles by Adjusting for the Effects of Heterogeneity

    Han, Buhm; Diogo, Dorothee; Eyre, Steve; Kallberg, Henrik; Zhernakova, Alexandra; Bowes, John; Padyukov, Leonid; Okada, Yukinori; Gonzalez-Gay, Miguel A.; Rantapaa-Dahlqvist, Solbritt; Martin, Javier; Huizinga, Tom W. J.; Plenge, Robert M.; Worthington, Jane; Gregersen, Peter K.; Klareskog, Lars; de Bakker, Paul I. W.; Raychaudhuri, Soumya

    2014-01-01

    Despite progress in defining human leukocyte antigen (HLA) alleles for anti-citrullinated-protein-autoantibody-positive (ACPA(+)) rheumatoid arthritis (RA), identifying HLA alleles for ACPA-negative (ACPA(-)) RA has been challenging because of clinical heterogeneity within clinical cohorts. We

  2. Nonlinear Poisson equation for heterogeneous media.

    Hu, Langhua; Wei, Guo-Wei

    2012-08-22

    The Poisson equation is a widely accepted model for electrostatic analysis. However, the Poisson equation is derived based on electric polarizations in a linear, isotropic, and homogeneous dielectric medium. This article introduces a nonlinear Poisson equation to take into consideration of hyperpolarization effects due to intensive charges and possible nonlinear, anisotropic, and heterogeneous media. Variational principle is utilized to derive the nonlinear Poisson model from an electrostatic energy functional. To apply the proposed nonlinear Poisson equation for the solvation analysis, we also construct a nonpolar solvation energy functional based on the nonlinear Poisson equation by using the geometric measure theory. At a fixed temperature, the proposed nonlinear Poisson theory is extensively validated by the electrostatic analysis of the Kirkwood model and a set of 20 proteins, and the solvation analysis of a set of 17 small molecules whose experimental measurements are also available for a comparison. Moreover, the nonlinear Poisson equation is further applied to the solvation analysis of 21 compounds at different temperatures. Numerical results are compared to theoretical prediction, experimental measurements, and those obtained from other theoretical methods in the literature. A good agreement between our results and experimental data as well as theoretical results suggests that the proposed nonlinear Poisson model is a potentially useful model for electrostatic analysis involving hyperpolarization effects. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. Acral peeling skin syndrome: a clinically and genetically heterogeneous disorder.

    Pavlovic, Sasha; Krunic, Aleksandar L; Bulj, Tanja K; Medenica, Maria M; Fong, Kenneth; Arita, Ken; McGrath, John A

    2012-01-01

    Acral peeling skin syndrome (APSS) is a rare, autosomal, recessive genodermatosis characterized by painless spontaneous exfoliation of the skin of the hands and feet at a subcorneal or intracorneal level. It usually presents at birth or appears later in childhood or early adulthood. Some cases result from mutations in the TGM5 gene that encodes transglutaminase 5, which has an important role in cross-linking cornified cell envelope proteins. We report a new APSS pedigree from Jordan that contains at least 10 affected family members, although sequencing of the TGM5 gene failed to disclose any pathogenic mutation(s). On the basis of probable consanguinity, we performed homozygosity mapping and identified areas of homozygosity on chromosomes 1, 6, 10, 13, and 16, although none of the intervals contained genes of clear relevance to cornification. APSS is a clinically and genetically heterogeneous disorder, and this Jordanian pedigree underscores the likelihood of still further heterogeneity. © 2011 Wiley Periodicals, Inc.

  4. Spatial coupling in heterogeneous catalysis

    Yamamoto, S. Y.; Surko, C. M.; Maple, M. B.

    1995-11-01

    Spatial coupling mechanisms are studied in the heterogeneous catalytic oxidation of carbon monoxide over platinum at atmospheric pressure under oscillatory conditions. Experiments are conducted in a continuous flow reactor, and the reaction rate is monitored using both infrared imaging and thermocouples. The catalysts are in the form of platinum annular thin films on washer-shaped quartz substrates, and they provide highly repeatable oscillatory behavior. Oscillations are typically spatially synchronized with the entire catalyst ``flashing'' on and off uniformly. Spatial coupling is investigated by introducing various barriers which split the annular ring in half. Infrared images show that coupling through the gas phase dominates coupling via the diffusion of CO on the surface or heat diffusion through the substrate. The introduction of a localized heat perturbation to the catalyst surface does not induce a transition in the reaction rate. Thus, it is likely that the primary mode of communication is through the gas-phase diffusion of reactants.

  5. Heterogeneities in nuclear waste glass

    Ladirat, Ch.

    1997-01-01

    The industrial vitrification of high level radioactive wastes is a 2 stage process. During the first stage, the concentrated solution is heated in a spinning resistance oven at the temperature of 400 Celsius degrees till evaporation and calcination. The second stage begins when the dry residue falls into a melting pot that is maintained at a temperature of 1100-1150 Celsius degrees. Glass fretting is added and the glass is elaborated through the fusion of the different elements present in the melting pot. Heterogeneities in the glass may be associated to: - the presence in the solution to vitrify of insoluble elements from the dissolution of the fuel (RuO 2 , Rh, Pd), - the presence of minuscule metal scraps (Zr) that have been produced during the cutting of the fuel element, - the failures to conform to the technical specifications of the vitrification process, for instance, temperatures or flow rates when introducing the different elements in the melting pot. (A.C.)

  6. Coordination Frictions and Job Heterogeneity

    Kennes, John; le Maire, Christian Daniel

    be readily solved with continuous exogenous worker heterogene- ity, where high type workers (high outside options and productivity) earn higher wages in high type jobs and are hired at least as frequently to the better job types as low type workers (low outside options and productivity). Third, we...... a number of new theoretical results, which are essential for the empirical application of this type of model to matched employer-employee microdata. First, we o¤er a robust equilibrium concept in which there is a continu- ous dispersion of job productivities and wages. Second, we show that our model can...... of these results preserve the essential tractability of the baseline model with aggregate shocks. Therefore, we o¤er a parsimonious, general equilibrium framework in which to study the process by which the contin- uous dispersion of wages and productivities varies over the business cycle for a large population...

  7. HETEROGENEOUS REBURNING BY MIXED FUELS

    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.

  8. Operando research in heterogeneous catalysis

    Groot, Irene

    2017-01-01

    This book is devoted to the emerging field of techniques for visualizing atomic-scale properties of active catalysts under actual working conditions, i.e. high gas pressures and high temperatures. It explains how to understand these observations in terms of the surface structures and dynamics and their detailed interplay with the gas phase. This provides an important new link between fundamental surface physics and chemistry, and applied catalysis. The book explains the motivation and the necessity of operando studies, and positions these with respect to the more traditional low-pressure investigations on the one hand and the reality of industrial catalysis on the other. The last decade has witnessed a rapid development of new experimental and theoretical tools for operando studies of heterogeneous catalysis. The book has a strong emphasis on the new techniques and illustrates how the challenges introduced by the harsh, operando conditions are faced for each of these new tools. Therefore, one can also read th...

  9. Surface science and heterogeneous catalysis

    Somorjai, G.A.

    1980-05-01

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

  10. Intertumoral Heterogeneity within Medulloblastoma Subgroups.

    Cavalli, Florence M G; Remke, Marc; Rampasek, Ladislav; Peacock, John; Shih, David J H; Luu, Betty; Garzia, Livia; Torchia, Jonathon; Nor, Carolina; Morrissy, A Sorana; Agnihotri, Sameer; Thompson, Yuan Yao; Kuzan-Fischer, Claudia M; Farooq, Hamza; Isaev, Keren; Daniels, Craig; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Lee, Ji Yeoun; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Vasiljevic, Alexandre; Faure-Conter, Cecile; Jouvet, Anne; Giannini, Caterina; Nageswara Rao, Amulya A; Li, Kay Ka Wai; Ng, Ho-Keung; Eberhart, Charles G; Pollack, Ian F; Hamilton, Ronald L; Gillespie, G Yancey; Olson, James M; Leary, Sarah; Weiss, William A; Lach, Boleslaw; Chambless, Lola B; Thompson, Reid C; Cooper, Michael K; Vibhakar, Rajeev; Hauser, Peter; van Veelen, Marie-Lise C; Kros, Johan M; French, Pim J; Ra, Young Shin; Kumabe, Toshihiro; López-Aguilar, Enrique; Zitterbart, Karel; Sterba, Jaroslav; Finocchiaro, Gaetano; Massimino, Maura; Van Meir, Erwin G; Osuka, Satoru; Shofuda, Tomoko; Klekner, Almos; Zollo, Massimo; Leonard, Jeffrey R; Rubin, Joshua B; Jabado, Nada; Albrecht, Steffen; Mora, Jaume; Van Meter, Timothy E; Jung, Shin; Moore, Andrew S; Hallahan, Andrew R; Chan, Jennifer A; Tirapelli, Daniela P C; Carlotti, Carlos G; Fouladi, Maryam; Pimentel, José; Faria, Claudia C; Saad, Ali G; Massimi, Luca; Liau, Linda M; Wheeler, Helen; Nakamura, Hideo; Elbabaa, Samer K; Perezpeña-Diazconti, Mario; Chico Ponce de León, Fernando; Robinson, Shenandoah; Zapotocky, Michal; Lassaletta, Alvaro; Huang, Annie; Hawkins, Cynthia E; Tabori, Uri; Bouffet, Eric; Bartels, Ute; Dirks, Peter B; Rutka, James T; Bader, Gary D; Reimand, Jüri; Goldenberg, Anna; Ramaswamy, Vijay; Taylor, Michael D

    2017-06-12

    While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Homogenization methods for heterogeneous assemblies

    Wagner, M.R.

    1980-01-01

    The third session of the IAEA Technical Committee Meeting is concerned with the problem of homogenization of heterogeneous assemblies. Six papers will be presented on the theory of homogenization and on practical procedures for deriving homogenized group cross sections and diffusion coefficients. That the problem of finding so-called ''equivalent'' diffusion theory parameters for the use in global reactor calculations is of great practical importance. In spite of this, it is fair to say that the present state of the theory of second homogenization is far from being satisfactory. In fact, there is not even a uniquely accepted approach to the problem of deriving equivalent group diffusion parameters. Common agreement exists only about the fact that the conventional flux-weighting technique provides only a first approximation, which might lead to acceptable results in certain cases, but certainly does not guarantee the basic requirement of conservation of reaction rates

  12. Thermoelectricity in Heterogeneous Nanofluidic Channels.

    Li, Long; Wang, Qinggong

    2018-05-01

    Ionic fluids are essential to energy conversion, water desalination, drug delivery, and lab-on-a-chip devices. Ionic transport in nanoscale confinements and complex physical fields still remain elusive. Here, a nanofluidic system is developed using nanochannels of heterogeneous surface properties to investigate transport properties of ions under different temperatures. Steady ionic currents are observed under symmetric temperature gradients, which is equivalent to generating electricity using waste heat (e.g., electronic chips and solar panels). The currents increase linearly with temperature gradient and nonlinearly with channel size. Contributions to ion motion from temperatures and channel properties are evaluated for this phenomenon. The findings provide insights into the study of confined ionic fluids in multiphysical fields, and suggest applications in thermal energy conversion, temperature sensors, and chip-level thermal management. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Transverse dispersion in heterogeneous fractures

    Dershowitz, Bill; Shuttle, Dawn; Klise, Kate; Outters, Nils; Hermanson, Jan

    2004-12-01

    This report evaluates the significance of transverse dispersion processes for solute transport in a single fracture. Transverse dispersion is a potentially significant process because it increases the fracture surface area available for sorptive and diffusive properties, and has the potential to transport solute between what would otherwise be distinctive, streamline pathways. Transverse dispersion processes are generally ignored in one-dimensional repository performance assessment approaches. This report provides an initial assessment of the magnitude of transverse dispersion effect in a single heterogeneous fracture on repository safety assessment. This study builds on a previous report which considered the network effects on transport dispersion including streamline routing and mixing at fracture intersections. The project uses FracMan software. This platform has been extensively used by SKB in other projects. FracMan software is designed to generate and analyze DFN's as well as to compute fluid flow in DFN's with the MAFIC Finite element method (FEM) code. Solute transport was modeled using the particle tracking inside MAFIC, the 2-D Laplace Transform Galerkin inside PAWorks/LTG, and the 1-D Laplace Transform approach designed to replicate FARF31 inside GoldSim.The study reported here focuses on a single, 20-meter scale discrete fracture, with simplified boundary conditions intended to represent the position of this fracture within a fracture network. The range of assumptions made regarding fracture heterogeneity were as follows: Base case, Heterogeneous fracture, geostatistical field, correlation length 0.01 m. Case 1a, Homogeneous fracture, transmissivity = 10 -7 m 2 /s. Case 1b, Heterogeneous fracture, non-channeled geostatistical field correlation length 5 m. Case 1c, Heterogeneous fracture, channeled, anisotropic geostatistical field. Case 1d, Heterogeneous fracture, fracture intersection zone (FIZ) permeability enhanced. Case 5, Simple channelized

  14. Kinetics of heterogeneous systems; La cinetique des milieux heterogenes

    Deniz, V [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1967-07-01

    In this report, a general transport theory treatment is presented for the kinetics study as applied to finite heterogeneous systems. The theory is applicable to experiments near the critical point as well as to pulsed neutron experiments on multiplying or non-multiplying lattices. The general method is also applied to exponential experiments on infinite non-diverging lattices. The particularity of the present study is the explicit introduction of heterogeneity in the formulation and the search for the dependence of the parameters on the buckling of the finite medium. As a result of this, the finite medium parameters are in the first place expressed in terms of the corresponding infinite medium ones through the buckling and the anisotropic migration areas, and in the second place all the parameters are expressed as integrals only over an unit cell instead of over the whole pile. A preliminary less detailed study is first made in order to distinguish clearly between what are called 'dynamic parameters' and 'static parameters', and to define the meanings given in this report to these two terms. In the appendices are given approximate one-group treatments for the study of the dynamic fine structure, the time constant in infinite lattices, and the anisotropic diffusion coefficients in non-multiplying lattices. (author) [French] On presente dans ce rapport une methode generale, utilisant la theorie du transport pour l'etude de la cinetique des milieux finis heterogenes. La theorie est applicable aussi bien aux experiences pres de la criticite qu'aux experiences par sources pulsees de neutrons sur des reseaux multiplicateurs ou non-multiplicateurs. La methode generale est aussi appliquee aux experiences exponentielles sur des reseaux infinis non-divergents. La particularite de l'etude est l'introduction explicite de l'heterogeneite dans la formulation et la recherche de la dependance des parametres par rapport au laplacien du reseau fini. Il en resulte d'une part que les

  15. In-situ characterization of heterogeneous catalysts

    Rodriguez, Jose A; Chupas, Peter J

    2013-01-01

    Helps researchers develop new catalysts for sustainable fuel and chemical production Reviewing the latest developments in the field, this book explores the in-situ characterization of heterogeneous catalysts, enabling readers to take full advantage of the sophisticated techniques used to study heterogeneous catalysts and reaction mechanisms. In using these techniques, readers can learn to improve the selectivity and the performance of catalysts and how to prepare catalysts as efficiently as possible, with minimum waste. In-situ Characterization of Heterogeneous Catalysts feat

  16. Heterogeneous inflation expectations, learning, and market outcomes

    Madeira, Carlos; Zafar, Basit

    2012-01-01

    Using the panel component of the Michigan Survey of Consumers, we show that individuals, in particular women and ethnic minorities, are highly heterogeneous in their expectations of inflation. We estimate a model of inflation expectations based on learning from experience that also allows for heterogeneity in both private information and updating. Our model vastly outperforms existing models of inflation expectations in explaining the heterogeneity in the data. We find that women, ethnic mino...

  17. Heterogeneity within populations of recombinant Chinese hamster ovary cells expressing human interferon-gamma.

    Coppen, S R; Newsam, R; Bull, A T; Baines, A J

    1995-04-20

    The Chinese hamster ovary (CHO) cell line has great commercial importance in the production of recombinant human proteins, especially those for therapeutic use. Much attention has been paid to CHO cell population physiology in order to define factors affecting product fidelity and yield. Such studies have revealed that recombinant proteins, including human interferon-gamma (IFN-gamma), can be heterogeneous both in glycosylation and in proteolytic processing. The type of heterogeneity observed depends on the growth physiology of the cell population, although the relationship between them is complex. In this article we report results of a cytological study of the CHO320 line which expresses recombinant human IFN-gamma. When grown in suspension culture, this cell line exhibited three types of heterogeneity: (1) heterogeneity of the production of IFN-gamma within the cell population, (2) heterogeneity of the number of nuclei and mitotic spindles in dividing cells, and (3) heterogeneity of cellular environment. The last of these arises from cell aggregates which form in suspension culture: Some cells are exposed to the culture medium; others are fully enclosed within the mass with little or no direct access to the medium. Thus, live cells producing IFN-gamma are heterogeneous in their environment, with variable access to O(2) and nutrients. Within the aggregates, it appears that live cells proliferate on a dead cell mass. The layer of live cells can be several cells deep. Specific cell-cell attachments are observed between the living cells in these aggregates. Two proteins, known to be required for the formation of certain types of intercellular junctions, spectrin and vinculin, have been localized to the regions of cell-cell contact. The aggregation of the cells appears to be an active process requiring protein synthesis. (c) 1995 John Wiley & Sons, Inc.

  18. Biomimetic heterogenous elastic tissue development.

    Tsai, Kai Jen; Dixon, Simon; Hale, Luke Richard; Darbyshire, Arnold; Martin, Daniel; de Mel, Achala

    2017-01-01

    There is an unmet need for artificial tissue to address current limitations with donor organs and problems with donor site morbidity. Despite the success with sophisticated tissue engineering endeavours, which employ cells as building blocks, they are limited to dedicated labs suitable for cell culture, with associated high costs and long tissue maturation times before available for clinical use. Direct 3D printing presents rapid, bespoke, acellular solutions for skull and bone repair or replacement, and can potentially address the need for elastic tissue, which is a major constituent of smooth muscle, cartilage, ligaments and connective tissue that support organs. Thermoplastic polyurethanes are one of the most versatile elastomeric polymers. Their segmented block copolymeric nature, comprising of hard and soft segments allows for an almost limitless potential to control physical properties and mechanical behaviour. Here we show direct 3D printing of biocompatible thermoplastic polyurethanes with Fused Deposition Modelling, with a view to presenting cell independent in-situ tissue substitutes. This method can expeditiously and economically produce heterogenous, biomimetic elastic tissue substitutes with controlled porosity to potentially facilitate vascularisation. The flexibility of this application is shown here with tubular constructs as exemplars. We demonstrate how these 3D printed constructs can be post-processed to incorporate bioactive molecules. This efficacious strategy, when combined with the privileges of digital healthcare, can be used to produce bespoke elastic tissue substitutes in-situ, independent of extensive cell culture and may be developed as a point-of-care therapy approach.

  19. Harvesting Information from Heterogeneous Sources

    Qureshi, Pir Abdul Rasool; Memon, Nasrullah; Wiil, Uffe Kock

    2011-01-01

    The abundance of information regarding any topic makes the Internet a very good resource. Even though searching the Internet is very easy, what remains difficult is to automate the process of information extraction from the available online information due to the lack of structure and the diversi...... with performance of our tool with respect to each format. Finally, the different potential applications of the proposed tool are discussed with special emphasis on open source intelligence....... in the sharing methods. Most of the times, information is stored in different proprietary formats, complying with different standards and protocols which makes tasks like data mining and information harvesting very difficult. In this paper, an information harvesting tool (heteroHarvest) is presented...... with objectives to address these problems by filtering the useful information and then normalizing the information in a singular non hypertext format. We also discuss state of the art tools along with the shortcomings and present the results of an analysis carried out over different heterogeneous formats along...

  20. Genetic heterogeneity in Usher syndrome.

    Keats, Bronya J B; Savas, Sevtap

    2004-09-15

    Mutations in seven different genes have been associated with Usher syndrome, and an additional four loci have been mapped. The identified genes encode myosin VIIa, harmonin (a PDZ-domain protein), cadherin 23, protocadherin 15, sans (a scaffold-like protein), usherin and clarin. Three clinical types of Usher syndrome have been described: USH1 patients have severe to profound congenital hearing loss, vestibular dysfunction, and retinal degeneration beginning in childhood, those with USH2 have moderate to severe congenital hearing loss, normal vestibular function, and later onset of retinitis pigmentosa, and USH3 patients have progressive hearing loss, which distinguishes them from the other two types. The shaker-1, waltzer, Ames waltzer, and Jackson shaker mice provide murine models for four of the genetic forms of Usher syndrome. Ongoing studies are enabling early diagnosis of Usher syndrome in children who present with hearing loss, thus providing time to prepare for the onset of visual loss. Copyright 2004 Wiley-Liss, Inc.

  1. Purchasing Power Parity and Heterogeneous Mean Reversion

    C.G. Koedijk (Kees); B. Tims (Ben); M.A. van Dijk (Mathijs)

    2005-01-01

    textabstractThis paper analyzes the properties of multivariate tests of purchasing power parity (PPP) that fail to take heterogeneity in the speed of mean reversion across real exchange rates into account. We compare the performance of homogeneous and heterogeneous unit root testing methodologies.

  2. Understanding the Executive Functioning Heterogeneity in Schizophrenia

    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…

  3. Monetary policy, banking and heterogeneous agents

    Wolski, M.

    2012-01-01

    The influence of heterogeneous expectations on monetary policy performance has gained a lot of attention in the recent years. It proved to be an important factor that, under some circumstances, may even destabilize the economy (Massaro, 2012). This paper investigates the phenomenon of heterogeneous

  4. Towards an Organizational Economics of Heterogeneous Capabilities

    Foss, Nicolai Juul

    The notion of “capability” has long been influential in management research as an approach to address firm-level heterogeneity and heterogeneity in competitive outcomes. I discuss how recent advances in economics may allow for a more rigorous understanding and measurement of capability that take...

  5. Characterizing heterogeneous cellular responses to perturbations.

    Slack, Michael D; Martinez, Elisabeth D; Wu, Lani F; Altschuler, Steven J

    2008-12-09

    Cellular populations have been widely observed to respond heterogeneously to perturbation. However, interpreting the observed heterogeneity is an extremely challenging problem because of the complexity of possible cellular phenotypes, the large dimension of potential perturbations, and the lack of methods for separating meaningful biological information from noise. Here, we develop an image-based approach to characterize cellular phenotypes based on patterns of signaling marker colocalization. Heterogeneous cellular populations are characterized as mixtures of phenotypically distinct subpopulations, and responses to perturbations are summarized succinctly as probabilistic redistributions of these mixtures. We apply our method to characterize the heterogeneous responses of cancer cells to a panel of drugs. We find that cells treated with drugs of (dis-)similar mechanism exhibit (dis-)similar patterns of heterogeneity. Despite the observed phenotypic diversity of cells observed within our data, low-complexity models of heterogeneity were sufficient to distinguish most classes of drug mechanism. Our approach offers a computational framework for assessing the complexity of cellular heterogeneity, investigating the degree to which perturbations induce redistributions of a limited, but nontrivial, repertoire of underlying states and revealing functional significance contained within distinct patterns of heterogeneous responses.

  6. Heterogeneous Embedded Real-Time Systems Environment

    2003-12-01

    AFRL-IF-RS-TR-2003-290 Final Technical Report December 2003 HETEROGENEOUS EMBEDDED REAL - TIME SYSTEMS ENVIRONMENT Integrated...HETEROGENEOUS EMBEDDED REAL - TIME SYSTEMS ENVIRONMENT 6. AUTHOR(S) Cosmo Castellano and James Graham 5. FUNDING NUMBERS C - F30602-97-C-0259

  7. An estimating function approach to linkage heterogeneity

    Testing linkage heterogeneity between two loci is an important issue in genetics. Currently, there are ... on linkage heterogeneity can help people to better understand complex .... χ2(F − 2) + cχ2 (1), where c is a constant (see Appendix). Here, it can be ..... gin, ancestry, gender, age, etc., for purpose of dividing sub- groups to ...

  8. Functional Heterogeneity and Senior Management Team Effectiveness

    Benoliel, Pascale; Somech, Anit

    2016-01-01

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

  9. Fixed export cost heterogeneity, trade and welfare

    Jørgensen, Jan Guldager; Schröder, Philipp J.H.

    2008-01-01

    -country intra-industry trade model where firms are of two different marginal costs types and where fixed export costs are heterogeneous across firms. This model traces many of the stylized facts of international trade. However, we find that with heterogeneous fixed export costs there exists a positive bilateral...

  10. Heterogeneous Beliefs, Public Information, and Option Markets

    Qin, Zhenjiang

    In an incomplete market setting with heterogeneous prior beliefs, I show that public information and strike price of option have substantial infl‡uence on asset pricing in option markets, by investigating an absolute option pricing model with negative exponential utility investors and normally...... distributed dividend. I demonstrate that heterogeneous prior variances give rise to the economic value of option markets. Investors speculate in option market and public information improves allocational efficiency of markets only when there is heterogeneity in prior variance. Heterogeneity in mean is neither...... a necessary nor sufficient condition for generating speculations in option markets. With heterogeneous beliefs, options are non-redundant assets which can facilitate side-betting and enable investors to take advantage of the disagreements and the differences in con…dence. This fact leads to a higher growth...

  11. Design Technology for Heterogeneous Embedded Systems

    O'Connor, Ian; Piguet, Christian

    2012-01-01

    Designing technology to address the problem of heterogeneous embedded systems, while remaining compatible with standard “More Moore” flows, i.e. capable of handling simultaneously both silicon complexity and system complexity, represents one of the most important challenges facing the semiconductor industry today. While the micro-electronics industry has built its own specific design methods to focus mainly on the management of complexity through the establishment of abstraction levels, the emergence of device heterogeneity requires new approaches enabling the satisfactory design of physically heterogeneous embedded systems for the widespread deployment of such systems. This book, compiled largely from a set of contributions from participants of past editions of the Winter School on Heterogeneous Embedded Systems Design Technology (FETCH), proposes a broad and holistic overview of design techniques used to tackle the various facets of heterogeneity in terms of technology and opportunities at the physical ...

  12. Heterogeneous Causal Effects and Sample Selection Bias

    Breen, Richard; Choi, Seongsoo; Holm, Anders

    2015-01-01

    The role of education in the process of socioeconomic attainment is a topic of long standing interest to sociologists and economists. Recently there has been growing interest not only in estimating the average causal effect of education on outcomes such as earnings, but also in estimating how...... causal effects might vary over individuals or groups. In this paper we point out one of the under-appreciated hazards of seeking to estimate heterogeneous causal effects: conventional selection bias (that is, selection on baseline differences) can easily be mistaken for heterogeneity of causal effects....... This might lead us to find heterogeneous effects when the true effect is homogenous, or to wrongly estimate not only the magnitude but also the sign of heterogeneous effects. We apply a test for the robustness of heterogeneous causal effects in the face of varying degrees and patterns of selection bias...

  13. Fiber Bundle Model Under Heterogeneous Loading

    Roy, Subhadeep; Goswami, Sanchari

    2018-03-01

    The present work deals with the behavior of fiber bundle model under heterogeneous loading condition. The model is explored both in the mean-field limit as well as with local stress concentration. In the mean field limit, the failure abruptness decreases with increasing order k of heterogeneous loading. In this limit, a brittle to quasi-brittle transition is observed at a particular strength of disorder which changes with k. On the other hand, the model is hardly affected by such heterogeneity in the limit where local stress concentration plays a crucial role. The continuous limit of the heterogeneous loading is also studied and discussed in this paper. Some of the important results related to fiber bundle model are reviewed and their responses to our new scheme of heterogeneous loading are studied in details. Our findings are universal with respect to the nature of the threshold distribution adopted to assign strength to an individual fiber.

  14. Quantification of heterogeneity observed in medical images

    Brooks, Frank J; Grigsby, Perry W

    2013-01-01

    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. 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. 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. 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

  15. Quantification of heterogeneity observed in medical images.

    Brooks, Frank J; Grigsby, Perry W

    2013-03-02

    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. 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. 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. 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.

  16. Heterogeneous counting on filter support media

    Long, E.; Kohler, V.; Kelly, M.J.

    1976-01-01

    Many investigators in the biomedical research area have used filter paper as the support for radioactive samples. This means that a heterogeneous counting of sample sometimes results. The count rate of a sample on a filter will be affected by positioning, degree of dryness, sample application procedure, the type of filter, and the type of cocktail used. Positioning of the filter (up or down) in the counting vial can cause a variation of 35% or more when counting tritiated samples on filter paper. Samples of varying degrees of dryness when added to the counting cocktail can cause nonreproducible counts if handled improperly. Count rates starting at 2400 CPM initially can become 10,000 CPM in 24 hours for 3 H-DNA (deoxyribonucleic acid) samples dried on standard cellulose acetate membrane filters. Data on cellulose nitrate filters show a similar trend. Sample application procedures in which the sample is applied to the filter in a small spot or on a large amount of the surface area can cause nonreproducible or very low counting rates. A tritiated DNA sample, when applied topically, gives a count rate of 4,000 CPM. When the sample is spread over the whole filter, 13,400 CPM are obtained with a much better coefficient of variation (5% versus 20%). Adding protein carrier (bovine serum albumin-BSA) to the sample to trap more of the tritiated DNA on the filter during the filtration process causes a serious beta absorption problem. Count rates which are one-fourth the count rate applied to the filter are obtained on calibrated runs. Many of the problems encountered can be alleviated by a proper choice of filter and the use of a liquid scintillation cocktail which dissolves the filter. Filter-Solv has been used to dissolve cellulose nitrate filters and filters which are a combination of cellulose nitrate and cellulose acetate. Count rates obtained for these dissolved samples are very reproducible and highly efficient

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

    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

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

    Salvador J. Diaz-Cano

    2012-02-01

    Full Text Available 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.

  19. Structure from Dynamics: Vibrational Dynamics of Interfacial Water as a Probe of Aqueous Heterogeneity

    2018-01-01

    The structural heterogeneity of water at various interfaces can be revealed by time-resolved sum-frequency generation spectroscopy. The vibrational dynamics of the O–H stretch vibration of interfacial water can reflect structural variations. Specifically, the vibrational lifetime is typically found to increase with increasing frequency of the O–H stretch vibration, which can report on the hydrogen-bonding heterogeneity of water. We compare and contrast vibrational dynamics of water in contact with various surfaces, including vapor, biomolecules, and solid interfaces. The results reveal that variations in the vibrational lifetime with vibrational frequency are very typical, and can frequently be accounted for by the bulk-like heterogeneous response of interfacial water. Specific interfaces exist, however, for which the behavior is less straightforward. These insights into the heterogeneity of interfacial water thus obtained contribute to a better understanding of complex phenomena taking place at aqueous interfaces, such as photocatalytic reactions and protein folding. PMID:29490138

  20. Passive acquisition of leukocyte proteins is associated with changes in phosphorylation of cellular proteins and cell-cell adhesion properties.

    Tabibzadeh, S. S.; Kong, Q. F.; Kapur, S.

    1994-01-01

    In this report, we show that interaction of neoplastic epithelial cells with vesicles derived from leukocytes results in passive acquisition by tumor cells of a diverse group of leukocyte proteins. Vesicles shed from leukocytes were heterogeneous and exhibited the specific proteins expressed on leukocyte subsets. Accordingly, epithelial cells differentially acquired leukocyte proteins associated with vesicles. Ultrastructural localization demonstrated that acquired proteins were associated wi...

  1. Adsorption of gases on heterogeneous surfaces

    Rudzinski, W

    1991-01-01

    All real solid surfaces are heterogeneous to a greater or lesser extent and this book provides a broad yet detailed survey of the present state of gas adsorption. Coverage is comprehensive and extends from basic principles to computer simulation of adsorption. Underlying concepts are clarified and the strengths and weaknesses of the various methods described are discussed.Key Features* Adsorption isotherm equations for various types of heterogeneous solid surfaces* Methods of determining the nature of surface heterogeneity and porosity from experimental data* Studies of pha

  2. A heterogeneous graph-based recommendation simulator

    Yeonchan, Ahn [Seoul National University; Sungchan, Park [Seoul National University; Lee, Matt Sangkeun [ORNL; Sang-goo, Lee [Seoul National University

    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.

  3. Computational Mechanics for Heterogeneous Materials

    Lechman, Jeremy B. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Baczewski, Andrew David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bond, Stephen [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Erikson, William W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lehoucq, Richard B. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mondy, Lisa Ann [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Noble, David R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Pierce, Flint [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Roberts, Christine [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); van Swol, Frank B. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Yarrington, Cole [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2013-11-01

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

  4. Possible heterogeneity of centres of binding 1,8-ANS in molecules of oxygenated hemoglobin

    Parul', D.A.; Bokut', S.B.; Milyutin, A.A.; Petrov, E.P.; Nemkovich, N.A.; Sobchuk, A.N.; Dzhagarov, B.M.

    1999-01-01

    Forming of oxygenated hemoglobin is one of effects of ionizing radiation action on organism. It was revealed heterogeneity of centers of binding of 1,8-ANS in intact molecule of oxygenated hemoglobin. Two types of binding centers possible reflect the existence of two regions in protein molecule with different accessibility to molecules of water

  5. Yeast cells contain a heterogeneous population of peroxisomes that segregate asymmetrically during cell division

    Kumar, Sanjeev; de Boer, Rinse; van der Klei, Ida J

    2018-01-01

    Here we used fluorescence microscopy and a peroxisome-targeted tandem fluorescent protein timer to determine the relative age of peroxisomes in yeast. Our data indicate that yeast cells contain a heterogeneous population of relatively old and younger peroxisomes. During budding the peroxisome

  6. Heterogeneity at the CETP gene locus. Influence on plasma CETP concentrations and HDL cholesterol levels

    Kuivenhoven, J.A.; de Knijff, P.; Boer, J M; Smalheer, H A; Botma, G.J.; Seidell, J C; Kastelein, J.J.; Pritchard, P H

    This study was designed to investigate the association(s) between heterogeneity at the cholesteryl ester transfer protein (CETP) gene locus, CETP plasma concentrations, and HDL cholesterol levels. Healthy men with the lowest, median, and highest deciles of HDL cholesterol were selected from a large

  7. Gap junctions suppress electrical but not [Ca(2+)] heterogeneity in resistance arteries

    Hald, Bjørn Olav; Welsh, Donald G; von Holstein-Rathlou, Niels-Henrik

    2014-01-01

    arises, a virtual arteriole was developed that introduces variation in the activities of ion-transport proteins between cells. By varying the level of heterogeneity and subpopulations of gap junctions (GJs), the resulting simulations shows that GJs suppress electrical variation but can only reduce...

  8. Selective Oxidations using Nanostructured Heterogeneous Catalysts

    Mielby, Jerrik Jørgen

    and because they produce H2O as the only by-product. Chapter 1 gives a short introduction to basic concepts in heterogeneous catalysis and green chemistry. Furthermore, the chapter gives an overview of the most important strategies to synthesise functional nanostructured materials and highlights how detailed......The aim of this thesis is to investigate and develop new efficient methods to oxidise alcohols and amines using heterogeneous catalysts and either O2 or H2O2 as oxidants. From an economic and environmental point of view, these oxidants are ideal, because they are cheap and readily available...... understanding of size, shape and structure can help in the development of new and more efficient heterogeneous catalysts. The chapter is not intended to give a complete survey, but rather to introduce some of the recent developments in the synthesis of nanostructured heterogeneous catalysts. Finally...

  9. Heterogeneous continuous-time random walks

    Grebenkov, Denis S.; Tupikina, Liubov

    2018-01-01

    We introduce a heterogeneous continuous-time random walk (HCTRW) model as a versatile analytical formalism for studying and modeling diffusion processes in heterogeneous structures, such as porous or disordered media, multiscale or crowded environments, weighted graphs or networks. We derive the exact form of the propagator and investigate the effects of spatiotemporal heterogeneities onto the diffusive dynamics via the spectral properties of the generalized transition matrix. In particular, we show how the distribution of first-passage times changes due to local and global heterogeneities of the medium. The HCTRW formalism offers a unified mathematical language to address various diffusion-reaction problems, with numerous applications in material sciences, physics, chemistry, biology, and social sciences.

  10. Understanding Heterogeneous Preferences of Cooperative Members

    Kalogeras, N.; Pennings, J.M.E.; Lans, van der I.A.; Garcia, P.; Dijk, van G.

    2009-01-01

    We study the heterogeneity in the preference structure of cooperative members. Using conjoint analysis the utility that members attach to intra-organizational and strategic attributes of their cooperative is elicited. Recognizing that members are not homogenous, a concomitant finitemixture

  11. Exploring the dynamic integration of heterogeneous services

    Makamba, M

    2016-08-01

    Full Text Available components for communication and collaboration amongst enterprises internally and externally. Since Internet has stimulated the use of services, different services have been developed for different purposes prompting those services to be heterogeneous due...

  12. Individual heterogeneity generating explosive system network dynamics.

    Manrique, Pedro D; Johnson, Neil F

    2018-03-01

    Individual heterogeneity is a key characteristic of many real-world systems, from organisms to humans. However, its role in determining the system's collective dynamics is not well understood. Here we study how individual heterogeneity impacts the system network dynamics by comparing linking mechanisms that favor similar or dissimilar individuals. We find that this heterogeneity-based evolution drives an unconventional form of explosive network behavior, and it dictates how a polarized population moves toward consensus. Our model shows good agreement with data from both biological and social science domains. We conclude that individual heterogeneity likely plays a key role in the collective development of real-world networks and communities, and it cannot be ignored.

  13. Pricing Liquidity Risk with Heterogeneous Investment Horizons

    Beber, Alessandro; Driessen, Joost; Neuberger, A.; Tuijp, P

    We develop an asset pricing model with stochastic transaction costs and investors with heterogeneous horizons. Depending on their horizon, investors hold different sets of assets in equilibrium. This generates segmentation and spillover effects for expected returns, where the liquidity (risk)

  14. Heterogeneous agents and decison making within firms

    Hung, Chung-yu

    2015-01-01

    This dissertation explores the implications of agents’ heterogeneity in decision making within situations where information is not completely contractible. Specifically, the study applies empirical methods across three chapters to examine the role of employees’ traits and their mutual relationships

  15. Heterogeneous treatment in the variational nodal method

    Fanning, T.H.

    1995-01-01

    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

  16. Individual heterogeneity generating explosive system network dynamics

    Manrique, Pedro D.; Johnson, Neil F.

    2018-03-01

    Individual heterogeneity is a key characteristic of many real-world systems, from organisms to humans. However, its role in determining the system's collective dynamics is not well understood. Here we study how individual heterogeneity impacts the system network dynamics by comparing linking mechanisms that favor similar or dissimilar individuals. We find that this heterogeneity-based evolution drives an unconventional form of explosive network behavior, and it dictates how a polarized population moves toward consensus. Our model shows good agreement with data from both biological and social science domains. We conclude that individual heterogeneity likely plays a key role in the collective development of real-world networks and communities, and it cannot be ignored.

  17. Exploring heterogeneous market hypothesis using realized volatility

    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.

  18. Heterogeneity in Models of Electoral Choice

    Rivers, Douglas

    1983-01-01

    Heterogeneity or the presence of a variety of decision rules in a population has usually been ignored in voting research. A method for handling heterogeneous preferences using rank order data is developed and applied to a simple issue-voting model. The estimated average effect of partisanship is substantially higher when the assumption of homogeneity is relaxed, though many self-identified partisans also use ideological criteria to evaluate candidates and many independents rely on partisan cr...

  19. A 1998 Workshop on Heterogeneous Computing

    1998-09-18

    Programming Heterogenous Computing Systems? Panel Chair: GulA. Agha, University of Illinois, Urbana -Champaign, IL, USA Modular Heterogeneous System...electrical engineering from the University of Illinois, Urbana -Champaign, in 1975. She worked at the I.B.M. T.J. Watson Research Center with the...Distributed System Environment". I Encuentro de Computaciön. Taller de Sistemas Distribuidos y Paralelos. Memorias . Queretaro, Qro. Mexico. September 1997

  20. Quantification of heterogeneity observed in medical images

    Brooks, Frank J; Grigsby, Perry W

    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 mod...

  1. The failure rate dynamics in heterogeneous populations

    Cha, Ji Hwan; Finkelstein, Maxim

    2013-01-01

    Most populations encountered in real world are heterogeneous. In reliability applications, the mixture (observed) failure rate, obviously, can be considered as a measure of ‘average’ quality in these populations. However, in addition to this average measure, some variability characteristics for failure rates can be very helpful in describing the time-dependent changes in quality of heterogeneous populations. In this paper, we discuss variance and the coefficient of variation of the corresponding random failure rate as variability measures for items in heterogeneous populations. Furthermore, there is often a risk that items of poor quality are selected for important missions. Therefore, along with the ‘average quality’ of a population, more ‘conservative’ quality measures should be also defined and studied. For this purpose, we propose the percentile and the tail-mixture of the failure rates as the corresponding conservative measures. Some illustrative examples are given. -- Highlights: ► This paper provides the insight on the variability measures in heterogeneous populations. ► The conservative quality measures in heterogeneous populations are defined. ► The utility of these measures is illustrated by meaningful examples. ► This paper provides a better understanding of the dynamics in heterogeneous populations

  2. Intratumor and Intertumor Heterogeneity in Melanoma.

    Grzywa, Tomasz M; Paskal, Wiktor; Włodarski, Paweł K

    2017-12-01

    Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Intratumor and Intertumor Heterogeneity in Melanoma

    Tomasz M. Grzywa

    2017-12-01

    Full Text Available Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed.

  4. Engineering Microbial Metabolite Dynamics and Heterogeneity.

    Schmitz, Alexander C; Hartline, Christopher J; Zhang, Fuzhong

    2017-10-01

    As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Probing Mantle Heterogeneity Across Spatial Scales

    Hariharan, A.; Moulik, P.; Lekic, V.

    2017-12-01

    Inferences of mantle heterogeneity in terms of temperature, composition, grain size, melt and crystal structure may vary across local, regional and global scales. Probing these scale-dependent effects require quantitative comparisons and reconciliation of tomographic models that vary in their regional scope, parameterization, regularization and observational constraints. While a range of techniques like radial correlation functions and spherical harmonic analyses have revealed global features like the dominance of long-wavelength variations in mantle heterogeneity, they have limited applicability for specific regions of interest like subduction zones and continental cratons. Moreover, issues like discrepant 1-D reference Earth models and related baseline corrections have impeded the reconciliation of heterogeneity between various regional and global models. We implement a new wavelet-based approach that allows for structure to be filtered simultaneously in both the spectral and spatial domain, allowing us to characterize heterogeneity on a range of scales and in different geographical regions. Our algorithm extends a recent method that expanded lateral variations into the wavelet domain constructed on a cubed sphere. The isolation of reference velocities in the wavelet scaling function facilitates comparisons between models constructed with arbitrary 1-D reference Earth models. The wavelet transformation allows us to quantify the scale-dependent consistency between tomographic models in a region of interest and investigate the fits to data afforded by heterogeneity at various dominant wavelengths. We find substantial and spatially varying differences in the spectrum of heterogeneity between two representative global Vp models constructed using different data and methodologies. Applying the orthonormality of the wavelet expansion, we isolate detailed variations in velocity from models and evaluate additional fits to data afforded by adding such complexities to long

  6. Overview of medium heterogeneity and transport processes

    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

  7. Implications of Heterogeneity in Multiple Myeloma

    Sanjay de Mel

    2014-01-01

    Full Text Available 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.

  8. Numerical calculations on heterogeneity of groundwater flow

    Follin, S.

    1992-01-01

    The upscaling of model parameters is a key issue in many research fields concerned with parameter heterogeneity. The upscaling process allows for fewer model blocks and relaxes the numerical problems caused by high contrasts in the hydraulic conductivity. The trade-offs are dependent on the object but the general drawback is an increasing uncertainty about the representativeness. The present study deals with numerical calculations of heterogeneity of groundwater flow and solute transport in hypothetical blocks of fractured hard rock in a '3m scale' and addresses both conceptual and practical problems in numerical simulation. Evidence that the hydraulic conductivity (K) of the rock mass between major fracture zones is highly heterogeneous in a 3m scale is provided by a large number of field investigations. The present uses the documented heterogeneity and investigates flow and transport in a two-dimensional stochastic continuum characterized by a variance in Y = In(K) of σ y 2 = 16, corresponding to about 12 log 10 cycles in K. The study considers anisotropy, channelling, non-Fickian and Fickian transport, and conditional simulation. The major conclusions are: * heterogeneity gives rise to anisotropy in the upscaling process, * the choice of support scale is crucial for the modelling of solute transport. As a consequence of the obtained results, a two-dimensional stochastic discontinuum model is presented, which provides a tool for linking stochastic continuum models to discrete fracture network models. (au) (14 figs., 136 refs.)

  9. Genetic variants influencing phenotypic variance heterogeneity.

    Ek, Weronica E; Rask-Andersen, Mathias; Karlsson, Torgny; Enroth, Stefan; Gyllensten, Ulf; Johansson, Åsa

    2018-03-01

    Most genetic studies identify genetic variants associated with disease risk or with the mean value of a quantitative trait. More rarely, genetic variants associated with variance heterogeneity are considered. In this study, we have identified such variance single-nucleotide polymorphisms (vSNPs) and examined if these represent biological gene × gene or gene × environment interactions or statistical artifacts caused by multiple linked genetic variants influencing the same phenotype. We have performed a genome-wide study, to identify vSNPs associated with variance heterogeneity in DNA methylation levels. Genotype data from over 10 million single-nucleotide polymorphisms (SNPs), and DNA methylation levels at over 430 000 CpG sites, were analyzed in 729 individuals. We identified vSNPs for 7195 CpG sites (P mean DNA methylation levels. We further showed that variance heterogeneity between genotypes mainly represents additional, often rare, SNPs in linkage disequilibrium (LD) with the respective vSNP and for some vSNPs, multiple low frequency variants co-segregating with one of the vSNP alleles. Therefore, our results suggest that variance heterogeneity of DNA methylation mainly represents phenotypic effects by multiple SNPs, rather than biological interactions. Such effects may also be important for interpreting variance heterogeneity of more complex clinical phenotypes.

  10. Detection of structural heterogeneity of glass melts

    Yue, Yuanzheng

    2004-01-01

    The structural heterogeneity of both supercooled liquid and molten states of silicate has been studied using calorimetric method. The objects of this study are basaltic glasses and liquids. Two experimental approaches are taken to detect the structural heterogeneity of the liquids. One is the hyp......The structural heterogeneity of both supercooled liquid and molten states of silicate has been studied using calorimetric method. The objects of this study are basaltic glasses and liquids. Two experimental approaches are taken to detect the structural heterogeneity of the liquids. One...... is the hyperquench-anneal-calorimetric scan approach, by which the structural information of a basaltic supercooled liquid and three binary silicate liquids is acquired. Another is the calorimetrically repeated up- and downscanning approach, by which the structural heterogeneity, the intermediate range order...... is discussed. The ordered structure of glass melts above the liquidus temperature is indirectly characterized by use of X-ray diffraction method. The new approaches are of importance for monitoring the glass melting and forming process and for improving the physical properties of glasses and glass fibers....

  11. Homogeneity and heterogeneity in amylase production by Bacillus subtilis under different growth conditions.

    Ploss, Tina N; Reilman, Ewoud; Monteferrante, Carmine G; Denham, Emma L; Piersma, Sjouke; Lingner, Anja; Vehmaanperä, Jari; Lorenz, Patrick; van Dijl, Jan Maarten

    2016-03-29

    Bacillus subtilis is an important cell factory for the biotechnological industry due to its ability to secrete commercially relevant proteins in large amounts directly into the growth medium. However, hyper-secretion of proteins, such as α-amylases, leads to induction of the secretion stress-responsive CssR-CssS regulatory system, resulting in up-regulation of the HtrA and HtrB proteases. These proteases degrade misfolded proteins secreted via the Sec pathway, resulting in a loss of product. The aim of this study was to investigate the secretion stress response in B. subtilis 168 cells overproducing the industrially relevant α-amylase AmyM from Geobacillus stearothermophilus, which was expressed from the strong promoter P(amyQ)-M. Here we show that activity of the htrB promoter as induced by overproduction of AmyM was "noisy", which is indicative for heterogeneous activation of the secretion stress pathway. Plasmids were constructed to allow real-time analysis of P(amyQ)-M promoter activity and AmyM production by, respectively, transcriptional and out-of-frame translationally coupled fusions with gfpmut3. Our results show the emergence of distinct sub-populations of high- and low-level AmyM-producing cells, reflecting heterogeneity in the activity of P(amyQ)-M. This most likely explains the heterogeneous secretion stress response. Importantly, more homogenous cell populations with regard to P(amyQ)-M activity were observed for the B. subtilis mutant strain 168degUhy32, and the wild-type strain 168 under optimized growth conditions. Expression heterogeneity of secretory proteins in B. subtilis can be suppressed by degU mutation and optimized growth conditions. Further, the out-of-frame translational fusion of a gene for a secreted target protein and gfp represents a versatile tool for real-time monitoring of protein production and opens novel avenues for Bacillus production strain improvement.

  12. Microbial population heterogeneity versus bioreactor heterogeneity: evaluation of Redox Sensor Green as an exogenous metabolic biosensor

    Baert, Jonathan; Delepierre, Anissa; Telek, Samuel

    2016-01-01

    Microbial heterogeneity in metabolic performances has attracted a lot of attention, considering its potential impact on industrial bioprocesses. However, little is known about the impact of extracellular perturbations (i.e. bioreactor heterogeneity) on cell-to-cell variability in metabolic...

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

    Fassinou Hotegni, V.N.; Lommen, W.J.M.; Agbossou, E.K.; Struik, P.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

  14. The Protein Model Portal.

    Arnold, Konstantin; Kiefer, Florian; Kopp, Jürgen; Battey, James N D; Podvinec, Michael; Westbrook, John D; Berman, Helen M; Bordoli, Lorenza; Schwede, Torsten

    2009-03-01

    Structural Genomics has been successful in determining the structures of many unique proteins in a high throughput manner. Still, the number of known protein sequences is much larger than the number of experimentally solved protein structures. Homology (or comparative) modeling methods make use of experimental protein structures to build models for evolutionary related proteins. Thereby, experimental structure determination efforts and homology modeling complement each other in the exploration of the protein structure space. One of the challenges in using model information effectively has been to access all models available for a specific protein in heterogeneous formats at different sites using various incompatible accession code systems. Often, structure models for hundreds of proteins can be derived from a given experimentally determined structure, using a variety of established methods. This has been done by all of the PSI centers, and by various independent modeling groups. The goal of the Protein Model Portal (PMP) is to provide a single portal which gives access to the various models that can be leveraged from PSI targets and other experimental protein structures. A single interface allows all existing pre-computed models across these various sites to be queried simultaneously, and provides links to interactive services for template selection, target-template alignment, model building, and quality assessment. The current release of the portal consists of 7.6 million model structures provided by different partner resources (CSMP, JCSG, MCSG, NESG, NYSGXRC, JCMM, ModBase, SWISS-MODEL Repository). The PMP is available at http://www.proteinmodelportal.org and from the PSI Structural Genomics Knowledgebase.

  15. Heterogeneous Metal Catalysts for Oxidation Reactions

    Md. Eaqub Ali

    2014-01-01

    Full Text Available Oxidation reactions may be considered as the heart of chemical synthesis. However, the indiscriminate uses of harsh and corrosive chemicals in this endeavor are threating to the ecosystems, public health, and terrestrial, aquatic, and aerial flora and fauna. Heterogeneous catalysts with various supports are brought to the spotlight because of their excellent capabilities to accelerate the rate of chemical reactions with low cost. They also minimize the use of chemicals in industries and thus are friendly and green to the environment. However, heterogeneous oxidation catalysis are not comprehensively presented in literature. In this short review, we clearly depicted the current state of catalytic oxidation reactions in chemical industries with specific emphasis on heterogeneous catalysts. We outlined here both the synthesis and applications of important oxidation catalysts. We believe it would serve as a reference guide for the selection of oxidation catalysts for both industries and academics.

  16. Voice over IP in Wireless Heterogeneous Networks

    Fathi, Hanane; Chakraborty, Shyam; Prasad, Ramjee

    with the deployment of wireless heterogeneous systems, both speech and data traffic are carrried over wireless links by the same IP-based packet-switched infrastructure. However, this combination faces some challenges due to the inherent properties of the wireless network. The requirements for good quality VoIP...... communications are difficult to achieve in a time-varying environment due to channel errors and traffic congestion and across different systems. The provision of VoIP in wireless heterogeneous networks requires a set of time-efficient control mechanisms to support a VoIP session with acceptable quality....... The focus of Voice over IP in Wierless Heterogeneous Networks is on mechanisms that affect the VoIP user satisfaction  while not explicitly involved in the media session. This relates to the extra delays introduced by the security and the signaling protocols used to set up an authorized VoIP session...

  17. Model of monopolistic competition with heterogeneous labor

    Filatov Alexander

    2017-01-01

    Full Text Available The paper presents a tool for modelling monopolistic competition markets, based on Dixit-Stiglitz ideology but taking into account heterogeneity at labor market. We analyse several modifications of a two-sector general equilibrium model. In the basic one with two levels of workers qualification their shares are determined endogenously on the base of comparison between the higher wage of the skilled worker and heterogeneous education costs, also taking into account the labor mobility between the manufacture and agriculture sector. The model is generalized for the case of continuous distribution of labor qualification. The impact of the model parameters (ratio of fixed and variable costs, market size, heterogeneity in productivity, elasticity of substitution, etc. on the obtained equilibrium prices, quantities, wages, number and size of firms, social welfare is investigated.

  18. Imperfect repair and lifesaving in heterogeneous populations

    Finkelstein, Maxim [Department of Mathematical Statistics, University of the Free State, PO Box 339, 9300 Bloemfontein (South Africa) and Max Planck Institute for Demographic Research, Rostock (Germany)]. E-mail: FinkelM.SCl@mail.uovs.ac.za

    2007-12-15

    In this theoretical paper we generalize the notion of minimal repair to the heterogeneous case, when the lifetime distribution function can be modeled by continuous or a discrete mixture of distributions. The statistical (black box) minimal repair and the minimal repair based on information just before the failure of an object are considered. The corresponding failure (intensity) rate processes are defined and analyzed. Demographic lifesaving model is also considered: each life is saved (cured) with some probability (or equivalently a proportion of individuals who would have died are now resuscitated and given another chance). Those who are saved experience the statistical minimal repair. Both of these models are based on the Poisson or non-homogeneous Poisson processes of underlying events, which allow for considering heterogeneity. We also consider the new model of imperfect repair in the homogeneous case and present generalizations to the heterogeneous setting.

  19. Heterogeneity in the WTP for recreational access

    Campbell, Danny; Vedel, Suzanne Elizabeth; Thorsen, Bo Jellesmark

    2014-01-01

    In this study we have addressed appropriate modelling of heterogeneity in willingness to pay (WTP) for environmental goods, and have demonstrated its importance using a case of forest access in Denmark. We compared WTP distributions for four models: (1) a multinomial logit model, (2) a mixed logit...... model assuming a univariate Normal distribution, (3) or assuming a multivariate Normal distribution allowing for correlation across attributes, and (4) a mixture of two truncated Normal distributions, allowing for correlation among attributes. In the first two models mean WTP for enhanced access...... was negative. However, models accounting for preference heterogeneity found a positive mean WTP, but a large sub-group with negative WTP. Accounting for preference heterogeneity can alter overall conclusions, which highlights the importance of this for policy recommendations....

  20. Deconstructing transcriptional heterogeneity in pluripotent stem cells

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

    2014-01-01

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

  1. Heterogeneous computing with OpenCL

    2013-01-01

    Heterogeneous Computing with OpenCL teaches OpenCL and parallel programming for complex systems that may include a variety of device architectures: multi-core CPUs, GPUs, and fully-integrated Accelerated Processing Units (APUs) such as AMD Fusion technology. Designed to work on multiple platforms and with wide industry support, OpenCL will help you more effectively program for a heterogeneous future. Written by leaders in the parallel computing and OpenCL communities, this book will give you hands-on OpenCL experience to address a range of fundamental parallel algorithms. The authors explore memory spaces, optimization techniques, graphics interoperability, extensions, and debugging and profiling. Intended to support a parallel programming course, Heterogeneous Computing with OpenCL includes detailed examples throughout, plus additional online exercises and other supporting materials.

  2. Foreign Entry and Heterogeneous Growth of Firms

    Deng, Paul Duo; Jefferson, Gary H.

    We adopt the framework of Schumpeterian creative destruction formalized by Aghion et al. (2009) to analyze the impact of foreign entry on the productivity growth of domestic firms. In the face of foreign entry, domestic firms exhibit heterogeneous patterns of growth depending on their technologic...... manufacturing. Our empirical results confirm that foreign entry indeed generates strong heterogeneous growth patterns among domestic firms.......We adopt the framework of Schumpeterian creative destruction formalized by Aghion et al. (2009) to analyze the impact of foreign entry on the productivity growth of domestic firms. In the face of foreign entry, domestic firms exhibit heterogeneous patterns of growth depending on their technological...... distance from foreign firms. Domestic firms with smaller technological distance from their foreign counterparts tend to experience faster productivity growth, while firms with larger technological distance tend to lag further behind. We test this hypothesis using a unique firm-level data of Chinese...

  3. Characterizing heterogeneous dynamics at hydrated electrode surfaces

    Willard, Adam P.; Limmer, David T.; Madden, Paul A.; Chandler, David

    2013-05-01

    In models of Pt 111 and Pt 100 surfaces in water, motions of molecules in the first hydration layer are spatially and temporally correlated. To interpret these collective motions, we apply quantitative measures of dynamic heterogeneity that are standard tools for considering glassy systems. Specifically, we carry out an analysis in terms of mobility fields and distributions of persistence times and exchange times. In so doing, we show that dynamics in these systems is facilitated by transient disorder in frustrated two-dimensional hydrogen bonding networks. The frustration is the result of unfavorable geometry imposed by strong metal-water bonding. The geometry depends upon the structure of the underlying metal surface. Dynamic heterogeneity of water on the Pt 111 surface is therefore qualitatively different than that for water on the Pt 100 surface. In both cases, statistics of this ad-layer dynamic heterogeneity responds asymmetrically to applied voltage.

  4. Characterizing heterogeneous dynamics at hydrated electrode surfaces.

    Willard, Adam P; Limmer, David T; Madden, Paul A; Chandler, David

    2013-05-14

    In models of Pt 111 and Pt 100 surfaces in water, motions of molecules in the first hydration layer are spatially and temporally correlated. To interpret these collective motions, we apply quantitative measures of dynamic heterogeneity that are standard tools for considering glassy systems. Specifically, we carry out an analysis in terms of mobility fields and distributions of persistence times and exchange times. In so doing, we show that dynamics in these systems is facilitated by transient disorder in frustrated two-dimensional hydrogen bonding networks. The frustration is the result of unfavorable geometry imposed by strong metal-water bonding. The geometry depends upon the structure of the underlying metal surface. Dynamic heterogeneity of water on the Pt 111 surface is therefore qualitatively different than that for water on the Pt 100 surface. In both cases, statistics of this ad-layer dynamic heterogeneity responds asymmetrically to applied voltage.

  5. Thermal inertia and surface heterogeneity on Mars

    Putzig, Nathaniel E.

    Thermal inertia derived from temperature observations is critical for understanding surface geology and assessing potential landing sites on Mars. Derivation methods generally assume uniform surface properties for any given observation. Consequently, horizontal heterogeneity and near-surface layering may yield apparent thermal inertia that varies with time of day and season. To evaluate the effects of horizontal heterogeneity, I modeled the thermal behavior of surfaces containing idealized material mixtures (dust, sand, duricrust, and rocks) and differing slope facets. These surfaces exhibit diurnal and seasonal variability in apparent thermal inertia of several 100 tiu, 1 even for components with moderately contrasting thermal properties. To isolate surface effects on the derived thermal inertia of Mars, I mapped inter- annual and seasonal changes in albedo and atmospheric dust opacity, accounting for their effects in a modified derivation algorithm. Global analysis of three Mars years of MGS-TES 2 data reveals diurnal and seasonal variations of ~200 tiu in the mid-latitudes and 600 tiu or greater in the polar regions. Correlation of TES results and modeled apparent thermal inertia of heterogeneous surfaces indicates pervasive surface heterogeneity on Mars. At TES resolution, the near-surface thermal response is broadly dominated by layering and is consistent with the presence of duricrusts over fines in the mid-latitudes and dry soils over ground ice in the polar regions. Horizontal surface mixtures also play a role and may dominate at higher resolution. In general, thermal inertia obtained from single observations or annually averaged maps may misrepresent surface properties. In lieu of a robust heterogeneous- surface derivation technique, repeat coverage can be used together with forward-modeling results to constrain the near-surface heterogeneity of Mars. 1 tiu == J m -2 K -1 s - 2 Mars Global Surveyor Thermal Emission Spectrometer

  6. An advanced method of heterogeneous reactor theory

    Kochurov, B.P.

    1994-08-01

    Recent approaches to heterogeneous reactor theory for numerical applications were presented in the course of 8 lectures given in JAERI. The limitations of initial theory known after the First Conference on Peacefull Uses of Atomic Energy held in Geneva in 1955 as Galanine-Feinberg heterogeneous theory:-matrix from of equations, -lack of consistent theory for heterogeneous parameters for reactor cell, -were overcome by a transformation of heterogeneous reactor equations to a difference form and by a development of a consistent theory for the characteristics of a reactor cell based on detailed space-energy calculations. General few group (G-number of groups) heterogeneous reactor equations in dipole approximation are formulated with the extension of two-dimensional problem to three-dimensions by finite Furie expansion of axial dependence of neutron fluxes. A transformation of initial matrix reactor equations to a difference form is presented. The methods for calculation of heterogeneous reactor cell characteristics giving the relation between vector-flux and vector-current on a cell boundary are based on a set of detailed space-energy neutron flux distribution calculations with zero current across cell boundary and G calculations with linearly independent currents across the cell boundary. The equations for reaction rate matrices are formulated. Specific methods were developed for description of neutron migration in axial and radial directions. The methods for resonance level's approach for numerous high-energy resonances. On the basis of these approaches the theory, methods and computer codes were developed for 3D space-time react or problems including simulation of slow processes with fuel burn-up, control rod movements, Xe poisoning and fast transients depending on prompt and delayed neutrons. As a result reactors with several thousands of channels having non-uniform axial structure can be feasibly treated. (author)

  7. Temperature dependent heterogeneous rotational correlation in lipids.

    Dadashvand, Neda; Othon, Christina M

    2016-11-15

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

  8. A molecular view of heterogeneous catalysis

    Christensen, Claus H.; Nørskov, Jens Kehlet

    2008-01-01

    The establishment of a molecular view of heterogeneous catalysis has been hampered for a number of reasons. There are, however, recent developments, which show that we are now on the way towards reaching a molecular-scale picture of the way solids work as catalysts. By a combination of new...... by enabling a rational design of new catalysts. We illustrate this important development in heterogeneous catalysis by highlighting recent examples of catalyst systems for which it has been possible to achieve such a detailed understanding. In particular, we emphasize examples where this progress has made...

  9. HETERO code, heterogeneous procedure for reactor calculation

    Jovanovic, S.M.; Raisic, N.M.

    1966-11-01

    This report describes the procedure for calculating the parameters of heterogeneous reactor system taking into account the interaction between fuel elements related to established geometry. First part contains the analysis of single fuel element in a diffusion medium, and criticality condition of the reactor system described by superposition of elements interactions. the possibility of performing such analysis by determination of heterogeneous system lattice is described in the second part. Computer code HETERO with the code KETAP (calculation of criticality factor η n and flux distribution) is part of this report together with the example of RB reactor square lattice

  10. Derivation of Batho's correction factor for heterogeneities

    Lulu, B.A.; Bjaerngard, B.E.

    1982-01-01

    Batho's correction factor for dose in a heterogeneous, layered medium is derived from the tissue--air ratio method (TARM). The reason why the Batho factor is superior to the TARM factor at low energy is ascribed to the fact that it accounts for the distribution of the scatter-generating matter along the centerline. The poor behavior of the Batho factor at high energies is explained as a consequence of the lack of electron equilibrium at appreciable depth below the surface. Key words: Batho factor, heterogeneity, inhomogeneity, tissue--air ratio method

  11. Heterogeneous cores for fast breeder reactor

    Schroeder, R.; Spenke, H.

    1980-01-01

    Firstly, the motivation for heterogeneous cores is discussed. This is followed by an outline of two reactor designs, both of which are variants of the combined ring and island core. These designs are presented by means of figures and detailed tables. Subsequently, a description of two international projects at fast critical zero energy facilities is given. Both of them support the nuclear design of heterogeneous cores. In addition to a survey of these projects, a typical experiment is discussed: the measurement of rate distributions. (orig.) [de

  12. Heterogeneous catalysis at nanoscale for energy applications

    Tao, Franklin (Feng); Kamat, Prashant V

    2015-01-01

    This book presents both the fundamentals concepts and latest achievements of a field that is growing in importance since it represents a possible solution for global energy problems.  It focuses on an atomic-level understanding of heterogeneous catalysis involved in important energy conversion processes. It presents a concise picture for the entire area of heterogeneous catalysis with vision at the atomic- and nano- scales, from synthesis, ex-situ and in-situ characterization, catalytic activity and selectivity, to mechanistic understanding based on experimental exploration and theoretical si

  13. Flows and chemical reactions in heterogeneous mixtures

    Prud'homme, Roger

    2014-01-01

    This book - a sequel of previous publications 'Flows and Chemical Reactions' and 'Chemical Reactions in Flows and Homogeneous Mixtures' - is devoted to flows with chemical reactions in heterogeneous environments.  Heterogeneous media in this volume include interfaces and lines. They may be the site of radiation. Each type of flow is the subject of a chapter in this volume. We consider first, in Chapter 1, the question of the generation of environments biphasic individuals: dusty gas, mist, bubble flow.  Chapter 2 is devoted to the study at the mesoscopic scale: particle-fluid exchange of mom

  14. Static multiplicities in heterogeneous azeotropic distillation sequences

    Esbjerg, Klavs; Andersen, Torben Ravn; Jørgensen, Sten Bay

    1998-01-01

    In this paper the results of a bifurcation analysis on heterogeneous azeotropic distillation sequences are given. Two sequences suitable for ethanol dehydration are compared: The 'direct' and the 'indirect' sequence. It is shown, that the two sequences, despite their similarities, exhibit very...... different static behavior. The method of Petlyuk and Avet'yan (1971), Bekiaris et al. (1993), which assumes infinite reflux and infinite number of stages, is extended to and applied on heterogeneous azeotropic distillation sequences. The predictions are substantiated through simulations. The static sequence...

  15. Pervasive Sensing: Addressing the Heterogeneity Problem

    O'Grady, Michael J; Murdoch, Olga; Kroon, Barnard; Lillis, David; Carr, Dominic; Collier, Rem W; O'Hare, Gregory M P

    2013-01-01

    Pervasive sensing is characterized by heterogeneity across a number of dimensions. This raises significant problems for those designing, implementing and deploying sensor networks, irrespective of application domain. Such problems include for example, issues of data provenance and integrity, security, and privacy amongst others. Thus engineering a network that is fit-for-purpose represents a significant challenge. In this paper, the issue of heterogeneity is explored from the perspective of those who seek to harness a pervasive sensing element in their applications. A initial solution is proposed based on the middleware construct.

  16. Addressing Longevity’ Heterogeneity in Pension Scheme Design

    Ayuso, Mercedes; Bravo, Jorge Miguel; Holzmann, Robert

    2017-01-01

    Ayuso, M., Bravo, J. M., & Holzmann, R. (2017). Addressing Longevity’ Heterogeneity in Pension Scheme Design. Journal of Finance and Economics, 6(1), 1-21. DOI: 10.12735/jfe.v6n1p1 This paper demonstrates that the link between heterogeneity in longevity and lifetime income across countries is mostly high and often increasing; that it translates into an implicit tax/subsidy, with rates reaching 20 percent and higher in some countries; that such rates risk perverting redistributive objective...

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

    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.

  18. RAIN: RNA-protein Association and Interaction Networks

    Junge, Alexander; Refsgaard, Jan Christian; Garde, Christian

    2017-01-01

    is challenging due to data heterogeneity. Here, we present a database of ncRNA-RNA and ncRNA-protein interactions and its integration with the STRING database of protein-protein interactions. These ncRNA associations cover four organisms and have been established from curated examples, experimental data...

  19. Simulation study on heterogeneous variance adjustment for observations with different measurement error variance

    Pitkänen, Timo; Mäntysaari, Esa A; Nielsen, Ulrik Sander

    2013-01-01

    of variance correction is developed for the same observations. As automated milking systems are becoming more popular the current evaluation model needs to be enhanced to account for the different measurement error variances of observations from automated milking systems. In this simulation study different...... models and different approaches to account for heterogeneous variance when observations have different measurement error variances were investigated. Based on the results we propose to upgrade the currently applied models and to calibrate the heterogeneous variance adjustment method to yield same genetic......The Nordic Holstein yield evaluation model describes all available milk, protein and fat test-day yields from Denmark, Finland and Sweden. In its current form all variance components are estimated from observations recorded under conventional milking systems. Also the model for heterogeneity...

  20. Targeting population heterogeneity in Saccharomyces cerevisiae batch fermentation for optimal cell factories

    Heins, Anna-Lena; Lencastre Fernandes, Rita; Lundin, L.

    )). Significant gradients of e.g. dissolved oxygen, substrates, and pH are typically observed in many industrial scale fermentation processes. Consequently, the microbial cells experience rapid changes in environmental conditions as they circulate throughout the reactor, which might pose stress on the cells...... and affect their metabolism and consequently affect the heterogeneity level of the population. To further investigate these phenomena and gain a deeper understanding of population heterogeneity, Saccharomyces cerevisiae growth reporter strains based on the expression of green fluorescent protein (GFP) were...... environmental factors on heterogeneity level and amount of living cells. A highly dynamic behavior with regard to subpopulation distribution during the different growth stages was seen for the batch cultivations. Moreover, it could be demonstrated that the glucose concentration had a clear influence...

  1. The biology of myelodysplastic syndromes: unity despite heterogeneity

    Azra Raza

    2010-06-01

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

  2. On the compensation effect in heterogeneous catalysis

    Pedersen, Thomas Bligaard; Honkala, Johanna Karoliina; Logadottir, Ashildur

    2003-01-01

    For a class of heterogeneously catalyzed reactions, we explain the compensation effect in terms of a switching of kinetic regimes leading to a concomitant change in the apparent activation energy and in the prefactor for the overall rate of the reaction. We first use the ammonia synthesis...

  3. µ-reactors for Heterogeneous Catalysis

    Jensen, Robert

    is described in detail. Since heating and temperature measurement is an extremely important point in heterogeneous catalysis an entire chapter is dedicated to this subject. Three different types of heaters have been implemented and tested both for repeatability and homogeneity of the heating as well...

  4. Kinetic equation of heterogeneous catalytic isotope exchange

    Trokhimets, A I [AN Belorusskoj SSR, Minsk. Inst. Fiziko-Organicheskoj Khimii

    1979-12-01

    A kinetic equation is derived for the bimolecular isotope exchange reaction between AXsub(n)sup(*) and BXsub(m)sup(o), all atoms of element X in each molecule being equivalent. The equation can be generalized for homogeneous and heterogeneous catalytic isotope exchange.

  5. Rate tracer studies of heterogeneous catalysis

    Happel, J; Kiang, S

    1977-10-01

    An analysis is presented of the extent to which parameters involved in transient tracing of isotopic species in heterogeneous catalysis can be determined by experiments in which tracer concentrations are measured as a function of time. Different treatments for open and closed systems with the over-all reaction at equilibrium or irreversible were developed.

  6. Cooperative and Heterogeneous Indoor Localization - Experiments

    Benoît, Denis; Raulefs, Ronald; Fleury, Bernard Henri

    2013-01-01

    In this paper we present the results of real-life localization experiments performed in an unprecedented cooperative and heterogeneous wireless context. These measurements are based on ZigBee and orthogonal frequency division multiplexing (OFDM) devices, respectively endowed with received signal...

  7. CM Net heterogeneous local network of microcomputers

    Gutche, R.Kh.

    1988-01-01

    Realization of the CM Net heterogeneous local network for the PDP-11 type computers with the RT-11 operational system control is described. The main advantage of the network is the realization of virtual disks in general form including a system unit. the network can be used everywhere, where the problem on computer connection by simple interfaces is stated. 6 refs

  8. The biodiversity conservation game with heterogeneous countries

    Winands, S.; Holm-Müller, K.; Weikard, H.P.

    2013-01-01

    Biodiversity is an essential resource, which we classify as conditionally-renewable. In order to achieve conservation and sustainable use of biodiversity virtually all nation states signed the United Nations Convention on Biological Diversity. In this paper we investigate how the heterogeneity of

  9. Prospect Theory in the Heterogeneous Agent Model

    Polach, J.; Kukačka, Jiří

    (2018) ISSN 1860-711X R&D Projects: GA ČR(CZ) GBP402/12/G097 Institutional support: RVO:67985556 Keywords : Heterogeneous Agent Model * Prospect Theory * Behavioral finance * Stylized facts Subject RIV: AH - Economic s OBOR OECD: Finance Impact factor: 0.931, year: 2016 http://library.utia.cas.cz/separaty/2018/E/kukacka-0488438.pdf

  10. Heterogeneous formation of HONO on carbonaceous aerosol

    Ammann, M.; Kalberer, M.; Tabor, K. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)] [and others

    1997-09-01

    Based on an on-line and in situ experimental approach, for the first time heterogeneous production of nitrous acid (HONO) on carbon aerosol at ambient pressure and low NO{sub 2} concentration has been quantified by use of a {sup 13}N tracer technique. (author) 1 fig., 4 refs.

  11. Heterogeneous sensory processing in persistent postherniotomy pain

    Aasvang, Eske Kvanner; Brandsborg, Birgitte; Jensen, Troels Staehelin

    2010-01-01

    (rho=0.58, p=0.002) to the hyperalgesic level on the painful side, again suggesting central nervous mechanisms in PPP. In conclusion, this study shows that a standardized trauma results in heterogeneous combinations of hypo- and hyperalgesia. Z-score evaluation of sensory function identifies...

  12. Indoor Location Fingerprinting with Heterogeneous Clients

    Kjærgaard, Mikkel Baun

    2011-01-01

    Heterogeneous wireless clients measure signal strength differently. This is a fundamental problem for indoor location fingerprinting, and it has a high impact on the positioning accuracy. Mapping-based solutions have been presented that require manual and error-prone calibration for each new clie...

  13. Physical Heterogeneity and Aquatic Community Function in ...

    The geomorphological character of a river network provides the template upon which evolution acts to create unique biological communities. Deciphering commonly observed patterns and processes within riverine landscapes resulting from the interplay between physical and biological components is a central tenet for the interdisciplinary field of river science. Relationships between the physical heterogeneity and food web character of functional process zones (FPZs) – large tracts of river with a similar geomorphic character - in the Kanawha River (West Virginia, USA) are examined in this study. Food web character was measured as food chain length (FCL), which reflects ecological community structure and ecosystem function. Our results show the same basal resources were present throughout the Kanawha River but their assimilation into the aquatic food web by primary consumers differed between FPZs. Differences in the trophic position of secondary consumers – fish - were also recorded between FPZs. Overall, both the morphological heterogeneity and heterogeneity of the river bed sediment of FPZs were significantly correlated with FCL. Specifically, FCL increases with greater FPZ physical heterogeneity, supporting tenet 8 of the river ecosystem synthesis. In previous research efforts, we delineated the functional process zones (FPZs) of the Kanawha River. In this study, we examined the relationship between the hydrogeomorphically-derived zones with food webs.

  14. Clinical heterogeneity in newly diagnosed Parkinson's disease

    Post, Bart; Speelman, Johannes D.; de Haan, Rob J.

    2008-01-01

    OBJECTIVE: To determine clinical heterogeneity in newly diagnosed Parkinson's disease using cluster analysis and to describe the subgroups in terms of impairment, disability, perceived quality of life, and use of dopaminergic therapy. METHODS: We conducted a k-means cluster analysis in a prospective

  15. Heterogeneous expectations in monetary DSGE models

    Massaro, D.

    2013-01-01

    This paper derives a general New Keynesian framework with heterogeneous expectations by explicitly solving the micro-foundations underpinning the model. The resulting reduced form is analytically tractable and encompasses the representative rational agent benchmark as a special case. We specify a

  16. Interpretable Categorization of Heterogeneous Time Series Data

    Lee, Ritchie; Kochenderfer, Mykel J.; Mengshoel, Ole J.; Silbermann, Joshua

    2017-01-01

    We analyze data from simulated aircraft encounters to validate and inform the development of a prototype aircraft collision avoidance system. The high-dimensional and heterogeneous time series dataset is analyzed to discover properties of near mid-air collisions (NMACs) and categorize the NMAC encounters. Domain experts use these properties to better organize and understand NMAC occurrences. Existing solutions either are not capable of handling high-dimensional and heterogeneous time series datasets or do not provide explanations that are interpretable by a domain expert. The latter is critical to the acceptance and deployment of safety-critical systems. To address this gap, we propose grammar-based decision trees along with a learning algorithm. Our approach extends decision trees with a grammar framework for classifying heterogeneous time series data. A context-free grammar is used to derive decision expressions that are interpretable, application-specific, and support heterogeneous data types. In addition to classification, we show how grammar-based decision trees can also be used for categorization, which is a combination of clustering and generating interpretable explanations for each cluster. We apply grammar-based decision trees to a simulated aircraft encounter dataset and evaluate the performance of four variants of our learning algorithm. The best algorithm is used to analyze and categorize near mid-air collisions in the aircraft encounter dataset. We describe each discovered category in detail and discuss its relevance to aircraft collision avoidance.

  17. Pricing strategies under heterogeneous service requirements

    Mandjes, M.R.H.

    2003-01-01

    This paper analyzes a communication network with heterogeneous customers. We investigate priority queueing as a way to differentiate between these users. Customers join the network as long as their utility (which is a function of the queueing delay) is larger than the price of the service. We focus

  18. Pricing strategies under heterogeneous service requirements

    Mandjes, M.R.H.

    This paper analyzes a communication network, used by customers with heterogeneous service requirements. We investigate priority queueing as a way to establish service differentiation. It is assumed that there is an infinite population of customers, who join the network as long as their utility

  19. Transient well flow in vertically heterogeneous aquifers.

    Hemker, C.J.

    1999-01-01

    A solution for the general problem of computing well flow in vertically heterogeneous aquifers is found by an integration of both analytical and numerical techniques. The radial component of flow is treated analytically; the drawdown is a continuous function of the distance to the well. The

  20. Vanishing microwave effects : influence of heterogeneity

    Dressen, M.H.C.L.; Kruijs, van de B.H.P.; Meuldijk, J.; Vekemans, J.A.J.M.; Hulshof, L.A.

    2007-01-01

    A consistent setup of experiments has been conducted to demonstrate an enhanced reaction rate under microwave irradiation as compared to conventional heating, i.e. a real microwave effect. It was found that addition of a cosolvent, diminishing the heterogeneous character of the reaction mixture,

  1. Effects of heterogeneity on bank efficiency scores

    Bos, J. W. B.; Koetter, M.; Kolari, J. W.; Kool, C. J. M.

    2009-01-01

    Bank efficiency estimates often serve as a proxy of managerial skill since they quantify sub-optimal production choices. But such deviations can also be due to omitted systematic differences among banks. In this study, we examine the effects of heterogeneity on bank efficiency scores. We compare

  2. Heterogeneous networking in the home environment

    Bolla, Raffaele; Davoli, Franco; Repetto, Matteo; Fragopoulos, Tasos; Serpanos, D.; Chessa, Stefano; Ferro, Erina

    2006-01-01

    The management and control at multiple protocol layers of a heterogeneous networking structure, to support multimedia applications in the home environment, is considered. The paper examines possible scenarios, and corresponding architectural solutions, also in the light of existing wireless and sensor networks technologies.

  3. Nonparametric estimation in models for unobservable heterogeneity

    Hohmann, Daniel

    2014-01-01

    Nonparametric models which allow for data with unobservable heterogeneity are studied. The first publication introduces new estimators and their asymptotic properties for conditional mixture models. The second publication considers estimation of a function from noisy observations of its Radon transform in a Gaussian white noise model.

  4. Accelerating Mathematics Achievement Using Heterogeneous Grouping

    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…

  5. Cooperative Radio Resource Management for Heterogeneous Networks

    Mihovska, Albena D.; Tragos, Elias; Luo, Jijun

    2009-01-01

    The heterogeneity in technology and also in ownership leads to complex systems and interworking problems, which can be seen from the ability to establish and maintain connections with required quality, in fault detection and location, in resource allocation and in charging of the usage of the net...

  6. Heterogeneous Distribution of Chromium on Mercury

    Nittler, L. R.; Boujibar, A.; Crapster-Pregont, E.; Frank, E. A.; McCoy, T. J.; McCubbin, F. M.; Starr, R. D.; Vander Kaaden, K. E.; Vorburger, A.; Weider, S. Z.

    2018-05-01

    Mercury's surface has an average Cr/Si ratio of 0.003 (Cr 800 ppm), with at least a factor of 2 systematic uncertainty. Cr is heterogeneously distributed and correlated with Mg, Ca, S, and Fe and anti-correlated with Al.

  7. Heterogeneous Computing in Economics: A Simplified Approach

    Dziubinski, Matt P.; Grassi, Stefano

    This paper shows the potential of heterogeneous computing in solving dynamic equilibrium models in economics. We illustrate the power and simplicity of the C++ Accelerated Massive Parallelism recently introduced by Microsoft. Starting from the same exercise as Aldrich et al. (2011) we document a ...

  8. Multilingual Federated Searching Across Heterogeneous Collections.

    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)

  9. BUFFER CAPACITY IN HETEROGENEOUS MULTICOMPONENT SYSTEMS. REVIEW

    Oxana Spinu

    2015-12-01

    Full Text Available The quantitative basis of the theory of buffer properties for two-phase acid-base buffer systems and for multicomponent heterogeneous systems has been derived. The analytical equations with respect to all components for diverse multicomponent systems were deduced. It has been established, that the buffer capacities of components are mutually proportional.

  10. Pricing Liquidity Risk with Heterogeneous Investment Horizons

    Beber, A.; Driessen, J.; Tuijp, P.F.A.

    2012-01-01

    We develop a new asset pricing model with stochastic transaction costs and investors with heterogenous horizons. Short-term investors hold only liquid assets in equilibrium. This generates segmentation effects in the pricing of liquid versus illiquid assets. Specifically, the liquidity (risk) premia

  11. Hydraulic fracturing in anisotropic and heterogeneous rocks

    Valliappan, V.; Remmers, J.J.C.; Barnhoorn, A.; Smeulders, D.M.J.

    2017-01-01

    In this paper, we present a two dimensional model for modelling the hydraulic fracture process in anisotropic and heterogeneous rocks. The model is formulated using extended finite elements (XFEM) in combination with Newton-Raphson method for spatial and Euler's implicit scheme for time. The

  12. Shock propagation in a heterogeneous medium

    Elbaz, D.

    2011-01-01

    In the frame of the inertial confinement fusion in direct drive, the use of foams as ablator allows the reduction of hydrodynamic instabilities created on the target by the direct laser irradiation. The foam is made up of carbon (CH) fibers impregnated of cryogenic deuterium-tritium (DT). In the past, studies have been carried out considering this foam to be a homogeneous medium. Yet, the foam presents heterogeneous features. We study the effects of this heterogeneity on the shock velocity when the laser irradiates the target. Thanks to experimental and numerical studies, we show that the shock propagates faster in the heterogeneous medium than in the homogeneous one with the same averaged density. This velocity gap depends on the presence rate of the CH fibers in the foam, the density ratio, the adiabatic coefficient and the foam geometry. We model the foam by different ways, more and more complex. The shock velocity modification is due to the baroclinicity which, during the interaction between the shock front and the interface, creates a vorticity deposition, responsible for the shock acceleration. Accordingly, an interface, which is plane and perpendicular to the front shock, maximizes the vorticity deposition and increases the velocity gaps between heterogeneous and homogeneous media. We found a correlation between the kinetic energy behind the shock front and the velocities relative difference. We compared our results with two analytical models. However, the system is not closed, so we can't for the moment develop a predictive model. (author) [fr

  13. Heterogeneous membranes filled with hypercrosslinked microparticle adsorbent

    Hradil, Jiří; Krystl, V.; Hrabánek, P.; Bernauer, B.; Kočiřík, Milan

    2005-01-01

    Roč. 65, 1-2 (2005), s. 57-68 ISSN 1381-5148 R&D Projects: GA ČR GA104/03/0680 Institutional research plan: CEZ:AV0Z40500505 Keywords : heterogeneous membranes * hypercrosslinked adsorbent * microparticle s Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.565, year: 2005

  14. Scale Reliability Evaluation with Heterogeneous Populations

    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…

  15. International Military Practice Amidst Ethical Heterogeneity

    2013-12-13

    importance of the multicultural environment cannot be understated, and the ethical make-up, moral philosophy, and cultural relativism (Robertson and...determinism, moral relativism . Rather, the development of students’ ethical and moral strength is achieved by engaging in learning opportunites...INTERNATIONAL MILITARY PRACTICE AMIDST ETHICAL HETEROGENEITY A thesis presented to the Faculty of the U.S. Army Command and

  16. Selection of workers and firm heterogeneity

    G.W.J. Hendrikse (George)

    1992-01-01

    textabstractA model based on differences between workers regarding their preferences for wage and leisure drives the heterogeneity of firms result. The more industrious workers are driven to small firms due to free riding in large firms. An industry consisting of small and large firms turns out to

  17. Visual Analytics for Heterogeneous Geoscience Data

    Pan, Y.; Yu, L.; Zhu, F.; Rilee, M. L.; Kuo, K. S.; Jiang, H.; Yu, H.

    2017-12-01

    Geoscience data obtained from diverse sources have been routinely leveraged by scientists to study various phenomena. The principal data sources include observations and model simulation outputs. These data are characterized by spatiotemporal heterogeneity originated from different instrument design specifications and/or computational model requirements used in data generation processes. Such inherent heterogeneity poses several challenges in exploring and analyzing geoscience data. First, scientists often wish to identify features or patterns co-located among multiple data sources to derive and validate certain hypotheses. Heterogeneous data make it a tedious task to search such features in dissimilar datasets. Second, features of geoscience data are typically multivariate. It is challenging to tackle the high dimensionality of geoscience data and explore the relations among multiple variables in a scalable fashion. Third, there is a lack of transparency in traditional automated approaches, such as feature detection or clustering, in that scientists cannot intuitively interact with their analysis processes and interpret results. To address these issues, we present a new scalable approach that can assist scientists in analyzing voluminous and diverse geoscience data. We expose a high-level query interface that allows users to easily express their customized queries to search features of interest across multiple heterogeneous datasets. For identified features, we develop a visualization interface that enables interactive exploration and analytics in a linked-view manner. Specific visualization techniques such as scatter plots to parallel coordinates are employed in each view to allow users to explore various aspects of features. Different views are linked and refreshed according to user interactions in any individual view. In such a manner, a user can interactively and iteratively gain understanding into the data through a variety of visual analytics operations. We

  18. Transient well flow in vertically heterogeneous aquifers

    Hemker, C. J.

    1999-11-01

    A solution for the general problem of computing well flow in vertically heterogeneous aquifers is found by an integration of both analytical and numerical techniques. The radial component of flow is treated analytically; the drawdown is a continuous function of the distance to the well. The finite-difference technique is used for the vertical flow component only. The aquifer is discretized in the vertical dimension and the heterogeneous aquifer is considered to be a layered (stratified) formation with a finite number of homogeneous sublayers, where each sublayer may have different properties. The transient part of the differential equation is solved with Stehfest's algorithm, a numerical inversion technique of the Laplace transform. The well is of constant discharge and penetrates one or more of the sublayers. The effect of wellbore storage on early drawdown data is taken into account. In this way drawdowns are found for a finite number of sublayers as a continuous function of radial distance to the well and of time since the pumping started. The model is verified by comparing results with published analytical and numerical solutions for well flow in homogeneous and heterogeneous, confined and unconfined aquifers. Instantaneous and delayed drainage of water from above the water table are considered, combined with the effects of partially penetrating and finite-diameter wells. The model is applied to demonstrate that the transient effects of wellbore storage in unconfined aquifers are less pronounced than previous numerical experiments suggest. Other applications of the presented solution technique are given for partially penetrating wells in heterogeneous formations, including a demonstration of the effect of decreasing specific storage values with depth in an otherwise homogeneous aquifer. The presented solution can be a powerful tool for the analysis of drawdown from pumping tests, because hydraulic properties of layered heterogeneous aquifer systems with

  19. Characterization of oil and gas reservoir heterogeneity

    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.

  20. Organized proteomic heterogeneity in colorectal cancer liver metastases and implications for therapies.

    Turtoi, Andrei; Blomme, Arnaud; Debois, Delphine; Somja, Joan; Delvaux, David; Patsos, Georgios; Di Valentin, Emmanuel; Peulen, Olivier; Mutijima, Eugène Nzaramba; De Pauw, Edwin; Delvenne, Philippe; Detry, Olivier; Castronovo, Vincent

    2014-03-01

    Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis displayed increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA-repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demonstrate their in vivo antibody-based targeting and highlight their potential usefulness for clinical applications. The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of targetable antigens. © 2014 by the American Association for the Study of Liver Diseases.

  1. Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties*

    Dalli, Jesmond; Montero-Melendez, Trinidad; Norling, Lucy V; Yin, Xiaoke; Hinds, Charles; Haskard, Dorian; Mayr, Manuel; Perretti, Mauro

    2013-01-01

    Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions. PMID:23660474

  2. Scaling the heterogeneously heated convective boundary layer

    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

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

    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.

  4. Collective Motion in Behaviorally Heterogeneous Systems

    Copenhagen, Katherine

    Collective motion is a widespread phenomenon in nature where individuals actively propel themselves, gather together and move as a group. Some examples of collective motion are bird flocks, fish schools, bacteria swarms, cell clusters, and crowds of people. Many models seek to understand the effects of activity in collective systems including things such as environmental disorder, density, and interaction details primarily at infinite size limits and with uniform populations. In this dissertation I investigate the effects of finite sizes and behavioral heterogeneity as it exists in nature. Behavioral heterogeneity can originate from several different sources. Mixed populations of individuals can have inherently different behaviors such as mutant bacteria, injured fish, or agents that prefer individualistic behavior over coordinated motion. Alternatively, agents may modify their own behavior based on some local environmental dependency, such as local substrate, or density. In cases such as mutant cheaters in bacteria or malfunctioning drones in swarms, mixed populations of behaviorally heterogeneous agents can be modelled as arising in the form of aligning and non-aligning agents. When this kind of heterogeneity is introduced, there is a critical carrying capacity of non-aligners above which the system is unable to form a cohesive ordered group. However, if the cohesion of the group is relaxed to allow for fracture, the system will actively sort out non-aligning agents the system will exist at a critical non-aligner fraction. A similar heterogeneity could result in a mixture of high and low noise individuals. In this case there is also a critical carry capacity beyond which the system is unable to reach an ordered state, however the nature of this transition depends on the model details. Agents which are part of an ordered collective may vary their behavior as the group changes environments such as a flock of birds flying into a cloud. Using a unique model of a

  5. Heterogeneous self-assembled media for biopolymerization

    Monnard, Pierre-Alain

    2011-01-01

    Heterogeneous media, such as micro-structured aqueous environments, could offer an alternative approach to the synthesis of biopolymers with novel functions. Structured media are here defined as specialized, self-assembled structures that are formed, e.g, by amphiphiles, such as liposomes, emulsion...... polymerization, the initial elongation rates clearly depended on the complementarity of the monomers with the templating nucleobases3. However, metal-ion catalyzed reactions deliver RNA analogs with heterogeneous linkages. Moreover, the usefulness of this medium in the form of quasi-compartmentalization extends...... beyond metal-ion catalysis reactions, as we have recently demonstrated the catalytic power of a dipeptide, SerHis, for the regioselective formation of phosphodiester bonds. These results in conjonction with the synthesis of nucleobases at -78˚C, the demonstration of ribozyme activity (RNA ligase ribozyme...

  6. Population dynamics on heterogeneous bacterial substrates

    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. Sparse covariance estimation in heterogeneous samples.

    Rodríguez, Abel; Lenkoski, Alex; Dobra, Adrian

    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.

  8. Optimization of Hierarchically Scheduled Heterogeneous Embedded Systems

    Pop, Traian; Pop, Paul; Eles, Petru

    2005-01-01

    We present an approach to the analysis and optimization of heterogeneous distributed embedded systems. The systems are heterogeneous not only in terms of hardware components, but also in terms of communication protocols and scheduling policies. When several scheduling policies share a resource......, they are organized in a hierarchy. In this paper, we address design problems that are characteristic to such hierarchically scheduled systems: assignment of scheduling policies to tasks, mapping of tasks to hardware components, and the scheduling of the activities. We present algorithms for solving these problems....... Our heuristics are able to find schedulable implementations under limited resources, achieving an efficient utilization of the system. The developed algorithms are evaluated using extensive experiments and a real-life example....

  9. Heterogeneously Catalyzed Oxidation Reactions Using Molecular Oxygen

    Beier, Matthias Josef

    Heterogeneously catalyzed selective oxidation reactions have attracted a lot of attention in recent time. The first part of the present thesis provides an overview over heterogeneous copper and silver catalysts for selective oxidations in the liquid phase and compared the performance and catalytic...... that both copper and silver can function as complementary catalyst materials to gold showing different catalytic properties and being more suitable for hydrocarbon oxidation reactions. Potential opportunities for future research were outlined. In an experimental study, the potential of silver as a catalyst...... revealed that all catalysts were more active in combination with ceria nanoparticles and that under the tested reaction conditions silver was equally or even more efficient than the gold catalysts. Calcination at 900 °C of silver on silica prepared by impregnation afforded a catalyst which was used...

  10. Modelling Configuration Knowledge in Heterogeneous Product Families

    Queva, Matthieu Stéphane Benoit; Männistö, Tomi; Ricci, Laurent

    2011-01-01

    Product configuration systems play an important role in the development of Mass Customisation. The configuration of complex product families may nowadays involve multiple design disciplines, e.g. hardware, software and services. In this paper, we present a conceptual approach for modelling...... the variability in such heterogeneous product families. Our approach is based on a framework that aims to cater for the different stakeholders involved in the modelling and management of the product family. The modelling approach is centred around the concepts of views, types and constraints and is illustrated...... by a motivation example. Furthermore, as a proof of concept, a prototype has been implemented for configuring a non-trivial heterogeneous product family....

  11. Spatial preference heterogeneity in forest recreation

    Abildtrup, Jens; Garcia, Serge; Olsen, Søren Bøye

    2013-01-01

    In this study, we analyze the preferences for recreational use of forests in Lorraine (Northeastern France), applying stated preference data. Our approach allows us to estimate individual-specific preferences for recreational use of different forest types. These estimates are used in a second stage...... in the estimation of welfare economic values for parking and picnic facilities in the analyzed model. The results underline the importance of considering spatial heterogeneity of preferences carrying out economic valuation of spatial-delineated environmental goods and that the spatial variation in willingness...... of the analysis where we test whether preferences depend on access to recreation sites. We find that there is significant preference heterogeneity with respect to most forest attributes. The spatial analysis shows that preferences for forests with parking and picnic facilities are correlated with having access...

  12. Synchronization in networks with heterogeneous coupling delays

    Otto, Andreas; Radons, Günter; Bachrathy, Dániel; Orosz, Gábor

    2018-01-01

    Synchronization in networks of identical oscillators with heterogeneous coupling delays is studied. A decomposition of the network dynamics is obtained by block diagonalizing a newly introduced adjacency lag operator which contains the topology of the network as well as the corresponding coupling delays. This generalizes the master stability function approach, which was developed for homogenous delays. As a result the network dynamics can be analyzed by delay differential equations with distributed delay, where different delay distributions emerge for different network modes. Frequency domain methods are used for the stability analysis of synchronized equilibria and synchronized periodic orbits. As an example, the synchronization behavior in a system of delay-coupled Hodgkin-Huxley neurons is investigated. It is shown that the parameter regions where synchronized periodic spiking is unstable expand when increasing the delay heterogeneity.

  13. Heterogeneous propellant internal ballistics: criticism and regeneration

    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).

  14. Micromechanics Based Failure Analysis of Heterogeneous Materials

    Sertse, Hamsasew M.

    In recent decades, heterogeneous materials are extensively used in various industries such as aerospace, defense, automotive and others due to their desirable specific properties and excellent capability of accumulating damage. Despite their wide use, there are numerous challenges associated with the application of these materials. One of the main challenges is lack of accurate tools to predict the initiation, progression and final failure of these materials under various thermomechanical loading conditions. Although failure is usually treated at the macro and meso-scale level, the initiation and growth of failure is a complex phenomena across multiple scales. The objective of this work is to enable the mechanics of structure genome (MSG) and its companion code SwiftComp to analyze the initial failure (also called static failure), progressive failure, and fatigue failure of heterogeneous materials using micromechanics approach. The initial failure is evaluated at each numerical integration point using pointwise and nonlocal approach for each constituent of the heterogeneous materials. The effects of imperfect interfaces among constituents of heterogeneous materials are also investigated using a linear traction-displacement model. Moreover, the progressive and fatigue damage analyses are conducted using continuum damage mechanics (CDM) approach. The various failure criteria are also applied at a material point to analyze progressive damage in each constituent. The constitutive equation of a damaged material is formulated based on a consistent irreversible thermodynamics approach. The overall tangent modulus of uncoupled elastoplastic damage for negligible back stress effect is derived. The initiation of plasticity and damage in each constituent is evaluated at each numerical integration point using a nonlocal approach. The accumulated plastic strain and anisotropic damage evolution variables are iteratively solved using an incremental algorithm. The damage analyses

  15. IDENTIFIABILITY VERSUS HETEROGENEITY IN GROUNDWATER MODELING SYSTEMS

    A M BENALI

    2003-06-01

    Full Text Available Review of history matching of reservoirs parameters in groundwater flow raises the problem of identifiability of aquifer systems. Lack of identifiability means that there exists parameters to which the heads are insensitive. From the guidelines of the study of the homogeneous case, we inspect the identifiability of the distributed transmissivity field of heterogeneous groundwater aquifers. These are derived from multiple realizations of a random function Y = log T  whose probability distribution function is normal. We follow the identifiability of the autocorrelated block transmissivities through the measure of the sensitivity of the local derivatives DTh = (∂hi  ∕ ∂Tj computed for each sample of a population N (0; σY, αY. Results obtained from an analysis of Monte Carlo type suggest that the more a system is heterogeneous, the less it is identifiable.

  16. Integrating CLIPS applications into heterogeneous distributed systems

    Adler, Richard M.

    1991-01-01

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

  17. Pressure dependence of dynamical heterogeneity in water

    Teboul, Victor

    2008-01-01

    Using molecular dynamics simulations we investigate the effect of pressure on the dynamical heterogeneity in water. We show that the effect of a pressure variation in water is qualitatively different from the effect of a temperature variation on the dynamical heterogeneity in the liquid. We observe a strong decrease of the aggregation of molecules of low mobility together with a decrease of the characteristic time associated with this aggregation. However, the aggregation of the most mobile molecules and the characteristic time of this aggregation are only slightly affected. In accordance with this result, the non-Gaussian parameter shows an important decrease with pressure while the characteristic time t* of the non-Gaussian parameter is only slightly affected. These results highlight then the importance of pressure variation investigations in low temperature liquids on approach to the glass transition

  18. Modeling and simulation of heterogeneous catalytic processes

    Dixon, Anthony

    2014-01-01

    Heterogeneous catalysis and mathematical modeling are essential components of the continuing search for better utilization of raw materials and energy, with reduced impact on the environment. Numerical modeling of chemical systems has progressed rapidly due to increases in computer power, and is used extensively for analysis, design and development of catalytic reactors and processes. This book presents reviews of the state-of-the-art in modeling of heterogeneous catalytic reactors and processes. Reviews by leading authorities in the respective areas Up-to-date reviews of latest techniques in modeling of catalytic processes Mix of US and European authors, as well as academic/industrial/research institute perspectives Connections between computation and experimental methods in some of the chapters.

  19. Cyber Insurance for Heterogeneous Wireless Networks

    Lu, Xiao; Niyato, Dusit; Jiang, Hai; Wang, Ping; Poor, H. Vincent

    2017-01-01

    Heterogeneous wireless networks (HWNs) composed of densely deployed base stations of different types with various radio access technologies have become a prevailing trend to accommodate ever-increasing traffic demand in enormous volume. Nowadays, users rely heavily on HWNs for ubiquitous network access that contains valuable and critical information such as financial transactions, e-health, and public safety. Cyber risks, representing one of the most significant threats to network security an...

  20. Lignin Valorization using Heterogenous Catalytic Oxidation

    Melián Rodríguez, Mayra; Shunmugavel, Saravanamurugan; Kegnæs, Søren

    The research interests in biomass conversion to fuels and chemicals has increased significantly in the last decade in view of current problems such as global warming, high oil prices, food crisis and other geopolitical scenarios. Many different reactions and processes to convert biomass into high...... of the reaction conditions 4. Here, we therefore present an overview of the recent research about conversion of some lignin model compounds using heterogeneous catalysis in oxidation reactions....

  1. Dynamical Systems Approach to Endothelial Heterogeneity

    Regan, Erzsébet Ravasz; Aird, William C.

    2012-01-01

    Rationale Objective Here we reexamine our current understanding of the molecular basis of endothelial heterogeneity. We introduce multistability as a new explanatory framework in vascular biology. Methods We draw on the field of non-linear dynamics to propose a dynamical systems framework for modeling multistability and its derivative properties, including robustness, memory, and plasticity. Conclusions Our perspective allows for both a conceptual and quantitative description of system-level features of endothelial regulation. PMID:22723222

  2. Heterogeneous agents and decison making within firms

    Hung, Chung-yu

    2015-01-01

    This dissertation explores the implications of agents’ heterogeneity in decision making within situations where information is not completely contractible. Specifically, the study applies empirical methods across three chapters to examine the role of employees’ traits and their mutual relationships in decision making within firms. The first chapter investigates the association between managerial ability and managers’ discretionary bonus decisions using a dataset from a Chinese hospital and sh...

  3. Cognitive resource management for heterogeneous cellular networks

    Liu, Yongkang

    2014-01-01

    This Springer Brief focuses on cognitive resource management in heterogeneous cellular networks (Het Net) with small cell deployment for the LTE-Advanced system. It introduces the Het Net features, presents practical approaches using cognitive radio technology in accommodating small cell data relay and optimizing resource allocation and examines the effectiveness of resource management among small cells given limited coordination bandwidth and wireless channel uncertainty. The authors introduce different network characteristics of small cell, investigate the mesh of small cell access points in

  4. Flow shop scheduling with heterogeneous workers

    Benavides, Alexander J.; Ritt, Marcus; Miralles Insa, Cristóbal Javier

    2014-01-01

    We propose an extension to the flow shop scheduling problem named Heterogeneous Flow Shop Scheduling Problem (Het-FSSP), where two simultaneous issues have to be resolved: finding the best worker assignment to the workstations, and solving the corresponding scheduling problem. This problem is motivated by Sheltered Work centers for Disabled, whose main objective is the labor integration of persons with disabilities, an important aim not only for these centers but for any company d...

  5. Scheduling Driven Partitioning of Heterogeneous Embedded Systems

    Pop, Paul; Eles, Petru; Peng, Zebo

    1998-01-01

    In this paper we present an algorithm for system level hardware/software partitioning of heterogeneous embedded systems. The system is represented as an abstract graph which captures both data-flow and the flow of control. Given an architecture consisting of several processors, ASICs and shared...... busses, our partitioning algorithm finds the partitioning with the smallest hardware cost and is able to predict and guarantee the performance of the system in terms of worst case delay....

  6. Phenotype heterogeneity in cancer cell populations

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

    2016-01-01

    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

  7. Phenotype heterogeneity in cancer cell populations

    Almeida, Luis [CNRS UMR 7598, LJLL, & INRIA MAMBA team, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, luis@ann.jussieu.fr (France); Chisholm, Rebecca [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, rebecca.chisholm@gmail.com (Australia); Clairambault, Jean [INRIA MAMBA team & LJLL, UMR 7598, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, jean.clairambault@inria.fr, Corresponding author (France); Escargueil, Alexandre [INSERM “Cancer Biology and Therapeutics”, Sorbonne Universités, UPMC Univ Paris 06, UMR-S 938, CDR St Antoine, Hôpital St Antoine, 184 Fbg. St Antoine, 75571 Paris cedex 12, France, alexandre.escargueil@upmc.fr (France); Lorenzi, Tommaso [CMLA, ENS Cachan, 61, Av. du Président Wilson, 94230 Cachan cedex & INRIA MAMBA team, & LJLL, UMR 7598, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, tommaso.lorenzi@gmail.com (France); Lorz, Alexander [Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598 & INRIA Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, alex.lorz@ann.jussieu.fr (France); Trélat, Emmanuel [Institut Universitaire de France, Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598, Boîte courrier 187, UPMC Univ Paris 06, 4 Pl. Jussieu, 75252 Paris cedex 05, France, emmanuel.trelat@upmc.fr (France)

    2016-06-08

    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

  8. Brand Community: Expertise heterogeneity and behavioural intentions

    Mazzola, Carlo Daniele

    2013-01-01

    The purpose of this dissertation is to demonstrate how individual consumers are able to interact among themselves inside the collective virtual community of consumption in order to co-create value. By using the concepts of resources from the Service Dominant Logic of Marketing, heterogeneity from Organizational Behavior literature, and cultural lens from Consumer Culture Theory, this dissertation considers both individual and collective interaction in order to demonstrate the relation b...

  9. Smart predictors in the heterogeneous agent model

    Baruník, Jozef; Vácha, Lukáš; Vošvrda, Miloslav

    2009-01-01

    Roč. 4, č. 2 (2009), s. 163-172 ISSN 1860-711X R&D Projects: GA ČR GP402/08/P207; GA ČR GA402/09/0965 Grant - others:GAUK(CZ) 46108 Institutional research plan: CEZ:AV0Z10750506 Keywords : Heterogeneous agent model * Market structure * Smart traders * Hurst exponent Subject RIV: AH - Economics

  10. Efficiency Wages in Heterogenous Labour Markets

    Pavel Ryska; Jan Prùša

    2011-01-01

    In this paper we tackle two shortcomings of present efficiency wage models. Firstly, they do not fully account for labour heterogeneity, thus implying that high-effort and low-effort units of labour are interchangeable. Secondly, building on this assumed homogeneity of labour, the models derive involuntary unemployment from effort decisions of workers, which are patently voluntary. We offer a consistent reformulation of the theory: Each of the effort or quality levels is regarded as a separat...

  11. On Aggregating Human Capital Across Heterogeneous Cohorts

    Growiec, Jakub; Groth, Christian

    experience. Under the scenarios considered here, the "macro-Mincer" (log-linear) relationship between aggregate human capital and average years of schooling is obtained only in cases which are inconsistent with heterogeneity in years of schooling and based on empirically implausible demographic survival laws....... Our numerical results indicate that the macro-Mincer equation can be a reasonable approximation of the true relationship only if returns to schooling and work experience are roughly constant across countries...

  12. Method of assessing heterogeneity in images

    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.

  13. Heterogeneous car buyers: a stylized fact

    Ana M. Aizcorbe; Benjamin Bridgman; Jeremy J. Nalewaik

    2009-01-01

    Using a new dataset, we document a systematic pattern in the demographic characteristics of car buyers over the model year: as vehicle prices fall over the model year, so do buyer incomes. This pattern is consistent with price-insensitive buyers purchasing early in the year, while others wait until prices decline, and suggests price skimming (i.e. intertemporal price discrimination). Such consumer heterogeneity over the model year raises questions for measuring quality improvements in new goods.

  14. Exchange rate variability, market activity and heterogeneity

    Rime, Dagfinn; Sucarrat, Genaro

    2007-01-01

    We study the role played by geographic and bank-size heterogeneity in the relation between exchange rate variability and market activity. We find some support for the hypothesis that increases in short-term global interbank market activity, which can be interpreted as due to variation in information arrival, increase variability. However, our results do not suggest that local short-term activity increases variability. With respect to long-term market activity, which can be interpreted as a me...

  15. Phenotype heterogeneity in cancer cell populations

    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

  16. Heterogeneous IP Ecosystem enabling Reuse (HIER)

    2017-03-22

    HIER project, DARPA also established additional concepts in the formation of the Common Heterogeneous Integration and IP Reuse Strategies (CHIPS...would need a major change to  business model to offer  Hard  or Soft IP – So CHIPS program can be a better fit to these firms • DoD‐Contractor IP pricing

  17. Heterogeneity, Bounded Rationality and Market Dysfunctionality

    Xue-Zhong He; Lei Shi

    2008-01-01

    As the main building blocks of the modern finance theory, homogeneity and rational expectation have faced difficulty in explaining many market anomalies, stylized factors, and market inefficiency in empirical studies. As a result, heterogeneity and bounded rationality have been used as an alterative paradigm of asset price dynamics and this paradigm has been widely recognized recently in both academic and financial market practitioners. Within the framework of Chiarella, Dieci and He (2006a, ...

  18. [Molecular heterogeneity of malignant pleural mesotheliomas].

    Tranchant, Robin; Montagne, François; Jaurand, Marie-Claude; Jean, Didier

    2018-01-01

    Malignant pleural mesothelioma (MPM) is predominantly an occupational cancer, most often linked to asbestos exposure. Malignant pleural mesothelioma prognosis is poor with a short survival median, due to the aggressiveness of tumor cells and the weak efficiency of conventional anti-cancer therapies. Clinical, histological, and molecular data suggest tumor heterogeneity between patients as it was also shown for other cancer types. Consequently, there is an urgent need to develop new therapies that take into account this heterogeneity and the molecular characteristics of malignant pleural mesothelioma, in particular by identifying new anti-cancer drugs targeting the molecular specificities of each malignant pleural mesothelioma. Malignant pleural mesothelioma is characterized by numerous molecular alterations at the chromosomal, genetic and epigenetic levels. Molecular classification based on gene expression profile has firstly defined two tumor groups, C1 and C2, and more recently, four groups. By integrating genetic and transcriptomic analysis, a C2 LN tumor subgroup of the C2 group has been identified and characterized. In addition to tumor heterogeneity between patients, intra-tumor heterogeneity is supported by several evidences. Most therapeutic strategies that take into account the tumor molecular characteristics have focused on targeted therapies based on mutated genes. A more appropriate strategy would be to consider better-defined tumor groups on the basis of several molecular alterations types as it has been proposed for the C2 LN subgroup. A robust definition of homogeneous tumor groups sharing common molecular characteristics is necessary for the development of effective precision medicine for malignant pleural mesothelioma. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  19. Dynamics of epidemics outbreaks in heterogeneous populations

    Brockmann, Dirk; Morales-Gallardo, Alejandro; Geisel, Theo

    2007-03-01

    The dynamics of epidemic outbreaks have been investigated in recent years within two alternative theoretical paradigms. The key parameter of mean field type of models such as the SIR model is the basic reproduction number R0, the average number of secondary infections caused by one infected individual. Recently, scale free network models have received much attention as they account for the high variability in the number of social contacts involved. These models predict an infinite basic reproduction number in some cases. We investigate the impact of heterogeneities of contact rates in a generic model for epidemic outbreaks. We present a system in which both the time periods of being infectious and the time periods between transmissions are Poissonian processes. The heterogeneities are introduced by means of strongly variable contact rates. In contrast to scale free network models we observe a finite basic reproduction number and, counterintuitively a smaller overall epidemic outbreak as compared to the homogeneous system. Our study thus reveals that heterogeneities in contact rates do not necessarily facilitate the spread to infectious disease but may well attenuate it.

  20. Coordinated Energy Management in Heterogeneous Processors

    Indrani Paul

    2014-01-01

    Full Text Available This paper examines energy management in a heterogeneous processor consisting of an integrated CPU–GPU for high-performance computing (HPC applications. Energy management for HPC applications is challenged by their uncompromising performance requirements and complicated by the need for coordinating energy management across distinct core types – a new and less understood problem. We examine the intra-node CPU–GPU frequency sensitivity of HPC applications on tightly coupled CPU–GPU architectures as the first step in understanding power and performance optimization for a heterogeneous multi-node HPC system. The insights from this analysis form the basis of a coordinated energy management scheme, called DynaCo, for integrated CPU–GPU architectures. We implement DynaCo on a modern heterogeneous processor and compare its performance to a state-of-the-art power- and performance-management algorithm. DynaCo improves measured average energy-delay squared (ED2 product by up to 30% with less than 2% average performance loss across several exascale and other HPC workloads.

  1. 48Ca HETEROGENEITY IN DIFFERENTIATED METEORITES

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

    2011-01-01

    Isotopic heterogeneities of 48 Ca have been found in numerous bulk meteorites that are correlated with 50 Ti and 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 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.

  2. Heterogeneity maintenance in glioblastoma: a social network.

    Bonavia, Rudy; Inda, Maria-del-Mar; Cavenee, Webster K; Furnari, Frank B

    2011-06-15

    Glioblastoma multiforme (GBM), the most common intracranial tumor in adults, is characterized by extensive heterogeneity at the cellular and molecular levels. This insidious feature arises inevitably in almost all cancers and has great significance for the general outcome of the malignancy, because it confounds our understanding of the disease and also intrinsically contributes to the tumor's aggressiveness and poses an obstacle to the design of effective therapies. The classic view that heterogeneity arises as the result of a tumor's "genetic chaos" and the more contemporary cancer stem cell (CSC) hypothesis tend to identify a single cell population as the therapeutic target: the prevailing clone over time in the first case and the CSC in the latter. However, there is growing evidence that the different tumor cell populations may not be simple bystanders. Rather, they can establish a complex network of interactions between each other and with the tumor microenvironment that eventually strengthens tumor growth and increases chances to escape therapy. These differing but complementary ideas about the origin and maintenance of tumor heterogeneity and its importance in GBM are reviewed here.

  3. Hierarchical unilamellar vesicles of controlled compositional heterogeneity.

    Maik Hadorn

    Full Text Available Eukaryotic life contains hierarchical vesicular architectures (i.e. organelles that are crucial for material production and trafficking, information storage and access, as well as energy production. In order to perform specific tasks, these compartments differ among each other in their membrane composition and their internal cargo and also differ from the cell membrane and the cytosol. Man-made structures that reproduce this nested architecture not only offer a deeper understanding of the functionalities and evolution of organelle-bearing eukaryotic life but also allow the engineering of novel biomimetic technologies. Here, we show the newly developed vesicle-in-water-in-oil emulsion transfer preparation technique to result in giant unilamellar vesicles internally compartmentalized by unilamellar vesicles of different membrane composition and internal cargo, i.e. hierarchical unilamellar vesicles of controlled compositional heterogeneity. The compartmentalized giant unilamellar vesicles were subsequently isolated by a separation step exploiting the heterogeneity of the membrane composition and the encapsulated cargo. Due to the controlled, efficient, and technically straightforward character of the new preparation technique, this study allows the hierarchical fabrication of compartmentalized giant unilamellar vesicles of controlled compositional heterogeneity and will ease the development of eukaryotic cell mimics that resemble their natural templates as well as the fabrication of novel multi-agent drug delivery systems for combination therapies and complex artificial microreactors.

  4. The heterogeneous response method in slab geometry

    Villarino, E.A.; Stamm'ler, R.J.J.

    1984-01-01

    The heterogeneous response method (HRM) has been developed to calculate the multigroup flux in a heterogeneous system, e.g. a fuel assembly, without having to resort to dubious homogenization recipes. Here, the method is described in slab geometry in a manner that facilitates its computerization. By dividing the system into subsystems or nodes, say pin cells, two levels of calculation are created, which define a set of local problems and a global problem, respectively. In the local problem, collision probabilities are used to obtain for a node in vacuum, its response fluxes caused by sources and in-currents. They preserve the heterogeneous character of the node. In the global problem, the nodes are coupled by cosine currents. A suitable transformation reduces the number of two unknown currents per interface to one unknown per node, its total transmitted in-current. The global equation system thus becomes a set of three-point relations, which can be solved efficiently. In cases typical of fuel-assembly situations, the HRM produces fluxes that compare very well with the direct solution of the entire system by collision probabilities, though at a fraction of the computer cost. Extension of the method to 2- and 3-D systems is discussed. (author)

  5. Temperature Dependence in Homogeneous and Heterogeneous Nucleation

    McGraw R. L.; Winkler, P. M.; Wagner, P. E.

    2017-08-01

    Heterogeneous nucleation on stable (sub-2 nm) nuclei aids the formation of atmospheric cloud condensation nuclei (CCN) by circumventing or reducing vapor pressure barriers that would otherwise limit condensation and new particle growth. Aerosol and cloud formation depend largely on the interaction between a condensing liquid and the nucleating site. A new paper published this year reports the first direct experimental determination of contact angles as well as contact line curvature and other geometric properties of a spherical cap nucleus at nanometer scale using measurements from the Vienna Size Analyzing Nucleus Counter (SANC) (Winkler et al., 2016). For water nucleating heterogeneously on silver oxide nanoparticles we find contact angles around 15 degrees compared to around 90 degrees for the macroscopically measured equilibrium angle for water on bulk silver. The small microscopic contact angles can be attributed via the generalized Young equation to a negative line tension that becomes increasingly dominant with increasing curvature of the contact line. These results enable a consistent theoretical description of heterogeneous nucleation and provide firm insight to the wetting of nanosized objects.

  6. Nanoscale-Agglomerate-Mediated Heterogeneous Nucleation.

    Cha, Hyeongyun; Wu, Alex; Kim, Moon-Kyung; Saigusa, Kosuke; Liu, Aihua; Miljkovic, Nenad

    2017-12-13

    Water vapor condensation on hydrophobic surfaces has received much attention due to its ability to rapidly shed water droplets and enhance heat transfer, anti-icing, water harvesting, energy harvesting, and self-cleaning performance. However, the mechanism of heterogeneous nucleation on hydrophobic surfaces remains poorly understood and is attributed to defects in the hydrophobic coating exposing the high surface energy substrate. Here, we observe the formation of high surface energy nanoscale agglomerates on hydrophobic coatings after condensation/evaporation cycles in ambient conditions. To investigate the deposition dynamics, we studied the nanoscale agglomerates as a function of condensation/evaporation cycles via optical and field emission scanning electron microscopy (FESEM), microgoniometric contact angle measurements, nucleation statistics, and energy dispersive X-ray spectroscopy (EDS). The FESEM and EDS results indicated that the nanoscale agglomerates stem from absorption of sulfuric acid based aerosol particles inside the droplet and adsorption of volatile organic compounds such as methanethiol (CH 3 SH), dimethyl disulfide (CH 3 SSCH), and dimethyl trisulfide (CH 3 SSSCH 3 ) on the liquid-vapor interface during water vapor condensation, which act as preferential sites for heterogeneous nucleation after evaporation. The insights gained from this study elucidate fundamental aspects governing the behavior of both short- and long-term heterogeneous nucleation on hydrophobic surfaces, suggest previously unexplored microfabrication and air purification techniques, and present insights into the challenges facing the development of durable dropwise condensing surfaces.

  7. Heterogeneity of schizophrenia: Genetic and symptomatic factors.

    Takahashi, Sakae

    2013-10-01

    Schizophrenia may have etiological heterogeneity, and may reflect common symptomatology caused by many genetic and environmental factors. In this review, we show the potential existence of heterogeneity in schizophrenia based on the results of our previous studies. In our study of the NOTCH4 gene, there were no significant associations between any single nucleotide polymorphisms (SNPs) of NOTCH4 and schizophrenia. However, exploratory analyses suggested that the SNP, rs3134928 may be associated with early-onset schizophrenia, and that rs387071 may be associated with schizophrenia characterized by negative symptoms. In our highly familial schizophrenia study, the African-American cohort without environmental exposure showed a possible linkage at marker 8p23.1 in the dominant model and in the European-American cohort, a marker at 22q13.32 showed a probable linkage in the recessive model. In the less familial schizophrenia families, these linkages were not shown. Based on our eye movement study, a putative subtype of schizophrenia with severe symptoms related to excitement/hostility, negative symptoms and disorganization may be associated with chromosome 22q11. We consider that a sample stratification approach may clarify the heterogeneity of schizophrenia. Therefore, this approach may lead to a more straightforward way of identifying susceptibility genes of schizophrenia. © 2013 Wiley Periodicals, Inc.

  8. Assessing local outcomes in heterogeneous gliomas

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

    2014-01-01

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

  9. Heterogeneity of Loss Aversion in Pathological Gambling.

    Takeuchi, Hideaki; Kawada, Ryosaku; Tsurumi, Kosuke; Yokoyama, Naoto; Takemura, Ariyoshi; Murao, Takuro; Murai, Toshiya; Takahashi, Hidehiko

    2016-12-01

    Pathological gambling (PG) is characterized by continual repeated gambling behavior despite negative consequences. PG is considered to be a disorder of altered decision-making under risk, and behavioral economics tools were utilized by studies on decision-making under risk. At the same time, PG was suggested to be a heterogeneous disorder in terms of personality traits as well as risk attitude. We aimed to examine the heterogeneity of PG in terms of loss aversion, which means that a loss is subjectively felt to be larger than the same amount of gain. Thirty-one male PG subjects and 26 male healthy control (HC) subjects underwent a behavioral economics task for estimation of loss aversion and personality traits assessment. Although loss aversion in PG subjects was not significantly different from that in HC subjects, distributions of loss aversion differed between PG and HC subjects. HC subjects were uniformly classified into three levels (low, middle, high) of loss aversion, whereas PG subjects were mostly classified into the two extremes, and few PG subjects were classified into the middle range. PG subjects with low and high loss aversion showed a significant difference in anxiety, excitement-seeking and craving intensity. Our study suggested that PG was a heterogeneous disorder in terms of loss aversion. This result might be useful for understanding cognitive and neurobiological mechanisms and the establishment of treatment strategies for PG.

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

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

    2016-06-01

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

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

    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.

  12. The implications of heterogeneity for repository performance assessments

    Jackson, C.P.; Porter, J.D.; Morris, S.T.; Herbert, A.W.

    1991-01-01

    We outline the current views of the Nirex Disposal Safety Assessment Team on heterogeneity, we describe the pragmatic approach to modelling the consequences of heterogeneity that is being currently used, we present work that is being undertaken in the Nirex Safety Assessment Research Programme to develop improved models and we discuss the implications of heterogeneity for site investigation. We point out the need to develop simple models for use in probabilistic analyses. Heterogeneity leads to dispersion, which is currently modelled using a simple diffusion-like model. We discuss the differences between structured heterogeneity, such as fracture zones, and random heterogeneity. We consider that the geostatistical approach to modelling random heterogeneity is probably that most suitable for the needs of Nirex. More measurements are needed in order to characterize heterogeneous media than to characterize homogeneous media. 18 refs., 4 figs

  13. Interest rate rules and macroeconomic stability under heterogeneous expectations

    Anufriev, M.; Assenza, T.; Hommes, C.; Massaro, D.

    2009-01-01

    The recent macroeconomic literature stresses the importance of managing heterogeneous expectations in the formulation of monetary policy. We use a stylized macro model of Howitt (1992) to investigate inflation dynamics under alternative interest rate rules when agents have heterogeneous expectations

  14. Influence of ionizing radiation on synthesis and molecular heterogeneity of catalase in tissue culture of Rauwolfia serpentina

    Komov, V.P.; Bespalova, E.V.; Strelkova, M.A.

    1998-01-01

    Changes in activity and molecular heterogeneity of catalase in tissue culture of Rauwolfia serpentina following irradiation in early growth period at the doses of 8 and 50 Gy has been studied. Ionizing radiation accelerate the synthesis and degradation rates of catalase and total protein. A comparative study of changes in enzyme and protein turnover during growth on irradiated and non-irradiated medium has been made [ru

  15. Communicating why land surface heterogeneity matters

    Tague, C.; Burke, W.; Bart, R. R.; Turpin, E.; Wood, T.; Gordon, D.

    2017-12-01

    As hydrologic scientists, we know that land surface heterogeneity can have nuanced and sometimes dramatic impacts on the water cycle. Land surface characteristics, including the structure and composition of vegetation and soil storage and drainage properties, alter how incoming precipitation is translated into streamflow and evapotranspiration. Land surface heterogeneity can explain why this partitioning of incoming precipitation cannot always be computed by a simple water budget calculation. We also know that land surface characteristics are dynamic - vegetation grows and changes with fire, disease and human actions and these changes will alter the partitioning of water - how much so, however depends itself on other site characteristics - soil water storage and the timing and magnitude of precipitation. This complex impact of space-time dynamics on the water cycle is something we need to effectively communicate to non-experts. For example, we may want to explain why sometimes forest management practices increase water availability but sometimes they don't - or why the impacts of urbanization or fire are location specific. If we do not communicate these dependencies we risk over-simplifying and eroding scientific credibility when observed effects don't match simple generalizations. On the other hand excessive detail can overwhelm and disengage audiences. So how do we help different communities public, private landowners, other scientists, NGOs, governments to better understand the role of space-time heterogeneity. To address this issue, we present some results from ongoing work that looks at the impact of fuel treatment of forest ecohydrology. This work stem from a collaboration between an ecohydrologic modeling team, social-scientists, a visual artist and compute graphics students. We use a coupled model, validated with field measurements, to show why spatial heterogeneity matters for understanding the impact of fuel treatments on the water cycle for the Sierra

  16. Cloning of transgenic tobacco BY-2 cells; an efficient method to analyse and reduce high natural heterogeneity of transgene expression.

    Nocarova, Eva; Fischer, Lukas

    2009-04-22

    Phenotypic characterization of transgenic cell lines, frequently used in plant biology studies, is complicated because transgene expression in individual cells is often heterogeneous and unstable. To identify the sources and to reduce this heterogeneity, we transformed tobacco (Nicotiana tabacum L.) BY-2 cells with a gene encoding green fluorescent protein (GFP) using Agrobacterium tumefaciens, and then introduced a simple cloning procedure to generate cell lines derived from the individual transformed cells. Expression of the transgene was monitored by analysing GFP fluorescence in the cloned lines and also in lines obtained directly after transformation. The majority ( approximately 90%) of suspension culture lines derived from calli that were obtained directly from transformation consisted of cells with various levels of GFP fluorescence. In contrast, nearly 50% of lines generated by cloning cells from the primary heterogeneous suspensions consisted of cells with homogenous GFP fluorescence. The rest of the lines exhibited "permanent heterogeneity" that could not be resolved by cloning. The extent of fluorescence heterogeneity often varied, even among genetically identical clones derived from the primary transformed lines. In contrast, the offspring of subsequent cloning of the cloned lines was uniform, showing GFP fluorescence intensity and heterogeneity that corresponded to the original clone. The results demonstrate that, besides genetic heterogeneity detected in some lines, the primary lines often contained a mixture of epigenetically different cells that could be separated by cloning. This indicates that a single integration event frequently results in various heritable expression patterns, which are probably accidental and become stabilized in the offspring of the primary transformed cells early after the integration event. Because heterogeneity in transgene expression has proven to be a serious problem, it is highly advisable to use transgenes tagged with

  17. Heterogeneity in Social Dilemmas: The Case of Social Support

    Vogt, S.B.

    2007-01-01

    Heterogeneous Social Dilemmas: The Case of Social Support” studies the level of social support between heterogeneous actors. We consider heterogeneity with respect to several individual properties: the likelihood of needing support, the costs of providing support, and the benefits from receiving

  18. Identifying and quantifying heterogeneity in high content analysis: application of heterogeneity indices to drug discovery.

    Albert H Gough

    Full Text Available One of the greatest challenges in biomedical research, drug discovery and diagnostics is understanding how seemingly identical cells can respond differently to perturbagens including drugs for disease treatment. Although heterogeneity has become an accepted characteristic of a population of cells, in drug discovery it is not routinely evaluated or reported. The standard practice for cell-based, high content assays has been to assume a normal distribution and to report a well-to-well average value with a standard deviation. To address this important issue we sought to define a method that could be readily implemented to identify, quantify and characterize heterogeneity in cellular and small organism assays to guide decisions during drug discovery and experimental cell/tissue profiling. Our study revealed that heterogeneity can be effectively identified and quantified with three indices that indicate diversity, non-normality and percent outliers. The indices were evaluated using the induction and inhibition of STAT3 activation in five cell lines where the systems response including sample preparation and instrument performance were well characterized and controlled. These heterogeneity indices provide a standardized method that can easily be integrated into small and large scale screening or profiling projects to guide interpretation of the biology, as well as the development of therapeutics and diagnostics. Understanding the heterogeneity in the response to perturbagens will become a critical factor in designing strategies for the development of therapeutics including targeted polypharmacology.

  19. Phosphorylation of SAF-A/hnRNP-U Serine 59 by Polo-Like Kinase 1 Is Required for Mitosis.

    Douglas, Pauline; Ye, Ruiqiong; Morrice, Nicholas; Britton, Sébastien; Trinkle-Mulcahy, Laura; Lees-Miller, Susan P

    2015-08-01

    Scaffold attachment factor A (SAF-A), also called heterogenous nuclear ribonuclear protein U (hnRNP-U), is phosphorylated on serine 59 by the DNA-dependent protein kinase (DNA-PK) in response to DNA damage. Since SAF-A, DNA-PK catalytic subunit (DNA-PKcs), and protein phosphatase 6 (PP6), which interacts with DNA-PKcs, have all been shown to have roles in mitosis, we asked whether DNA-PKcs phosphorylates SAF-A in mitosis. We show that SAF-A is phosphorylated on serine 59 in mitosis, that phosphorylation requires polo-like kinase 1 (PLK1) rather than DNA-PKcs, that SAF-A interacts with PLK1 in nocodazole-treated cells, and that serine 59 is dephosphorylated by protein phosphatase 2A (PP2A) in mitosis. Moreover, cells expressing SAF-A in which serine 59 is mutated to alanine have multiple characteristics of aberrant mitoses, including misaligned chromosomes, lagging chromosomes, polylobed nuclei, and delayed passage through mitosis. Our findings identify serine 59 of SAF-A as a new target of both PLK1 and PP2A in mitosis and reveal that both phosphorylation and dephosphorylation of SAF-A serine 59 by PLK1 and PP2A, respectively, are required for accurate and timely exit from mitosis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Bird diversity and environmental heterogeneity in North America: A test of the area-heterogeneity trade-off

    Rachel Chocron; Curtis H. Flather; Ronen Kadmon

    2015-01-01

    Aim: Deterministic niche theory predicts that increasing environmental heterogeneity increases species richness. In contrast, a recent stochastic model suggests that heterogeneity has a unimodal effect on species richness since high levels of heterogeneity reduce the effective area available per species, thereby increasing the likelihood of stochastic...

  1. Quantum Heterogeneous Computing for Satellite Positioning Optimization

    Bass, G.; Kumar, V.; Dulny, J., III

    2016-12-01

    Hard optimization problems occur in many fields of academic study and practical situations. We present results in which quantum heterogeneous computing is used to solve a real-world optimization problem: satellite positioning. Optimization problems like this can scale very rapidly with problem size, and become unsolvable with traditional brute-force methods. Typically, such problems have been approximately solved with heuristic approaches; however, these methods can take a long time to calculate and are not guaranteed to find optimal solutions. Quantum computing offers the possibility of producing significant speed-up and improved solution quality. There are now commercially available quantum annealing (QA) devices that are designed to solve difficult optimization problems. These devices have 1000+ quantum bits, but they have significant hardware size and connectivity limitations. We present a novel heterogeneous computing stack that combines QA and classical machine learning and allows the use of QA on problems larger than the quantum hardware could solve in isolation. We begin by analyzing the satellite positioning problem with a heuristic solver, the genetic algorithm. The classical computer's comparatively large available memory can explore the full problem space and converge to a solution relatively close to the true optimum. The QA device can then evolve directly to the optimal solution within this more limited space. Preliminary experiments, using the Quantum Monte Carlo (QMC) algorithm to simulate QA hardware, have produced promising results. Working with problem instances with known global minima, we find a solution within 8% in a matter of seconds, and within 5% in a few minutes. Future studies include replacing QMC with commercially available quantum hardware and exploring more problem sets and model parameters. Our results have important implications for how heterogeneous quantum computing can be used to solve difficult optimization problems in any

  2. High-throughput heterogeneous catalyst research

    Turner, Howard W.; Volpe, Anthony F., Jr.; Weinberg, W. H.

    2009-06-01

    With the discovery of abundant and low cost crude oil in the early 1900's came the need to create efficient conversion processes to produce low cost fuels and basic chemicals. Enormous investment over the last century has led to the development of a set of highly efficient catalytic processes which define the modern oil refinery and which produce most of the raw materials and fuels used in modern society. Process evolution and development has led to a refining infrastructure that is both dominated and enabled by modern heterogeneous catalyst technologies. Refineries and chemical manufacturers are currently under intense pressure to improve efficiency, adapt to increasingly disadvantaged feedstocks including biomass, lower their environmental footprint, and continue to deliver their products at low cost. This pressure creates a demand for new and more robust catalyst systems and processes that can accommodate them. Traditional methods of catalyst synthesis and testing are slow and inefficient, particularly in heterogeneous systems where the structure of the active sites is typically complex and the reaction mechanism is at best ill-defined. While theoretical modeling and a growing understanding of fundamental surface science help guide the chemist in designing and synthesizing targets, even in the most well understood areas of catalysis, the parameter space that one needs to explore experimentally is vast. The result is that the chemist using traditional methods must navigate a complex and unpredictable diversity space with a limited data set to make discoveries or to optimize known systems. We describe here a mature set of synthesis and screening technologies that together form a workflow that breaks this traditional paradigm and allows for rapid and efficient heterogeneous catalyst discovery and optimization. We exemplify the power of these new technologies by describing their use in the development and commercialization of a novel catalyst for the

  3. Brachytherapy dose measurements in heterogeneous tissues

    Paiva F, G.; Luvizotto, J.; Salles C, T.; Guimaraes A, P. C.; Dalledone S, P. de T.; Yoriyaz, H.; Rubo, R.

    2014-08-01

    Recently, Beau lieu et al. published an article providing guidance for Model-Based Dose Calculation Algorithms (MBDCAs), where tissue heterogeneity considerations are addressed. It is well-known that T G-43 formalism which considers only water medium is limited and significant dose differences have been found comparing both methodologies. The aim of the present work is to experimentally quantify dose values in heterogeneous medium using different dose measurement methods and techniques and compare them with those obtained with Monte Carlo simulations. Experiments have been performed using a Nucletron micro Selectron-Hdr Ir-192 brachytherapy source and a heterogeneous phantom composed by PMMA and different tissue equivalent cylinders like bone, lungs and muscle. Several dose measurements were obtained using tissue equivalent materials with height 1.8 cm and 4.3 cm positioned between the radiation source and the detectors. Radiochromic films, TLDs and MOSFET S have been used for the dose measurements. Film dosimetry has been performed using two methodologies: a) linearization for dose-response curve based on calibration curves to create a functional form that linearize s the dose response and b) 177 multichannel analysis dosimetry where the multiple color channels are analyzed allowing to address not only disturbances in the measurements caused by thickness variation in the film layer, but also, separate other external influences in the film response. All experiments have been simulated using the MCNP5 Monte Carlo radiation transport code. Comparison of experimental results are in good agreement with calculated dose values with differences less than 6% for almost all cases. (Author)

  4. Deciphering cancer heterogeneity: the biological space

    Stephanie eRoessler

    2014-04-01

    Full Text Available Most lethal solid tumors including hepatocellular carcinoma (HCC are considered incurable due to extensive heterogeneity in clinical presentation and tumor biology. Tumor heterogeneity may result from different cells of origin, patient ethnicity, etiology, underlying disease and diversity of genomic and epigenomic changes which drive tumor development. Cancer genomic heterogeneity thereby impedes treatment options and poses a significant challenge to cancer management. Studies of the HCC genome have revealed that although various genomic signatures identified in different HCC subgroups share a common prognosis, each carries unique molecular changes which are linked to different sets of cancer hallmarks whose misregulation has been proposed by Hanahan and Weinberg to be essential for tumorigenesis. We hypothesize that these specific sets of cancer hallmarks collectively occupy different tumor biological space representing the misregulation of different biological processes. In principle, a combination of different cancer hallmarks can result in new convergent molecular networks that are unique to each tumor subgroup and represent ideal druggable targets. Due to the ability of the tumor to adapt to external factors such as treatment or changes in the tumor microenvironment, the tumor biological space is elastic. Our ability to identify distinct groups of cancer patients with similar tumor biology who are most likely to respond to a specific therapy would have a significant impact on improving patient outcome. It is currently a challenge to identify a particular hallmark or a newly emerged convergent molecular network for a particular tumor. Thus, it is anticipated that the integration of multiple levels of data such as genomic mutations, somatic copy number aberration, gene expression, proteomics, and metabolomics, may help us grasp the tumor biological space occupied by each individual, leading to improved therapeutic intervention and outcome.

  5. Emerging heterogeneous integrated photonic platforms on silicon

    Fathpour Sasan

    2015-05-01

    Full Text Available 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

  6. Phenotypic heterogeneity in modeling cancer evolution.

    Ali Mahdipour-Shirayeh

    Full Text Available The unwelcome evolution of malignancy during cancer progression emerges through a selection process in a complex heterogeneous population structure. In the present work, we investigate evolutionary dynamics in a phenotypically heterogeneous population of stem cells (SCs and their associated progenitors. The fate of a malignant mutation is determined not only by overall stem cell and non-stem cell growth rates but also differentiation and dedifferentiation rates. We investigate the effect of such a complex population structure on the evolution of malignant mutations. We derive exactly calculated results for the fixation probability of a mutant arising in each of the subpopulations. The exactly calculated results are in almost perfect agreement with the numerical simulations. Moreover, a condition for evolutionary advantage of a mutant cell versus the wild type population is given in the present study. We also show that microenvironment-induced plasticity in invading mutants leads to more aggressive mutants with higher fixation probability. Our model predicts that decreasing polarity between stem and non-stem cells' turnover would raise the survivability of non-plastic mutants; while it would suppress the development of malignancy for plastic mutants. The derived results are novel and general with potential applications in nature; we discuss our model in the context of colorectal/intestinal cancer (at the epithelium. However, the model clearly needs to be validated through appropriate experimental data. This novel mathematical framework can be applied more generally to a variety of problems concerning selection in heterogeneous populations, in other contexts such as population genetics, and ecology.

  7. Executive Functioning Heterogeneity in Pediatric ADHD.

    Kofler, Michael J; Irwin, Lauren N; Soto, Elia F; Groves, Nicole B; Harmon, Sherelle L; Sarver, Dustin E

    2018-04-28

    Neurocognitive heterogeneity is increasingly recognized as a valid phenomenon in ADHD, with most estimates suggesting that executive dysfunction is present in only about 33%-50% of these children. However, recent critiques question the veracity of these estimates because our understanding of executive functioning in ADHD is based, in large part, on data from single tasks developed to detect gross neurological impairment rather than the specific executive processes hypothesized to underlie the ADHD phenotype. The current study is the first to comprehensively assess heterogeneity in all three primary executive functions in ADHD using a criterion battery that includes multiple tests per construct (working memory, inhibitory control, set shifting). Children ages 8-13 (M = 10.37, SD = 1.39) with and without ADHD (N = 136; 64 girls; 62% Caucasian/Non-Hispanic) completed a counterbalanced series of executive function tests. Accounting for task unreliability, results indicated significantly improved sensitivity and specificity relative to prior estimates, with 89% of children with ADHD demonstrating objectively-defined impairment on at least one executive function (62% impaired working memory, 27% impaired inhibitory control, 38% impaired set shifting; 54% impaired on one executive function, 35% impaired on two or all three executive functions). Children with working memory deficits showed higher parent- and teacher-reported ADHD inattentive and hyperactive/impulsive symptoms (BF 10  = 5.23 × 10 4 ), and were slightly younger (BF 10  = 11.35) than children without working memory deficits. Children with vs. without set shifting or inhibitory control deficits did not differ on ADHD symptoms, age, gender, IQ, SES, or medication status. Taken together, these findings confirm that ADHD is characterized by neurocognitive heterogeneity, while suggesting that contemporary, cognitively-informed criteria may provide improved precision for identifying a

  8. Brachytherapy dose measurements in heterogeneous tissues

    Paiva F, G.; Luvizotto, J.; Salles C, T.; Guimaraes A, P. C.; Dalledone S, P. de T.; Yoriyaz, H. [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil); Rubo, R., E-mail: gabrielpaivafonseca@gmail.com [Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, 05403-900 Sao Paulo (Brazil)

    2014-08-15

    Recently, Beau lieu et al. published an article providing guidance for Model-Based Dose Calculation Algorithms (MBDCAs), where tissue heterogeneity considerations are addressed. It is well-known that T G-43 formalism which considers only water medium is limited and significant dose differences have been found comparing both methodologies. The aim of the present work is to experimentally quantify dose values in heterogeneous medium using different dose measurement methods and techniques and compare them with those obtained with Monte Carlo simulations. Experiments have been performed using a Nucletron micro Selectron-Hdr Ir-192 brachytherapy source and a heterogeneous phantom composed by PMMA and different tissue equivalent cylinders like bone, lungs and muscle. Several dose measurements were obtained using tissue equivalent materials with height 1.8 cm and 4.3 cm positioned between the radiation source and the detectors. Radiochromic films, TLDs and MOSFET S have been used for the dose measurements. Film dosimetry has been performed using two methodologies: a) linearization for dose-response curve based on calibration curves to create a functional form that linearize s the dose response and b) 177 multichannel analysis dosimetry where the multiple color channels are analyzed allowing to address not only disturbances in the measurements caused by thickness variation in the film layer, but also, separate other external influences in the film response. All experiments have been simulated using the MCNP5 Monte Carlo radiation transport code. Comparison of experimental results are in good agreement with calculated dose values with differences less than 6% for almost all cases. (Author)

  9. Generic evolution of mixing in heterogeneous media

    De Dreuzy, J.; Carrera, J.; Dentz, M.; Le Borgne, T.

    2011-12-01

    Mixing in heterogeneous media results from the competition bewteen flow fluctuations and local scale diffusion. Flow fluctuations quickly create concentration contrasts and thus heterogeneity of the concentration field, which is slowly homogenized by local scale diffusion. Mixing first deviates from Gaussian mixing, which represents the potential mixing induced by spreading before approaching it. This deviation fundamentally expresses the evolution of the interaction between spreading and local scale diffusion. We characterize it by the ratio γ of the non-Gaussian to the Gaussian mixing states. We define the Gaussian mixing state as the integrated squared concentration of the Gaussian plume that has the same longitudinal dispersion as the real plume. The non-Gaussian mixing state is the difference between the overall mixing state defined as the integrated squared concentration and the Gaussian mixing state. The main advantage of this definition is to use the full knowledge previously acquired on dispersion for characterizing mixing even when the solute concentration field is highly non Gaussian. Using high precision numerical simulations, we show that γ quickly increases, peaks and slowly decreases. γ can be derived from two scales characterizing spreading and local mixing, at least for large flux-weighted solute injection conditions into classically log-normal Gaussian correlated permeability fields. The spreading scale is directly related to the longitudinal dispersion. The local mixing scale is the largest scale over which solute concentrations can be considered locally uniform. More generally, beyond the characteristics of its maximum, γ turns out to have a highly generic scaling form. Its fast increase and slow decrease depend neither on the heterogeneity level, nor on the ratio of diffusion to advection, nor on the injection conditions. They might even not depend on the particularities of the flow fields as the same generic features also prevail for

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

    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.

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

    V. Nicodeme eFassinou Hotegni

    2014-12-01

    Full Text Available 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, 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 association 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.

  12. Symmetric wetting heterogeneity suppresses fluid displacement hysteresis in granular piles

    Moosavi, R.; Schröter, M.; Herminghaus, S.

    2018-02-01

    We investigate experimentally the impact of heterogeneity on the capillary pressure hysteresis in fluid invasion of model porous media. We focus on symmetric heterogeneity, where the contact angles the fluid interface makes with the oil-wet (θ1) and the water-wet (θ2) beads add up to π . While enhanced heterogeneity is usually known to increase hysteresis phenomena, we find that hysteresis is greatly reduced when heterogeneities in wettability are introduced. On the contrary, geometric heterogeneity (like bidisperse particle size) does not lead to such an effect. We provide a qualitative explanation of this surprising result, resting on rather general geometric arguments.

  13. Trade, Industry Structure and Different Sources of Firm-heterogeneity

    Schröder, Philipp J.H.; Jørgensen, Jan Guldager

    Recently the workhorse model of intra-industry trade has been augmented with heterogeneous cost structures at the firm level. In principle there exist various sources of heterogeneity, yet the literature appears -- for convenience or other reasons -- to settle on marginal cost heterogeneity...... as the preferred modelling device. The present paper develops a unified model framework allowing a systematic comparison of marginal and fixed cost heterogeneity. We find that both types of heterogeneity are in fact able to capture the central stylized facts of international trade. For example can either source...

  14. Understanding as Integration of Heterogeneous Representations

    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.

  15. Design of sintering-stable heterogeneous catalysts

    Gallas-Hulin, Agata

    One of the major issues in the use of metal nanoparticles in heterogeneous catalysis is sintering. Sintering occurs at elevated temperatures because of increased mobility of nanoparticles, leading to their agglomeration and, as a consequence, to the deactivation of the catalyst. It is an emerging...... problem especially for the noble metals-based catalysis. These metals being expensive and scarce, it is worth developing catalyst systems which preserve their activity over time. Encapsulation of nanoparticles inside zeolites is one of the ways to prevent sintering. Entrapment of nanoparticles inside...

  16. Brief introductory remarks on heterogeneous photocatalysis

    Serpone, Nick [Laboratory of Pure and Applied Studies in Catalysis, Environment and Materials, Department of Chemistry, Concordia University, Montreal, QU (Canada)

    1995-08-01

    Special attention is paid to heterogeneous photocatalysis, in particular to photocatalysis utilizing titania (anatase, TiO{sub 2}) since both H{sub 2}O{sub 2} and O{sub 3} absorb no sunlight, while TiO{sub 2} does absorb sunlight, though not extensively. It is also worth noting that many of the pollutants existing in water absorb little of the sunlight, either because their spectral properties do not overlap with the sun`s spectrum (AM1) or because sunlight never reaches the pollutants, particularly when these are adsorbed in sediments in rivers and lakes.

  17. HIGH TEMPERATURE, HIGH POWER HETEROGENEOUS NUCLEAR REACTOR

    Hammond, R.P.; Wykoff, W.R.; Busey, H.M.

    1960-06-14

    A heterogeneous nuclear reactor is designed comprising a stationary housing and a rotatable annular core being supported for rotation about a vertical axis in the housing, the core containing a plurality of radial fuel- element supporting channels, the cylindrical empty space along the axis of the core providing a central plenum for the disposal of spent fuel elements, the core cross section outer periphery being vertically gradated in radius one end from the other to provide a coolant duct between the core and the housing, and means for inserting fresh fuel elements in the supporting channels under pressure and while the reactor is in operation.

  18. Genetic heterogeneity in Pakistani microcephaly families

    Sajid Hussain, M; Bakhtiar, Syeda Marriam; Farooq, Muhammad

    2013-01-01

    Autosomal recessive primary microcephaly (MCPH) is caused by mutations in at least eight different genes involved either in cell division or DNA repair. Most mutations are identified in consanguine families from Pakistan, Iran and India. To further assess their genetic heterogeneity and mutational...... mutation. One third of the families were linked to ASPM followed by WDR62 confirming previous data. We identified three novel ASPM mutations, four novel WDR62 mutations, one novel MCPH1 mutation and two novel CEP152 mutations. CEP152 mutations have not been described before in the Pakistani population....

  19. Modelling Preference Heterogeneity for Theatre Tickets

    Baldin, Andrea; Bille, Trine

    2018-01-01

    This article analyses the behavioural choice for theatre tickets using a rich data set for 2010–2013 from the sale system of the Royal Danish National Theatre. A consumer who decides to attend a theatre production faces multiple sources of price variation that involves a choice by the consumer...... among different ticket alternatives. Three modelling approaches are proposed in order to model ticket purchases: conditional logit with socio-demographic characteristics, nested logit and latent class. These models allow us explicitly to take into account consumers’ preference heterogeneity with respect...... of behaviour in the choice of theatre ticket....

  20. Cooperative networking in a heterogeneous wireless medium

    Ismail, Muhammad

    2013-01-01

    This brief focuses on radio resource allocation in a heterogeneous wireless medium. It presents radio resource allocation algorithms with decentralized implementation, which support both single-network and multi-homing services. The brief provides a set of cooperative networking algorithms, which rely on the concepts of short-term call traffic load prediction, network cooperation, convex optimization, and decomposition theory. In the proposed solutions, mobile terminals play an active role in the resource allocation operation, instead of their traditional role as passive service recipients in the networking environment.

  1. Nonlinear lattice waves in heterogeneous media

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

    2014-01-01

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

  2. Grafting heterogeneous catalyst with gamma radiation

    Garnett, J.L.; Long, M.A.; Levot, R.G.

    1984-01-01

    A process for the production of a heterogeneous catalyst comprises the steps of: irradiating an organic macromolecular substrate or a metal substrate with ionising or ultra violet radiation in the presence of a monomer selected from the group consisting of o-, m-, or p- styryl diphenyl phosphine and o-, m- or p- phenyl acrylyl diphenyl phosphine, to graft the monomer to the substrate; and reacting the graft copolymer with a homogeneous catalyst selected from the group consisting of catalytic metal salts and catalytic organometallic complexes such that the graft copolymer conjugate becomes a ligand of the catalyst

  3. Wind resource assessment in heterogeneous terrain

    Vanderwel, C.; Placidi, M.; Ganapathisubramani, B.

    2017-03-01

    High-resolution particle image velocimetry data obtained in rough-wall boundary layer experiments are re-analysed to examine the influence of surface roughness heterogeneities on wind resource. Two different types of heterogeneities are examined: (i) surfaces with repeating roughness units of the order of the boundary layer thickness (Placidi & Ganapathisubramani. 2015 J. Fluid Mech. 782, 541-566. (doi:10.1017/jfm.2015.552)) and (ii) surfaces with streamwise-aligned elevated strips that mimic adjacent hills and valleys (Vanderwel & Ganapathisubramani. 2015 J. Fluid Mech. 774, 1-12. (doi:10.1017/jfm.2015.228)). For the first case, the data show that the power extraction potential is highly dependent on the surface morphology with a variation of up to 20% in the available wind resource across the different surfaces examined. A strong correlation is shown to exist between the frontal and plan solidities of the rough surfaces and the equivalent wind speed, and hence the wind resource potential. These differences are also found in profiles of graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="RSTA20160109IM1"/> and graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="RSTA20160109IM2"/> (where U is the streamwise velocity), which act as proxies for thrust and power output. For the second case, the secondary flows that cause low- and high-momentum pathways when the spacing between adjacent hills is beyond a critical value result in significant variations in wind resource availability. Contour maps of graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="RSTA20160109IM3"/> and graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="RSTA20160109IM4"/> show a large difference in thrust and power potential (over 50%) between hills and valleys (at a fixed vertical height). These variations do not seem to be present when adjacent hills are close to each other (i.e. when the spacing is much less than the boundary layer thickness). The

  4. Organizational Economics of Capability and Heterogeneity

    Argyres, Nicholas S.; Felin, Teppo; Foss, Nicolai Juul

    2012-01-01

    For decades, the literatures on firm capabilities and organizational economics have been at odds with each other, specifically relative to explaining organizational boundaries and heterogeneity. We briefly trace the history of the relationship between the capabilities literature and organizational...... economics, and we point to the dominance of a “capabilities first” logic in this relationship. We argue that capabilities considerations are inherently intertwined with questions about organizational boundaries and internal organization, and we use this point to respond to the prevalent capabilities first...... logic. We offer an integrative research agenda that focuses first on the governance of capabilities and then on the capability of governance....

  5. Thermal conductivity of heterogeneous LWR MOX fuels

    Staicu, D.; Barker, M.

    2013-11-01

    It is generally observed that the thermal conductivity of LWR MOX fuel is lower than that of pure UO2. For MOX, the degradation is usually only interpreted as an effect of the substitution of U atoms by Pu. This hypothesis is however in contradiction with the observations of Duriez and Philiponneau showing that the thermal conductivity of MOX is independent of the Pu content in the ranges 3-15 and 15-30 wt.% PuO2 respectively. Attributing this degradation to Pu only implies that stoichiometric heterogeneous MOX can be obtained, while we show that any heterogeneity in the plutonium distribution in the sample introduces a variation in the local stoichiometry which in turn has a strong impact on the thermal conductivity. A model quantifying this effect is obtained and a new set of experimental results for homogeneous and heterogeneous MOX fuels is presented and used to validate the proposed model. In irradiated fuels, this effect is predicted to disappear early during irradiation. The 3, 6 and 10 wt.% Pu samples have a similar thermal conductivity. Comparison of the results for this homogeneous microstructure with MIMAS (heterogeneous) fuel of the same composition showed no difference for the Pu contents of 3, 5.9, 6, 7.87 and 10 wt.%. A small increase of the thermal conductivity was obtained for 15 wt.% Pu. This increase is of about 6% when compared to the average of the values obtained for 3, 6 and 10 wt.% Pu. For comparison purposes, Duriez also measured the thermal conductivity of FBR MOX with 21.4 wt.% Pu with O/M = 1.982 and a density close to 95% TD and found a value in good agreement with the estimation obtained using the formula of Philipponneau [8] for FBR MOX, and significantly lower than his results corresponding to the range 3-15 wt.% Pu. This difference in thermal conductivity is of about 20%, i.e. higher than the measurement uncertainties.Thus, a significant difference was observed between FBR and PWR MOX fuels, but was not explained. This difference

  6. Dynamic contact angle cycling homogenizes heterogeneous surfaces.

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Shock interactions with heterogeneous energetic materials

    Yarrington, Cole D.; Wixom, Ryan R.; Damm, David L.

    2018-03-01

    The complex physical phenomenon of shock wave interaction with material heterogeneities has significant importance and nevertheless remains little understood. In many materials, the observed macroscale response to shock loading is governed by characteristics of the microstructure. Yet, the majority of computational studies aimed at predicting phenomena affected by these processes, such as the initiation and propagation of detonation waves in explosives or shock propagation in geological materials, employ continuum material and reactive burn model treatment. In an effort to highlight the grain-scale processes that underlie the observable effects in an energetic system, a grain-scale model for hexanitrostilbene (HNS) has been developed. The measured microstructures were used to produce synthetic computational representations of the pore structure, and a density functional theory molecular dynamics derived equation of state (EOS) was used for the fully dense HNS matrix. The explicit inclusion of the microstructure along with a fully dense EOS resulted in close agreement with historical shock compression experiments. More recent experiments on the dynamic reaction threshold were also reproduced by inclusion of a global kinetics model. The complete model was shown to reproduce accurately the expected response of this heterogeneous material to shock loading. Mesoscale simulations were shown to provide a clear insight into the nature of threshold behavior and are a way to understand complex physical phenomena.

  8. Heterogeneous dipolar theory of the exponential pile

    Mastrangelo, P.V.

    1981-01-01

    We present a heterogeneous theory of the exponential pile, closely related to NORDHEIM-SCALETTAR's. It is well adapted to lattice whose pitch is relatively large (D-2O, grahpite) and the dimensions of whose channels are not negligible. The anisotropy of neutron diffusion is taken into account by the introduction of dipolar parameters. We express the contribution of each channel to the total flux in the moderator by means of multipolar coefficients. In order to be able to apply conditions of continuity between the flux and their derivatives, on the side of the moderator, we develop in a Fourier series the fluxes found at the periphery of each channel. Using Wronski's relations of Bessel's functions, we express the multipolar coefficients of the surfaces of each channel, on the side of the moderator, by means of the harmonics of each flux and their derivatives. We retain only monopolar (A 0 sub(g)) and dipolar (A 1 sub(g)) coefficients; those of a higher order are ignored. We deduce from these coefficients the systems of homogeneous equations of the exponential pile with monopoles on their own and monopoles plus dipoles. It should be noted that the systems of homogeneous equations of the critical pile are contained in those of the exponential pile. In another article, we develop the calculation of monopolar and dipolar heterogeneous parameters. (orig.)

  9. Heterogeneous Photocatalysis: Recent Advances and Applications

    Alex Omo Ibhadon

    2013-03-01

    Full Text Available Semiconductor heterogeneous photocatalysis, the subject of this review, is a versatile, low-cost and environmentally benign treatment technology for a host of pollutants. These may be of biological, organic and inorganic in origin within water and air. The efficient and successful application of photocatalysis demands that the pollutant, the catalyst and source of illumination are in close proximity or contact with each other. The ability of advanced oxidation technology to remove low levels of persistent organic pollutants as well as microorganisms in water has been widely demonstrated and, progressively, the technology is now being commercialized in many areas of the world including developing nations. This review considers recent developments in the research and application of heterogeneous semiconductor photocatalysis for the treatment of low-level concentrations of pollutants in water and air using titanium dioxide as a “model” semiconductor. The review considers charge transport characteristics on the semiconductor surface, photocatalyst reactor design and organic degradation mechanistic pathways. The effects of photoreactor operating parameters on the photocatalytic process are discussed in addition to mineralization and disinfection kinetics.

  10. Heterogeneous Parking Market Subject to Parking Rationing

    Saeed Asadi Bagloee

    2015-01-01

    Full Text Available Different types of drivers and parking spaces delineate a heterogeneous parking market for which the literature has yet to provide a model applicable to the real world. The main obstacle is computational complexities of considering various parking restrictions along with traffic congestion on the road network. In this study, the heterogeneity aspects are considered within a Logit parking choice model. A mathematical programming problem was introduced to explicitly consider parking capacities and parking rationing constraints. The parking rationing is defined as any arrangement to reserve parking space for some specific demand such as parking permit, private parking, VIP parking, and different parking durations. Introduction of parking rationing in the presence of other constraints is a unique factor in this study which makes the model more realistic. The algorithm was tested on a central business district case study. The results prove that the algorithm is able to converge rapidly. Among the algorithm’s output are shadow prices of the parking capacity and parking rationing constraints. The shadow prices contain important information which is key to addressing a variety of parking issues, such as the location of parking shortages, identification of fair parking charges, viability of parking permits, and the size of reserved parking.

  11. Age heterogeneity of soil organic matter

    Rethemeyer, J.; Grootes, P.M.; Bruhn, F.; Andersen, N.; Nadeau, M.J.; Kramer, C.; Gleixner, G.

    2004-01-01

    Accelerator mass spectrometry (AMS) radiocarbon measurements were used to investigate the heterogeneity of organic matter in soils of agricultural long-term trial sites in Germany and Great Britain. The strong age heterogeneity of the soil organic matter (SOM) is reflected by highly variable 14 C values of different organic components, ranging from modern (>100 pMC) to 7% modern carbon (pMC). At the field experiment in Halle (Germany), located in a heavily industrialized area, an increase of 14 C content with increasing depth was observed even though the input of modern plant debris should be highest in the topsoil. This is attributed to a significant contribution of old carbon (of up to 50% in the topsoil) to SOM. As a test to exclude the old carbon contamination, more specific SOM fractions were extracted. However, even a phospholipid fraction representing viable microbial biomass that is supposed to be short-lived in SOM, shows a strong influence of old, refractory carbon, when radiocarbon dated. In contrast, 14 C data of other field trials distant from industrial areas indicate that there inputs of old carbon to the soil are lower or even absent. Such locations are more favorable to study SOM stabilization and to quantify turnover of organic carbon in soils

  12. Heterogeneous architecture to process swarm optimization algorithms

    Maria A. Dávila-Guzmán

    2014-01-01

    Full Text Available Since few years ago, the parallel processing has been embedded in personal computers by including co-processing units as the graphics processing units resulting in a heterogeneous platform. This paper presents the implementation of swarm algorithms on this platform to solve several functions from optimization problems, where they highlight their inherent parallel processing and distributed control features. In the swarm algorithms, each individual and dimension problem are parallelized by the granularity of the processing system which also offer low communication latency between individuals through the embedded processing. To evaluate the potential of swarm algorithms on graphics processing units we have implemented two of them: the particle swarm optimization algorithm and the bacterial foraging optimization algorithm. The algorithms’ performance is measured using the acceleration where they are contrasted between a typical sequential processing platform and the NVIDIA GeForce GTX480 heterogeneous platform; the results show that the particle swarm algorithm obtained up to 36.82x and the bacterial foraging swarm algorithm obtained up to 9.26x. Finally, the effect to increase the size of the population is evaluated where we show both the dispersion and the quality of the solutions are decreased despite of high acceleration performance since the initial distribution of the individuals can converge to local optimal solution.

  13. Capturing Structural Heterogeneity in Chromatin Fibers.

    Ekundayo, Babatunde; Richmond, Timothy J; Schalch, Thomas

    2017-10-13

    Chromatin fiber organization is implicated in processes such as transcription, DNA repair and chromosome segregation, but how nucleosomes interact to form higher-order structure remains poorly understood. We solved two crystal structures of tetranucleosomes with approximately 11-bp DNA linker length at 5.8 and 6.7 Å resolution. Minimal intramolecular nucleosome-nucleosome interactions result in a fiber model resembling a flat ribbon that is compatible with a two-start helical architecture, and that exposes histone and DNA surfaces to the environment. The differences in the two structures combined with electron microscopy reveal heterogeneous structural states, and we used site-specific chemical crosslinking to assess the diversity of nucleosome-nucleosome interactions through identification of structure-sensitive crosslink sites that provide a means to characterize fibers in solution. The chromatin fiber architectures observed here provide a basis for understanding heterogeneous chromatin higher-order structures as they occur in a genomic context. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Asthma in childhood: a complex, heterogeneous disease

    Hai Lee Chung

    2011-01-01

    Full Text Available Asthma in childhood is a heterogeneous disease with different phenotypes and variable clinical manifestations, which depend on the age, gender, genetic background, and environmental influences of the patients. Several longitudinal studies have been conducted to classify the phenotypes of childhood asthma, on the basis of the symptoms, triggers of wheezing illness, or pathophysiological features of the disease. These studies have provided us with important information about the different wheezing phenotypes in young children and about potential mechanisms and risk factors for the development of chronic asthma. The goal of these studies was to provide a better insight into the causes and natural course of childhood asthma. It is well-known that complicated interactions between genes and environmental factors contribute to the development of asthma. Because childhood is a period of rapid growth in both the lungs and the immune system, developmental factors should be considered in the pathogenesis of childhood asthma. The pulmonary system continues to grow and develop until linear growth is completed. Longitudinal studies have reported significant age-related immune development during postnatal early life. These observations suggest that the phenotypes of childhood asthma vary among children and also in an individual child over time. Improved classification of heterogeneous conditions of the disease will help determine novel strategies for primary and secondary prevention and for the development of individualized treatment for childhood asthma.

  15. Reducing the Diagnostic Heterogeneity of Schizoaffective Disorder.

    Seldin, Katherine; Armstrong, Kristan; Schiff, Max L; Heckers, Stephan

    2017-01-01

    Clinical outcome studies of schizoaffective disorder patients have yielded conflicting results. One reason is the heterogeneity of samples drawn from the schizoaffective disorder population. Here, we studied schizoaffective disorder patients who showed marked functional impairment and continuous signs of illness for at least 6 months (i.e., DSM criteria B and C for schizophrenia). We assessed 176 chronic psychosis patients with a structured interview (SCID-IV-TR) and the Diagnostic Interview for Genetic Studies schizoaffective disorder module. We diagnosed 114 patients with schizophrenia and 62 with schizoaffective disorder. The two groups were similar with regard to age, gender, and race. We tested for group differences in antecedent risk factors, clinical features, and functional outcome. The schizoaffective disorder group differed from the schizophrenia group on two measures only: they showed higher rates of suicidality (more suicide attempts, p  schizoaffective disorder patients meet DSM criteria B and C for schizophrenia, they resemble schizophrenia patients on several measures used to assess validity. The increased rate of anxiety disorders and suicidality warrants clinical attention. Our data suggest that a more explicit definition of schizoaffective disorder reduces heterogeneity and may increase validity.

  16. Characterizing hydrogeologic heterogeneity using lithologic data

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

    1995-01-01

    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

  17. Visual EKF-SLAM from Heterogeneous Landmarks.

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

    2016-04-07

    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.

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

    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/.

  19. Total protein

    ... page: //medlineplus.gov/ency/article/003483.htm Total protein To use the sharing features on this page, please enable JavaScript. The total protein test measures the total amount of two classes ...

  20. Proteins engineering

    2000-01-01

    At the - Departement d'Ingenierie et d'etudes de proteines (Deip) of the CEA more than seventy researchers are working hard to understand the function of proteins. For that they use the molecular labelling technique (F.M.)

  1. Whey Protein

    ... reliable information about the safety of taking whey protein if you are pregnant or breast feeding. Stay on the safe side and avoid use. Milk allergy: If you are allergic to cow's milk, avoid using whey protein.

  2. Probing spatial heterogeneity in supercooled glycerol and temporal heterogeneity with single-molecule FRET in polyprolines

    Xia, Ted

    2010-01-01

    This thesis presents two lines of research. On the one hand, we investigate heterogeneity in supercooled glycerol by means of rheometry, small-angle neutron scattering, and fluorescence imaging. We find from the rheological experiments that supercooled glycerol can behave like weak solids at

  3. Heterogeneous Roles and Heterogeneous Practices: Understanding the Adoption and Uses of Nonprofit Performance Evaluations

    Eckerd, Adam; Moulton, Stephanie

    2011-01-01

    Evaluating the performance of nonprofit organizations has been of growing importance for the last several decades. Although there is much good that can come out of self-improvement, there is substantial heterogeneity within the sector that calls into question the usefulness of "across the board" evaluation tools. In this article, the authors…

  4. Usher syndrome: molecular links of pathogenesis, proteins and pathways.

    Kremer, H.; Wijk, E. van; Marker, T.; Wolfrum, U.; Roepman, R.

    2006-01-01

    Usher syndrome is the most common form of deaf-blindness. The syndrome is both clinically and genetically heterogeneous, and to date, eight causative genes have been identified. The proteins encoded by these genes are part of a dynamic protein complex that is present in hair cells of the inner ear

  5. Interdependence of laforin and malin proteins for their stability and ...

    https://www.ias.ac.in/article/fulltext/jbsc/040/05/0863-0871. Keywords. Epilepsy; locus heterogeneity; post-translational modification; protein-protein interaction. Abstract. Lafora disease (LD), an autosomal recessive and fatal form of neurodegenerative disorder, is characterized by the presence of polyglucosan inclusions in ...

  6. HTLV-1 induced molecular mimicry in neurological disease.

    Lee, S M; Morcos, Y; Jang, H; Stuart, J M; Levin, M C

    2005-01-01

    As a model for molecular mimicry, we study patients infected with human T-lymphotropic virus type 1 (HTLV-1) who develop a neurological disease called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease with important biological similarities to multiple sclerosis (MS) (Khan et al. 2001; Levin et al. 1998, 2002a; Levin and Jacobson 1997). The study of HAM/TSP, a disease associated with a known environmental agent (HTLV-1), allows for the direct comparison of the infecting agent with host antigens. Neurological disease in HAM/TSP patients is associated with immune responses to HTLV-1-tax (a regulatory and immunodominant protein) and human histocompatibility leukocyte antigen (HLA) DRB1*0101 (Bangham 2000; Jacobson et al. 1990; Jeffery et al. 1999; Lal 1996). Recently, we showed that HAM/TSP patients make antibodies to heterogeneous nuclear ribonuclear protein A1 (hnRNP A1), a neuron-specific autoantigen (Levin et al. 2002a). Monoclonal antibodies to tax cross-reacted with hnRNP A1, indicating molecular mimicry between the two proteins. Infusion of cross-reactive antibodies with an ex vivo system completely inhibited neuronal firing indicative of their pathogenic nature (Kalume et al. 2004; Levin et al. 2002a). These data demonstrate a clear link between chronic viral infection and autoimmune disease of the central nervous system (CNS) in humans and, we believe, in turn will give insight into the pathogenesis of MS.

  7. Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature

    Maria-del-Mar Inda

    2014-01-01

    Full Text Available Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM, the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.

  8. Glioblastoma multiforme: a look inside its heterogeneous nature.

    Inda, Maria-Del-Mar; Bonavia, Rudy; Seoane, Joan

    2014-01-27

    Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.

  9. Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature

    Inda, Maria-del-Mar; Bonavia, Rudy; Seoane, Joan

    2014-01-01

    Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape

  10. Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature

    Inda, Maria-del-Mar, E-mail: mminda@vhio.net; Bonavia, Rudy [Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 119-129 Passeig Vall d’Hebron, Barcelona 08035 (Spain); Seoane, Joan [Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 119-129 Passeig Vall d’Hebron, Barcelona 08035 (Spain); Catalan Institution of Research and Advanced Studies (ICREA), Barcelona 08035 (Spain)

    2014-01-27

    Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.

  11. Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding

    Iskander, Kendra N.; Osuchowski, Marcin F.; Stearns-Kurosawa, Deborah J.; Kurosawa, Shinichiro; Stepien, David; Valentine, Catherine

    2013-01-01

    Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed. PMID:23899564

  12. Cell signaling heterogeneity is modulated by both cell-intrinsic and -extrinsic mechanisms: An integrated approach to understanding targeted therapy.

    Kim, Eunjung; Kim, Jae-Young; Smith, Matthew A; Haura, Eric B; Anderson, Alexander R A

    2018-03-01

    During the last decade, our understanding of cancer cell signaling networks has significantly improved, leading to the development of various targeted therapies that have elicited profound but, unfortunately, short-lived responses. This is, in part, due to the fact that these targeted therapies ignore context and average out heterogeneity. Here, we present a mathematical framework that addresses the impact of signaling heterogeneity on targeted therapy outcomes. We employ a simplified oncogenic rat sarcoma (RAS)-driven mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) signaling pathway in lung cancer as an experimental model system and develop a network model of the pathway. We measure how inhibition of the pathway modulates protein phosphorylation as well as cell viability under different microenvironmental conditions. Training the model on this data using Monte Carlo simulation results in a suite of in silico cells whose relative protein activities and cell viability match experimental observation. The calibrated model predicts distributional responses to kinase inhibitors and suggests drug resistance mechanisms that can be exploited in drug combination strategies. The suggested combination strategies are validated using in vitro experimental data. The validated in silico cells are further interrogated through an unsupervised clustering analysis and then integrated into a mathematical model of tumor growth in a homogeneous and resource-limited microenvironment. We assess posttreatment heterogeneity and predict vast differences across treatments with similar efficacy, further emphasizing that heterogeneity should modulate treatment strategies. The signaling model is also integrated into a hybrid cellular automata (HCA) model of tumor growth in a spatially heterogeneous microenvironment. As a proof of concept, we simulate tumor responses to targeted therapies in a spatially segregated tissue structure containing tumor

  13. Design nanocrack patterns in heterogeneous films

    Salac, David; Lu Wei

    2006-01-01

    Nanowires have significant potential in future technologies such as nanomechanical devices and electronics. Recent experiments suggest that nanowires with sub-100 nm diameters may be fabricated by filling cracks with various materials. The geometry of cracks becomes important on such a length scale, and the practical application of the approach requires an understanding of crack evolution in heterogeneous films. This paper proposes a level-set approach to model directed nanocracks on pre-patterned substrates. The approach does not require the explicit tracking of crack fronts and thus allows the simulation of complex crack patterns. Results indicate that pre-patterning a substrate can lead to various well controlled nanocrack patterns, suggesting a possibility to make designed and complex nanowires difficult to obtain with other methods

  14. Chinese Immigrant Wealth: Heterogeneity in Adaptation

    Agius Vallejo, Jody; Aronson, Brian

    2016-01-01

    Chinese immigrants are a diverse and growing group whose members provide a unique opportunity to examine within-immigrant group differences in adaptation. In this paper, we move beyond thinking of national-origin groups as homogenous and study variation among Chinese immigrants in wealth ownership, a critical indicator of adaptation that attracts relatively little attention in the immigration literature. We develop an analytical approach that considers national origin, tenure in the U.S., and age to examine heterogeneity in economic adaptation among the immigrant generation. Our results show that variations among Chinese immigrants explain within-group differences in net worth, asset ownership, and debt. These differences also account for important variation between Chinese immigrants, natives, and other immigrant groups and provide important, new insight into the processes that lead to immigrant adaptation and long-term class stability. PMID:27977737

  15. Heterogeneous distributed databases: A case study

    Stewart, Tracy R.; Mukkamala, Ravi

    1991-01-01

    Alternatives are reviewed for accessing distributed heterogeneous databases and a recommended solution is proposed. The current study is limited to the Automated Information Systems Center at the Naval Sea Combat Systems Engineering Station at Norfolk, VA. This center maintains two databases located on Digital Equipment Corporation's VAX computers running under the VMS operating system. The first data base, ICMS, resides on a VAX11/780 and has been implemented using VAX DBMS, a CODASYL based system. The second database, CSA, resides on a VAX 6460 and has been implemented using the ORACLE relational database management system (RDBMS). Both databases are used for configuration management within the U.S. Navy. Different customer bases are supported by each database. ICMS tracks U.S. Navy ships and major systems (anti-sub, sonar, etc.). Even though the major systems on ships and submarines have totally different functions, some of the equipment within the major systems are common to both ships and submarines.

  16. The genetic validation of heterogeneity in schizophrenia.

    Tsutsumi, Atsushi; Glatt, Stephen J; Kanazawa, Tetsufumi; Kawashige, Seiya; Uenishi, Hiroyuki; Hokyo, Akira; Kaneko, Takao; Moritani, Makiko; Kikuyama, Hiroki; Koh, Jun; Matsumura, Hitoshi; Yoneda, Hiroshi

    2011-10-07

    Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To overcome this state of uncertainty, the SZGene database has been established by including all published case-control genetic association studies appearing in peer-reviewed journals. In the current study, we aimed to determine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our case-control samples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of seven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative diagnostic manual, the DSM-IV. Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven top-ranked variants (p Japanese population. It is also important to aggregate the updated positive variants in the SZGene database when the replication work is conducted.

  17. Heterogeneous fundamentalists and market maker inventories

    Carraro, Alessandro; Ricchiuti, Giorgio

    2015-01-01

    In this paper, we develop a heterogeneous agents model of asset price and inventory with a market maker who considers the excess demand of two groups of agents that employ the same trading rule (i.e. fundamentalists) with different beliefs on the fundamental value. The dynamics of our model is driven by a bi-dimensional discrete non-linear map. We show that the market maker has a destabilizing role when she actively manages the inventory. Moreover, inventory share and the distance between agents’ beliefs strongly influence the results: market instability and periodic, or even, chaotic price fluctuations can be generated. Finally, we show through simulations that endogenous fluctuations of the fractions of agents may trigger instability for a larger set of parameters.

  18. Nitrate reduction in geologically heterogeneous catchments

    Refsgaard, Jens Christian; Auken, Esben; Bamberg, Charlotte A.

    2014-01-01

    In order to fulfil the requirements of the EU Water Framework Directive nitrate load from agricultural areas to surface water in Denmark needs to be reduced by about 40%. The regulations imposed until now have been uniform, i.e. the same restrictions for all areas independent of the subsurface...... conditions. Studies have shown that on a national basis about 2/3 of the nitrate leaching from the root zone is reduced naturally, through denitrification, in the subsurface before reaching the streams. Therefore, it is more cost-effective to identify robust areas, where nitrate leaching through the root...... the entire catchment. However, as distributed models often do not include local scale hydrogeological heterogeneities, they are typically not able to make accurate predictions at scales smaller than they are calibrated. We present a framework for assessing nitrate reduction in the subsurface...

  19. Fractional diffusion equation for heterogeneous medium

    Polo L, M. A.; Espinosa M, E. G.; Espinosa P, G.; Del Valle G, E.

    2011-11-01

    The asymptotic diffusion approximation for the Boltzmann (transport) equation was developed in 1950 decade in order to describe the diffusion of a particle in an isotropic medium, considers that the particles have a diffusion infinite velocity. In this work is developed a new approximation where is considered that the particles have a finite velocity, with this model is possible to describe the behavior in an anomalous medium. According with these ideas the model was obtained from the Fick law, where is considered that the temporal term of the current vector is not negligible. As a result the diffusion equation of fractional order which describes the dispersion of particles in a highly heterogeneous or disturbed medium is obtained, i.e., in a general medium. (Author)

  20. Cognitive interference management in heterogeneous networks

    Marabissi, Dania

    2015-01-01

    This brief investigates the role of interference management in Heterogeneous Networks (Het Nets), focusing on cognitive approaches and the use of beamforming. Key concepts of Het Nets are introduced and different deployment strategies are examined, such as sharing the same frequency band of the macro cells or using new high frequency bands. Particular attention is devoted to co-channel deployment and to the problem of interference management, addressing various strategies that can be adopted to handle the interference between the cells. In addition, the brief explores cognitive small cells which are able to avoid or limit interference by using suitable beamforming and resource allocation schemes. The suggested solutions are supported by numerical results in terms of performance evaluations and comparisons.

  1. AXAF user interfaces for heterogeneous analysis environments

    Mandel, Eric; Roll, John; Ackerman, Mark S.

    1992-01-01

    The AXAF Science Center (ASC) will develop software to support all facets of data center activities and user research for the AXAF X-ray Observatory, scheduled for launch in 1999. The goal is to provide astronomers with the ability to utilize heterogeneous data analysis packages, that is, to allow astronomers to pick the best packages for doing their scientific analysis. For example, ASC software will be based on IRAF, but non-IRAF programs will be incorporated into the data system where appropriate. Additionally, it is desired to allow AXAF users to mix ASC software with their own local software. The need to support heterogeneous analysis environments is not special to the AXAF project, and therefore finding mechanisms for coordinating heterogeneous programs is an important problem for astronomical software today. The approach to solving this problem has been to develop two interfaces that allow the scientific user to run heterogeneous programs together. The first is an IRAF-compatible parameter interface that provides non-IRAF programs with IRAF's parameter handling capabilities. Included in the interface is an application programming interface to manipulate parameters from within programs, and also a set of host programs to manipulate parameters at the command line or from within scripts. The parameter interface has been implemented to support parameter storage formats other than IRAF parameter files, allowing one, for example, to access parameters that are stored in data bases. An X Windows graphical user interface called 'agcl' has been developed, layered on top of the IRAF-compatible parameter interface, that provides a standard graphical mechanism for interacting with IRAF and non-IRAF programs. Users can edit parameters and run programs for both non-IRAF programs and IRAF tasks. The agcl interface allows one to communicate with any command line environment in a transparent manner and without any changes to the original environment. For example, the authors

  2. Community characterization of heterogeneous complex systems

    Tumminello, Michele; Miccichè, Salvatore; Lillo, Fabrizio; Mantegna, Rosario N; Varho, Jan; Piilo, Jyrki

    2011-01-01

    We introduce an analytical statistical method for characterizing the communities detected in heterogeneous complex systems. By proposing a suitable null hypothesis, our method makes use of the hypergeometric distribution to assess the probability that a given property is over-expressed in the elements of a community with respect to all the elements of the investigated set. We apply our method to two specific complex networks, namely a network of world movies and a network of physics preprints. The characterization of the elements and of the communities is done in terms of languages and countries for the movie network and of journals and subject categories for papers. We find that our method is able to characterize clearly the communities identified. Moreover our method works well both for large and for small communities

  3. Applications of neutron scattering to heterogeneous catalysis

    Parker, Stewart F; Lennon, David

    2016-01-01

    Historically, most studies of heterogeneous catalysts that have used neutron vibrational spectroscopy have employed indirect geometry instruments with a low (<40 cm -1 ) final energy. In this paper we examine the reasons why this has been the case and highlight the advantages and disadvantages of this approach. We then show how some of these may be overcome by the use of direct geometry spectrometers. We illustrate the use of direct geometry spectrometers with examples from reforming of methane to synthesis gas (CO + H 2 ) over Ni/Al 2 O 3 catalysts and an operando study of CO oxidation. We conclude with a proposal for a unique instrument that combines both indirect and direct geometry spectrometers. (paper)

  4. Job scheduling in a heterogenous grid environment

    Oliker, Leonid; Biswas, Rupak; Shan, Hongzhang; Smith, Warren

    2004-02-11

    Computational grids have the potential for solving large-scale scientific problems using heterogeneous and geographically distributed resources. However, a number of major technical hurdles must be overcome before this potential can be realized. One problem that is critical to effective utilization of computational grids is the efficient scheduling of jobs. This work addresses this problem by describing and evaluating a grid scheduling architecture and three job migration algorithms. The architecture is scalable and does not assume control of local site resources. The job migration policies use the availability and performance of computer systems, the network bandwidth available between systems, and the volume of input and output data associated with each job. An extensive performance comparison is presented using real workloads from leading computational centers. The results, based on several key metrics, demonstrate that the performance of our distributed migration algorithms is significantly greater than that of a local scheduling framework and comparable to a non-scalable global scheduling approach.

  5. Designing Scientific Software for Heterogeneous Computing

    Glimberg, Stefan Lemvig

    , algorithms and data structures must be designed to utilize the underlying parallel architecture. The architectural changes in hardware design within the last decade, from single to multi and many-core architectures, require software developers to identify and properly implement methods that both exploit...... makes parallel software design applicable, but also a challenge for scientific software developers at all levels. We have developed a generic C++ library for fast prototyping of large-scale PDEs solvers based on flexible-order finite difference approximations on structured regular grids. The library...... is designed with a high abstraction interface to improve developer productivity. The library is based on modern template-based design concepts as described in Glimberg, Engsig-Karup, Nielsen & Dammann (2013). The library utilizes heterogeneous CPU/GPU environments in order to maximize computational throughput...

  6. Mathematical modeling in mechanics of heterogeneous media

    Fedorov, A.V.; Fomin, V.M.

    1991-01-01

    The paper reviews the work carried out at the Department of Multi-Phase Media Mechanics of the Institute of Theoretical and Applied Mechanics of the Siberian Division of the USSR Academy of Sciences. It deals with mathematical models for the flow of gas mixtures and solid particles that account for phase transitions and chemical reactions. This work is concerned with the problems of construction of laws of conservation, determination of the type of equations of heterogeneous media mechanics, structure of shock waves, and combined discontinuities in mixtures. The theory of ideal and nonideal detonation in suspension of matter in gases is discussed. Self-similar flows of gas mixtures and responding particles, as well as the problem of breakup of discontinuity for suspension of matter in gases, is studied. 42 refs

  7. Metabolic heterogeneity in clonal microbial populations.

    Takhaveev, Vakil; Heinemann, Matthias

    2018-02-21

    In the past decades, numerous instances of phenotypic diversity were observed in clonal microbial populations, particularly, on the gene expression level. Much less is, however, known about phenotypic differences that occur on the level of metabolism. This is likely explained by the fact that experimental tools probing metabolism of single cells are still at an early stage of development. Here, we review recent exciting discoveries that point out different causes for metabolic heterogeneity within clonal microbial populations. These causes range from ecological factors and cell-inherent dynamics in constant environments to molecular noise in gene expression that propagates into metabolism. Furthermore, we provide an overview of current methods to quantify the levels of metabolites and biomass components in single cells. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Network printing in a heterogenous environment

    Beyer, C.; Schroth, G.

    2001-01-01

    Mail and printing are often said to be the most visible services for the user in the network. Though many people talked about the paperless bureau a few years ago it seems that the more digital data is accessible, the more it gets printed. Print management in a heterogenous network environments is typically crossing all operating systems. Each of those brings its own requirements and different printing system implementations with individual user interfaces. The scope is to give the user the advantage and features of the native interface of their operating system while making administration tasks as easy as possible by following the general ideas of a centralised network service on the server side

  9. Mobility management in LTE heterogeneous networks

    Karandikar, Abhay; Mehta, Mahima

    2017-01-01

    This book is the first of its kind, compiling information on the Long-Term Evolution (LTE) standards, which are enhanced to address new mobility-related challenges in Heterogeneous Networks (HetNets). It identifies the related challenges and discusses solutions and the simulation methodology for modeling HetNet mobility – cutting-edge information that was previously accessible only in the form of 3GPP specifications and documents, and research papers. The book reviews the current LTE mobility framework and discusses some of the changes for enhancing mobility management in HetNets. It describes the measurement procedures, handover (HO) mechanisms and HO success/failure scenarios. HetNets are intended to provide very high spectral efficiency while ensuring seamless coverage by deploying low-power nodes within the umbrella macrocell network. While mobility management in homogeneous networks is well understood, LTE standards are being enhanced to address the HetNet-specific mobility management challenges emergi...

  10. Heterogeneity and plasticity of epidermal stem cells

    Schepeler, Troels; Page, Mahalia E; Jensen, Kim Bak

    2014-01-01

    The epidermis is an integral part of our largest organ, the skin, and protects us against the hostile environment. It is a highly dynamic tissue that, during normal steady-state conditions, undergoes constant turnover. Multiple stem cell populations residing in autonomously maintained compartments...... facilitate this task. In this Review, we discuss stem cell behaviour during normal tissue homeostasis, regeneration and disease within the pilosebaceous unit, an integral structure of the epidermis that is responsible for hair growth and lubrication of the epithelium. We provide an up-to-date view...... of the pilosebaceous unit, encompassing the heterogeneity and plasticity of multiple discrete stem cell populations that are strongly influenced by external cues to maintain their identity and function....

  11. Surface decontamination by heterogeneous foams and suspensions

    Polyakov, A.; Poluektov, P.; Emets, E.; Kuchumov, V.; Rybakov, K.; Teterin, E.

    2000-01-01

    A variety of methods was used to investigate the surface of stainless steel as delivered or treated (electrochemically polished, machine ground). Micro X-ray spectral analysis evidenced a uniform distribution of alloying elements. Auger spectroscopy revealed the layer-by-layer composition by elements and the thickness of the superficial oxide film. The distribution of heterogeneous uranium dioxide powders on the stainless steel surface was examined by microprobe analysis (using Comebax). In the order of increasing contamination by uranium dioxide, the surfaces can be arranged as: untreated - polished - ground. The behaviour of hydrogen peroxide in alkaline solutions was studied by spectrophotometry and laser analysis. Decontamination of stainless steel surfaces from UO 2 by microgaseous emulsions in alkaline media with surfactants present was tested. The decontamination factor was determined as a function of the size and volume of gas bubbles. It was shown to rise with increasing gas content. (author)

  12. Comprehensive Monitoring for Heterogeneous Geographically Distributed Storage

    Ratnikova, N. [Fermilab; Karavakis, E. [CERN; Lammel, S. [Fermilab; Wildish, T. [Princeton U.

    2015-12-23

    Storage capacity at CMS Tier-1 and Tier-2 sites reached over 100 Petabytes in 2014, and will be substantially increased during Run 2 data taking. The allocation of storage for the individual users analysis data, which is not accounted as a centrally managed storage space, will be increased to up to 40%. For comprehensive tracking and monitoring of the storage utilization across all participating sites, CMS developed a space monitoring system, which provides a central view of the geographically dispersed heterogeneous storage systems. The first prototype was deployed at pilot sites in summer 2014, and has been substantially reworked since then. In this paper we discuss the functionality and our experience of system deployment and operation on the full CMS scale.

  13. Chinese Immigrant Wealth: Heterogeneity in Adaptation.

    Keister, Lisa A; Agius Vallejo, Jody; Aronson, Brian

    2016-01-01

    Chinese immigrants are a diverse and growing group whose members provide a unique opportunity to examine within-immigrant group differences in adaptation. In this paper, we move beyond thinking of national-origin groups as homogenous and study variation among Chinese immigrants in wealth ownership, a critical indicator of adaptation that attracts relatively little attention in the immigration literature. We develop an analytical approach that considers national origin, tenure in the U.S., and age to examine heterogeneity in economic adaptation among the immigrant generation. Our results show that variations among Chinese immigrants explain within-group differences in net worth, asset ownership, and debt. These differences also account for important variation between Chinese immigrants, natives, and other immigrant groups and provide important, new insight into the processes that lead to immigrant adaptation and long-term class stability.

  14. Chinese Immigrant Wealth: Heterogeneity in Adaptation.

    Lisa A Keister

    Full Text Available Chinese immigrants are a diverse and growing group whose members provide a unique opportunity to examine within-immigrant group differences in adaptation. In this paper, we move beyond thinking of national-origin groups as homogenous and study variation among Chinese immigrants in wealth ownership, a critical indicator of adaptation that attracts relatively little attention in the immigration literature. We develop an analytical approach that considers national origin, tenure in the U.S., and age to examine heterogeneity in economic adaptation among the immigrant generation. Our results show that variations among Chinese immigrants explain within-group differences in net worth, asset ownership, and debt. These differences also account for important variation between Chinese immigrants, natives, and other immigrant groups and provide important, new insight into the processes that lead to immigrant adaptation and long-term class stability.

  15. Recent developments in anisotropic heterogeneous shell theory

    Grigorenko, Alexander Ya; Grigorenko, Yaroslav M; Vlaikov, Georgii G

    2016-01-01

    This volume focuses on the relevant general theory and presents some first applications, namely those based on classical shell theory. After a brief introduction, during which the history and state-of-the-art are discussed, the first chapter presents the mechanics of anisotropic heterogeneous shells, covering all relevant assumptions and the basic relations of 3D elasticity, classical and refined shell models. The second chapter examines the numerical techniques that are used, namely discrete orthogonalization, spline-collocation and Fourier series, while the third highlights applications based on classical theory, in particular, the stress-strain state of shallow shells, non-circular shells, shells of revolution, and free vibrations of conical shells. The book concludes with a summary and an outlook bridging the gap to the second volume.

  16. Spatially heterogeneous ages in glassy dynamics

    Castillo, Horacio E.; Chamon, Claudio Chamon; Cugliandolo, Leticia F.; Iguain, Jose Luis; Kennett, Malcolm P.

    2003-09-01

    We construct a framework for the study of fluctuations in the nonequilibrium relaxation of glassy systems with and without quenched disorder. We study two types of two-time local correlators with the aim of characterizing the heterogeneous evolution in these systems: in one case we average the local correlators over histories of the thermal noise, in the other case we simply coarse-grain the local correlators obtained for a given noise realization. We explain why the noise-averaged correlators describe the fingerprint of quenched disorder when it exists, while the coarse-grained correlators are linked to noise-induced mesoscopic fluctuations. We predict constraints on the distribution of the fluctuations of the coarse-grained quantities. In particular, we show that locally defined correlations and responses are connected by a generalized local out-of-equilibrium fluctuation-dissipation relation. We argue that large size heterogeneities in the age of the system survive in the long-time limit. A symmetry of the underlying theory, namely invariance under reparametrizations of the time coordinates, underlies these results. We establish a connection between the probabilities of spatial distributions of local coarse-grained quantities and the theory of dynamic random manifolds. We define, and discuss the behavior of, a two-time dependent correlation length from the spatial decay of the fluctuations in the two-time local functions. We characterize the fluctuations in the system in terms of their fractal properties. For concreteness, we present numerical tests performed on disordered spin models in finite and infinite dimensions. Finally, we explain how these ideas can be applied to the analysis of the dynamics of other glassy systems that can be either spin models without disorder or atomic and molecular glassy systems. (author)

  17. Neutronic of heterogenous gas cooled reactors

    Maturana, Roberto Hernan

    2008-01-01

    At present, one of the main technical features of the advanced gas cooled reactor under development is its fuel element concept, which implies a neutronic homogeneous design, thus requiring higher enrichment compared with present commercial nuclear power plants.In this work a neutronic heterogeneous gas cooled reactor design is analyzed by studying the neutronic design of the Advanced Gas cooled Reactor (AGR), a low enrichment, gas cooled and graphite moderated nuclear power plant.A search of merit figures (some neutronic parameter, characteristic dimension, or a mixture of both) which are important and have been optimized during the reactor design stage is been done, to aim to comprise how a gas heterogeneous reactor is been design, given that semi-infinity arrangement criteria of rods in LWRs and clusters in HWRs can t be applied for a solid moderator and a gas refrigerator.The WIMS code for neutronic cell calculations is been utilized to model the AGR fuel cell and to calculate neutronic parameters such as the multiplication factor and the pick factor, as function of the fuel burnup.Also calculation is been done for various nucleus characteristic dimensions values (fuel pin radius, fuel channel pitch) and neutronic parameters (such as fuel enrichment), around the design established parameters values.A fuel cycle cost analysis is carried out according to the reactor in study, and the enrichment effect over it is been studied.Finally, a thermal stability analysis is been done, in subcritical condition and at power level, to study this reactor characteristic reactivity coefficients.Present results shows (considering the approximation used) a first set of neutronic design figures of merit consistent with the AGR design. [es

  18. Heterogeneous recombination among Hepatitis B virus genotypes.

    Castelhano, Nadine; Araujo, Natalia M; Arenas, Miguel

    2017-10-01

    The rapid evolution of Hepatitis B virus (HBV) through both evolutionary forces, mutation and recombination, allows this virus to generate a large variety of adapted variants at both intra and inter-host levels. It can, for instance, generate drug resistance or the diverse viral genotypes that currently exist in the HBV epidemics. Concerning the latter, it is known that recombination played a major role in the emergence and genetic diversification of novel genotypes. In this regard, the quantification of viral recombination in each genotype can provide relevant information to devise expectations about the evolutionary trends of the epidemic. Here we measured the amount of this evolutionary force by estimating global and local recombination rates in >4700 HBV complete genome sequences corresponding to nine (A to I) HBV genotypes. Counterintuitively, we found that genotype E presents extremely high levels of recombination, followed by genotypes B and C. On the other hand, genotype G presents the lowest level, where recombination is almost negligible. We discuss these findings in the light of known characteristics of these genotypes. Additionally, we present a phylogenetic network to depict the evolutionary history of the studied HBV genotypes. This network clearly classified all genotypes into specific groups and indicated that diverse pairs of genotypes are derived from a common ancestor (i.e., C-I, D-E and, F-H) although still the origin of this virus presented large uncertainty. Altogether we conclude that the amount of observed recombination is heterogeneous among HBV genotypes and that this heterogeneity can influence on the future expansion of the epidemic. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The heterogeneous dynamics of economic complexity.

    Cristelli, Matthieu; Tacchella, Andrea; Pietronero, Luciano

    2015-01-01

    What will be the growth of the Gross Domestic Product (GDP) or the competitiveness of China, United States, and Vietnam in the next 3, 5 or 10 years? Despite this kind of questions has a large societal impact and an extreme value for economic policy making, providing a scientific basis for economic predictability is still a very challenging problem. Recent results of a new branch--Economic Complexity--have set the basis for a framework to approach such a challenge and to provide new perspectives to cast economic prediction into the conceptual scheme of forecasting the evolution of a dynamical system as in the case of weather dynamics. We argue that a recently introduced non-monetary metrics for country competitiveness (fitness) allows for quantifying the hidden growth potential of countries by the means of the comparison of this measure for intangible assets with monetary figures, such as GDP per capita. This comparison defines the fitness-income plane where we observe that country dynamics presents strongly heterogeneous patterns of evolution. The flow in some zones is found to be laminar while in others a chaotic behavior is instead observed. These two regimes correspond to very different predictability features for the evolution of countries: in the former regime, we find strong predictable pattern while the latter scenario exhibits a very low predictability. In such a framework, regressions, the usual tool used in economics, are no more the appropriate strategy to deal with such a heterogeneous scenario and new concepts, borrowed from dynamical systems theory, are mandatory. We therefore propose a data-driven method--the selective predictability scheme--in which we adopt a strategy similar to the methods of analogues, firstly introduced by Lorenz, to assess future evolution of countries.

  20. A quantitative geologic study of heterogeneity

    Davis, J.M.; Phillips, F.M.

    1990-01-01

    Spatial variation of hydraulic conductivity has been generally recognized as the dominant medium-dependent control on the transport and dispersion of contaminants in ground water. An empirical study focusing on the relationship between patters of sedimentology and patterns of permeability is being conducted at an outcrop of the Pliocene/Pleistocene Sierra Ladrones formation, central New Mexico. Methods of geostatistics and sedimentary basin analysis are employed to study the problem of aquifer heterogeneity. An air permeameter provides a means of obtaining extensive field measurements of air-flow rates through the sediments. These flow rates are subsequently used to characterize the permeability distribution of the outcrop. Both the geologic information and the air-flow rate data provide the basis for analysis of aquifer heterogeneity. Preliminary geologic mapping indicates that the sediments in the study area are the products of an arid fluvial/interfluvial depositional environment. Probability distribution analysis of the air-flow rate data suggests that the permeability of these sediments is log-normally distributed. The air permeability data are used to estimate variograms and correlation lengths in both the horizontal and vertical directions. At the scale of 10's of centimeters, the horizontal variograms exhibit exponential variogram behaviour . When two distinct lithologies are present, the correlation structure appears to be a nested exponential. Variogram analysis of estimated mean permeability at the scale of meters also shows evidence of a nested correlation structure in the horizontal direction and a periodic correlation structure in the vertical direction. Results of this study suggest that there is a direct connection between observable geologic structure and permeability statistics. (Author) (35 refs., 10 figs., 5 tabs.)

  1. The Heterogeneous Dynamics of Economic Complexity

    Cristelli, Matthieu; Tacchella, Andrea; Pietronero, Luciano

    2015-01-01

    What will be the growth of the Gross Domestic Product (GDP) or the competitiveness of China, United States, and Vietnam in the next 3, 5 or 10 years? Despite this kind of questions has a large societal impact and an extreme value for economic policy making, providing a scientific basis for economic predictability is still a very challenging problem. Recent results of a new branch—Economic Complexity—have set the basis for a framework to approach such a challenge and to provide new perspectives to cast economic prediction into the conceptual scheme of forecasting the evolution of a dynamical system as in the case of weather dynamics. We argue that a recently introduced non-monetary metrics for country competitiveness (fitness) allows for quantifying the hidden growth potential of countries by the means of the comparison of this measure for intangible assets with monetary figures, such as GDP per capita. This comparison defines the fitness-income plane where we observe that country dynamics presents strongly heterogeneous patterns of evolution. The flow in some zones is found to be laminar while in others a chaotic behavior is instead observed. These two regimes correspond to very different predictability features for the evolution of countries: in the former regime, we find strong predictable pattern while the latter scenario exhibits a very low predictability. In such a framework, regressions, the usual tool used in economics, are no more the appropriate strategy to deal with such a heterogeneous scenario and new concepts, borrowed from dynamical systems theory, are mandatory. We therefore propose a data-driven method—the selective predictability scheme—in which we adopt a strategy similar to the methods of analogues, firstly introduced by Lorenz, to assess future evolution of countries. PMID:25671312

  2. Diagnosis and heterogeneity of MS in MRI

    Holst, B.; Fiehler, J.; Schippling, S.

    2008-01-01

    An efficient therapy of MS requires a quick and reliable diagnosis of the disease. MRI is the most leading paraclinical examination for MS diagnosis. Even though there is no pathognomic finding in MRI, there are MS characteristics with respect to morphology and localization. To exclude other neurological disorders and distinguish between different characteristics within MS, the use of contrast agent is advantageous. Postulated MRI criteria have been increasingly adjusted to the clinical routine and have become clearer, more sensitive, and more specific. Different imaging criteria will be introduced. In addition to the McDonald criteria of 2001 and 2005, new criteria will be presented in which the use of contrast agent is replaced by a second MRI and the dissemination in time and space is simplified. Different pathomechanisms which help to separate MS patients into subgroups are postulated. The diverse pathomechanisms also enable the development of new pharmaceuticals to manipulate the immunologic course in different stages. For varying therapy approaches, it is increasingly important to differentiate the heterogeneous appearance forms into subtypes. The two visible main components of the disorder in MRI are inflammation and neurodegeneration and are responsible for different clinical courses. Both are interdependent and independent of each other. We introduce a stratification which uses both components as a function of their different outcomes to compose subgroups. The previous challenge with respect to MRI was to support the diagnosis of MS via MRI criteria. A future problem will be the heterogeneity and classification of subgroups. This article gives an overview of both problems. (orig.)

  3. Spatially correlated heterogeneous aspirations to enhance network reciprocity

    Tanimoto, Jun; Nakata, Makoto; Hagishima, Aya; Ikegaya, Naoki

    2012-02-01

    Perc & Wang demonstrated that aspiring to be the fittest under conditions of pairwise strategy updating enhances network reciprocity in structured populations playing 2×2 Prisoner's Dilemma games (Z. Wang, M. Perc, Aspiring to the fittest and promoted of cooperation in the Prisoner's Dilemma game, Physical Review E 82 (2010) 021115; M. Perc, Z. Wang, Heterogeneous aspiration promotes cooperation in the Prisoner's Dilemma game, PLOS one 5 (12) (2010) e15117). Through numerical simulations, this paper shows that network reciprocity is even greater if heterogeneous aspirations are imposed. We also suggest why heterogeneous aspiration fosters network reciprocity. It distributes strategy updating speed among agents in a manner that fortifies the initially allocated cooperators' clusters against invasion. This finding prompted us to further enhance the usual heterogeneous aspiration cases for heterogeneous network topologies. We find that a negative correlation between degree and aspiration level does extend cooperation among heterogeneously structured agents.

  4. Heterogeneous Epidemic Model for Assessing Data Dissemination in Opportunistic Networks

    Rozanova, Liudmila; Alekseev, Vadim; Temerev, Alexander

    2014-01-01

    that amount of data transferred between network nodes possesses a Pareto distribution, implying scale-free properties. In this context, more heterogeneity in susceptibility means the less severe epidemic progression, and, on the contrary, more heterogeneity in infectivity leads to more severe epidemics...... — assuming that the other parameter (either heterogeneity or susceptibility) stays fixed. The results are general enough to be useful for estimating the epidemic progression with no significant acquired immunity — in the cases where Pareto distribution holds....

  5. Sampling strategies to capture single-cell heterogeneity

    Satwik Rajaram; Louise E. Heinrich; John D. Gordan; Jayant Avva; Kathy M. Bonness; Agnieszka K. Witkiewicz; James S. Malter; Chloe E. Atreya; Robert S. Warren; Lani F. Wu; Steven J. Altschuler

    2017-01-01

    Advances in single-cell technologies have highlighted the prevalence and biological significance of cellular heterogeneity. A critical question is how to design experiments that faithfully capture the true range of heterogeneity from samples of cellular populations. Here, we develop a data-driven approach, illustrated in the context of image data, that estimates the sampling depth required for prospective investigations of single-cell heterogeneity from an existing collection of samples. ...

  6. Cognitive Heterogeneous Reconfigurable Optical Networks (CHRON): Enabling Technologies and Techniques

    Tafur Monroy, Idelfonso; Zibar, Darko; Guerrero Gonzalez, Neil

    2011-01-01

    We present the approach of cognition applied to heterogeneous optical networks developed in the framework of the EU project CHRON: Cognitive Heterogeneous Reconfigurable Optical Network. We introduce and discuss in particular the technologies and techniques that will enable a cognitive optical...... network to observe, act, learn and optimizes its performance, taking into account its high degree of heterogeneity with respect to quality of service, transmission and switching techniques....

  7. Heterogeneity of Opioid Binding Sites in Guinea Pig Spinal Cord

    1984-11-30

    MEDICAL CENTER WILFORD HALL AIR FORCE MEDICAL CENTER Title of Thesis: "Heterogeneity of Opioid Binding Sites in Guinea Pig Spinal Cord" Name of...that the use of any copyrighted material in the dissertation manuscript entitled: "Heterogeneity of Opioid Binding Sites in Guinea Pig Spinal Cord...University of the Health Sciences 11 Abstract Title of Thesis: Heterogenity of Opioid Binding Sites In Guinea Pig Spinal Cord Gary Dean Zarr MAJ/ANC

  8. Mass spectrometric analysis of protein interactions

    Borch, Jonas; Jørgensen, Thomas J. D.; Roepstorff, Peter

    2005-01-01

    Mass spectrometry is a powerful tool for identification of interaction partners and structural characterization of protein interactions because of its high sensitivity, mass accuracy and tolerance towards sample heterogeneity. Several tools that allow studies of protein interaction are now...... available and recent developments that increase the confidence of studies of protein interaction by mass spectrometry include quantification of affinity-purified proteins by stable isotope labeling and reagents for surface topology studies that can be identified by mass-contributing reporters (e.g. isotope...... labels, cleavable cross-linkers or fragment ions. The use of mass spectrometers to study protein interactions using deuterium exchange and for analysis of intact protein complexes recently has progressed considerably....

  9. Unobserved heterogeneity in the power law nonhomogeneous Poisson process

    Asfaw, Zeytu Gashaw; Lindqvist, Bo Henry

    2015-01-01

    A study of possible consequences of heterogeneity in the failure intensity of repairable systems is presented. The basic model studied is the nonhomogeneous Poisson process with power law intensity function. When several similar systems are under observation, the assumption that the corresponding processes are independent and identically distributed is often questionable. In practice there may be an unobserved heterogeneity among the systems. The heterogeneity is modeled by introduction of unobserved gamma distributed frailties. The relevant likelihood function is derived, and maximum likelihood estimation is illustrated. In a simulation study we then compare results when using a power law model without taking into account heterogeneity, with the corresponding results obtained when the heterogeneity is accounted for. A motivating data example is also given. - Highlights: • Consequences of overlooking heterogeneity in similar repairable systems are studied. • Likelihood functions are established for power law NHPP w/ and w/o heterogeneity. • ML estimators for parameters of power law NHPP with heterogeneity are derived. • A simulation study shows the effects of heterogeneity and its ignorance in models

  10. Holistic Framework For Establishing Interoperability of Heterogeneous Software Development Tools

    Puett, Joseph

    2003-01-01

    This dissertation presents a Holistic Framework for Software Engineering (HFSE) that establishes collaborative mechanisms by which existing heterogeneous software development tools and models will interoperate...

  11. Simple heterogeneity parametrization for sea surface temperature and chlorophyll

    Skákala, Jozef; Smyth, Timothy J.

    2016-06-01

    Using satellite maps this paper offers a complex analysis of chlorophyll & SST heterogeneity in the shelf seas around the southwest of the UK. The heterogeneity scaling follows a simple power law and is consequently parametrized by two parameters. It is shown that in most cases these two parameters vary only relatively little with time. The paper offers a detailed comparison of field heterogeneity between different regions. How much heterogeneity is in each region preserved in the annual median data is also determined. The paper explicitly demonstrates how one can use these results to calculate representative measurement area for in situ networks.

  12. Autophagy capacity and sub-mitochondrial heterogeneity shape Bnip3-induced mitophagy regulation of apoptosis.

    Choe, Sehyo Charley; Hamacher-Brady, Anne; Brady, Nathan Ryan

    2015-08-08

    determined by levels and spatial localization of autophagy capacity, and subcellular mitochondrial protein heterogeneities. Our model identifies mechanisms and conditions that alter the mitophagy decision within mitochondrial subpopulations to an extent sufficient to shape cellular outcome to apoptotic stimuli. Overall, our modeling approach provides means to suggest new experiments and implement findings at multiple scales in order to understand how network topologies and subcellular heterogeneities can influence signaling events at individual organelle level, and hence, determine the emergence of heterogeneity in cellular decisions due the actions of the collective intra-cellular population.

  13. Heterogeneous iris image hallucination using sparse representation on a learned heterogeneous patch dictionary

    Li, Yung-Hui; Zheng, Bo-Ren; Ji, Dai-Yan; Tien, Chung-Hao; Liu, Po-Tsun

    2014-09-01

    Cross sensor iris matching may seriously degrade the recognition performance because of the sensor mis-match problem of iris images between the enrollment and test stage. In this paper, we propose two novel patch-based heterogeneous dictionary learning method to attack this problem. The first method applies the latest sparse representation theory while the second method tries to learn the correspondence relationship through PCA in heterogeneous patch space. Both methods learn the basic atoms in iris textures across different image sensors and build connections between them. After such connections are built, at test stage, it is possible to hallucinate (synthesize) iris images across different sensors. By matching training images with hallucinated images, the recognition rate can be successfully enhanced. The experimental results showed the satisfied results both visually and in terms of recognition rate. Experimenting with an iris database consisting of 3015 images, we show that the EER is decreased 39.4% relatively by the proposed method.

  14. Biodiesel forming reactions using heterogeneous catalysis

    Liu, Yijun

    Biodiesel synthesis from biomass provides a means for utilizing effectively renewable resources, a way to convert waste vegetable oils and animal fats to a useful product, a way to recycle carbon dioxide for a combustion fuel, and production of a fuel that is biodegradable, non-toxic, and has a lower emission profile than petroleum-diesel. Free fatty acid (FFA) esterification and triglyceride (TG) transesterification with low molecular weight alcohols constitute the synthetic routes to prepare biodiesel from lipid feedstocks. This project was aimed at developing a better understanding of important fundamental issues involved in heterogeneous catalyzed biodiesel forming reactions using mainly model compounds, representing part of on-going efforts to build up a rational base for assay, design, and performance optimization of solid acids/bases in biodiesel synthesis. As FFA esterification proceeds, water is continuously formed as a byproduct and affects reaction rates in a negative manner. Using sulfuric acid (as a catalyst) and acetic acid (as a model compound for FFA), the impact of increasing concentrations of water on acid catalysis was investigated. The order of the water effect on reaction rate was determined to be -0.83. Sulfuric acid lost up to 90% activity as the amount of water present increased. The nature of the negative effect of water on esterification was found to go beyond the scope of reverse hydrolysis and was associated with the diminished acid strength of sulfuric acid as a result of the preferential solvation by water molecules of its catalytic protons. The results indicate that as esterification progresses and byproduct water is produced, deactivation of a Bronsted acid catalyst like H2SO4 occurs. Using a solid composite acid (SAC-13) as an example of heterogeneous catalysts and sulfuric acid as a homogeneous reference, similar reaction inhibition by water was demonstrated for homogeneous and heterogeneous catalysis. This similarity together with

  15. Heterogeneous recycling in SFR core periphery

    Varaine, Frederic; Buiron, Laurent; Boucher, Lionel; Chabert, Christine

    2008-01-01

    In the framework of next generation fast reactor design, the management of minor actinides (MA) is one of the key issues. The Transmutation of MA can be achieving with various modes of transmutation and waste management. Two ways for transmutation: - The homogeneous mode where the minor actinides to be transmuted are directly mixed with 'standard' fuel of the reactor, - The heterogeneous way for which the actinides to be transmuted are separated from the fuel itself, in limited number of S/A (targets) devoted to actinides transmutation. Associated with two ways for actinides management: - The multiple recycling: in this case whole or part of minor actinides and plutonium at the end of each reactor cycle is sent back in the following cycle. In that way, only reprocessing losses go to the waste, - The once-through way: in this case the minor actinides are transmuted in targets where very high burn up is reached. Fast reactors offer the best performances to transmute the minor actinides in homogeneous or heterogeneous way at industrial scale. The safety criteria are acceptable for all solutions if the MA content is not over 2.5% of the total heavy nuclides. In this context, the last results obtained for minor actinides transmutation in sodium fast reactor depleted uranium radial blankets are presented. This concept is based on a heterogeneous multiple recycling model. The use of the oxide matrix allows to reprocess such S/A in the spent fuel standard flow. For the study, we use a preliminary design of a 3600 MWth sodium Fast Reactor in progress at CEA. We investigate the transmutation performances of (U+Np+Am+Cm)O 2 fuel in radial blankets assemblies. We focus on two upper and lower assumptions in order to investigate the feasibility domain for this concept: one with a minor actinides (MA) content of 10%, and the second one with an enrichment of MA close to 40%. The CEA is studying scenarios of principle for the French case through a dynamic vision of the nuclear

  16. Application of phasor plot and autofluorescence correction for study of heterogeneous cell population

    Szmacinski, Henryk; Toshchakov, Vladimir; Lakowicz, Joseph R.

    2014-01-01

    Abstract. Protein-protein interactions in cells are often studied using fluorescence resonance energy transfer (FRET) phenomenon by fluorescence lifetime imaging microscopy (FLIM). Here, we demonstrate approaches to the quantitative analysis of FRET in cell population in a case complicated by a highly heterogeneous donor expression, multiexponential donor lifetime, large contribution of cell autofluorescence, and significant presence of unquenched donor molecules that do not interact with the acceptor due to low affinity of donor-acceptor binding. We applied a multifrequency phasor plot to visualize FRET FLIM data, developed a method for lifetime background correction, and performed a detailed time-resolved analysis using a biexponential model. These approaches were applied to study the interaction between the Toll Interleukin-1 receptor (TIR) domain of Toll-like receptor 4 (TLR4) and the decoy peptide 4BB. TLR4 was fused to Cerulean fluorescent protein (Cer) and 4BB peptide was labeled with Bodipy TMRX (BTX). Phasor displays for multifrequency FLIM data are presented. The analytical procedure for lifetime background correction is described and the effect of correction on FLIM data is demonstrated. The absolute FRET efficiency was determined based on the phasor plot display and multifrequency FLIM data analysis. The binding affinity between TLR4-Cer (donor) and decoy peptide 4BB-BTX (acceptor) was estimated in a heterogeneous HeLa cell population. PMID:24770662

  17. Evolution and development of model membranes for physicochemical and functional studies of the membrane lateral heterogeneity.

    Morigaki, Kenichi; Tanimoto, Yasushi

    2018-03-14

    One of the main questions in the membrane biology is the functional roles of membrane heterogeneity and molecular localization. Although segregation and local enrichment of protein/lipid components (rafts) have been extensively studied, the presence and functions of such membrane domains still remain elusive. Along with biochemical, cell observation, and simulation studies, model membranes are emerging as an important tool for understanding the biological membrane, providing quantitative information on the physicochemical properties of membrane proteins and lipids. Segregation of fluid lipid bilayer into liquid-ordered (Lo) and liquid-disordered (Ld) phases has been studied as a simplified model of raft in model membranes, including giant unilamellar vesicles (GUVs), giant plasma membrane vesicles (GPMVs), and supported lipid bilayers (SLB). Partition coefficients of membrane proteins between Lo and Ld phases were measured to gauze their affinities to lipid rafts (raftophilicity). One important development in model membrane is patterned SLB based on the microfabrication technology. Patterned Lo/Ld phases have been applied to study the partition and function of membrane-bound molecules. Quantitative information of individual molecular species attained by model membranes is critical for elucidating the molecular functions in the complex web of molecular interactions. The present review gives a short account of the model membranes developed for studying the lateral heterogeneity, especially focusing on patterned model membranes on solid substrates. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins.

    Uversky, Vladimir N

    2016-03-25

    Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Heterogeneity of mammary lesions represent molecular differences

    Namba, Ruria; Gregg, Jeffrey P; Maglione, Jeannie E; Davis, Ryan R; Baron, Colin A; Liu, Stephenie; Carmack, Condie E; Young, Lawrence JT; Borowsky, Alexander D; Cardiff, Robert D

    2006-01-01

    Human breast cancer is a heterogeneous disease, histopathologically, molecularly and phenotypically. The molecular basis of this heterogeneity is not well understood. We have used a mouse model of DCIS that consists of unique lines of mammary intraepithelial neoplasia (MIN) outgrowths, the premalignant lesion in the mouse that progress to invasive carcinoma, to understand the molecular changes that are characteristic to certain phenotypes. Each MIN-O line has distinguishable morphologies, metastatic potentials and estrogen dependencies. We utilized oligonucleotide expression arrays and high resolution array comparative genomic hybridization (aCGH) to investigate whole genome expression patterns and whole genome aberrations in both the MIN-O and tumor from four different MIN-O lines that each have different phenotypes. From the whole genome analysis at 35 kb resolution, we found that chromosome 1, 2, 10, and 11 were frequently associated with whole chromosome gains in the MIN-Os. In particular, two MIN-O lines had the majority of the chromosome gains. Although we did not find any whole chromosome loss, we identified 3 recurring chromosome losses (2F1-2, 3E4, 17E2) and two chromosome copy number gains on chromosome 11. These interstitial deletions and duplications were verified with a custom made array designed to interrogate the specific regions at approximately 550 bp resolution. We demonstrated that expression and genomic changes are present in the early premalignant lesions and that these molecular profiles can be correlated to phenotype (metastasis and estrogen responsiveness). We also identified expression changes associated with genomic instability. Progression to invasive carcinoma was associated with few additional changes in gene expression and genomic organization. Therefore, in the MIN-O mice, early premalignant lesions have the major molecular and genetic changes required and these changes have important phenotypic significance. In contrast, the changes

  20. Heterogeneity of Bovine Peripheral Blood Monocytes

    Jamal Hussen

    2017-12-01

    Full Text Available Peripheral blood monocytes of several species can be divided into different subpopulations with distinct phenotypic and functional properties. Herein, we aim at reviewing published work regarding the heterogeneity of the recently characterized bovine monocyte subsets. As the heterogeneity of human blood monocytes was widely studied and reviewed, this work focuses on comparing bovine monocyte subsets with their human counterparts regarding their phenotype, adhesion and migration properties, inflammatory and antimicrobial functions, and their ability to interact with neutrophilic granulocytes. In addition, the differentiation of monocyte subsets into functionally polarized macrophages is discussed. Regarding phenotype and distribution in blood, bovine monocyte subsets share similarities with their human counterparts. However, many functional differences exist between monocyte subsets from the two species. In contrast to their pro-inflammatory functions in human, bovine non-classical monocytes show the lowest phagocytosis and reactive oxygen species generation capacity, an absent ability to produce the pro-inflammatory cytokine IL-1β after inflammasome activation, and do not have a role in the early recruitment of neutrophils into inflamed tissues. Classical and intermediate monocytes of both species also differ in their response toward major monocyte-attracting chemokines (CCL2 and CCL5 and neutrophil degranulation products (DGP in vitro. Such differences between homologous monocyte subsets also extend to the development of monocyte-derived macrophages under the influence of chemokines like CCL5 and neutrophil DGP. Whereas the latter induce the differentiation of M1-polarized macrophages in human, bovine monocyte-derived macrophages develop a mixed M1/M2 macrophage phenotype. Although only a few bovine clinical trials analyzed the correlation between changes in monocyte composition and disease, they suggest that functional differences between

  1. Unraveling Macrophage Heterogeneity in Erythroblastic Islands

    Katie Giger Seu

    2017-09-01

    found that VCAM-1, F4/80, and CD169 are expressed heterogeneously by the central macrophages within the EBIs, while CD11b, although abundantly expressed by cells within the islands, is not expressed on the EBI macrophages. Moreover, differences in the phenotype of EBIs in rats compared to mice point to potential functional differences between these species. These data demonstrate the usefulness of IFC in analysis and characterization of EBIs and more importantly in exploring the heterogeneity and plasticity of EBI macrophages.

  2. From tomographic images to fault heterogeneities

    A. Amato

    1994-06-01

    Full Text Available Local Earthquake Tomography (LET is a useful tool for imaging lateral heterogeneities in the upper crust. The pattern of P- and S-wave velocity anomalies, in relation to the seismicity distribution along active fault zones. can shed light on the existence of discrete seismogenic patches. Recent tomographic studies in well monitored seismic areas have shown that the regions with large seismic moment release generally correspond to high velocity zones (HVZ's. In this paper, we discuss the relationship between the seismogenic behavior of faults and the velocity structure of fault zones as inferred from seismic tomography. First, we review some recent tomographic studies in active strike-slip faults. We show examples from different segments of the San Andreas fault system (Parkfield, Loma Prieta, where detailed studies have been carried out in recent years. We also show two applications of LET to thrust faults (Coalinga, Friuli. Then, we focus on the Irpinia normal fault zone (South-Central Italy, where a Ms = 6.9 earthquake occurred in 1980 and many thousands of attershock travel time data are available. We find that earthquake hypocenters concentrate in HVZ's, whereas low velocity zones (LVZ’ s appear to be relatively aseismic. The main HVZ's along which the mainshock rupture bas propagated may correspond to velocity weakening fault regions, whereas the LVZ's are probably related to weak materials undergoing stable slip (velocity strengthening. A correlation exists between this HVZ and the area with larger coseismic slip along the fault, according to both surface evidence (a fault scarp as high as 1 m and strong ground motion waveform modeling. Smaller wave-length, low-velocity anomalies detected along the fault may be the expression of velocity strengthening sections, where aseismic slip occurs. According to our results, the rupture at the nucleation depth (~ 10-12 km is continuous for the whole fault lenoth (~ 30 km, whereas at shallow depth

  3. Integrating mean and variance heterogeneities to identify differentially expressed genes.

    Ouyang, Weiwei; An, Qiang; Zhao, Jinying; Qin, Huaizhen

    2016-12-06

    In functional genomics studies, tests on mean heterogeneity have been widely employed to identify differentially expressed genes with distinct mean expression levels under different experimental conditions. Variance heterogeneity (aka, the difference between condition-specific variances) of gene expression levels is simply neglected or calibrated for as an impediment. The mean heterogeneity in the expression level of a gene reflects one aspect of its distribution alteration; and variance heterogeneity induced by condition change may reflect another aspect. Change in condition may alter both mean and some higher-order characteristics of the distributions of expression levels of susceptible genes. In this report, we put forth a conception of mean-variance differentially expressed (MVDE) genes, whose expression means and variances are sensitive to the change in experimental condition. We mathematically proved the null independence of existent mean heterogeneity tests and variance heterogeneity tests. Based on the independence, we proposed an integrative mean-variance test (IMVT) to combine gene-wise mean heterogeneity and variance heterogeneity induced by condition change. The IMVT outperformed its competitors under comprehensive simulations of normality and Laplace settings. For moderate samples, the IMVT well controlled type I error rates, and so did existent mean heterogeneity test (i.e., the Welch t test (WT), the moderated Welch t test (MWT)) and the procedure of separate tests on mean and variance heterogeneities (SMVT), but the likelihood ratio test (LRT) severely inflated type I error rates. In presence of variance heterogeneity, the IMVT appeared noticeably more powerful than all the valid mean heterogeneity tests. Application to the gene profiles of peripheral circulating B raised solid evidence of informative variance heterogeneity. After adjusting for background data structure, the IMVT replicated previous discoveries and identified novel experiment

  4. Acknowledging patient heterogeneity in economic evaluation : a systematic literature review.

    Grutters, Janneke P C; Sculpher, Mark; Briggs, Andrew H; Severens, Johan L; Candel, Math J; Stahl, James E; De Ruysscher, Dirk; Boer, Albert; Ramaekers, Bram L T; Joore, Manuela A

    2013-02-01

    Patient heterogeneity is the part of variability that can be explained by certain patient characteristics (e.g. age, disease stage). Population reimbursement decisions that acknowledge patient heterogeneity could potentially save money and increase population health. To date, however, economic evaluations pay only limited attention to patient heterogeneity. The objective of the present paper is to provide a comprehensive overview of the current knowledge regarding patient heterogeneity within economic evaluation of healthcare programmes. A systematic literature review was performed to identify methodological papers on the topic of patient heterogeneity in economic evaluation. Data were obtained using a keyword search of the PubMed database and manual searches. Handbooks were also included. Relevant data were extracted regarding potential sources of patient heterogeneity, in which of the input parameters of an economic evaluation these occur, methods to acknowledge patient heterogeneity and specific concerns associated with this acknowledgement. A total of 20 articles and five handbooks were included. The relevant sources of patient heterogeneity (demographics, preferences and clinical characteristics) and the input parameters where they occurred (baseline risk, treatment effect, health state utility and resource utilization) were combined in a framework. Methods were derived for the design, analysis and presentation phases of an economic evaluation. Concerns related mainly to the danger of false-positive results and equity issues. By systematically reviewing current knowledge regarding patient heterogeneity within economic evaluations of healthcare programmes, we provide guidance for future economic evaluations. Guidance is provided on which sources of patient heterogeneity to consider, how to acknowledge them in economic evaluation and potential concerns. The improved acknowledgement of patient heterogeneity in future economic evaluations may well improve the

  5. Green's Function and Stress Fields in Stochastic Heterogeneous Continua

    Negi, Vineet

    Many engineering materials used today are heterogenous in composition e.g. Composites - Polymer Matrix Composites, Metal Matrix Composites. Even, conventional engineering materials - metals, plastics, alloys etc. - may develop heterogeneities, like inclusions and residual stresses, during the manufacturing process. Moreover, these materials may also have intrinsic heterogeneities at a nanoscale in the form of grain boundaries in metals, crystallinity in amorphous polymers etc. While, the homogenized constitutive models for these materials may be satisfactory at a macroscale, recent studies of phenomena like fatigue failure, void nucleation, size-dependent brittle-ductile transition in polymeric nanofibers reveal a major play of micro/nanoscale physics in these phenomena. At this scale, heterogeneities in a material may no longer be ignored. Thus, this demands a study into the effects of various material heterogeneities. In this work, spatial heterogeneities in two material properties - elastic modulus and yield stress - have been investigated separately. The heterogeneity in the elastic modulus is studied in the context of Green's function. The Stochastic Finite Element method is adopted to get the mean statistics of the Green's function defined on a stochastic heterogeneous 2D infinite space. A study of the elastic-plastic transition in a domain having stochastic heterogenous yield stress was done using Mont-Carlo methods. The statistics for various stress and strain fields during the transition were obtained. Further, the effects of size of the domain and the strain-hardening rate on the stress fields during the heterogeneous elastic-plastic transition were investigated. Finally, a case is made for the role of the heterogenous elastic-plastic transition in damage nucleation and growth.

  6. Local electric fields and molecular properties in heterogeneous environments through polarizable embedding

    List, Nanna Holmgaard; Jensen, Hans Jørgen Aagaard; Kongsted, Jacob

    2016-01-01

    chemical reference calculations. For the lowest π → π∗ transition in DsRed, inclusion of effective external field effects gives rise to a 1.9- and 3.5-fold reduction in the 1PA and 2PA cross-sections, respectively. The effective external field is, however, strongly influenced by the heterogeneity...... (1PA and 2PA, respectively) properties of PRODAN-methanol clusters as well as the fluorescent protein DsRed. Our results demonstrate the necessity of accounting for both the dynamical reaction field and effective external field contributions to the local field in order to reproduce full quantum...

  7. Information content of long-range NMR data for the characterization of conformational heterogeneity

    Andrałojć, Witold [University of Florence, Center for Magnetic Resonance (CERM) (Italy); Berlin, Konstantin; Fushman, David, E-mail: fushman@umd.edu [University of Maryland, Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization (United States); Luchinat, Claudio, E-mail: luchinat@cerm.unifi.it; Parigi, Giacomo; Ravera, Enrico [University of Florence, Center for Magnetic Resonance (CERM) (Italy); Sgheri, Luca [CNR, Istituto per le Applicazioni del Calcolo, Sezione di Firenze (Italy)

    2015-07-15

    Long-range NMR data, namely residual dipolar couplings (RDCs) from external alignment and paramagnetic data, are becoming increasingly popular for the characterization of conformational heterogeneity of multidomain biomacromolecules and protein complexes. The question addressed here is how much information is contained in these averaged data. We have analyzed and compared the information content of conformationally averaged RDCs caused by steric alignment and of both RDCs and pseudocontact shifts caused by paramagnetic alignment, and found that, despite the substantial differences, they contain a similar amount of information. Furthermore, using several synthetic tests we find that both sets of data are equally good towards recovering the major state(s) in conformational distributions.

  8. Dysmorphic disorders: clinical and nosological heterogeneity

    V. E. Medvedev

    2016-01-01

    Full Text Available The clinical picture of dysmorphophobia (DMP (dysmorphia, DM has been inadequately investigated; its descriptions are contradictory.Objective: to study the clinical structure of DMP (DM on a sample of plastic or cosmetic surgery patients.Patients and methods. An examination was made in of 103 patients, including 81 (78.6% women (mean age, 35.8±4.9 years and 22 (21.4% men (mean age, 30.9±5.7 years, who had gone to a clinic of cosmetic or plastic surgery with complaints of objectively unverified appearance defects and DM signs and given consent to take part in the investigation. All the patients underwent clinical and psychopathological examination; in so doing the follow-up data in the past 1-3 tears were borne in mind. Their somatic condition was analyzed on the basis of the data available in the medical documents and the results of laboratory, clinical, and instrumental studies.Results. The dysmorphic syndrome has been found to have overvalued, hypochondriacal, obsessive-compulsive, depressive, and delusional forms. It has been established that DM can manifest within schizophrenia, personality disorders, affective disorders, and organic mental diseases. Differential diagnostic criteria for different types of DM in heterogeneous psychopathological disorders are given.

  9. The genetic validation of heterogeneity in schizophrenia

    Moritani Makiko

    2011-10-01

    Full Text Available Abstract Introduction Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To overcome this state of uncertainty, the SZGene database has been established by including all published case-control genetic association studies appearing in peer-reviewed journals. In the current study, we aimed to determine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our case-control samples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of seven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative diagnostic manual, the DSM-IV. Methods Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven top-ranked variants (p Results No statistically significant deviation between cases and controls was observed in the genetic risk-index derived from all seven variants on the top-ranked polymorphisms. In fact, the average risk-index score in the schizophrenia group (6.5+/-1.57 was slightly lower than among controls (6.6+/-1.39. Conclusion The current work illustrates the difficulty in identifying universal and definitive risk-conferring polymorphisms for schizophrenia. Our employed number of samples was small, so we can not preclude the possibility that some or all of these variants are minor risk factors for schizophrenia in the Japanese population. It is also important to aggregate the updated positive variants in the SZGene database when the replication work is conducted.

  10. Functionally heterogenous ryanodine receptors in avian cerebellum.

    Sierralta, J; Fill, M; Suárez-Isla, B A

    1996-07-19

    The functional heterogeneity of the ryanodine receptor (RyR) channels in avian cerebellum was defined. Heavy endoplasmic reticulum microsomes had significant levels of ryanodine and inositol 1,4,5-trisphosphate binding. Scatchard analysis and kinetic studies indicated the existence of at least two distinct ryanodine binding sites. Ryanodine binding was calcium-dependent but was not significantly enhanced by caffeine. Incorporation of microsomes into planar lipid bilayers revealed ion channels with pharmacological features (calcium, magnesium, ATP, and caffeine sensitivity) similar to the RyR channels found in mammalian striated muscle. Despite a wide range of unitary conductances (220-500 picosiemens, symmetrical cesium methanesulfonate), ryanodine locked both channels into a characteristic slow gating subconductance state, positively identifying them as RyR channels. Two populations of avian RyR channels were functionally distinguished by single channel calcium sensitivity. One population was defined by a bell-shaped calcium sensitivity analogous to the skeletal muscle RyR isoform (type I). The calcium sensitivity of the second RyR population was sigmoidal and analogous to the cardiac muscle RyR isoform (type II). These data show that there are at least two functionally distinct RyR channel populations in avian cerebellum. This leads to the possibility that these functionally distinct RyR channels are involved in different intracellular calcium signaling pathways.

  11. Heterogeneous coupling along Makran subduction zone

    Zarifi, Z.; Raeesi, M.

    2010-12-01

    The Makran subduction zone, located in the southeast of Iran and southern Pakistan, extends for almost 900 km along the Eurasian-Arabian plate boundary. The seismic activities in the eastern and western Makran exhibit very different patterns. The eastern Makran characterized by infrequent large earthquakes and low level of seismicity. The only large instrumentally recorded earthquake in the eastern Makran, the 27 Nov. 1945 (Mw=8.1) earthquake, was followed by tsunami waves with the maximum run-up height of 13 m and disastrous effects in Pakistan, India, Iran and Oman. The western Makran, however, is apparently quiescent without strong evidence on occurrence of large earthquakes in historical times, which makes it difficult to ascertain whether the slab subducts aseismically or experiences large earthquakes separated by long periods exceeding the historical records. We used seismicity and Trench Parallel Free air and Bouguer Anomalies (TPGA and TPBA) to study the variation in coupling in the slab interface. Using a 3D mechanical Finite Element (FE) model, we show how heterogeneous coupling can influence the rate of deformation in the overriding lithosphere and the state of stress in the outer rise, overriding, and subducting plates within the shortest expected cycle of earthquake. We test the results of FE model against the observed focal mechanism of earthquakes and available GPS measurements in Makran subduction zone.

  12. Coordinated Collaboration between Heterogeneous Distributed Energy Resources

    Shahin Abdollahy

    2014-01-01

    Full Text Available A power distribution feeder, where a heterogeneous set of distributed energy resources is deployed, is examined by simulation. The energy resources include PV, battery storage, natural gas GenSet, fuel cells, and active thermal storage for commercial buildings. The resource scenario considered is one that may exist in a not too distant future. Two cases of interaction between different resources are examined. One interaction involves a GenSet used to partially offset the duty cycle of a smoothing battery connected to a large PV system. The other example involves the coordination of twenty thermal storage devices, each associated with a commercial building. Storage devices are intended to provide maximum benefit to the building, but it is shown that this can have a deleterious effect on the overall system, unless the action of the individual storage devices is coordinated. A network based approach is also introduced to calculate some type of effectiveness metric to all available resources which take part in coordinated operation. The main finding is that it is possible to achieve synergy between DERs on a system; however this required a unified strategy to coordinate the action of all devices in a decentralized way.

  13. Sousse: extreme genetic heterogeneity in North Africa.

    Fadhlaoui-Zid, Karima; Garcia-Bertrand, Ralph; Alfonso-Sánchez, Miguel A; Zemni, Ramzi; Benammar-Elgaaied, Amel; Herrera, Rene J

    2015-01-01

    The male genetic landscape of the territory currently known as Tunisia is hampered by the scarcity of data, especially from cosmopolitan areas such as the coastal city of Sousse. In order to alleviate this lacuna, 220 males from Sousse were examined, for the first time, for more than 50 Y-chromosome single-nucleotide polymorphisms (Y-SNPs) markers and compared with 3099 individuals from key geographically targeted locations in North Africa, Europe and the Near East. The paternal lineages observed belong to a common set of Y haplogroups previously described in North Africa. In addition to the prominent autochthonous North African E-M81 haplogroup which is exclusively represented by its subclade E-M183 (44.55% of Y-chromosomes), a number of Near Eastern Neolithic lineages including E-M78, J-M267 and J-M172 account for 39% of the Y-chromosomes detected. Principal component analysis based on haplogroup frequencies, multidimensional scaling based on Rst genetic distances and analyses of molecular variance using both Y-chromosome short tandem repeat haplotypes and Y-SNP haplogroup data revealed that the Tunisian and North African groups, as a whole, are intra- and inter-specific diverse with Sousse being highly heterogeneous.

  14. Heterogeneous scalable framework for multiphase flows

    Morris, Karla Vanessa [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2013-09-01

    Two categories of challenges confront the developer of computational spray models: those related to the computation and those related to the physics. Regarding the computation, the trend towards heterogeneous, multi- and many-core platforms will require considerable re-engineering of codes written for the current supercomputing platforms. Regarding the physics, accurate methods for transferring mass, momentum and energy from the dispersed phase onto the carrier fluid grid have so far eluded modelers. Significant challenges also lie at the intersection between these two categories. To be competitive, any physics model must be expressible in a parallel algorithm that performs well on evolving computer platforms. This work created an application based on a software architecture where the physics and software concerns are separated in a way that adds flexibility to both. The develop spray-tracking package includes an application programming interface (API) that abstracts away the platform-dependent parallelization concerns, enabling the scientific programmer to write serial code that the API resolves into parallel processes and threads of execution. The project also developed the infrastructure required to provide similar APIs to other application. The API allow object-oriented Fortran applications direct interaction with Trilinos to support memory management of distributed objects in central processing units (CPU) and graphic processing units (GPU) nodes for applications using C++.

  15. Mechanistic insights into heterogeneous methane activation

    Latimer, Allegra A.; Aljama, Hassan; Kakekhani, Arvin; Yoo, Jong Suk; Kulkarni, Ambarish

    2017-01-01

    While natural gas is an abundant chemical fuel, its low volumetric energy density has prompted a search for catalysts able to transform methane into more useful chemicals. This search has often been aided through the use of transition state (TS) scaling relationships, which estimate methane activation TS energies as a linear function of a more easily calculated descriptor, such as final state energy, thus avoiding tedious TS energy calculations. It has been shown that methane can be activated via a radical or surface-stabilized pathway, both of which possess a unique TS scaling relationship. Herein, we present a simple model to aid in the prediction of methane activation barriers on heterogeneous catalysts. Analogous to the universal radical TS scaling relationship introduced in a previous publication, we show that a universal TS scaling relationship that transcends catalysts classes also seems to exist for surface-stabilized methane activation if the relevant final state energy is used. We demonstrate that this scaling relationship holds for several reducible and irreducible oxides, promoted metals, and sulfides. By combining the universal scaling relationships for both radical and surface-stabilized methane activation pathways, we show that catalyst reactivity must be considered in addition to catalyst geometry to obtain an accurate estimation for the TS energy. Here, this model can yield fast and accurate predictions of methane activation barriers on a wide range of catalysts, thus accelerating the discovery of more active catalysts for methane conversion.

  16. Adapting RRT growth for heterogeneous environments

    Denny, Jory; Morales, Marco; Rodriguez, Samuel; Amato, Nancy M.

    2013-01-01

    Rapidly-exploring Random Trees (RRTs) are effective for a wide range of applications ranging from kinodynamic planning to motion planning under uncertainty. However, RRTs are not as efficient when exploring heterogeneous environments and do not adapt to the space. For example, in difficult areas an expensive RRT growth method might be appropriate, while in open areas inexpensive growth methods should be chosen. In this paper, we present a novel algorithm, Adaptive RRT, that adapts RRT growth to the current exploration area using a two level growth selection mechanism. At the first level, we select groups of expansion methods according to the visibility of the node being expanded. Second, we use a cost-sensitive learning approach to select a sampler from the group of expansion methods chosen. Also, we propose a novel definition of visibility for RRT nodes which can be computed in an online manner and used by Adaptive RRT to select an appropriate expansion method. We present the algorithm and experimental analysis on a broad range of problems showing not only its adaptability, but efficiency gains achieved by adapting exploration methods appropriately. © 2013 IEEE.

  17. Deciphering dendritic cell heterogenity in immunity

    Michaël eChopin

    2012-02-01

    Full Text Available Dendritic cells (DCs are specialized antigen presenting cells that are exquisitely adapted to sense pathogens and induce the development of adaptive immune responses. They form a complex network of phenotypically and functionally distinct subsets. Within this network, individual DC subsets display highly specific roles in local immunosurveillance, migration and antigen presentation. This division of labor amongst DCs offers great potential to tune the immune response by harnessing subset-specific attributes of DCs in the clinical setting. Until recently, our understanding of DC subsets has been limited and paralleled by poor clinical translation and efficacy. We have now begun to unravel how different DC subsets develop within a complex multilayered system. These finding open up exciting possibilities for targeted manipulation of DC subsets. Furthermore, ground-breaking developments overcoming a major translational obstacle – identification of similar DC populations in mouse and man – now set the stage for significant advances in the field. Here we explore the determinants that underpin cellular and transcriptional heterogeneity within the DC network, how these influence DC distribution and localization at steady-state, and the capacity of DCs to present antigens via direct or cross-presentation during pathogen infection.

  18. Heterogeneous MEMS device assembly and integration

    Topart, Patrice; Picard, Francis; Ilias, Samir; Alain, Christine; Chevalier, Claude; Fisette, Bruno; Paultre, Jacques E.; Généreux, Francis; Legros, Mathieu; Lepage, Jean-François; Laverdière, Christian; Ngo Phong, Linh; Caron, Jean-Sol; Desroches, Yan

    2014-03-01

    In recent years, smart phone applications have both raised the pressure for cost and time to market reduction, and the need for high performance MEMS devices. This trend has led the MEMS community to develop multi-die packaging of different functionalities or multi-technology (i.e. wafer) approaches to fabricate and assemble devices respectively. This paper reports on the fabrication, assembly and packaging at INO of various MEMS devices using heterogeneous assembly at chip and package-level. First, the performance of a giant (e.g. about 3 mm in diameter), electrostatically actuated beam steering mirror is presented. It can be rotated about two perpendicular axes to steer an optical beam within an angular cone of up to 60° in vector scan mode with an angular resolution of 1 mrad and a response time of 300 ms. To achieve such angular performance relative to mirror size, the microassembly was performed from sub-components fabricated from 4 different wafers. To combine infrared detection with inertial sensing, an electroplated proof mass was flip-chipped onto a 256×1 pixel uncooled bolometric FPA and released using laser ablation. In addition to the microassembly technology, performance results of packaged devices are presented. Finally, to simulate a 3072×3 pixel uncooled detector for cloud and fire imaging in mid and long-wave IR, the staggered assembly of six 512×3 pixel FPAs with a less than 50 micron pixel co-registration is reported.

  19. Heat transfer in heterogeneous propellant combustion systems

    Brewster, M.Q.

    1992-01-01

    This paper reports that heat transfer plays an important role in several critical areas of heterogeneous, solid-propellant combustion systems. These areas include heat feedback to the propellant surface, heat transfer between burning aluminum droplets and their surroundings, heat transfer to internal insulation systems, and heat transfer to aft-end equipment. Gas conduction dominates heat feedback to the propellant surface in conventional ammonium perchlorate (AP) composite propellants, although particle radiative feedback also plays a significant role in combustion of metalized propellants. Particle radiation plays a dominant role in heat transfer to internal insulation, compared with that of convection. However, conduction by impingement of burning aluminum particles, which has not been extensively studied, may also be significant. Radiative heat loss plays an important role in determining the burning rate of molten aluminum particles due to a highly luminous, oxide particle-laden, detached flame envelope. Radiation by aluminum oxide smoke particles also plays a dominant role in heat transfer from the exhaust plume to aft-end equipment. Uncertainties in aluminum oxide particle-size distribution and optical properties still make it difficult to predict radiative plume heat transfer accurately from first principles

  20. Lizard locomotion in heterogeneous granular media

    Schiebel, Perrin; Goldman, Daniel

    2014-03-01

    Locomotion strategies in heterogeneous granular environments (common substrates in deserts), are relatively unexplored. The zebra-tailed lizard (C. draconoides) is a useful model organism for such studies owing to its exceptional ability to navigate a variety of desert habitats at impressive speed (up to 50 body-lengths per second) using both quadrapedal and bidepal gaits. In laboratory experiments, we challenge the lizards to run across a field of boulders (2.54 cm diameter glass spheres or 3.8 cm 3D printed spheres) placed in a lattice pattern and embedded in a loosely packed granular medium of 0.3 mm diameter glass particles. Locomotion kinematics of the lizard are recorded using high speed cameras, with and without the scatterers. The data reveals that unlike the lizard's typical quadrupedal locomotion using a diagonal gait, when scatterers are present the lizard is most successful when using a bipedal gait, with a raised center of mass (CoM). We propose that the kinematics of bipedal running in conjunction with the lizard's long toes and compliant hind foot are the keys to this lizard's successful locomotion in the presence of such obstacles. NSF PoLS

  1. Adaptive heterogeneous multi-robot teams

    Parker, L.E.

    1998-11-01

    This research addresses the problem of achieving fault tolerant cooperation within small- to medium-sized teams of heterogeneous mobile robots. The author describes a novel behavior-based, fully distributed architecture, called ALLIANCE, that utilizes adaptive action selection to achieve fault tolerant cooperative control in robot missions involving loosely coupled, largely independent tasks. The robots in this architecture possess a variety of high-level functions that they can perform during a mission, and must at all times select an appropriate action based on the requirements of the mission, the activities of other robots, the current environmental conditions, and their own internal states. Since such cooperative teams often work in dynamic and unpredictable environments, the software architecture allows the team members to respond robustly and reliably to unexpected environmental changes and modifications in the robot team that may occur due to mechanical failure, the learning of new skills, or the addition or removal of robots from the team by human intervention. After presenting ALLIANCE, the author describes in detail the experimental results of an implementation of this architecture on a team of physical mobile robots performing a cooperative box pushing demonstration. These experiments illustrate the ability of ALLIANCE to achieve adaptive, fault-tolerant cooperative control amidst dynamic changes in the capabilities of the robot team.

  2. Adjoint spectrum calculation in fuel heterogeneous cells

    Suster, Luis Carlos

    1998-01-01

    In most codes for cells calculation, the multigroup cross sections are generated taking into consideration the conservation of the reaction rates in the forward spectrum. However, for certain uses of the perturbation theory it's necessary to use the average of the parameters for energy macrogroups over the forward and the adjoint spectra. In this thesis the adjoint spectrum was calculated from the adjoint neutron balance equations, that were obtained for a heterogeneous unit cell. The collision probabilities method was used to obtain these equations. In order optimize the computational run-time, the Gaussian quadrature method was used in the calculation of the neutron balance equations, forward and adjoint. This method of integration was also used for the Doppler broadening functions calculation, necessary for obtaining the energy dependent cross sections. In order to calculate the reaction rates and the average cross sections, using both the forward and the adjoint neutron spectra, the most important resonances of the U 238 were considered. The results obtained with the method show significant differences for the different cross sections weighting schemes. (author)

  3. Expanding the genetic heterogeneity of intellectual disability.

    Anazi, Shams; Maddirevula, Sateesh; Salpietro, Vincenzo; Asi, Yasmine T; Alsahli, Saud; Alhashem, Amal; Shamseldin, Hanan E; AlZahrani, Fatema; Patel, Nisha; Ibrahim, Niema; Abdulwahab, Firdous M; Hashem, Mais; Alhashmi, Nadia; Al Murshedi, Fathiya; Al Kindy, Adila; Alshaer, Ahmad; Rumayyan, Ahmed; Al Tala, Saeed; Kurdi, Wesam; Alsaman, Abdulaziz; Alasmari, Ali; Banu, Selina; Sultan, Tipu; Saleh, Mohammed M; Alkuraya, Hisham; Salih, Mustafa A; Aldhalaan, Hesham; Ben-Omran, Tawfeg; Al Musafri, Fatima; Ali, Rehab; Suleiman, Jehan; Tabarki, Brahim; El-Hattab, Ayman W; Bupp, Caleb; Alfadhel, Majid; Al Tassan, Nada; Monies, Dorota; Arold, Stefan T; Abouelhoda, Mohamed; Lashley, Tammaryn; Houlden, Henry; Faqeih, Eissa; Alkuraya, Fowzan S

    2017-11-01

    Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

  4. Modelling Preference Heterogeneity for Theatre Tickets

    Baldin, Andrea; Bille, Trine

    This paper analyzes the behavioural choice for theatre tickets using a rich dataset for 2010-2013 from the sale system of the Royal Danish National Theatre. A consumer who decides to attend a theater production faces multiple sources of price variation that depends on: socio-economic characterist......This paper analyzes the behavioural choice for theatre tickets using a rich dataset for 2010-2013 from the sale system of the Royal Danish National Theatre. A consumer who decides to attend a theater production faces multiple sources of price variation that depends on: socio......-economic characteristics, quality of the seat, day of the performance and timing of purchase. Except for the first case, factors of price differentiation involves a choice by the consumer among different ticket alternatives. Two modelling approaches, namely multinomial logit (with socio-demographic characteristics......) and latent class are proposed in order to model ticket purchase behaviour. These models allow us explicitly to take into account consumers' preference heterogeneity with respect to the attributes associated to each ticket alternative In addition, the distribution of the willingness-to-pay (WTP) of choice...

  5. Simulating tumor growth in confined heterogeneous environments

    Gevertz, Jana L; Torquato, Salvatore; Gillies, George T

    2008-01-01

    The holy grail of computational tumor modeling is to develop a simulation tool that can be utilized in the clinic to predict neoplastic progression and propose individualized optimal treatment strategies. In order to develop such a predictive model, one must account for many of the complex processes involved in tumor growth. One interaction that has not been incorporated into computational models of neoplastic progression is the impact that organ-imposed physical confinement and heterogeneity have on tumor growth. For this reason, we have taken a cellular automaton algorithm that was originally designed to simulate spherically symmetric tumor growth and generalized the algorithm to incorporate the effects of tissue shape and structure. We show that models that do not account for organ/tissue geometry and topology lead to false conclusions about tumor spread, shape and size. The impact that confinement has on tumor growth is more pronounced when a neoplasm is growing close to, versus far from, the confining boundary. Thus, any clinical simulation tool of cancer progression must not only consider the shape and structure of the organ in which a tumor is growing, but must also consider the location of the tumor within the organ if it is to accurately predict neoplastic growth dynamics

  6. Expanding the genetic heterogeneity of intellectual disability

    Anazi, Shams

    2017-09-22

    Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

  7. Expanding the genetic heterogeneity of intellectual disability

    Anazi, Shams; Maddirevula, Sateesh; Salpietro, Vincenzo; Asi, Yasmine T.; Alsahli, Saud; Alhashem, Amal; Shamseldin, Hanan E.; AlZahrani, Fatema; Patel, Nisha; Ibrahim, Niema; Abdulwahab, Firdous M.; Hashem, Mais; Alhashmi, Nadia; Al Murshedi, Fathiya; Al Kindy, Adila; Alshaer, Ahmad; Rumayyan, Ahmed; Al Tala, Saeed; Kurdi, Wesam; Alsaman, Abdulaziz; Alasmari, Ali; Banu, Selina; Sultan, Tipu; Saleh, Mohammed M.; Alkuraya, Hisham; Salih, Mustafa A.; Aldhalaan, Hesham; Ben-Omran, Tawfeg; Al Musafri, Fatima; Ali, Rehab; Suleiman, Jehan; Tabarki, Brahim; El-Hattab, Ayman W.; Bupp, Caleb; Alfadhel, Majid; Al Tassan, Nada; Monies, Dorota; Arold, Stefan T.; Abouelhoda, Mohamed; Lashley, Tammaryn; Houlden, Henry; Faqeih, Eissa; Alkuraya, Fowzan S.

    2017-01-01

    Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

  8. Modelling of heterogeneous clustering in aluminium

    Smith, A.E.; Bourgeois, L.; Nie, J.-F.; Muddle, B.C.

    2003-01-01

    Full text: Ab initio modelling of heterogeneous clustering in aluminium has been carried out in order to study the precipitation hardening of alloys. This process is based on the addition of small amounts of solute element to the pure metal. With increasing computational power, atomic scale effects can now be better simulated to determine the nature of the hardening mechanism. Comparisons are made between results obtained from two computational packages. These are the Linear Augmented Plane Wave WEEN2K and the plane wave pseudopotential density functional theory package fhi98md. The study of the optimal geometry of very small size clusters inside aluminium has begun with the testing of initial convergence conditions by determination of binding energies for a variety of super cell sizes of the aluminium host crystal. These are compared with total energy calculations for small size precipitates of copper and transition metals of fixed geometry. Such local optimal determinations are seen as precursors to full Monte Carlo calculations of the notional best local geometry for larger precipitates

  9. Adapting RRT growth for heterogeneous environments

    Denny, Jory

    2013-11-01

    Rapidly-exploring Random Trees (RRTs) are effective for a wide range of applications ranging from kinodynamic planning to motion planning under uncertainty. However, RRTs are not as efficient when exploring heterogeneous environments and do not adapt to the space. For example, in difficult areas an expensive RRT growth method might be appropriate, while in open areas inexpensive growth methods should be chosen. In this paper, we present a novel algorithm, Adaptive RRT, that adapts RRT growth to the current exploration area using a two level growth selection mechanism. At the first level, we select groups of expansion methods according to the visibility of the node being expanded. Second, we use a cost-sensitive learning approach to select a sampler from the group of expansion methods chosen. Also, we propose a novel definition of visibility for RRT nodes which can be computed in an online manner and used by Adaptive RRT to select an appropriate expansion method. We present the algorithm and experimental analysis on a broad range of problems showing not only its adaptability, but efficiency gains achieved by adapting exploration methods appropriately. © 2013 IEEE.

  10. Heterogeneity of limbal basal epithelial progenitor cells.

    Hayashida, Yasutaka; Li, Wei; Chen, Ying-Ting; He, Hua; Chen, Szu-yu; Kheirkah, Ahmad; Zhu, Ying-Tien; Matsumoto, Yukihiro; Tseng, Scheffer C G

    2010-11-01

    Although corneal epithelial stem cells (SCs) are located at the limbus between the cornea and the conjunctiva, not all limbal basal epithelial cells are SCs. Using 2 dispase digestions to remove different amounts of limbal basal epithelial cells for cross-sections, flat mounts, and cytospin preparations, double immunostaining to pancytokeratins (PCK) and vimentin (Vim) identified 3 p63+ epithelial progenitors such as PCK-/Vim+, PCK/Vim, and PCK-/Vim+ and 1 p63+ mesenchymal cell, PCK-/Vim+. PCK-/Vim- progenitors had the smallest cell size were 10-20 times more enriched on collagen I-coated dishes in the 5-minute rapid adherent fraction that contained the highest percentage of p63+ cells but the lowest percentage of cytokeratin12+ cells, and gave rise to high Ki67 labeling and vivid clonal growth. In contrast, PCK+/Vim+ and PCK+/Vim- progenitors were found more in the slow-adherent fraction and yielded poor clonal growth. PCK/Vim progenitors and clusters of PCK-/Vim+ mesenchymal cells, which were neither melanocytes nor Langerhans cells, were located in the limbal basal region. Therefore, differential expression of PCK and Vim helps identify small PCK-/Vim- cells as the most likely candidate for SCs among a hierarchy of heterogeneous limbal basal progenitors, and their close association with PCK-/Vim+ presumed "niche" cells.

  11. Heterogeneous equilibrium in mplybdenum-iodine system

    Klinkova, L.A.

    1983-01-01

    Heterogeneous equilibrium in the Mo-J system is studied to reveal regions of existence of molybdenum iodides, is studied. The investigation is performed for atomic ratio I/Mo=0.02-7.5 in the temperature range of 300-1370 K using methods of thermographic, X-ray phase, chemical and optical analyses of phases quenched after isothermal annealing. It is shown that higher molybdenum iodides (Mo1 4 , MoJ 5 , MoJ 6 ) are thermally unstable compounds and exist in the Mo-J system at low temperatures (360-490 K). Above 470 K higher iodides dissociate up to molybdenum triiodide. MoJ 3 under the pressure of iodine vapors is stable up to 970 K. Molybdenum diiodide is the product of triiodide decomposition and forms in the Mo-J system in the 700-1270 K range. At the J/Mo>>3 ratio the product of triiodide decomposition is MoJsub(2.87) which is thermally unstable up to 570 K, while in iodine atmosphere - up to 1170 K

  12. Inferring Molecular Processes Heterogeneity from Transcriptional Data.

    Gogolewski, Krzysztof; Wronowska, Weronika; Lech, Agnieszka; Lesyng, Bogdan; Gambin, Anna

    2017-01-01

    RNA microarrays and RNA-seq are nowadays standard technologies to study the transcriptional activity of cells. Most studies focus on tracking transcriptional changes caused by specific experimental conditions. Information referring to genes up- and downregulation is evaluated analyzing the behaviour of relatively large population of cells by averaging its properties. However, even assuming perfect sample homogeneity, different subpopulations of cells can exhibit diverse transcriptomic profiles, as they may follow different regulatory/signaling pathways. The purpose of this study is to provide a novel methodological scheme to account for possible internal, functional heterogeneity in homogeneous cell lines, including cancer ones. We propose a novel computational method to infer the proportion between subpopulations of cells that manifest various functional behaviour in a given sample. Our method was validated using two datasets from RNA microarray experiments. Both experiments aimed to examine cell viability in specific experimental conditions. The presented methodology can be easily extended to RNA-seq data as well as other molecular processes. Moreover, it complements standard tools to indicate most important networks from transcriptomic data and in particular could be useful in the analysis of cancer cell lines affected by biologically active compounds or drugs.

  13. Protein politics

    Vijver, Marike

    2005-01-01

    This study is part of the program of the interdisciplinary research group Profetas (protein foods, environment, technology and society). Profetas consists of technological, environmental and socio-economic research projects on protein food systems which result in the development of scenarios and

  14. Protein adhesives

    Charles R. Frihart; Linda F. Lorenz

    2018-01-01

    Nature uses a wide variety of chemicals for providing adhesion internally (e.g., cell to cell) and externally (e.g., mussels to ships and piers). This adhesive bonding is chemically and mechanically complex, involving a variety of proteins, carbohydrates, and other compounds.Consequently,the effect of protein structures on adhesive properties is only partially...

  15. Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma

    Barreca, A; Martinengo, C; Annaratone, L; Righi, L; Chiappella, A; Ladetto, M; Demurtas, A; Chiusa, L; Stacchini, A; Crosetto, N; Oudenaarden, A van; Chiarle, R

    2014-01-01

    Most follicular lymphomas (FLs) are genetically defined by the t(14;18)(q32;q21) translocation that juxtaposes the BCL2 gene to the immunoglobulin heavy chain (IgH) 3' regulatory regions (IgH-3'RRs). Despite this recurrent translocation, FL cases are heterogeneous in terms of intratumoral clonal diversity for acquired mutations and variations in the tumor microenvironment. Here we describe an additional mechanism that contributes to inter- and intratumoral heterogeneity in FLs. By applying a novel single-molecule RNA fluorescence-based in situ hybridization (FISH) technique to detect mRNA molecules of BCL2 and IgH in single cells, we found marked heterogeneity in the number of BCL2 mRNA transcripts within individual lymphoma cells. Moreover, BCL2 mRNA molecules correlated with IgH mRNA molecules in individual cells both in t(14;18) lymphoma cell lines and in patient samples. Consistently, a strong correlation between BCL2 and IgH protein levels was found in a series of 205 primary FL cases by flow cytometry and immunohistochemistry. Inter- and intratumoral heterogeneity of BCL2 expression determined resistance to drugs commonly used in FL treatment and affected overall survival of FL patients. These data demonstrate that BCL2 and IgH expressions are heterogeneous and coregulated in t(14;18)-translocated cells, and determine the response to therapy in FL patients

  16. Quantitative and ecological aspects of Listeria monocytogenes population heterogeneity

    Metselaar, K.I.

    2016-01-01

    Bacterial stress response and heterogeneity therein is one of the biggest challenges posed by minimal processing. Heterogeneity and resulting tailing representing a more resistant fraction of the population, can have several causes and can be transient or stably in nature. Stable increased stress

  17. Potential energy landscapes of elemental and heterogeneous chalcogen clusters

    Mauro, John C.; Loucks, Roger J.; Balakrishnan, Jitendra; Varshneya, Arun K.

    2006-01-01

    We describe the potential energy landscapes of elemental S 8 , Se 8 , and Te 8 clusters using disconnectivity graphs. Inherent structures include both ring and chain configurations, with rings especially dominant in Se 8 . We also map the potential energy landscapes of heterogeneous Se n (S,Te) 8-n clusters, which offer insights into the structure of heterogeneous chalcogen glasses

  18. Social support among heterogeneous partners : an experimental test

    Vogt, Sonja; Weesie, Jeroen

    2006-01-01

    This paper studies how dyadic social support is affected by heterogeneity of the partners.We distinguish heterogeneity with respect to three parameters: the likelihood of needing support; the benefits from receiving support; and the costs of providing support. Hypotheses are based on a

  19. Synthesis of heterogeneous catalyst for the production of biodiesel ...

    This study explore the comparison of a suitable heterogeneous catalyst for conversion of triglyceride into fatty acid methyl ester. A series of heterogeneous cerium, manganese, and zinc oxide catalyst supported at mixture of cinder was prepared by co-precipitation and applied for conversion of triglyceride in oil to biodiesel ...

  20. Real-Time Monitoring of Heterogeneous Catalysis with Mass Spectrometry

    Young, Mark A.

    2009-01-01

    Heterogeneous, gas-solid processes constitute an important class of catalytic reactions that play a key role in a variety of applications, such as industrial processing and environmental controls. Heterogeneous catalytic chemistry can be demonstrated in a simple heated flow reactor containing a fragment of the catalytic converter from a vehicular…